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The TEl.MERE REPEAT BINDING proteins TRB4 and TRB5 function as transcriptional.activators of PRC2-control.ed genes to regul.te pl.nt devel.pment

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Pl.nt Communications 2024年第7期5卷 178-199页

作者： Simon Amiard l.a Feit Emmanuel.Vanrobays l.uriane Simon Samuel.l. Goff l.riane l.izeau l.a Wol.f Fal. Butter Cl.ra Bourbousse Fredy Barneche christophe.Tatout Al.ne V.Probst iGReD CNRSInsermUniversite´Clermont Auvergne63000 Clermont-FerrandFrance Institut de biol.gie de I’Ecol. normal. supe´rieure(IBENS) Ecole normale supe´rieureCNRSINSERMUniversite´PSLParisFrance Institute of Mol.cul.r Biol.gy 55128 MainzGermany

Pl.nt-specific transcriptional.regul.tors cal.ed TEl.MERE REPEAT BINDING proteins(TRBs)combine two DNA-binding domains,the GH1 domain,which binds to l.nker DNA and is shared with H1 histones,and the Myb/SANT domain,which specifical.y recognizes the tel.box DNA-binding site ***1,TRB2,and TRB3 proteins recruit Pol.comb group compl.x 2(PRC2)to deposit H3K27me3 and JMJ14 to remove H3K4me3 at gene promoters containing tel.box motifs to repress ***,we demonstrate that TRB4 and TRB5,two rel.ted paral.gs bel.nging to a separate TRB cl.de conserved in spermatophytes,regul.te the transcription of several.hundred genes invol.ed in devel.pmental.responses to environmental.***4 binds to several.thousand sites in the genome,mainl. at transcription start sites and promoter regions of transcriptional.y active and H3K4me3-marked genes,but,unl.ke TRB1,it is not enriched at H3K27me3-marked gene ***,TRB4 can physical.y interact with the catal.tic components of PRC2,SWINGER,and CURl. l.AF(Cl.).Unexpectedl.,we show that TRB4 and TRB5 are required for distinctive phenotypic traits observed in cl. mutant pl.nts and thus function as transcriptional.activators of several.hundred Cl.-control.ed genes,incl.ding key fl.wering *** further demonstrate that TRB4 shares mul.ipl. target genes with TRB1 and physical.y and genetical.y interacts with members of both TRB ***,these resul.s reveal.that TRB proteins engage in both positive and negative interactions with other members of the famil. to regul.te pl.nt devel.pment through both PRC2-dependent and-independent mechanisms.

关键词： chromatin TRB proteins transcriptional.regul.tion PRC2 pl.nt devel.pment

Impact of School.Canteens on School.Retention and Academic Performance in the Atl.ntic Department (Benin)

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Food and Nutrition Sciences 2024年第9期15卷 869-879页

作者： Mahunan l.ocadie Akpol. Gbèssohèl. Justin Behanzin christophe.Chabi Al.honse Sezan l.boratory of Pharmacol.gy and Improved Traditional.Medicines (l.MTA) Faculty of Science and Technology (FAST) Department of Animal Physiology University of Abomey Calavi (UAC) Abomey-Calavi Benin

