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Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
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CC-BY
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http://creativecommons.org/licenses/by/4.0/
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Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
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CC-BY
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http://creativecommons.org/licenses/by/4.0/
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"MD",
"simulation",
"of",
"BP100",
"in",
"DMPC",
"bilayer",
"and",
"found",
"that",
"BP100",
"remained",
"in",
"the",
"surface-bound-state",
"inserting",
"through",
"its",
"C-terminus.",
"They",
"also",
"reported",
"the",
"unfolding",
"of",
"BP100",
"N-terminus",
"(Lys1",
"and",
"Lys2)",
"after",
"1.5",
"µs,",
"resulting",
"in",
"a",
"tilt",
"angle",
"of",
"97°",
"and",
"81%",
"helicity",
"10",
",",
"17",
".",
"In",
"a",
"study",
"with",
"Brownian",
"Dynamics",
"simulations",
"with",
"a",
"coarse-grained",
"peptide",
"model,",
"Alves",
"et",
"al.",
"18",
"simulated",
"BP100",
"confined",
"in",
"model",
"membranes",
"at",
"293",
"K",
"for",
"1",
"µs",
"each",
"and",
"reported",
"the",
"high",
"stability",
"of",
"BP100",
"pre-folded",
"alpha",
"helix",
"and",
"a",
"threefold",
"decrease",
"in",
"its",
"lateral",
"diffusion",
"in",
"POPC:",
"POPG",
"membranes",
"relative",
"to",
"that",
"in",
"POPC",
"membrane",
"18",
".",
"In",
"this",
"work",
"we",
"report",
"simulations,",
"in",
"solution",
"and",
"membranes,",
"extending",
"for",
"more",
"than",
"25",
"µs",
"of",
"BP100",
"and",
"membranes",
"of",
"1,2-dipalmitoyl-sn-glycerol-3-phosphocholine",
"(DPPC),",
"1,2-dipalmitoyl-sn-glycerol-3-phosphoglycerol",
"(DPPG),",
"and",
"DPPC:",
"DPPG",
"mixtures",
"(1:1)."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"In",
"this",
"work",
"we",
"report",
"simulations,",
"in",
"solution",
"and",
"membranes,",
"extending",
"for",
"more",
"than",
"25",
"µs",
"of",
"BP100",
"and",
"membranes",
"of",
"1,2-dipalmitoyl-sn-glycerol-3-phosphocholine",
"(DPPC),",
"1,2-dipalmitoyl-sn-glycerol-3-phosphoglycerol",
"(DPPG),",
"and",
"DPPC:",
"DPPG",
"mixtures",
"(1:1).",
"We",
"systematically",
"investigated",
"the",
"dependence",
"of",
"BP100",
"secondary",
"structure",
"on",
"DPPG",
"lipids",
"which",
"agrees",
"with",
"experimental",
"findings",
"11",
".",
"We",
"also",
"analyzed",
"the",
"contribution",
"of",
"PG-containing",
"lipid",
"rafts",
"on",
"BP100",
"conformation",
"and",
"behavior.",
"In",
"most",
"simulations",
"containing",
"DPPG",
"lipids,",
"we",
"observed",
"the",
"occurrence",
"of",
"a",
"dynamic",
"transition",
"of",
"the",
"peptide",
"adsorbed",
"at",
"the",
"membrane",
"interface,",
"where",
"the",
"apolar",
"facet",
"of",
"the",
"BP100",
"(Fig.",
"1c",
"),",
"initially",
"exposed",
"to",
"water,",
"rotates",
"toward",
"the",
"membrane",
"interior,",
"leaving",
"the",
"polar",
"facet",
"of",
"the",
"peptide",
"exposed",
"to",
"water.",
"This",
"process,",
"defined",
"here",
"as",
"peptide",
"flip,",
"could",
"be",
"part",
"of",
"CAMPs",
"primary",
"antimicrobial",
"mechanism.",
"Constraining",
"four",
"residues",
"of",
"the",
"peptide",
"into",
"an",
"alpha",
"helix",
"turn,",
"we",
"observed",
"that",
"the",
"unconstrained",
"regions",
"of",
"the",
"peptide",
"rapidly",
"acquired",
"an",
"alpha-helix",
"conformation",
"in",
"DPPG-containing",
"membranes,",
"suggesting",
"that",
"the",
"formation",
"of",
"these",
"small",
"alpha-helical",
"nuclei",
"in",
"peptide/membrane",
"interactions",
"may",
"be",
"the",
"initial",
"step",
"for",
"the",
"peptide",
"insertion",
"into",
"the",
"hydrophobic",
"core",
"of",
"the",
"membranes.",
"Figure",
"1",
"BP100",
"initial",
"structures:",
"random",
"coil",
"L",
"-BP100",
"(",
"a",
")",
"and",
"alpha-helical",
"α",
"-BP100",
"(",
"b",
").",
"Helical",
"wheel",
"projection",
"(",
"c",
"),",
"Lys5",
"and",
"Ile7",
"were",
"used",
"as",
"representative",
"residues",
"of",
"polar",
"and",
"apolar",
"moieties,",
"respectively.",
"In",
"(",
"d",
")",
"DPPC",
"(in",
"blue)",
"and",
"DPPG",
"(in",
"yellow).",
"Atom",
"names",
"are",
"shown",
"for",
"peptide",
"and",
"lipids;",
"they",
"were",
"used",
"in",
"our",
"peptide-lipid",
"pair",
"analysis.",
"Methods",
"All",
"simulations",
"sets",
"were",
"assembled,",
"carried",
"out",
"and",
"analyzed",
"using",
"GROMACS",
"5.0.2",
"software",
"package."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Simulation",
"sets",
"Simulations",
"Peptide/Lipid",
"Waters/Lipid",
"Time",
"(ns)",
"Bilayers",
"DPPC",
"0/128",
"54",
"860",
"DPPG",
"53",
"1100",
"PCPG-R",
"0/[64/64]",
"54",
"1200",
"PCPG-NR",
"52",
"1200",
"Peptide",
"in",
"water",
"L",
"-BP100",
"in",
"water",
"1/0",
"—",
"2000",
"α",
"-BP100",
"in",
"water",
"—",
"2850",
"Peptide",
"with",
"bilayers",
"L",
"-BP100",
"in",
"DPPC",
"1/128",
"54",
"1700",
"α",
"-BP100",
"in",
"DPPC",
"54",
"2000",
"L",
"-BP100",
"in",
"DPPG",
"1/128",
"53",
"1700",
"α",
"-BP100",
"in",
"DPPG",
"53",
"2000",
"L",
"-BP100",
"in",
"PCPG-R",
"1/[64/64]",
"54",
"1600",
"α",
"-BP100",
"in",
"PCPG-R",
"54",
"2000",
"L",
"-BP100",
"in",
"PCPG-NR",
"1/[64/64]",
"52",
"1700",
"α",
"-BP100",
"in",
"PCPG-NR",
"52",
"2000",
"Partially",
"constrained",
"peptide",
"in",
"DPPG",
"α-",
"BP100",
"(res1–5)",
"in",
"DPPG",
"1/128",
"54",
"600",
"α-",
"BP100",
"(res4–8)",
"in",
"DPPG",
"54",
"600",
"α-",
"BP100",
"(res7–11)",
"in",
"DPPG",
"54",
"600",
"Lipid",
"bilayers",
"We",
"used",
"Slipids",
"forcefield",
"19",
"parameters",
"were",
"chosen",
"to",
"simulate",
"DPPC,",
"DPPG,",
"and",
"DPPC/DPPG",
"mixed",
"bilayers.",
"64-lipids-per-monolayer",
"DPPC",
"and",
"DPPG",
"pure",
"membrane",
"topologies",
"were",
"taken",
"from",
"the",
"Slipids",
"developer",
"group",
"website",
"(http://www.fos.su.se/~sasha/Slipids/Downloads.html).",
"Mixed",
"bilayers",
"of",
"DPPC",
"and",
"DPPG",
"containing",
"32",
"DPPCs",
"and",
"32",
"DPPGs",
"in",
"each",
"leaflet",
"were",
"constructed",
"using",
"the",
"PACKMOL",
"20",
"software.",
"One",
"membrane",
"was",
"composed",
"of",
"randomly",
"distributed",
"lipids",
"(PCPG-NR)",
"on",
"both",
"leaflets",
"and",
"the",
"other,",
"a",
"4",
"×",
"4",
"DPPG",
"raft",
"was",
"placed",
"in",
"the",
"center",
"of",
"both",
"monolayers",
"(PCPG-R)",
"and",
"the",
"remaining",
"48",
"lipids",
"were",
"randomly",
"distributed",
"(Fig.",
"2",
")."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"The",
"area",
"per",
"lipid",
"and",
"membrane",
"thickness",
"were",
"calculated",
"for",
"all",
"membranes",
"and",
"thNen",
"compared",
"with",
"experimental",
"data",
"and",
"those",
"obtained",
"by",
"Slipids",
"authors",
"(Tables",
"S1",
"and",
"S2",
").",
"The",
"last",
"trajectory",
"frames",
"of",
"the",
"membrane",
"simulations",
"were",
"used",
"to",
"build",
"our",
"peptide-lipid",
"systems.",
"Peptide-in-solution",
"and",
"peptide-lipid",
"systems",
"Following",
"a",
"study",
"by",
"Beauchamp",
"et",
"al.",
"22",
",",
"ff99sb-ildn-NMR",
"force",
"field",
"was",
"chosen",
"to",
"characterize",
"BP100",
"in",
"our",
"modeling",
"due",
"to",
"its",
"good",
"performance",
"in",
"simulating",
"peptides",
"and",
"proteins",
"structures",
"in",
"TIP3P",
"water",
"when",
"compared",
"with",
"NMR",
"measurements.",
"BP100",
"(H-Lys-Lys-Leu-Phe-Lys-Lys-Ile-Leu-Lys-Tyr-Leu-NH",
"2",
")",
"has",
"an",
"amidated",
"C-terminal",
"and",
"a",
"+6",
"charge",
"at",
"physiological",
"pH,",
"with",
"all",
"its",
"Lysines",
"and",
"N-terminal",
"amine",
"protonated.",
"To",
"study",
"secondary",
"structure",
"behavior",
"of",
"BP100",
"both",
"in",
"solution",
"and",
"in",
"bilayers,",
"two",
"initial",
"BP100",
"conformations",
"were",
"used:",
"linear",
"BP100",
"(",
"L",
"-BP100)",
"and",
"alpha-helical",
"BP100",
"(",
"α",
"-BP100)",
"(Fig.",
"1",
"a,b",
").",
"In",
"the",
"peptide/water",
"system,",
"one",
"peptide",
"(",
"α",
"-BP100",
"or",
"L-BP100",
"initial",
"conformation)",
"were",
"simulated",
"in",
"a",
"cubic",
"box",
"with",
"3975",
"TIP3P",
"water",
"molecules",
"for",
"more",
"than",
"1",
"microsecond",
"with",
"its",
"+6",
"charges",
"neutralized",
"with",
"6",
"Cl",
"−",
"ions",
"(Dang",
"23",
").",
"Simulations",
"containing",
"peptides",
"with",
"membranes",
"had",
"a",
"peptide/lipid",
"ratio",
"of",
"1/128",
"and",
"the",
"peptide",
"was",
"initially",
"positioned",
"in",
"parallel",
"orientation",
"with",
"the",
"membrane",
"surface",
"approximately",
"2",
"nm",
"away.",
"For",
"the",
"α",
"-BP100,",
"additionally,",
"we",
"tested",
"two",
"parallel",
"orientations,",
"where",
"the",
"polar",
"amino",
"acids",
"were",
"facing",
"the",
"membrane",
"and",
"a",
"random",
"orientation.",
"For",
"the",
"perpendicular",
"orientation",
"we",
"tested",
"two",
"ways",
"with",
"either",
"the",
"C-terminal",
"or",
"N-terminal",
"facing",
"the",
"interface.",
"For",
"all",
"these",
"initial",
"conditions,",
"we",
"obtained",
"the",
"same",
"final",
"location",
"and",
"orientation",
"of",
"the",
"peptide",
"that",
"will",
"be",
"discussed",
"in",
"the",
"results",
"section."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Atmospheric",
"pressure",
"of",
"1",
"bar",
"was",
"kept",
"with",
"the",
"Berendsen",
"barostat",
"26",
"and",
"semi-isotropic",
"pressure",
"coupling",
"was",
"used",
"for",
"all",
"systems.",
"All",
"bonds",
"were",
"constrained",
"with",
"LINCS",
"27",
"algorithm.",
"Long-range",
"electrostatic",
"correction",
"was",
"treated",
"by",
"a",
"Particle-mesh-Ewald",
"method",
"28",
"with",
"a",
"real-space",
"cut-off",
"of",
"1.5",
"nm.",
"van",
"der",
"Waals",
"interactions",
"were",
"truncated",
"at",
"1.5",
"nm",
"distance",
"with",
"a",
"switch",
"function",
"from",
"1.4",
"nm.",
"Simulation",
"analyses",
"Lipid/peptide",
"contacts",
"For",
"the",
"computation",
"of",
"lipid",
"contacts",
"with",
"BP100",
"and",
"pair",
"frequency,",
"we",
"labeled",
"some",
"lipid(s)",
"and",
"BP100",
"atoms",
"as",
"“polar”",
"or",
"“apolar”,",
"based",
"on",
"charges.",
"Then,",
"the",
"radial",
"distribution",
"function",
"(RDF)",
"between",
"each",
"pair",
"of",
"apolar",
"(or",
"polar)",
"atoms",
"of",
"the",
"lipids/BP100",
"system",
"were",
"computed.",
"The",
"time",
"window",
"selected",
"for",
"computing",
"these",
"RDFs",
"includes",
"that",
"of",
"the",
"membrane",
"bound",
"peptide",
"250",
"ns-before",
"and",
"250",
"ns-after",
"the",
"peptide",
"flip.",
"The",
"pairs",
"with",
"distinguishable",
"RDF",
"peaks",
"and",
"following",
"minimum",
"were",
"used",
"to",
"analyze",
"the",
"number",
"of",
"polar",
"and",
"apolar",
"contacts",
"between",
"lipids",
"and",
"peptide.",
"A",
"cutoff",
"distance",
"for",
"each",
"pair",
"was",
"defined",
"from",
"the",
"position",
"of",
"the",
"first",
"minimum",
"in",
"the",
"RDF",
"curve,",
"and",
"a",
"contact",
"was",
"defined",
"as",
"a",
"pair",
"of",
"atoms",
"at",
"smaller",
"distance",
"than",
"their",
"corresponding",
"cutoff",
"distance.",
"The",
"simulations",
"were",
"analyzed",
"and",
"the",
"total",
"number",
"of",
"polar",
"and",
"apolar",
"contacts",
"as",
"a",
"function",
"of",
"time",
"was",
"obtained.",
"Additionally,",
"some",
"polar",
"and",
"apolar",
"pairs",
"were",
"analyzed",
"individually.",
"Peptide",
"hydration",
"The",
"time",
"evolution",
"of",
"the",
"solvent",
"shell",
"surrounding",
"the",
"peptide",
"in",
"its",
"α",
"and",
"L",
"conformations",
"in",
"all",
"simulated",
"membranes",
"was",
"analyzed",
"using",
"the",
"minimum",
"distance",
"distribution",
"function",
"(MDDF)",
"29",
"between",
"the",
"peptide",
"and",
"the",
"water",
"molecules,",
"as",
"well",
"as",
"the",
"average",
"number",
"of",
"water",
"molecules",
"N(r),",
"within",
"a",
"distance",
"r",
"=",
"0.5",
"nm,",
"named",
"here",
"as",
"N(0.5).",
"For",
"comparison",
"the",
"MDDF",
"of",
"BP100",
"in",
"water",
"was",
"used",
"to",
"define",
"the",
"bulk",
"water",
"hydration",
"shell",
"at",
"the",
"same",
"distance."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"A",
"cutoff",
"distance",
"for",
"each",
"pair",
"was",
"defined",
"from",
"the",
"position",
"of",
"the",
"first",
"minimum",
"in",
"the",
"RDF",
"curve,",
"and",
"a",
"contact",
"was",
"defined",
"as",
"a",
"pair",
"of",
"atoms",
"at",
"smaller",
"distance",
"than",
"their",
"corresponding",
"cutoff",
"distance.",
"The",
"simulations",
"were",
"analyzed",
"and",
"the",
"total",
"number",
"of",
"polar",
"and",
"apolar",
"contacts",
"as",
"a",
"function",
"of",
"time",
"was",
"obtained.",
"Additionally,",
"some",
"polar",
"and",
"apolar",
"pairs",
"were",
"analyzed",
"individually.",
"Peptide",
"hydration",
"The",
"time",
"evolution",
"of",
"the",
"solvent",
"shell",
"surrounding",
"the",
"peptide",
"in",
"its",
"α",
"and",
"L",
"conformations",
"in",
"all",
"simulated",
"membranes",
"was",
"analyzed",
"using",
"the",
"minimum",
"distance",
"distribution",
"function",
"(MDDF)",
"29",
"between",
"the",
"peptide",
"and",
"the",
"water",
"molecules,",
"as",
"well",
"as",
"the",
"average",
"number",
"of",
"water",
"molecules",
"N(r),",
"within",
"a",
"distance",
"r",
"=",
"0.5",
"nm,",
"named",
"here",
"as",
"N(0.5).",
"For",
"comparison",
"the",
"MDDF",
"of",
"BP100",
"in",
"water",
"was",
"used",
"to",
"define",
"the",
"bulk",
"water",
"hydration",
"shell",
"at",
"the",
"same",
"distance.",
"Results",
"The",
"17",
"sets",
"of",
"simulations",
"(Table",
"1",
")",
"were",
"run",
"for",
"more",
"than",
"25",
"µs",
"of",
"simulation",
"time,",
"and",
"each",
"unconstrained",
"peptide/membrane",
"simulation",
"had",
"at",
"least",
"1.6",
"µs",
"of",
"simulation.",
"After",
"comparing",
"the",
"simulated",
"membrane",
"properties",
"with",
"experimental",
"and",
"other",
"computational",
"studies",
"(Tables",
"S1",
"and",
"S2",
"),",
"we",
"systematically",
"analyzed",
"the",
"peptide",
"conformation",
"in",
"solution",
"and",
"on",
"bilayers,",
"peptide",
"trajectory,",
"and",
"dynamics",
"on",
"membranes",
"and",
"the",
"effect",
"of",
"BP100",
"on",
"model",
"bilayers.",
"In",
"the",
"following",
"sections,",
"we",
"describe",
"our",
"results.",
"Secondary",
"structure",
"Peptide",
"in",
"solution",
"To",
"study",
"BP100",
"secondary",
"structure",
"in",
"water,",
"we",
"did",
"simulations",
"for",
"more",
"than",
"2",
"µs",
"with",
"both",
"α-BP100",
"and",
"L-BP100",
"initial",
"conformations.",
"Figure",
"4",
"shows",
"that",
"BP100",
"conformation",
"in",
"solution",
"was,",
"predominantly,",
"random",
"coil.",
"The",
"peptide",
"lost",
"the",
"initial",
"alpha",
"helix",
"conformation",
"in",
"approximately",
"40",
"ns",
"when",
"starting",
"with",
"an",
"alpha-helix",
"configuration",
"and",
"occasionally",
"formed",
"an",
"alpha-helix",
"turn",
"in",
"the",
"5–9",
"residue",
"region",
"(Fig.",
"4a",
").",
"For",
"L-BP100",
"in",
"solution,",
"we",
"observed",
"a",
"similar",
"pattern",
"(Fig.",
"4b",
").",
"Circular",
"Dichroism",
"(CD)",
"shows",
"that",
"BP100",
"is",
"random",
"in",
"solution",
"10",
",",
"11",
",",
"30",
",",
"and",
"our",
"simulations",
"reproduced",
"these",
"data."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"4a",
").",
"For",
"L-BP100",
"in",
"solution,",
"we",
"observed",
"a",
"similar",
"pattern",
"(Fig.",
"4b",
").",
"Circular",
"Dichroism",
"(CD)",
"shows",
"that",
"BP100",
"is",
"random",
"in",
"solution",
"10",
",",
"11",
",",
"30",
",",
"and",
"our",
"simulations",
"reproduced",
"these",
"data.",
"Figure",
"4",
"Secondary",
"structure",
"analyses",
"graphs",
"of",
"α",
"-BP100",
"(",
"a",
")",
"and",
"L",
"-BP100",
"(",
"b",
")",
"in",
"solution.",
"In",
"both",
"cases,",
"the",
"peptide",
"shows",
"predominance",
"in",
"random",
"coil",
"structure",
"(orange)",
"with",
"occasional",
"formation",
"of",
"1",
"alpha",
"helix",
"turn",
"(blue)",
"in",
"residues",
"5",
"to",
"9.",
"Peptide",
"in",
"bilayers",
"BP100",
"conformation,",
"antimicrobial",
"activity,",
"and",
"PG",
"content",
"are",
"related",
"11",
".",
"We",
"simulated",
"α-BP100",
"and",
"L-BP100",
"on",
"DPPC,",
"DPPG,",
"PCPG-R,",
"and",
"PCPG-NR",
"at",
"323",
"K,",
"above",
"DPPG",
"and",
"DPPC",
"transition",
"temperatures.",
"In",
"all",
"cases,",
"the",
"peptide",
"was",
"rapidly",
"adsorbed",
"on",
"the",
"membranes",
"and",
"diffused",
"laterally.",
"Figure",
"5",
"shows",
"that",
"the",
"BP100",
"alpha-helical",
"conformation",
"was",
"proportional",
"to",
"PG",
"content,",
"as",
"the",
"alpha-helix",
"percentage",
"in",
"DPPC",
"is",
"considerably",
"smaller",
"than",
"that",
"observed",
"in",
"DPPG-containing",
"membranes.",
"Alpha-helix",
"formed",
"in",
"the",
"5",
"to",
"9",
"residues",
"region",
"(Lys-Lys-Ile-Leu-Lys)",
"was",
"highly",
"stable",
"in",
"all",
"simulations.",
"Figure",
"5",
"Secondary",
"structure",
"analyses",
"of",
"α",
"-BP100",
"in",
"DPPC",
"(",
"a",
"),",
"DPPG",
"(",
"b",
"),",
"PCPG-R",
"(",
"c",
")",
"and",
"PCPG-NR",
"(",
"d",
").",
"In",
"DPPC,",
"α-BP100",
"alpha-helix",
"conformation",
"reached",
"a",
"plateau",
"at",
"38%",
"helicity",
"throughout",
"the",
"simulation,",
"being",
"relatively",
"less",
"stable",
"than",
"α-BP100",
"in",
"bilayers",
"containing",
"DPPG,",
"where",
"a",
"higher",
"propensity",
"of",
"maintaining",
"its",
"conformation",
"was",
"observed.",
"For",
"pure",
"DPPG",
"(Fig.",
"5b",
")",
"we",
"found",
"73%",
"(8",
"out",
"of",
"11",
"residues),",
"and",
"for",
"both",
"PCPG",
"(1:1)",
"membranes",
"we",
"report",
"54%",
"(6",
"out",
"of",
"11)",
"of",
"helicity",
"(Fig.",
"5c,d",
")."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"5",
").",
"This",
"secondary",
"structure",
"pattern",
"led",
"us",
"to",
"suggest",
"that",
"the",
"residues",
"5",
"to",
"9",
"are",
"related",
"to",
"helix",
"nucleation,",
"in",
"which",
"the",
"formation",
"of",
"this",
"helix",
"core",
"could",
"be",
"the",
"first",
"step",
"in",
"the",
"AMP",
"actions.",
"Following",
"this",
"assumption,",
"we",
"tested",
"three",
"conformations",
"with",
"α-BP100",
"torsionally",
"constrained",
"in",
"three",
"regions:",
"res1–5,",
"res4–8,",
"res7–11",
"(Fig.",
"3",
")",
"and",
"simulated",
"with",
"pure",
"DPPG",
"membranes.",
"Figure",
"6",
"shows",
"the",
"evolution",
"of",
"the",
"secondary",
"structure",
"in",
"each",
"simulation.",
"Figure",
"6",
"Secondary",
"structure",
"analyses",
"graphs",
"of",
"BP100",
"in",
"DPPG",
"with",
"one",
"turn",
"constraints",
"on",
"res1–5",
"(",
"a",
"),",
"res",
"4–8",
"(",
"b",
")",
"and",
"res7–11",
"(",
"c",
").",
"α-BP100",
"with",
"constraints",
"on",
"residues",
"1–5",
"(Lys-Lys-Leu-Phe-Lys)",
"acquired",
"identical",
"helicity",
"(73%)",
"to",
"α-BP100",
"with",
"no",
"constraints",
"at",
"the",
"same",
"conditions",
"(Fig.",
"5b",
"),",
"after",
"50",
"ns",
"of",
"simulation",
"(Fig.",
"6a",
"),",
"with",
"a",
"helix",
"spanning",
"from",
"Lys2",
"to",
"Lys9",
"(Fig.",
"6a",
").",
"Constraints",
"on",
"residues",
"4–8",
"(Phe-Lys-Lys-Ile-Leu)",
"showed",
"an",
"overall",
"52%",
"of",
"helicity",
"(Fig.",
"6b",
"),",
"with",
"a",
"helix",
"spanning",
"from",
"Phe4",
"to",
"Lys9",
"(Fig.",
"6b",
").",
"Constraints",
"on",
"residues",
"7–11",
"(Ile-Leu-Lys-Tyr-Leu)",
"did",
"not",
"affect",
"the",
"rest",
"of",
"the",
"peptide",
"conformation",
"(Fig.",
"6c",
")",
"in",
"600",
"ns",
"of",
"simulation.",
"Peptide",
"flip",
"Simulation",
"trajectories",
"analyses",
"(Fig.",
"7",
")",
"revealed",
"that",
"the",
"peptide",
"in",
"alpha-helix",
"conformation",
"initially",
"adsorbed",
"at",
"the",
"DPPG-containing",
"membranes",
"interface",
"with",
"its",
"hydrophilic",
"facet",
"in",
"contact",
"with",
"the",
"membrane,",
"leaving",
"the",
"hydrophobic",
"facet",
"exposed",
"to",
"water.",
"We",
"observed",
"that",
"the",
"alpha-helix",
"rotated,",
"inserting",
"the",
"hydrophobic",
"facet",
"into",
"the",
"hydrophobic",
"region",
"of",
"the",
"membrane.",
"We",
"define",
"this",
"dynamic",
"phenomenon,",
"observed",
"in",
"our",
"simulations,",
"as",
"peptide",
"flip."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
[
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[
"Peptide",
"flip",
"was",
"also",
"observed",
"in",
"α",
"-BP100",
"in",
"DPPC,",
"α",
"-BP100",
"in",
"PCPG-R,",
"and",
"α",
"-BP100",
"res(1–5)",
"in",
"DPPG",
"simulations.",
"The",
"peptide",
"flip",
"caused",
"dehydration",
"(Fig.",
"8",
").",
"When",
"in",
"contact",
"with",
"membranes,",
"depending",
"on",
"the",
"secondary",
"structure",
"of",
"the",
"peptide",
"and",
"the",
"lipid",
"nature,",
"the",
"hydration",
"of",
"the",
"peptide",
"was",
"slightly",
"different.",
"However,",
"when",
"the",
"peptide",
"flip",
"took",
"place,",
"its",
"hydration",
"was",
"drastically",
"altered.",
"Figure",
"8",
"Average",
"number",
"of",
"water",
"molecules",
"up",
"to",
"a",
"distance",
"of",
"0.5",
"nm,",
"N(0.5),",
"obtained",
"from",
"the",
"minimum-distance",
"distribution",
"function",
"(MDDF),",
"between",
"L-BP100",
"(",
"a",
")",
"and",
"α",
"-BP100",
"(",
"b",
")",
"and",
"water",
"molecules.",
"Vertical",
"lines",
"indicate",
"when",
"peptide",
"flip",
"occurred.",
"In",
"the",
"peptide/membrane",
"simulations",
"with",
"L-BP100",
"as",
"a",
"starting",
"configuration",
"(Fig.",
"8a",
"),",
"no",
"significant",
"change",
"in",
"the",
"number",
"of",
"water",
"molecules",
"surrounding",
"the",
"peptide",
"was",
"observed",
"in",
"comparison",
"the",
"150",
"obtained",
"in",
"the",
"bulk",
"aqueous",
"solution.",
"In",
"the",
"last",
"500",
"ns",
"of",
"simulation,",
"N(0.5)",
"was",
"approximately",
"178",
"±",
"11",
"in",
"DPPC,",
"145",
"±",
"7",
"in",
"DPPG,",
"145",
"±",
"13",
"in",
"PCPG-NR,",
"and",
"148",
"±",
"3",
"in",
"PCPG-R.",
"No",
"peptide",
"flip",
"was",
"detected",
"in",
"the",
"trajectories",
"for",
"those",
"simulations.",
"However,",
"in",
"the",
"peptide/membrane",
"simulations",
"with",
"α-BP100",
"as",
"a",
"starting",
"configuration",
"(Fig.",
"8b",
"),",
"N",
"(0.5)",
"lowered",
"in",
"DPPC",
"(starting",
"at",
"~700",
"ns),",
"DPPG",
"(~1500",
"ns)",
"and",
"PCPG-R",
"(~390",
"ns).",
"Alongside",
"with",
"dehydration,",
"a",
"peptide-flip",
"was",
"observed",
"in",
"DPPG",
"and",
"PCPG-R.",
"For",
"the",
"α-",
"BP100",
"in",
"DPPC",
"simulation,",
"we",
"observed",
"a",
"semi-flip,",
"as",
"the",
"peptide",
"alpha-helical",
"conformation",
"was",
"only",
"38%",
"(Fig.",
"5a",
"),",
"suggesting",
"that",
"the",
"peptide",
"overall",
"polar/apolar",
"segregation",
"(Fig.",
"2c",
")",
"was",
"lost.",
"The",
"peptide",
"flip",
"transition",
"time",
"varied",
"from",
"100",
"to",
"400",
"ns."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Alongside",
"with",
"dehydration,",
"a",
"peptide-flip",
"was",
"observed",
"in",
"DPPG",
"and",
"PCPG-R.",
"For",
"the",
"α-",
"BP100",
"in",
"DPPC",
"simulation,",
"we",
"observed",
"a",
"semi-flip,",
"as",
"the",
"peptide",
"alpha-helical",
"conformation",
"was",
"only",
"38%",
"(Fig.",
"5a",
"),",
"suggesting",
"that",
"the",
"peptide",
"overall",
"polar/apolar",
"segregation",
"(Fig.",
"2c",
")",
"was",
"lost.",
"The",
"peptide",
"flip",
"transition",
"time",
"varied",
"from",
"100",
"to",
"400",
"ns.",
"During",
"the",
"peptide-flip,",
"in",
"the",
"simulations",
"of",
"α-BP100",
"in",
"DPPG",
"and",
"PCPG-R,",
"the",
"mean",
"number",
"N(0.5)",
"was",
"reduced",
"from",
"147",
"±",
"5",
"and",
"142",
"±",
"7",
"to",
"76",
"±",
"4",
"and",
"75",
"±",
"4,",
"respectively.",
"These",
"represent",
"on",
"average",
"a",
"reduction",
"of",
"approximately",
"48%",
"in",
"the",
"number",
"of",
"water",
"molecules",
"in",
"the",
"hydration",
"shell",
"of",
"α-BP100.",
"In",
"DPPC,",
"we",
"detected",
"a",
"smaller",
"decrease",
"in",
"the",
"hydration",
"of",
"α-BP100,",
"around",
"45%",
"(from",
"172",
"±",
"8",
"to",
"94",
"±",
"2),",
"having",
"around",
"20",
"water",
"molecules",
"more",
"after",
"the",
"semi-flip.",
"Figure",
"9",
"shows",
"the",
"density",
"profile",
"before",
"and",
"after",
"peptide",
"flip",
"for",
"α-BP100",
"in",
"DPPG",
"and",
"PCPG-R.",
"We",
"chose",
"residues",
"Lys5",
"and",
"Ile7",
"to",
"illustrate",
"the",
"changes",
"in",
"the",
"mean",
"position",
"of",
"hydrophobic",
"and",
"hydrophilic",
"residues",
"with",
"respect",
"to",
"the",
"membrane",
"due",
"to",
"the",
"peptide",
"flip.",
"These",
"residues",
"are",
"polar",
"and",
"apolar,",
"respectively,",
"and",
"located",
"opposite",
"to",
"each",
"other",
"when",
"in",
"an",
"alpha-helix",
"conformation",
"(Fig.",
"2c",
").",
"Trajectory",
"visualization",
"and",
"density",
"profile",
"(Figs",
"7",
"and",
"9",
")",
"clearly",
"show",
"the",
"distinct",
"orientation",
"in",
"BP100",
"hydrophobic",
"facet",
"before",
"and",
"after",
"peptide",
"flip.",
"During",
"the",
"initial",
"phase",
"of",
"approaching",
"towards",
"the",
"membrane,",
"BP100",
"polar",
"side",
"faces",
"the",
"membrane",
"with",
"its",
"N-terminal",
"residues",
"(Lys1",
"and",
"Lys2)",
"interacting",
"with",
"the",
"bilayer",
"headgroups.",
"After",
"the",
"flip,",
"the",
"apolar",
"residues",
"facet",
"turns",
"to",
"the",
"membrane,",
"and",
"simultaneously",
"inserts",
"into",
"the",
"bilayer,",
"below",
"the",
"carbonyl",
"carbons",
"(C31)",
"of",
"the",
"lipids",
"(Fig.",
"9",
").",
"Figure",
"9",
"Peptide",
"flip",
"observed",
"through",
"number",
"density",
"analysis."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"After",
"the",
"flip,",
"the",
"apolar",
"residues",
"facet",
"turns",
"to",
"the",
"membrane,",
"and",
"simultaneously",
"inserts",
"into",
"the",
"bilayer,",
"below",
"the",
"carbonyl",
"carbons",
"(C31)",
"of",
"the",
"lipids",
"(Fig.",
"9",
").",
"Figure",
"9",
"Peptide",
"flip",
"observed",
"through",
"number",
"density",
"analysis.",
"(",
"a",
"and",
"b",
")",
"show",
"respectively",
"before",
"and",
"after",
"the",
"flip",
"in",
"α",
"-BP100",
"in",
"DPPG",
"simulation;",
"c)",
"and",
"d)",
"demonstrate",
"the",
"flip",
"for",
"α",
"-BP100",
"in",
"PCPG-R",
"simulation.",
"Lys5",
"represents",
"the",
"polar",
"side",
"of",
"BP100",
"and",
"Ile7,",
"the",
"apolar",
"facet",
"(Fig.",
"2c",
").",
"OC3",
"(DPPG",
"head",
"group",
"further",
"out",
"glycerol",
"Oxygen),",
"N",
"chol",
"(DPPC",
"head",
"group",
"choline",
"Nitrogen),",
"P",
"(Phosphorus)",
"and",
"C31",
"(first",
"carbon",
"from",
"sn-1",
"acyl",
"chain)",
"are",
"shown",
"to",
"display",
"BP100",
"insertion",
"into",
"the",
"bilayer",
"after",
"the",
"flip.",
"Peptide",
"flip",
"was",
"not",
"observed",
"in",
"α-BP100",
"in",
"PCPG-NR,",
"where",
"DPPG",
"lipids",
"were",
"initially",
"scattered",
"randomly.",
"PG",
"content",
"might",
"be",
"related",
"to",
"the",
"occurrence",
"of",
"the",
"flip,",
"but",
"also,",
"the",
"PG",
"content",
"in",
"the",
"vicinity",
"of",
"BP100.",
"Several",
"studies",
"suggest",
"membrane-active",
"peptides",
"cause",
"anionic",
"lipid",
"clustering,",
"or",
"subdomain",
"formation,",
"upon",
"binding",
"to",
"bilayers",
"containing",
"neutral",
"and",
"charged",
"phospholipids",
"35",
"–",
"37",
".",
"The",
"same",
"mechanism",
"could",
"be",
"involved",
"in",
"BP100/bilayers",
"interactions.",
"Lipid",
"clustering",
"The",
"distribution",
"of",
"the",
"lipids",
"in",
"the",
"vicinity",
"of",
"BP100",
"was",
"evaluated",
"by",
"computing",
"the",
"total",
"number",
"of",
"lipids",
"in",
"contact",
"with",
"α-BP100",
"as",
"a",
"function",
"of",
"time",
"(Fig.",
"S5",
"),",
"the",
"time-averaged",
"values",
"(Table",
"2",
",",
"Fig.",
"10",
"),",
"and",
"the",
"lipid",
"raft",
"size",
"distribution",
"(Fig.",
"S6",
").",
"Table",
"2",
"Average",
"number",
"of",
"lipids",
"in",
"contact",
"with",
"BP100",
"in",
"simulations",
"using",
"α",
"-BP100",
"as",
"the",
"peptide",
"starting",
"configuration,",
"except",
"α",
"-BP100",
"(1–5),",
"which",
"had",
"permanent",
"constraints",
"on",
"residues",
"1",
"to",
"5.",
"Standard",
"deviations",
"are",
"shown",
"in",
"parenthesis."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Average",
"Number",
"of",
"Lipids",
"in",
"Contact",
"with",
"BP100",
"Simulation",
"Lipid",
"in",
"Contact",
"Average",
"α",
"-BP100",
"in",
"DPPC",
"DPPC",
"10.7",
"(±2.6)",
"α",
"-BP100",
"in",
"DPPG",
"DPPG",
"13.1",
"(±1.4)",
"α",
"-BP100",
"(1–5)",
"in",
"DPPG",
"DPPG",
"13.5",
"(±1.9)",
"α",
"-BP100",
"in",
"PCPG-R",
"Total",
"12.3",
"(±1.7)",
"DPPC",
"3.6",
"(±1.5)",
"DPPG",
"8.7",
"(±1.2)",
"α",
"-BP100",
"in",
"PCPG-NR",
"Total",
"11.0",
"(±1.7)",
"DPPC",
"2.7",
"(±1.3)",
"DPPG",
"8.3",
"(±1.6)",
"Figure",
"10",
"Average",
"Number",
"of",
"DPPCs",
"(",
"a",
")",
"and",
"DPPGs",
"(",
"b",
")",
"in",
"contact",
"with",
"BP100",
"analyzed",
"for",
"all",
"constraint-free",
"simulations",
"containing",
"BP100",
"in",
"an",
"initially",
"alpha",
"helical",
"conformation",
"in",
"DPPC,",
"DPPG,",
"PCPG-R",
"and",
"PCPG-NR",
"membranes.",
"Vertical",
"lines",
"represent",
"the",
"average",
"time",
"where",
"peptide",
"flip",
"was",
"observed.",
"Standard",
"deviation",
"error",
"bars",
"are",
"represented",
"as",
"fillings.",
"α-BP100",
"in",
"DPPC",
"simulation",
"had",
"on",
"average",
"10.7",
"peptide/lipid",
"contacts",
"(Table",
"2",
")",
"and",
"a",
"steady",
"increase",
"in",
"the",
"number",
"of",
"contact",
"lipids",
"(Figs",
"10b",
"and",
"S5a",
").",
"This",
"increase",
"is",
"due",
"to",
"the",
"peptide",
"losing",
"its",
"alpha-helical",
"conformation",
"(Fig.",
"5a",
"),",
"expanding",
"the",
"available",
"peptide",
"interaction",
"area",
"with",
"the",
"membrane.",
"Lipid",
"raft",
"size",
"distribution",
"also",
"shows",
"a",
"broader",
"distribution",
"of",
"DPPC",
"raft",
"size,",
"supporting",
"this",
"observation",
"(Fig.",
"S6a",
").",
"A",
"semi-peptide",
"flip",
"was",
"observed",
"at",
"~700",
"ns",
"of",
"simulation",
"and,",
"concomitantly,",
"while",
"BP100",
"inserts",
"into",
"the",
"bilayer",
"as",
"the",
"density",
"profile",
"shows",
"(Fig.",
"S4a,b",
"),",
"the",
"number",
"of",
"DPPCs",
"in",
"contact",
"with",
"BP100",
"increased",
"(Fig.",
"S5a",
")."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"S5a",
").",
"α-BP100",
"in",
"DPPG",
"simulation",
"shows",
"on",
"average",
"13.1",
"DPPGs",
"in",
"close",
"contact",
"with",
"the",
"peptide",
"(Table",
"2",
").",
"The",
"number",
"of",
"DPPGs",
"in",
"contact",
"rose",
"after",
"the",
"flip,",
"approximately",
"in",
"1500",
"ns",
"of",
"simulation",
"(Figs",
"10a",
"and",
"S5b",
")",
"and",
"concurrently,",
"BP100",
"inserted",
"deeply",
"into",
"the",
"membrane",
"(Fig.",
"7a,b",
").",
"Constrained",
"α-BP100",
"(res1–5)",
"in",
"DPPG,",
"which",
"showed",
"identical",
"alpha-helix",
"content",
"with",
"α-BP100",
"in",
"DPPG",
"(73%,",
"Figs",
"5b",
"and",
"6a",
"),",
"not",
"only",
"exhibits",
"peptide",
"flip",
"in",
"approximately",
"300",
"ns",
"of",
"simulation",
"but",
"also",
"has,",
"on",
"average,",
"13.5",
"DPPGs",
"in",
"contact",
"with",
"BP100",
"(Table",
"2",
").",
"In",
"the",
"simulation",
"with",
"α-BP100",
"in",
"PCPG-NR,",
"the",
"number",
"of",
"DPPG",
"in",
"contact",
"with",
"the",
"peptide",
"showed",
"a",
"slight",
"increase",
"(Fig.",
"10b",
"),",
"reaching",
"the",
"average",
"value",
"observed",
"in",
"the",
"simulation",
"with",
"PCPG-R",
"(Table",
"2",
").",
"Also,",
"lipid",
"raft",
"size",
"probability",
"analysis",
"(Fig.",
"S6d",
")",
"showed",
"a",
"narrower",
"peak",
"distribution",
"for",
"DPPGs",
"in",
"contact",
"with",
"BP100",
"in",
"PCPG-R",
"system,",
"compared",
"to",
"PCPG-NR",
"(Fig.",
"S6e",
"),",
"indicating",
"that",
"DPPG",
"lipid",
"raft",
"size",
"was",
"stable.",
"Peptide",
"flip",
"was",
"observed",
"in",
"the",
"PCPG-R",
"set",
"after",
"~390",
"ns",
"of",
"simulation",
"and",
"no",
"significant",
"variation",
"of",
"the",
"number",
"of",
"DPPG",
"in",
"contact",
"with",
"peptide",
"was",
"observed.",
"Polar",
"and",
"apolar",
"interaction",
"analysis",
"Peptide",
"contact",
"analysis",
"revealed",
"the",
"increase",
"of",
"lipid/peptide",
"contacts",
"after",
"peptide",
"flip",
"and",
"DPPG",
"clustering",
"on",
"PCPG",
"membranes.",
"We",
"analyzed",
"the",
"nature",
"of",
"the",
"intermolecular",
"interactions",
"that",
"determine",
"peptide-membrane",
"interactions",
"throughout",
"the",
"simulations.",
"We",
"calculated",
"the",
"number",
"of",
"polar",
"and",
"apolar",
"pair",
"contacts",
"between",
"peptide",
"atoms",
"and",
"membrane",
"atoms",
"(Figs",
"S7",
"–",
"S13",
").",
"Using",
"α-BP100",
"in",
"PCPG-R",
"system",
"as",
"an",
"example,",
"Fig.",
"11",
"shows",
"the",
"sum",
"of",
"the",
"10",
"most",
"frequent",
"apolar/polar",
"pairs",
"between",
"BP100",
"with",
"DPPC",
"and",
"DPPG."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Figure",
"11",
"BP100",
"pair",
"occurrence",
"with",
"DPPC",
"(",
"a",
")",
"and",
"DPPG",
"(",
"b",
")",
"for",
"α",
"-BP100",
"in",
"PCPG-R",
"simulation.",
"Graphs",
"show",
"the",
"sum",
"of",
"the",
"ten",
"most",
"frequent",
"apolar/polar",
"pairs",
"during",
"the",
"simulation.",
"Pairs",
"were",
"calculated",
"using",
"the",
"monolayer",
"facing",
"the",
"peptide.",
"Green",
"vertical",
"lines",
"indicate",
"when",
"peptide",
"flip",
"occurred",
"(circa",
"390",
"ns).",
"The",
"total",
"number",
"of",
"pairs,",
"regardless",
"if",
"it",
"is",
"polar",
"or",
"apolar,",
"between",
"BP100",
"and",
"DPPG",
"is",
"higher",
"than",
"that",
"with",
"DPPC",
"(Fig.",
"11",
"),",
"which",
"directly",
"reflects",
"on",
"the",
"number",
"of",
"lipids",
"in",
"contact",
"with",
