238648
VIGCK6G3
2024
1
apa
50
date
asc
1391
https://www.edyp.fr/web/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3A%22zotpress-b4907dd8eef43702e088df74794369db%22%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%224PWUJ7PV%22%2C%22library%22%3A%7B%22id%22%3A238648%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Antunes%20et%20al.%22%2C%22parsedDate%22%3A%222024-01%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EAntunes%2C%20A.%20V.%2C%20Shahinas%2C%20M.%2C%20Swale%2C%20C.%2C%20Farhat%2C%20D.%20C.%2C%20Ramakrishnan%2C%20C.%2C%20Bruley%2C%20C.%2C%20Cannella%2C%20D.%2C%20Robert%2C%20M.%20G.%2C%20Corrao%2C%20C.%2C%20Cout%26%23xE9%3B%2C%20Y.%2C%20Hehl%2C%20A.%20B.%2C%20Bougdour%2C%20A.%2C%20Coppens%2C%20I.%2C%20%26amp%3B%20Hakimi%2C%20M.-A.%20%282024%29.%20In%20vitro%20production%20of%20cat-restricted%20Toxoplasma%20pre-sexual%20stages.%20%3Ci%3ENature%3C%5C%2Fi%3E%2C%20%3Ci%3E625%3C%5C%2Fi%3E%287994%29%2C%20366%26%23x2013%3B376.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41586-023-06821-y%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41586-023-06821-y%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22In%20vitro%20production%20of%20cat-restricted%20Toxoplasma%20pre-sexual%20stages%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ana%20Vera%22%2C%22lastName%22%3A%22Antunes%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Martina%22%2C%22lastName%22%3A%22Shahinas%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Christopher%22%2C%22lastName%22%3A%22Swale%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Dayana%20C.%22%2C%22lastName%22%3A%22Farhat%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Chandra%22%2C%22lastName%22%3A%22Ramakrishnan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Christophe%22%2C%22lastName%22%3A%22Bruley%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Dominique%22%2C%22lastName%22%3A%22Cannella%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marie%20G.%22%2C%22lastName%22%3A%22Robert%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Charlotte%22%2C%22lastName%22%3A%22Corrao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yohann%22%2C%22lastName%22%3A%22Cout%5Cu00e9%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Adrian%20B.%22%2C%22lastName%22%3A%22Hehl%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alexandre%22%2C%22lastName%22%3A%22Bougdour%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Isabelle%22%2C%22lastName%22%3A%22Coppens%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mohamed-Ali%22%2C%22lastName%22%3A%22Hakimi%22%7D%5D%2C%22abstractNote%22%3A%22Sexual%20reproduction%20of%20Toxoplasma%20gondii%2C%20confined%20to%20the%20felid%20gut%2C%20remains%20largely%20uncharted%20owing%20to%20ethical%20concerns%20regarding%20the%20use%20of%20cats%20as%20model%20organisms.%20Chromatin%20modifiers%20dictate%20the%20developmental%20fate%20of%20the%20parasite%20during%20its%20multistage%20life%20cycle%2C%20but%20their%20targeting%20to%20stage-specific%20cistromes%20is%20poorly%20described1%2C2.%20Here%20we%20found%20that%20the%20transcription%20factors%20AP2XII-1%20and%20AP2XI-2%20operate%20during%20the%20tachyzoite%20stage%2C%20a%20hallmark%20of%20acute%20toxoplasmosis%2C%20to%20silence%20genes%20necessary%20for%20merozoites%2C%20a%20developmental%20stage%20critical%20for%20subsequent%20sexual%20commitment%20and%20transmission%20to%20the%20next%20host%2C%20including%20humans.%20Their%20conditional%20and%20simultaneous%20depletion%20leads%20to%20a%20marked%20change%20in%20the%20transcriptional%20program%2C%20promoting%20a%20full%20transition%20from%20tachyzoites%20to%20merozoites.%20These%20in%20vitro-cultured%20pre-gametes%20have%20unique%20protein%20markers%20and%20undergo%20typical%20asexual%20endopolygenic%20division%20cycles.%20In%20tachyzoites%2C%20AP2XII-1%20and%20AP2XI-2%20bind%20DNA%20as%20heterodimers%20at%20merozoite%20promoters%20and%20recruit%20MORC%20and%20HDAC3%20%28ref.%5Cu20091%29%2C%20thereby%20limiting%20chromatin%20accessibility%20and%20transcription.%20Consequently%2C%20the%20commitment%20to%20merogony%20stems%20from%20a%20profound%20epigenetic%20rewiring%20orchestrated%20by%20AP2XII-1%20and%20AP2XI-2.%20Successful%20production%20of%20merozoites%20in%20vitro%20paves%20the%20way%20for%20future%20studies%20on%20Toxoplasma%20sexual%20development%20without%20the%20need%20for%20cat%20infections%20and%20holds%20promise%20for%20the%20development%20of%20therapies%20to%20prevent%20parasite%20transmission.%22%2C%22date%22%3A%222024-01%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41586-023-06821-y%22%2C%22ISSN%22%3A%221476-4687%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22VIGCK6G3%22%5D%2C%22dateModified%22%3A%222024-01-11T07%3A33%3A15Z%22%7D%7D%2C%7B%22key%22%3A%227HFZJDXV%22%2C%22library%22%3A%7B%22id%22%3A238648%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Casanova%20et%20al.%22%2C%22parsedDate%22%3A%222024-01-31%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ECasanova%2C%20A.%20G.%2C%20Roth%2C%20G.%20S.%2C%20Hausmann%2C%20S.%2C%20Lu%2C%20X.%2C%20Bischoff%2C%20L.%20J.%20M.%2C%20Froeliger%2C%20E.%20M.%2C%20Belmudes%2C%20L.%2C%20Bourova-Flin%2C%20E.%2C%20Flores%2C%20N.%20M.%2C%20Benitez%2C%20A.%20M.%2C%20Chasan%2C%20T.%2C%20Caporicci%2C%20M.%2C%20Vayr%2C%20J.%2C%20Blanchet%2C%20S.%2C%20Ielasi%2C%20F.%2C%20Rousseaux%2C%20S.%2C%20Hainaut%2C%20P.%2C%20Gozani%2C%20O.%2C%20Le%20Romancer%2C%20M.%2C%20%26%23x2026%3B%20Reynoird%2C%20N.%20%282024%29.%20Cytoskeleton%20remodeling%20induced%20by%20SMYD2%20methyltransferase%20drives%20breast%20cancer%20metastasis.%20%3Ci%3ECell%20Discovery%3C%5C%2Fi%3E%2C%20%3Ci%3E10%3C%5C%2Fi%3E%281%29%2C%201%26%23x2013%3B22.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41421-023-00644-x%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41421-023-00644-x%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Cytoskeleton%20remodeling%20induced%20by%20SMYD2%20methyltransferase%20drives%20breast%20cancer%20metastasis%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alexandre%20G.%22%2C%22lastName%22%3A%22Casanova%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gael%20S.%22%2C%22lastName%22%3A%22Roth%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Simone%22%2C%22lastName%22%3A%22Hausmann%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xiaoyin%22%2C%22lastName%22%3A%22Lu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ludivine%20J.%20M.%22%2C%22lastName%22%3A%22Bischoff%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Emilie%20M.%22%2C%22lastName%22%3A%22Froeliger%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lucid%22%2C%22lastName%22%3A%22Belmudes%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ekaterina%22%2C%22lastName%22%3A%22Bourova-Flin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Natasha%20M.