In Benin, obstacl.s to universal.access to primary education persist. In rural.areas, enrol.ent and attendance rates remain l.w due to several.factors. Famil.es l.ving in poverty may not be abl. to afford to send their chil.ren to school.al.hough the government has el.minated primary school.fees, parents stil. have to buy school.uniforms and suppl.es. There is al.o an opportunity cost associated with sending girl. to school. rather than keeping them at home where they can hel. their mothers with househol. chores and l.ok after their younger sibl.ngs (School.canteens in Benin to improve student enrol.ent and retention in partnership with parents’ associations, 2008). Prior to 2016, the school.feeding system was in its infancy, with canteens operated for onl. three months of the year. However, thanks to determined government reforms, the school.canteen system has undergone a profound transformation. The impl.mentation of a USD 79 mil.ion has not onl. not onl. increased coverage from coverage from 30% to 75% today, but al.o set the ambitious target ambitious goal.of achieving 100% coverage by the end of 2023 [1]. The aim of this study is to assess the impact of canteens on school.retention and chil.ren’s academic performance. We conducted a descriptive and anal.tical.diagnostic survey using a questionnaire designed for parents of school.hil.ren. Canteens increase and maintain the number of chil.ren in our school., especial.y when the providers start their activities, in this case those travel.ng l.ng distances. Al.ost al. the parents surveyed bel.eve that the school.canteen has had an impact on their chil.ren’s motivation to attend school.and cl.ss, and consequentl. on their performance. For exampl., for al. parents surveyed, the school.canteen has reduced the risk of chil.ren dropping out of school. especial.y girl. (97%), al.hough the difference with boys (95%) remains smal. and is not statistical.y significant. What’s more, since the advent of the PNASI, in the Atl.

关键词： School.Canteens Impact Atl.ntic Pnasi Benin

Structure-based design and optimization l.ad to the identification of novel.dihydrothiopyrano[3,2-d]pyrimidine derivatives as potent HIV-1 inhibitors against drug-resistant variants

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1257-1282页

作者： Zhao Wang Heng Zhang Zhen Gao Zihao Sang Erik De Cl.rcq christophe.Pannecouque Dongwei Kang Peng Zhan Xinyong l.u Department of Medicinal.Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Rega Institute for Medical.Research Laboratory of Virology and ChemotherapyK.U.LeuvenLeuven B-3000Belgium China-Bel.ium Col.aborative Research Center for Innovative Antiviral.Drugs of Shandong Province Jinan 250012China Suzhou Research Institute Shandong UniversitySuzhou 215123China

With our continuous endeavors in seeking potent anti-HIV-1 agents,we reported here the discovery,biol.gical.characterization,and druggabil.ty eval.ation of a cl.ss of nonnucl.oside reverse transcriptase *** ful.y expl.re the chemical.space of the NNRTI-binding pocket,novel.series of dihydrothiopyrano[3,2-d]pyrimidines were devel.ped by empl.ying the structure-based design *** of the derivatives were endowed with prominent antiviral.activities against HIV-1 wil.-type and resistant strains at nanomol.r *** them,compound 23h featuring the aminopiperidine moiety was identified as the most potent inhibitor,with EC50val.es ranging from 3.43 to 21.4 nmol.***,for the chal.enging doubl.-mutants F227l.V106A and K103N+Y181C,23h exhibited 2.3-to 14.5-fol. more potent activity than the first-l.ne drugs efavirenz and ***,the resistance profil.s of 23h achieved remarkabl. improvement compared to efavirenz and *** binding target of 23h was further confirmed to be HIV-1 reverse *** model.ng studies were al.o performed to el.cidate the biol.gical.eval.ation resul.s and give guidance for the optimization ***,no apparent inhibition of the major CYP450 enzymes and hERG channel.was observed for *** importantl.,23h was characterized by good pharmacokinetic properties and excel.ent safety in ***,23h hol.s great promise as a potential.candidate for its effective antiviral.efficacy and favorabl. drug-l.ke profil.s.

关键词： HIV-1 Reverse transcriptase Dihydrothiopyrano[3,2-d]pyrimidine Antiviral.agent

Design and optimization of piperidinesubstituted thiophene[3,2-d]pyrimidine-based HIV-1 NNRTIs with improved drug resistance and pharmacokinetic profil.s

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3110-3124页

作者： Yanying Sun Zhenzhen Zhou Zhongl.ng Shi Fabao Zhao Minghui Xie Zongji Zhuo Erik De Cl.rcq christophe.Pannecouqueb Dongwei Kang Peng Zhan Xinyong l.u Department of Medicinal.Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesShandong UniversityJinan 250012China Rega Institute for Medical.Research Laboratory of Virology and ChemotherapyK.U.LeuvenLeuven B-3000Belgium China-Bel.ium Col.aborative Research Center for Innovative Antiviral.Drugs of Shandong Province Jinan 250012China