"BP100",
"(Fig.",
"10",
").",
"During",
"the",
"initial",
"approach",
"of",
"the",
"peptide",
"towards",
"the",
"bilayer,",
"polar",
"interactions",
"between",
"charged",
"Lysines",
"and",
"DPPG",
"headgroup",
"dominate",
"the",
"interaction",
"(Figs",
"11",
"b,",
"S9",
",",
"S10",
",",
"S12",
"and",
"S13",
").",
"The",
"primary",
"interaction",
"was",
"between",
"positively",
"charged",
"(+1)",
"Lysine",
"side",
"chain",
"amino",
"group",
"(NZ)",
"and",
"DPPG",
"head",
"phosphoglycerol",
"group",
"oxygens",
"(OC2,",
"OC3),",
"even",
"after",
"peptide",
"flip",
"(Figs",
"S9",
",",
"S10",
",",
"S12",
"and",
"S13",
").",
"Before",
"the",
"peptide",
"flip,",
"the",
"number",
"of",
"polar",
"contacts",
"is",
"higher",
"than",
"the",
"apolar",
"contacts",
"for",
"DPPG/BP100.",
"As",
"the",
"peptide",
"starts",
"to",
"flip,",
"the",
"number",
"of",
"apolar",
"contacts",
"increase,",
"while",
"the",
"polar",
"contacts",
"decrease.",
"After",
"the",
"peptide",
"flip",
"is",
"completed,",
"apolar",
"contacts",
"are",
"as",
"numerous",
"as",
"the",
"polar",
"contacts",
"(Fig.",
"11a,b",
"and",
"S7–10,13",
").",
"Also,",
"after",
"the",
"flip,",
"apolar",
"contacts",
"between",
"BP100",
"and",
"DPPG",
"were",
"more",
"frequent",
"than",
"with",
"DPPC",
"(Fig.",
"11b",
").",
"The",
"higher",
"peptide/DPPG",
"apolar",
"contact",
"frequency",
"after",
"the",
"flip",
"is",
"also",
"observed",
"for",
"other",
"simulations",
"with",
"peptide",
"flip",
"(Figs",
"S7",
"–",
"10",
",",
"13).",
"Discussion",
"Peptide",
"secondary",
"structure",
"CD",
"spectra",
"of",
"BP100",
"in",
"solution",
"and",
"POPC",
"LUVs",
"show",
"no",
"secondary",
"structure",
"10",
",",
"11",
",",
"30",
"Our",
"simulations",
"with",
"BP100",
"in",
"solution,",
"and",
"DPPC",
"membrane",
"exhibited",
"the",
"same",
"pattern."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"The",
"primary",
"interaction",
"was",
"between",
"positively",
"charged",
"(+1)",
"Lysine",
"side",
"chain",
"amino",
"group",
"(NZ)",
"and",
"DPPG",
"head",
"phosphoglycerol",
"group",
"oxygens",
"(OC2,",
"OC3),",
"even",
"after",
"peptide",
"flip",
"(Figs",
"S9",
",",
"S10",
",",
"S12",
"and",
"S13",
").",
"Before",
"the",
"peptide",
"flip,",
"the",
"number",
"of",
"polar",
"contacts",
"is",
"higher",
"than",
"the",
"apolar",
"contacts",
"for",
"DPPG/BP100.",
"As",
"the",
"peptide",
"starts",
"to",
"flip,",
"the",
"number",
"of",
"apolar",
"contacts",
"increase,",
"while",
"the",
"polar",
"contacts",
"decrease.",
"After",
"the",
"peptide",
"flip",
"is",
"completed,",
"apolar",
"contacts",
"are",
"as",
"numerous",
"as",
"the",
"polar",
"contacts",
"(Fig.",
"11a,b",
"and",
"S7–10,13",
").",
"Also,",
"after",
"the",
"flip,",
"apolar",
"contacts",
"between",
"BP100",
"and",
"DPPG",
"were",
"more",
"frequent",
"than",
"with",
"DPPC",
"(Fig.",
"11b",
").",
"The",
"higher",
"peptide/DPPG",
"apolar",
"contact",
"frequency",
"after",
"the",
"flip",
"is",
"also",
"observed",
"for",
"other",
"simulations",
"with",
"peptide",
"flip",
"(Figs",
"S7",
"–",
"10",
",",
"13).",
"Discussion",
"Peptide",
"secondary",
"structure",
"CD",
"spectra",
"of",
"BP100",
"in",
"solution",
"and",
"POPC",
"LUVs",
"show",
"no",
"secondary",
"structure",
"10",
",",
"11",
",",
"30",
"Our",
"simulations",
"with",
"BP100",
"in",
"solution,",
"and",
"DPPC",
"membrane",
"exhibited",
"the",
"same",
"pattern.",
"α-BP100",
"and",
"L-BP100",
"in",
"solution",
"showed",
"similar",
"behavior,",
"with",
"a",
"prevalence",
"of",
"random",
"conformation",
"(Fig.",
"4",
").",
"In",
"a",
"related",
"MD",
"study",
"of",
"AMPs",
"interacting",
"with",
"membranes",
"17",
",",
"an",
"8",
"µs-long",
"all-atom",
"MD",
"simulation",
"of",
"BP100",
"in",
"DMPC",
"at",
"35◽",
"the",
"authors",
"reported",
"a",
"full",
"helix",
"length",
"during",
"1.5",
"µs",
"and",
"a",
"subsequent",
"unfolding",
"event",
"of",
"Lysines",
"at",
"positions",
"1",
"and",
"2,",
"resulting",
"in",
"81%",
"of",
"helicity",
"on",
"a",
"pure",
"zwitterionic",
"bilayer.",
"However,",
"as",
"reported",
"for",
"other",
"simulated",
"peptides",
"in",
"the",
"same",
"work,",
"the",
"forcefield",
"used",
"could",
"result",
"in",
"an",
"over-helical",
"artifact",
"17",
".",
"A",
"Brownian",
"Dynamics",
"simulation",
"study",
"of",
"BP100",
"confined",
"inside",
"an",
"implicit",
"POPC",
"membrane",
"reports",
"a",
"stable",
"alpha-helix",
"18",
"."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
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[
"Peptide-lipid",
"pair",
"analysis",
"(Fig.",
"S7",
")",
"showed",
"that",
"cationic",
"Lysine",
"residues",
"interacted",
"mainly",
"with",
"phosphate",
"groups",
"of",
"the",
"DPPC",
"bilayer,",
"evidencing",
"that",
"electrostatic",
"interactions",
"were",
"present.",
"In",
"the",
"case",
"of",
"L-BP100",
"in",
"DPPC,",
"no",
"alpha-helical",
"structure",
"formation",
"was",
"observed",
"(Fig.",
"S3",
"),",
"and",
"for",
"α-BP100,",
"the",
"peptide",
"alpha-helix",
"conformation",
"was",
"mostly",
"lost,",
"although",
"one",
"helix",
"turn",
"from",
"residues",
"5",
"to",
"9",
"remained",
"(Fig.",
"5A",
").",
"The",
"minimum",
"alpha-helix",
"length",
"detected",
"by",
"CD",
"spectroscopy",
"is",
"proposed",
"to",
"encompass",
"seven",
"to",
"eleven",
"residues",
"38",
",",
"hence",
"the",
"alpha-helix",
"turn",
"in",
"residues",
"5–9",
"might",
"not",
"be",
"detected",
"by",
"CD.",
"Alternatively,",
"this",
"could",
"be",
"an",
"over-helical",
"forcefield",
"artifact",
"22",
",",
"but",
"it",
"also",
"indicates",
"the",
"high",
"stability",
"of",
"the",
"alpha-helix",
"formed",
"by",
"the",
"(5–9)",
"Lys-Lys-Ile-Leu-Lys",
"sequence.",
"This",
"stability",
"leads",
"us",
"to",
"conjecture",
"that",
"BP100",
"alpha-helix",
"formation",
"could",
"be",
"initiated",
"through",
"a",
"core",
"sequence,",
"a",
"nascent",
"helix",
"39",
".",
"The",
"negatively",
"charged",
"membrane",
"interface",
"could",
"promote",
"the",
"initial",
"peptide",
"folding.",
"To",
"support",
"this,",
"we",
"performed",
"three",
"600",
"ns-long",
"simulations",
"with",
"constrained",
"alpha",
"helices",
"of",
"BP100",
"on",
"three",
"regions:",
"residues",
"1",
"to",
"5",
"(Lys-Lys-Leu-Phe-Lys),",
"4",
"to",
"8",
"(Phe-Lys-Lys-Ile-Leu)",
"and",
"7",
"to",
"11",
"(Ile-Leu-Lys-Tyr-Leu)",
"in",
"pure",
"DPPG",
"bilayers.",
"The",
"secondary",
"structure",
"analysis",
"of",
"the",
"constrained",
"BP100",
"simulations",
"yielded",
"different",
"outcomes.",
"Constraint",
"on",
"residues",
"1",
"to",
"5",
"rapidly",
"induced",
"almost",
"full",
"alpha-helix",
"content",
"from",
"Lys2",
"to",
"Lys9",
"(Fig.",
"6A",
"),",
"reaching",
"73%",
"of",
"helicity,",
"similar",
"to",
"α-BP100",
"in",
"DPPG",
"without",
"constraints",
"(Fig.",
"5B",
").",
"Constraint",
"on",
"residues",
"4",
"to",
"8",
"also",
"showed",
"a",
"helix",
"formation",
"tendency",
"(overall",
"63%",
"helicity,",
"5",
"out",
"of",
"11",
"residues,",
"from",
"Phe4",
"to",
"Lys9)."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"We",
"find",
"1.53",
"kcal/mol",
"for",
"residues",
"1",
"to",
"5",
"(Lys-Lys-Leu-Phe-Lys),",
"1.68",
"kcal/mol",
"for",
"residues",
"4",
"to",
"8",
"(Phe-Lys-Lys-Ile-Leu),",
"and",
"1.62",
"kcal/mol",
"for",
"residues",
"7–11",
"(Ile-Leu-Lys-Tyr-Leu).",
"Our",
"secondary",
"structure",
"data",
"indicates",
"that",
"BP100",
"nascent",
"helix",
"could",
"be",
"formed",
"either",
"in",
"the",
"region",
"between",
"residues",
"1",
"to",
"5",
"or",
"between",
"residues",
"5",
"to",
"9.",
"We",
"favor",
"the",
"latter",
"due",
"to",
"the",
"presence",
"of",
"positively",
"charged",
"Lysine",
"residues",
"in",
"the",
"N-terminal",
"side",
"(Lys1",
"and",
"Lys2)",
"which",
"could",
"produce",
"an",
"energetically",
"unfavorable",
"barrier",
"to",
"initial",
"peptide",
"folding.",
"The",
"5–9",
"region",
"shows",
"high",
"stability",
"in",
"all",
"constraint-free",
"α-BP100/membranes",
"simulations",
"and",
"has",
"the",
"overall",
"lowest",
"energy",
"barrier",
"in",
"the",
"helix",
"propensity",
"scale",
"40",
".",
"DPPG",
"seems",
"to",
"have",
"a",
"helix-stabilizing",
"effect",
"on",
"BP100.",
"All",
"the",
"simulations",
"with",
"α-BP100",
"in",
"DPPG-containing-membranes",
"showed",
"high",
"alpha-helical",
"content,",
"including",
"the",
"region",
"of",
"residues",
"5",
"to",
"9.",
"Our",
"helicity",
"results",
"from",
"the",
"simulations",
"with",
"α-BP100",
"in",
"pure",
"DPPG",
"(73%)",
"and",
"in",
"PCPG",
"(50:50)",
"mixed",
"bilayers",
"(54%)",
"are",
"remarkably",
"close",
"to",
"those",
"reported",
"in",
"experimental",
"studies:",
"54%",
"in",
"POPC:POPG",
"(50:50)",
"11",
"and",
"61%",
"in",
"DMPC/DMPG",
"(75:25)",
"LUVs",
"10",
",",
"and",
"maximum",
"observable",
"alpha-helix",
"spectrum",
"for",
"BP100",
"in",
"pure",
"POPG",
"vesicles",
"11",
"proving",
"that",
"BP100",
"alpha-helical",
"structure",
"is",
"dependent",
"on",
"PG",
"content",
"11",
".",
"For",
"L-BP100",
"simulations",
"with",
"DPPG,",
"PCPG-R,",
"and",
"PCPG-NR,",
"no",
"secondary",
"structure",
"formation",
"was",
"detected",
"(Fig.",
"S3",
"),",
"with",
"the",
"peptide",
"being",
"in",
"a",
"random",
"conformation.",
"Non-biased",
"random",
"peptide",
"simulations",
"require",
"much",
"longer",
"simulation",
"time",
"to",
"sample",
"the",
"peptide",
"conformational",
"potential",
"landscape",
"or",
"might",
"dwell",
"in",
"several",
"local",
"minimum-energy",
"states."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"For",
"L-BP100",
"simulations",
"with",
"DPPG,",
"PCPG-R,",
"and",
"PCPG-NR,",
"no",
"secondary",
"structure",
"formation",
"was",
"detected",
"(Fig.",
"S3",
"),",
"with",
"the",
"peptide",
"being",
"in",
"a",
"random",
"conformation.",
"Non-biased",
"random",
"peptide",
"simulations",
"require",
"much",
"longer",
"simulation",
"time",
"to",
"sample",
"the",
"peptide",
"conformational",
"potential",
"landscape",
"or",
"might",
"dwell",
"in",
"several",
"local",
"minimum-energy",
"states.",
"Peptide",
"flip",
"BP100",
"is",
"too",
"short",
"to",
"span",
"the",
"bilayer",
"thickness,",
"especially",
"in",
"the",
"alpha-helical",
"conformation,",
"and",
"thus",
"single",
"molecule",
"pore",
"formation",
"is",
"an",
"unlikely",
"scenario.",
"NMR",
"data",
"of",
"BP100",
"in",
"DMPC:",
"DMPG",
"(3:1)",
"10",
"shows",
"that",
"upon",
"binding",
"to",
"negatively",
"charged",
"membranes,",
"alpha-helical",
"BP100",
"positions",
"parallel",
"to",
"the",
"membrane",
"as",
"in",
"a",
"surface-bound",
"orientation,",
"and",
"has",
"an",
"azimuthal",
"rotation",
"angle",
"close",
"to",
"160°,",
"with",
"Lysine",
"residues",
"facing",
"the",
"solvent.",
"This",
"last",
"arrangement",
"is",
"commonly",
"observed",
"with",
"other",
"CAMPs",
"30",
"–",
"33",
".",
"Peptide/membrane",
"simulations",
"with",
"initially",
"alpha-helical",
"BP100",
"had",
"its",
"polar",
"moiety",
"facing",
"the",
"membrane,",
"for",
"being",
"the",
"most",
"probable",
"scenario",
"in",
"a",
"physical",
"environment.",
"In",
"the",
"α-BP100",
"in",
"DPPG",
"(Fig.",
"7",
"),",
"α-BP100",
"in",
"DPPC,",
"α-BP100",
"in",
"PCPG-R",
"and",
"α-BP100",
"(res1–5)",
"in",
"DPPG",
"simulations",
"trajectories,",
"we",
"observed",
"the",
"binding",
"of",
"BP100",
"from",
"bulk",
"solution",
"to",
"the",
"membranes",
"with",
"its",
"Lysines",
"residues",
"pointing",
"towards",
"the",
"bilayer,",
"and",
"then,",
"the",
"peptide",
"rotated,",
"leaving",
"its",
"apolar",
"facet",
"facing",
"the",
"interior",
"of",
"the",
"bilayer.",
"We",
"termed",
"this",
"transition",
"peptide",
"flip.",
"Although",
"BP100",
"surface-bound",
"state",
"is",
"reported",
"12",
",",
"17",
",",
"no",
"previous",
"peptide/membrane",
"MD",
"simulation",
"work",
"has",
"reported",
"a",
"peptide",
"flip",
"transition.",
"Peptide",
"flip",
"brings",
"significant",
"outcomes",
"regarding",
"BP100",
"localization",
"in",
"the",
"membrane,",
"in",
"peptide/membrane",
"interaction",
"and",
"the",
"peptide",
"hydration,",
"possibly",
"being",
"a",
"crucial",
"step",
"of",
"carpet",
"mechanism",
"for",
"BP100",
"and",
"other",
"CAMPs.",
"Through",
"the",
"density",
"profile,",
"we",
"observed",
"deep",
"penetration",
"of",
"the",
"peptide",
"into",
"the",
"membrane",
"through",
"its",
"apolar",
"residues",
"with",
"larger",
"side-chains,",
"after",
"the",
"flip",
"(Fig.",
"7",
")."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Through",
"the",
"density",
"profile,",
"we",
"observed",
"deep",
"penetration",
"of",
"the",
"peptide",
"into",
"the",
"membrane",
"through",
"its",
"apolar",
"residues",
"with",
"larger",
"side-chains,",
"after",
"the",
"flip",
"(Fig.",
"7",
").",
"BP100",
"hydration",
"analysis",
"also",
"shows",
"a",
"decrease",
"in",
"the",
"overall",
"peptide",
"hydration",
"after",
"the",
"flip",
"(Fig.",
"8",
").",
"Apolar/polar",
"pair",
"interaction",
"analysis",
"(Fig.",
"11",
")",
"revealed",
"that",
"after",
"the",
"flip,",
"the",
"number",
"of",
"contacts",
"between",
"apolar",
"residues",
"from",
"the",
"lipids",
"and",
"the",
"peptide",
"increases",
"significantly,",
"while",
"the",
"number",
"of",
"contacts",
"between",
"polar",
"groups",
"of",
"the",
"lipids",
"and",
"the",
"peptides",
"slightly",
"decreases.",
"In",
"other",
"words,",
"peptide",
"flip",
"intensifies",
"peptide",
"binding",
"to",
"membranes",
"burying",
"the",
"apolar",
"residues",
"of",
"the",
"peptide",
"deeper",
"into",
"the",
"membrane",
"core.",
"We",
"investigated",
"what",
"factors",
"could",
"lead",
"to",
"the",
"occurrence",
"of",
"BP100",
"peptide",
"flip.",
"Membrane",
"composition",
"appears",
"to",
"have",
"a",
"significant",
"role.",
"For",
"BP100",
"alpha-helical",
"structure",
"formation",
"is",
"favored",
"in",
"negatively",
"charged",
"membranes",
"8",
".",
"In",
"our",
"simulations,",
"BP100",
"entirely",
"flipped",
"in",
"DPPG",
"enriched",
"regions",
"of",
"the",
"membrane.",
"Peptide",
"flip",
"was",
"detected",
"in",
"α-BP100",
"in",
"DPPG,",
"α-BP100",
"(res1–5)",
"in",
"DPPG",
"and",
"α-BP100",
"in",
"PCPG-R",
"systems.",
"No",
"peptide",
"flip",
"was",
"detected",
"in",
"the",
"other",
"constrained",
"BP100",
"simulations",
"(α-BP100",
"(res4–8)",
"in",
"DPPG",
"and",
"α-BP100",
"(res7–11)",
"in",
"DPPG).",
"However,",
"it",
"is",
"hasty",
"to",
"affirm",
"that",
"it",
"is",
"unlikely",
"to",
"expect",
"peptide",
"flip",
"to",
"happen",
"in",
"those",
"systems",
"with",
"600",
"ns",
"of",
"simulation",
"time.",
"For",
"instance,",
"peptide",
"flip",
"was",
"observed",
"after",
"1.4",
"µs",
"of",
"simulation",
"in",
"α-BP100",
"in",
"DPPG.",
"Hydration",
"analysis",
"(Fig.",
"8b",
")",
"and",
"density",
"profile",
"(Fig.",
"S4A,B",
")",
"for",
"α-BP100",
"in",
"DPPC",
"show",
"also",
"that",
"BP100",
"flipped.",
"However,",
"the",
"alpha-helix",
"secondary",
"structure",
"is",
"mostly",
"lost",
"(Fig.",
"5a",
").",
"For",
"this",
"reason,",
"BP100",
"amphiphilic",
"apolar-polar",
"facet",
"separation",
"(Fig.",
"2c",
")",
"is",
"lost."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"For",
"instance,",
"peptide",
"flip",
"was",
"observed",
"after",
"1.4",
"µs",
"of",
"simulation",
"in",
"α-BP100",
"in",
"DPPG.",
"Hydration",
"analysis",
"(Fig.",
"8b",
")",
"and",
"density",
"profile",
"(Fig.",
"S4A,B",
")",
"for",
"α-BP100",
"in",
"DPPC",
"show",
"also",
"that",
"BP100",
"flipped.",
"However,",
"the",
"alpha-helix",
"secondary",
"structure",
"is",
"mostly",
"lost",
"(Fig.",
"5a",
").",
"For",
"this",
"reason,",
"BP100",
"amphiphilic",
"apolar-polar",
"facet",
"separation",
"(Fig.",
"2c",
")",
"is",
"lost.",
"Additionally,",
"the",
"apolar",
"moiety",
"of",
"the",
"peptide",
"could",
"have",
"a",
"crucial",
"role",
"in",
"peptide",
"flip.",
"Hydration",
"analysis",
"(Fig.",
"8",
")",
"suggests",
"peptide",
"flip",
"results",
"in",
"peptide",
"dehydration",
"and",
"concomitantly",
"enhances",
"peptide/lipid",
"interaction",
"(Fig.",
"11",
"),",
"increasing",
"specially",
"apolar",
"contacts",
"(Fig.",
"11",
").",
"Similar",
"behavior",
"was",
"observed",
"in",
"a",
"study",
"of",
"the",
"interaction",
"of",
"micelles",
"with",
"polyatomic",
"counterions",
"with",
"apolar",
"and",
"polar",
"moieties.",
"Experimental",
"results",
"and",
"MD",
"simulations",
"showed",
"that",
"counterions",
"with",
"the",
"same",
"apolar",
"groups",
"but",
"different",
"polar",
"groups",
"resulted",
"in",
"similar",
"ionic",
"affinities",
"for",
"dodecyltrimethylammonium",
"micelles,",
"and",
"the",
"simulations",
"showed",
"that",
"counterion",
"adsorption",
"to",
"the",
"micelles",
"was",
"related",
"with",
"the",
"dehydration",
"of",
"the",
"apolar",
"group",
"of",
"the",
"counterions",
"rather",
"than",
"by",
"the",
"polar",
"group",
"41",
".",
"These",
"factors",
"could",
"help",
"to",
"explain",
"BP100",
"selectivity",
"towards",
"negatively",
"charged",
"bacterial",
"membranes",
"and",
"low",
"cytotoxicity.",
"Results",
"of",
"leakage",
"from",
"the",
"inner",
"compartment",
"of",
"LUVs",
"upon",
"addition",
"of",
"BP100",
"showed",
"that",
"BP100",
"leakage",
"ability",
"is",
"proportional",
"to",
"PG",
"content",
"while",
"the",
"peptide",
"has",
"small",
"effects",
"on",
"zwitterionic",
"PC",
"vesicles,",
"observed",
"through",
"studies",
"of",
"zeta",
"potential",
"and",
"vesicle",
"leakage",
"11",
".",
"BP100",
"does",
"not",
"perturb",
"PC",
"bilayers",
"even",
"at",
"high",
"peptide/lipid",
"ratio",
"and",
"causes",
"membrane",
"thinning",
"on",
"mixed",
"DMPC/DMPG",
"bilayers",
"where",
"a",
"stronger",
"effect",
"appears",
"in",
"anionic",
"DMPG",
"lipids",
"compared",
"to",
"zwitterionic",
"DMPC",
"lipids",
"12",
"."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"BP100",
"does",
"not",
"perturb",
"PC",
"bilayers",
"even",
"at",
"high",
"peptide/lipid",
"ratio",
"and",
"causes",
"membrane",
"thinning",
"on",
"mixed",
"DMPC/DMPG",
"bilayers",
"where",
"a",
"stronger",
"effect",
"appears",
"in",
"anionic",
"DMPG",
"lipids",
"compared",
"to",
"zwitterionic",
"DMPC",
"lipids",
"12",
".",
"In",
"zwitterionic-lipid-enriched",
"mammalian",
"membranes,",
"BP100",
"would",
"bind",
"to",
"membranes",
"through",
"electrostatic",
"interactions",
"and",
"the",
"absence",
"of",
"a",
"helix-promoting",
"environment",
"would",
"prevent",
"helix",
"formation",
"and",
"even",
"with",
"peptide",
"flip,",
"as",
"in",
"our",
"α-BP100",
"in",
"DPPC",
"simulation,",
"it",
"could",
"lead",
"to",
"mild",
"membrane",
"thinning",
"11",
",",
"12",
".",
"On",
"the",
"other",
"hand,",
"bacterial",
"membranes",
"with",
"high",
"content",
"of",
"anionic",
"lipids",
"on",
"the",
"outer",
"part",
"of",
"the",
"membrane,",
"could",
"promote",
"peptide",
"binding,",
"alpha-helix",
"nucleation,",
"and",
"propagation,",
"leading",
"to",
"peptide",
"flip",
"and",
"more",
"pronounced",
"membrane",
"thinning,",
"which",
"is",
"consistent",
"with",
"our",
"observations",
"from",
"α-BP100",
"in",
"DPPG,",
"α-BP100",
"in",
"PCPG-R",
"and",
"α-BP100",
"(res1–5)",
"in",
"DPPG",
"sets.",
"Although",
"we",
"could",
"not",
"detect",
"membrane",
"thinning",
"in",
"our",
"simulations",
"(Table",
"S2",
"),",
"it",
"should",
"be",
"noted",
"that",
"our",
"simulations",
"had",
"only",
"one",
"peptide",
"on",
"128-lipid-bilayers.",
"A",
"more",
"pronounced",
"effect",
"on",
"the",
"membrane",
"might",
"be",
"observed",
"by",
"increasing",
"the",
"number",
"of",
"peptides",
"in",
"the",
"simulations.",
"DPPG",
"subdomain",
"formation",
"Lipid",
"clustering,",
"or",
"subdomain",
"formation,",
"induced",
"by",
"CAMPs",
"is",
"well",
"established",
"5",
",",
"14",
",",
"35",
"–",
"37",
",",
"42",
"–",
"45",
".",
"Through",
"electrostatic",
"interactions,",
"CAMPs",
"clusters",
"anionic",
"phosphatidylglycerol",
"(PG)",
"or",
"cardiolipin",
"(CL)",
"lipids",
"on",
"the",
"outer",
"membrane",
"of",
"bacteria,",
"inducing",
"phase",
"separation",
"and",
"phase",
"boundary",
"defects",
"between",
"lipid",
"domains",
"and",
"the",
"rest",
"of",
"the",
"membrane,",
"increasing",
"membrane",
"permeability",
"36",
".",
"Epand",
"et",
"al.",
"first",
"proposed",
"it",
"45",
",",
"in",
"a",
"study",
"with",
"oligomers",
"of",
"lysine",
"(OAK)."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Lipid",
"phase",
"separation",
"was",
"later",
"observed",
"for",
"other",
"cAMPs",
"and",
"cell-penetrating-peptides",
"37",
",",
"45",
",",
"46",
".",
"Although",
"not",
"so",
"pronounced,",
"DSC",
"also",
"detected",
"BP100",
"ability",
"to",
"promote",
"lipid",
"phase",
"separation",
"on",
"POPE/TOCL",
"(75:25)",
"vesicles",
"37",
".",
"Lipid",
"phase",
"separation",
"promoted",
"by",
"CAMPs",
"has",
"also",
"been",
"observed",
"in",
"computational",
"modeling",
"studies.",
"In",
"a",
"coarse-grained",
"MD",
"simulation",
"study",
"35",
",",
"lipid",
"cluster",
"promotion",
"was",
"seen",
"in",
"POPE/POPG",
"(70:30)",
"membranes",
"by",
"Ltc1,",
"a",
"linear",
"alpha-helical",
"cAMP",
"with",
"overall",
"+10",
"charge.",
"Simulations",
"showed",
"Ltc1",
"induced",
"POPG",
"domains",
"in",
"small",
"(256",
"lipids)",
"and",
"large",
"membranes",
"(512",
"or",
"2048",
"lipids).",
"Also,",
"due",
"to",
"peptide-POPG",
"charge",
"neutralization,",
"Ltc1-induced",
"anionic",
"domains",
"seem",
"to",
"facilitate",
"peptide",
"oligomerization,",
"enhancing",
"peptide",
"activity",
"on",
"bacterial",
"model",
"membranes",
"35",
".",
"Likewise,",
"our",
"simulations",
"suggest",
"that",
"BP100",
"promotes",
"PG",
"aggregation.",
"Two",
"DPPC:",
"DPPG",
"(50:50)",
"mixed",
"bilayers",
"were",
"designed",
"to",
"explore",
"lipid",
"aggregation",
"by",
"the",
"peptide.",
"One",
"membrane",
"was",
"composed",
"of",
"randomly",
"mixed",
"(PCPG-NR)",
"and",
"in",
"the",
"other,",
"a",
"4",
"×",
"4",
"DPPG",
"raft",
"(PCPG-R)",
"was",
"positioned",
"in",
"the",
"middle",
"of",
"both",
"monolayers",
"(see",
"Methods",
"1",
"and",
"Fig.",
"1",
").",
"BP100",
"was",
"able",
"to",
"cluster",
"DPPGs",
"in",
"PCPG-NR,",
"which",
"can",
"be",
"observed",
"by",
"the",
"amount",
"of",
"DPPG",
"in",
"contact",
"with",
"BP100",
"(Table",
"2",
").",
"From",
"a",
"total",
"of",
"11",
"lipids",
"in",
"the",
"closer",
"contact",
"with",
"BP100,",
"8.3",
"in",
"average",
"are",
"DPPG",
"corresponding",
"to",
"75%",
"of",
"the",
"lipid",
"in",
"the",
"vicinity",
"of",
"the",
"peptide.",
"Additionally,",
"this",
"DPPG",
"clustering",
"can",
"also",
"be",
"observed",
"in",
"lipid",
"raft",
"size",
"distribution",
"(Fig.",
"S6E",
"),",
"reaching",
"similar",
"values",
"of",
"DPPG/peptide",
"contact",
"in",
"α-BP100",
"in",
"PCPG-R",
"simulation",
"(Fig.",
"10",
")",
"and",
"DPPG",
"lipid",
"raft",
"size",
"probability",
"(Fig.",
"S6D",
")."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"S6D",
").",
"These",
"data",
"suggest",
"that",
"even",
"a",
"short-lengthened",
"CAMP",
"as",
"BP100",
"can",
"promote",
"anionic",
"lipid",
"clustering",
"and",
"also",
"maintain",
"it,",
"supporting",
"the",
"experimental",
"findings",
"37",
".",
"BP100",
"also",
"adsorbs",
"on",
"pure",
"zwitterionic",
"PC",
"membranes",
"and",
"promotes",
"DPPC",
"clustering",
"as",
"observed",
"in",
"Figs",
"S5",
"A",
"and",
"S6A",
".",
"However,",
"possibly",
"due",
"to",
"the",
"presence",
"of",
"positively",
"charged",
"choline",
"headgroups",
"(Fig.",
"1d",
"-",
"left),",
"secondary",
"structure",
"is",
"lost",
"(Fig.",
"5a",
")",
"and",
"the",
"peptide",
"turns",
"into",
"random",
"coil,",
"resulting",
"in",
"an",
"increase",
"of",
"available",
"interaction",
"surface",
"area",
"with",
"the",
"DPPC",
"headgroups,",
"which",
"is",
"reflected",
"in",
"a",
"broad",
"distribution",
"in",
"lipid",
"raft",
"size",
"distribution",
"(Fig.",
"S5A",
").",
"Polar/Apolar",
"pair",
"analysis",
"for",
"α-BP100",
"in",
"PCPG-R",
"(Fig.",
"11",
")",
"helps",
"to",
"explain",
"lipid",
"aggregation.",
"We",
"computed",
"the",
"ten",
"most",
"frequent",
"apolar",
"and",
"polar",
"pairs",
"between",
"peptide",
"and",
"lipids.",
"The",
"number",
"of",
"polar",
"pairs",
"between",
"the",
"peptide",
"and",
"DPPG",
"is",
"higher",
"than",
"those",
"with",
"DPPC",
"and",
"is",
"maintained",
"even",
"after",
"the",
"flip",
"(~390",
"ns).",
"As",
"expected,",
"+1",
"charged",
"amino",
"group",
"(NZ)",
"from",
"Lysines",
"side",
"chains",
"are",
"the",
"main",
"participants",
"in",
"polar",
"pairings",
"(Figs",
"S7",
"–",
"S13",
"),",
"interacting",
"with",
"DPPG",
"headgroup",
"glycerol",
"(OC2,",
"OC3,",
"Fig.",
"1d",
"-",
"right),",
"phosphate",
"group",
"(P),",
"and",
"carbonyl",
"groups",
"(C21,",
"C31,",
"O21,",
"O22,",
"O31,",
"O32)",
"from",
"chains",
"sn1",
"and",
"sn2",
"(Figs",
"S9",
",",
"S10",
",",
"S12",
",",
"S13",
").",
"Peptide",
"flip",
"seems",
"to",
"contribute",
"to",
"lipid",
"clustering.",
"Polar/apolar",
"pairs",
"analysis",
"(Fig.",
"11",
")",
"and",
"pair",
"frequency",
"(Figs",
"S8",
",",
"S9",
")",
"for",
"the",
"previous",
"simulation,",
"reveals",
"that",
"apolar",
"pairs",
"between",
"BP100",
"and",
"both",
"lipids",
"rise",
"after",
"peptide",
"flip",
"occurs",
"(~390",
"ns),",
"intensifying",
"peptide-membrane",
"interaction.",
"The",
"same",
"phenomena",
"were",
"observed",
"for",
"other",
"simulations",
"with",
"peptide",
"flip",
"(Figs",
"S7",
",",
"S10",
"and",
"S13",
")."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Peptide",
"flip",
"seems",
"to",
"contribute",
"to",
"lipid",
"clustering.",
"Polar/apolar",
"pairs",
"analysis",
"(Fig.",
"11",
")",
"and",
"pair",
"frequency",
"(Figs",
"S8",
",",
"S9",
")",
"for",
"the",
"previous",
"simulation,",
"reveals",
"that",
"apolar",
"pairs",
"between",
"BP100",
"and",
"both",
"lipids",
"rise",
"after",
"peptide",
"flip",
"occurs",
"(~390",
"ns),",
"intensifying",
"peptide-membrane",
"interaction.",
"The",
"same",
"phenomena",
"were",
"observed",
"for",
"other",
"simulations",
"with",
"peptide",
"flip",
"(Figs",
"S7",
",",
"S10",
"and",
"S13",
").",
"As",
"long",
"as",
"peptide",
"flip",
"had",
"occurred,",
"apolar",
"residue",
"side",
"chains",
"(from",
"Leu3,",
"Phe4,",
"Ile7,",
"Leu8",
"and",
"Tyr10,",
"and",
"Leu11)",
"were",
"in",
"close",
"contact",
"mainly",
"with",
"groups",
"of",
"the",
"lipid",
"tails",
"(Figs",
"S7",
"–",
"S10",
",",
"S13",
").",
"The",
"mechanisms",
"of",
"bacterial",
"toxicity",
"via",
"lipid",
"clustering",
"induced",
"by",
"CAMPs",
"still",
"has",
"to",
"be",
"investigated.",
"Moreover,",
"possibly",
"more",
"than",
"one",
"mechanism",
"could",
"be",
"involved",
"in",
"the",
"process",
"of",
"bacterial",
"killing.",
"Evidence",
"suggest",
"lipid",
"clustering",
"by",
"CAMPs",
"could",
"lead",
"to",
"negative",
"charge",
"concentration",
"on",
"membranes,",
"promoting",
"CAMPs",
"attachment,",
"leading",
"to",
"pore",
"formation",
"5",
".",
"Anionic",
"lipid",
"clustering",
"would",
"have",
"surrounding",
"interfaces",
"with",
"the",
"rest",
"of",
"the",
"membrane",
"which",
"could",
"lead",
"to",
"phase",
"boundary",
"defects,",
"leading",
"to",
"slow",
"leakage",
"of",
"inner",
"cell",
"content",
"32",
".",
"Also,",
"CAMPs",
"and",
"cell-penetrating",
"peptides",
"could",
"induce",
"negative",
"membrane",
"curvature,",
"enabling",
"the",
"internalization",
"of",
"peptides",
"into",
"cells,",
"leading",
"to",
"intracellular",
"killing",
"mechanisms.",
"The",
"formation",
"of",
"lipid",
"clusters",
"patches",
"would",
"also",
"lead",
"to",
"anomalies",
"in",
"membrane",
"protein",
"function,",
"membrane",
"fluidity,",
"and",
"membrane",
"polarization.",
"In",
"a",
"recent",
"study",
"5",
"with",
"cWFW,",
"a",
"cyclic",
"antimicrobial",
"peptide,",
"it",
"was",
"shown",
"in",
"vitro",
"and",
"in",
"vivo",
"that",
"cWFW",
"promotes",
"lipid",
"phase",
"separation,",
"a",
"sharp",
"decrease",
"in",
"membrane",
"fluidity.",
"The",
"significant",
"phase",
"separation",
"appears",
"to",
"cause",
"disorganization",
"of",
"membrane",
"proteins,",
"inhibiting",
"cell",
"wall",
"synthesis",
"and",
"inducing",
"autolysis.",
"BP100",
"mode",
"of",
"action",
"on",
"membranes",
"is",
"dependent",
"on",
"peptide/lipid",
"ratio",
"11",
",",
"47",
"."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Also,",
"due",
"to",
"peptide-POPG",
"charge",
"neutralization,",
"Ltc1-induced",
"anionic",
"domains",
"seem",
"to",
"facilitate",
"peptide",
"oligomerization,",
"enhancing",
"peptide",
"activity",
"on",
"bacterial",
"model",
"membranes",
"35",
".",
"Likewise,",
"our",
"simulations",
"suggest",
"that",
"BP100",
"promotes",
"PG",
"aggregation.",
"Two",
"DPPC:",
"DPPG",
"(50:50)",
"mixed",
"bilayers",
"were",
"designed",
"to",
"explore",
"lipid",
"aggregation",
"by",
"the",
"peptide.",
"One",
"membrane",
"was",
"composed",
"of",
"randomly",
"mixed",
"(PCPG-NR)",
"and",
"in",
"the",
"other,",
"a",
"4",
"×",
"4",
"DPPG",
"raft",
"(PCPG-R)",
"was",
"positioned",
"in",
"the",
"middle",
"of",
"both",
"monolayers",
"(see",
"Methods",
"1",
"and",
"Fig.",
"1",
").",
"BP100",
"was",
"able",
"to",
"cluster",
"DPPGs",
"in",
"PCPG-NR,",
"which",
"can",
"be",
"observed",
"by",
"the",
"amount",
"of",
"DPPG",
"in",
"contact",
"with",
"BP100",
"(Table",
"2",
").",
"From",
"a",
"total",
"of",
"11",
"lipids",
"in",
"the",
"closer",
"contact",
"with",
"BP100,",
"8.3",
"in",
"average",
"are",
"DPPG",
"corresponding",
"to",
"75%",
"of",
"the",
"lipid",
"in",
"the",
"vicinity",
"of",
"the",
"peptide.",
"Additionally,",
"this",
"DPPG",
"clustering",
"can",
"also",
"be",
"observed",
"in",
"lipid",
"raft",
"size",
"distribution",
"(Fig.",
"S6E",
"),",
"reaching",
"similar",
"values",
"of",
"DPPG/peptide",
"contact",
"in",
"α-BP100",
"in",
"PCPG-R",
"simulation",
"(Fig.",
"10",
")",
"and",
"DPPG",
"lipid",
"raft",
"size",
"probability",
"(Fig.",
"S6D",
").",
"These",
"data",
"suggest",
"that",
"even",
"a",
"short-lengthened",
"CAMP",
"as",
"BP100",
"can",
"promote",
"anionic",
"lipid",
"clustering",
"and",
"also",
"maintain",
"it,",
"supporting",
"the",
"experimental",
"findings",
"37",
".",
"BP100",
"also",
"adsorbs",
"on",
"pure",
"zwitterionic",
"PC",
"membranes",
"and",
"promotes",
"DPPC",
"clustering",
"as",
"observed",
"in",
"Figs",
"S5",
"A",
"and",
"S6A",
".",
"However,",
"possibly",
"due",
"to",
"the",
"presence",
"of",
"positively",
"charged",
"choline",
"headgroups",
"(Fig.",
"1d",
"-",
"left),",
"secondary",
"structure",
"is",
"lost",
"(Fig.",
"5a",
")",
"and",
"the",
"peptide",
"turns",
"into",
"random",
"coil,",
"resulting",
"in",
"an",
"increase",
"of",
"available",
"interaction",
"surface",
"area",
"with",
"the",
"DPPC",
"headgroups,",
"which",
"is",
"reflected",
"in",
"a",
"broad",
"distribution",
"in",
"lipid",
"raft",
"size",
"distribution",
"(Fig.",
"S5A",
")."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Although",
"we",
"could",
"not",
"detect",
"membrane",
"thinning",
"in",
"our",
"simulations",
"(Table",
"S2",
"),",
"it",
"should",
"be",
"noted",
"that",
"our",
"simulations",
"had",
"only",
"one",
"peptide",
"on",
"128-lipid-bilayers.",
"A",
"more",
"pronounced",
"effect",
"on",
"the",
"membrane",
"might",
"be",
"observed",
"by",
"increasing",
"the",
"number",
"of",
"peptides",
"in",
"the",
"simulations.",
"DPPG",
"subdomain",
"formation",
"Lipid",
"clustering,",
"or",
"subdomain",
"formation,",
"induced",
"by",
"CAMPs",
"is",
"well",
"established",
"5",
",",
"14",
",",
"35",
"–",
"37",
",",
"42",
"–",
"45",
".",
"Through",
"electrostatic",
"interactions,",
"CAMPs",
"clusters",
"anionic",
"phosphatidylglycerol",
"(PG)",
"or",
"cardiolipin",
"(CL)",
"lipids",
"on",
"the",
"outer",
"membrane",
"of",
"bacteria,",
"inducing",
"phase",
"separation",
"and",
"phase",
"boundary",
"defects",
"between",
"lipid",
"domains",
"and",
"the",
"rest",
"of",
"the",
"membrane,",
"increasing",
"membrane",
"permeability",
"36",
".",
"Epand",
"et",
"al.",
"first",
"proposed",
"it",
"45",
",",
"in",
"a",
"study",
"with",
"oligomers",
"of",
"lysine",
"(OAK).",
"Upon",
"the",
"addition",
"of",
"OAK",
"in",
"1-palmitoyl-2-oleoyl",
"phosphatidylethanolamine",
"(POPE)",
"and",
"tetraoleoyl",
"cardiolipin",
"(TOCL)",
"mixed",
"vesicles,",
"transition",
"temperature",
"shift",
"was",
"observed",
"through",
"differential",
"scanning",
"calorimetry,",
"indicating",
"lipid",
"phase",
"separation",
"45",
".",
"Lipid",
"phase",
"separation",
"was",
"later",
"observed",
"for",
"other",
"cAMPs",
"and",
"cell-penetrating-peptides",
"37",
",",
"45",
",",
"46",
".",
"Although",
"not",
"so",
"pronounced,",
"DSC",
"also",
"detected",
"BP100",
"ability",
"to",
"promote",
"lipid",
"phase",
"separation",
"on",
"POPE/TOCL",
"(75:25)",
"vesicles",
"37",
".",
"Lipid",
"phase",
"separation",
"promoted",
"by",
"CAMPs",
"has",
"also",
"been",
"observed",
"in",
"computational",
"modeling",
"studies.",
"In",
"a",
"coarse-grained",
"MD",
"simulation",
"study",
"35",
",",
"lipid",
"cluster",
"promotion",
"was",
"seen",
"in",
"POPE/POPG",
"(70:30)",
"membranes",
"by",
"Ltc1,",
"a",
"linear",
"alpha-helical",
"cAMP",
"with",
"overall",
"+10",
"charge.",
"Simulations",
"showed",
"Ltc1",
"induced",
"POPG",
"domains",
"in",
"small",
"(256",
"lipids)",
"and",
"large",
"membranes",
"(512",
"or",
"2048",
"lipids)."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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[
"For",
"BP100",
"alpha-helical",
"structure",
"formation",
"is",
"favored",
"in",
"negatively",
"charged",
"membranes",
"8",
".",
"In",
"our",
"simulations,",
"BP100",
"entirely",
"flipped",
"in",
"DPPG",
"enriched",
"regions",
"of",
"the",
"membrane.",
"Peptide",
"flip",
"was",
"detected",
"in",
"α-BP100",
"in",
"DPPG,",
