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| 1 | Vitamin B12 modulates Parkinson’s disease LRRK2 kinase activity through allosteric regulation and confers neuroprotection显示文摘Missense mutations in Leucine-Rich Repeat Kinase 2(LRRK2)cause the majority of familial and some sporadic forms of Parkinson’s disease(PD).The hyperactivity of LRRK2 kinase induced by the pathogenic mutations underlies neurotoxicity,promoting the development of LRRK2 kinase inhibitors as therapeutics.Many potent and specific small-molecule LRRK2 inhibitors have been reported with promise.However,nearly all inhibitors are ATP competitive—some with unwanted side effects and unclear clinical outcome—alternative types of LRRK2 inhibitors are lacking.Herein we identify 5′-deoxyadenosylcobalamin(AdoCbl),a physiological form of the essential micronutrient vitamin B12 as a mixed-type allosteric inhibitor of LRRK2 kinase activity.Multiple assays show that AdoCbl directly binds LRRK2,leading to the alterations of protein conformation and ATP binding in LRRK2.STD-NMR analysis of a LRRK2 homologous kinase reveals the contact sites in AdoCbl that interface with the kinase domain.Furthermore,we provide evidence that AdoCbl modulates LRRK2 activity through disrupting LRRK2 dimerization.Treatment with AdoCbl inhibits LRRK2 kinase activity in cultured cells and brain tissue,and prevents neurotoxicity in cultured primary rodent neurons as well as in transgenic C.elegans and D.melanogaster expressing LRRK2 disease variants.Finally,AdoCbl alleviates deficits in dopamine release sustainability caused by LRRK2 disease variants in mouse models.Our study uncovers vitamin B12 as a novel class of LRRK2 kinase modulator with a distinct mechanism,which can be harnessed to develop new LRRK2-based PD therapeutics in the future. | Adam Schaffner Xianting Li Yacob Gomez-Llorente Emmanouela Leandrou Anna Memou Nicolina Clemente Chen Yao Farinaz Afsari Lianteng Zhi Nina Pan Keita Morohashi Xiaoluan Hua Ming-Ming Zhou Chunyu Wang Hui Zhang Shu G.Chen Christopher J.Elliott Hardy Rideout Iban Ubarretxena-Belandia Zhenyu Yue | 2019 | Cell Research2019，29，4： | 7 |
| 2 | Early modifications of hepatic perfusion measured by functional CT in a rat model of hepatocellular carcinoma using a blood pool contrast agent显示文摘 | Laure S. Fournier Charles Andre Cuenod Cedric Bazelaire Nathalie Siauve Christophe Rosty Phuong Lan Tran Guy Frija Olivier Clement | 2004 | European Radiology2004，，11： | 3 |
| 3 | Plantgrowth-promoting bacteria in rhizo-and endosphere of plants:their role,colonization,mechanisms involved and prospects forutilization显示文摘 | Stephase Compant Christophe Clement Angela Sessitsch | 2010 | Soil biology&Biochemistry2010，42，： | 1 |
| 4 | Numerical optimization of turbomachinery bladings显示文摘 | STePHANE BURGUBURU CLEMENT TOUSSAINT CHRISTOPHE BONHOMME | 2004 | Journal of Turbomachinery2004，126，： | 1 |
| 5 | Early modifications of hepatic perfusion measured by functional CT in a rat model of hepatocellular carcinoma using a blood pool contrast agent显示文摘 | Laure S. Fournier Charles Andre Cuenod Cedric Bazelaire Nathalie Siauve Christophe Rosty Phuong Lan Tran Guy Frija Olivier Clement | 2004 | European Radiology2004，，11： | 1 |
| 6 | Biological mechanisms that promote weight regain following weight loss in obese humans显示文摘 | Christopher N. Ochner Dulce M. Barrios Clement D. Lee F. Xavier Pi-Sunyer | 2013 | Physiology & Behavior2013，，： | 1 |
| 7 | Francis levy enhancement of mechanical properties of TiN/AlN multilayers by modifying the number and the quality of interfaces 显示文摘 | Anne Thobor Christophe Rousselot Christine Clement | 2000 | Surface and Coatings Technology2000，，124： | 1 |
| 8 | Antagonistic actinomycetes from Moroccan soil to control the grapevine gray mold显示文摘 | SOUAD LOQMAN ESSAID AIT BARKA CHRISTOPHE CLEMENT | 2009 | World J Microbiol Biotechnol2009，25，： | 1 |
| 9 | HMG-CoA Reductase Inhibitors (Statins) Characterized as Direct Inhibitors of P-Glycoprotein显示文摘 | Er-jia Wang Christopher N. Casciano Robert P. Clement William W. Johnson | 2001 | Pharmaceutical Research2001，，6： | 1 |
| 10 | Numerical optimization of turbomachinery bladings显示文摘 | Stephane Burgubum Clement Toussaint Christophe Bonhomme | 2004 | ASME Journal of Turbomachinery2004，，126： | 1 |
| 11 | Enhancement of mechanical properties of TiN/AlN multilayers by modifying the number and the quality of interfaces显示文摘 | Anne Thobor Christophe Rousselot Christine Clement | 2000 | Surface and Coatings Technology2000，124，： | 1 |
| 12 | Molecular characterization and spatial expression of the sunflower ABP1 gene显示文摘 | CLEMENT T DENISE M MICHEL W CHRISTOPHE H MALEK A ANDRE S | 2003 | Plant Molecular Biology2003，52，： | 1 |
| 13 | Design and conduct of studies to meet residue chemistry requirements显示文摘 | Clement R P Simmons R D Christopher R J | 1992 | Xenobiotics and Food Producing Animals1992，，： | 1 |