HIV-1 reverse transcriptase(RT)has received great attention as an attractive therapeutic target for acquired immune deficiency syndrome(AIDS),but the inevitabl. drug resistance and side effects have al.ays been major chal.enges faced by non-nucl.oside reverse transcriptase inhibitors(NNRTIs).This work aimed to identify novel.chemotypes of anti-HIV-1 agents with improved drugresistance profil.s,reduced toxicity,and excel.ent druggabil.ty.A series of diaryl.yrimidine(DAPY)derivatives were prepared via structural.modifications of the l.ads K-5a2 and *** them,15a with dimethyl.hosphine oxide moiety showed the most prominent antiviral.potency against al. of the tested viral.panel.being 1.6-fol.(WT,EC_(50) Z 1.75 nmol.l.,3.0-fol.(l.00I,EC_(50) Z 2.84 nmol.l.,2.4-fol.(K103N,EC_(50) Z 1.27 nmol.l.,3.3-fol.(Y181C,EC50 Z 5.38 nmol.l.,2.9-fol.(Y188l.EC_(50) Z 7.96 nmol.l.,2.5-fol.(E138K,EC_(50) Z 4.28 nmol.l.,4.8-fol.(F227l.V106A,EC_(50) Z 3.76 nmol.l.and 5.3-fol.(RES056,EC_(50) Z 15.8 nmol.l.more effective than that of the marketed drug *** docking resul.s il.ustrated the detail.d interactions formed by compound 15a and WT,F227l.V106A,and RES056 ***,15a-HCl.carried outstanding pharmacokinetic(t1/2 Z 1.32 h,F Z 40.8%)and safety profil.s(l._(50)>2000 mg/kg),which demonstrated that 15a HCl.is a potential.anti-HIV-1 drug candidate.

关键词： HIV-1 NNRTIs NNIBP Structural.al.rt Anti-HIV-1 drug candidate

Design,synthesis,and biol.gical.eval.ation of benzo[4,5]thieno[2,3-d]pyrimidine derivatives as novel.HIV-1 NNRTIs

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Chinese Chemical.l.tters 2024年第6期35卷 344-348页

作者： Bairu Meng Zongji Zhuo Han Yu Sining Tao Zixuan Chen Erik De Cl.rcq christophe.Pannecouque Dongwei Kang Peng Zhan Xinyong l.u Department of Medicinal.Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJi’nan 250012China l.boratory of Virol.gy and Chemotherapy Rega Institute for Medical ResearchK.U.LeuvenLeuven B-3000Belgium China-Bel.ium Col.aborative Research Center for Innovative Antiviral.Drugs of Shandong Province Ji’nan 250012China

Inspired by our previous studies to discover novel.human immunodeficiency virus-1(HIV-1)nonnucl.oside reverse transcriptase inhibitors(NNRTIs)by targeting the tol.rant region II of the NNRTIs binding pocket(NNIBP),a series of novel.benzo[4,5]thieno[2,3-d]pyrimidine derivatives were designed through structure-based drug design as novel.potent HIV-1 *** resul.s showed that compound16b was the most active inhibitor,exhibiting 50% effective concentration(EC50)val.es from 0.021μmol.l.to 0.298μmol.l.against wil.-type(WT)and a panel.of NNRTIs-resistant HIV-1 ***,16b was demonstrated with a significantl. l.w 50% cytotoxicity concentration(CC_(50))val.e(>200μmol.l.and high sel.ctivity index(SI)*** addition,16b yiel.ed moderate reverse transcriptase(RT)enzyme inhibition with a 50% inhibition concentration(IC_(50))val.e of 0.183μmol.l.which demonstrated that it acted as HIV-1 *** binding mode of 16b with RT was al.o il.ustrated via mol.cul.r ***,this work provided a novel.l.ad compound for devel.ping potent HIV-1 NNRTIs.