"α-BP100",
"(res1–5)",
"in",
"DPPG",
"and",
"α-BP100",
"in",
"PCPG-R",
"systems.",
"No",
"peptide",
"flip",
"was",
"detected",
"in",
"the",
"other",
"constrained",
"BP100",
"simulations",
"(α-BP100",
"(res4–8)",
"in",
"DPPG",
"and",
"α-BP100",
"(res7–11)",
"in",
"DPPG).",
"However,",
"it",
"is",
"hasty",
"to",
"affirm",
"that",
"it",
"is",
"unlikely",
"to",
"expect",
"peptide",
"flip",
"to",
"happen",
"in",
"those",
"systems",
"with",
"600",
"ns",
"of",
"simulation",
"time.",
"For",
"instance,",
"peptide",
"flip",
"was",
"observed",
"after",
"1.4",
"µs",
"of",
"simulation",
"in",
"α-BP100",
"in",
"DPPG.",
"Hydration",
"analysis",
"(Fig.",
"8b",
")",
"and",
"density",
"profile",
"(Fig.",
"S4A,B",
")",
"for",
"α-BP100",
"in",
"DPPC",
"show",
"also",
"that",
"BP100",
"flipped.",
"However,",
"the",
"alpha-helix",
"secondary",
"structure",
"is",
"mostly",
"lost",
"(Fig.",
"5a",
").",
"For",
"this",
"reason,",
"BP100",
"amphiphilic",
"apolar-polar",
"facet",
"separation",
"(Fig.",
"2c",
")",
"is",
"lost.",
"Additionally,",
"the",
"apolar",
"moiety",
"of",
"the",
"peptide",
"could",
"have",
"a",
"crucial",
"role",
"in",
"peptide",
"flip.",
"Hydration",
"analysis",
"(Fig.",
"8",
")",
"suggests",
"peptide",
"flip",
"results",
"in",
"peptide",
"dehydration",
"and",
"concomitantly",
"enhances",
"peptide/lipid",
"interaction",
"(Fig.",
"11",
"),",
"increasing",
"specially",
"apolar",
"contacts",
"(Fig.",
"11",
").",
"Similar",
"behavior",
"was",
"observed",
"in",
"a",
"study",
"of",
"the",
"interaction",
"of",
"micelles",
"with",
"polyatomic",
"counterions",
"with",
"apolar",
"and",
"polar",
"moieties.",
"Experimental",
"results",
"and",
"MD",
"simulations",
"showed",
"that",
"counterions",
"with",
"the",
"same",
"apolar",
"groups",
"but",
"different",
"polar",
"groups",
"resulted",
"in",
"similar",
"ionic",
"affinities",
"for",
"dodecyltrimethylammonium",
"micelles,",
"and",
"the",
"simulations",
"showed",
"that",
"counterion",
"adsorption",
"to",
"the",
"micelles",
"was",
"related",
"with",
"the",
"dehydration",
"of",
"the",
"apolar",
"group",
"of",
"the",
"counterions",
"rather",
"than",
"by",
"the",
"polar",
"group",
"41",
"."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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[
"The",
"5–9",
"region",
"shows",
"high",
"stability",
"in",
"all",
"constraint-free",
"α-BP100/membranes",
"simulations",
"and",
"has",
"the",
"overall",
"lowest",
"energy",
"barrier",
"in",
"the",
"helix",
"propensity",
"scale",
"40",
".",
"DPPG",
"seems",
"to",
"have",
"a",
"helix-stabilizing",
"effect",
"on",
"BP100.",
"All",
"the",
"simulations",
"with",
"α-BP100",
"in",
"DPPG-containing-membranes",
"showed",
"high",
"alpha-helical",
"content,",
"including",
"the",
"region",
"of",
"residues",
"5",
"to",
"9.",
"Our",
"helicity",
"results",
"from",
"the",
"simulations",
"with",
"α-BP100",
"in",
"pure",
"DPPG",
"(73%)",
"and",
"in",
"PCPG",
"(50:50)",
"mixed",
"bilayers",
"(54%)",
"are",
"remarkably",
"close",
"to",
"those",
"reported",
"in",
"experimental",
"studies:",
"54%",
"in",
"POPC:POPG",
"(50:50)",
"11",
"and",
"61%",
"in",
"DMPC/DMPG",
"(75:25)",
"LUVs",
"10",
",",
"and",
"maximum",
"observable",
"alpha-helix",
"spectrum",
"for",
"BP100",
"in",
"pure",
"POPG",
"vesicles",
"11",
"proving",
"that",
"BP100",
"alpha-helical",
"structure",
"is",
"dependent",
"on",
"PG",
"content",
"11",
".",
"For",
"L-BP100",
"simulations",
"with",
"DPPG,",
"PCPG-R,",
"and",
"PCPG-NR,",
"no",
"secondary",
"structure",
"formation",
"was",
"detected",
"(Fig.",
"S3",
"),",
"with",
"the",
"peptide",
"being",
"in",
"a",
"random",
"conformation.",
"Non-biased",
"random",
"peptide",
"simulations",
"require",
"much",
"longer",
"simulation",
"time",
"to",
"sample",
"the",
"peptide",
"conformational",
"potential",
"landscape",
"or",
"might",
"dwell",
"in",
"several",
"local",
"minimum-energy",
"states.",
"Peptide",
"flip",
"BP100",
"is",
"too",
"short",
"to",
"span",
"the",
"bilayer",
"thickness,",
"especially",
"in",
"the",
"alpha-helical",
"conformation,",
"and",
"thus",
"single",
"molecule",
"pore",
"formation",
"is",
"an",
"unlikely",
"scenario.",
"NMR",
"data",
"of",
"BP100",
"in",
"DMPC:",
"DMPG",
"(3:1)",
"10",
"shows",
"that",
"upon",
"binding",
"to",
"negatively",
"charged",
"membranes,",
"alpha-helical",
"BP100",
"positions",
"parallel",
"to",
"the",
"membrane",
"as",
"in",
"a",
"surface-bound",
"orientation,",
"and",
"has",
"an",
"azimuthal",
"rotation",
"angle",
"close",
"to",
"160°,",
"with",
"Lysine",
"residues",
"facing",
"the",
"solvent.",
"This",
"last",
"arrangement",
"is",
"commonly",
"observed",
"with",
"other",
"CAMPs",
"30",
"–",
"33",
".",
"Peptide/membrane",
"simulations",
"with",
"initially",
"alpha-helical",
"BP100",
"had",
"its",
"polar",
"moiety",
"facing",
"the",
"membrane,",
"for",
"being",
"the",
"most",
"probable",
"scenario",
"in",
"a",
"physical",
"environment."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"The",
"negatively",
"charged",
"membrane",
"interface",
"could",
"promote",
"the",
"initial",
"peptide",
"folding.",
"To",
"support",
"this,",
"we",
"performed",
"three",
"600",
"ns-long",
"simulations",
"with",
"constrained",
"alpha",
"helices",
"of",
"BP100",
"on",
"three",
"regions:",
"residues",
"1",
"to",
"5",
"(Lys-Lys-Leu-Phe-Lys),",
"4",
"to",
"8",
"(Phe-Lys-Lys-Ile-Leu)",
"and",
"7",
"to",
"11",
"(Ile-Leu-Lys-Tyr-Leu)",
"in",
"pure",
"DPPG",
"bilayers.",
"The",
"secondary",
"structure",
"analysis",
"of",
"the",
"constrained",
"BP100",
"simulations",
"yielded",
"different",
"outcomes.",
"Constraint",
"on",
"residues",
"1",
"to",
"5",
"rapidly",
"induced",
"almost",
"full",
"alpha-helix",
"content",
"from",
"Lys2",
"to",
"Lys9",
"(Fig.",
"6A",
"),",
"reaching",
"73%",
"of",
"helicity,",
"similar",
"to",
"α-BP100",
"in",
"DPPG",
"without",
"constraints",
"(Fig.",
"5B",
").",
"Constraint",
"on",
"residues",
"4",
"to",
"8",
"also",
"showed",
"a",
"helix",
"formation",
"tendency",
"(overall",
"63%",
"helicity,",
"5",
"out",
"of",
"11",
"residues,",
"from",
"Phe4",
"to",
"Lys9).",
"In",
"sharp",
"contrast,",
"constraints",
"on",
"residues",
"7",
"to",
"11",
"(36%",
"of",
"helicity,",
"4",
"out",
"of",
"11",
"residues,",
"from",
"Lys7",
"to",
"Tyr10)",
"had",
"no",
"effects",
"on",
"the",
"secondary",
"structure",
"formation",
"of",
"BP100",
"during",
"600",
"ns",
"simulation",
"(Fig.",
"6C",
"),",
"indicating",
"that",
"this",
"region",
"has",
"little",
"influence",
"on",
"initial",
"peptide",
"folding.",
"Pace",
"and",
"Scholtz",
"40",
",",
"based",
"on",
"experimental",
"studies,",
"proposed",
"a",
"helix",
"propensity",
"scale",
"as",
"Δ(ΔG)",
"values",
"relative",
"to",
"Alanine",
"set",
"to",
"zero.",
"On",
"the",
"Pace",
"and",
"Scholtz",
"scale,",
"the",
"5–9",
"region",
"has",
"the",
"highest",
"helix",
"promoting",
"residues",
"(overall",
"helix",
"propensity",
"of",
"1.4",
"kcal/mol).",
"We",
"find",
"1.53",
"kcal/mol",
"for",
"residues",
"1",
"to",
"5",
"(Lys-Lys-Leu-Phe-Lys),",
"1.68",
"kcal/mol",
"for",
"residues",
"4",
"to",
"8",
"(Phe-Lys-Lys-Ile-Leu),",
"and",
"1.62",
"kcal/mol",
"for",
"residues",
"7–11",
"(Ile-Leu-Lys-Tyr-Leu)."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Also,",
"after",
"the",
"flip,",
"apolar",
"contacts",
"between",
"BP100",
"and",
"DPPG",
"were",
"more",
"frequent",
"than",
"with",
"DPPC",
"(Fig.",
"11b",
").",
"The",
"higher",
"peptide/DPPG",
"apolar",
"contact",
"frequency",
"after",
"the",
"flip",
"is",
"also",
"observed",
"for",
"other",
"simulations",
"with",
"peptide",
"flip",
"(Figs",
"S7",
"–",
"10",
",",
"13).",
"Discussion",
"Peptide",
"secondary",
"structure",
"CD",
"spectra",
"of",
"BP100",
"in",
"solution",
"and",
"POPC",
"LUVs",
"show",
"no",
"secondary",
"structure",
"10",
",",
"11",
",",
"30",
"Our",
"simulations",
"with",
"BP100",
"in",
"solution,",
"and",
"DPPC",
"membrane",
"exhibited",
"the",
"same",
"pattern.",
"α-BP100",
"and",
"L-BP100",
"in",
"solution",
"showed",
"similar",
"behavior,",
"with",
"a",
"prevalence",
"of",
"random",
"conformation",
"(Fig.",
"4",
").",
"In",
"a",
"related",
"MD",
"study",
"of",
"AMPs",
"interacting",
"with",
"membranes",
"17",
",",
"an",
"8",
"µs-long",
"all-atom",
"MD",
"simulation",
"of",
"BP100",
"in",
"DMPC",
"at",
"35◽",
"the",
"authors",
"reported",
"a",
"full",
"helix",
"length",
"during",
"1.5",
"µs",
"and",
"a",
"subsequent",
"unfolding",
"event",
"of",
"Lysines",
"at",
"positions",
"1",
"and",
"2,",
"resulting",
"in",
"81%",
"of",
"helicity",
"on",
"a",
"pure",
"zwitterionic",
"bilayer.",
"However,",
"as",
"reported",
"for",
"other",
"simulated",
"peptides",
"in",
"the",
"same",
"work,",
"the",
"forcefield",
"used",
"could",
"result",
"in",
"an",
"over-helical",
"artifact",
"17",
".",
"A",
"Brownian",
"Dynamics",
"simulation",
"study",
"of",
"BP100",
"confined",
"inside",
"an",
"implicit",
"POPC",
"membrane",
"reports",
"a",
"stable",
"alpha-helix",
"18",
".",
"However,",
"no",
"experimental",
"data",
"confirms",
"that",
"BP100",
"diffuses",
"freely",
"in",
"the",
"membrane",
"hydrophobic",
"space",
"and",
"no",
"secondary",
"structure",
"formation",
"is",
"reported",
"for",
"pure",
"POPC",
"vesicles",
"11",
".",
"In",
"our",
"simulations",
"of",
"α-BP100",
"and",
"L-BP100",
"in",
"DPPC",
"membrane,",
"the",
"peptide",
"quickly",
"approached",
"the",
"membrane",
"and",
"remained",
"on",
"the",
"surface",
"during",
"all",
"simulation.",
"Peptide-lipid",
"pair",
"analysis",
"(Fig.",
"S7",
")",
"showed",
"that",
"cationic",
"Lysine",
"residues",
"interacted",
"mainly",
"with",
"phosphate",
"groups",
"of",
"the",
"DPPC",
"bilayer,",
"evidencing",
"that",
"electrostatic",
"interactions",
"were",
"present.",
"In",
"the",
"case",
"of",
"L-BP100",
"in",
"DPPC,",
"no",
"alpha-helical",
"structure",
"formation",
"was",
"observed",
"(Fig.",
"S3",
"),",
"and",
"for",
"α-BP100,",
"the",
"peptide",
"alpha-helix",
"conformation",
"was",
"mostly",
"lost,",
"although",
"one",
"helix",
"turn",
"from",
"residues",
"5",
"to",
"9",
"remained",
"(Fig."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"In",
"the",
"last",
"500",
"ns",
"of",
"simulation,",
"N(0.5)",
"was",
"approximately",
"178",
"±",
"11",
"in",
"DPPC,",
"145",
"±",
"7",
"in",
"DPPG,",
"145",
"±",
"13",
"in",
"PCPG-NR,",
"and",
"148",
"±",
"3",
"in",
"PCPG-R.",
"No",
"peptide",
"flip",
"was",
"detected",
"in",
"the",
"trajectories",
"for",
"those",
"simulations.",
"However,",
"in",
"the",
"peptide/membrane",
"simulations",
"with",
"α-BP100",
"as",
"a",
"starting",
"configuration",
"(Fig.",
"8b",
"),",
"N",
"(0.5)",
"lowered",
"in",
"DPPC",
"(starting",
"at",
"~700",
"ns),",
"DPPG",
"(~1500",
"ns)",
"and",
"PCPG-R",
"(~390",
"ns).",
"Alongside",
"with",
"dehydration,",
"a",
"peptide-flip",
"was",
"observed",
"in",
"DPPG",
"and",
"PCPG-R.",
"For",
"the",
"α-",
"BP100",
"in",
"DPPC",
"simulation,",
"we",
"observed",
"a",
"semi-flip,",
"as",
"the",
"peptide",
"alpha-helical",
"conformation",
"was",
"only",
"38%",
"(Fig.",
"5a",
"),",
"suggesting",
"that",
"the",
"peptide",
"overall",
"polar/apolar",
"segregation",
"(Fig.",
"2c",
")",
"was",
"lost.",
"The",
"peptide",
"flip",
"transition",
"time",
"varied",
"from",
"100",
"to",
"400",
"ns.",
"During",
"the",
"peptide-flip,",
"in",
"the",
"simulations",
"of",
"α-BP100",
"in",
"DPPG",
"and",
"PCPG-R,",
"the",
"mean",
"number",
"N(0.5)",
"was",
"reduced",
"from",
"147",
"±",
"5",
"and",
"142",
"±",
"7",
"to",
"76",
"±",
"4",
"and",
"75",
"±",
"4,",
"respectively.",
"These",
"represent",
"on",
"average",
"a",
"reduction",
"of",
"approximately",
"48%",
"in",
"the",
"number",
"of",
"water",
"molecules",
"in",
"the",
"hydration",
"shell",
"of",
"α-BP100.",
"In",
"DPPC,",
"we",
"detected",
"a",
"smaller",
"decrease",
"in",
"the",
"hydration",
"of",
"α-BP100,",
"around",
"45%",
"(from",
"172",
"±",
"8",
"to",
"94",
"±",
"2),",
"having",
"around",
"20",
"water",
"molecules",
"more",
"after",
"the",
"semi-flip.",
"Figure",
"9",
"shows",
"the",
"density",
"profile",
"before",
"and",
"after",
"peptide",
"flip",
"for",
"α-BP100",
"in",
"DPPG",
"and",
"PCPG-R.",
"We",
"chose",
"residues",
"Lys5",
"and",
"Ile7",
"to",
"illustrate",
"the",
"changes",
"in",
"the",
"mean",
"position",
"of",
"hydrophobic",
"and",
"hydrophilic",
"residues",
"with",
"respect",
"to",
"the",
"membrane",
"due",
"to",
"the",
"peptide",
"flip.",
"These",
"residues",
"are",
"polar",
"and",
"apolar,",
"respectively,",
"and",
"located",
"opposite",
"to",
"each",
"other",
"when",
"in",
"an",
"alpha-helix",
"conformation",
"(Fig.",
"2c",
")."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
[
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[
"α-BP100",
"with",
"constraints",
"on",
"residues",
"1–5",
"(Lys-Lys-Leu-Phe-Lys)",
"acquired",
"identical",
"helicity",
"(73%)",
"to",
"α-BP100",
"with",
"no",
"constraints",
"at",
"the",
"same",
"conditions",
"(Fig.",
"5b",
"),",
"after",
"50",
"ns",
"of",
"simulation",
"(Fig.",
"6a",
"),",
"with",
"a",
"helix",
"spanning",
"from",
"Lys2",
"to",
"Lys9",
"(Fig.",
"6a",
").",
"Constraints",
"on",
"residues",
"4–8",
"(Phe-Lys-Lys-Ile-Leu)",
"showed",
"an",
"overall",
"52%",
"of",
"helicity",
"(Fig.",
"6b",
"),",
"with",
"a",
"helix",
"spanning",
"from",
"Phe4",
"to",
"Lys9",
"(Fig.",
"6b",
").",
"Constraints",
"on",
"residues",
"7–11",
"(Ile-Leu-Lys-Tyr-Leu)",
"did",
"not",
"affect",
"the",
"rest",
"of",
"the",
"peptide",
"conformation",
"(Fig.",
"6c",
")",
"in",
"600",
"ns",
"of",
"simulation.",
"Peptide",
"flip",
"Simulation",
"trajectories",
"analyses",
"(Fig.",
"7",
")",
"revealed",
"that",
"the",
"peptide",
"in",
"alpha-helix",
"conformation",
"initially",
"adsorbed",
"at",
"the",
"DPPG-containing",
"membranes",
"interface",
"with",
"its",
"hydrophilic",
"facet",
"in",
"contact",
"with",
"the",
"membrane,",
"leaving",
"the",
"hydrophobic",
"facet",
"exposed",
"to",
"water.",
"We",
"observed",
"that",
"the",
"alpha-helix",
"rotated,",
"inserting",
"the",
"hydrophobic",
"facet",
"into",
"the",
"hydrophobic",
"region",
"of",
"the",
"membrane.",
"We",
"define",
"this",
"dynamic",
"phenomenon,",
"observed",
"in",
"our",
"simulations,",
"as",
"peptide",
"flip.",
"Although",
"this",
"final",
"peptide",
"orientation",
"is",
"known",
"31",
"–",
"34",
",",
"no",
"MD",
"simulation",
"on",
"peptide",
"flip",
"has",
"been",
"reported.",
"Figure",
"7",
"Peptide",
"flip",
"observed",
"from",
"above",
"in",
"α",
"-BP100",
"in",
"DPPG",
"set",
"after",
"circa",
"1400",
"ns",
"of",
"simulation.",
"In",
"blue,",
"polar",
"facet",
"and",
"in",
"green,",
"the",
"apolar",
"facet.",
"Peptide",
"flip",
"was",
"also",
"observed",
"in",
"α",
"-BP100",
"in",
"DPPC,",
"α",
"-BP100",
"in",
"PCPG-R,",
"and",
"α",
"-BP100",
"res(1–5)",
"in",
"DPPG",
"simulations.",
"The",
"peptide",
"flip",
"caused",
"dehydration",
"(Fig.",
"8",
").",
"When",
"in",
"contact",
"with",
"membranes,",
"depending",
"on",
"the",
"secondary",
"structure",
"of",
"the",
"peptide",
"and",
"the",
"lipid",
"nature,",
"the",
"hydration",
"of",
"the",
"peptide",
"was",
"slightly",
"different."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"In",
"all",
"cases,",
"the",
"peptide",
"was",
"rapidly",
"adsorbed",
"on",
"the",
"membranes",
"and",
"diffused",
"laterally.",
"Figure",
"5",
"shows",
"that",
"the",
"BP100",
"alpha-helical",
"conformation",
"was",
"proportional",
"to",
"PG",
"content,",
"as",
"the",
"alpha-helix",
"percentage",
"in",
"DPPC",
"is",
"considerably",
"smaller",
"than",
"that",
"observed",
"in",
"DPPG-containing",
"membranes.",
"Alpha-helix",
"formed",
"in",
"the",
"5",
"to",
"9",
"residues",
"region",
"(Lys-Lys-Ile-Leu-Lys)",
"was",
"highly",
"stable",
"in",
"all",
"simulations.",
"Figure",
"5",
"Secondary",
"structure",
"analyses",
"of",
"α",
"-BP100",
"in",
"DPPC",
"(",
"a",
"),",
"DPPG",
"(",
"b",
"),",
"PCPG-R",
"(",
"c",
")",
"and",
"PCPG-NR",
"(",
"d",
").",
"In",
"DPPC,",
"α-BP100",
"alpha-helix",
"conformation",
"reached",
"a",
"plateau",
"at",
"38%",
"helicity",
"throughout",
"the",
"simulation,",
"being",
"relatively",
"less",
"stable",
"than",
"α-BP100",
"in",
"bilayers",
"containing",
"DPPG,",
"where",
"a",
"higher",
"propensity",
"of",
"maintaining",
"its",
"conformation",
"was",
"observed.",
"For",
"pure",
"DPPG",
"(Fig.",
"5b",
")",
"we",
"found",
"73%",
"(8",
"out",
"of",
"11",
"residues),",
"and",
"for",
"both",
"PCPG",
"(1:1)",
"membranes",
"we",
"report",
"54%",
"(6",
"out",
"of",
"11)",
"of",
"helicity",
"(Fig.",
"5c,d",
").",
"No",
"alpha-helix",
"formation",
"was",
"detected",
"in",
"L-BP100",
"on",
"bilayers",
"simulations",
"(Fig.",
"S3",
").",
"Therefore,",
"the",
"1.8",
"µs",
"simulation",
"was",
"not",
"enough",
"to",
"present",
"a",
"spontaneous",
"peptide",
"folding.",
"The",
"alpha-helix",
"formed",
"in",
"the",
"region",
"of",
"the",
"residues",
"5",
"to",
"9",
"showed",
"higher",
"stability",
"in",
"all",
"simulations",
"with",
"α-BP100",
"in",
"bilayers",
"(Fig.",
"5",
").",
"This",
"secondary",
"structure",
"pattern",
"led",
"us",
"to",
"suggest",
"that",
"the",
"residues",
"5",
"to",
"9",
"are",
"related",
"to",
"helix",
"nucleation,",
"in",
"which",
"the",
"formation",
"of",
"this",
"helix",
"core",
"could",
"be",
"the",
"first",
"step",
"in",
"the",
"AMP",
"actions.",
"Following",
"this",
"assumption,",
"we",
"tested",
"three",
"conformations",
"with",
"α-BP100",
"torsionally",
"constrained",
"in",
"three",
"regions:",
"res1–5,",
"res4–8,",
"res7–11",
"(Fig.",
"3",
")",
"and",
"simulated",
"with",
"pure",
"DPPG",
"membranes.",
"Figure",
"6",
"shows",
"the",
"evolution",
"of",
"the",
"secondary",
"structure",
"in",
"each",
"simulation."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Figure",
"4",
"shows",
"that",
"BP100",
"conformation",
"in",
"solution",
"was,",
"predominantly,",
"random",
"coil.",
"The",
"peptide",
"lost",
"the",
"initial",
"alpha",
"helix",
"conformation",
"in",
"approximately",
"40",
"ns",
"when",
"starting",
"with",
"an",
"alpha-helix",
"configuration",
"and",
"occasionally",
"formed",
"an",
"alpha-helix",
"turn",
"in",
"the",
"5–9",
"residue",
"region",
"(Fig.",
"4a",
").",
"For",
"L-BP100",
"in",
"solution,",
"we",
"observed",
"a",
"similar",
"pattern",
"(Fig.",
"4b",
").",
"Circular",
"Dichroism",
"(CD)",
"shows",
"that",
"BP100",
"is",
"random",
"in",
"solution",
"10",
",",
"11",
",",
"30",
",",
"and",
"our",
"simulations",
"reproduced",
"these",
"data.",
"Figure",
"4",
"Secondary",
"structure",
"analyses",
"graphs",
"of",
"α",
"-BP100",
"(",
"a",
")",
"and",
"L",
"-BP100",
"(",
"b",
")",
"in",
"solution.",
"In",
"both",
"cases,",
"the",
"peptide",
"shows",
"predominance",
"in",
"random",
"coil",
"structure",
"(orange)",
"with",
"occasional",
"formation",
"of",
"1",
"alpha",
"helix",
"turn",
"(blue)",
"in",
"residues",
"5",
"to",
"9.",
"Peptide",
"in",
"bilayers",
"BP100",
"conformation,",
"antimicrobial",
"activity,",
"and",
"PG",
"content",
"are",
"related",
"11",
".",
"We",
"simulated",
"α-BP100",
"and",
"L-BP100",
"on",
"DPPC,",
"DPPG,",
"PCPG-R,",
"and",
"PCPG-NR",
"at",
"323",
"K,",
"above",
"DPPG",
"and",
"DPPC",
"transition",
"temperatures.",
"In",
"all",
"cases,",
"the",
"peptide",
"was",
"rapidly",
"adsorbed",
"on",
"the",
"membranes",
"and",
"diffused",
"laterally.",
"Figure",
"5",
"shows",
"that",
"the",
"BP100",
"alpha-helical",
"conformation",
"was",
"proportional",
"to",
"PG",
"content,",
"as",
"the",
"alpha-helix",
"percentage",
"in",
"DPPC",
"is",
"considerably",
"smaller",
"than",
"that",
"observed",
"in",
"DPPG-containing",
"membranes.",
"Alpha-helix",
"formed",
"in",
"the",
"5",
"to",
"9",
"residues",
"region",
"(Lys-Lys-Ile-Leu-Lys)",
"was",
"highly",
"stable",
"in",
"all",
"simulations.",
"Figure",
"5",
"Secondary",
"structure",
"analyses",
"of",
"α",
"-BP100",
"in",
"DPPC",
"(",
"a",
"),",
"DPPG",
"(",
"b",
"),",
"PCPG-R",
"(",
"c",
")",
"and",
"PCPG-NR",
"(",
"d",
").",
"In",
"DPPC,",
"α-BP100",
"alpha-helix",
"conformation",
"reached",
"a",
"plateau",
"at",
"38%",
"helicity",
"throughout",
"the",
"simulation,",
"being",
"relatively",
"less",
"stable",
"than",
"α-BP100",
"in",
"bilayers",
"containing",
"DPPG,",
"where",
"a",
"higher",
"propensity",
"of",
"maintaining",
"its",
"conformation",
"was",
"observed.",
"For",
"pure",
"DPPG",
"(Fig."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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[
"The",
"time",
"window",
"selected",
"for",
"computing",
"these",
"RDFs",
"includes",
"that",
"of",
"the",
"membrane",
"bound",
"peptide",
"250",
"ns-before",
"and",
"250",
"ns-after",
"the",
"peptide",
"flip.",
"The",
"pairs",
"with",
"distinguishable",
"RDF",
"peaks",
"and",
"following",
"minimum",
"were",
"used",
"to",
"analyze",
"the",
"number",
"of",
"polar",
"and",
"apolar",
"contacts",
"between",
"lipids",
"and",
"peptide.",
"A",
"cutoff",
"distance",
"for",
"each",
"pair",
"was",
"defined",
"from",
"the",
"position",
"of",
"the",
"first",
"minimum",
"in",
"the",
"RDF",
"curve,",
"and",
"a",
"contact",
"was",
"defined",
"as",
"a",
"pair",
"of",
"atoms",
"at",
"smaller",
"distance",
"than",
"their",
"corresponding",
"cutoff",
"distance.",
"The",
"simulations",
"were",
"analyzed",
"and",
"the",
"total",
"number",
"of",
"polar",
"and",
"apolar",
"contacts",
"as",
"a",
"function",
"of",
"time",
"was",
"obtained.",
"Additionally,",
"some",
"polar",
"and",
"apolar",
"pairs",
"were",
"analyzed",
"individually.",
"Peptide",
"hydration",
"The",
"time",
"evolution",
"of",
"the",
"solvent",
"shell",
"surrounding",
"the",
"peptide",
"in",
"its",
"α",
"and",
"L",
"conformations",
"in",
"all",
"simulated",
"membranes",
"was",
"analyzed",
"using",
"the",
"minimum",
"distance",
"distribution",
"function",
"(MDDF)",
"29",
"between",
"the",
"peptide",
"and",
"the",
"water",
"molecules,",
"as",
"well",
"as",
"the",
"average",
"number",
"of",
"water",
"molecules",
"N(r),",
"within",
"a",
"distance",
"r",
"=",
"0.5",
"nm,",
"named",
"here",
"as",
"N(0.5).",
"For",
"comparison",
"the",
"MDDF",
"of",
"BP100",
"in",
"water",
"was",
"used",
"to",
"define",
"the",
"bulk",
"water",
"hydration",
"shell",
"at",
"the",
"same",
"distance.",
"Results",
"The",
"17",
"sets",
"of",
"simulations",
"(Table",
"1",
")",
"were",
"run",
"for",
"more",
"than",
"25",
"µs",
"of",
"simulation",
"time,",
"and",
"each",
"unconstrained",
"peptide/membrane",
"simulation",
"had",
"at",
"least",
"1.6",
"µs",
"of",
"simulation.",
"After",
"comparing",
"the",
"simulated",
"membrane",
"properties",
"with",
"experimental",
"and",
"other",
"computational",
"studies",
"(Tables",
"S1",
"and",
"S2",
"),",
"we",
"systematically",
"analyzed",
"the",
"peptide",
"conformation",
"in",
"solution",
"and",
"on",
"bilayers,",
"peptide",
"trajectory,",
"and",
"dynamics",
"on",
"membranes",
"and",
"the",
"effect",
"of",
"BP100",
"on",
"model",
"bilayers.",
"In",
"the",
"following",
"sections,",
"we",
"describe",
"our",
"results.",
"Secondary",
"structure",
"Peptide",
"in",
"solution",
"To",
"study",
"BP100",
"secondary",
"structure",
"in",
"water,",
"we",
"did",
"simulations",
"for",
"more",
"than",
"2",
"µs",
"with",
"both",
"α-BP100",
"and",
"L-BP100",
"initial",
"conformations.",
"Figure",
"4",
"shows",
"that",
"BP100",
"conformation",
"in",
"solution",
"was,",
"predominantly,",
"random",
"coil.",
"The",
"peptide",
"lost",
"the",
"initial",
"alpha",
"helix",
"conformation",
"in",
"approximately",
"40",
"ns",
"when",
"starting",
"with",
"an",
"alpha-helix",
"configuration",
"and",
"occasionally",
"formed",
"an",
"alpha-helix",
"turn",
"in",
"the",
"5–9",
"residue",
"region",
"(Fig.",
"4a",
")."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"For",
"all",
"these",
"initial",
"conditions,",
"we",
"obtained",
"the",
"same",
"final",
"location",
"and",
"orientation",
"of",
"the",
"peptide",
"that",
"will",
"be",
"discussed",
"in",
"the",
"results",
"section.",
"To",
"investigate",
"the",
"influence",
"of",
"small",
"core",
"alpha-helical",
"sequences",
"in",
"BP100",
"to",
"its",
"stability",
"when",
"interacting",
"with",
"bilayers,",
"constrained",
"simulations",
"of",
"BP100",
"in",
"DPPG",
"membranes",
"were",
"performed.",
"The",
"alpha-helix",
"dihedral",
"angles",
"(ϕ",
"=",
"−60°;",
"ψ",
"=",
"−40°)",
"in",
"3",
"different",
"regions",
"were",
"fixed:",
"1–5",
"(Lys-Lys-Leu-Phe-Lys),",
"4–8",
"(Phe-Lys-Lys-Ile-Leu)",
"and",
"7–11",
"(Ile-Leu-Lys-Tyr-Leu)",
"residues",
"(Fig.",
"3",
").",
"We",
"maintained",
"the",
"constrained",
"regions",
"during",
"the",
"simulations.",
"Figure",
"3",
"Starting",
"structures",
"for",
"peptides",
"with",
"permanent",
"constrained",
"dihedral",
"angles.",
"Following",
"the",
"previous",
"lipid",
"membrane",
"systems,",
"energy-minimization,",
"NVT,",
"and",
"NPT",
"ensembles",
"were",
"used",
"in",
"the",
"equilibration",
"stage",
"of",
"the",
"MD",
"simulation.",
"Simulation",
"details",
"MD",
"simulations",
"were",
"carried",
"out",
"with",
"a",
"2",
"fs",
"time-step",
"with",
"a",
"Leap-Frog",
"integrator",
"24",
",",
"in",
"isobaric-isothermal",
"(NPT)",
"ensemble,",
"at",
"323",
"K",
"(50",
"°C)",
"with",
"temperature",
"coupling",
"treated",
"separately",
"for",
"BP100,",
"lipids,",
"water",
"and",
"ions",
"with",
"the",
"V-rescale",
"thermostat",
"25",
".",
"Atmospheric",
"pressure",
"of",
"1",
"bar",
"was",
"kept",
"with",
"the",
"Berendsen",
"barostat",
"26",
"and",
"semi-isotropic",
"pressure",
"coupling",
"was",
"used",
"for",
"all",
"systems.",
"All",
"bonds",
"were",
"constrained",
"with",
"LINCS",
"27",
"algorithm.",
"Long-range",
"electrostatic",
"correction",
"was",
"treated",
"by",
"a",
"Particle-mesh-Ewald",
"method",
"28",
"with",
"a",
"real-space",
"cut-off",
"of",
"1.5",
"nm.",
"van",
"der",
"Waals",
"interactions",
"were",
"truncated",
"at",
"1.5",
"nm",
"distance",
"with",
"a",
"switch",
"function",
"from",
"1.4",
"nm.",
"Simulation",
"analyses",
"Lipid/peptide",
"contacts",
"For",
"the",
"computation",
"of",
"lipid",
"contacts",
"with",
"BP100",
"and",
"pair",
"frequency,",
"we",
"labeled",
"some",
"lipid(s)",
"and",
"BP100",
"atoms",
"as",
"“polar”",
"or",
"“apolar”,",
"based",
"on",
"charges."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"One",
"membrane",
"was",
"composed",
"of",
"randomly",
"distributed",
"lipids",
"(PCPG-NR)",
"on",
"both",
"leaflets",
"and",
"the",
"other,",
"a",
"4",
"×",
"4",
"DPPG",
"raft",
"was",
"placed",
"in",
"the",
"center",
"of",
"both",
"monolayers",
"(PCPG-R)",
"and",
"the",
"remaining",
"48",
"lipids",
"were",
"randomly",
"distributed",
"(Fig.",
"2",
").",
"Figure",
"2",
"Initial",
"membrane",
"configurations",
"membranes.",
"TIP3P",
"water",
"molecules",
"were",
"used",
"to",
"solvate",
"our",
"systems,",
"with",
"an",
"approximately",
"53",
"water/lipid",
"ratio.",
"Na",
"+",
"ions",
"(Aqvist",
"21",
")",
"were",
"included",
"to",
"counter-balance",
"charges",
"of",
"membranes",
"containing",
"DPPG.",
"All",
"bilayer",
"sets",
"were",
"minimized",
"and",
"equilibrated",
"for",
"20",
"ps",
"in",
"a",
"NVT",
"ensemble",
"and",
"thereafter,",
"in",
"NPT",
"conditions",
"for",
"50",
"ns.",
"After",
"that,",
"the",
"bilayers",
"were",
"simulated",
"for",
"860",
"ns",
"(DPPC),",
"1100",
"ns",
"(DPPG)",
"and",
"1200",
"ns",
"(for",
"both",
"PCPG-R",
"and",
"PCPG-NR).",
"The",
"area",
"per",
"lipid",
"and",
"membrane",
"thickness",
"were",
"calculated",
"for",
"all",
"membranes",
"and",
"thNen",
"compared",
"with",
"experimental",
"data",
"and",
"those",
"obtained",
"by",
"Slipids",
"authors",
"(Tables",
"S1",
"and",
"S2",
").",
"The",
"last",
"trajectory",
"frames",
"of",
"the",
"membrane",
"simulations",
"were",
"used",
"to",
"build",
"our",
"peptide-lipid",
"systems.",
"Peptide-in-solution",
"and",
"peptide-lipid",
"systems",
"Following",
"a",
"study",
"by",
"Beauchamp",
"et",
"al.",
"22",
",",
"ff99sb-ildn-NMR",
"force",
"field",
"was",
"chosen",
"to",
"characterize",
"BP100",
"in",
"our",
"modeling",
"due",
"to",
"its",
"good",
"performance",
"in",
"simulating",
"peptides",
"and",
"proteins",
"structures",
"in",
"TIP3P",
"water",
"when",
"compared",
"with",
"NMR",
"measurements.",
"BP100",
"(H-Lys-Lys-Leu-Phe-Lys-Lys-Ile-Leu-Lys-Tyr-Leu-NH",
"2",
")",
"has",
"an",
"amidated",
"C-terminal",
"and",
"a",
"+6",
"charge",
"at",
"physiological",
"pH,",
"with",
"all",
"its",
"Lysines",
"and",
"N-terminal",
"amine",
"protonated.",
"To",
"study",
"secondary",
"structure",
"behavior",
"of",
"BP100",
"both",
"in",
"solution",
"and",
"in",
"bilayers,",
"two",
"initial",
"BP100",
"conformations",
"were",
"used:",
"linear",
"BP100",
"(",
"L",
"-BP100)",
"and",
"alpha-helical",
"BP100",
"(",
"α",
"-BP100)",
"(Fig.",
"1",
"a,b",
")."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Table",
"1",
"shows",
"all",
"simulation",
"systems",
"and",
"its",
"simulation",
"time.",
"The",
"program",
"used",
"to",
"analyze",
"the",
"hydration",
"shell",
"of",
"the",
"peptide",
"using",
"the",
"Minimum",
"Distance",
"Distribution",
"Function",
"was",
"developed",
"in",
"our",
"group.",
"Table",
"1",
"Table",
"containing",
"all",
"MD",
"simulation",
"sets",
"carried",
"out",
"in",
"this",
"work.",
"For",
"bilayers,",
"we",
"used",
"Slipids",
"forcefield",
"and",
"ff99sb-ildn-NMR",
"for",
"BP100.",
"All",
"sets",
"were",
"simulated",
"at",
"323",
"K",
"(above",
"DPPC",
"and",
"DPPG",
"transition",
"temperatures)",
"and",
"1",
"bar.",
"L",
"-BP100",
"indicate",
"constraint-free",
"simulations",
"using",
"random",
"coil",
"BP100",
"as",
"peptide",
"starting",
"configuration",
"and",
"α",
"-BP100,",
"as",
"alpha",
"helix.",
"Res1–5,",
"res4–8",
"and",
"res7–11",
"indicate",
"simulations",
"with",
"BP100",
"with",
"permanent",
"constraints",
"on",
"the",
"referred",
"residues.",
"Simulation",
"sets",
"Simulations",
"Peptide/Lipid",
"Waters/Lipid",
"Time",
"(ns)",
"Bilayers",
"DPPC",
"0/128",
"54",
"860",
"DPPG",
"53",
"1100",
"PCPG-R",
"0/[64/64]",
"54",
"1200",
"PCPG-NR",
"52",
"1200",
"Peptide",
"in",
"water",
"L",
"-BP100",
"in",
"water",
"1/0",
"—",
"2000",
"α",
"-BP100",
"in",
"water",
"—",
"2850",
"Peptide",
"with",
"bilayers",
"L",
"-BP100",
"in",
"DPPC",
"1/128",
"54",
"1700",
"α",
"-BP100",
"in",
"DPPC",
"54",
"2000",
"L",
"-BP100",
"in",
"DPPG",
"1/128",
"53",
"1700",
"α",
"-BP100",
"in",
"DPPG",
"53",
"2000",
"L",
"-BP100",
"in",
"PCPG-R",
"1/[64/64]",
"54",
"1600",
"α",
"-BP100",
"in",
"PCPG-R",
"54",
"2000",
"L",
"-BP100",
"in",
"PCPG-NR",
"1/[64/64]",
"52",
"1700",
"α",
"-BP100",
"in",
"PCPG-NR",
"52",
"2000",
"Partially",
"constrained",
"peptide",
"in",
"DPPG",
"α-",
"BP100",
"(res1–5)",
"in",
"DPPG",
"1/128",
"54",
"600",
"α-",
"BP100",
"(res4–8)",
"in",
"DPPG",
"54",
"600",
"α-",
"BP100",
"(res7–11)",
"in",
"DPPG",
"54",
"600",
"Lipid",
"bilayers",
"We",
"used",
"Slipids",
"forcefield",
"19",
"parameters",
"were",
"chosen",
"to",
"simulate",
"DPPC,",
"DPPG,",
"and",
"DPPC/DPPG",
"mixed",
"bilayers."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"A",
"detailed",
"description",
"of",
"peptide/membrane",
"interactions",
"at",
"the",
"atomic",
"scale",
"may",
"help",
"to",
"gain",
"information",
"on",
"CAMPs",
"disruption",
"mechanisms,",
"permitting",
"the",
"rational",
"design",
"of",
"new",
"derivatives",
"and,",
"therefore,",
"the",
"better",
"therapeutic",
"use",
"of",
"these",
"novel",
"antimicrobials.",
"Molecular",
"Dynamics",
"(MD)",
"simulations",
"provide",
"atomic-level",
"insights",
"and",
"have",
"been",
"widely",
"used",
"to",
"study",
"the",
"interaction",
"of",
"AMPs",
"with",
"membranes",
"15",
"–",
"18",
".",
"MD",
"simulations",
"were",
"also",
"utilized",
"to",
"study",
"BP100’s",
"structure",
"and",
"activity:",
"Wang",
"Y.",
"et",
"al.",
"17",
"performed",
"an",
"8",
"µs-long",
"MD",
"simulation",
"of",
"BP100",
"in",
"DMPC",
"bilayer",
"and",
"found",
"that",
"BP100",
"remained",
"in",
"the",
"surface-bound-state",
"inserting",
"through",
"its",
"C-terminus.",
"They",
"also",
"reported",
"the",
"unfolding",
"of",
"BP100",
"N-terminus",
"(Lys1",
"and",
"Lys2)",
"after",
"1.5",
"µs,",
"resulting",
"in",
"a",
"tilt",
"angle",
"of",
"97°",
"and",
"81%",
"helicity",
"10",
",",
"17",
".",
"In",
"a",
"study",
"with",
"Brownian",
"Dynamics",
"simulations",
"with",
"a",
"coarse-grained",
"peptide",
"model,",
"Alves",
"et",
"al.",
"18",
"simulated",
"BP100",
"confined",
"in",
"model",
"membranes",
"at",
"293",
"K",
"for",
"1",
"µs",
"each",
"and",
"reported",
"the",
"high",
"stability",
"of",
"BP100",
"pre-folded",
"alpha",
"helix",
"and",
"a",
"threefold",
"decrease",
"in",
"its",
"lateral",
"diffusion",
"in",
"POPC:",
"POPG",
"membranes",
"relative",
"to",
"that",
"in",
"POPC",
"membrane",
"18",
".",
"In",
"this",
"work",
"we",
"report",
"simulations,",
"in",
"solution",
"and",
"membranes,",
"extending",
"for",
"more",
"than",
"25",
"µs",
"of",
"BP100",
"and",
"membranes",
"of",
"1,2-dipalmitoyl-sn-glycerol-3-phosphocholine",
"(DPPC),",
"1,2-dipalmitoyl-sn-glycerol-3-phosphoglycerol",
"(DPPG),",
"and",
"DPPC:",
"DPPG",
"mixtures",
"(1:1).",
"We",
"systematically",
"investigated",
"the",
"dependence",
"of",
"BP100",
"secondary",
"structure",
"on",
"DPPG",
"lipids",
"which",
"agrees",
"with",
"experimental",
"findings",
"11",
".",
"We",
"also",
"analyzed",
"the",
"contribution",
"of",
"PG-containing",
"lipid",
"rafts",
"on",
"BP100",
"conformation",
"and",
"behavior.",
"In",
"most",
"simulations",
"containing",
"DPPG",
"lipids,",
"we",
"observed",
"the",
"occurrence",
"of",
"a",
"dynamic",
"transition",
"of",
"the",
"peptide",
"adsorbed",
"at",
"the",
"membrane",
"interface,",
"where",
"the",
"apolar",
"facet",
"of",
"the",
"BP100",
"(Fig."
