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Heterogeneity of mature oligodendrocytes in the central nervous system

Neural Regeneration Research 2025年第5期20卷 1336-1349页

作者： Chao Weng Adam M.R.Groh Moein Yaqubi Qiao-Ling Cui Jo Anne Stratton G.R.Wayne Moore Jack P.Antel Neuroimmunology Unit Montreal Neurological Institute-HospitalDepartment of Neurology and NeurosurgeryMcGill UniversityMontrealQCCanada Department of Neurology Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous *** evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to *** the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is *** delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature ***,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination ***,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system *** and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric ***,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined *** studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte *** research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,

关键词： aging central nervous system diseases electron microscopy heterogeneity immunohistochemistry myelin sheath natural history neuroglia oligodendroglia single-cell gene expression analysis

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A new class of HIV-1 inhibitors and the target identification via proteomic profiling

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Science China Chemistry 2018年第11期61卷 1430-1439页

作者： Ying-Zi Ge Bin Zhou Ruo-Xuan Xiao Xiao-Jing Yuan Hu Zhou Ye-Chun Xu Mark A.Wainberg Ying-Shan Han Jian-Min Yue State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences mcgill university aids centre Lady Davis Institute for Medical Research Jewish General Hospital

Anti-HIV screening with the MT-4/MTT assay on a focused library of structurally diverse natural products has led to the discovery of a group of steroids with potent activities, which include four new ergostane-type steroids, named amotsterols A-D （1-4）, together with two known analogs. Among them, the most potent amotsterol D （4） exhibited anti-HIV activity against wild- type and some clinically relevant multidrug resistant HIV-I strains. Subsequent studies on its target identification through a proteomic approach found that compound 4 might target PKM2, a rate limiting enzyme ofglycolysis, in host cells to restrict HIV replication. The docking model of compound 4 to PKM2 showed that the two hydroxyl groups of 4 form hydrogen bonds with the two parallel Y390 in each subunit of PKM2 separately, and the ring C of 4 is sandwiched between the two parallel aromatic rings ofF26. The identified hit compound may have the potential to be further developed as a novel anti-HIVagent. These results demonstrated that an integrated approach, which combines new chemical structures and phenotypic screening with a proteomic approach, could not only identify novel HIV-1 inhibitors, but also elucidate the unknown targets of compound interactions in antiviral drug discovery.

关键词： ergostane-type steroids anti-HIV target identification PKM2

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Dynamic changes in the expression of apoptosis-related genes in differentiating gonocytes and in seminomas

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Asian Journal of Andrology 2015年第3期17卷 403-414页

作者： Gurpreet Manku The Research Institute of the mcgill university Health centre McGill University Montreal Quebec Canada Departments of Medicine McGill University Montreal Quebec Canada Department of Pharmacology and Therapeutics McGill University Montreal Quebec Canada

Apoptosis is an integral part of the spermatogenic process, necessary to maintain a proper ratio of Sertoli to germ cell numbers and provide an adequate microenvironment to germ cells. Apoptosis may also represent a protective mechanism mediating the elimination of abnormal germ cells. Extensive apoptosis occurs between the first and second postnatal weeks, at the point when gonocytes, precursors of spermatogonial stem cells, should have migrated toward the basement membrane of the tubules and differentiated into spermatogonia. The mechanisms regulating this process are not well-understood. Gonocytes undergo phases of proliferation, migration, and differentiation which occur in a timely and closely regulated manner. Gonocytes failing to migrate and differentiate properly undergo apoptosis. Inadequate gonocyte differentiation has been suggested to lead to testicular germ cell tumor （TGCT） formation. Here, we examined the expression levels of apoptosis-related genes during gonocyte differentiation by quantitative real-time polymerase chain reaction, identifying 48 pro- and anti-apoptotic genes increased by at least two-fold in rat gonocytes induced to differentiate by retinoic acid, when compared to untreated gonocytes. Further analysis of the most highly expressed genes identified the pro-apoptotic genes Gadd45a and Cycs as upregulated in differentiating gonocytes and in spermatogonia compared with gonocytes. These genes were also significantly downregulated in seminomas, the most common type of TGCT, compared with normal human testicular tissues. These results indicate that apoptosis-related genes are actively regulated during gonocyte differentiation. Moreover, the down-regulation of pro-apoptotic genes in seminomas suggests that they could represent new therapeutic targets in the treatment of TGCTs.