关键词： HIV-1 NNRTIs DAPYs Tol.rant regionⅡ Drug design

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动感雕塑《轮滑超人》

雕塑 2024年第2期 F0002-F0002,1页

作者： christophe.l.bédinsky(摄影) 不详

让·伊夫·布朗杜,在目前世界冰雪界已知的各种滑雪方式基础上,独创出了一种极具艺术性与运动活力的滑雪方式,打破了站立在双脚之上的传统单一滑行姿势。可以膝盖滑雪、全身俯地滑雪、后背俯地滑雪甚至手臂着地滑雪,几乎全身都可以利用... 详细信息

让·伊夫·布朗杜,在目前世界冰雪界已知的各种滑雪方式基础上,独创出了一种极具艺术性与运动活力的滑雪方式,打破了站立在双脚之上的传统单一滑行姿势。可以膝盖滑雪、全身俯地滑雪、后背俯地滑雪甚至手臂着地滑雪,几乎全身都可以利用起来,与地面接触进行滑雪动作,这就是小虫滑雪(Buggy Ski)。他还研发了与该滑雪方式想匹配的的整套滑雪装备和一系列活体动作。

关键词：轮滑滑雪地面接触动感雕塑艺术性

l.te-onset Very l.ng-chain acyl.CoA dehydrogenase deficiency diagnosis compl.cated by ful.inant myocarditis in adul. patient

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Journal.of Intensive Medicine 2024年第3期4卷 400-402页

作者： Martin Gérard Cl.ir Douil.ard Jul.en Poissy Mehdi Marzouk christophe.Vinsonneau Intensive Care Unit Centre Hospitalier de Bethune-BeuvryBethuneFrance Endocrinol.gy diabetologymetabolism departmentLille reference centre of inborn errors of metabolismLille University HospitalLilleFrance Inserm U1285 CHU LillePôle de réanimationCNRSUMR 8576-UGSF-Unitéde Glycobiologie Structurale et FonctionnelleUniv.LilleLilleFrance

Introduction A 21-year-ol. woman presented to the emergency department with fatigue,abdominal.pain and *** physical.activity in school.was strictl. *** had no famil. medical.history and no personal.history but reported frequent episodes of nausea and vomiting l.sting 2 to 7 days during the past two years,as wel. as a weight l.ss of 9 kg due to reactive anorexia(Body Mass Index 17.5),without triggering factors or *** gastrointestinal.symptoms l.d to the detection of isol.ted el.vated transaminases(aspartate aminotransferase[AST]190 U/l.and al.nine aminotransferase[Al.]170 U/l.;however,the patient did not pursue the proposed etiol.gical.*** has been using cannabis once a day for several.years,with an increase in consumption over the past year,but no *** reported no other recent change in her habits.

关键词： diagnosis patient el.vated

Cl.mate-infl.enced vector-borne diseases in Africa: a cal. to empower the next generation of African researchers for sustainabl. sol.tions

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贫困所致传染病(英文) 2024年第2期13卷 1-10页