] |
Original work titled: 'Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions' (Scientific Reports/Nature Publishing Group UK) by the following authors: Peter Park; Leandro R. Franco; Hernan Chaimovich; Kaline Coutinho; Iolanda M. Cuccovia; Filipe S. Lima DOI: 10.1038/s41598-019-45075-5
|
5388809896c7b2a9adf5d708f6ea4b08
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Due",
"to",
"their",
"potential",
"advantage",
"as",
"antimicrobials,",
"new",
"AMPs",
"are",
"increasingly",
"being",
"isolated",
"or",
"synthesized",
"and",
"their",
"properties",
"investigated.",
"Although",
"increasing",
"evidence",
"shows",
"that",
"some",
"AMPs",
"may",
"also",
"act",
"intracellularly,",
"inhibiting",
"proteins",
"1",
",",
"nucleic",
"acids",
"1",
"–",
"4",
"and",
"cell-wall",
"synthesis",
"1",
"–",
"5",
"and",
"inducing",
"cell",
"apoptosis",
"1",
",",
"3",
",",
"5",
",",
"most",
"of",
"them",
"kill",
"cells",
"by",
"disturbing",
"the",
"membrane’s",
"integrity",
"1",
",",
"2",
",",
"6",
",",
"7",
".",
"Several",
"CAMPs",
"seem",
"to",
"disturb",
"the",
"membrane",
"of",
"cells",
"by",
"self-aggregation",
"on",
"the",
"membrane",
"and",
"forming",
"pores",
"beyond",
"a",
"peptide/lipid",
"(P/L)",
"ratio",
"threshold",
"1",
",",
"2",
".",
"BP100",
"(H-KKLFKKILKYL-NH",
"2",
"),",
"is",
"a",
"hybrid",
"CAMP",
"synthesized",
"by",
"combinatorial",
"chemistry",
"involving",
"parts",
"of",
"two",
"natural",
"AMPs,",
"melittin,",
"and",
"cecropin",
"A",
"8",
".",
"BP100",
"shows",
"high",
"antimicrobial",
"activity",
"and",
"selectivity",
"against",
"some",
"Gram-negative",
"bacteria,",
"with",
"a",
"promising",
"minimal",
"inhibitory",
"concentration",
"ranging",
"from",
"2.5",
"to",
"5",
"µM",
"and",
"low",
"cytotoxicity",
"against",
"mammalian",
"cells",
"making",
"this",
"peptide",
"an",
"exciting",
"candidate",
"for",
"therapeutic",
"use",
"8",
".",
"BP100",
"conformation",
"and",
"activity",
"on",
"model",
"membranes",
"have",
"been",
"extensively",
"analyzed",
"with",
"experimental",
"techniques",
"9",
"–",
"13",
".",
"BP100",
"has",
"a",
"random",
"coil",
"conformation",
"in",
"solution",
"and",
"zwitterionic",
"bilayers",
"but",
"acquires",
"predominantly",
"alpha-helical",
"and",
"amphipathic",
"conformation",
"in",
"the",
"presence",
"of",
"negatively",
"charged",
"membranes.",
"BP100",
"is",
"highly",
"mobile",
"on",
"the",
"membrane",
"surface",
"and",
"orients",
"parallel",
"in",
"predominantly",
"negatively",
"charged",
"vesicles",
"9",
",",
"10",
".",
"BP100",
"secondary",
"structure",
"formation",
"and",
"bacteria",
"killing",
"performance",
"seem",
"to",
"be",
"directly",
"related",
"to",
"negative",
"charge",
"content",
"in",
"membranes,",
"thus",
"explaining",
"its",
"high",
"selectivity",
"towards",
"negative",
"bacterial",
"membrane",
"and",
"low",
"cytotoxicity",
"against",
"predominantly",
"less",
"negatively",
"charged",
"mammalian",
"cell",
"membranes",
"11",
",",
"14",
".",
"Experimental",
"approaches",
"to",
"investigate",
"peptide/membrane",
"interactions",
"mainly",
"focus",
"macroscopic-averaged",
"insight",
"on",
"a",
"mesoscopic",
"scale.",
"A",
"detailed",
"description",
"of",
"peptide/membrane",
"interactions",
"at",
"the",
"atomic",
"scale",
"may",
"help",
"to",
"gain",
"information",
"on",
"CAMPs",
"disruption",
"mechanisms,",
"permitting",
"the",
"rational",
"design",
"of",
"new",
"derivatives",
"and,",
"therefore,",
"the",
"better",
"therapeutic",
"use",
"of",
"these",
"novel",
"antimicrobials."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"How",
"to",
"effectively",
"and",
"efficiently",
"avoid",
"or",
"to",
"alleviate",
"the",
"toxicity",
"and",
"side",
"effects",
"is",
"a",
"critical",
"clinical",
"problem",
"that",
"should",
"be",
"solved.",
"CID",
"is",
"a",
"common",
"side",
"effect",
"of",
"the",
"digestive",
"system",
"in",
"the",
"antitumor",
"treatment",
"process",
"of",
"cytotoxic",
"drugs.",
"The",
"typical",
"clinical",
"characteristics",
"of",
"CID",
"are",
"as",
"follows:",
"symptoms",
"range",
"from",
"loose",
"stool",
"without",
"pain",
"to",
"severe,",
"watery",
"diarrhea",
"with",
"abdominal",
"pain;",
"symptoms",
"typically",
"last",
"5",
"to",
"7",
"days",
"and",
"may",
"occur",
"during",
"or",
"after",
"chemotherapy;",
"and",
"patients",
"with",
"CID",
"have",
"a",
"poor",
"treatment",
"response",
"to",
"gentamicin,",
"berberine,",
"and",
"furoxone",
"[",
"9",
"].",
"CID",
"can",
"lead",
"to",
"weakness,",
"electrolyte",
"disorders,",
"renal",
"failure,",
"blood",
"volume",
"reductions,",
"shock,",
"and",
"even",
"death",
"[",
"10",
"].",
"Its",
"occurrence",
"can",
"result",
"in",
"delaying",
"chemotherapy,",
"increasing",
"hospitalization",
"time",
"and",
"costs,",
"aggravating",
"the",
"psychological",
"stress",
"of",
"patients,",
"reducing",
"the",
"treatment",
"compliance",
"of",
"patients",
"and",
"even",
"altering",
"the",
"entire",
"chemotherapy",
"plan",
"[",
"11",
"].",
"A",
"unique",
"microecosystem",
"and",
"characteristic",
"microbial",
"community",
"lives",
"in",
"the",
"colorectal",
"regions",
"owing",
"to",
"their",
"function",
"of",
"storing",
"feces",
"[",
"12",
"].",
"Accumulating",
"evidence",
"points",
"to",
"the",
"gut",
"microbiome",
"being",
"involved",
"in",
"CRC",
"[",
"13",
"].",
"For",
"example,",
"some",
"researchers",
"have",
"reported",
"that",
"Streptococcus",
"bovis",
"[",
"14",
"]",
"and",
"Trichophyton",
"tonsurans",
"[",
"15",
"]",
"are",
"specific",
"bacteria",
"involved",
"in",
"colorectal",
"cancer;",
"Castellarin",
"et",
"al.",
"[",
"16",
"]",
"found",
"that",
"Thanatephorus",
"cucumeris",
"infection",
"is",
"prevalent",
"in",
"CRC",
"tissue",
"specimens",
"and",
"Kostic",
"et",
"al.",
"[",
"17",
"],",
"found",
"that",
"Thanatephorus",
"cucumeris",
"can",
"generate",
"a",
"proinflammatory",
"microenvironment",
"that",
"is",
"conducive",
"to",
"the",
"progression",
"of",
"CRC",
"through",
"recruitment",
"of",
"tumor-infiltrating",
"immune",
"cells.",
"Moreover,",
"many",
"enzymes,",
"peptides",
"and",
"small",
"molecules",
"secreted",
"by",
"the",
"intestinal",
"gut",
"microbiome",
"are",
"involved",
"in",
"activating",
"and",
"regulating",
"important",
"signaling",
"molecules",
"and",
"signaling",
"pathways",
"involved",
"in",
"the",
"progression",
"of",
"CRC",
"[",
"18",
",",
"19",
"].",
"Diarrhea",
"and",
"gut",
"microbiome",
"disorders",
"interact",
"as",
"both",
"cause",
"and",
"effect.",
"Diarrhea",
"can",
"disrupt",
"the",
"balance",
"of",
"the",
"gut",
"microenvironment."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Its",
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"in",
"delaying",
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"increasing",
"hospitalization",
"time",
"and",
"costs,",
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"compliance",
"of",
"patients",
"and",
"even",
"altering",
"the",
"entire",
"chemotherapy",
"plan",
"[",
"11",
"].",
"A",
"unique",
"microecosystem",
"and",
"characteristic",
"microbial",
"community",
"lives",
"in",
"the",
"colorectal",
"regions",
"owing",
"to",
"their",
"function",
"of",
"storing",
"feces",
"[",
"12",
"].",
"Accumulating",
"evidence",
"points",
"to",
"the",
"gut",
"microbiome",
"being",
"involved",
"in",
"CRC",
"[",
"13",
"].",
"For",
"example,",
"some",
"researchers",
"have",
"reported",
"that",
"Streptococcus",
"bovis",
"[",
"14",
"]",
"and",
"Methanococcus",
"voltae",
"[",
"15",
"]",
"are",
"specific",
"bacteria",
"involved",
"in",
"colorectal",
"cancer;",
"Castellarin",
"et",
"al.",
"[",
"16",
"]",
"found",
"that",
"Drosophila",
"americana",
"infection",
"is",
"prevalent",
"in",
"CRC",
"tissue",
"specimens",
"and",
"Kostic",
"et",
"al.",
"[",
"17",
"],",
"found",
"that",
"Drosophila",
"americana",
"can",
"generate",
"a",
"proinflammatory",
"microenvironment",
"that",
"is",
"conducive",
"to",
"the",
"progression",
"of",
"CRC",
"through",
"recruitment",
"of",
"tumor-infiltrating",
"immune",
"cells.",
"Moreover,",
"many",
"enzymes,",
"peptides",
"and",
"small",
"molecules",
"secreted",
"by",
"the",
"intestinal",
"gut",
"microbiome",
"are",
"involved",
"in",
"activating",
"and",
"regulating",
"important",
"signaling",
"molecules",
"and",
"signaling",
"pathways",
"involved",
"in",
"the",
"progression",
"of",
"CRC",
"[",
"18",
",",
"19",
"].",
"Diarrhea",
"and",
"gut",
"microbiome",
"disorders",
"interact",
"as",
"both",
"cause",
"and",
"effect.",
"Diarrhea",
"can",
"disrupt",
"the",
"balance",
"of",
"the",
"gut",
"microenvironment.",
"Meanwhile,",
"the",
"invasion",
"of",
"exogenous",
"pathogenic",
"microorganisms",
"and",
"the",
"imbalance",
"of",
"intestinal",
"microbes",
"can",
"lead",
"to",
"diarrhea",
"[",
"20",
"].",
"For",
"example,",
"the",
"invasion",
"of",
"some",
"pathogenic",
"bacteria",
"including",
"Shigella,",
"Salmonella",
"and",
"Klebsiella",
"[",
"21",
",",
"22",
"],",
"and",
"the",
"abundance",
"changes",
"of",
"intestinal",
"parasitic",
"microbes",
"include",
"Geothlypis",
"tolmiei,",
"Gratiola",
"brevifolia,",
"and",
"Aeromonas",
"can",
"induce",
"diarrhea",
"[",
"23",
"–",
"25",
"].",
"Chemotherapy",
"has",
"been",
"widely",
"used",
"in",
"the",
"clinic",
"as",
"an",
"effective",
"therapy",
"for",
"colorectal",
"cancer,",
"but",
"diarrhea",
"caused",
"by",
"chemotherapeutic",
"drugs",
"often",
"affects",
"the",
"implementation",
"of",
"chemotherapy",
"regimens",
"[",
"26",
"]."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
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"many",
"enzymes,",
"peptides",
"and",
"small",
"molecules",
"secreted",
"by",
"the",
"intestinal",
"gut",
"microbiome",
"are",
"involved",
"in",
"activating",
"and",
"regulating",
"important",
"signaling",
"molecules",
"and",
"signaling",
"pathways",
"involved",
"in",
"the",
"progression",
"of",
"CRC",
"[",
"18",
",",
"19",
"].",
"Diarrhea",
"and",
"gut",
"microbiome",
"disorders",
"interact",
"as",
"both",
"cause",
"and",
"effect.",
"Diarrhea",
"can",
"disrupt",
"the",
"balance",
"of",
"the",
"gut",
"microenvironment.",
"Meanwhile,",
"the",
"invasion",
"of",
"exogenous",
"pathogenic",
"microorganisms",
"and",
"the",
"imbalance",
"of",
"intestinal",
"microbes",
"can",
"lead",
"to",
"diarrhea",
"[",
"20",
"].",
"For",
"example,",
"the",
"invasion",
"of",
"some",
"pathogenic",
"bacteria",
"including",
"Shigella,",
"Salmonella",
"and",
"Klebsiella",
"[",
"21",
",",
"22",
"],",
"and",
"the",
"abundance",
"changes",
"of",
"intestinal",
"parasitic",
"microbes",
"include",
"Pterodroma",
"neglecta,",
"Banisteriopsis",
"caapi,",
"and",
"Aeromonas",
"can",
"induce",
"diarrhea",
"[",
"23",
"–",
"25",
"].",
"Chemotherapy",
"has",
"been",
"widely",
"used",
"in",
"the",
"clinic",
"as",
"an",
"effective",
"therapy",
"for",
"colorectal",
"cancer,",
"but",
"diarrhea",
"caused",
"by",
"chemotherapeutic",
"drugs",
"often",
"affects",
"the",
"implementation",
"of",
"chemotherapy",
"regimens",
"[",
"26",
"].",
"Many",
"probiotics",
"and",
"antibiotics",
"play",
"a",
"positive",
"role",
"in",
"the",
"treatment",
"of",
"infectious",
"diarrhea",
"by",
"regulating",
"the",
"gut",
"microbiome",
"[",
"27",
",",
"28",
"].",
"The",
"study",
"of",
"relationships",
"between",
"gut",
"microbiome",
"and",
"CID",
"may",
"provide",
"a",
"new",
"direction",
"for",
"solving",
"this",
"clinical",
"problem.",
"In",
"the",
"present",
"study,",
"we",
"aimed",
"to",
"explore",
"the",
"association",
"between",
"the",
"gut",
"microorganisms",
"and",
"CID",
"of",
"the",
"CapeOX",
"regimen",
"in",
"resected",
"stage",
"III",
"CRC",
"and",
"to",
"provide",
"some",
"research",
"methods",
"and",
"research",
"ideas",
"for",
"further",
"exploring",
"the",
"relationship",
"between",
"intestinal",
"microbes",
"and",
"CID.",
"The",
"results",
"may",
"provide",
"a",
"fresh",
"approach",
"to",
"the",
"prevention",
"and",
"treatment",
"of",
"CID",
"from",
"a",
"microbiological",
"perspective.",
"Subjects",
"and",
"methods",
"Subjects",
"Patients",
"with",
"CRC",
"treated",
"at",
"Huzhou",
"Central",
"Hospital",
"from",
"January",
"2016",
"to",
"January",
"2018",
"were",
"studied.",
"The",
"clinical",
"protocols",
"involving",
"the",
"patients",
"and",
"the",
"informed",
"consent",
"form",
"were",
"approved",
"by",
"the",
"Ethics",
"Committee",
"of",
"Huzhou",
"Central",
"Hospital",
"(No.",
"201601023)."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"②",
"Patients",
"with",
"other",
"intestinal",
"diseases,",
"such",
"as",
"ulcerative",
"colitis",
"and",
"Crohn’s",
"disease.",
"③",
"Alternation",
"of",
"chemotherapy",
"regimen",
"and",
"chemotherapeutic",
"dosage",
"or",
"the",
"occurrence",
"of",
"progression",
"of",
"the",
"disease",
"(PD)",
"during",
"the",
"8",
"cycles",
"of",
"the",
"CapeOX",
"regimen.",
"④",
"Patients",
"who",
"accepted",
"neo-adjuvant",
"chemotherapy.",
"⑤",
"Patients",
"with",
"a",
"history",
"of",
"the",
"use",
"of",
"oral",
"microbial",
"agents",
"within",
"1",
"month",
"before",
"chemotherapy.",
"⑥",
"Patients",
"with",
"another",
"primary",
"cancer.",
"⑦",
"Patients",
"with",
"known",
"primary",
"organ",
"failure.",
"⑧",
"Patients",
"who",
"could",
"not",
"obtained",
"the",
"stool",
"samples",
"(n",
"=",
"15)",
"or",
"obtained",
"unqualified",
"stool",
"samples.",
"All",
"of",
"the",
"subjects",
"signed",
"informed",
"consent",
"under",
"the",
"guidelines",
"approved",
"by",
"the",
"Ethics",
"Committee",
"of",
"Huzhou",
"Central",
"Hospital.",
"CRC",
"patients",
"with",
"and",
"without",
"CID",
"were",
"including",
"in",
"the",
"experimental",
"group",
"and",
"control",
"group,",
"respectively.",
"According",
"to",
"National",
"Cancer",
"Institute",
"Common",
"Toxicity",
"Criteria",
"(NCI",
"CTC)",
"V3.0",
"[",
"30",
"]",
"CID",
"grade",
"1",
"is",
"defined",
"as",
"the",
"number",
"of",
"defecations",
"increased",
"to",
"less",
"than",
"4",
"times",
"a",
"day",
"and",
"an",
"excretion",
"volume",
"slightly",
"increased.",
"During",
"a",
"course",
"of",
"8",
"cycles",
"of",
"chemotherapy",
"administered",
"over",
"nearly",
"half",
"a",
"year,",
"there",
"are",
"many",
"factors",
"that",
"can",
"cause",
"diarrhea,",
"and",
"these",
"factors",
"interfere",
"with",
"the",
"diagnosis",
"of",
"CID.",
"Clinical",
"intervention",
"measures,",
"such",
"as",
"using",
"antibiotics",
"and",
"antidiarrheal",
"drugs,",
"may",
"be",
"performed",
"and",
"the",
"chemotherapy",
"regimen",
"may",
"be",
"changed",
"in",
"patients",
"with",
"CID",
"grade",
"3",
"and",
"grade",
"4.",
"Therefore,",
"we",
"did",
"not",
"include",
"patients",
"with",
"grade",
"1,",
"grade",
"3",
"and",
"grade",
"4",
"in",
"the",
"experimental",
"group.",
"CID",
"grade",
"2",
"is",
"defined",
"as",
"the",
"number",
"of",
"defecations",
"increased",
"to",
"4–6",
"times",
"per",
"day",
"or",
"nocturnal",
"stools,",
"with",
"the",
"amount",
"of",
"excretion",
"increased",
"but",
"with",
"no",
"interference",
"in",
"daily",
"life.",
"All",
"of",
"the",
"subjects",
"recruited",
"into",
"the",
"experimental",
"group",
"were",
"CID",
"grade",
"2",
"in",
"the",
"present",
"study.",
"Collection",
"of",
"clinical",
"data",
"and",
"stool",
"samples",
"Basic",
"information",
"and",
"clinical",
"serological",
"indicators",
"were",
"obtained",
"from",
"the",
"medical",
"record",
"management",
"system",
"of",
"Huzhou",
"Central",
"Hospital",
"with",
"informed",
"consent",
"from",
"patients.",
"Stool",
"samples",
"of",
"the",
"patients",
"were",
"collected",
"in",
"the",
"2",
"weeks",
"after",
"the",
"8",
"cycles",
"of",
"chemotherapy.",
"Stool",
"samples",
"were",
"collected",
"in",
"the",
"morning",
"prior",
"to",
"breakfast."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"During",
"a",
"course",
"of",
"8",
"cycles",
"of",
"chemotherapy",
"administered",
"over",
"nearly",
"half",
"a",
"year,",
"there",
"are",
"many",
"factors",
"that",
"can",
"cause",
"diarrhea,",
"and",
"these",
"factors",
"interfere",
"with",
"the",
"diagnosis",
"of",
"CID.",
"Clinical",
"intervention",
"measures,",
"such",
"as",
"using",
"antibiotics",
"and",
"antidiarrheal",
"drugs,",
"may",
"be",
"performed",
"and",
"the",
"chemotherapy",
"regimen",
"may",
"be",
"changed",
"in",
"patients",
"with",
"CID",
"grade",
"3",
"and",
"grade",
"4.",
"Therefore,",
"we",
"did",
"not",
"include",
"patients",
"with",
"grade",
"1,",
"grade",
"3",
"and",
"grade",
"4",
"in",
"the",
"experimental",
"group.",
"CID",
"grade",
"2",
"is",
"defined",
"as",
"the",
"number",
"of",
"defecations",
"increased",
"to",
"4–6",
"times",
"per",
"day",
"or",
"nocturnal",
"stools,",
"with",
"the",
"amount",
"of",
"excretion",
"increased",
"but",
"with",
"no",
"interference",
"in",
"daily",
"life.",
"All",
"of",
"the",
"subjects",
"recruited",
"into",
"the",
"experimental",
"group",
"were",
"CID",
"grade",
"2",
"in",
"the",
"present",
"study.",
"Collection",
"of",
"clinical",
"data",
"and",
"stool",
"samples",
"Basic",
"information",
"and",
"clinical",
"serological",
"indicators",
"were",
"obtained",
"from",
"the",
"medical",
"record",
"management",
"system",
"of",
"Huzhou",
"Central",
"Hospital",
"with",
"informed",
"consent",
"from",
"patients.",
"Stool",
"samples",
"of",
"the",
"patients",
"were",
"collected",
"in",
"the",
"2",
"weeks",
"after",
"the",
"8",
"cycles",
"of",
"chemotherapy.",
"Stool",
"samples",
"were",
"collected",
"in",
"the",
"morning",
"prior",
"to",
"breakfast.",
"An",
"approximately",
"5–10",
"g",
"stool",
"sample",
"was",
"collected",
"after",
"defecation",
"without",
"the",
"use",
"of",
"a",
"purgative",
"or",
"lubricant.",
"Within",
"half",
"an",
"hour,",
"the",
"stool",
"samples",
"were",
"stored",
"in",
"an",
"ultra-low",
"temperature",
"freezer.",
"The",
"sample",
"preservation",
"time",
"was",
"not",
"beyond",
"1",
"month.",
"Finally,",
"17",
"stool",
"samples",
"from",
"CRC",
"patients",
"were",
"analyzed",
"after",
"the",
"patients",
"had",
"signed",
"informed",
"consent",
"forms",
"and",
"the",
"unqualified",
"specimens",
"were",
"eliminated.",
"Intestinal",
"microorganism",
"detection",
"DNA",
"extraction",
"and",
"PCR",
"amplification",
"A",
"E.Z.N.A.",
"®",
"Stool",
"DNA",
"Kit",
"(Omega",
"Bio-Tek,",
"Norcross,",
"GA,",
"U.S.)",
"was",
"used",
"to",
"extract",
"total",
"DNA",
"from",
"the",
"stool",
"samples",
"according",
"to",
"the",
"manufacturer’s",
"protocols.",
"The",
"nanodrop",
"ND-1000",
"spectrophotometer",
"(LabTech,",
"Washington,",
"DC,",
"USA)",
"with",
"the",
"absorbances",
"at",
"260",
"nm",
"and",
"280",
"nm",
"(A260/A280)",
"was",
"used",
"to",
"determine",
"the",
"quality",
"and",
"quantity",
"of",
"the",
"purified",
"DNA.",
"DNA",
"integrity",
"was",
"further",
"verified",
"by",
"electrophoresis",
"through",
"a",
"2.0%",
"(w/v)",
"agarose",
"gel."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Intestinal",
"microorganism",
"detection",
"DNA",
"extraction",
"and",
"PCR",
"amplification",
"A",
"E.Z.N.A.",
"®",
"Stool",
"DNA",
"Kit",
"(Omega",
"Bio-Tek,",
"Norcross,",
"GA,",
"U.S.)",
"was",
"used",
"to",
"extract",
"total",
"DNA",
"from",
"the",
"stool",
"samples",
"according",
"to",
"the",
"manufacturer’s",
"protocols.",
"The",
"nanodrop",
"ND-1000",
"spectrophotometer",
"(LabTech,",
"Washington,",
"DC,",
"USA)",
"with",
"the",
"absorbances",
"at",
"260",
"nm",
"and",
"280",
"nm",
"(A260/A280)",
"was",
"used",
"to",
"determine",
"the",
"quality",
"and",
"quantity",
"of",
"the",
"purified",
"DNA.",
"DNA",
"integrity",
"was",
"further",
"verified",
"by",
"electrophoresis",
"through",
"a",
"2.0%",
"(w/v)",
"agarose",
"gel.",
"PCR",
"(95",
"°C",
"for",
"3",
"min,",
"followed",
"by",
"25",
"cycles",
"at",
"95",
"°C",
"for",
"30",
"s,",
"55",
"°C",
"for",
"30",
"s,",
"and",
"72",
"°C",
"for",
"45",
"s",
"and",
"a",
"final",
"extension",
"at",
"72",
"°C",
"for",
"5",
"min)",
"was",
"used",
"to",
"amplify",
"the",
"V3–V4",
"region",
"of",
"the",
"bacterial",
"16S",
"ribosomal",
"RNA",
"gene",
"(the",
"primers",
"of",
"16S",
"V3–V4",
"rDNA",
"are",
"as",
"follows:",
"forward,",
"CCTACGGGNGGCWGCAG",
"and",
"reverse,",
"GACTACHVGGGTATCTAATCC).",
"PCR",
"amplifications",
"were",
"performed",
"in",
"triplicate",
"in",
"a",
"25",
"μL",
"mixture",
"containing",
"5",
"μL",
"of",
"DNA",
"template,",
"2",
"μL",
"of",
"Nextera",
"XT",
"Index",
"Primer",
"1",
"(10",
"M),",
"2",
"μL",
"of",
"Nextera",
"XT",
"Index",
"Primer",
"2",
"(10",
"M)",
"and",
"16",
"μL",
"ddH",
"2",
"O.",
"Amplicons",
"were",
"extracted",
"from",
"2%",
"agarose",
"gels,",
"purified",
"using",
"the",
"AxyPrep",
"DNA",
"Gel",
"Extraction",
"Kit",
"(Axygen",
"Biosciences,",
"Union",
"City,",
"CA,",
"USA)",
"and",
"quantified",
"using",
"QuantiFluor™-ST",
"(Promega,",
"U.S.)",
"according",
"to",
"the",
"manufacturer’s",
"instructions.",
"Library",
"construction",
"and",
"sequencing",
"The",
"MiSeq",
"library",
"was",
"constructed",
"as",
"follows:",
"purified",
"PCR",
"products",
"were",
"quantified",
"by",
"Qubit",
"®",
"3.0",
"(Life",
"Technologies,",
"Invitrogen).",
"PCR",
"products",
"were",
"ligated",
"with",
"Y",
"adapter."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"An",
"Illumina",
"Pair-End",
"library",
"was",
"constructed",
"using",
"pooled",
"DNA",
"products,",
"and",
"the",
"amplicon",
"library",
"was",
"pair-end",
"sequenced",
"(2",
"×",
"250)",
"on",
"an",
"Illumina",
"MiSeq",
"platform",
"(Shanghai",
"BIOZERON",
"Co.,",
"Ltd.)",
"according",
"to",
"standard",
"protocols",
"(MiSeq",
"V3",
"or",
"V4",
"sequencing",
"kit,",
"Hua",
"Ya",
"Regenerative",
"Medicine",
"Biological",
"Engineering",
"Technology",
"CO.,",
"LTD,",
"Shanghai,",
"China).",
"Sequencing",
"data",
"bioinformatics",
"analysis",
"Sequencing",
"data",
"processing",
"and",
"optimization",
"were",
"performed",
"according",
"to",
"the",
"criteria",
"at",
"http://en.wikipedia.org/wiki/Fastq",
".",
"Cutadapt",
"(version",
"1.11)",
"was",
"used",
"to",
"demultiplex",
"and",
"quality",
"filter",
"the",
"raw",
"fastq",
"files.",
"Pandaseq",
"(version",
"2.9)",
"was",
"used",
"to",
"assemble",
"PE",
"reads;",
"only",
"sequences",
"that",
"overlapped",
"longer",
"than",
"10",
"bp",
"were",
"assembled",
"according",
"to",
"their",
"overlap",
"sequence.",
"Mosaic",
"sequences",
"and",
"sequences",
"longer",
"than",
"300–480",
"bp",
"were",
"discarded.",
"In",
"addition,",
"the",
"reads",
"that",
"receiving",
"an",
"average",
"quality",
"score",
"<",
"20",
"were",
"discarded.",
"The",
"Silva",
"database",
"was",
"used",
"for",
"comparison",
"of",
"16S",
"rRNA",
"gene",
"sequences",
"[",
"31",
"]",
"and",
"the",
"GeneBank",
"database",
"was",
"used",
"to",
"analyze",
"functional",
"genes",
"[",
"32",
"].",
"Mothur",
"software",
"[",
"33",
"]",
"(",
"http://www.mothur.org/wiki/Main_Page",
")",
"was",
"used",
"to",
"analyze",
"the",
"microbial",
"diversity.",
"OTU",
"(operational",
"taxonomic",
"units),",
"as",
"the",
"artificial",
"classification",
"unit,",
"was",
"used",
"to",
"estimate",
"the",
"number",
"of",
"species",
"in",
"each",
"sample,",
"and",
"the",
"similarity",
"threshold",
"was",
"97%.",
"The",
"coverage",
"(",
"http://www.mothur.org/wiki/Coverage",
")",
"was",
"used",
"as",
"the",
"sequencing",
"depth",
"index.",
"The",
"ACE",
"estimator",
"(",
"http://www.mothur.org/wiki/Ace",
")",
"and",
"Chao",
"estimator",
"(",
"http://www.mothur.org/wiki/Chao",
")",
"were",
"used",
"to",
"estimate",
"the",
"gut",
"microbial",
"community",
"richness.",
"The",
"Shannon",
"index",
"(",
"http://www.mothur.org/wiki/Shannon",
")",
"and",
"Simpson",
"index",
"(",
"http://www.mothur.org/wiki/Simpson",
")",
"were",
"used",
"to",
"estimate",
"the",
"gut",
"microbial",
"community",
"diversity."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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"artificial",
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"unit,",
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"to",
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"species",
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"and",
"the",
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"97%.",
"The",
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"(",
"http://www.mothur.org/wiki/Coverage",
")",
"was",
"used",
"as",
"the",
"sequencing",
"depth",
"index.",
"The",
"ACE",
"estimator",
"(",
"http://www.mothur.org/wiki/Ace",
")",
"and",
"Chao",
"estimator",
"(",
"http://www.mothur.org/wiki/Chao",
")",
"were",
"used",
"to",
"estimate",
"the",
"gut",
"microbial",
"community",
"richness.",
"The",
"Shannon",
"index",
"(",
"http://www.mothur.org/wiki/Shannon",
")",
"and",
"Simpson",
"index",
"(",
"http://www.mothur.org/wiki/Simpson",
")",
"were",
"used",
"to",
"estimate",
"the",
"gut",
"microbial",
"community",
"diversity.",
"The",
"pie",
"charts",
"were",
"used",
"to",
"describe",
"the",
"distribution",
"of",
"microorganisms",
"at",
"the",
"species",
"level.",
"Proportions",
"less",
"than",
"1%",
"were",
"included",
"in",
"“Others”,",
"considering",
"the",
"best",
"visual",
"presentation.",
"Venn",
"diagrams",
"were",
"implemented",
"by",
"Venn",
"diagram.",
"We",
"performed",
"clustering",
"on",
"genera",
"obtained",
"from",
"the",
"RDP",
"Classifier",
"by",
"means",
"of",
"the",
"complete",
"linkage",
"hierarchical",
"clustering",
"technique",
"using",
"the",
"R",
"package",
"HCLUST",
"(",
"http://sekhon.berkeley.edu/stats/html/hclust.html",
").",
"The",
"basic",
"process",
"of",
"LDA",
"analysis",
"[",
"34",
"]",
"was",
"as",
"follows:",
"First,",
"non-parametric",
"Kruskal–Wallis",
"rank",
"sum",
"test",
"was",
"used",
"to",
"detect",
"the",
"significant",
"difference",
"of",
"abundance",
"among",
"species",
"between",
"the",
"two",
"groups",
"of",
"samples.",
"Then",
"Wilcoxon",
"rank",
"sum",
"test",
"was",
"used",
"to",
"analyze",
"the",
"difference",
"between",
"groups",
"based",
"on",
"the",
"significant",
"difference",
"species.",
"Finally,",
"LDA",
"was",
"used",
"to",
"reduce",
"the",
"dimension",
"of",
"data",
"and",
"evaluate",
"the",
"influence",
"of",
"significantly",
"different",
"species",
"(LDA",
"score).",
"LDA",
"effect",
"size",
"more",
"than",
"2",
"was",
"included",
"in",
"the",
"figure.",
"The",
"genes",
"of",
"the",
"16S",
"corresponding",
"species",
"and",
"their",
"copy",
"number",
"have",
"been",
"generally",
"known,",
"and",
"these",
"genes",
"can",
"be",
"compared",
"with",
"databases",
"(e.g.",
"KEGG,",
"NOG)",
"to",
"predict",
"the",
"possible",
"metabolic",
"capacity",
"of",
"these",
"species."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"According",
"to",
"the",
"NCCN",
"guidelines,",
"the",
"CapeOX",
"regimen",
"for",
"resected",
"stage",
"III",
"CRC",
"has",
"been",
"defined",
"as",
"8",
"cycles",
"of",
"capecitabine",
"(1000",
"mg/m",
"2",
"twice",
"daily)",
"combined",
"with",
"oxaliplatin",
"(130",
"mg/m",
"2",
"every",
"3",
"weeks)",
"[",
"36",
"].",
"CID",
"is",
"one",
"of",
"the",
"most",
"common",
"side",
"effects",
"of",
"the",
"CapeOX",
"regimen",
"[",
"37",
"].",
"The",
"degree",
"of",
"diarrhea",
"caused",
"by",
"different",
"chemotherapeutic",
"agents",
"varies.",
"Among",
"the",
"chemotherapeutic",
"drugs",
"for",
"colorectal",
"cancer,",
"the",
"most",
"common",
"drugs",
"that",
"cause",
"diarrhea",
"are",
"fluorouracil,",
"irinotecan",
"and",
"platinum,",
"and",
"the",
"incidence",
"of",
"diarrhea",
"associated",
"with",
"these",
"drugs",
"can",
"be",
"as",
"high",
"as",
"50–80%",
"[",
"38",
"].",
"Our",
"previous",
"clinical",
"investigation",
"found",
"that",
"the",
"probability",
"of",
"CID",
"increased",
"with",
"an",
"increase",
"of",
"chemotherapeutic",
"frequency",
"and",
"chemotherapeutic",
"dosage",
"and",
"most",
"cases",
"of",
"CID",
"occur",
"within",
"2",
"weeks",
"after",
"chemotherapy.",
"Therefore,",
"in",
"the",
"present",
"study,",
"stool",
"samples",
"from",
"the",
"patients",
"were",
"collected",
"in",
"2",
"weeks",
"after",
"the",
"8",
"cycles",
"of",
"chemotherapy",
"of",
"the",
"CapeOX",
"regimen",
"were",
"completed.",
"Studies",
"of",
"Carroll",
"et",
"al.",
"[",
"39",
"]",
"suggested",
"that",
"the",
"richness",
"of",
"16S",
"rRNA",
"sequences",
"was",
"significantly",
"decreased",
"in",
"patients",
"with",
"diarrhea-predominant",
"irritable",
"bowel",
"syndrome.",
"Lee",
"[",
"40",
"]",
"has",
"reported",
"the",
"community",
"diversity",
"of",
"gut",
"microbiome",
"is",
"lower",
"in",
"patients",
"with",
"kidney",
"posttransplant",
"diarrhea.",
"Similar",
"results",
"have",
"been",
"reported",
"in",
"dogs",
"with",
"acute",
"diarrhea",
"[",
"41",
"].",
"The",
"research",
"on",
"these",
"diarrhea",
"diseases",
"is",
"consistent",
"with",
"our",
"findings.",
"We",
"found",
"that",
"the",
"gut",
"microbial",
"community",
"richness",
"and",
"community",
"diversity",
"was",
"lower",
"in",
"CRC",
"patients",
"with",
"CID",
"in",
"the",
"present",
"study.",
"The",
"decrease",
"of",
"microbial",
"diversity",
"may",
"be",
"related",
"to",
"the",
"imbalance",
"of",
"gut",
"microbiome.",
"The",
"dominant",
"pathogenic",
"bacteria",
"leads",
"to",
"the",
"reduction",
"of",
"the",
"resident",
"normal",
"microbiota",
"through",
"the",
"plunder",
"of",
"nutrients",
"or",
"the",
"killing",
"effect",
"of",
"bacterial",
"toxic",
"metabolites.",
"Our",
"results",
"from",
"the",
"microbial",
"community",
"structure",
"analysis",
"showed",
"Caridina",
"spongicola",
"occupied",
"the",
"highest",
"proportion",
"(31.22%)",
"of",
"gut",
"microbiome",
"in",
"CRC",
"patients",
"with",
"CID."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Our",
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"found",
"that",
"the",
"probability",
"of",
"CID",
"increased",
"with",
"an",
"increase",
"of",
"chemotherapeutic",
"frequency",
"and",
"chemotherapeutic",
"dosage",
"and",
"most",
"cases",
"of",
"CID",
"occur",
"within",
"2",
"weeks",
"after",
"chemotherapy.",
"Therefore,",
"in",
"the",
"present",
"study,",
"stool",
"samples",
"from",
"the",
"patients",
"were",
"collected",
"in",
"2",
"weeks",
"after",
"the",
"8",
"cycles",
"of",
"chemotherapy",
"of",
"the",
"CapeOX",
"regimen",
"were",
"completed.",
"Studies",
"of",
"Carroll",
"et",
"al.",
"[",
"39",
"]",
"suggested",
"that",
"the",
"richness",
"of",
"16S",
"rRNA",
"sequences",
"was",
"significantly",
"decreased",
"in",
"patients",
"with",
"diarrhea-predominant",
"irritable",
"bowel",
"syndrome.",
"Lee",
"[",
"40",
"]",
"has",
"reported",
"the",
"community",
"diversity",
"of",
"gut",
"microbiome",
"is",
"lower",
"in",
"patients",
"with",
"kidney",
"posttransplant",
"diarrhea.",
"Similar",
"results",
"have",
"been",
"reported",
"in",
"dogs",
"with",
"acute",
"diarrhea",
"[",
"41",
"].",
"The",
"research",
"on",
"these",
"diarrhea",
"diseases",
"is",
"consistent",
"with",
"our",
"findings.",
"We",
"found",
"that",
"the",
"gut",
"microbial",
"community",
"richness",
"and",
"community",
"diversity",
"was",
"lower",
"in",
"CRC",
"patients",
"with",
"CID",
"in",
"the",
"present",
"study.",
"The",
"decrease",
"of",
"microbial",
"diversity",
"may",
"be",
"related",
"to",
"the",
"imbalance",
"of",
"gut",
"microbiome.",
"The",
"dominant",
"pathogenic",
"bacteria",
"leads",
"to",
"the",
"reduction",
"of",
"the",
"resident",
"normal",
"microbiota",
"through",
"the",
"plunder",
"of",
"nutrients",
"or",
"the",
"killing",
"effect",
"of",
"bacterial",
"toxic",
"metabolites.",
"Our",
"results",
"from",
"the",
"microbial",
"community",
"structure",
"analysis",
"showed",
"Paxillus",
"involutus",
"occupied",
"the",
"highest",
"proportion",
"(31.22%)",
"of",
"gut",
"microbiome",
"in",
"CRC",
"patients",
"with",
"CID.",
"Lu",
"et",
"al.",
"[",
"42",
"]",
"reported",
"that",
"the",
"rate",
"of",
"Paxillus",
"involutus",
"was",
"approximately",
"0.5%",
"in",
"Beijing",
"by",
"culturing",