%22%2C%22lastName%22%3A%22Flores%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ana%20Morales%22%2C%22lastName%22%3A%22Benitez%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Tourkian%22%2C%22lastName%22%3A%22Chasan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marcello%22%2C%22lastName%22%3A%22Caporicci%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jessica%22%2C%22lastName%22%3A%22Vayr%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sandrine%22%2C%22lastName%22%3A%22Blanchet%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Francesco%22%2C%22lastName%22%3A%22Ielasi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sophie%22%2C%22lastName%22%3A%22Rousseaux%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Pierre%22%2C%22lastName%22%3A%22Hainaut%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Or%22%2C%22lastName%22%3A%22Gozani%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Muriel%22%2C%22lastName%22%3A%22Le%20Romancer%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yohann%22%2C%22lastName%22%3A%22Cout%5Cu00e9%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Andres%22%2C%22lastName%22%3A%22Palencia%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Pawel%20K.%22%2C%22lastName%22%3A%22Mazur%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nicolas%22%2C%22lastName%22%3A%22Reynoird%22%7D%5D%2C%22abstractNote%22%3A%22Malignant%20forms%20of%20breast%20cancer%20refractory%20to%20existing%20therapies%20remain%20a%20major%20unmet%20health%20issue%2C%20primarily%20due%20to%20metastatic%20spread.%20A%20better%20understanding%20of%20the%20mechanisms%20at%20play%20will%20provide%20better%20insights%20for%20alternative%20treatments%20to%20prevent%20breast%20cancer%20cell%20dispersion.%20Here%2C%20we%20identify%20the%20lysine%20methyltransferase%20SMYD2%20as%20a%20clinically%20actionable%20master%20regulator%20of%20breast%20cancer%20metastasis.%20While%20SMYD2%20is%20overexpressed%20in%20aggressive%20breast%20cancers%2C%20we%20notice%20that%20it%20is%20not%20required%20for%20primary%20tumor%20growth.%20However%2C%20mammary-epithelium%20specific%20SMYD2%20ablation%20increases%20mouse%20overall%20survival%20by%20blocking%20the%20primary%20tumor%20cell%20ability%20to%20metastasize.%20Mechanistically%2C%20we%20identify%20BCAR3%20as%20a%20genuine%20physiological%20substrate%20of%20SMYD2%20in%20breast%20cancer%20cells.%20BCAR3%20monomethylated%20at%20lysine%20K334%20%28K334me1%29%20is%20recognized%20by%20a%20novel%20methyl-binding%20domain%20present%20in%20FMNLs%20proteins.%20These%20actin%20cytoskeleton%20regulators%20are%20recruited%20at%20the%20cell%20edges%20by%20the%20SMYD2%20methylation%20signaling%20and%20modulate%20lamellipodia%20properties.%20Breast%20cancer%20cells%20with%20impaired%20BCAR3%20methylation%20lose%20migration%20and%20invasiveness%20capacity%20in%20vitro%20and%20are%20ineffective%20in%20promoting%20metastases%20in%20vivo.%20Remarkably%2C%20SMYD2%20pharmacologic%20inhibition%20efficiently%20impairs%20the%20metastatic%20spread%20of%20breast%20cancer%20cells%2C%20PDX%20and%20aggressive%20mammary%20tumors%20from%20genetically%20engineered%20mice.%20This%20study%20provides%20a%20rationale%20for%20innovative%20therapeutic%20prevention%20of%20malignant%20breast%20cancer%20metastatic%20progression%20by%20targeting%20the%20SMYD2-BCAR3-FMNL%20axis.%22%2C%22date%22%3A%222024-01-31%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41421-023-00644-x%22%2C%22ISSN%22%3A%222056-5968%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41421-023-00644-x%22%2C%22collections%22%3A%5B%22VIGCK6G3%22%5D%2C%22dateModified%22%3A%222024-01-31T17%3A07%3A19Z%22%7D%7D%2C%7B%22key%22%3A%225UEZDUPD%22%2C%22library%22%3A%7B%22id%22%3A238648%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Burger%22%2C%22parsedDate%22%3A%222024-02-15%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EBurger%2C%20T.%20%282024%29.%20Fudging%20the%20volcano-plot%20without%20dredging%20the%20data.%20%3Ci%3ENature%20Communications%3C%5C%2Fi%3E%2C%20%3Ci%3E15%3C%5C%2Fi%3E%281%29%2C%201392.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41467-024-45834-7%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41467-024-45834-7%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Fudging%20the%20volcano-plot%20without%20dredging%20the%20data%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Thomas%22%2C%22lastName%22%3A%22Burger%22%7D%5D%2C%22abstractNote%22%3A%22Selecting%20omic%20biomarkers%20using%20both%20their%20effect%20size%20and%20their%20differential%20status%20significance%20%28i.e.%2C%20selecting%20the%20%5Cu201cvolcano-plot%20outer%20spray%5Cu201d%29%20has%20long%20been%20equally%20biologically%20relevant%20and%20statistically%20troublesome.%20However%2C%20recent%20proposals%20are%20paving%20the%20way%20to%20resolving%20this%20dilemma.%22%2C%22date%22%3A%222024-02-15%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41467-024-45834-7%22%2C%22ISSN%22%3A%222041-1723%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22VIGCK6G3%22%5D%2C%22dateModified%22%3A%222024-02-27T09%3A01%3A45Z%22%7D%7D%2C%7B%22key%22%3A%22VZRNHLQ8%22%2C%22library%22%3A%7B%22id%22%3A238648%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Al%20Tarrass%20et%20al.%22%2C%22parsedDate%22%3A%222024-03-04%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EAl%20Tarrass%2C%20M.%2C%20Belmudes%2C%20L.%2C%20Ko%26%23xE7%3Ba%2C%20D.%2C%20Azemard%2C%20V.%2C%20Liu%2C%20H.%2C%20Al%20Tabosh%2C%20T.%2C%20Ciais%2C%20D.%2C%20Desroches-Castan%2C%20A.%2C%20Battail%2C%20C.%2C%20Cout%26%23xE9%3B%2C%20Y.%2C%20Bouvard%2C%20C.%2C%20%26amp%3B%20Bailly%2C%20S.%20%282024%29.%20Large-scale%20phosphoproteomics%20reveals%20activation%20of%20the%20MAPK%5C%2FGADD45%26%23x3B2%3B%5C%2FP38%20axis%20and%20cell%20cycle%20inhibition%20in%20response%20to%20BMP9%20and%20BMP10%20stimulation%20in%20endothelial%20cells.%20%3Ci%3ECell%20Communication%20and%20Signaling%3A%20CCS%3C%5C%2Fi%3E%2C%20%3Ci%3E22%3C%5C%2Fi%3E%281%29%2C%20158.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1186%5C%2Fs12964-024-01486-0%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1186%5C%2Fs12964-024-01486-0%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Large-scale%20phosphoproteomics%20reveals%20activation%20of%20the%20MAPK%5C%2FGADD45%5Cu03b2%5C%2FP38%20axis%20and%20cell%20cycle%20inhibition%20in%20response%20to%20BMP9%20and%20BMP10%20stimulation%20in%20endothelial%20cells%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mohammad%22%2C%22lastName%22%3A%22Al%20Tarrass%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lucid%22%2C%22lastName%22%3A%22Belmudes%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Dzenis%22%2C%22lastName%22%3A%22Ko%5Cu00e7a%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Valentin%22%2C%22lastName%22%3A%22Azemard%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hequn%22%2C%22lastName%22%3A%22Liu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Tala%22%2C%22lastName%22%3A%22Al%20Tabosh%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Delphine%22%2C%22lastName%22%3A%22Ciais%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Agn%5Cu00e8s%22%2C%22lastName%22%3A%22Desroches-Castan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Christophe%22%2C%22lastName%22%3A%22Battail%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yohann%22%2C%22lastName%22%3A%22Cout%5Cu00e9%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Claire%22%2C%22lastName%22%3A%22Bouvard%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sabine%22%2C%22lastName%22%3A%22Bailly%22%7D%5D%2C%22abstractNote%22%3A%22BACKGROUND%3A%20BMP9%20and%20BMP10%20are%20two%20major%20regulators%20of%20vascular%20homeostasis.