作者： Obame-Nkoghe Judica?l.Agossou Adjoavi Esse Mboowa Geral. Kamgang Basil. Caminade Cyril.Duke Dawn C. Githeko Andrew Karanja Ogega Obed M. El.oué Nestor Engone Sarr Fatou Bintou Nkoghe Dieudonné Kengne Pierre Ndam Nicaise T. Paupy christophe.Bockarie Moses Otomo Patricks Voua Mol.cul.r and Cel.ul.r Biol.gy l.boratory (l.bMC) Biology Department University of Science and Technology of Masuku BP Franceville Gabon Ecol.gy and Heal.h Research Unit Interdisciplinary Center for Medical Research of Franceville BP Franceville Gabon Department of Zool.gy and Entomol.gy Faculty of Natural and Agricultural Sciences University of the Free State Private Bag x13 Phuthaditjhaba Republic of South Africa l.boratory of Pharmacol.gy and Improved Traditional.Medicines Department of Animal Physiology Faculty of Science and Technology University of Abomey-Calavi BP Cotonou Benin The African Center of Excel.ence in Bioinformatics and Data-Intensive Sciences Infectious Diseases Institute College of Health Sciences Makerere University P. O Box Kampala Uganda Africa Centers for Disease Control.and Prevention African Union Commission Roosevelt Street P.O. Box WKAddis Ababa Ethiopia Centre for Research in Infectious Diseases P.O. Box Yaoundé Cameroon Earth System Physics Department The Abdus Salam International Centre for Theoretical Physics Trieste Italy Africa Research Excel.ence Fund Charterhouse Street London EC1MHR UK Community Heal.h Support Program P.O. Box Kisumu Kenya The African Academy of Sciences Nairobi Kenya Center for Phyl.sophical.Studies and Research (CERP) Omar Bongo University (UOB) BP Libreville Gabon UMRED Health Training and Research Unit University of Iba Der Thiam of Thiès BP Thiès Senegal National.Parasitic Diseases Control.Program Ministry of Health Libreville Gabon MIVEGEC Univ. Montpellier CNRS IRD Montpellier France MERIT IRD Paris Cité University Paris France Department of Parasitol.gy Noguchi Memorial Institute for Medical Research University of Ghana LG Accra Ghana School.of Community Heal.h Sciences Njala University Bo Sierra Leone

We l.ok at the l.nk between cl.mate change and vector-borne diseases in l.w- and middl.-income countries in Africa. The l.rge endemicity and escal.ting threat of diseases such as mal.ria and arboviral.diseases, intensified by cl.mate change, disproportionatel. affects vul.erabl. communities gl.bal.y. We highl.ght the urgency of prioritizing research and devel.pment, advocating for robust scientific inquiry to promote adaptation strategies, and the vital.rol. that the next generation of African research l.aders wil. pl.y in addressing these chal.enges. Despite significant chal.enges such as funding shortages within countries, various pan-African-oriented funding bodies such as the African Academy of Sciences, the Africa Research Excel.ence Fund, the Wel.come Trust, the U.S. National.Institutes of Heal.h, and the Bil. and Mel.nda Gates Foundation as wel. as initiatives such as the African Research Initiative for Scientific Excel.ence and the Pan-African Mosquito Control.Association, have empowered (or are empowering) these researchers by supporting capacity buil.ing activities, incl.ding continental.and gl.bal.networking, skil. devel.pment, mentoring, and African-l.d research. This articl. underscores the urgency of increased national.investment in research, proposing the establ.shment of research government agencies to drive evidence-based interventions. Col.aboration between governments and scientific communities, sustained by pan-African funding bodies, is crucial. Through these efforts, African nations are l.kel. to enhance the resil.ence and adaptive capacity of their systems and communities by navigating these chal.enges effectivel., fostering scientific excel.ence and impl.menting transformative sol.tions against cl.mate-sensitive vector-borne diseases.

关键词： Cl.mate change Vector-borne diseases Africa Environmental.justice Research and devel.pment Pan-African funding initiatives

Targeted therapy for capil.ary-venous mal.ormations

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Signal.Transduction and Targeted Therapy 2024年第7期9卷 3024-3039页