"the",
"stool",
"pathogens",
"from",
"outpatients",
"with",
"diarrhea",
"syndromes",
"using",
"the",
"Vitek2",
"Compact",
"instrument.",
"Zhang",
"et",
"al.",
"[",
"22",
"]",
"only",
"isolated",
"43",
"Paxillus",
"involutus",
"strains",
"from",
"551",
"stool",
"specimens",
"from",
"diarrhea",
"patients.",
"Although",
"the",
"study",
"may",
"have",
"be",
"interfered",
"by",
"other",
"factors",
"such",
"as",
"geographical",
"location,",
"nosocomial",
"infection,",
"or",
"pollution",
"contamination",
"in",
"the",
"fecal",
"collection",
"process.",
"The",
"increased",
"proportion",
"of",
"Paxillus",
"involutus",
"in",
"patients",
"with",
"CID",
"remains",
"a",
"phenomenon",
"of",
"concern.",
"Microorganisms",
"can",
"adjust",
"and",
"modify",
"their",
"surroundings",
"due",
"to",
"their",
"metabolic",
"products.",
"A",
"series",
"of",
"enzymes",
"and",
"genes",
"participate",
"in",
"the",
"process",
"of",
"metabolism",
"[",
"12",
"]."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Fig.",
"4",
"Functional",
"analysis.",
"The",
"Picrust",
"software",
"was",
"used",
"to",
"analyze",
"the",
"pathway",
"based",
"on",
"the",
"KEGG",
"database.",
"The",
"significant",
"differences",
"in",
"functional",
"metabolism",
"are",
"shown",
"in",
"the",
"figure",
"Discussion",
"The",
"CapeOX",
"regimen",
"is",
"recommended",
"as",
"the",
"postoperative",
"adjuvant",
"chemotherapy",
"regimen",
"in",
"resected",
"CRC",
"patients",
"with",
"stage",
"III",
"or",
"high-risk",
"stage",
"II",
"[",
"35",
"].",
"The",
"high-risk",
"factors",
"in",
"stage",
"II",
"may",
"affect",
"the",
"accuracy",
"of",
"experimental",
"results,",
"Thus,",
"CRC",
"patients",
"with",
"stage",
"III",
"were",
"recruited",
"in",
"the",
"present",
"study.",
"According",
"to",
"the",
"NCCN",
"guidelines,",
"the",
"CapeOX",
"regimen",
"for",
"resected",
"stage",
"III",
"CRC",
"has",
"been",
"defined",
"as",
"8",
"cycles",
"of",
"capecitabine",
"(1000",
"mg/m",
"2",
"twice",
"daily)",
"combined",
"with",
"oxaliplatin",
"(130",
"mg/m",
"2",
"every",
"3",
"weeks)",
"[",
"36",
"].",
"CID",
"is",
"one",
"of",
"the",
"most",
"common",
"side",
"effects",
"of",
"the",
"CapeOX",
"regimen",
"[",
"37",
"].",
"The",
"degree",
"of",
"diarrhea",
"caused",
"by",
"different",
"chemotherapeutic",
"agents",
"varies.",
"Among",
"the",
"chemotherapeutic",
"drugs",
"for",
"colorectal",
"cancer,",
"the",
"most",
"common",
"drugs",
"that",
"cause",
"diarrhea",
"are",
"fluorouracil,",
"irinotecan",
"and",
"platinum,",
"and",
"the",
"incidence",
"of",
"diarrhea",
"associated",
"with",
"these",
"drugs",
"can",
"be",
"as",
"high",
"as",
"50–80%",
"[",
"38",
"].",
"Our",
"previous",
"clinical",
"investigation",
"found",
"that",
"the",
"probability",
"of",
"CID",
"increased",
"with",
"an",
"increase",
"of",
"chemotherapeutic",
"frequency",
"and",
"chemotherapeutic",
"dosage",
"and",
"most",
"cases",
"of",
"CID",
"occur",
"within",
"2",
"weeks",
"after",
"chemotherapy.",
"Therefore,",
"in",
"the",
"present",
"study,",
"stool",
"samples",
"from",
"the",
"patients",
"were",
"collected",
"in",
"2",
"weeks",
"after",
"the",
"8",
"cycles",
"of",
"chemotherapy",
"of",
"the",
"CapeOX",
"regimen",
"were",
"completed.",
"Studies",
"of",
"Carroll",
"et",
"al.",
"[",
"39",
"]",
"suggested",
"that",
"the",
"richness",
"of",
"16S",
"rRNA",
"sequences",
"was",
"significantly",
"decreased",
"in",
"patients",
"with",
"diarrhea-predominant",
"irritable",
"bowel",
"syndrome.",
"Lee",
"[",
"40",
"]",
"has",
"reported",
"the",
"community",
"diversity",
"of",
"gut",
"microbiome",
"is",
"lower",
"in",
"patients",
"with",
"kidney",
"posttransplant",
"diarrhea.",
"Similar",
"results",
"have",
"been",
"reported",
"in",
"dogs",
"with",
"acute",
"diarrhea",
"[",
"41",
"].",
"The",
"research",
"on",
"these",
"diarrhea",
"diseases",
"is",
"consistent",
"with",
"our",
"findings."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"The",
"increased",
"proportion",
"of",
"Petroica",
"boodang",
"in",
"patients",
"with",
"CID",
"remains",
"a",
"phenomenon",
"of",
"concern.",
"Microorganisms",
"can",
"adjust",
"and",
"modify",
"their",
"surroundings",
"due",
"to",
"their",
"metabolic",
"products.",
"A",
"series",
"of",
"enzymes",
"and",
"genes",
"participate",
"in",
"the",
"process",
"of",
"metabolism",
"[",
"12",
"].",
"Functional",
"analysis",
"of",
"these",
"enzymes",
"and",
"genes",
"would",
"be",
"conducive",
"to",
"understand",
"the",
"whole",
"microecological",
"environment.",
"In",
"the",
"present",
"study,",
"we",
"screened",
"75",
"differentiated",
"microorganisms",
"at",
"the",
"species",
"level",
"by",
"using",
"LDA",
"effect",
"size",
"analysis",
"as",
"well",
"as",
"23",
"pathways",
"associated",
"with",
"differential",
"microorganisms",
"by",
"using",
"KEGG",
"databases.",
"These",
"differential",
"pathways",
"are",
"related",
"to",
"microbial",
"metabolites,",
"cell",
"proliferation",
"and",
"death,",
"immune",
"system,",
"and",
"many",
"other",
"aspects.",
"These",
"differentiated",
"microorganisms,",
"their",
"metabolic",
"products",
"and",
"the",
"relevant",
"pathways",
"make",
"up",
"the",
"intestinal",
"microecosystem",
"that",
"causes",
"CID.",
"These",
"results",
"may",
"provide",
"characteristic",
"microorganisms",
"or",
"potential",
"molecular",
"targets",
"for",
"the",
"treatment",
"and",
"prevention",
"of",
"CID.",
"It",
"must",
"be",
"emphasized",
"that",
"small",
"sample",
"size",
"and",
"potential",
"sample",
"contamination",
"may",
"affect",
"the",
"accuracy",
"of",
"the",
"present",
"study.",
"Strict",
"inclusion",
"and",
"exclusion",
"criteria",
"was",
"performed",
"in",
"this",
"study.",
"Subjects",
"in",
"the",
"experimental",
"group",
"were",
"only",
"included",
"the",
"resected",
"stage",
"III",
"colorectal",
"cancer",
"(CRC)",
"patients",
"who",
"voluntarily",
"accepted",
"and",
"completed",
"8",
"cycles",
"of",
"the",
"CapeOX",
"regimen",
"and",
"accompanied",
"with",
"grade",
"2",
"of",
"CID.",
"Thus,",
"the",
"small",
"sample",
"size",
"limits",
"the",
"applicability",
"of",
"the",
"findings.",
"A",
"multi-center,",
"large",
"study",
"will",
"provide",
"more",
"powerful",
"data",
"to",
"support",
"the",
"clarification",
"of",
"the",
"microbial",
"differences",
"in",
"CRC",
"patients",
"with",
"CID.",
"Conclusion",
"Chemotherapy",
"induced",
"diarrhea",
"(CID)",
"is",
"a",
"common",
"side",
"effect",
"in",
"patients",
"receiving",
"chemotherapy",
"for",
"cancer.",
"In",
"the",
"present",
"study,",
"We",
"found",
"that",
"the",
"gut",
"microbial",
"community",
"structure",
"and",
"community",
"diversity",
"have",
"changed",
"in",
"CRC",
"patients",
"with",
"CID.",
"The",
"gut",
"microbial",
"community",
"richness",
"and",
"community",
"diversity",
"were",
"lower",
"in",
"CID.",
"Petroica",
"boodang",
"was",
"the",
"most",
"predominant",
"species",
"among",
"the",
"gut",
"microbiome",
"in",
"CRC",
"patients",
"with",
"CID.",
"It",
"may",
"provide",
"novel",
"insights",
"into",
"the",
"prevention",
"and",
"treatment",
"of",
"patients",
"with",
"CID",
"to",
"improve",
"patients’",
"quality",
"of",
"life",
"and",
"chemotherapy",
"tolerance."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Lee",
"[",
"40",
"]",
"has",
"reported",
"the",
"community",
"diversity",
"of",
"gut",
"microbiome",
"is",
"lower",
"in",
"patients",
"with",
"kidney",
"posttransplant",
"diarrhea.",
"Similar",
"results",
"have",
"been",
"reported",
"in",
"dogs",
"with",
"acute",
"diarrhea",
"[",
"41",
"].",
"The",
"research",
"on",
"these",
"diarrhea",
"diseases",
"is",
"consistent",
"with",
"our",
"findings.",
"We",
"found",
"that",
"the",
"gut",
"microbial",
"community",
"richness",
"and",
"community",
"diversity",
"was",
"lower",
"in",
"CRC",
"patients",
"with",
"CID",
"in",
"the",
"present",
"study.",
"The",
"decrease",
"of",
"microbial",
"diversity",
"may",
"be",
"related",
"to",
"the",
"imbalance",
"of",
"gut",
"microbiome.",
"The",
"dominant",
"pathogenic",
"bacteria",
"leads",
"to",
"the",
"reduction",
"of",
"the",
"resident",
"normal",
"microbiota",
"through",
"the",
"plunder",
"of",
"nutrients",
"or",
"the",
"killing",
"effect",
"of",
"bacterial",
"toxic",
"metabolites.",
"Our",
"results",
"from",
"the",
"microbial",
"community",
"structure",
"analysis",
"showed",
"Porphyromonas",
"endodontalis",
"occupied",
"the",
"highest",
"proportion",
"(31.22%)",
"of",
"gut",
"microbiome",
"in",
"CRC",
"patients",
"with",
"CID.",
"Lu",
"et",
"al.",
"[",
"42",
"]",
"reported",
"that",
"the",
"rate",
"of",
"Porphyromonas",
"endodontalis",
"was",
"approximately",
"0.5%",
"in",
"Beijing",
"by",
"culturing",
"the",
"stool",
"pathogens",
"from",
"outpatients",
"with",
"diarrhea",
"syndromes",
"using",
"the",
"Vitek2",
"Compact",
"instrument.",
"Zhang",
"et",
"al.",
"[",
"22",
"]",
"only",
"isolated",
"43",
"Porphyromonas",
"endodontalis",
"strains",
"from",
"551",
"stool",
"specimens",
"from",
"diarrhea",
"patients.",
"Although",
"the",
"study",
"may",
"have",
"be",
"interfered",
"by",
"other",
"factors",
"such",
"as",
"geographical",
"location,",
"nosocomial",
"infection,",
"or",
"pollution",
"contamination",
"in",
"the",
"fecal",
"collection",
"process.",
"The",
"increased",
"proportion",
"of",
"Porphyromonas",
"endodontalis",
"in",
"patients",
"with",
"CID",
"remains",
"a",
"phenomenon",
"of",
"concern.",
"Microorganisms",
"can",
"adjust",
"and",
"modify",
"their",
"surroundings",
"due",
"to",
"their",
"metabolic",
"products.",
"A",
"series",
"of",
"enzymes",
"and",
"genes",
"participate",
"in",
"the",
"process",
"of",
"metabolism",
"[",
"12",
"].",
"Functional",
"analysis",
"of",
"these",
"enzymes",
"and",
"genes",
"would",
"be",
"conducive",
"to",
"understand",
"the",
"whole",
"microecological",
"environment.",
"In",
"the",
"present",
"study,",
"we",
"screened",
"75",
"differentiated",
"microorganisms",
"at",
"the",
"species",
"level",
"by",
"using",
"LDA",
"effect",
"size",
"analysis",
"as",
"well",
"as",
"23",
"pathways",
"associated",
"with",
"differential",
"microorganisms",
"by",
"using",
"KEGG",
"databases.",
"These",
"differential",
"pathways",
"are",
"related",
"to",
"microbial",
"metabolites,",
"cell",
"proliferation",
"and",
"death,",
"immune",
"system,",
"and",
"many",
"other",
"aspects.",
"These",
"differentiated",
"microorganisms,",
"their",
"metabolic",
"products",
"and",
"the",
"relevant",
"pathways",
"make",
"up",
"the",
"intestinal",
"microecosystem",
"that",
"causes",
"CID."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"The",
"innermost",
"layer",
"shows",
"the",
"taxonomic",
"tree.",
"The",
"circle",
"from",
"the",
"inside",
"to",
"the",
"outside",
"represents",
"different",
"taxon",
"levels",
"from",
"phylum",
"to",
"genus.",
"Yellow",
"circles",
"represent",
"no",
"statistical",
"difference",
"in",
"species",
"between",
"the",
"two",
"groups,",
"and",
"red",
"circles",
"and",
"green",
"circles",
"represent",
"the",
"higher",
"abundance",
"of",
"genus",
"in",
"the",
"control",
"group",
"and",
"the",
"chemotherapy-induced",
"diarrhea",
"group,",
"respectively.",
"The",
"lowercase",
"English",
"letters",
"corresponding",
"to",
"the",
"different",
"bacteria",
"are",
"shown",
"in",
"the",
"legends",
"The",
"functional",
"analysis",
"of",
"16S",
"rRNA",
"genes",
"associated",
"with",
"CID",
"during",
"the",
"CapeOX",
"regimen",
"for",
"CRC",
"It",
"has",
"been",
"confirmed",
"that",
"many",
"gene",
"function",
"annotation",
"databases",
"are",
"associated",
"with",
"corresponding",
"16S",
"rRNA",
"gene",
"sequences.",
"Functional",
"analysis",
"of",
"enzymes",
"and",
"genes",
"would",
"be",
"conducive",
"to",
"understand",
"the",
"whole",
"microecological",
"environment.",
"As",
"shown",
"in",
"Fig.",
"4",
",",
"the",
"figure",
"shows",
"the",
"results",
"of",
"the",
"functional",
"analysis.",
"Overall,",
"23",
"pathways",
"(p",
"<",
"0.001)",
"associated",
"with",
"statistically",
"significant",
"differences",
"might",
"be",
"involved",
"in",
"CID",
"during",
"the",
"CapeOX",
"regimen",
"for",
"adjuvant",
"chemotherapy",
"in",
"resected",
"stage",
"III",
"colorectal",
"cancer.",
"These",
"differential",
"pathways",
"are",
"related",
"to",
"microbial",
"metabolites,",
"cell",
"proliferation",
"and",
"death,",
"immune",
"system,",
"and",
"many",
"other",
"aspects.",
"Fig.",
"4",
"Functional",
"analysis.",
"The",
"Picrust",
"software",
"was",
"used",
"to",
"analyze",
"the",
"pathway",
"based",
"on",
"the",
"KEGG",
"database.",
"The",
"significant",
"differences",
"in",
"functional",
"metabolism",
"are",
"shown",
"in",
"the",
"figure",
"Discussion",
"The",
"CapeOX",
"regimen",
"is",
"recommended",
"as",
"the",
"postoperative",
"adjuvant",
"chemotherapy",
"regimen",
"in",
"resected",
"CRC",
"patients",
"with",
"stage",
"III",
"or",
"high-risk",
"stage",
"II",
"[",
"35",
"].",
"The",
"high-risk",
"factors",
"in",
"stage",
"II",
"may",
"affect",
"the",
"accuracy",
"of",
"experimental",
"results,",
"Thus,",
"CRC",
"patients",
"with",
"stage",
"III",
"were",
"recruited",
"in",
"the",
"present",
"study.",
"According",
"to",
"the",
"NCCN",
"guidelines,",
"the",
"CapeOX",
"regimen",
"for",
"resected",
"stage",
"III",
"CRC",
"has",
"been",
"defined",
"as",
"8",
"cycles",
"of",
"capecitabine",
"(1000",
"mg/m",
"2",
"twice",
"daily)",
"combined",
"with",
"oxaliplatin",
"(130",
"mg/m",
"2",
"every",
"3",
"weeks)",
"[",
"36",
"].",
"CID",
"is",
"one",
"of",
"the",
"most",
"common",
"side",
"effects",
"of",
"the",
"CapeOX",
"regimen",
"[",
"37",
"].",
"The",
"degree",
"of",
"diarrhea",
"caused",
"by",
"different",
"chemotherapeutic",
"agents",
"varies."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"The",
"cladogram",
"in",
"Fig.",
"3",
"c",
"displays",
"the",
"composition",
"and",
"proportion",
"of",
"microorganisms",
"at",
"different",
"taxonomic",
"levels.",
"The",
"cladogram",
"showed",
"that",
"the",
"abundance",
"of",
"these",
"bacteria",
"including",
"Actinomycetaceae,",
"Micrococcaceae,",
"Bacteroidaceae,",
"Porphyromonadaceae,",
"Ruminococcaceae,",
"Erysipelotrichaceae,",
"Leptotrichiaceae,",
"Enterobacteriaceae",
"(Klebsiella",
"belongs",
"to",
"Enterobacteriaceae)",
"and",
"Synergistaceae",
"had",
"significant",
"differences",
"at",
"family",
"level",
"between",
"the",
"two",
"groups.",
"Fig.",
"3",
"Differential",
"microbes",
"analysis.",
"The",
"samples",
"were",
"divided",
"into",
"two",
"groups",
"according",
"to",
"patients",
"with",
"or",
"without",
"CID.",
"The",
"number",
"of",
"OTUs",
"that",
"were",
"exclusive",
"or",
"shared",
"by",
"the",
"two",
"groups",
"were",
"visualized",
"by",
"a",
"Venn",
"Chart",
"(",
"a",
").",
"The",
"strip",
"figure",
"in",
"b",
"displays",
"the",
"LDA",
"effect",
"size",
"analysis.",
"LDA",
"effect",
"size",
"analysis",
"was",
"used",
"to",
"compare",
"the",
"differences",
"in",
"microbial",
"abundance",
"between",
"the",
"two",
"groups",
"(",
"b",
").",
"LDA",
"scores",
"over",
"2",
"mean",
"that",
"the",
"differences",
"are",
"statistically",
"significant",
"(p",
"<",
"0.05).",
"The",
"cladogram",
"in",
"c",
"displays",
"the",
"composition",
"and",
"proportion",
"of",
"microorganisms",
"at",
"different",
"taxonomic",
"levels.",
"The",
"innermost",
"layer",
"shows",
"the",
"taxonomic",
"tree.",
"The",
"circle",
"from",
"the",
"inside",
"to",
"the",
"outside",
"represents",
"different",
"taxon",
"levels",
"from",
"phylum",
"to",
"genus.",
"Yellow",
"circles",
"represent",
"no",
"statistical",
"difference",
"in",
"species",
"between",
"the",
"two",
"groups,",
"and",
"red",
"circles",
"and",
"green",
"circles",
"represent",
"the",
"higher",
"abundance",
"of",
"genus",
"in",
"the",
"control",
"group",
"and",
"the",
"chemotherapy-induced",
"diarrhea",
"group,",
"respectively.",
"The",
"lowercase",
"English",
"letters",
"corresponding",
"to",
"the",
"different",
"bacteria",
"are",
"shown",
"in",
"the",
"legends",
"The",
"functional",
"analysis",
"of",
"16S",
"rRNA",
"genes",
"associated",
"with",
"CID",
"during",
"the",
"CapeOX",
"regimen",
"for",
"CRC",
"It",
"has",
"been",
"confirmed",
"that",
"many",
"gene",
"function",
"annotation",
"databases",
"are",
"associated",
"with",
"corresponding",
"16S",
"rRNA",
"gene",
"sequences.",
"Functional",
"analysis",
"of",
"enzymes",
"and",
"genes",
"would",
"be",
"conducive",
"to",
"understand",
"the",
"whole",
"microecological",
"environment.",
"As",
"shown",
"in",
"Fig.",
"4",
",",
"the",
"figure",
"shows",
"the",
"results",
"of",
"the",
"functional",
"analysis."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"As",
"shown",
"in",
"Fig.",
"2",
",",
"the",
"stacked",
"bar",
"graph",
"showed",
"that",
"the",
"percent",
"of",
"Sphingosinicella",
"xenopeptidilytica",
"was",
"35%",
"and",
"it",
"occupied",
"the",
"highest",
"proportion",
"in",
"the",
"experimental",
"group",
"(CID+).",
"But",
"the",
"rate",
"was",
"only",
"3%",
"in",
"the",
"control",
"group",
"(CID−).",
"Fig.",
"2",
"Microbial",
"community",
"structure",
"analysis.",
"The",
"distribution",
"of",
"microorganisms",
"from",
"the",
"same",
"group",
"was",
"merged",
"into",
"the",
"whole.",
"The",
"stacked",
"bar",
"graph",
"was",
"used",
"to",
"describe",
"the",
"distribution",
"of",
"microorganisms",
"at",
"the",
"species",
"level.",
"CID-",
"and",
"CID+",
"represent",
"the",
"control",
"group",
"and",
"experimental",
"group,",
"respectively",
"The",
"difference",
"in",
"microbial",
"abundance",
"associated",
"with",
"CID",
"of",
"the",
"CapeOX",
"regimen",
"for",
"CRC",
"The",
"samples",
"were",
"divided",
"into",
"two",
"groups",
"according",
"to",
"patients",
"with",
"or",
"without",
"CID.",
"As",
"shown",
"in",
"Fig.",
"3",
"a,",
"there",
"were",
"220",
"shared",
"OTUs",
"and",
"that",
"the",
"numbers",
"of",
"unique",
"OTUs",
"in",
"the",
"control",
"group",
"and",
"experimental",
"group",
"were",
"645",
"and",
"34,",
"respectively.",
"LDA",
"effect",
"size",
"analysis",
"was",
"used",
"to",
"compare",
"the",
"differences",
"in",
"microbial",
"abundance",
"between",
"the",
"two",
"groups.",
"LDA",
"Effect",
"Size",
"analysis",
"(Fig.",
"3",
"b)",
"showed",
"that",
"there",
"were",
"75",
"microorganisms",
"with",
"significant",
"differences",
"at",
"the",
"genus",
"level",
"between",
"the",
"two",
"groups.",
"The",
"length",
"of",
"the",
"histogram",
"indicates",
"that",
"some",
"microorganisms",
"such",
"as",
"Proteobacteria,",
"Enterobacteriales,",
"Gammaproteobacteria,",
"Enterobacteriaceae,",
"Klebsiella,",
"Clostridiales,",
"Clostridia,",
"Ruminococcaceae,",
"Bacteroidetes,",
"Bacteroidia,",
"Bacteroidales,",
"Bacteroides",
"and",
"Bacteroidaceae",
"have",
"a",
"larger",
"influence.",
"The",
"cladogram",
"in",
"Fig.",
"3",
"c",
"displays",
"the",
"composition",
"and",
"proportion",
"of",
"microorganisms",
"at",
"different",
"taxonomic",
"levels.",
"The",
"cladogram",
"showed",
"that",
"the",
"abundance",
"of",
"these",
"bacteria",
"including",
"Actinomycetaceae,",
"Micrococcaceae,",
"Bacteroidaceae,",
"Porphyromonadaceae,",
"Ruminococcaceae,",
"Erysipelotrichaceae,",
"Leptotrichiaceae,",
"Enterobacteriaceae",
"(Klebsiella",
"belongs",
"to",
"Enterobacteriaceae)",
"and",
"Synergistaceae",
"had",
"significant",
"differences",
"at",
"family",
"level",
"between",
"the",
"two",
"groups."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"The",
"statistically",
"significant",
"differences",
"of",
"the",
"ACE",
"estimator",
"and",
"Chao",
"estimator",
"between",
"the",
"experimental",
"group",
"and",
"control",
"group",
"indicated",
"that",
"the",
"community",
"richness",
"of",
"the",
"gut",
"microbiome",
"was",
"lower",
"in",
"the",
"patients",
"with",
"chemotherapy-induced",
"diarrhea",
"(p",
"<",
"0.05,",
"vs",
"control",
"group).",
"The",
"smaller",
"Shannon",
"index",
"and",
"larger",
"Simpson",
"index",
"indicate",
"that",
"the",
"gut",
"microbial",
"community",
"diversity",
"was",
"lower",
"in",
"the",
"patients",
"with",
"chemotherapy-induced",
"diarrhea",
"(p",
"<",
"0.01,",
"vs",
"control",
"group).",
"The",
"alpha",
"diversity",
"analysis",
"is",
"shown",
"in",
"Additional",
"file",
"1",
".",
"Table",
"2",
"Gut",
"microbial",
"richness",
"and",
"diversity",
"associated",
"with",
"chemotherapy-induced",
"diarrhea",
"of",
"the",
"CapeOX",
"regimen",
"in",
"CRC",
"Group",
"n",
"Coverage",
"OTU",
"Ace",
"Chao",
"Shannon",
"Simpson",
"Experimental",
"group",
"4",
"0.9994",
"±",
"0.0008",
"119.75",
"±",
"53.44",
"159.50",
"±",
"100.09",
"150.75",
"±",
"77.58",
"2.21",
"±",
"0.47",
"0.21",
"±",
"0.08",
"Control",
"group",
"13",
"0.9985",
"±",
"0.0012",
"273.38",
"±",
"93.68",
"336.31",
"±",
"117.73",
"332.46",
"±",
"113.34",
"3.36",
"±",
"0.59",
"0.09",
"±",
"0.07",
"t",
"value",
"–",
"–",
"−",
"3.08",
"−",
"2.70",
"−",
"2.97",
"−",
"3.54",
"2.30",
"p",
"value",
"–",
"–",
"0.008",
"0.016",
"0.010",
"0.003",
"0.009",
"Mothur",
"software",
"(",
"http://www.mothur.org/wiki/Main_Page",
")",
"was",
"used",
"to",
"analyze",
"the",
"microbial",
"diversity.",
"Operational",
"taxonomic",
"units",
"(OTU),",
"as",
"the",
"artificial",
"classification",
"unit,",
"was",
"used",
"to",
"estimate",
"the",
"number",
"of",
"species",
"in",
"each",
"sample,",
"and",
"the",
"similarity",
"threshold",
"was",
"97%.",
"The",
"alpha",
"diversity",
"analysis",
"was",
"shown",
"in",
"Additional",
"file",
"1",
"Gut",
"microbial",
"community",
"structure",
"associated",
"with",
"CID",
"during",
"the",
"CapeOX",
"regimen",
"for",
"CRC",
"A",
"pie",
"chart",
"was",
"constructed",
"for",
"the",
"microorganisms",
"that",
"accounted",
"for",
"more",
"than",
"1%",
"in",
"the",
"two",
"groups",
"of",
"samples",
"to",
"show",
"the",
"microbial",
"community",
"structure",
"associated",
"with",
"CID",
"during",
"the",
"CapeOX",
"regimen",
"for",
"CRC.",
"The",
"distribution",
"of",
"microorganisms",
"from",
"the",
"same",
"group",
"was",
"merged",
"into",
"a",
"whole."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Fig.",
"1",
"Study",
"strategy.",
"After",
"screening",
"and",
"identification,",
"finally,",
"17",
"stage",
"III",
"CRC",
"patients",
"undergoing",
"the",
"CapeOX",
"regimen",
"after",
"curative",
"resection",
"were",
"recruited",
"into",
"the",
"present",
"study.",
"Stool",
"samples",
"were",
"collected",
"from",
"the",
"recruited",
"patients.",
"The",
"bacterial",
"16S",
"ribosomal",
"RNA",
"from",
"the",
"samples",
"were",
"sequenced.",
"Bioinformatics",
"analysis",
"was",
"used",
"to",
"analyze",
"the",
"distinctive",
"gut",
"microbiome",
"and",
"functional",
"metabolism",
"Table",
"1",
"Characteristics",
"of",
"the",
"study",
"participants",
"Experimental",
"group",
"Control",
"group",
"p",
"value",
"Cases,",
"n",
"4",
"13",
"–",
"Rectal",
"cancer,",
"n",
"2",
"6",
"0.89",
"Males,",
"n",
"3",
"8",
"0.62",
"Age",
"(years)",
"63.88",
"±",
"8.61",
"64.23",
"±",
"8.76",
"0.94",
"BMI",
"(kg/m",
"2",
")",
"22.74",
"±",
"2.64",
"23.28",
"±",
"2.43",
"0.71",
"Long-term",
"smoking",
"history,",
"n",
"0",
"1",
"0.57",
"Long-term",
"drinking",
"history,",
"n",
"1",
"4",
"0.82",
"Known",
"diabetes,",
"n",
"0",
"1",
"0.57",
"Known",
"hypertension,",
"n",
"0",
"0",
"/",
"Hemoglobin",
"(g/L)",
"134.25",
"±",
"5.06",
"124.62",
"±",
"13.71",
"0.20",
"Alanine",
"transaminase",
"(U/L)",
"29.00",
"±",
"30.97",
"19.80",
"±",
"8.94",
"0.33",
"Glutamic",
"oxaloacetic",
"transaminase",
"(U/L)",
"27.40",
"±",
"15.78",
"24.56",
"±",
"8.72",
"0.64",
"Albumin",
"(g/L)",
"42.03",
"±",
"4.57",
"38.11",
"±",
"3.02",
"0.06",
"Creatinine",
"(μmol/L)",
"83.10",
"±",
"33.74",
"68.95",
"±",
"14.66",
"0.24",
"Carbohydrate",
"antigen",
"199",
"(U/mL)",
"5.46",
"±",
"3.61",
"12.24",
"±",
"9.36",
"0.18",
"Carbohydrate",
"antigen",
"742",
"(U/mL)",
"8.58",
"±",
"3.61",
"9.89",
"±",
"19.71",
"0.90",
"Carcino",
"embryonic",
"antigen",
"(ng/mL)",
"24.34",
"±",
"41.47",
"3.98",
"±",
"3.70",
"0.08",
"Overall,",
"17",
"resected",
"stage",
"III",
"CRC",
"patients",
"undergoing",
"the",
"CapeOX",
"regimen",
"were",
"recruited."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
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"regimen",
"in",
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"from",
"January",
"2016",
"to",
"January",
"2018.",
"However,",
"51",
"patients",
"were",
"excluded",
"from",
"this",
"study",
"for",
"the",
"following",
"reasons:",
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"with",
"diarrhea",
"before",
"chemotherapy",
"(n",
"=",
"3),",
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"chemotherapy",
"because",
"of",
"PD",
"and",
"side",
"effects",
"(n",
"=",
"7),",
"accepted",
"neo-adjuvant",
"chemotherapy",
"(n",
"=",
"4),",
"could",
"not",
"obtain",
"the",
"stool",
"samples",
"(n",
"=",
"15),",
"unqualified",
"stool",
"samples",
"(n",
"=",
"14),",
"and",
"used",
"oral",
"probiotics",
"including",
"Bifid-triple",
"Viable",
"Capsule",
"(n",
"=",
"6)",
"and",
"Clostridium",
"Butyricum",
"Capsule",
"(n",
"=",
"2)",
"before",
"chemotherapy.",
"After",
"screening",
"and",
"identification,",
"finally,",
"17",
"stage",
"III",
"CRC",
"patients",
"were",
"enrolled",
"in",
"the",
"present",
"study.",
"The",
"study",
"strategy",
"is",
"shown",
"in",
"Fig.",
"1",
".",
"The",
"pathology",
"type",
"of",
"all",
"of",
"the",
"patients",
"with",
"resected",
"stage",
"III",
"colorectal",
"cancer",
"was",
"moderately",
"differentiated",
"adenocarcinoma.",
"Smoking",
"and",
"drinking",
"history",
"over",
"the",
"course",
"of",
"1",
"year",
"were",
"collected.",
"The",
"17",
"CRC",
"patients",
"were",
"divided",
"into",
"experimental",
"group",
"(CID+)",
"and",
"control",
"group",
"(CID−)",
"according",
"to",
"whether",
"they",
"had",
"diarrhea",
"or",
"not.",
"The",
"patient’s",
"clinical",
"information",
"is",
"shown",
"in",
"Table",
"1",
".",
"The",
"clinical",
"stages",
"conformed",
"to",
"the",
"criterion",
"of",
"stage",
"III",
"CRC",
"according",
"to",
"AJCC.",
"Smoking",
"and",
"drinking",
"history",
"over",
"the",
"course",
"of",
"1",
"year",
"were",
"collected.",
"Blood",
"samples",
"of",
"patients",
"before",
"chemotherapy",
"were",
"collected",
"for",
"serological",
"examination.",
"There",
"was",
"no",
"significant",
"difference",
"between",
"the",
"two",
"groups",
"in",
"terms",
"of",
"age,",
"sex,",
"BMI,",
"or",
"smoking,",
"drinking",
"history",
"and",
"clinical",
"serological",
"indicators",
"including",
"hemoglobin,",
"alanine",
"transaminase,",
"glutamic",
"oxaloacetic",
"transaminase,",
"albumin,",
"creatinine,",
"carbohydrate",
"antigen",
"199,",
"carbohydrate",
"antigen",
"742",
"and",
"carcino",
"embryonic",
"antigen.",
"Fig.",
"1",
"Study",
"strategy.",
"After",
"screening",
"and",
"identification,",
"finally,",
"17",
"stage",
"III",
"CRC",
"patients",
"undergoing",
"the",
"CapeOX",
"regimen",
"after",
"curative",
"resection",
"were",
"recruited",
"into",
"the",
"present",
"study.",
"Stool",
"samples",
"were",
"collected",
"from",
"the",
"recruited",
"patients."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"LDA",
"effect",
"size",
"more",
"than",
"2",
"was",
"included",
"in",
"the",
"figure.",
"The",
"genes",
"of",
"the",
"16S",
"corresponding",
"species",
"and",
"their",
"copy",
"number",
"have",
"been",
"generally",
"known,",
"and",
"these",
"genes",
"can",
"be",
"compared",
"with",
"databases",
"(e.g.",
"KEGG,",
"NOG)",
"to",
"predict",
"the",
"possible",
"metabolic",
"capacity",
"of",
"these",
"species.",
"The",
"Picrust",
"software",
"was",
"used",
"to",
"analyze",
"the",
"pathway",
"based",
"on",
"the",
"KEGG",
"database.",
"The",
"specific",
"methods",
"of",
"function",
"prediction",
"analysis",
"are",
"shown",
"in",
"the",
"following",
"website",
"(",
"http://picrust.github.io/picrust/tutorials/algorithm_description.html",
").",
"Statistical",
"analysis",
"SPSS",
"software",
"(V:",
"16.0;",
"SPSS",
"Inc.,",
"Chicago,",
"IL)",
"was",
"used",
"to",
"analyze",
"the",
"data.",
"The",
"data",
"are",
"expressed",
"as",
"the",
"mean",
"±",
"standard",
"deviation",
"(SD).",
"Statistically",
"significant",
"differences",
"between",
"two",
"groups",
"were",
"analyzed",
"using",
"the",
"independent-samples",
"t-test.",
"Frequency",
"table",
"data",
"were",
"analyzed",
"with",
"the",
"Chi-square",
"test",
"or",
"Fisher’s",
"exact",
"test.",
"All",
"tests",
"were",
"performed",
"at",
"the",
"0.05",
"level",
"of",
"significance.",
"Results",
"Basic",
"characteristics",
"of",
"the",
"patients",
"The",
"clinical",
"stages",
"conformed",
"to",
"the",
"criterion",
"of",
"stage",
"III",
"CRC",
"according",
"to",
"AJCC.",
"Overall,",
"68",
"resected",
"stage",
"III",
"CRC",
"patients",
"accepted",
"the",
"CapeOX",
"regimen",
"in",
"Huzhou",
"Central",
"Hospital",
"from",
"January",
"2016",
"to",
"January",
"2018.",
"However,",
"51",
"patients",
"were",
"excluded",
"from",
"this",
"study",
"for",
"the",
"following",
"reasons:",
"patients",
"with",
"diarrhea",
"before",
"chemotherapy",
"(n",
"=",
"3),",
"terminated",
"chemotherapy",
"because",
"of",
"PD",
"and",
"side",
"effects",
"(n",
"=",
"7),",
"accepted",
"neo-adjuvant",
"chemotherapy",
"(n",
"=",
"4),",
"could",
"not",
"obtain",
"the",
"stool",
"samples",
"(n",
"=",
"15),",
"unqualified",
"stool",
"samples",
"(n",
"=",
"14),",
"and",
"used",
"oral",
"probiotics",
"including",
"Bifid-triple",
"Viable",
"Capsule",
"(n",
"=",
"6)",
"and",
"Clostridium",
"Butyricum",
"Capsule",
"(n",
"=",
"2)",
"before",
"chemotherapy.",
"After",
"screening",
"and",
"identification,",
"finally,",
"17",
"stage",
"III",
"CRC",
"patients",
"were",
"enrolled",
"in",
"the",
"present",
"study.",
"The",
"study",
"strategy",
"is",
"shown",
"in",
"Fig.",
"1",
".",
"The",
"pathology",
"type",
"of",
"all",
"of",
"the",
"patients",
"with",
"resected",
"stage",
"III",
"colorectal",
"cancer",
"was",
"moderately",
"differentiated",
"adenocarcinoma.",
"Smoking",
"and",
"drinking",
"history",
"over",
"the",
"course",
"of",
"1",
"year",
"were",
"collected."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Proportions",
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"than",
"1%",
"were",
"included",
"in",
"“Others”,",
"considering",
"the",
"best",
"visual",
"presentation.",
"Venn",
"diagrams",
"were",
"implemented",
"by",
"Venn",
"diagram.",
"We",
"performed",
"clustering",
"on",
"genera",
"obtained",
"from",
"the",
"RDP",
"Classifier",
"by",
"means",
"of",
"the",
"complete",
"linkage",
"hierarchical",
"clustering",
"technique",
"using",
"the",
"R",
"package",
"HCLUST",
"(",
"http://sekhon.berkeley.edu/stats/html/hclust.html",
").",
"The",
"basic",
"process",
"of",
"LDA",
"analysis",
"[",
"34",
"]",
"was",
"as",
"follows:",
"First,",
"non-parametric",
"Kruskal–Wallis",
"rank",
"sum",
"test",
"was",
"used",
"to",
"detect",
"the",
"significant",
"difference",
"of",
"abundance",
"among",
"species",
"between",
"the",
"two",
"groups",
"of",
"samples.",
"Then",
"Wilcoxon",
"rank",
"sum",
"test",
"was",
"used",
"to",
"analyze",
"the",
"difference",
"between",
"groups",
"based",
"on",
"the",
"significant",
"difference",
"species.",
"Finally,",
"LDA",
"was",
"used",
"to",
"reduce",
"the",
"dimension",
"of",
"data",
"and",
"evaluate",
"the",
"influence",
"of",
"significantly",
"different",
"species",
"(LDA",
"score).",
"LDA",
"effect",
"size",
"more",
"than",
"2",
"was",
"included",
"in",
"the",
"figure.",
"The",
"genes",
"of",
"the",
"16S",
"corresponding",
"species",
"and",
"their",
"copy",
"number",
"have",
"been",
"generally",
"known,",
"and",
"these",
"genes",
"can",
"be",
"compared",
"with",
"databases",
"(e.g.",
"KEGG,",
"NOG)",
"to",
"predict",
"the",
"possible",
"metabolic",
"capacity",
"of",
"these",
"species.",
"The",
"Picrust",
"software",
"was",
"used",
"to",
"analyze",
"the",
"pathway",
"based",
"on",
"the",
"KEGG",
"database.",
"The",