%20These%20two%20ligands%20bind%20with%20high%20affinity%20to%20the%20endothelial%20type%20I%20kinase%20receptor%20ALK1%2C%20together%20with%20a%20type%20II%20receptor%2C%20leading%20to%20the%20direct%20phosphorylation%20of%20the%20SMAD%20transcription%20factors.%20Apart%20from%20this%20canonical%20pathway%2C%20little%20is%20known.%20Interestingly%2C%20mutations%20in%20this%20signaling%20pathway%20have%20been%20identified%20in%20two%20rare%20cardiovascular%20diseases%2C%20hereditary%20hemorrhagic%20telangiectasia%20and%20pulmonary%20arterial%20hypertension.%5CnMETHODS%3A%20To%20get%20an%20overview%20of%20the%20signaling%20pathways%20modulated%20by%20BMP9%20and%20BMP10%20stimulation%20in%20endothelial%20cells%2C%20we%20employed%20an%20unbiased%20phosphoproteomic-based%20strategy.%20Identified%20phosphosites%20were%20validated%20by%20western%20blot%20analysis%20and%20regulated%20targets%20by%20RT-qPCR.%20Cell%20cycle%20analysis%20was%20analyzed%20by%20flow%20cytometry.%5CnRESULTS%3A%20Large-scale%20phosphoproteomics%20revealed%20that%20BMP9%20and%20BMP10%20treatment%20induced%20a%20very%20similar%20phosphoproteomic%20profile.%20These%20BMPs%20activated%20a%20non-canonical%20transcriptional%20SMAD-dependent%20MAPK%20pathway%20%28MEKK4%5C%2FP38%29.%20We%20were%20able%20to%20validate%20this%20signaling%20pathway%20and%20demonstrated%20that%20this%20activation%20required%20the%20expression%20of%20the%20protein%20GADD45%5Cu03b2.%20In%20turn%2C%20activated%20P38%20phosphorylated%20the%20heat%20shock%20protein%20HSP27%20and%20the%20endocytosis%20protein%20Eps15%20%28EGF%20receptor%20pathway%20substrate%29%2C%20and%20regulated%20the%20expression%20of%20specific%20genes%20%28E-selectin%2C%20hyaluronan%20synthase%202%20and%20cyclooxygenase%202%29.%20This%20study%20also%20highlighted%20the%20modulation%20in%20phosphorylation%20of%20proteins%20involved%20in%20transcriptional%20regulation%20%28phosphorylation%20of%20the%20endothelial%20transcription%20factor%20ERG%29%20and%20cell%20cycle%20inhibition%20%28CDK4%5C%2F6%20pathway%29.%20Accordingly%2C%20we%20found%20that%20BMP10%20induced%20a%20G1%20cell%20cycle%20arrest%20and%20inhibited%20the%20mRNA%20expression%20of%20E2F2%2C%20cyclinD1%20and%20cyclinA1.%5CnCONCLUSIONS%3A%20Overall%2C%20our%20phosphoproteomic%20screen%20identified%20numerous%20proteins%20whose%20phosphorylation%20state%20is%20impacted%20by%20BMP9%20and%20BMP10%20treatment%2C%20paving%20the%20way%20for%20a%20better%20understanding%20of%20the%20molecular%20mechanisms%20regulated%20by%20BMP%20signaling%20in%20vascular%20diseases.%22%2C%22date%22%3A%222024-03-04%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1186%5C%2Fs12964-024-01486-0%22%2C%22ISSN%22%3A%221478-811X%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22VIGCK6G3%22%5D%2C%22dateModified%22%3A%222024-03-06T07%3A31%3A28Z%22%7D%7D%2C%7B%22key%22%3A%22EUBBWVZA%22%2C%22library%22%3A%7B%22id%22%3A238648%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Janet-Maitre%20et%20al.%22%2C%22parsedDate%22%3A%222024-03-13%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EJanet-Maitre%2C%20M.%2C%20Job%2C%20V.%2C%20Bour%2C%20M.%2C%20Robert-Genthon%2C%20M.%2C%20Brugi%26%23xE8%3Bre%2C%20S.%2C%20Triponney%2C%20P.%2C%20Cobessi%2C%20D.%2C%20Cout%26%23xE9%3B%2C%20Y.%2C%20Jeannot%2C%20K.%2C%20%26amp%3B%20Attr%26%23xE9%3Be%2C%20I.%20%282024%29.%20Pseudomonas%20aeruginosa%20MipA-MipB%20envelope%20proteins%20act%20as%20new%20sensors%20of%20polymyxins.%20%3Ci%3EMBio%3C%5C%2Fi%3E%2C%20%3Ci%3E15%3C%5C%2Fi%3E%283%29%2C%20e0221123.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1128%5C%2Fmbio.02211-23%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1128%5C%2Fmbio.02211-23%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Pseudomonas%20aeruginosa%20MipA-MipB%20envelope%20proteins%20act%20as%20new%20sensors%20of%20polymyxins%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Manon%22%2C%22lastName%22%3A%22Janet-Maitre%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Viviana%22%2C%22lastName%22%3A%22Job%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Maxime%22%2C%22lastName%22%3A%22Bour%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Myl%5Cu00e8ne%22%2C%22lastName%22%3A%22Robert-Genthon%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sabine%22%2C%22lastName%22%3A%22Brugi%5Cu00e8re%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Pauline%22%2C%22lastName%22%3A%22Triponney%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22David%22%2C%22lastName%22%3A%22Cobessi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yohann%22%2C%22lastName%22%3A%22Cout%5Cu00e9%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Katy%22%2C%22lastName%22%3A%22Jeannot%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ina%22%2C%22lastName%22%3A%22Attr%5Cu00e9e%22%7D%5D%2C%22abstractNote%22%3A%22Due%20to%20the%20rising%20incidence%20of%20antibiotic-resistant%20infections%2C%20the%20last-line%20antibiotics%2C%20polymyxins%2C%20have%20resurged%20in%20the%20clinics%20in%20parallel%20with%20new%20bacterial%20strategies%20of%20escape.%20The%20Gram-negative%20opportunistic%20pathogen%20Pseudomonas%20aeruginosa%20develops%20resistance%20to%20colistin%5C%2Fpolymyxin%20B%20by%20distinct%20molecular%20mechanisms%2C%20mostly%20through%20modification%20of%20the%20lipid%20A%20component%20of%20the%20LPS%20by%20proteins%20encoded%20within%20the%20arnBCDATEF-ugd%20%28arn%29%20operon.%20In%20this%20work%2C%20we%20characterized%20a%20polymyxin-induced%20operon%20named%20mipBA%2C%20present%20in%20P.%20aeruginosa%20strains%20devoid%20of%20the%20arn%20operon.%20We%20showed%20that%20mipBA%20is%20activated%20by%20the%20ParR%5C%2FParS%20two-component%20regulatory%20system%20in%20response%20to%20polymyxins.%20Structural%20modeling%20revealed%20that%20MipA%20folds%20as%20an%20outer-membrane%20%5Cu03b2-barrel%2C%20harboring%20an%20internal%20negatively%20charged%20channel%2C%20able%20to%20host%20a%20polymyxin%20molecule%2C%20while%20the%20lipoprotein%20MipB%20adopts%20a%20%5Cu03b2-lactamase%20fold%20with%20two%20additional%20C-terminal%20domains.%20Experimental%20work%20confirmed%20that%20MipA%20and%20MipB%20localize%20to%20the%20bacterial%20envelope%2C%20and%20they%20co-purify%20in%20vitro.%20Nano%20differential%20scanning%20fluorimetry%20showed%20that%20polymyxins%20stabilized%20MipA%20in%20a%20specific%20and%20dose-dependent%20manner.%20Mass%20spectrometry-based%20quantitative%20proteomics%20on%20P.%20aeruginosa%20membranes%20demonstrated%20that%20%5Cu2206mipBA%20synthesized%20fourfold%20less%20MexXY-OprA%20proteins%20in%20response%20to%20polymyxin%20B%20compared%20to%20the%20wild-type%20strain.%20The%20decrease%20was%20a%20direct%20consequence%20of%20impaired%20transcriptional%20activation%20of%20the%20mex%20operon%20operated%20by%20ParR%5C%2FParS.%20We%20propose%20MipA%5C%2FMipB%20to%20act%20as%20membrane%20%28co%29sensors%20working%20in%20concert%20to%20activate%20ParS%20histidine%20kinase%20and%20help%20the%20bacterium%20to%20cope%20with%20polymyxin-mediated%20envelope%20stress%20through%20synthesis%20of%20the%20efflux%20pump%2C%20MexXY-OprA.IMPORTANCEDue%20to%20the%20emergence%20of%20multidrug-resistant%20isolates%2C%20antibiotic%20options%20may%20be%20limited%20to%20polymyxins%20to%20eradicate%20Gram-negative%20infections.