| 14 | Invading from the garden? A comparison of leaf herbivory for exotic and native plants in natural and ornamental settings显示文摘敌人版本假设建议那异国情调的种能由在他们的新奇环境逃离食肉动物和寄生虫变得侵略。Agrawal 等。(敌人版本?有同种的植物对的一个实验并且多样未葬、地下敌人。生态学, 86, 29792989 ) 建议在哪个介绍种类的损坏是低的区域或时间为本国的产地的侵略提供机会。我们测试了装饰背景是否可以为树和灌木向区域提供 herbivory 的底层,潜在地便于侵略成功。首先,我们在辛辛那提在装饰、自然的背景在本国、异国情调的种类之中比较了叶 herbivory 的层次,俄亥俄,美国。在第二研究,我们比较了 herbivory 的层次为侵略并且 noninvasive 在自然、装饰的背景之间的异国情调的种类。我们比为本国的种类为异国情调的种类发现了叶损坏的底层;然而,我们发现在叶损坏的数量的差别都没在装饰或自然的背景受苦。我们的结果不提供装饰背景为异国情调的植物种类从 herbivory 负担得起另外的版本的任何证据。 | Stephen F. Matter Jessica R.Brzyski Christopher J. Harrison Sara Hyams Clement Loo Jessica Loomis Hannah R. Lubbers Leeann Seastrum Trevor I. Stamper Adam M. Stein Richard Stokes Brandy S. Wilkerson | 2012 | Insect Science2012，19，6： | 0 |
| 15 | Development of a standardized in vitro approach to evaluate microphysical,chemical,and toxicological properties of combustion-derived fine and ultrafine particles显示文摘Ultrafine particles represent a growing concern in the public health community but their precise role in many illnesses is still unknown. This lack of knowledge is related to the experimental difficulty in linking their biological effects to their multiple properties, which are important determinants of toxicity. Our aim is to propose an interdisciplinary approach to study fine(FP) and ultrafine(UFP) particles, generated in a controlled manner using a mini CAST(Combustion Aerosol Standard) soot generator used with two different operating conditions(CAST1 and CAST3). The chemical characterization was performed by an untargeted analysis using ultra-high resolution mass spectrometry. In conjunction with this approach, subsequent analysis by gas chromatography–mass spectrometry(GC–MS) was performed to identify polycyclic aromatic hydrocarbons(PAH). CAST1 enabled the generation of FP with a predominance of small PAH molecules, and CAST3 enabled the generation of UFP, which presented higher numbers of carbon atoms corresponding to larger PAH molecules. Healthy normal human bronchial epithelial(NHBE) cells differentiated at the air-liquid interface(ALI) were directly exposed to these freshly emitted FP and UFP. Expression of MUC5AC, FOXJ1, OCLN and ZOI as well as microscopic observation confirmed the ciliated pseudostratified epithelial phenotype. Study of the mass deposition efficiency revealed a difference between the two operating conditions, probably due to the morphological differences between the two categories of particles. We demonstrated that only NHBE cells exposed to CAST3 particles induced upregulation in the gene expression of IL-8 and NQO1. This approach offers new perspectives to study FP and UFP with stable and controlled properties. | Ana Teresa Juarez-Facio Clement Castilla Cecile Corbiere Helene Lavanant Carlos Afonso Christophe Morin Nadine Merlet-Machour Laurence Chevalier Jean-Marie Vaugeois Jerome Yon Christelle Monteil | 2022 | Journal of Environmental Sciences2022，34，3： | 0 |
| 16 | Estimating the population density of the Asian tapir (Tapirus indicus) in a selectively logged forest in Peninsular Malaysia显示文摘The endangered Asian tapir(Tapirus indicus)is threatened by large-scale habitat loss,forest fragmentation and increased hunting pressure.Conservation planning for this species,however,is hampered by a severe paucity of information on its ecology and population status.We present the first Asian tapir population density estimate from a camera trapping study targeting tigers in a selectively logged forest within Peninsular Malaysia using a spatially explicit capture-recapture maximum likelihood based framework.With a trap effort of 2496 nights,17 individuals were identified corresponding to a density(standard error)estimate of 9.49(2.55)adult ta-pirs/100 km2.Although our results include several caveats,we believe that our density estimate still serves as an important baseline to facilitate the monitoring of tapir population trends in Peninsular Malaysia.Our study also highlights the potential of extracting vital ecological and population information for other cryptic individual-ly identifiable animals from tiger-centric studies,especially with the use of a spatially explicit capture-recapture maximum likelihood based framework. | D.Mark RAYAN Shariff Wan MOHAMAD Leejiah DORWARD Sheema Abdul AZIZ Gopalasamy Reuben CLEMENTS Wong Chai Thiam CHRISTOPHER Carl TRAEHOLT David MAGINTAN | 2012 | Integrative Zoology2012，7，4： | 0 |
| 17 | '核事故后恢复国际会议论文集:福岛及其他地区的辐射防护经验教训'介绍显示文摘也许福岛第一核电站事故最重要的教训是,我们没有做好充分准备,无法应对重大核事故的长期后果。这并不完全令人惊讶,因为四分之一世纪前的切尔诺贝利事故是核电站放射性物质大规模释放的特例。巧合的是,国际放射防护委员会(ICRP)发布了第111号出版物“ICRP建议书的应用:核事故或辐射紧急情况后保护长期受污染地区的人们”(ICRP,2009年),主要基于福岛事故发生前的切尔诺贝利事故的经验。它花了这么长时间的一个原因是,许多人认为切尔诺贝利事故是一种反常现象。自切尔诺贝利事故以来的几十年里,在为立即对另一起重大事故作出紧急反应作准备方面取得了进展,但对事故后果却很少考虑。 | Christopher H. Clement | 2022 | 辐射防护2022，42，3： | 0 |
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