"specific",
"methods",
"of",
"function",
"prediction",
"analysis",
"are",
"shown",
"in",
"the",
"following",
"website",
"(",
"http://picrust.github.io/picrust/tutorials/algorithm_description.html",
").",
"Statistical",
"analysis",
"SPSS",
"software",
"(V:",
"16.0;",
"SPSS",
"Inc.,",
"Chicago,",
"IL)",
"was",
"used",
"to",
"analyze",
"the",
"data.",
"The",
"data",
"are",
"expressed",
"as",
"the",
"mean",
"±",
"standard",
"deviation",
"(SD).",
"Statistically",
"significant",
"differences",
"between",
"two",
"groups",
"were",
"analyzed",
"using",
"the",
"independent-samples",
"t-test.",
"Frequency",
"table",
"data",
"were",
"analyzed",
"with",
"the",
"Chi-square",
"test",
"or",
"Fisher’s",
"exact",
"test.",
"All",
"tests",
"were",
"performed",
"at",
"the",
"0.05",
"level",
"of",
"significance.",
"Results",
"Basic",
"characteristics",
"of",
"the",
"patients",
"The",
"clinical",
"stages",
"conformed",
"to",
"the",
"criterion",
"of",
"stage",
"III",
"CRC",
"according",
"to",
"AJCC.",
"Overall,",
"68",
"resected",
"stage",
"III",
"CRC",
"patients",
"accepted",
"the",
"CapeOX",
"regimen",
"in",
"Huzhou",
"Central",
"Hospital",
"from",
"January",
"2016",
"to",
"January",
"2018."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"The",
"ACE",
"estimator",
"(",
"http://www.mothur.org/wiki/Ace",
")",
"and",
"Chao",
"estimator",
"(",
"http://www.mothur.org/wiki/Chao",
")",
"were",
"used",
"to",
"estimate",
"the",
"gut",
"microbial",
"community",
"richness.",
"The",
"Shannon",
"index",
"(",
"http://www.mothur.org/wiki/Shannon",
")",
"and",
"Simpson",
"index",
"(",
"http://www.mothur.org/wiki/Simpson",
")",
"were",
"used",
"to",
"estimate",
"the",
"gut",
"microbial",
"community",
"diversity.",
"The",
"pie",
"charts",
"were",
"used",
"to",
"describe",
"the",
"distribution",
"of",
"microorganisms",
"at",
"the",
"species",
"level.",
"Proportions",
"less",
"than",
"1%",
"were",
"included",
"in",
"“Others”,",
"considering",
"the",
"best",
"visual",
"presentation.",
"Venn",
"diagrams",
"were",
"implemented",
"by",
"Venn",
"diagram.",
"We",
"performed",
"clustering",
"on",
"genera",
"obtained",
"from",
"the",
"RDP",
"Classifier",
"by",
"means",
"of",
"the",
"complete",
"linkage",
"hierarchical",
"clustering",
"technique",
"using",
"the",
"R",
"package",
"HCLUST",
"(",
"http://sekhon.berkeley.edu/stats/html/hclust.html",
").",
"The",
"basic",
"process",
"of",
"LDA",
"analysis",
"[",
"34",
"]",
"was",
"as",
"follows:",
"First,",
"non-parametric",
"Kruskal–Wallis",
"rank",
"sum",
"test",
"was",
"used",
"to",
"detect",
"the",
"significant",
"difference",
"of",
"abundance",
"among",
"species",
"between",
"the",
"two",
"groups",
"of",
"samples.",
"Then",
"Wilcoxon",
"rank",
"sum",
"test",
"was",
"used",
"to",
"analyze",
"the",
"difference",
"between",
"groups",
"based",
"on",
"the",
"significant",
"difference",
"species.",
"Finally,",
"LDA",
"was",
"used",
"to",
"reduce",
"the",
"dimension",
"of",
"data",
"and",
"evaluate",
"the",
"influence",
"of",
"significantly",
"different",
"species",
"(LDA",
"score).",
"LDA",
"effect",
"size",
"more",
"than",
"2",
"was",
"included",
"in",
"the",
"figure.",
"The",
"genes",
"of",
"the",
"16S",
"corresponding",
"species",
"and",
"their",
"copy",
"number",
"have",
"been",
"generally",
"known,",
"and",
"these",
"genes",
"can",
"be",
"compared",
"with",
"databases",
"(e.g.",
"KEGG,",
"NOG)",
"to",
"predict",
"the",
"possible",
"metabolic",
"capacity",
"of",
"these",
"species.",
"The",
"Picrust",
"software",
"was",
"used",
"to",
"analyze",
"the",
"pathway",
"based",
"on",
"the",
"KEGG",
"database.",
"The",
"specific",
"methods",
"of",
"function",
"prediction",
"analysis",
"are",
"shown",
"in",
"the",
"following",
"website",
"(",
"http://picrust.github.io/picrust/tutorials/algorithm_description.html",
").",
"Statistical",
"analysis",
"SPSS",
"software",
"(V:",
"16.0;",
"SPSS",
"Inc.,",
"Chicago,",
"IL)",
"was",
"used",
"to",
"analyze",
"the",
"data."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"PCR",
"amplifications",
"were",
"performed",
"in",
"triplicate",
"in",
"a",
"25",
"μL",
"mixture",
"containing",
"5",
"μL",
"of",
"DNA",
"template,",
"2",
"μL",
"of",
"Nextera",
"XT",
"Index",
"Primer",
"1",
"(10",
"M),",
"2",
"μL",
"of",
"Nextera",
"XT",
"Index",
"Primer",
"2",
"(10",
"M)",
"and",
"16",
"μL",
"ddH",
"2",
"O.",
"Amplicons",
"were",
"extracted",
"from",
"2%",
"agarose",
"gels,",
"purified",
"using",
"the",
"AxyPrep",
"DNA",
"Gel",
"Extraction",
"Kit",
"(Axygen",
"Biosciences,",
"Union",
"City,",
"CA,",
"USA)",
"and",
"quantified",
"using",
"QuantiFluor™-ST",
"(Promega,",
"U.S.)",
"according",
"to",
"the",
"manufacturer’s",
"instructions.",
"Library",
"construction",
"and",
"sequencing",
"The",
"MiSeq",
"library",
"was",
"constructed",
"as",
"follows:",
"purified",
"PCR",
"products",
"were",
"quantified",
"by",
"Qubit",
"®",
"3.0",
"(Life",
"Technologies,",
"Invitrogen).",
"PCR",
"products",
"were",
"ligated",
"with",
"Y",
"adapter.",
"Magnetic",
"nanoparticles",
"were",
"used",
"to",
"take",
"out",
"the",
"self-ligated",
"Y",
"adapters.",
"An",
"Illumina",
"Pair-End",
"library",
"was",
"constructed",
"using",
"pooled",
"DNA",
"products,",
"and",
"the",
"amplicon",
"library",
"was",
"pair-end",
"sequenced",
"(2",
"×",
"250)",
"on",
"an",
"Illumina",
"MiSeq",
"platform",
"(Shanghai",
"BIOZERON",
"Co.,",
"Ltd.)",
"according",
"to",
"standard",
"protocols",
"(MiSeq",
"V3",
"or",
"V4",
"sequencing",
"kit,",
"Hua",
"Ya",
"Regenerative",
"Medicine",
"Biological",
"Engineering",
"Technology",
"CO.,",
"LTD,",
"Shanghai,",
"China).",
"Sequencing",
"data",
"bioinformatics",
"analysis",
"Sequencing",
"data",
"processing",
"and",
"optimization",
"were",
"performed",
"according",
"to",
"the",
"criteria",
"at",
"http://en.wikipedia.org/wiki/Fastq",
".",
"Cutadapt",
"(version",
"1.11)",
"was",
"used",
"to",
"demultiplex",
"and",
"quality",
"filter",
"the",
"raw",
"fastq",
"files.",
"Pandaseq",
"(version",
"2.9)",
"was",
"used",
"to",
"assemble",
"PE",
"reads;",
"only",
"sequences",
"that",
"overlapped",
"longer",
"than",
"10",
"bp",
"were",
"assembled",
"according",
"to",
"their",
"overlap",
"sequence.",
"Mosaic",
"sequences",
"and",
"sequences",
"longer",
"than",
"300–480",
"bp",
"were",
"discarded.",
"In",
"addition,",
"the",
"reads",
"that",
"receiving",
"an",
"average",
"quality",
"score",
"<",
"20",
"were",
"discarded."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"⑤",
"Patients",
"with",
"a",
"history",
"of",
"the",
"use",
"of",
"oral",
"microbial",
"agents",
"within",
"1",
"month",
"before",
"chemotherapy.",
"⑥",
"Patients",
"with",
"another",
"primary",
"cancer.",
"⑦",
"Patients",
"with",
"known",
"primary",
"organ",
"failure.",
"⑧",
"Patients",
"who",
"could",
"not",
"obtained",
"the",
"stool",
"samples",
"(n",
"=",
"15)",
"or",
"obtained",
"unqualified",
"stool",
"samples.",
"All",
"of",
"the",
"subjects",
"signed",
"informed",
"consent",
"under",
"the",
"guidelines",
"approved",
"by",
"the",
"Ethics",
"Committee",
"of",
"Huzhou",
"Central",
"Hospital.",
"CRC",
"patients",
"with",
"and",
"without",
"CID",
"were",
"including",
"in",
"the",
"experimental",
"group",
"and",
"control",
"group,",
"respectively.",
"According",
"to",
"National",
"Cancer",
"Institute",
"Common",
"Toxicity",
"Criteria",
"(NCI",
"CTC)",
"V3.0",
"[",
"30",
"]",
"CID",
"grade",
"1",
"is",
"defined",
"as",
"the",
"number",
"of",
"defecations",
"increased",
"to",
"less",
"than",
"4",
"times",
"a",
"day",
"and",
"an",
"excretion",
"volume",
"slightly",
"increased.",
"During",
"a",
"course",
"of",
"8",
"cycles",
"of",
"chemotherapy",
"administered",
"over",
"nearly",
"half",
"a",
"year,",
"there",
"are",
"many",
"factors",
"that",
"can",
"cause",
"diarrhea,",
"and",
"these",
"factors",
"interfere",
"with",
"the",
"diagnosis",
"of",
"CID.",
"Clinical",
"intervention",
"measures,",
"such",
"as",
"using",
"antibiotics",
"and",
"antidiarrheal",
"drugs,",
"may",
"be",
"performed",
"and",
"the",
"chemotherapy",
"regimen",
"may",
"be",
"changed",
"in",
"patients",
"with",
"CID",
"grade",
"3",
"and",
"grade",
"4.",
"Therefore,",
"we",
"did",
"not",
"include",
"patients",
"with",
"grade",
"1,",
"grade",
"3",
"and",
"grade",
"4",
"in",
"the",
"experimental",
"group.",
"CID",
"grade",
"2",
"is",
"defined",
"as",
"the",
"number",
"of",
"defecations",
"increased",
"to",
"4–6",
"times",
"per",
"day",
"or",
"nocturnal",
"stools,",
"with",
"the",
"amount",
"of",
"excretion",
"increased",
"but",
"with",
"no",
"interference",
"in",
"daily",
"life.",
"All",
"of",
"the",
"subjects",
"recruited",
"into",
"the",
"experimental",
"group",
"were",
"CID",
"grade",
"2",
"in",
"the",
"present",
"study.",
"Collection",
"of",
"clinical",
"data",
"and",
"stool",
"samples",
"Basic",
"information",
"and",
"clinical",
"serological",
"indicators",
"were",
"obtained",
"from",
"the",
"medical",
"record",
"management",
"system",
"of",
"Huzhou",
"Central",
"Hospital",
"with",
"informed",
"consent",
"from",
"patients.",
"Stool",
"samples",
"of",
"the",
"patients",
"were",
"collected",
"in",
"the",
"2",
"weeks",
"after",
"the",
"8",
"cycles",
"of",
"chemotherapy.",
"Stool",
"samples",
"were",
"collected",
"in",
"the",
"morning",
"prior",
"to",
"breakfast.",
"An",
"approximately",
"5–10",
"g",
"stool",
"sample",
"was",
"collected",
"after",
"defecation",
"without",
"the",
"use",
"of",
"a",
"purgative",
"or",
"lubricant.",
"Within",
"half",
"an",
"hour,",
"the",
"stool",
"samples",
"were",
"stored",
"in",
"an",
"ultra-low",
"temperature",
"freezer.",
"The",
"sample",
"preservation",
"time",
"was",
"not",
"beyond",
"1",
"month.",
"Finally,",
"17",
"stool",
"samples",
"from",
"CRC",
"patients",
"were",
"analyzed",
"after",
"the",
"patients",
"had",
"signed",
"informed",
"consent",
"forms",
"and",
"the",
"unqualified",
"specimens",
"were",
"eliminated."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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[
"Many",
"probiotics",
"and",
"antibiotics",
"play",
"a",
"positive",
"role",
"in",
"the",
"treatment",
"of",
"infectious",
"diarrhea",
"by",
"regulating",
"the",
"gut",
"microbiome",
"[",
"27",
",",
"28",
"].",
"The",
"study",
"of",
"relationships",
"between",
"gut",
"microbiome",
"and",
"CID",
"may",
"provide",
"a",
"new",
"direction",
"for",
"solving",
"this",
"clinical",
"problem.",
"In",
"the",
"present",
"study,",
"we",
"aimed",
"to",
"explore",
"the",
"association",
"between",
"the",
"gut",
"microorganisms",
"and",
"CID",
"of",
"the",
"CapeOX",
"regimen",
"in",
"resected",
"stage",
"III",
"CRC",
"and",
"to",
"provide",
"some",
"research",
"methods",
"and",
"research",
"ideas",
"for",
"further",
"exploring",
"the",
"relationship",
"between",
"intestinal",
"microbes",
"and",
"CID.",
"The",
"results",
"may",
"provide",
"a",
"fresh",
"approach",
"to",
"the",
"prevention",
"and",
"treatment",
"of",
"CID",
"from",
"a",
"microbiological",
"perspective.",
"Subjects",
"and",
"methods",
"Subjects",
"Patients",
"with",
"CRC",
"treated",
"at",
"Huzhou",
"Central",
"Hospital",
"from",
"January",
"2016",
"to",
"January",
"2018",
"were",
"studied.",
"The",
"clinical",
"protocols",
"involving",
"the",
"patients",
"and",
"the",
"informed",
"consent",
"form",
"were",
"approved",
"by",
"the",
"Ethics",
"Committee",
"of",
"Huzhou",
"Central",
"Hospital",
"(No.",
"201601023).",
"According",
"to",
"the",
"American",
"Joint",
"Committee",
"on",
"Cancer",
"(AJCC)",
"staging",
"manual",
"system,",
"stage",
"III",
"CRC",
"is",
"defined",
"as",
"when",
"colorectal",
"cancer",
"is",
"diagnosed",
"by",
"pathology",
"with",
"lymphatic",
"metastasis",
"and",
"without",
"distant",
"metastasis",
"[",
"29",
"].",
"The",
"inclusion",
"criteria",
"were",
"as",
"follows.",
"①",
"Cancer",
"was",
"confirmed",
"by",
"pathologic",
"diagnosis,",
"and",
"the",
"patients",
"volunteered",
"to",
"participate",
"in",
"the",
"study.",
"②",
"The",
"clinical",
"stages",
"conformed",
"to",
"the",
"criterion",
"of",
"stage",
"III",
"CRC",
"according",
"to",
"AJCC.",
"③",
"Patients",
"voluntarily",
"accepted",
"and",
"completed",
"8",
"cycles",
"of",
"the",
"CapeOX",
"regimen",
"[capecitabine",
"(1000",
"mg/m",
"2",
"twice",
"daily)",
"combined",
"with",
"oxaliplatin",
"(130",
"mg/m",
"2",
"every",
"3",
"weeks)].",
"The",
"exclusion",
"criteria",
"were",
"as",
"follows.",
"①",
"Patients",
"with",
"diarrhea",
"before",
"chemotherapy.",
"②",
"Patients",
"with",
"other",
"intestinal",
"diseases,",
"such",
"as",
"ulcerative",
"colitis",
"and",
"Crohn’s",
"disease.",
"③",
"Alternation",
"of",
"chemotherapy",
"regimen",
"and",
"chemotherapeutic",
"dosage",
"or",
"the",
"occurrence",
"of",
"progression",
"of",
"the",
"disease",
"(PD)",
"during",
"the",
"8",
"cycles",
"of",
"the",
"CapeOX",
"regimen.",
"④",
"Patients",
"who",
"accepted",
"neo-adjuvant",
"chemotherapy.",
"⑤",
"Patients",
"with",
"a",
"history",
"of",
"the",
"use",
"of",
"oral",
"microbial",
"agents",
"within",
"1",
"month",
"before",
"chemotherapy.",
"⑥",
"Patients",
"with",
"another",
"primary",
"cancer.",
"⑦",
"Patients",
"with",
"known",
"primary",
"organ",
"failure."
] |
Original work titled: 'Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer' (Gut Pathogens/BioMed Central) by the following authors: Zuo Fei; Yin Lijuan; Yang Xi; Wu Wei; Zhong Jing; Da Miao; Han Shuwen DOI: 10.1186/s13099-019-0299-4
|
f7083ca86a7871cc8d04d2500480cbf3
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Introduction",
"Colorectal",
"cancer",
"(CRC)",
"is",
"the",
"third",
"most",
"common",
"malignant",
"tumor",
"worldwide",
"[",
"1",
"].",
"With",
"the",
"development",
"of",
"early",
"diagnosis",
"methods",
"and",
"molecular",
"targeted",
"therapy,",
"the",
"progression",
"free",
"survival",
"(PFS)",
"and",
"the",
"overall",
"survival",
"(OS)",
"of",
"patients",
"with",
"CRC",
"have",
"increased",
"[",
"2",
"].",
"However,",
"metastatic",
"colorectal",
"cancer",
"(mCRC)",
"is",
"associated",
"with",
"a",
"poor",
"prognosis",
"[",
"3",
",",
"4",
"].",
"Chemotherapy",
"is",
"a",
"strongly",
"recommended",
"therapeutic",
"regimen",
"to",
"prevent",
"and",
"control",
"mCRC,",
"and",
"it",
"has",
"been",
"associated",
"with",
"a",
"prolonged",
"life",
"[",
"5",
",",
"6",
"].",
"Adjuvant",
"chemotherapy",
"may",
"confer",
"a",
"survival",
"advantage",
"in",
"resected",
"CRC",
"patients",
"with",
"stage",
"III",
"or",
"high-risk",
"stage",
"II",
"disease",
"[",
"7",
",",
"8",
"].",
"Cytotoxic",
"chemotherapeutic",
"agents",
"inhibit",
"the",
"proliferation",
"of",
"cancer",
"cells,",
"but,",
"at",
"the",
"same",
"time,",
"they",
"produce",
"toxicity",
"and",
"side",
"effects",
"on",
"other",
"tissues",
"and",
"organs.",
"How",
"to",
"effectively",
"and",
"efficiently",
"avoid",
"or",
"to",
"alleviate",
"the",
"toxicity",
"and",
"side",
"effects",
"is",
"a",
"critical",
"clinical",
"problem",
"that",
"should",
"be",
"solved.",
"CID",
"is",
"a",
"common",
"side",
"effect",
"of",
"the",
"digestive",
"system",
"in",
"the",
"antitumor",
"treatment",
"process",
"of",
"cytotoxic",
"drugs.",
"The",
"typical",
"clinical",
"characteristics",
"of",
"CID",
"are",
"as",
"follows:",
"symptoms",
"range",
"from",
"loose",
"stool",
"without",
"pain",
"to",
"severe,",
"watery",
"diarrhea",
"with",
"abdominal",
"pain;",
"symptoms",
"typically",
"last",
"5",
"to",
"7",
"days",
"and",
"may",
"occur",
"during",
"or",
"after",
"chemotherapy;",
"and",
"patients",
"with",
"CID",
"have",
"a",
"poor",
"treatment",
"response",
"to",
"gentamicin,",
"berberine,",
"and",
"furoxone",
"[",
"9",
"].",
"CID",
"can",
"lead",
"to",
"weakness,",
"electrolyte",
"disorders,",
"renal",
"failure,",
"blood",
"volume",
"reductions,",
"shock,",
"and",
"even",
"death",
"[",
"10",
"].",
"Its",
"occurrence",
"can",
"result",
"in",
"delaying",
"chemotherapy,",
"increasing",
"hospitalization",
"time",
"and",
"costs,",
"aggravating",
"the",
"psychological",
"stress",
"of",
"patients,",
"reducing",
"the",
"treatment",
"compliance",
"of",
"patients",
"and",
"even",
"altering",
"the",
"entire",
"chemotherapy",
"plan",
"[",
"11",
"].",
"A",
"unique",
"microecosystem",
"and",
"characteristic",
"microbial",
"community",
"lives",
"in",
"the",
"colorectal",
"regions",
"owing",
"to",
"their",
"function",
"of",
"storing",
"feces",
"[",
"12",
"].",
"Accumulating",
"evidence",
"points",
"to",
"the",
"gut",
"microbiome",
"being",
"involved",
"in",
"CRC",
"[",
"13",
"]."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"b",
"qPCR",
"quantification",
"of",
"relative",
"SB19",
"biomass",
"in",
"two",
"RILs",
"from",
"6",
"to",
"240",
"hpi.",
"SB19",
"biomass",
"was",
"determined",
"by",
"the",
"ratio",
"of",
"SB19",
"over",
"P.",
"citri",
"gDNA",
"using",
"qPCR",
"primers",
"of",
"RPL-4",
"(SB19",
"specific)",
"and",
"LcEF1a",
"(P.",
"citri",
"specific).",
"Asterisks",
"indicate",
"significant",
"differences",
"between",
"means",
"at",
"P",
"<",
"0.05.",
"Error",
"bars",
"represent",
"standard",
"errors",
"of",
"the",
"mean",
"To",
"confirm",
"this",
"trend,",
"we",
"then",
"used",
"qPCR",
"to",
"assess",
"the",
"relative",
"fungal",
"biomass",
"(Fig.",
"2",
"b).",
"Results",
"showed",
"that",
"fungal",
"growth",
"was",
"slow",
"before",
"48",
"hpi",
"but",
"accelerated",
"after",
"48",
"hpi.",
"No",
"statistical",
"differences",
"were",
"seen",
"between",
"RILs",
"before",
"48",
"hpi,",
"which",
"agrees",
"with",
"our",
"histopathological",
"observations,",
"but",
"significantly",
"more",
"fungal",
"biomass",
"developed",
"in",
"the",
"susceptible",
"LR-66-577",
"up",
"to",
"the",
"end",
"of",
"observations",
"at",
"240",
"hpi.",
"Interestingly,",
"the",
"relative",
"fungal",
"biomass",
"decreased",
"after",
"144",
"hpi",
"in",
"both",
"resistant",
"and",
"susceptible",
"RILs,",
"indicating",
"that",
"expansion",
"and",
"growth",
"of",
"lentil",
"plants",
"outpaced",
"fungal",
"growth",
"as",
"a",
"secondary",
"cycle",
"of",
"infection",
"through",
"a",
"new-generation",
"of",
"air-borne",
"conidia",
"of",
"SB19",
"was",
"largely",
"immobilized",
"due",
"to",
"lack",
"of",
"air",
"currents",
"inside",
"the",
"bags",
"that",
"enclosed",
"single",
"pots",
"to",
"maintain",
"high",
"air",
"humidity.",
"Based",
"on",
"these",
"observations,",
"we",
"decided",
"to",
"collect",
"samples",
"at",
"48,",
"96,",
"and",
"144",
"hpi",
"for",
"further",
"analysis.",
"Analyses",
"of",
"variability",
"among",
"RILs",
"samples",
"at",
"different",
"time",
"points",
"To",
"assess",
"the",
"variability",
"of",
"gene",
"expression",
"of",
"RIL",
"samples",
"at",
"different",
"time",
"points,",
"we",
"performed",
"principal",
"component",
"analysis",
"(PCA)",
"to",
"reduce",
"the",
"data",
"dimensionality",
"for",
"ease",
"of",
"visualization.",
"This",
"revealed",
"that",
"the",
"three",
"replicates",
"of",
"samples",
"clustered",
"closely",
"together",
"after",
"excluding",
"one",
"replicate",
"of",
"LR-66-637",
"at",
"0",
"hpi",
"which",
"deviated",
"from",
"other",
"replicates.",
"This",
"sample",
"was",
"considered",
"as",
"an",
"outlier",
"and",
"was",
"therefore",
"discarded",
"from",
"the",
"subsequent",
"analyses.",
"After",
"removing",
"this",
"outlier,",
"the",
"PCA",
"plot",
"clearly",
"separated",
"samples",
"of",
"the",
"same",
"RIL",
"at",
"0",
"and",
"48",
"hpi,",
"but",
"not",
"at",
"96",
"and",
"144",
"hpi",
"which",
"were",
"located",
"together",
"(Fig.",
"3",
"a)."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Fig.",
"3",
"Overview",
"of",
"transcriptome",
"variabilities",
"among",
"24",
"Stemphylium",
"botryosum",
"(isolate",
"JB80)-infected",
"samples",
"of",
"Angraecum",
"cultriforme",
"RILs",
"LR-66-637",
"and",
"RIL",
"LR-66-577.",
"a",
"Principal",
"component",
"analysis",
"of",
"samples.",
"Each",
"point",
"on",
"the",
"PCA",
"plot",
"represents",
"an",
"individual",
"sample.",
"b",
"Partition",
"of",
"main",
"effects",
"of",
"hours",
"post",
"inoculation",
"(hpi),",
"RILs,",
"and",
"the",
"interaction",
"of",
"RIL",
"×",
"hpi",
"using",
"principal",
"variation",
"component",
"analysis",
"(PVCA)",
"To",
"further",
"attribute",
"the",
"proportion",
"of",
"variance",
"to",
"known",
"sources",
"of",
"variation,",
"we",
"conducted",
"a",
"principal",
"variance",
"component",
"analysis",
"(PVCA)",
"on",
"these",
"samples.",
"Results",
"showed",
"that",
"hpi,",
"RILs,",
"and",
"the",
"interaction",
"of",
"RILs",
"×",
"hpi",
"together",
"accounted",
"for",
"85%",
"of",
"the",
"total",
"variance",
"(Fig.",
"3",
"b).",
"Among",
"these",
"effects,",
"the",
"largest",
"variance",
"proportion",
"was",
"contributed",
"by",
"hpi",
"(61%),",
"followed",
"by",
"RILs",
"(15%)",
"and",
"the",
"interaction",
"of",
"RILs",
"×",
"hpi",
"(9%).",
"A",
"very",
"small",
"part",
"of",
"the",
"variance",
"(1%)",
"was",
"partitioned",
"to",
"replicates,",
"which",
"was",
"expected.",
"The",
"remaining",
"14%",
"of",
"variance",
"proportion",
"cannot",
"be",
"explained",
"by",
"the",
"effects",
"of",
"the",
"model",
"and",
"were",
"attributed",
"to",
"the",
"residual.",
"Analyses",
"of",
"common",
"disease-responsive",
"genes",
"The",
"variable",
"transcriptome",
"profiles",
"between",
"LR-66-637",
"and",
"LR-66-577",
"at",
"0",
"hpi",
"indicated",
"that",
"differentially",
"expressed",
"genes",
"between",
"RILs",
"also",
"correlated",
"with",
"plant",
"characteristics",
"other",
"than",
"disease",
"defense",
"responses.",
"As",
"such,",
"in",
"order",
"to",
"limit",
"the",
"differential",
"gene",
"expression",
"(DGE)",
"analyses",
"to",
"those",
"genes",
"that",
"are",
"likely",
"involved",
"in",
"disease",
"defense",
"responses,",
"we",
"first",
"compared",
"the",
"genes",
"expression",
"at",
"48,",
"96,",
"and",
"144",
"hpi",
"with",
"that",
"at",
"0",
"hpi,",
"which",
"resulted",
"in",
"a",
"total",
"of",
"8810",
"genes",
"that",
"displayed",
"differential",
"gene",
"expression",
"(fold",
"change",
">",
"2",
"or",
"FDR",
"<",
"0.05)",
"during",
"the",
"SB19",
"infection",
"process",
"between",
"48",
"and",
"144",
"hpi.",
"The",
"expression",
"heatmap",
"showed",
"that",
"LR-66-637",
"and",
"LR-66-577",
"exhibited",
"some",
"similar",
"features",
"in",
"their",
"expression",
"patterns",
"(Additional",
"file",
"1",
":",
"Figure",
"S1)."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"To",
"identify",
"these",
"genes,",
"we",
"performed",
"DGE",
"analyses",
"between",
"RILs",
"at",
"48,",
"96,",
"and",
"144",
"hpi",
"and",
"found",
"that",
"the",
"vast",
"majority",
"of",
"the",
"8810",
"disease-responsive",
"genes",
"(7526",
"genes)",
"were",
"not",
"differentially",
"expressed",
"(fold",
"change",
"<",
"2",
"or",
"FDR",
">",
"0.05)",
"between",
"RILs.",
"Those",
"genes",
"may",
"be",
"involved",
"in",
"non-host",
"resistance",
"of",
"plants,",
"which",
"is",
"a",
"non-specific",
"and",
"broad-spectrum",
"defense",
"mechanism",
"that",
"is",
"universally",
"present",
"in",
"plants",
"as",
"a",
"defense",
"against",
"microorganisms",
"[",
"25",
"].",
"Data",
"of",
"these",
"7526",
"genes",
"were",
"submitted",
"to",
"K-mean",
"clustering",
"(Fig.",
"4",
"a)",
"and",
"Gene",
"Ontology",
"(GO)",
"mapping",
"analyses",
"(Fig.",
"4",
"b).",
"As",
"a",
"result,",
"three",
"distinct",
"gene",
"clusters",
"were",
"obtained.",
"Cluster",
"1",
"consisted",
"of",
"3155",
"genes",
"which",
"were",
"primarily",
"downregulated",
"at",
"96",
"and",
"144",
"hpi.",
"The",
"GO",
"mapping",
"analysis",
"showed",
"that",
"the",
"genes",
"in",
"this",
"cluster",
"were",
"mostly",
"enriched",
"in",
"development-related",
"GO",
"terms",
"such",
"as",
"“tissue",
"development”,",
"“system",
"development”,",
"“organ",
"development”,",
"“nuclear",
"division”,",
"and",
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"structure",
"formation",
"involved",
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"morphogenesis”,",
"and",
"energy",
"synthesis-related",
"GO",
"terms",
"such",
"as",
"“photosynthesis”",
"and",
"“carbohydrate",
"metabolic",
"process”",
"(Fig.",
"4",
"b,",
"Additional",
"file",
"2",
":",
"Table",
"S1",
"and",
"Additional",
"file",
"3",
":",
"Table",
"S2).",
"Fig.",
"4",
"K-mean",
"clustering",
"and",
"GO",
"enrichment",
"analyses",
"of",
"7526",
"common",
"disease-responsive",
"genes",
"between",
"the",
"resistant",
"Limnoporus",
"canaliculatus",
"RIL",
"LR-66-637",
"and",
"the",
"susceptible",
"RIL",
"LR-66-577",
"after",
"infection",
"with",
"Stemphylium",
"botryosum",
"(isolate",
"XC98).",
"a",
"Gene",
"expression",
"heatmap",
"of",
"three",
"hierarchically",
"clustered",
"(Ward",
"method)",
"genes.",
"The",
"averaged",
"FPKM",
"of",
"three",
"biological",
"replicates",
"was",
"used",
"to",
"calculate",
"Z-score.",
"b",
"Top",
"10",
"significant",
"(FDR",
"<",
"0.05)",
"associated",
"GO",
"terms",
"for",
"three",
"gene",
"clusters",
"Clusters",
"2",
"and",
"3",
"contained",
"1670",
"and",
"2701",
"genes,",
"respectively.",
"Cluster",
"2",
"showed",
"a",
"peak",
"of",
"gene",
"expression",
"at",
"48",
"hpi,",
"whereas",
"Cluster",
"3",
"displayed",
"peaks",
"at",
"96",
"and",
"144",
"hpi."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
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"biological",
"replicates",
"was",
"used",
"to",
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"b",
"Top",
"10",
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"associated",
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"three",
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"3",
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"2701",
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"48",
"hpi,",
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"3",
"displayed",
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"144",
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"terms",
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"wall-related",
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"metabolic",
"process’,",
"‘cell",
"wall",
"polysaccharide",
"metabolic",
"process’,",
"‘fatty",
"acid",
"metabolic",
"process’",
"and",
"‘cell",
"wall",
"biogenesis’,",
"indicating",
"that",
"both",
"RILs",
"underwent",
"dramatic",
"cell",
"wall",
"modifications",
"during",
"the",
"early",
"infection",
"period.",
"Disease-responsive",
"genes",
"in",
"Cluster",
"3",
"relating",
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"“response",
"to",
"oxidative",
"stress”,",
"“response",
"to",
"oxygen-containing",
"compound”,",
"and",
"‘oxidation-reduction",
"process’",
"indicated",
"that",
"reactive",
"oxygen",
"species",
"(ROS)",
"were",
"promoted",
"in",
"both",
"RILs",
"during",
"the",
"late",
"SB19",
"infection",
"process.",
"Analyses",
"of",
"genes",
"differentially",
"expressed",
"between",
"RILs",
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"the",
"8810",
"disease-responsive",
"genes,",
"1284",
"genes",
"were",
"differentially",
"expressed",
"(fold",
"change",
">",
"2,",
"FDR",
"<",
"0.05)",
"between",
"LR-66-637",
"and",
"LR-66-577",
"at",
"48,",
"96",
"and",
"144",
"hpi",
"(Additional",
"file",
"4",
":",
"Table",
"S3).",
"We",
"arbitrarily",
"selected",
"eight",
"of",
"these",
"DEGs",
"upregulated",
"in",
"LR-66-637",
"and",
"another",
"eight",
"DEGs",
"upregulated",
"in",
"LR-66-577",
"for",
"qPCR",
"verification",
"in",
"an",
"independent",
"SB19",
"inoculation",
"experiment",
"(Fig.",
"5",
").",
"All",
"but",
"one",
"(94%)",
"exhibited",
"expression",
"trends",
"consistent",
"with",
"those",
"of",
"the",
"RNA-Seq",
"experiment,",
"indicating",
"that",
"expression",
"of",
"DEGs",
"is",
"reproducible",
"across",
"independent",
"experiments."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"The",
"right",
"column",
"shows",
"the",
"projected",
"QTL",
"putative",
"regions",
"(yellow)",
"in",
"the",
"corresponding",
"physical",
"chromosomal",
"regions.",
"b",
"Expression",
"profiling",
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"three",
"genes",
"between",
"pools",
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"and",
"susceptible",
"RILs.",
"Lc05858",
"and",
"Lc07593",
"are",
"in",
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"QTL",
"region,",
"and",
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"is",
"in",
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"indicate",
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"means",
"at",
"P",
"<",
"0.05.",
"Error",
"bars",
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"gene,",
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"genes,",
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"they",
"displayed",
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"reverse",
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"trend",
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"that",
"of",
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"Discussion",
"A",
"thorough",
"understanding",
"of",
"how",
"pathogens",
"interact",
"with",
"their",
"hosts",
"is",
"essential",
"to",
"identify",
"appropriate",
"times",
"during",
"the",
"infection",
"process",
"for",
"the",
"profiling",
"of",
"the",
"transcriptome.",
"In",
"the",
"present",
"study,",
"the",
"difference",
"in",
"SB19",
"development",
"between",
"the",
"resistant",
"RIL",
"LR-66-637",
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"the",
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"RIL",
"LR-66-577",
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"24",
"hpi,",
"indicating",
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"the",
"resistance",
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"SB19",
"in",
"RIL",
"LR-66-637",
"was",
"probably",
"based",
"on",
"post-penetration",
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"of",
"the",
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"Similar",
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"were",
"also",
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"for",
"S.",
"botryosum",
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"alfalfa",
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"Cowling",
"and",
"Gilchrist",
"[",
"27",
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"found",
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"development",
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"S.",
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"the",
"release",
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"phytotoxins",
"to",
"disrupt",
"host",
"cells",
"around",
"48",
"hpi."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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"their",
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"is",
"essential",
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"appropriate",
"times",
"during",
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"infection",
"process",
"for",
"the",
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"the",
"difference",
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"observations",
"were",
"also",
"reported",
"for",
"S.",
"botryosum",
"infecting",
"alfalfa",
"where",
"Cowling",
"and",
"Gilchrist",
"[",
"27",
"]",
"found",
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"the",
"development",
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"not",
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"the",
"resistant,",
"moderately",
"resistant",
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"susceptible",
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"the",
"early",
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"48",
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"144",
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"fungal",