%20Pseudomonas%20aeruginosa%2C%20a%20leading%20opportunistic%20pathogen%2C%20has%20the%20ability%20to%20develop%20resistance%20to%20these%20cationic%20lipopeptides%20by%20modifying%20its%20lipopolysaccharide%20through%20proteins%20encoded%20within%20the%20arn%20operon.%20Herein%2C%20we%20describe%20a%20sub-group%20of%20P.%20aeruginosa%20strains%20lacking%20the%20arn%20operon%20yet%20exhibiting%20adaptability%20to%20polymyxins.%20Exposition%20to%20sub-lethal%20polymyxin%20concentrations%20induced%20the%20expression%20and%20production%20of%20two%20envelope-associated%20proteins.%20Among%20those%2C%20MipA%2C%20an%20outer-membrane%20barrel%2C%20is%20able%20to%20specifically%20bind%20polymyxins%20with%20an%20affinity%20in%20the%2010-%5Cu00b5M%20range.%20Using%20membrane%20proteomics%20and%20phenotypic%20assays%2C%20we%20showed%20that%20MipA%20and%20MipB%20participate%20in%20the%20adaptive%20response%20to%20polymyxins%20via%20ParR%5C%2FParS%20regulatory%20signaling.%20We%20propose%20a%20new%20model%20wherein%20the%20MipA-MipB%20module%20functions%20as%20a%20novel%20polymyxin%20sensing%20mechanism.%22%2C%22date%22%3A%222024-03-13%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1128%5C%2Fmbio.02211-23%22%2C%22ISSN%22%3A%222150-7511%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22VIGCK6G3%22%5D%2C%22dateModified%22%3A%222024-04-08T06%3A32%3A11Z%22%7D%7D%2C%7B%22key%22%3A%22SY5HCIYN%22%2C%22library%22%3A%7B%22id%22%3A238648%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Alempic%20et%20al.%22%2C%22parsedDate%22%3A%222024-04-05%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EAlempic%2C%20J.-M.%2C%20Bisio%2C%20H.%2C%20Villalta%2C%20A.%2C%20Santini%2C%20S.%2C%20Lartigue%2C%20A.%2C%20Schmitt%2C%20A.%2C%20Bugnot%2C%20C.%2C%20Notaro%2C%20A.%2C%20Belmudes%2C%20L.%2C%20Adrait%2C%20A.%2C%20Poirot%2C%20O.%2C%20Ptchelkine%2C%20D.%2C%20De%20Castro%2C%20C.%2C%20Cout%26%23xE9%3B%2C%20Y.%2C%20%26amp%3B%20Abergel%2C%20C.%20%282024%29.%20Functional%20redundancy%20revealed%20by%20the%20deletion%20of%20the%20mimivirus%20GMC-oxidoreductase%20genes.%20%3Ci%3EMicroLife%3C%5C%2Fi%3E%2C%20uqae006.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Ffemsml%5C%2Fuqae006%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Ffemsml%5C%2Fuqae006%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Functional%20redundancy%20revealed%20by%20the%20deletion%20of%20the%20mimivirus%20GMC-oxidoreductase%20genes%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jean-Marie%22%2C%22lastName%22%3A%22Alempic%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hugo%22%2C%22lastName%22%3A%22Bisio%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alejandro%22%2C%22lastName%22%3A%22Villalta%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S%5Cu00e9bastien%22%2C%22lastName%22%3A%22Santini%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Audrey%22%2C%22lastName%22%3A%22Lartigue%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alain%22%2C%22lastName%22%3A%22Schmitt%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Claire%22%2C%22lastName%22%3A%22Bugnot%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Anna%22%2C%22lastName%22%3A%22Notaro%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lucid%22%2C%22lastName%22%3A%22Belmudes%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Annie%22%2C%22lastName%22%3A%22Adrait%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Olivier%22%2C%22lastName%22%3A%22Poirot%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Denis%22%2C%22lastName%22%3A%22Ptchelkine%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Cristina%22%2C%22lastName%22%3A%22De%20Castro%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yohann%22%2C%22lastName%22%3A%22Cout%5Cu00e9%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Chantal%22%2C%22lastName%22%3A%22Abergel%22%7D%5D%2C%22abstractNote%22%3A%22Abstract%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20The%20mimivirus%201.2Mb%20genome%20was%20shown%20to%20be%20organized%20into%20a%20nucleocapsid-like%20genomic%20fiber%20encased%20in%20the%20nucleoid%20compartment%20inside%20the%20icosahedral%20capsid%20%28Villalta%20et%20al.%202022%29.%20The%20genomic%20fiber%20protein%20shell%20is%20composed%20of%20a%20mixture%20of%20two%20GMC-oxidoreductase%20paralogs%2C%20one%20of%20them%20being%20the%20main%20component%20of%20the%20glycosylated%20layer%20of%20fibrils%20at%20the%20surface%20of%20the%20virion%20%28Rodrigues%20et%20al.%202015%29.%20In%20this%20study%2C%20we%20determined%20the%20effect%20of%20the%20deletion%20of%20each%20of%20the%20corresponding%20genes%20on%20the%20genomic%20fiber%20and%20the%20layer%20of%20surface%20fibrils.%20First%2C%20we%20deleted%20the%20GMC-oxidoreductase%20the%20most%20abundant%20in%20the%20genomic%20fiber%2C%20and%20determined%20its%20structure%20and%20composition%20in%20the%20mutant.%20As%20expected%2C%20it%20was%20composed%20of%20the%20second%20GMC-oxidoreductase%20and%20contained%205-%20and%206-start%20helices%20similar%20to%20the%20wild-type%20fiber.%20This%20result%20led%20us%20to%20propose%20a%20model%20explaining%20their%20coexistence.%20Then%2C%20we%20deleted%20the%20GMC-oxidoreductase%20the%20most%20abundant%20in%20the%20layer%20of%20fibrils%20to%20analyze%20its%20protein%20composition%20in%20the%20mutant.%20Second%2C%20we%20showed%20that%20the%20fitness%20of%20single%20mutants%20and%20the%20double%20mutant%20were%20not%20decreased%20compared%20to%20the%20wild-type%20viruses%20in%20laboratory%20conditions.%20Third%2C%20we%20determined%20that%20deleting%20the%20GMC-oxidoreductase%20genes%20did%20not%20impact%20the%20glycosylation%20or%20the%20glycan%20composition%20of%20the%20layer%20of%20surface%20fibrils%2C%20despite%20modifying%20their%20protein%20composition.%20Since%20the%20glycosylation%20machinery%20and%20glycan%20composition%20of%20members%20of%20different%20clades%20are%20different%20%28Notaro%20et%20al.%202021%2C%20Notaro%20et%20al.%202022%29%2C%20we%20expanded%20the%20analysis%20of%20the%20protein%20composition%20of%20the%20layer%20of%20fibrils%20to%20members%20of%20the%20B%20and%20C%20clades%20and%20showed%20that%20it%20was%20different%20among%20the%20three%20clades%20and%20even%20among%20isolates%20within%20the%20same%20clade.%20Taken%20together%2C%20the%20results%20obtained%20on%20two%20distinct%20central%20processes%20%28genome%20packaging%20and%20virion%20coating%29%20illustrate%20an%20unexpected%20functional%20redundancy%20in%20members%20of%20the%20family%20Mimiviridae%2C%20suggesting%20this%20may%20be%20the%20major%20evolutionary%20force%20behind%20their%20giant%20genomes.%22%2C%22date%22%3A%222024-04-05%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1093%5C%2Ffemsml%5C%2Fuqae006%22%2C%22ISSN%22%3A%222633-6693%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Facademic.oup.com%5C%2Fmicrolife%5C%2Fadvance-article%5C%2Fdoi%5C%2F10.1093%5C%2Ffemsml%5C%2Fuqae006%5C%2F7641406%22%2C%22collections%22%3A%5B%22VIGCK6G3%22%5D%2C%22dateModified%22%3A%222024-04-08T06%3A31%3A40Z%22%7D%7D%2C%7B%22key%22%3A%22MQLXLEPL%22%2C%22library%22%3A%7B%22id%22%3A238648%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22P%5Cu00e9rez%20Compte%20et%20al.