关键词： apoptosis differentiation gonocytes seminomas spermatogonia

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Rab proteins implicated in lipid storage and mobilization

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The Journal of Biomedical Research 2014年第3期28卷 169-177页

作者： Robert Scott Kiss Tommy Nilsson Department of Medicine McGill University Research Institute of mcgill university Health centre

Abnormal intracellular accumulation or transport of lipids contributes greatly to the pathogenesis of human diseases. In the liver, excess accumulation of triacylglycerol （TG） leads to fatty liver disease encompassing steatosis, steatohepatitis and fibrosis. This places individuals at risk of developing cirrhosis, hepatocellular carcinoma or hepatic decompensation and also contributes to the emergence of insulin resistance and dyslipidemias affecting many other organs. Excessive accumulation of TG in adipose tissue contributes to insulin resistance as well as to the release of cytokines attracting leucocytes leading to a pro-inflammatory state. Pathological accumulation of cholesteryl ester （CE） in macrophages in the arterial wall is the progenitor of atherosclerotic plaques and heart disease. Overconsumption of dietary fat, cholesterol and carbohydrates explains why these diseases are on the increase yet offers few clues for how to prevent or treat individuals. Dietary regimes have proven futile and barfing surgery, no realistic alternatives are at hand as effective drugs are few and not without side effects. Overweight and obesity-related diseases are no longer restricted to the developed world and as such, constitute a global problem. Development of new drugs and treatment strategies are a priority yet requires as a first step, elucidation of the molecular pathophysiology underlying each associated disease state. The lipid droplet （LD）, an up to now over- looked intracellular organelle, appears at the heart of each pathophysiology linking key regulatory and metabolic processes as well as constituting the site of storage of both TGs and CEs. As the molecular machinery and mechanisms of LDs of each cell type are being elucidated, regulatory proteins used to control various cellular processes are emerging. Of these and the subject of this review, small GTPases belonging to the Rab protein family appear as important molecular switches used in the regulation of the in

关键词： lipid droplet rab protein effector GTPase GAP GEF

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Ferroptosis:copper-iron connection in cuprizone-induced demyelination

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Neural Regeneration Research 2022年第1期17卷 89-90页

作者： Priya Jhelum Samuel David centre for Research in Neuroscience and Brain Program The Research Institute of the McGill University Health CentreMontrealQCCanada

Redox active metals such as iron,copper,zinc,and manganese play important roles in promoting a variety of biochemical reactions essential for cellular *** is made possible by the ability of these metals to accept and donate *** in the form of iron-sulfur clusters and heme plays a key role in adenosine triphosphate generation in mitochondria as well as numerous other enzymatic *** the other hand.

关键词： function. copper metals

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Assessing healthcare workers’knowledge and confidence in the diagnosis,management and prevention of Monkeypox

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World Journal of Clinical Cases 2025年第1期13卷 38-47页

作者： Epipode Ntawuyamara Thierry Ingabire Innocent Yandemye Polycarpe Ndayikeza Bina Bhandari Yan-Hua Liang Department of Dermatology Cosmetology and VenereologyShenzhen Hospital of Southern Medical UniversityShenzhen 518101Guangdong ProvinceChina Department of Dermatology and Venereology Kamenge Teaching HospitalUniversity of BurundiBujumbura 1020Burundi Department of Infectious Diseases Kamenge Teaching HospitalUniversity of BurundiBujumbura 1020Burundi General Directorate of Healthcare Supply Modern and Traditional MedicineNutrition and RegistrationMinistry of Public Health and Fight Against HIV/AIDSBujumbura 1055Burundi Department of Epidemiology National Institute of Public HealthBujumbura 350Burundi General Directorate of Planification Ministry of Public Health and Fight Against HIV/AIDSBujumbura 1055Burundi