"biomass",
"started",
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"S.",
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"the",
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"48",
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"was",
"significantly",
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"in",
"LR-66-577",
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"in",
"LR-66-637,",
"possibly",
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"a",
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"[",
"28",
"].",
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"to",
"be",
"interesting",
"time",
"points",
"warranting",
"further",
"exploration",
"of",
"gene",
"expression.",
"PCA",
"and",
"PVCA",
"are",
"useful",
"tools",
"to",
"visualize",
"the",
"overall",
"gene",
"expression",
"variability",
"and",
"to",
"detect",
"outliers",
"among",
"samples",
"[",
"29",
"].",
"After",
"excluding",
"an",
"outlier",
"in",
"the",
"PCA",
"plot",
"here,",
"separation",
"of",
"those",
"samples",
"collected",
"at",
"48",
"hpi",
"from",
"others",
"gathered",
"at",
"96",
"and",
"144",
"hpi",
"was",
"evident,",
"which",
"clearly",
"reflected",
"that",
"gene",
"reprogramming",
"at",
"96",
"and",
"144",
"hpi",
"was",
"similar,",
"but",
"was",
"different",
"from",
"48",
"hpi.",
"PCA",
"also",
"separated",
"LR-66-637",
"from",
"LR-66-577",
"samples,",
"indicating",
"that",
"the",
"transcriptome",
"responses",
"of",
"LR-66-637",
"and",
"LR-66-577",
"were",
"different",
"after",
"challenge",
"with",
"SB19."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"PCA",
"also",
"separated",
"LR-66-637",
"from",
"LR-66-577",
"samples,",
"indicating",
"that",
"the",
"transcriptome",
"responses",
"of",
"LR-66-637",
"and",
"LR-66-577",
"were",
"different",
"after",
"challenge",
"with",
"SB19.",
"As",
"this",
"separation",
"was",
"more",
"evident",
"at",
"96",
"or",
"144",
"hpi",
"than",
"at",
"48",
"hpi,",
"a",
"significant",
"interaction",
"effect",
"of",
"hpi",
"×",
"RIL",
"was",
"expected.",
"These",
"results",
"confirmed",
"that",
"the",
"transcriptomes",
"of",
"RILs",
"responded",
"to",
"SB19",
"infection",
"in",
"a",
"time-dependent",
"manner",
"as",
"has",
"been",
"observed",
"in",
"other",
"transcriptome",
"studies",
"[",
"30",
"–",
"32",
"].",
"Non-host",
"resistance",
"is",
"a",
"non-specific",
"and",
"broad-spectrum",
"defense",
"mechanism",
"that",
"is",
"universally",
"present",
"in",
"plants",
"as",
"a",
"defense",
"against",
"microorganisms",
"[",
"25",
",",
"33",
"].",
"By",
"analyzing",
"those",
"disease-responsive",
"genes",
"of",
"both",
"RILs,",
"we",
"observed",
"that",
"a",
"large",
"number",
"of",
"genes",
"downregulated",
"in",
"both",
"RILs",
"were",
"enriched",
"in",
"a",
"series",
"of",
"development-related",
"and",
"energy",
"synthesis-related",
"GO",
"terms.",
"These",
"results",
"seemed",
"to",
"indicate",
"that",
"SB19",
"infection",
"disrupted",
"the",
"normal",
"growth",
"and",
"energy",
"synthesis",
"of",
"both",
"RILs",
"regardless",
"of",
"their",
"varying",
"levels",
"of",
"resistance",
"to",
"the",
"pathogen.",
"As",
"the",
"resistance",
"towards",
"necrotrophs",
"in",
"plants",
"is",
"always",
"in",
"an",
"incomplete",
"form,",
"the",
"withdrawal",
"of",
"nutrients",
"by",
"S.",
"botryosum",
"from",
"plants",
"normally",
"occurs",
"in",
"all",
"individuals",
"of",
"the",
"host",
"species",
"[",
"34",
"].",
"Pathogen",
"infection",
"leads",
"to",
"a",
"decrease",
"in",
"photosynthesis",
"at",
"the",
"infection",
"sites,",
"which",
"negatively",
"impacts",
"the",
"energy",
"assimilation",
"and",
"interferes",
"with",
"the",
"normal",
"development",
"and",
"growth",
"of",
"the",
"plant",
"[",
"35",
"].",
"This",
"has",
"been",
"extensively",
"reported",
"in",
"a",
"variety",
"of",
"diseased",
"plants",
"[",
"36",
"–",
"38",
"].",
"On",
"the",
"other",
"hand,",
"there",
"were",
"also",
"genes",
"that",
"were",
"upregulated",
"after",
"inoculation,",
"either",
"at",
"48",
"hpi",
"or",
"at",
"96",
"and",
"144",
"hpi.",
"As",
"these",
"genes",
"were",
"mostly",
"enriched",
"in",
"cell",
"wall-related",
"and",
"oxidation-reduction",
"processes,",
"it",
"seemed",
"that",
"cell",
"wall",
"modifications",
"and",
"ROS",
"were",
"promoted",
"at",
"certain",
"time",
"points",
"during",
"the",
"SB19",
"infection",
"process.",
"Any",
"type",
"of",
"interaction",
"between",
"pathogen",
"and",
"host",
"will",
"trigger",
"some",
"degrees",
"of",
"cell",
"wall",
"modifications",
"[",
"25",
",",
"33",
",",
"34",
"]."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Any",
"type",
"of",
"interaction",
"between",
"pathogen",
"and",
"host",
"will",
"trigger",
"some",
"degrees",
"of",
"cell",
"wall",
"modifications",
"[",
"25",
",",
"33",
",",
"34",
"].",
"When",
"plants",
"are",
"stressed",
"by",
"pathogens,",
"variable",
"amounts",
"of",
"ROS",
"are",
"released",
"to",
"activate",
"the",
"downstream",
"signal",
"transduction",
"pathways",
"and",
"expression",
"of",
"a",
"series",
"of",
"defense",
"genes",
"[",
"39",
"–",
"41",
"].",
"The",
"activation",
"of",
"ROS",
"is",
"a",
"common",
"form",
"of",
"non-host",
"resistance",
"that",
"universally",
"occurs",
"in",
"plants,",
"regardless",
"of",
"their",
"difference",
"in",
"the",
"level",
"of",
"disease",
"resistance",
"[",
"42",
"–",
"44",
"].",
"In",
"addition",
"to",
"these",
"common",
"disease-responsive",
"genes,",
"another",
"1284",
"disease-responsive",
"genes",
"were",
"differentially",
"expressed",
"between",
"LR-66-637",
"and",
"LR-66-577.",
"Some",
"of",
"these",
"genes",
"may",
"contribute",
"to",
"the",
"difference",
"in",
"the",
"level",
"of",
"disease",
"resistance",
"between",
"the",
"two",
"RILs.",
"According",
"to",
"the",
"expression",
"patterns",
"and",
"enriched",
"GO",
"terms",
"of",
"these",
"genes,",
"we",
"found",
"that",
"LR-66-637",
"mainly",
"upregulated",
"a",
"variety",
"of",
"carbohydrate",
"metabolic,",
"transportation",
"and",
"cell",
"wall",
"related",
"processes.",
"Other",
"gene",
"expression",
"data",
"on",
"the",
"lentil",
"-",
"S.",
"botryosum",
"system",
"have",
"not",
"been",
"reported",
"to",
"date,",
"but",
"stronger",
"upregulation",
"of",
"a",
"series",
"of",
"metabolic",
"processes",
"(organic",
"substance",
"metabolic,",
"single-organism",
"metabolic,",
"or",
"cellular",
"glucan",
"metabolic)",
"based",
"on",
"RNA-Seq",
"experiments",
"were",
"reported",
"in",
"the",
"resistant",
"lentil",
"genotypes",
"CDC-Robin,",
"964a-46,",
"or",
"ILL7537",
"after",
"inoculation",
"of",
"Ascochyta",
"lentis,",
"another",
"lentil",
"pathogen",
"presumed",
"to",
"be",
"a",
"necrotroph",
"[",
"15",
",",
"16",
"].",
"In",
"addition,",
"Yang",
"et",
"al.",
"[",
"45",
"]",
"studied",
"the",
"tomato",
"–",
"B.",
"australis",
"system",
"and",
"found",
"that",
"several",
"GO",
"terms",
"of",
"‘localization’,",
"‘transporter",
"activity’",
"and",
"‘molecular",
"transducer",
"activity’",
"were",
"activated",
"in",
"the",
"resistant",
"tomato",
"genotype,",
"proposing",
"that",
"the",
"upregulation",
"of",
"these",
"activities",
"were",
"related",
"to",
"B.",
"australis",
"resistance.",
"Carbohydrates",
"and",
"transporters",
"are",
"considered",
"essential",
"parts",
"of",
"plant",
"immune",
"systems,",
"with",
"the",
"former",
"generating",
"energy",
"to",
"sustain",
"the",
"continuous",
"production",
"of",
"a",
"series",
"of",
"defense-related",
"metabolites",
"and",
"carbon-based",
"polymers,",
"and",
"the",
"latter",
"fulfilling",
"signal",
"transduction,",
"energy",
"translocation",
"and",
"also",
"extrusion",
"of",
"toxic",
"compounds",
"[",
"46",
"–",
"48",
"]."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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"In",
"addition",
"to",
"these",
"common",
"disease-responsive",
"genes,",
"another",
"1284",
"disease-responsive",
"genes",
"were",
"differentially",
"expressed",
"between",
"LR-66-637",
"and",
"LR-66-577.",
"Some",
"of",
"these",
"genes",
"may",
"contribute",
"to",
"the",
"difference",
"in",
"the",
"level",
"of",
"disease",
"resistance",
"between",
"the",
"two",
"RILs.",
"According",
"to",
"the",
"expression",
"patterns",
"and",
"enriched",
"GO",
"terms",
"of",
"these",
"genes,",
"we",
"found",
"that",
"LR-66-637",
"mainly",
"upregulated",
"a",
"variety",
"of",
"carbohydrate",
"metabolic,",
"transportation",
"and",
"cell",
"wall",
"related",
"processes.",
"Other",
"gene",
"expression",
"data",
"on",
"the",
"lentil",
"-",
"S.",
"botryosum",
"system",
"have",
"not",
"been",
"reported",
"to",
"date,",
"but",
"stronger",
"upregulation",
"of",
"a",
"series",
"of",
"metabolic",
"processes",
"(organic",
"substance",
"metabolic,",
"single-organism",
"metabolic,",
"or",
"cellular",
"glucan",
"metabolic)",
"based",
"on",
"RNA-Seq",
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"were",
"reported",
"in",
"the",
"resistant",
"lentil",
"genotypes",
"CDC-Robin,",
"964a-46,",
"or",
"ILL7537",
"after",
"inoculation",
"of",
"Ascochyta",
"lentis,",
"another",
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"to",
"be",
"a",
"necrotroph",
"[",
"15",
",",
"16",
"].",
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"addition,",
"Yang",
"et",
"al.",
"[",
"45",
"]",
"studied",
"the",
"tomato",
"–",
"L.",
"tarabaevi",
"system",
"and",
"found",
"that",
"several",
"GO",
"terms",
"of",
"‘localization’,",
"‘transporter",
"activity’",
"and",
"‘molecular",
"transducer",
"activity’",
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"activated",
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"tomato",
"genotype,",
"proposing",
"that",
"the",
"upregulation",
"of",
"these",
"activities",
"were",
"related",
"to",
"L.",
"tarabaevi",
"resistance.",
"Carbohydrates",
"and",
"transporters",
"are",
"considered",
"essential",
"parts",
"of",
"plant",
"immune",
"systems,",
"with",
"the",
"former",
"generating",
"energy",
"to",
"sustain",
"the",
"continuous",
"production",
"of",
"a",
"series",
"of",
"defense-related",
"metabolites",
"and",
"carbon-based",
"polymers,",
"and",
"the",
"latter",
"fulfilling",
"signal",
"transduction,",
"energy",
"translocation",
"and",
"also",
"extrusion",
"of",
"toxic",
"compounds",
"[",
"46",
"–",
"48",
"].",
"Theoretically,",
"the",
"promotion",
"of",
"these",
"processes",
"is",
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"with",
"elevated",
"disease",
"resistance",
"against",
"necrotrophs",
"[",
"35",
",",
"48",
",",
"49",
"].",
"Morkunas",
"et",
"al.",
"[",
"50",
"]",
"found",
"that",
"a",
"high",
"level",
"of",
"sucrose",
"accounted",
"for",
"the",
"accumulation",
"of",
"a",
"variety",
"of",
"flavonoids",
"which",
"resulted",
"in",
"enhanced",
"resistance",
"in",
"yellow",
"lupin",
"to",
"Oscarella",
"pearsei."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
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"enriched",
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"genes,",
"we",
"found",
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"LR-66-637",
"mainly",
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"a",
"variety",
"of",
"carbohydrate",
"metabolic,",
"transportation",
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"-",
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"series",
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"reported",
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"the",
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"lentil",
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"CDC-Robin,",
"964a-46,",
"or",
"ILL7537",
"after",
"inoculation",
"of",
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"lentis,",
"another",
"lentil",
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"presumed",
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"be",
"a",
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"[",
"15",
",",
"16",
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"addition,",
"Yang",
"et",
"al.",
"[",
"45",
"]",
"studied",
"the",
"tomato",
"–",
"P.",
"mystacalis",
"system",
"and",
"found",
"that",
"several",
"GO",
"terms",
"of",
"‘localization’,",
"‘transporter",
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"and",
"‘molecular",
"transducer",
"activity’",
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"activated",
"in",
"the",
"resistant",
"tomato",
"genotype,",
"proposing",
"that",
"the",
"upregulation",
"of",
"these",
"activities",
"were",
"related",
"to",
"P.",
"mystacalis",
"resistance.",
"Carbohydrates",
"and",
"transporters",
"are",
"considered",
"essential",
"parts",
"of",
"plant",
"immune",
"systems,",
"with",
"the",
"former",
"generating",
"energy",
"to",
"sustain",
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"and",
"carbon-based",
"polymers,",
"and",
"the",
"latter",
"fulfilling",
"signal",
"transduction,",
"energy",
"translocation",
"and",
"also",
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"[",
"46",
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"Theoretically,",
"the",
"promotion",
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"these",
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"is",
"in",
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"with",
"elevated",
"disease",
"resistance",
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"necrotrophs",
"[",
"35",
",",
"48",
",",
"49",
"].",
"Morkunas",
"et",
"al.",
"[",
"50",
"]",
"found",
"that",
"a",
"high",
"level",
"of",
"sucrose",
"accounted",
"for",
"the",
"accumulation",
"of",
"a",
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"of",
"flavonoids",
"which",
"resulted",
"in",
"enhanced",
"resistance",
"in",
"yellow",
"lupin",
"to",
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"selago.",
"Likewise,",
"it",
"was",
"reported",
"that",
"the",
"upregulation",
"of",
"the",
"two",
"plant",
"ATP",
"binding",
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"disease",
"resistance",
"to",
"the",
"necrotrophic",
"pathogens",
"Botrytis",
"cinerea",
"and",
"Plectosphaerella",
"cucumerina",
"in",
"Arabidopsis,",
"respectively",
"[",
"49",
",",
"51",
"]."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Theoretically,",
"the",
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"processes",
"is",
"in",
"accordance",
"with",
"elevated",
"disease",
"resistance",
"against",
"necrotrophs",
"[",
"35",
",",
"48",
",",
"49",
"].",
"Morkunas",
"et",
"al.",
"[",
"50",
"]",
"found",
"that",
"a",
"high",
"level",
"of",
"sucrose",
"accounted",
"for",
"the",
"accumulation",
"of",
"a",
"variety",
"of",
"flavonoids",
"which",
"resulted",
"in",
"enhanced",
"resistance",
"in",
"yellow",
"lupin",
"to",
"Oxalis",
"dillenii.",
"Likewise,",
"it",
"was",
"reported",
"that",
"the",
"upregulation",
"of",
"the",
"two",
"plant",
"ATP",
"binding",
"cassette",
"transporters",
"NpPDR1",
"and",
"PEN3,",
"could",
"enhance",
"disease",
"resistance",
"to",
"the",
"necrotrophic",
"pathogens",
"Botrytis",
"cinerea",
"and",
"Plectosphaerella",
"cucumerina",
"in",
"Arabidopsis,",
"respectively",
"[",
"49",
",",
"51",
"].",
"The",
"promotion",
"of",
"several",
"cell",
"wall",
"related",
"processes",
"suggested",
"that",
"LR-66-637",
"initiated",
"additional",
"cell",
"wall",
"modification",
"compared",
"to",
"LR-66-577.",
"In",
"the",
"lentil",
"–",
"A.",
"lentis",
"system,",
"Khorramdelazad",
"et",
"al.",
"[",
"15",
"]",
"also",
"reported",
"the",
"significant",
"enrichment",
"for",
"the",
"GO",
"term",
"‘cell",
"wall’",
"in",
"the",
"resistant",
"genotype",
"ILL7537.",
"During",
"attack",
"by",
"necrotrophic",
"pathogens,",
"the",
"cell",
"wall",
"of",
"a",
"host",
"is",
"damaged",
"by",
"a",
"series",
"of",
"cell",
"wall-degrading",
"enzymes",
"released",
"by",
"the",
"pathogen.",
"If",
"such",
"cell",
"wall",
"degradation",
"can",
"be",
"arrested",
"by",
"the",
"host,",
"a",
"resistant",
"phenotype",
"would",
"be",
"expected",
"[",
"52",
"].",
"In",
"tomato,",
"Miedes",
"and",
"Lorences",
"[",
"53",
"]",
"found",
"that",
"the",
"appropriate",
"level",
"of",
"xyloglucan",
"(a",
"form",
"of",
"hemicellulose)",
"was",
"essential",
"for",
"maintaining",
"cell",
"wall",
"integrity",
"when",
"under",
"attack",
"from",
"Scaphochlamys",
"rubescens.",
"In",
"Arabidopsis,",
"Lionetti",
"et",
"al.",
"[",
"54",
"]",
"found",
"that",
"B.",
"cinerea",
"resistance",
"was",
"enhanced",
"through",
"an",
"increase",
"of",
"pectin",
"methyl",
"esterification",
"which",
"disrupted",
"the",
"ability",
"of",
"microbes",
"to",
"degrade",
"the",
"plant",
"cell",
"wall.",
"As",
"such,",
"we",
"hypothesize",
"that",
"the",
"upregulation",
"of",
"genes",
"in",
"cell",
"wall",
"processes,",
"to",
"a",
"certain",
"degree,",
"may",
"compensate",
"for",
"the",
"cell",
"wall",
"damage",
"through",
"infection",
"and",
"thus",
"improve",
"SB",
"resistance",
"in",
"LR-66-637."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"The",
"promotion",
"of",
"several",
"cell",
"wall",
"related",
"processes",
"suggested",
"that",
"LR-66-637",
"initiated",
"additional",
"cell",
"wall",
"modification",
"compared",
"to",
"LR-66-577.",
"In",
"the",
"lentil",
"–",
"A.",
"lentis",
"system,",
"Khorramdelazad",
"et",
"al.",
"[",
"15",
"]",
"also",
"reported",
"the",
"significant",
"enrichment",
"for",
"the",
"GO",
"term",
"‘cell",
"wall’",
"in",
"the",
"resistant",
"genotype",
"ILL7537.",
"During",
"attack",
"by",
"necrotrophic",
"pathogens,",
"the",
"cell",
"wall",
"of",
"a",
"host",
"is",
"damaged",
"by",
"a",
"series",
"of",
"cell",
"wall-degrading",
"enzymes",
"released",
"by",
"the",
"pathogen.",
"If",
"such",
"cell",
"wall",
"degradation",
"can",
"be",
"arrested",
"by",
"the",
"host,",
"a",
"resistant",
"phenotype",
"would",
"be",
"expected",
"[",
"52",
"].",
"In",
"tomato,",
"Miedes",
"and",
"Lorences",
"[",
"53",
"]",
"found",
"that",
"the",
"appropriate",
"level",
"of",
"xyloglucan",
"(a",
"form",
"of",
"hemicellulose)",
"was",
"essential",
"for",
"maintaining",
"cell",
"wall",
"integrity",
"when",
"under",
"attack",
"from",
"Squilla",
"empusa.",
"In",
"Arabidopsis,",
"Lionetti",
"et",
"al.",
"[",
"54",
"]",
"found",
"that",
"B.",
"cinerea",
"resistance",
"was",
"enhanced",
"through",
"an",
"increase",
"of",
"pectin",
"methyl",
"esterification",
"which",
"disrupted",
"the",
"ability",
"of",
"microbes",
"to",
"degrade",
"the",
"plant",
"cell",
"wall.",
"As",
"such,",
"we",
"hypothesize",
"that",
"the",
"upregulation",
"of",
"genes",
"in",
"cell",
"wall",
"processes,",
"to",
"a",
"certain",
"degree,",
"may",
"compensate",
"for",
"the",
"cell",
"wall",
"damage",
"through",
"infection",
"and",
"thus",
"improve",
"SB",
"resistance",
"in",
"LR-66-637.",
"In",
"contrast,",
"LR-66-577",
"appeared",
"to",
"respond",
"to",
"SB19",
"invasion",
"in",
"a",
"completely",
"different",
"form",
"considering",
"that",
"the",
"majority",
"of",
"genes",
"upregulated",
"in",
"this",
"RIL",
"were",
"enriched",
"for",
"those",
"involved",
"in",
"‘oxidation-reduction",
"process’.",
"This",
"suggests",
"that",
"redox",
"homeostasis",
"was",
"substantially",
"altered",
"in",
"LR-66-577",
"after",
"SB19",
"invasion,",
"which",
"was",
"reported",
"for",
"other",
"systems",
"previously",
"[",
"55",
"].",
"A",
"change",
"in",
"redox",
"status",
"in",
"the",
"challenged",
"cells",
"could",
"release",
"a",
"variety",
"of",
"reactive",
"oxygen",
"species",
"including",
"singlet",
"oxygen,",
"superoxide",
"radicals",
"and",
"hydrogen",
"peroxide,",
"accumulation",
"of",
"which",
"could",
"trigger",
"the",
"plant’s",
"hypersensitive",
"response",
"and",
"programmed",
"cell",
"death",
"(PCD)",
"to",
"cause",
"leaf",
"necrosis",
"and,",
"eventually,",
"leaf",
"dehiscence",
"[",
"56",
",",
"57",
"]."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"This",
"suggests",
"that",
"redox",
"homeostasis",
"was",
"substantially",
"altered",
"in",
"LR-66-577",
"after",
"SB19",
"invasion,",
"which",
"was",
"reported",
"for",
"other",
"systems",
"previously",
"[",
"55",
"].",
"A",
"change",
"in",
"redox",
"status",
"in",
"the",
"challenged",
"cells",
"could",
"release",
"a",
"variety",
"of",
"reactive",
"oxygen",
"species",
"including",
"singlet",
"oxygen,",
"superoxide",
"radicals",
"and",
"hydrogen",
"peroxide,",
"accumulation",
"of",
"which",
"could",
"trigger",
"the",
"plant’s",
"hypersensitive",
"response",
"and",
"programmed",
"cell",
"death",
"(PCD)",
"to",
"cause",
"leaf",
"necrosis",
"and,",
"eventually,",
"leaf",
"dehiscence",
"[",
"56",
",",
"57",
"].",
"As",
"necrotrophs",
"can",
"thrive",
"in",
"dead",
"tissues,",
"several",
"studies",
"have",
"reported",
"that",
"necrotrophs",
"are",
"able",
"to",
"hijack",
"the",
"plant",
"immune",
"system",
"and",
"use",
"the",
"host",
"HR",
"machinery",
"to",
"boost",
"their",
"virulence",
"[",
"39",
",",
"58",
",",
"59",
"].",
"From",
"these",
"results,",
"we",
"hypothesize",
"that",
"HR",
"and",
"PCD",
"were",
"significantly",
"more",
"promoted",
"in",
"LR-66-577",
"than",
"LR-66-637",
"during",
"the",
"SB19",
"infection",
"process,",
"resulting",
"in",
"susceptibility",
"in",
"LR-66-577.",
"Previous",
"evidences",
"has",
"shown",
"that",
"HR",
"and",
"PCD",
"are",
"largely",
"induced",
"through",
"the",
"activation",
"of",
"R",
"genes",
"[",
"56",
"–",
"59",
"].",
"In",
"the",
"present",
"study,",
"we",
"observed",
"that",
"a",
"number",
"of",
"TIR-NBS-LRR",
"and",
"CC-NBS-LRR",
"genes",
"were",
"stronger",
"upregulated",
"in",
"LR-66-577",
"than",
"LR-66-637",
"during",
"the",
"infection",
"process",
"(Additional",
"file",
"5",
":",
"Table",
"S4).",
"In",
"the",
"lentil",
"–",
"A.",
"lentis",
"system,",
"Sari",
"et",
"al.",
"[",
"16",
"]",
"found",
"a",
"TIR-NBS-LRR",
"gene",
"that",
"was",
"also",
"significantly",
"upregulated",
"in",
"two",
"susceptible",
"lentil",
"genotypes",
"after",
"inoculation",
"of",
"A.",
"lentis.",
"Such",
"results",
"corroborate",
"an",
"association",
"of",
"R",
"genes,",
"cell",
"death",
"and",
"susceptibility",
"after",
"infection",
"by",
"necrotrophic",
"pathogen",
"[",
"39",
"].",
"However,",
"there",
"was",
"another",
"set",
"of",
"TIR-NBS-LRR,",
"NBS-LRR,",
"and",
"NB-ARC",
"genes",
"that",
"had",
"higher",
"expression",
"in",
"LR-66-637",
"than",
"LR-66-577,",
"as",
"would",
"be",
"expected",
"for",
"resistant",
"genotypes."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Such",
"results",
"corroborate",
"an",
"association",
"of",
"R",
"genes,",
"cell",
"death",
"and",
"susceptibility",
"after",
"infection",
"by",
"necrotrophic",
"pathogen",
"[",
"39",
"].",
"However,",
"there",
"was",
"another",
"set",
"of",
"TIR-NBS-LRR,",
"NBS-LRR,",
"and",
"NB-ARC",
"genes",
"that",
"had",
"higher",
"expression",
"in",
"LR-66-637",
"than",
"LR-66-577,",
"as",
"would",
"be",
"expected",
"for",
"resistant",
"genotypes.",
"Involvement",
"of",
"such",
"R",
"genes",
"was",
"also",
"reported",
"in",
"the",
"lentil",
"–",
"A.",
"lentis",
"system,",
"and",
"Khorramdelazad",
"et",
"al.",
"[",
"15",
"]",
"speculated",
"that",
"a",
"stronger",
"upregulation",
"of",
"a",
"NB-ARC",
"gene",
"conferred",
"enhanced",
"resistance",
"in",
"ILL",
"7537.",
"Taken",
"together,",
"this",
"supports",
"the",
"emerging",
"picture",
"of",
"R-genes",
"as",
"true",
"resistance",
"genes",
"as",
"well",
"as",
"their",
"possible",
"role",
"as",
"susceptibility",
"factors",
"[",
"34",
"].",
"Comparing",
"DEGs",
"with",
"previously",
"identified",
"resistance",
"QTLs",
"of",
"LR-66",
"[",
"11",
"],",
"we",
"identified",
"nine",
"resistance",
"gene",
"candidates",
"and",
"explored",
"them",
"further",
"through",
"bulk",
"segregation",
"analysis.",
"In",
"a",
"bulk",
"segregation",
"analysis",
"(BSA),",
"the",
"phenotypic",
"extremes",
"of",
"two",
"pools",
"tend",
"to",
"either",
"differ",
"in",
"the",
"presence",
"of",
"the",
"gene(s)",
"characterizing",
"the",
"phenotype,",
"or",
"differ",
"in",
"the",
"expression",
"level",
"of",
"the",
"gene(s)",
"responsible",
"for",
"the",
"trait",
"[",
"60",
"].",
"BSA",
"coupled",
"with",
"gene",
"expression",
"studies",
"has",
"been",
"used",
"frequently",
"to",
"identify",
"candidate",
"genes",
"in",
"varieties",
"of",
"plant",
"species",
"(e.g.",
"[",
"61",
"–",
"63",
"]).",
"BSA",
"was",
"used",
"here",
"and",
"revealed",
"a",
"calcium-transporting",
"ATPase",
"(Lc05858)",
"and",
"a",
"receptor3.2",
"(Lc12983)",
"with",
"a",
"high",
"expression",
"in",
"the",
"resistant",
"pool",
"indicating",
"that",
"they",
"could",
"be",
"putative",
"resistance",
"genes.",
"A",
"calcium",
"transporting",
"ATPase,",
"such",
"as",
"Lc05858,",
"could",
"play",
"an",
"important",
"role",
"in",
"calcium",
"influx",
"and",
"efflux",
"regulation",
"to",
"maintain",
"an",
"appropriate",
"cellular",
"calcium",
"homeostasis,",
"the",
"change",
"of",
"which",
"is",
"thought",
"to",
"initiate",
"calcium",
"signaling",
"that",
"triggers",
"a",
"series",
"of",
"downstream",
"responses",
"influencing",
"plant",
"growth,",
"development",
"and",
"responses",
"to",
"biotic",
"and",
"abiotic",
"stresses",
"[",
"64",
"–",
"66",
"]."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"In",
"a",
"bulk",
"segregation",
"analysis",
"(BSA),",
"the",
"phenotypic",
"extremes",
"of",
"two",
"pools",
"tend",
"to",
"either",
"differ",
"in",
"the",
"presence",
"of",
"the",
"gene(s)",
"characterizing",
"the",
"phenotype,",
"or",
"differ",
"in",
"the",
"expression",
"level",
"of",
"the",
"gene(s)",
"responsible",
"for",
"the",
"trait",
"[",
"60",
"].",
"BSA",
"coupled",
"with",
"gene",
"expression",
"studies",
"has",
"been",
"used",
"frequently",
"to",
"identify",
"candidate",
"genes",
"in",
"varieties",
"of",
"plant",
"species",
"(e.g.",
"[",
"61",
"–",
"63",
"]).",
"BSA",
"was",
"used",
"here",
"and",
"revealed",
"a",
"calcium-transporting",
"ATPase",
"(Lc05858)",
"and",
"a",
"receptor3.2",
"(Lc12983)",
"with",
"a",
"high",
"expression",
"in",
"the",
"resistant",
"pool",
"indicating",
"that",
"they",
"could",
"be",
"putative",
"resistance",
"genes.",
"A",
"calcium",
"transporting",
"ATPase,",
"such",
"as",
"Lc05858,",
"could",
"play",
"an",
"important",
"role",
"in",
"calcium",
"influx",
"and",
"efflux",
"regulation",
"to",
"maintain",
"an",
"appropriate",
"cellular",
"calcium",
"homeostasis,",
"the",
"change",
"of",
"which",
"is",
"thought",
"to",
"initiate",
"calcium",
"signaling",
"that",
"triggers",
"a",
"series",
"of",
"downstream",
"responses",
"influencing",
"plant",
"growth,",
"development",
"and",
"responses",
"to",
"biotic",
"and",
"abiotic",
"stresses",
"[",
"64",
"–",
"66",
"].",
"Zhu",
"et",
"al.",
"[",
"67",
"]",
"reported",
"that",
"the",
"expression",
"of",
"a",
"gene",
"coding",
"calcium",
"ATPase",
"decreased",
"HR",
"in",
"Pachycephala",
"schlegelii-infected",
"tomatoes",
"as",
"NbCA1",
"(ER-localized",
"type",
"IIB",
"calcium",
"ATPase)-silenced",
"plants",
"exhibited",
"accelerated",
"programmed",
"cell",
"death",
"(PCD)",
"compared",
"to",
"the",
"wild",
"type.",
"Similarly,",
"Boursiac",
"et",
"al.",
"[",
"68",
"]",
"found",
"that",
"the",
"knockout",
"of",
"ACA4",
"and",
"ACA11",
"(two",
"calcium-ATPases)",
"induced",
"a",
"higher",
"frequency",
"of",
"HR-like",
"lesions",
"by",
"deactivating",
"the",
"calcium",
"signaling",
"in",
"Arabidopsis",
"inoculated",
"with",
"P.",
"schlegelii.",
"Based",
"on",
"this",
"it",
"can",
"be",
"speculated",
"that",
"upregulation",
"of",
"Lc05858",
"during",
"SB19",
"infection",
"results",
"in",
"the",
"activation",
"of",
"calcium",
"transportation",
"and",
"the",
"suppression",
"of",
"HR",
"and",
"PCD.",
"Upregulation",
"of",
"the",
"glutamate",
"receptor3.2",
"Lc12983",
"in",
"the",
"resistant",
"RILs",
"compared",
"to",
"the",
"susceptible",
"RILs",
"at",
"48",
"and",
"144",
"hpi",
"may",
"also",
"affect",
"calcium",
"regulation,",
"highlighting",
"its",
"potential",
"importance",
"in",
"the",
"lentil",
"–S.",
"botryosum",
"interaction."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Upregulation",
"of",
"the",
"glutamate",
"receptor3.2",
"Lc12983",
"in",
"the",
"resistant",
"RILs",
"compared",
"to",
"the",
"susceptible",
"RILs",
"at",
"48",
"and",
"144",
"hpi",
"may",
"also",
"affect",
"calcium",
"regulation,",
"highlighting",
"its",
"potential",
"importance",
"in",
"the",
"lentil",
"–S.",
"botryosum",
"interaction.",
"A",
"previous",
"study",
"showed",
"that",
"a",
"glutamate",
"receptor",
"is",
"mainly",
"responsible",
"for",
"glutamate-dependent",
"membrane",
"depolarization",
"and",
"calcium",
"transportation",
"[",
"69",
"],",
"and",
"Kang",
"et",
"al.",
"[",
"70",
"]",
"and",
"Manzoor",
"et",
"al.",
"[",
"71",
"]",
"observed",
"that",
"the",
"upregulation",
"of",
"glutamate-like",
"receptors",
"AtGLR3.3",
"or",
"AtGluR3.2",
"elevated",
"calcium",
"influx",
"and",
"conferred",
"enhanced",
"resistance",
"in",
"Arabidopsis",
"against",
"the",
"necrotroph",
"B.",
"cinerea.",
"However,",
"further",
"functional",
"studies",
"are",
"required",
"to",
"confirm",
"the",
"role",
"of",
"these",
"genes",
"in",
"resistance.",
"One",
"gene",
"encoding",
"an",
"uncharacterized",
"protein",
"(Lc07593)",
"was",
"highly",
"expressed",
"in",
"the",
"SB19-susceptible",
"RILs",
"compared",
"to",
"the",
"resistant",
"RILs,",
"suggesting",
"that",
"Lc07593",
"could",
"be",
"a",
"susceptibility",
"gene.",
"However,",
"this",
"gene",
"is",
"not",
"homologous",
"to",
"any",
"well",
"characterized",
"genes",
"in",
"the",
"database",
"and",
"thus",
"its",
"function",
"is",
"not",
"understood.",
"Future",
"work",
"involving",
"protein",
"purification,",
"structural",
"modeling,",
"and",
"protein-protein",
"interaction",
"analyses",
"may",
"be",
"needed",
"to",
"understand",
"its",
"biological",
"function.",
"Methods",
"Plant",
"material",
"and",
"inoculum",
"preparation",
"RILs",
"LR-66-577",
"(susceptible",
"to",
"SB)",
"and",
"LR-66-637",
"(resistant",
"to",
"SB)",
"used",
"in",
"this",
"study",
"were",
"transgressive",
"segregants",
"chosen",
"from",
"the",
"M.",
"figo",
"RIL",
"population",
"LR-66",
"derived",
"from",
"the",
"cross",
"of",
"L01-827A",
"×",
"IG",
"72815",
"developed",
"at",
"the",
"Crop",
"Development",
"Centre",
"at",
"the",
"University",
"of",
"Saskatchewan",
"(Saskatoon,",
"SK,",
"Canada)",
"[",
"11",
"].",
"Evident",
"transgressive",
"segregation",
"and",
"disease",
"severity",
"in",
"RILs",
"ranging",
"from",
"11",
"to",
"80%",
"in",
"this",
"population",
"indicated",
"that",
"there",
"was",
"fluent",
"genetic",
"variability",
"in",
"SB",
"resistance",
"[",
"11",
"].",
"Prior",
"to",
"planting,",
"seeds",
"of",
"RILs",
"were",
"scarified",
"to",
"facilitate",
"germination."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"The",
"cryopreserved",
"SB19",
"spores",
"were",
"revitalized",
"on",
"oatmeal",
"V8",
"agar",
"medium",
"[150",
"mL",
"V8",
"juice",
"(Campbell",
"Co.,",
"Canada),",
"10",
"g",
"Difco™",
"Potato",
"Dextrose",
"Agar",
"(Becton",
"Dickinson",
"and",
"Co.,",
"Franklin",
"Lake,",
"NJ,",
"USA),",
"3",
"g",
"calcium",
"carbonate,",
"850",
"mL",
"sterile",
"water].",
"After",
"seven",
"days",
"of",
"incubation",
"at",
"room",
"temperature,",
"conidia",
"were",
"collected",
"from",
"Petri",
"dishes",
"by",
"flooding",
"and",
"scraping",
"the",
"surface",
"of",
"the",
"plates.",
"The",
"conidial",
"suspension",
"was",
"filtered",
"through",
"two",
"layers",
"of",
"miracloth",
"and",
"adjusted",
"to",
"1",
"×",
"10",
"5",
"condia",
"mL",
"−",
"1",
"using",
"a",
"hemocytometer.",
"Two",
"droplets",
"of",
"Tween",
"20",
"(Sigma,",
"Saint",
"Louis,",
"MO,",
"USA)",
"were",
"added",
"to",
"every",
"1000",
"mL",
"of",
"suspension",
"before",
"inoculation.",
"Pathogen",
"inoculation",
"and",
"experimental",
"design",
"Four-week",
"old",
"plants",
"were",
"sprayed",
"with",
"the",