%22%2C%22parsedDate%22%3A%222024-04-29%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EP%26%23xE9%3Brez%20Compte%2C%20D.%2C%20Etourneau%2C%20L.%2C%20Hesse%2C%20A.-M.%2C%20Kraut%2C%20A.%2C%20Barthelon%2C%20J.%2C%20Sturm%2C%20N.%2C%20Borges%2C%20H.%2C%20Biennier%2C%20S.%2C%20Cour%26%23xE7%3Bon%2C%20M.%2C%20de%20Saint%20Loup%2C%20M.%2C%20Mignot%2C%20V.%2C%20Costentin%2C%20C.%2C%20Burger%2C%20T.%2C%20Cout%26%23xE9%3B%2C%20Y.%2C%20Bruley%2C%20C.%2C%20Decaens%2C%20T.%2C%20Jaquinod%2C%20M.%2C%20Boursier%2C%20J.%2C%20%26amp%3B%20Brun%2C%20V.%20%282024%29.%20Plasma%20ALS%20and%20Gal-3BP%20differentiate%20early%20from%20advanced%20liver%20fibrosis%20in%20MASLD%20patients.%20%3Ci%3EBiomarker%20Research%3C%5C%2Fi%3E%2C%20%3Ci%3E12%3C%5C%2Fi%3E%281%29%2C%2044.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1186%5C%2Fs40364-024-00583-z%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1186%5C%2Fs40364-024-00583-z%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Plasma%20ALS%20and%20Gal-3BP%20differentiate%20early%20from%20advanced%20liver%20fibrosis%20in%20MASLD%20patients%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22David%22%2C%22lastName%22%3A%22P%5Cu00e9rez%20Compte%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lucas%22%2C%22lastName%22%3A%22Etourneau%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Anne-Marie%22%2C%22lastName%22%3A%22Hesse%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alexandra%22%2C%22lastName%22%3A%22Kraut%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Justine%22%2C%22lastName%22%3A%22Barthelon%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nathalie%22%2C%22lastName%22%3A%22Sturm%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22H%5Cu00e9l%5Cu00e8ne%22%2C%22lastName%22%3A%22Borges%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Salom%5Cu00e9%22%2C%22lastName%22%3A%22Biennier%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marie%22%2C%22lastName%22%3A%22Cour%5Cu00e7on%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marc%22%2C%22lastName%22%3A%22de%20Saint%20Loup%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Victoria%22%2C%22lastName%22%3A%22Mignot%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Charlotte%22%2C%22lastName%22%3A%22Costentin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Thomas%22%2C%22lastName%22%3A%22Burger%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yohann%22%2C%22lastName%22%3A%22Cout%5Cu00e9%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Christophe%22%2C%22lastName%22%3A%22Bruley%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Thomas%22%2C%22lastName%22%3A%22Decaens%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Michel%22%2C%22lastName%22%3A%22Jaquinod%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J%5Cu00e9r%5Cu00f4me%22%2C%22lastName%22%3A%22Boursier%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Virginie%22%2C%22lastName%22%3A%22Brun%22%7D%5D%2C%22abstractNote%22%3A%22BACKGROUND%3A%20Metabolic%20dysfunction-associated%20steatotic%20liver%20disease%20%28MASLD%29%20is%20estimated%20to%20affect%2030%25%20of%20the%20world%27s%20population%2C%20and%20its%20prevalence%20is%20increasing%20in%20line%20with%20obesity.%20Liver%20fibrosis%20is%20closely%20related%20to%20mortality%2C%20making%20it%20the%20most%20important%20clinical%20parameter%20for%20MASLD.%20It%20is%20currently%20assessed%20by%20liver%20biopsy%20-%20an%20invasive%20procedure%20that%20has%20some%20limitations.%20There%20is%20thus%20an%20urgent%20need%20for%20a%20reliable%20non-invasive%20means%20to%20diagnose%20earlier%20MASLD%20stages.%5CnMETHODS%3A%20A%20discovery%20study%20was%20performed%20on%20158%20plasma%20samples%20from%20histologically-characterised%20MASLD%20patients%20using%20mass%20spectrometry%20%28MS%29-based%20quantitative%20proteomics.%20Differentially%20abundant%20proteins%20were%20selected%20for%20verification%20by%20ELISA%20in%20the%20same%20cohort.%20They%20were%20subsequently%20validated%20in%20an%20independent%20MASLD%20cohort%20%28n%5Cu2009%3D%5Cu2009200%29.%5CnRESULTS%3A%20From%20the%2072%20proteins%20differentially%20abundant%20between%20patients%20with%20early%20%28F0-2%29%20and%20advanced%20fibrosis%20%28F3-4%29%2C%20we%20selected%20Insulin-like%20growth%20factor-binding%20protein%20complex%20acid%20labile%20subunit%20%28ALS%29%20and%20Galectin-3-binding%20protein%20%28Gal-3BP%29%20for%20further%20study.%20In%20our%20validation%20cohort%2C%20AUROCs%20with%2095%25%20CIs%20of%200.744%20%5B0.673%5Cu00a0-%5Cu00a00.816%5D%20and%200.735%20%5B0.661%5Cu00a0-%5Cu00a00.81%5D%20were%20obtained%20for%20ALS%20and%20Gal-3BP%2C%20respectively.%20Combining%20ALS%20and%20Gal-3BP%20improved%20the%20assessment%20of%20advanced%20liver%20fibrosis%2C%20giving%20an%20AUROC%20of%200.796%20%5B0.731.%200.862%5D.%20The%20%7BALS%3B%20Gal-3BP%7D%20model%20surpassed%20classic%20fibrosis%20panels%20in%20predicting%20advanced%20liver%20fibrosis.%5CnCONCLUSIONS%3A%20Further%20investigations%20with%20complementary%20cohorts%20will%20be%20needed%20to%20confirm%20the%20usefulness%20of%20ALS%20and%20Gal-3BP%20individually%20and%20in%20combination%20with%20other%20biomarkers%20for%20diagnosis%20of%20liver%20fibrosis.%20With%20the%20availability%20of%20ELISA%20assays%2C%20these%20findings%20could%20be%20rapidly%20clinically%20translated%2C%20providing%20direct%20benefits%20for%20patients.%22%2C%22date%22%3A%222024-04-29%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1186%5C%2Fs40364-024-00583-z%22%2C%22ISSN%22%3A%222050-7771%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22VIGCK6G3%22%5D%2C%22dateModified%22%3A%222024-04-29T13%3A51%3A47Z%22%7D%7D%2C%7B%22key%22%3A%22G3L8NCN2%22%2C%22library%22%3A%7B%22id%22%3A238648%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Pastor%20et%20al.%22%2C%22parsedDate%22%3A%222024-05-22%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EPastor%2C%20F.%2C%20Charles%2C%20E.%2C%20Belmudes%2C%20L.%2C%20Chabrolles%2C%20H.%2C%20Cescato%2C%20M.%2C%20Rivoire%2C%20M.%2C%20Burger%2C%20T.%2C%20Passot%2C%20G.%2C%20Durantel%2C%20D.%2C%20Lucifora%2C%20J.%2C%20Cout%26%23xE9%3B%2C%20Y.%2C%20%26amp%3B%20Salvetti%2C%20A.%20%282024%29.%20Deciphering%20the%20phospho-signature%20induced%20by%20hepatitis%20B%20virus%20in%20primary%20human%20hepatocytes.%20%3Ci%3EFrontiers%20in%20Microbiology%3C%5C%2Fi%3E%2C%20%3Ci%3E15%3C%5C%2Fi%3E%2C%201415449.