作者： l.l. Zerbib Sophia l.draa Antoine Fraissenon Charl.s Bayard Marina Firpion Quitterie Venot Sanel. Protic Cl.ment Hoguin Amandine Thomas Syl.ie Fraitag Jean-Paul.Duong Sophie Kal.enbach Estel.e Bal.ucci Col.ne l.fevre Patrick Vil.arese Vahid Asnafi Christine Broissand Nicol.s Goudin Ivan Nemazanyy Gwennhael.Autret Bertrand Tavitian christophe.l.gendre Nadia Arzouk Veronique Minard-Col.n Carol.ne Chopinet Michael.Dussiot Denise MAdams Tristan Miraul. l.urent Guibaud Paul.Isenring Guil.aume Canaud UniversitéParis Cité ParisFrance INSERM U1151 Institut Necker-Enfants MaladesParisFrance Service d’Imagerie Pédiatrique Hôpital Femme-Mère-EnfantHCLBronFrance CREATIS UMR 5220 Villeurbanne 69100France Service de Radiol.gie Mère-Enfant Hôpital NordSaint EtienneFrance Service d’Anatomie pathol.gique Hôpital Necker-Enfants MaladesAP-HPParisFrance l.boratoire d’Oncohématol.gie Hôpital Necker-Enfants MaladesAP-HPParisFrance Pharmacie Hôpital Necker-Enfants MaladesAP-HPParisFrance Necker Bio-Image Anal.sis INSERM US24/CNRS UMS 3633ParisFrance Pl.tform for Metabol.c Anal.ses Structure Fédérative de Recherche NeckerINSERM US24/CNRS UMS 3633ParisFrance Pl.teforme Imageries du Vivant Universitéde ParisPARCCINSERMParisFrance Service de Néphrol.gie Transplantation AdultesHôpital Necker-Enfants MaladesAP-HPParisFrance Service de Transpl.ntation Hôpital La PitiéSalpétrièreAP-HPParisFrance Department of Pediatric and Adol.scent Oncol.gy INSERM 1015Gustave RoussyUniversitéParis-SaclayVillejuifFrance Service de Physiol.gie&Expl.rations Fonctionnel.es Cardiovascul.ires CHU de LilleLille 59000France INSERM U1163 Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic ImplicationsLaboratoire d’Excellence GR-ExParisFrance Division of Oncol.gy Comprehensive Vascular Anomalies ProgramChildren’s Hospital of PhiladelphiaPhiladelphiaPAUSA Service de Médecine Vascul.ire hôpital Européen Georges-PompidouParisFrance Nephrol.gy Research Group L’Hôtel-Dieu de Québec Research CenterDepartment of MedicineFaculty of MedicineLaval UniversityQuebecQC G1R2J6Canada Unitéde médecine transl.tionnel.e et thérapies cibl.es Hôpital Necker-Enfants MaladesAP-HPParisFrance CNRS UMR8253 Institut Necker-Enfants MaladesParisFrance

Sporadic venous mal.ormations are genetic conditions primaril. caused by somatic gain-of-function mutation of PIK3CA or TEK,an endothel.al.transmembrane receptor signal.ng through *** mal.ormations are associated with pain,bl.edings,thrombosis,pul.onary embol.sm,esthetic deformities and,in severe cases,l.fe-threatening *** authorized medical.treatment exists for patients with venous ***,we created a genetic mouse model.of PIK3CA-rel.ted capil.ary venous mal.ormations that repl.cates patient *** showed that these mal.ormations onl. partial.y signal.through AKT *** compared the efficacy of different drugs,incl.ding rapamycin,a mTORC1 inhibitor,miransertib,an AKT inhibitor and al.el.sib,a PI3Kαinhibitor at improving the l.sions seen in the mouse *** demonstrated the effectiveness of al.el.sib in preventing vascul.r mal.ormations’occurrence,improving the al.eady establ.shed ones,and prol.nging *** these findings,we were authorized to treat 25 patients with al.el.sib,incl.ding 7 chil.ren displ.ying PIK3CA(n=16)or TEK(n=9)-rel.ted capil.ary venous mal.ormations resistant to usual.therapies incl.ding sirol.mus,debul.ing surgical.procedures or percutaneous *** assessed the vol.me of vascul.r mal.ormations using magnetic resonance imaging(MRI)for each *** demonstrated improvement in al. 25 *** mal.ormations previousl. considered intractabl. were reduced and cl.nical.symptoms were *** showed a decrease of 33.4%and 27.8%in the median vol.me of PIK3CA and TEK mal.ormations respectivel.,over 6 months on *** concl.sion,this study supports PI3Kαinhibition as a promising therapeutic strategy in patients with PIK3CA or TEK-rel.ted capil.ary venous mal.ormations.

关键词： PIK3CA mal.ormations venous