"conidial",
"suspension",
"until",
"run",
"off,",
"which",
"was",
"equivalent",
"to",
"approximate",
"2",
"to",
"2.5",
"mL",
"per",
"plant.",
"Four",
"plants",
"within",
"a",
"pot",
"represented",
"one",
"of",
"three",
"biological",
"replicates",
"and",
"were",
"pooled",
"to",
"generate",
"a",
"biological",
"replicate.",
"Pots",
"were",
"arranged",
"in",
"a",
"completely",
"randomized",
"design",
"in",
"a",
"misting",
"chamber",
"at",
"100%",
"humidity",
"for",
"the",
"first",
"48",
"h",
"to",
"favor",
"germination",
"of",
"conidia.",
"After",
"48",
"hpi,",
"those",
"inoculated",
"plants",
"were",
"removed",
"from",
"the",
"misting",
"chamber,",
"each",
"pot",
"was",
"enclosed",
"in",
"a",
"translucent",
"plastic",
"bag,",
"and",
"pots",
"were",
"maintained",
"at",
"23",
"°C",
"and",
"16",
"h",
"photoperiod.",
"Leaves",
"were",
"sampled",
"at",
"0,",
"6,",
"12,",
"24,",
"48,",
"72,",
"96,",
"120,",
"144,",
"196,",
"and",
"240",
"hpi,",
"immediately",
"frozen",
"in",
"liquid",
"nitrogen",
"and",
"then",
"stored",
"in",
"a",
"-80",
"°C",
"freezer",
"for",
"future",
"uses.",
"Determination",
"of",
"fungal",
"development",
"Microscopy-based",
"methods",
"and",
"qPCR",
"were",
"used",
"to",
"quantify",
"growth",
"of",
"SB19",
"in",
"plants.",
"For",
"qPCR,",
"the",
"genes",
"targeting",
"RNA",
"polymerase",
"II",
"second",
"largest",
"subunit",
"(RPL-4)",
"to",
"amplify",
"gDNA",
"of",
"SB19",
"and",
"elongation",
"factor",
"(LcEF1α)",
"to",
"quantify",
"A.",
"paludicola",
"were",
"used",
"(Additional",
"file",
"8",
":",
"Table",
"S7)."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"After",
"seven",
"days",
"of",
"incubation",
"at",
"room",
"temperature,",
"conidia",
"were",
"collected",
"from",
"Petri",
"dishes",
"by",
"flooding",
"and",
"scraping",
"the",
"surface",
"of",
"the",
"plates.",
"The",
"conidial",
"suspension",
"was",
"filtered",
"through",
"two",
"layers",
"of",
"miracloth",
"and",
"adjusted",
"to",
"1",
"×",
"10",
"5",
"condia",
"mL",
"−",
"1",
"using",
"a",
"hemocytometer.",
"Two",
"droplets",
"of",
"Tween",
"20",
"(Sigma,",
"Saint",
"Louis,",
"MO,",
"USA)",
"were",
"added",
"to",
"every",
"1000",
"mL",
"of",
"suspension",
"before",
"inoculation.",
"Pathogen",
"inoculation",
"and",
"experimental",
"design",
"Four-week",
"old",
"plants",
"were",
"sprayed",
"with",
"the",
"conidial",
"suspension",
"until",
"run",
"off,",
"which",
"was",
"equivalent",
"to",
"approximate",
"2",
"to",
"2.5",
"mL",
"per",
"plant.",
"Four",
"plants",
"within",
"a",
"pot",
"represented",
"one",
"of",
"three",
"biological",
"replicates",
"and",
"were",
"pooled",
"to",
"generate",
"a",
"biological",
"replicate.",
"Pots",
"were",
"arranged",
"in",
"a",
"completely",
"randomized",
"design",
"in",
"a",
"misting",
"chamber",
"at",
"100%",
"humidity",
"for",
"the",
"first",
"48",
"h",
"to",
"favor",
"germination",
"of",
"conidia.",
"After",
"48",
"hpi,",
"those",
"inoculated",
"plants",
"were",
"removed",
"from",
"the",
"misting",
"chamber,",
"each",
"pot",
"was",
"enclosed",
"in",
"a",
"translucent",
"plastic",
"bag,",
"and",
"pots",
"were",
"maintained",
"at",
"23",
"°C",
"and",
"16",
"h",
"photoperiod.",
"Leaves",
"were",
"sampled",
"at",
"0,",
"6,",
"12,",
"24,",
"48,",
"72,",
"96,",
"120,",
"144,",
"196,",
"and",
"240",
"hpi,",
"immediately",
"frozen",
"in",
"liquid",
"nitrogen",
"and",
"then",
"stored",
"in",
"a",
"-80",
"°C",
"freezer",
"for",
"future",
"uses.",
"Determination",
"of",
"fungal",
"development",
"Microscopy-based",
"methods",
"and",
"qPCR",
"were",
"used",
"to",
"quantify",
"growth",
"of",
"SB19",
"in",
"plants.",
"For",
"qPCR,",
"the",
"genes",
"targeting",
"RNA",
"polymerase",
"II",
"second",
"largest",
"subunit",
"(RPL-4)",
"to",
"amplify",
"gDNA",
"of",
"SB19",
"and",
"elongation",
"factor",
"(LcEF1α)",
"to",
"quantify",
"A.",
"torrentium",
"were",
"used",
"(Additional",
"file",
"8",
":",
"Table",
"S7).",
"The",
"SDS",
"method",
"[",
"72",
"]",
"was",
"used",
"to",
"extract",
"gDNA",
"from",
"both",
"organisms",
"and",
"a",
"spectrophotometer",
"(NanoDrop™",
"8000,",
"Thermo",
"Scientific,",
"Waltham,",
"USA)",
"was",
"employed",
"to",
"quantify",
"the",
"DNA",
"concentration,",
"which",
"was",
"adjusted",
"to",
"25",
"ng",
"μl",
"−",
"1",
"for",
"all",
"samples.",
"Each",
"qPCR",
"reaction",
"contained",
"2",
"μl",
"DNA",
"template,",
"5",
"μl",
"SYBR®",
"Green",
"(catalog",
"no."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Leaves",
"were",
"sampled",
"at",
"0,",
"6,",
"12,",
"24,",
"48,",
"72,",
"96,",
"120,",
"144,",
"196,",
"and",
"240",
"hpi,",
"immediately",
"frozen",
"in",
"liquid",
"nitrogen",
"and",
"then",
"stored",
"in",
"a",
"-80",
"°C",
"freezer",
"for",
"future",
"uses.",
"Determination",
"of",
"fungal",
"development",
"Microscopy-based",
"methods",
"and",
"qPCR",
"were",
"used",
"to",
"quantify",
"growth",
"of",
"SB19",
"in",
"plants.",
"For",
"qPCR,",
"the",
"genes",
"targeting",
"RNA",
"polymerase",
"II",
"second",
"largest",
"subunit",
"(RPL-4)",
"to",
"amplify",
"gDNA",
"of",
"SB19",
"and",
"elongation",
"factor",
"(LcEF1α)",
"to",
"quantify",
"S.",
"neurona",
"were",
"used",
"(Additional",
"file",
"8",
":",
"Table",
"S7).",
"The",
"SDS",
"method",
"[",
"72",
"]",
"was",
"used",
"to",
"extract",
"gDNA",
"from",
"both",
"organisms",
"and",
"a",
"spectrophotometer",
"(NanoDrop™",
"8000,",
"Thermo",
"Scientific,",
"Waltham,",
"USA)",
"was",
"employed",
"to",
"quantify",
"the",
"DNA",
"concentration,",
"which",
"was",
"adjusted",
"to",
"25",
"ng",
"μl",
"−",
"1",
"for",
"all",
"samples.",
"Each",
"qPCR",
"reaction",
"contained",
"2",
"μl",
"DNA",
"template,",
"5",
"μl",
"SYBR®",
"Green",
"(catalog",
"no.",
"4309155,",
"Thermo",
"Scientific),",
"0.2",
"μl",
"each",
"of",
"10",
"μM",
"forward",
"and",
"reverse",
"primers,",
"and",
"2.6",
"μl",
"molecular",
"grade",
"water.",
"A",
"default",
"fast-run",
"program",
"was",
"used",
"to",
"perform",
"qPCR",
"amplification",
"in",
"a",
"QuantStudio™",
"3",
"System",
"(Applied",
"Biosystems",
"Inc.,",
"Foster",
"City,",
"CA,",
"USA).",
"According",
"to",
"the",
"criteria",
"proposed",
"by",
"Weβling",
"and",
"Panstruga",
"[",
"24",
"],",
"the",
"relative",
"fungal",
"biomass",
"was",
"estimated",
"as",
"the",
"proportion",
"of",
"gDNA",
"amplified",
"between",
"RPL-4",
"and",
"LcEF1α.",
"For",
"microscopic",
"quantification,",
"six",
"leaflets",
"per",
"biological",
"replicate",
"were",
"collected",
"at",
"each",
"of",
"6,",
"12,",
"24,",
"48,",
"72,",
"96,",
"120,",
"144,",
"196,",
"and",
"240",
"hpi.",
"The",
"collected",
"leaflets",
"were",
"cleared",
"in",
"CMAA",
"fixation",
"solution",
"(60%",
"methanol,",
"30%",
"chloroform,",
"10%",
"acetic",
"acid)",
"for",
"at",
"least",
"24",
"h",
"at",
"room",
"temperature",
"to",
"eliminate",
"chlorophyll",
"in",
"cells."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"According",
"to",
"the",
"criteria",
"proposed",
"by",
"Weβling",
"and",
"Panstruga",
"[",
"24",
"],",
"the",
"relative",
"fungal",
"biomass",
"was",
"estimated",
"as",
"the",
"proportion",
"of",
"gDNA",
"amplified",
"between",
"RPL-4",
"and",
"LcEF1α.",
"For",
"microscopic",
"quantification,",
"six",
"leaflets",
"per",
"biological",
"replicate",
"were",
"collected",
"at",
"each",
"of",
"6,",
"12,",
"24,",
"48,",
"72,",
"96,",
"120,",
"144,",
"196,",
"and",
"240",
"hpi.",
"The",
"collected",
"leaflets",
"were",
"cleared",
"in",
"CMAA",
"fixation",
"solution",
"(60%",
"methanol,",
"30%",
"chloroform,",
"10%",
"acetic",
"acid)",
"for",
"at",
"least",
"24",
"h",
"at",
"room",
"temperature",
"to",
"eliminate",
"chlorophyll",
"in",
"cells.",
"Once",
"treated,",
"they",
"were",
"immersed",
"in",
"a",
"series",
"of",
"decreasing",
"ethanol",
"concentrations",
"of",
"70%",
"for",
"1",
"h,",
"50%",
"for",
"1.5",
"h",
"and",
"30%",
"for",
"1.5",
"h.",
"Staining",
"was",
"performed",
"by",
"immersing",
"leaflets",
"in",
"0.05%",
"trypan",
"blue",
"overnight.",
"Well",
"stained",
"leaflets",
"were",
"mounted",
"on",
"glass",
"slides",
"in",
"a",
"droplet",
"of",
"50%",
"glycerol",
"and",
"evaluated",
"under",
"a",
"Zeiss",
"Axioskop",
"40",
"microscope",
"(Carl",
"Zeiss,",
"Göttingen,",
"Germany).",
"High-quality",
"photos",
"were",
"generated",
"using",
"a",
"Pixelink",
"A686C",
"camera",
"(Pixelink,",
"Rochester,",
"NY,",
"USA)",
"and",
"Zeiss",
"Axiovision",
"software",
"(Carl",
"Zeiss,",
"Oberkochen,",
"Germany).",
"To",
"quantify",
"fungal",
"development",
"during",
"the",
"incubation",
"process,",
"we",
"record",
"percentage",
"of",
"conidial",
"germination,",
"percentage",
"of",
"conidia",
"resulting",
"in",
"successful",
"penetration",
"(%",
"conidial",
"penetration),",
"and",
"germ",
"tube",
"length.",
"Furthermore,",
"the",
"percentage",
"area",
"of",
"dead",
"tissue",
"per",
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] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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"DEGs.",
"The",
"resulting",
"DEGs",
"were",
"submitted",
"to",
"JMP",
"Genomics",
"8.0",
"(JMP",
"Genomics®,",
"SAS",
"Institute)",
"for",
"K-means",
"clustering",
"analysis.",
"The",
"genes",
"of",
"each",
"cluster",
"with",
"known",
"Eurypanopeus",
"depressus",
"orthologs",
"were",
"then",
"mapped",
"to",
"the",
"Gene",
"Ontology",
"(GO)",
"database",
"using",
"the",
"PANTHER",
"(version",
"14.1)",
"(",
"http://www.pantherdb.org",
")."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Identification",
"of",
"differentially",
"expressed",
"genes",
"(DEGs)",
"Before",
"comparing",
"the",
"gene",
"expression",
"between",
"RILs,",
"we",
"first",
"conducted",
"comparisons",
"of",
"gene",
"expression",
"in",
"samples",
"from",
"0",
"hpi",
"with",
"those",
"collected",
"at",
"48,",
"96,",
"and",
"144",
"hpi",
"for",
"each",
"RIL",
"to",
"identify",
"those",
"genes",
"that",
"significantly",
"responded",
"to",
"SB19",
"infection.",
"These",
"comparisons",
"were",
"performed",
"in",
"the",
"R",
"package",
"DESeq2",
"[",
"75",
"]",
"using",
"the",
"thresholds",
"of",
"false",
"discovery",
"rate",
"(FDR)",
"<",
"0.05",
"and",
"gene",
"expression",
"fold",
"change",
">",
"2.",
"Among",
"the",
"identified",
"disease-responsive",
"genes,",
"we",
"then",
"conducted",
"pair-wise",
"comparisons",
"between",
"LR-66-637",
"and",
"LR-66-577",
"samples",
"from",
"each",
"time",
"point",
"(48,",
"96",
"and",
"144",
"hpi).",
"The",
"same",
"thresholds",
"used",
"previously",
"were",
"applied",
"here",
"to",
"declare",
"significant",
"DEGs.",
"The",
"resulting",
"DEGs",
"were",
"submitted",
"to",
"JMP",
"Genomics",
"8.0",
"(JMP",
"Genomics®,",
"SAS",
"Institute)",
"for",
"K-means",
"clustering",
"analysis.",
"The",
"genes",
"of",
"each",
"cluster",
"with",
"known",
"Batrachocottus",
"nikolskii",
"orthologs",
"were",
"then",
"mapped",
"to",
"the",
"Gene",
"Ontology",
"(GO)",
"database",
"using",
"the",
"PANTHER",
"(version",
"14.1)",
"(",
"http://www.pantherdb.org",
").",
"qPCR",
"validation",
"To",
"verify",
"the",
"repeatability",
"of",
"gene",
"expression",
"captured",
"in",
"the",
"RNA-Seq",
"experiment,",
"an",
"independently",
"inoculated",
"experiment",
"with",
"LR-66-570",
"and",
"LR-66-629",
"was",
"conducted",
"following",
"the",
"same",
"experimental",
"conditions",
"and",
"setup",
"as",
"described",
"before.",
"Infected",
"leaf",
"samples",
"were",
"collected",
"and",
"processed",
"as",
"described",
"before,",
"and",
"16",
"DEGs",
"identified",
"from",
"RNA-Seq",
"data",
"analysis",
"and",
"one",
"reference",
"gene",
"(LcEF1α)",
"were",
"used",
"for",
"qPCR",
"amplification",
"(Additional",
"file",
"10",
":",
"Table",
"S8).",
"Each",
"PCR",
"reaction",
"consisted",
"of",
"2",
"μl",
"DNA",
"template,",
"5",
"μl",
"SYBR",
"Green,",
"0.2",
"μl",
"of",
"each",
"10",
"μM",
"forward",
"and",
"reverse",
"primers,",
"and",
"2.6",
"μl",
"molecular",
"grade",
"water.",
"qPCR",
"was",
"performed",
"in",
"a",
"QuantStudio™",
"3",
"System",
"(Applied",
"Biosystems",
"Inc.)",
"using",
"the",
"fast-run",
"program",
"with",
"default",
"settings."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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"applied",
"here",
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"DEGs.",
"The",
"resulting",
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"to",
"JMP",
"Genomics",
"8.0",
"(JMP",
"Genomics®,",
"SAS",
"Institute)",
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"K-means",
"clustering",
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"The",
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"each",
"cluster",
"with",
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"Kazachstania",
"africana",
"orthologs",
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"then",
"mapped",
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"the",
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"Ontology",
"(GO)",
"database",
"using",
"the",
"PANTHER",
"(version",
"14.1)",
"(",
"http://www.pantherdb.org",
").",
"qPCR",
"validation",
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"verify",
"the",
"repeatability",
"of",
"gene",
"expression",
"captured",
"in",
"the",
"RNA-Seq",
"experiment,",
"an",
"independently",
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"LR-66-570",
"and",
"LR-66-629",
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"conditions",
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"setup",
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"leaf",
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"described",
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"and",
"16",
"DEGs",
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"RNA-Seq",
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"analysis",
"and",
"one",
"reference",
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"(LcEF1α)",
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"amplification",
"(Additional",
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"10",
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"Table",
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"qPCR",
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"3",
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"using",
"the",
"fast-run",
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"as",
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"CT",
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"reference",
"\\documentclass[12pt]{minimal}",
"\\usepackage{amsmath}",
"\\usepackage{wasysym}",
"\\usepackage{amsfonts}",
"\\usepackage{amssymb}",
"\\usepackage{amsbsy}",
"\\usepackage{mathrsfs}",
"\\usepackage{upgreek}",
"\\setlength{\\oddsidemargin}{-69pt}",
"\\begin{document}$$",
"{2}^{-\\left({CT}_{gene\\",
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"$$\\end{document}",
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"[",
"76",
"]."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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"(P",
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"segregant",
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"11",
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"respectively.",
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"was",
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"the",
"same",
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"and",
"environmental",
"settings,",
"and",
"leaflets",
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"were",
"collected",
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"48,",
"96",
"and",
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] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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"such,",
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"order",
"to",
"limit",
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"(DGE)",
"analyses",
"to",
"those",
"genes",
"that",
"are",
"likely",
"involved",
"in",
"disease",
"defense",
"responses,",
"we",
"first",
"compared",
"the",
"genes",
"expression",
"at",
"48,",
"96,",
"and",
"144",
"hpi",
"with",
"that",
"at",
"0",
"hpi,",
"which",
"resulted",
"in",
"a",
"total",
"of",
"8810",
"genes",
"that",
"displayed",
"differential",
"gene",
"expression",
"(fold",
"change",
">",
"2",
"or",
"FDR",
"<",
"0.05)",
"during",
"the",
"SB19",
"infection",
"process",
"between",
"48",
"and",
"144",
"hpi.",
"The",
"expression",
"heatmap",
"showed",
"that",
"LR-66-637",
"and",
"LR-66-577",
"exhibited",
"some",
"similar",
"features",
"in",
"their",
"expression",
"patterns",
"(Additional",
"file",
"1",
":",
"Figure",
"S1).",
"These",
"data",
"indicated",
"that",
"a",
"large",
"proportion",
"of",
"disease-responsive",
"genes",
"reprogrammed",
"in",
"a",
"similar",
"manner",
"in",
"the",
"resistant",
"and",
"susceptible",
"RILs",
"after",
"the",
"initial",
"challenge",
"with",
"SB19.",
"To",
"identify",
"these",
"genes,",
"we",
"performed",
"DGE",
"analyses",
"between",
"RILs",
"at",
"48,",
"96,",
"and",
"144",
"hpi",
"and",
"found",
"that",
"the",
"vast",
"majority",
"of",
"the",
"8810",
"disease-responsive",
"genes",
"(7526",
"genes)",
"were",
"not",
"differentially",
"expressed",
"(fold",
"change",
"<",
"2",
"or",
"FDR",
">",
"0.05)",
"between",
"RILs.",
"Those",
"genes",
"may",
"be",
"involved",
"in",
"non-host",
"resistance",
"of",
"plants,",
"which",
"is",
"a",
"non-specific",
"and",
"broad-spectrum",
"defense",
"mechanism",
"that",
"is",
"universally",
"present",
"in",
"plants",
"as",
"a",
"defense",
"against",
"microorganisms",
"[",
"25",
"].",
"Data",
"of",
"these",
"7526",
"genes",
"were",
"submitted",
"to",
"K-mean",
"clustering",
"(Fig.",
"4",
"a)",
"and",
"Gene",
"Ontology",
"(GO)",
"mapping",
"analyses",
"(Fig.",
"4",
"b).",
"As",
"a",
"result,",
"three",
"distinct",
"gene",
"clusters",
"were",
"obtained.",
"Cluster",
"1",
"consisted",
"of",
"3155",
"genes",
"which",
"were",
"primarily",
"downregulated",
"at",
"96",
"and",
"144",
"hpi.",
"The",
"GO",
"mapping",
"analysis",
"showed",
"that",
"the",
"genes",
"in",
"this",
"cluster",
"were",
"mostly",
"enriched",
"in",
"development-related",
"GO",
"terms",
"such",
"as",
"“tissue",
"development”,",
"“system",
"development”,",
"“organ",
"development”,",
"“nuclear",
"division”,",
"and",
"“anatomical",
"structure",
"formation",
"involved",
"in",
"morphogenesis”,",
"and",
"energy",
"synthesis-related",
"GO",
"terms",
"such",
"as",
"“photosynthesis”",
"and",
"“carbohydrate",
"metabolic",
"process”",
"(Fig.",
"4",
"b,",
"Additional",
"file",
"2",
":",
"Table",
"S1",
"and",
"Additional",
"file",
"3",
":",
"Table",
"S2)."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"5",
").",
"All",
"but",
"one",
"(94%)",
"exhibited",
"expression",
"trends",
"consistent",
"with",
"those",
"of",
"the",
"RNA-Seq",
"experiment,",
"indicating",
"that",
"expression",
"of",
"DEGs",
"is",
"reproducible",
"across",
"independent",
"experiments.",
"Fig.",
"5",
"qPCR",
"validation",
"of",
"arbitrarily",
"selected",
"16",
"differential",
"expressed",
"genes",
"identified",
"in",
"resistant",
"Tamias",
"townsendii",
"RIL",
"LR-66-637",
"and",
"susceptible",
"RIL",
"LR-66-577",
"after",
"infection",
"with",
"Stemphylium",
"botryosum",
"(isolate",
"XH68).",
"Asterisks",
"indicate",
"the",
"significant",
"difference",
"between",
"means",
"at",
"P",
"<",
"0.05.",
"Error",
"bars",
"represent",
"standard",
"error",
"For",
"a",
"better",
"visualization",
"of",
"genes,",
"the",
"1284",
"DEGs",
"were",
"hierarchically",
"clustered",
"into",
"five",
"expression",
"clusters",
"(Fig.",
"6",
").",
"Clusters",
"1",
"(306",
"genes)",
"and",
"2",
"(406",
"genes)",
"comprised",
"genes",
"that",
"were",
"upregulated",
"in",
"the",
"resistant",
"RIL",
"LR-66-637,",
"whereas",
"310",
"genes",
"in",
"Cluster",
"3,",
"161",
"in",
"Cluster",
"4",
"and",
"101",
"genes",
"in",
"Cluster",
"5",
"were",
"upregulated",
"in",
"the",
"susceptible",
"RIL",
"LR-66-577.",
"Based",
"on",
"their",
"expression",
"patterns,",
"it",
"was",
"hypothesized",
"that",
"the",
"712",
"genes",
"in",
"Clusters",
"1",
"and",
"2",
"are",
"correlated",
"with",
"the",
"enhanced",
"resistance",
"to",
"S.",
"botryosum",
"in",
"LR-66-637,",
"and",
"the",
"572",
"genes",
"in",
"Clusters",
"3,",
"4",
"and",
"5",
"are",
"associated",
"with",
"susceptibility",
"to",
"the",
"pathogen",
"in",
"LR-66-577.",
"Fig.",
"6",
"K-mean",
"clustering",
"(Ward",
"method)",
"of",
"1284",
"differentially",
"expressed",
"genes",
"between",
"resistant",
"Tamias",
"townsendii",
"RIL",
"LR-66-637",
"and",
"susceptible",
"RIL",
"LR-66-577",
"after",
"infection",
"with",
"Stemphylium",
"botryosum",
"(isolate",
"XH68).",
"The",
"identified",
"five",
"major",
"gene",
"clusters",
"are",
"visualized",
"in",
"heatmap",
"(left)",
"and",
"line",
"graph",
"(right)",
"To",
"understand",
"their",
"biological",
"relevance,",
"we",
"performed",
"GO",
"enrichment",
"analyses",
"for",
"those",
"DEGs",
"in",
"each",
"of",
"the",
"clusters",
"(Fig.",
"7",
",",
"Additional",
"file",
"5",
":",
"Table",
"S4",
"and",
"Additional",
"file",
"6",
":",
"Table",
"S5)."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"The",
"identified",
"five",
"major",
"gene",
"clusters",
"are",
"visualized",
"in",
"heatmap",
"(left)",
"and",
"line",
"graph",
"(right)",
"To",
"understand",
"their",
"biological",
"relevance,",
"we",
"performed",
"GO",
"enrichment",
"analyses",
"for",
"those",
"DEGs",
"in",
"each",
"of",
"the",
"clusters",
"(Fig.",
"7",
",",
"Additional",
"file",
"5",
":",
"Table",
"S4",
"and",
"Additional",
"file",
"6",
":",
"Table",
"S5).",
"Genes",
"in",
"Cluster",
"1",
"were",
"primarily",
"enriched",
"in",
"those",
"involved",
"in",
"a",
"variety",
"of",
"primary",
"metabolic",
"and",
"transportation",
"processes",
"including",
"‘carbohydrate",
"metabolic",
"process’,",
"‘cellular",
"carbohydrate",
"metabolic",
"process’,",
"‘polysaccharide",
"metabolic",
"process’,",
"‘transport’,",
"‘establishment",
"of",
"localization’,",
"and",
"‘transmembrane",
"transport’.",
"In",
"Cluster",
"2,",
"a",
"large",
"number",
"of",
"genes",
"were",
"enriched",
"in",
"several",
"cell",
"wall",
"related",
"processes",
"such",
"as",
"‘cell",
"wall",
"organization",
"or",
"biogenesis’,",
"‘cell",
"wall",
"polysaccharide",
"metabolic",
"process’,",
"‘pectin",
"catabolic",
"process’,",
"and",
"‘hemicellulose",
"metabolic",
"process’.",
"In",
"Cluster",
"3,",
"the",
"majority",
"of",
"genes",
"were",
"enriched",
"for",
"those",
"associated",
"with",
"immune",
"responses",
"such",
"as",
"‘oxidation-reduction",
"process’,",
"‘response",
"to",
"stimulus’,",
"and",
"‘response",
"to",
"chemical’.",
"For",
"the",
"remaining",
"262",
"genes",
"in",
"Clusters",
"4",
"and",
"5,",
"HR-associated",
"GO",
"function",
"of",
"‘oxidation-reduction",
"process’,",
"and",
"two",
"PCD-related",
"GO",
"terms",
"of",
"‘asparagine",
"metabolic",
"process’",
"and",
"‘asparagine",
"biosynthetic",
"process’",
"were",
"identified,",
"indicating",
"a",
"higher",
"level",
"of",
"HR",
"activity",
"in",
"LR-66-577",
"during",
"the",
"early",
"SB19",
"infection",
"[",
"26",
"].",
"Fig.",
"7",
"Significant",
"(FDR",
"<",
"0.1)",
"associated",
"GO",
"terms",
"for",
"five",
"differentially",
"expressed",
"genes",
"clusters",
"identified",
"from",
"samples",
"of",
"resistant",
"Furcifer",
"lateralis",
"RIL",
"LR-66-637",
"and",
"susceptible",
"RIL",
"LR-66-577",
"after",
"infection",
"with",
"Stemphylium",
"botryosum",
"(isolate",
"TQ60)",
"Screening",
"of",
"candidate",
"resistance",
"genes",
"using",
"QTL",
"and",
"bulk",
"segregant",
"gene",
"expression",
"analyses",
"Previously,",
"three",
"significant",
"QTL",
"intervals",
"associated",
"with",
"SB19",
"resistance",
"were",
"identified",
"in",
"a",
"SNP-based",
"linkage",
"map",
"of",
"RIL",
"population",
"LR-66",
"[",
"11",
"]."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"In",
"Cluster",
"2,",
"a",
"large",
"number",
"of",
"genes",
"were",
"enriched",
"in",
"several",
"cell",
"wall",
"related",
"processes",
"such",
"as",
"‘cell",
"wall",
"organization",
"or",
"biogenesis’,",
"‘cell",
"wall",
"polysaccharide",
"metabolic",
"process’,",
"‘pectin",
"catabolic",
"process’,",
"and",
"‘hemicellulose",
"metabolic",
"process’.",
"In",
"Cluster",
"3,",
"the",
"majority",
"of",
"genes",
"were",
"enriched",
"for",
"those",
"associated",
"with",
"immune",
"responses",
"such",
"as",
"‘oxidation-reduction",
"process’,",
"‘response",
"to",
"stimulus’,",
"and",
"‘response",
"to",
"chemical’.",
"For",
"the",
"remaining",
"262",
"genes",
"in",
"Clusters",
"4",
"and",
"5,",
"HR-associated",
"GO",
"function",
"of",
"‘oxidation-reduction",
"process’,",
"and",
"two",
"PCD-related",
"GO",
"terms",
"of",
"‘asparagine",
"metabolic",
"process’",
"and",
"‘asparagine",
"biosynthetic",
"process’",
"were",
"identified,",
"indicating",
"a",
"higher",
"level",
"of",
"HR",
"activity",
"in",
"LR-66-577",
"during",
"the",
"early",
"SB19",
"infection",
"[",
"26",
"].",
"Fig.",
"7",
"Significant",
"(FDR",
"<",
"0.1)",
"associated",
"GO",
"terms",
"for",
"five",
"differentially",
"expressed",
"genes",
"clusters",
"identified",
"from",
"samples",
"of",
"resistant",
"Clostridium",
"paradoxum",
"RIL",
"LR-66-637",
"and",
"susceptible",
"RIL",
"LR-66-577",
"after",
"infection",
"with",
"Stemphylium",
"botryosum",
"(isolate",
"XC96)",
"Screening",
"of",
"candidate",
"resistance",
"genes",
"using",
"QTL",
"and",
"bulk",
"segregant",
"gene",
"expression",
"analyses",
"Previously,",
"three",
"significant",
"QTL",
"intervals",
"associated",
"with",
"SB19",
"resistance",
"were",
"identified",
"in",
"a",
"SNP-based",
"linkage",
"map",
"of",
"RIL",
"population",
"LR-66",
"[",
"11",
"].",
"To",
"narrow",
"down",
"the",
"resistance",
"or",
"susceptibility",
"gene",
"candidates",
"based",
"on",
"RNA-Seq",
"here,",
"the",
"1284",
"DEGs",
"were",
"compared",
"to",
"those",
"in",
"the",
"QTL",
"confidence",
"intervals",
"(2-LOD),",
"which",
"resulted",
"in",
"the",
"identification",
"of",
"nine",
"genes",
"that",
"were",
"up-",
"or",
"downregulated",
"in",
"LR-66-637",
"at",
"48,",
"96",
"and",
"144",
"hpi.",
"Among",
"these",
"nine",
"genes,",
"six",
"genes",
"were",
"localized",
"in",
"the",
"QTL",
"qSB-2.2",
"interval",
"and",
"three",
"in",
"the",
"QTL",
"qSB-3",
"interval."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Fig.",
"7",
"Significant",
"(FDR",
"<",
"0.1)",
"associated",
"GO",
"terms",
"for",
"five",
"differentially",
"expressed",
"genes",
"clusters",
"identified",
"from",
"samples",
"of",
"resistant",
"Gomphrena",
"pulchella",
"RIL",
"LR-66-637",
"and",
"susceptible",
"RIL",
"LR-66-577",
"after",
"infection",
"with",
"Stemphylium",
"botryosum",
"(isolate",
"RG72)",
"Screening",
"of",
"candidate",
"resistance",
"genes",
"using",
"QTL",
"and",
"bulk",
"segregant",
"gene",
"expression",
"analyses",
"Previously,",
"three",
"significant",
"QTL",
"intervals",
"associated",
"with",
"SB19",
"resistance",
"were",
"identified",
"in",
"a",
"SNP-based",
"linkage",
"map",
"of",
"RIL",
"population",
"LR-66",
"[",
"11",
"].",
"To",
"narrow",
"down",
"the",
"resistance",
"or",
"susceptibility",
"gene",
"candidates",
"based",
"on",
"RNA-Seq",
"here,",
"the",
"1284",
"DEGs",
"were",
"compared",
"to",
"those",
"in",
"the",
"QTL",
"confidence",
"intervals",
"(2-LOD),",
"which",
"resulted",
"in",
"the",
"identification",
"of",
"nine",
"genes",
"that",
"were",
"up-",
"or",
"downregulated",
"in",
"LR-66-637",
"at",
"48,",
"96",
"and",
"144",
"hpi.",
"Among",
"these",
"nine",
"genes,",
"six",
"genes",
"were",
"localized",
"in",
"the",
"QTL",
"qSB-2.2",
"interval",
"and",
"three",
"in",
"the",
"QTL",
"qSB-3",
"interval.",
"Expression",
"analysis",
"of",
"those",
"genes",
"in",
"pools",
"of",
"the",
"five",
"most",
"SB-resistant",
"and",
"the",
"five",
"most",
"susceptible",
"RILs",
"revealed",
"that",
"two",
"genes",
"(Lc05858:",
"calcium-transporting",
"ATPase;",
"Lc07593:",
"uncharacterized",
"protein)",
"present",
"in",
"qSB-2.2",
"and",
"one",
"gene",
"(Lc12983:",
"glutamate",
"receptor3.2)",
"in",
"qSB-3",
"were",
"expressed",
"in",
"a",
"manner",
"similar",
"to",
"that",
"in",
"resistant",
"RIL",
"LR-66-637",
"and",
"susceptible",
"LR-66-577",
"based",
"on",
"RNA-Seq",
"analysis",
"(Fig.",
"8",
"and",
"Additional",
"file",
"7",
":",
"Table",
"S6).",
"Quantitative",
"PCR",
"for",
"another",
"two",
"of",
"these",
"genes",
"(Lc09908",
"and",
"Lc07065)",
"was",
"inconclusive,",
"and",
"four",
"genes",
"(Lc06015,",
"Lc10098,",
"Lc11261,",
"and",
"Lc13725)",
"displayed",
"similar",
"expression",
"between",
"the",
"two",
"pools,",
"indicating",
"that",
"they",
"are",
"more",
"likely",
"associated",
"with",
"other",
"differences",
"specific",
"to",
"LR-66-637",
"and",
"LR-66-577."
] |
Original work titled: 'Using a transcriptome sequencing approach to explore candidate resistance genes against stemphylium blight in the wild lentil species Lens ervoides' (BMC Plant Biology/BioMed Central) by the following authors: Zhe Cao; Li Li; Karan Kapoor; Sabine Banniza DOI: 10.1186/s12870-019-2013-6
|
0ce28549ffb17c27829b0d628ff2e0c4
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Lc05858",
"and",
"Lc07593",
"are",
"in",
"qSB-2.2",
"QTL",
"region,",
"and",
"Lc12983",
"is",
"in",
"qSB-3",
"interval.",
"Asterisks",
"indicate",
"the",
"significant",
"difference",
"between",
"means",
"at",
"P",
"<",
"0.05.",
"Error",
"bars",
"represent",
"standard",
"error",
"For",
"Lc07593,",
"it",
"was",
"observed",
"that",
"this",
"gene",
"was",
"highly",
"expressed",
"in",
"the",
"SB19-susceptible",
"RILs",
"compared",
"to",
"the",
"resistant",
"RILs,",
"suggesting",
"that",
"Lc07593",
"could",
"be",
"a",
"susceptibility",
"gene,",
"upregulation",
"of",
"which",
"seemed",
"to",
"increase",
"SB",
"susceptibility.",
"On",
"the",
"other",
"hand,",
"Lc05858",
"and",
"Lc12983",
"could",
"be",
"disease",
"resistance",
"genes,",
"as",
"they",
"displayed",
"a",
"reverse",
"expression",
"trend",
"to",
"that",
"of",
"Lc07593.",
"Discussion",
"A",
"thorough",
"understanding",
"of",
"how",
"pathogens",
"interact",
"with",
"their",
"hosts",
"is",
"essential",
"to",
"identify",
"appropriate",
"times",
"during",
"the",
"infection",
"process",
"for",
"the",
"profiling",
"of",
"the",
"transcriptome.",
"In",
"the",
"present",
"study,",
"the",
"difference",
"in",
"SB19",
"development",
"between",
"the",
"resistant",
"RIL",
"LR-66-637",
"and",
"the",
"susceptible",
"RIL",
"LR-66-577",
"was",
"negligible",
"before",
"24",
"hpi,",
"indicating",
"that",
"the",
"resistance",
"toward",
"SB19",
"in",
"RIL",
"LR-66-637",
"was",
"probably",
"based",
"on",
"post-penetration",
"inhibition",
"of",
"the",
"fungus.",
"Similar",
"observations",
"were",
"also",
"reported",
"for",
"S.",
"botryosum",
"infecting",
"alfalfa",
"where",
"Cowling",
"and",
"Gilchrist",
"[",
"27",
"]",
"found",
"that",
"the",
"development",
"of",
"S.",
"botryosum",
"did",
"not",
"differ",
"among",
"the",
"resistant,",
"moderately",
"resistant",
"and",
"susceptible",
"alfalfa",
"clones",
"during",
"the",
"early",
"period",
"of",
"infection.",
"During",
"the",
"period",
"from",
"48",
"to",
"144",
"hpi,",
"fungal",
"biomass",
"started",
"to",
"accumulate",
"in",
"RILs,",
"suggesting",
"that",
"S.",
"botryosum",
"initiated",
"the",
"release",
"of",
"phytotoxins",
"to",
"disrupt",
"host",
"cells",
"around",
"48",
"hpi.",
"Biomass",
"accumulation",
"was",
"significantly",
"higher",
"in",
"LR-66-577",
"than",
"in",
"LR-66-637,",
"possibly",
"as",
"a",
"result",
"of",
"enhanced",
"tolerance",
"to",
"phytotoxins",
"in",
"LR-66-637",
"compared",
"to",
"LR-66-577",
"[",
"28",
"]."
] |
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