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3389%5C%2Ffmicb.2024.1415449%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3389%5C%2Ffmicb.2024.1415449%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Deciphering%20the%20phospho-signature%20induced%20by%20hepatitis%20B%20virus%20in%20primary%20human%20hepatocytes%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Florentin%22%2C%22lastName%22%3A%22Pastor%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Emilie%22%2C%22lastName%22%3A%22Charles%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lucid%22%2C%22lastName%22%3A%22Belmudes%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22H%5Cu00e9l%5Cu00e8ne%22%2C%22lastName%22%3A%22Chabrolles%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marion%22%2C%22lastName%22%3A%22Cescato%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Michel%22%2C%22lastName%22%3A%22Rivoire%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Thomas%22%2C%22lastName%22%3A%22Burger%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Guillaume%22%2C%22lastName%22%3A%22Passot%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22David%22%2C%22lastName%22%3A%22Durantel%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Julie%22%2C%22lastName%22%3A%22Lucifora%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yohann%22%2C%22lastName%22%3A%22Cout%5Cu00e9%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Anna%22%2C%22lastName%22%3A%22Salvetti%22%7D%5D%2C%22abstractNote%22%3A%22Phosphorylation%20is%20a%20major%20post-translation%20modification%20%28PTM%29%20of%20proteins%20which%20is%20finely%20tuned%20by%20the%20activity%20of%20several%20hundred%20kinases%20and%20phosphatases.%20It%20controls%20most%20if%20not%20all%20cellular%20pathways%20including%20anti-viral%20responses.%20Accordingly%2C%20viruses%20often%20induce%20important%20changes%20in%20the%20phosphorylation%20of%20host%20factors%20that%20can%20either%20promote%20or%20counteract%20viral%20replication.%20Among%20more%20than%20500%20kinases%20constituting%20the%20human%20kinome%20only%20few%20have%20been%20described%20as%20important%20for%20the%20hepatitis%20B%20virus%20%28HBV%29%20infectious%20cycle%2C%20and%20most%20of%20them%20intervene%20during%20early%20or%20late%20infectious%20steps%20by%20phosphorylating%20the%20viral%20Core%20%28HBc%29%20protein.%20In%20addition%2C%20little%20is%20known%20on%20the%20consequences%20of%20HBV%20infection%20on%20the%20activity%20of%20cellular%20kinases.%20The%20objective%20of%20this%20study%20was%20to%20investigate%20the%20global%20impact%20of%20HBV%20infection%20on%20the%20cellular%20phosphorylation%20landscape%20early%20after%20infection.%20For%20this%2C%20primary%20human%20hepatocytes%20%28PHHs%29%20were%20challenged%20or%20not%20with%20HBV%2C%20and%20a%20mass%20spectrometry%20%28MS%29-based%20quantitative%20phosphoproteomic%20analysis%20was%20conducted%202-%20and%207-days%20post-infection.%20The%20results%20indicated%20that%20while%2C%20as%20expected%2C%20HBV%20infection%20only%20minimally%20modified%20the%20cell%20proteome%2C%20significant%20changes%20were%20observed%20in%20the%20phosphorylation%20state%20of%20several%20host%20proteins%20at%20both%20time%20points.%20Gene%20enrichment%20and%20ontology%20analyses%20of%20up-%20and%20down-phosphorylated%20proteins%20revealed%20common%20and%20distinct%20signatures%20induced%20by%20infection.%20In%20particular%2C%20HBV%20infection%20resulted%20in%20up-phosphorylation%20of%20proteins%20involved%20in%20DNA%20damage%20signaling%20and%20repair%2C%20RNA%20metabolism%2C%20in%20particular%20splicing%2C%20and%20cytoplasmic%20cell-signaling.%20Down-phosphorylated%20proteins%20were%20mostly%20involved%20in%20cell%20signaling%20and%20communication.%20Validation%20studies%20carried%20out%20on%20selected%20up-phosphorylated%20proteins%2C%20revealed%20that%20HBV%20infection%20induced%20a%20DNA%20damage%20response%20characterized%20by%20the%20appearance%20of%2053BP1%20foci%2C%20the%20inactivation%20of%20which%20by%20siRNA%20increased%20cccDNA%20levels.%20In%20addition%2C%20among%20up-phosphorylated%20RNA%20binding%20proteins%20%28RBPs%29%2C%20SRRM2%2C%20a%20major%20scaffold%20of%20nuclear%20speckles%20behaved%20as%20an%20antiviral%20factor.%20In%20accordance%20with%20these%20findings%2C%20kinase%20prediction%20analysis%20indicated%20that%20HBV%20infection%20upregulates%20the%20activity%20of%20major%20kinases%20involved%20in%20DNA%20repair.%20These%20results%20strongly%20suggest%20that%20HBV%20infection%20triggers%20an%20intrinsic%20anti-viral%20response%20involving%20DNA%20repair%20factors%20and%20RBPs%20that%20contribute%20to%20reduce%20HBV%20replication%20in%20cell%20culture%20models.%22%2C%22date%22%3A%222024-5-22%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.3389%5C%2Ffmicb.2024.1415449%22%2C%22ISSN%22%3A%221664-302X%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.frontiersin.org%5C%2Farticles%5C%2F10.3389%5C%2Ffmicb.2024.1415449%5C%2Ffull%22%2C%22collections%22%3A%5B%22VIGCK6G3%22%5D%2C%22dateModified%22%3A%222024-05-27T13%3A36%3A16Z%22%7D%7D%2C%7B%22key%22%3A%22F8XFEEZ7%22%2C%22library%22%3A%7B%22id%22%3A238648%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Anoud%20et%20al.%22%2C%22parsedDate%22%3A%222024-07-09%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EAnoud%2C%20M.%2C%20Delagoutte%2C%20E.%2C%20Helleu%2C%20Q.%2C%20Brion%2C%20A.%2C%20Duvernois-Berthet%2C%20E.%2C%20As%2C%20M.%2C%20Marques%2C%20X.%2C%20Lamribet%2C%20K.%2C%20Senamaud-Beaufort%2C%20C.%2C%20Jourdren%2C%20L.%2C%20Adrait%2C%20A.%2C%20Heinrich%2C%20S.%2C%20Toutirais%2C%20G.%2C%20Hamlaoui%2C%20S.%2C%20Gropplero%2C%20G.%2C%20Giovannini%2C%20I.%2C%20Ponger%2C%20L.%2C%20Geze%2C%20M.%2C%20Blugeon%2C%20C.%2C%20%26%23x2026%3B%20Concordet%2C%20J.-P.%20%282024%29.%20Comparative%20transcriptomics%20reveal%20a%20novel%20tardigrade-specific%20DNA-binding%20protein%20induced%20in%20response%20to%20ionizing%20radiation.%20%3Ci%3EELife%3C%5C%2Fi%3E%2C%20%3Ci%3E13%3C%5C%2Fi%3E%2C%20RP92621.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.7554%5C%2FeLife.92621%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.7554%5C%2FeLife.92621%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Comparative%20transcriptomics%20reveal%20a%20novel%20tardigrade-specific%20DNA-binding%20protein%20induced%20in%20response%20to%20ionizing%20radiation%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marwan%22%2C%22lastName%22%3A%22Anoud%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Emmanuelle%22%2C%22lastName%22%3A%22Delagoutte%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Quentin%22%2C%22lastName%22%3A%22Helleu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alice%22%2C%22lastName%22%3A%22Brion%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Evelyne%22%2C%22lastName%22%3A%22Duvernois-Berthet%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marie%22%2C%22lastName%22%3A%22As%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xavier%22%2C%22lastName%22%3A%22Marques%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Khadija%22%2C%22lastName%22%3A%22Lamribet%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Catherine%22%2C%22lastName%22%3A%22Senamaud-Beaufort%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Laurent%22%2C%22lastName%22%3A%22Jourdren%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Annie%22%2C%22lastName%22%3A%22Adrait%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sophie%22%2C%22lastName%22%3A%22Heinrich%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Geraldine%22%2C%22lastName%22%3A%22Toutirais%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sahima%22%2C%22lastName%22%3A%22Hamlaoui%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Giacomo%22%2C%22lastName%22%3A%22Gropplero%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ilaria%22%2C%22lastName%22%3A%22Giovannini%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Loic%22%2C%22lastName%22%3A%22Ponger%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marc%22%2C%22lastName%22%3A%22Geze%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Corinne%22%2C%22lastName%22%3A%22Blugeon%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yohann%22%2C%22lastName%22%3A%22Cout%5Cu00e9%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Roberto%22%2C%22lastName%22%3A%22Guidetti%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lorena%22%2C%22lastName%22%3A%22Rebecchi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Carine%22%2C%22lastName%22%3A%22Giovannangeli%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Anne%22%2C%22lastName%22%3A%22De%20Cian%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jean-Paul%22%2C%22lastName%22%3A%22Concordet%22%7D%5D%2C%22abstractNote%22%3A%22Tardigrades%20are%20microscopic%20animals%20renowned%20for%20their%20ability%20to%20withstand%20extreme%20conditions%2C%20including%20high%20doses%20of%20ionizing%20radiation%20%28IR%29.%20To%20better%20understand%20their%20radio-resistance%2C%20we%20first%20characterized%20induction%20and%20repair%20of%20DNA%20double-%20and%20single-strand%20breaks%20after%20exposure%20to%20IR%20in%20the%20model%20species%20Hypsibius%20exemplaris.%20Importantly%2C%20we%20found%20that%20the%20rate%20of%20single-strand%20breaks%20induced%20was%20roughly%20equivalent%20to%20that%20in%20human%20cells%2C%20suggesting%20that%20DNA%20repair%20plays%20a%20predominant%20role%20in%20tardigrades%27%20radio-resistance.%20To%20identify%20novel%20tardigrade-specific%20genes%20involved%2C%20we%20next%20conducted%20a%20comparative%20transcriptomics%20analysis%20across%20three%20different%20species.%20In%20all%20three%20species%2C%20many%20DNA%20repair%20genes%20were%20among%20the%20most%20strongly%20overexpressed%20genes%20alongside%20a%20novel%20tardigrade-specific%20gene%2C%20which%20we%20named%20Tardigrade%20DNA%20damage%20Response%201%20%28TDR1%29.%20We%20found%20that%20TDR1%20protein%20interacts%20with%20DNA%20and%20forms%20aggregates%20at%20high%20concentration%20suggesting%20it%20may%20condensate%20DNA%20and%20preserve%20chromosome%20organization%20until%20DNA%20repair%20is%20accomplished.%20Remarkably%2C%20when%20expressed%20in%20human%20cells%2C%20TDR1%20improved%20resistance%20to%20Bleomycin%2C%20a%20radiomimetic%20drug.%20Based%20on%20these%20findings%2C%20we%20propose%20that%20TDR1%20is%20a%20novel%20tardigrade-specific%20gene%20conferring%20resistance%20to%20IR.%20Our%20study%20sheds%20light%20on%20mechanisms%20of%20DNA%20repair%20helping%20cope%20with%20high%20levels%20of%20DNA%20damage%20inflicted%20by%20IR.%22%2C%22date%22%3A%222024-07-09%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.7554%5C%2FeLife.92621%22%2C%22ISSN%22%3A%222050-084X%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22VIGCK6G3%22%5D%2C%22dateModified%22%3A%222024-08-05T06%3A51%3A13Z%22%7D%7D%2C%7B%22key%22%3A%2283ZNWX35%22%2C%22library%22%3A%7B%22id%22%3A238648%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Bagdadi%20et%20al.%22%2C%22parsedDate%22%3A%222024-08-05%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EBagdadi%2C%20N.%2C%20Wu%2C%20J.%2C%20Delaroche%2C%20J.%2C%20Serre%2C%20L.%2C%20Delphin%2C%20C.%2C%20De%20Andrade%2C%20M.%2C%20Carcel%2C%20M.%2C%20Nawabi%2C%20H.%2C%20Pinson%2C%20B.%2C%20V%26%23xE9%3Brin%2C%20C.%2C%20Cout%26%23xE9%3B%2C%20Y.%2C%20Gory-Faur%26%23xE9%3B%2C%20S.%2C%20Andrieux%2C%20A.%2C%20Stoppin-Mellet%2C%20V.%2C%20%26amp%3B%20Arnal%2C%20I.%20%282024%29.%20Stable%20GDP-tubulin%20islands%20rescue%20dynamic%20microtubules.%20%3Ci%3EThe%20Journal%20of%20Cell%20Biology%3C%5C%2Fi%3E%2C%20%3Ci%3E223%3C%5C%2Fi%3E%288%29%2C%20e202307074.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1083%5C%2Fjcb.202307074%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1083%5C%2Fjcb.202307074%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Stable%20GDP-tubulin%20islands%20rescue%20dynamic%20microtubules%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nassiba%22%2C%22lastName%22%3A%22Bagdadi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Juliette%22%2C%22lastName%22%3A%22Wu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Julie%22%2C%22lastName%22%3A%22Delaroche%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Laurence%22%2C%22lastName%22%3A%22Serre%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Christian%22%2C%22lastName%22%3A%22Delphin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Manon%22%2C%22lastName%22%3A%22De%20Andrade%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marion%22%2C%22lastName%22%3A%22Carcel%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Homaira%22%2C%22lastName%22%3A%22Nawabi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Beno%5Cu00eet%22%2C%22lastName%22%3A%22Pinson%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Claire%22%2C%22lastName%22%3A%22V%5Cu00e9rin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yohann%22%2C%22lastName%22%3A%22Cout%5Cu00e9%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sylvie%22%2C%22lastName%22%3A%22Gory-Faur%5Cu00e9%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Annie%22%2C%22lastName%22%3A%22Andrieux%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Virginie%22%2C%22lastName%22%3A%22Stoppin-Mellet%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Isabelle%22%2C%22lastName%22%3A%22Arnal%22%7D%5D%2C%22abstractNote%22%3A%22Microtubules%20are%20dynamic%20polymers%20that%20interconvert%20between%20phases%20of%20growth%20and%20shrinkage%2C%20yet%20they%20provide%20structural%20stability%20to%20cells.%20Growth%20involves%20hydrolysis%20of%20GTP-tubulin%20to%20GDP-tubulin%2C%20which%20releases%20energy%20that%20is%20stored%20within%20the%20microtubule%20lattice%20and%20destabilizes%20it%3B%20a%20GTP%20cap%20at%20microtubule%20ends%20is%20thought%20to%20prevent%20GDP%20subunits%20from%20rapidly%20dissociating%20and%20causing%20catastrophe.%20Here%2C%20using%20in%20vitro%20reconstitution%20assays%2C%20we%20show%20that%20GDP-tubulin%2C%20usually%20considered%20inactive%2C%20can%20itself%20assemble%20into%20microtubules%2C%20preferentially%20at%20the%20minus%20end%2C%20and%20promote%20persistent%20growth.%20GDP-tubulin-assembled%20microtubules%20are%20highly%20stable%2C%20displaying%20no%20detectable%20spontaneous%20shrinkage.%20Strikingly%2C%20islands%20of%20GDP-tubulin%20within%20dynamic%20microtubules%20stop%20shrinkage%20events%20and%20promote%20rescues.%20Microtubules%20thus%20possess%20an%20intrinsic%20capacity%20for%20stability%2C%20independent%20of%20accessory%20proteins.%20This%20finding%20provides%20novel%20mechanisms%20to%20explain%20microtubule%20dynamics.%22%2C%22date%22%3A%222024-08-05%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1083%5C%2Fjcb.202307074%22%2C%22ISSN%22%3A%221540-8140%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22VIGCK6G3%22%5D%2C%22dateModified%22%3A%222024-05-21T06%3A45%3A41Z%22%7D%7D%2C%7B%22key%22%3A%22TQUVWLIW%22%2C%22library%22%3A%7B%22id%22%3A238648%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Neumann%20et%20al.%22%2C%22parsedDate%22%3A%222024-08-12%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ENeumann%2C%20A.%20P.%2C%20Sage%2C%20E.%2C%20Boll%2C%20D.%2C%20Reinhardt-Szyba%2C%20M.%2C%20Fon%2C%20W.%2C%20Masselon%2C%20C.%2C%20Hentz%2C%20S.%2C%20Sader%2C%20J.%20E.%2C%20Makarov%2C%20A.%2C%20%26amp%3B%20Roukes%2C%20M.%20L.%20%282024%29.%20A%20Hybrid%20Orbitrap-Nanoelectromechanical%20Systems%20Approach%20for%20the%20Analysis%20of%20Individual%2C%20Intact%20Proteins%20in%20Real%20Time.%20%3Ci%3EAngewandte%20Chemie%20%28International%20Ed.%20in%20English%29%3C%5C%2Fi%3E%2C%20%3Ci%3E63%3C%5C%2Fi%3E%2833%29%2C%20e202317064.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1002%5C%2Fanie.202317064%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1002%5C%2Fanie.202317064%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22A%20Hybrid%20Orbitrap-Nanoelectromechanical%20Systems%20Approach%20for%20the%20Analysis%20of%20Individual%2C%20Intact%20Proteins%20in%20Real%20Time%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Adam%20P.%22%2C%22lastName%22%3A%22Neumann%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Eric%22%2C%22lastName%22%3A%22Sage%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Dmitri%22%2C%22lastName%22%3A%22Boll%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Maria%22%2C%22lastName%22%3A%22Reinhardt-Szyba%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Warren%22%2C%22lastName%22%3A%22Fon%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Christophe%22%2C%22lastName%22%3A%22Masselon%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S%5Cu00e9bastien%22%2C%22lastName%22%3A%22Hentz%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22John%20E.%22%2C%22lastName%22%3A%22Sader%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alexander%22%2C%22lastName%22%3A%22Makarov%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Michael%20L.%22%2C%22lastName%22%3A%22Roukes%22%7D%5D%2C%22abstractNote%22%3A%22Nanoelectromechanical%20systems%20%28NEMS%29-based%20mass%20spectrometry%20%28MS%29%20is%20an%20emerging%20technique%20that%20enables%20determination%20of%20the%20mass%20of%20individual%20adsorbed%20particles%20by%20driving%20nanomechanical%20devices%20at%20resonance%20and%20monitoring%20the%20real-time%20changes%20in%20their%20resonance%20frequencies%20induced%20by%20each%20single%20molecule%20adsorption%20event.%20We%20incorporate%20NEMS%20into%20an%20Orbitrap%20mass%20spectrometer%20and%20report%20our%20progress%20towards%20leveraging%20the%20single-molecule%20capabilities%20of%20the%20NEMS%20to%20enhance%20the%20dynamic%20range%20of%20conventional%20MS%20instrumentation%20and%20to%20offer%20new%20capabilities%20for%20performing%20deep%20proteomic%20analysis%20of%20clinically%20relevant%20samples.%20We%20use%20the%20hybrid%20instrument%20to%20deliver%20E.%5Cu2005coli%20GroEL%20molecules%20%28801%5Cu2005kDa%29%20to%20the%20NEMS%20devices%20in%20their%20native%2C%20intact%20state.%20Custom%20ion%20optics%20are%20used%20to%20focus%20the%20beam%20down%20to%2040%5Cu2005%5Cu03bcm%20diameter%20with%20a%20maximum%20flux%20of%2025%5Cu2005molecules%5C%2Fsecond.%20The%20mass%20spectrum%20obtained%20with%20NEMS-MS%20shows%20good%20agreement%20with%20the%20known%20mass%20of%20GroEL.%22%2C%22date%22%3A%222024-08-12%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1002%5C%2Fanie.202317064%22%2C%22ISSN%22%3A%221521-3773%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22VIGCK6G3%22%5D%2C%22dateModified%22%3A%222024-08-23T07%3A00%3A51Z%22%7D%7D%5D%7D
Antunes, A. V., Shahinas, M., Swale, C., Farhat, D. C., Ramakrishnan, C., Bruley, C., Cannella, D., Robert, M. G., Corrao, C., Couté, Y., Hehl, A. B., Bougdour, A., Coppens, I., & Hakimi, M.-A. (2024). In vitro production of cat-restricted Toxoplasma pre-sexual stages. Nature, 625(7994), 366–376. https://doi.org/10.1038/s41586-023-06821-y
Casanova, A. G., Roth, G. S., Hausmann, S., Lu, X., Bischoff, L. J. M., Froeliger, E. M., Belmudes, L., Bourova-Flin, E., Flores, N. M., Benitez, A. M., Chasan, T., Caporicci, M., Vayr, J., Blanchet, S., Ielasi, F., Rousseaux, S., Hainaut, P., Gozani, O., Le Romancer, M., … Reynoird, N. (2024). Cytoskeleton remodeling induced by SMYD2 methyltransferase drives breast cancer metastasis. Cell Discovery, 10(1), 1–22. https://doi.org/10.1038/s41421-023-00644-x
Burger, T. (2024). Fudging the volcano-plot without dredging the data. Nature Communications, 15(1), 1392. https://doi.org/10.1038/s41467-024-45834-7
Al Tarrass, M., Belmudes, L., Koça, D., Azemard, V., Liu, H., Al Tabosh, T., Ciais, D., Desroches-Castan, A., Battail, C., Couté, Y., Bouvard, C., & Bailly, S. (2024). Large-scale phosphoproteomics reveals activation of the MAPK/GADD45β/P38 axis and cell cycle inhibition in response to BMP9 and BMP10 stimulation in endothelial cells. Cell Communication and Signaling: CCS, 22(1), 158. https://doi.org/10.1186/s12964-024-01486-0
Janet-Maitre, M., Job, V., Bour, M., Robert-Genthon, M., Brugière, S., Triponney, P., Cobessi, D., Couté, Y., Jeannot, K., & Attrée, I. (2024). Pseudomonas aeruginosa MipA-MipB envelope proteins act as new sensors of polymyxins. MBio, 15(3), e0221123. https://doi.org/10.1128/mbio.02211-23
Alempic, J.-M., Bisio, H., Villalta, A., Santini, S., Lartigue, A., Schmitt, A., Bugnot, C., Notaro, A., Belmudes, L., Adrait, A., Poirot, O., Ptchelkine, D., De Castro, C., Couté, Y., & Abergel, C. (2024). Functional redundancy revealed by the deletion of the mimivirus GMC-oxidoreductase genes. MicroLife, uqae006. https://doi.org/10.1093/femsml/uqae006
Pérez Compte, D., Etourneau, L., Hesse, A.-M., Kraut, A., Barthelon, J., Sturm, N., Borges, H., Biennier, S., Courçon, M., de Saint Loup, M., Mignot, V., Costentin, C., Burger, T., Couté, Y., Bruley, C., Decaens, T., Jaquinod, M., Boursier, J., & Brun, V. (2024). Plasma ALS and Gal-3BP differentiate early from advanced liver fibrosis in MASLD patients. Biomarker Research, 12(1), 44. https://doi.org/10.1186/s40364-024-00583-z
Pastor, F., Charles, E., Belmudes, L., Chabrolles, H., Cescato, M., Rivoire, M., Burger, T., Passot, G., Durantel, D., Lucifora, J., Couté, Y., & Salvetti, A. (2024). Deciphering the phospho-signature induced by hepatitis B virus in primary human hepatocytes. Frontiers in Microbiology, 15, 1415449. https://doi.org/10.3389/fmicb.2024.1415449
Anoud, M., Delagoutte, E., Helleu, Q., Brion, A., Duvernois-Berthet, E., As, M., Marques, X., Lamribet, K., Senamaud-Beaufort, C., Jourdren, L., Adrait, A., Heinrich, S., Toutirais, G., Hamlaoui, S., Gropplero, G., Giovannini, I., Ponger, L., Geze, M., Blugeon, C., … Concordet, J.-P. (2024). Comparative transcriptomics reveal a novel tardigrade-specific DNA-binding protein induced in response to ionizing radiation. ELife, 13, RP92621. https://doi.org/10.7554/eLife.92621
Bagdadi, N., Wu, J., Delaroche, J., Serre, L., Delphin, C., De Andrade, M., Carcel, M., Nawabi, H., Pinson, B., Vérin, C., Couté, Y., Gory-Fauré, S., Andrieux, A., Stoppin-Mellet, V., & Arnal, I. (2024). Stable GDP-tubulin islands rescue dynamic microtubules. The Journal of Cell Biology, 223(8), e202307074. https://doi.org/10.1083/jcb.202307074
Neumann, A. P., Sage, E., Boll, D., Reinhardt-Szyba, M., Fon, W., Masselon, C., Hentz, S., Sader, J. E., Makarov, A., & Roukes, M. L. (2024). A Hybrid Orbitrap-Nanoelectromechanical Systems Approach for the Analysis of Individual, Intact Proteins in Real Time. Angewandte Chemie (International Ed. in English), 63(33), e202317064. https://doi.org/10.1002/anie.202317064