BACKGROUND Monkeypox(Mpox),is a disease of global public health concern,as it does not affect only countries in western and central *** To assess Burundi healthcare workers(HCWs)s’level of knowledge and confidence in the diagnosis and management of *** We conducted a cross-sectional study via an online survey designed mainly from the World Health Organization course distributed among Burundi HCWs from June-July *** questionnaire comprises 8 socioprofessional-related questions,22 questions about Mpox disease knowledge,and 3 questions to assess confidence in Mpox diagnosis and *** data were analyzed via SPSS software version 25.0.A P value<0.05 was considered to indicate statistical *** The study sample comprised 471 HCWs who were mainly medical doctors(63.9%)and nurses(30.1%).None of the 22 questions concerning Mpox knowledge had at least 50%correct responses.A very low number of HCWs(17.4%)knew that Mpox has a *** confidence level to diagnose(21.20%),treat(18.00%)or prevent(23.30%)Mpox was low among *** confidence level in the diagnosis of Mpox was associated with the HCWs’age(P value=0.009),sex(P value<0.001),work experience(P value=0.002),and residence(P value<0.001).The confidence level to treat Mpox was significantly associated with the HCWs’age(P value=0.050),sex(P value<0.001),education(P value=0.033)and occupation(P value=0.005).The confidence level to prevent Mpox was associated with the HCWs’education(P value<0.001),work experience(P value=0.002),residence(P value<0.001)and type of work institution(P value=0.003).CONCLUSION This study revealed that HCWs have the lowest level of knowledge regarding Mpox and a lack of confidence in the ability to diagnose,treat or prevent *** is an urgent need to organize continuing medical education programs on Mpox epidemiology and preparedness for Burundi *** encourage future researchers to assess potential hesitancy toward Mpox vaccination and its asso

关键词： Monkeypox Public health emergency of international concern Healthcare workers Epidemic Preparedness Knowledge Confidence

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Non-alcoholic fatty liver disease-a chronic disease of the 21^(st) century

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The Journal of Biomedical Research 2018年第5期32卷 327-335页

作者： Peter Metrakos Tommy Nilsson Cancer Research Program Block-E The Research Institute of the McGill University Health Centre and Department of Medicine McGill University

Non-alcoholic fatty liver disease（NAFLD） comprises a spectrum of metabolic states ranging from simple steatosis to inflammation with associated fibrosis to cirrhosis. Though accumulation of hepatic fat is not associated with a significant increase in mortality rates, hepatic inflammation is, as this augments the risk of terminal liver disease, i.e.,cirrhosis, hepatic decompensation（liver failure） and/or hepatocellular carcinoma. Disease progression is usually slow, over a decade or more and, for the most part, remains asymptomatic. Recent estimates suggest that the global prevalence of NAFLD is high, about one in four. In most cases, NAFLD overlaps with overweight, obesity,cardiovascular disease and the metabolic syndrome with numerous contributing parameters including a dysregulation of adipose tissue, insulin resistance, type 2 diabetes, changes in the gut microbiome, neuronal and hormonal dysregulation and metabolic stress. NAFLD is diagnosed incidentally, despite its high prevalence. Non-invasive imaging techniques have emerged, making it possible to determine degree of steatosis as well asfibrosis. Despite this,the benefit of routine diagnostics remains uncertain. A better understanding of the（molecular） pathogenesis of NAFLD is needed combined with long-term studies where benefits of treatment can be assessed to determine costbenefit ratios. This review summarizes the current state of knowledge and possible areas of treatment.

关键词： non-alcoholic fatty liver disease pathogenesis molecular mechanism diagnostics biomarker

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Co-adsorption of gaseous benzene, toluene, ethylbenzene,m-xylene(BTEX) and SO_2 on recyclable Fe_3O_4 nanoparticles at 0–101% relative humidities

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Journal of Environmental Sciences 2015年第5期27卷 164-174页

作者： Connie Z.Ye Parisa A.Ariya Department of Chemistry McGill University Department of Atmospheric and Oceanic Sciences McGill University

We herein used Fe3O4 nanoparticles（NPs） as an adsorption interface for the concurrent removal of gaseous benzene, toluene, ethylbenzene and m-xylene（BTEX） and sulfur dioxide（SO2）, at different relative humidities（RH）. X-ray diffraction, Brunauer-Emmett-Teller, and transmission electron microscopy were deployed for nanoparticle surface ***-dispersed Fe3O4（Fe2O3·Fe O） NPs synthesized with oleic acid（OA） as surfactant, and uncoated poly-dispersed Fe3O4 NPs demonstrated comparable removal *** experiments of BTEX on NPs were measured using gas chromatography equipped with flame ionization detection, which indicated high removal efficiencies（up to（95 ± 2）%） under dry conditions. The humidity effect and competitive adsorption were investigated using toluene as a model compound. It was observed that the removal efficiencies decreased as a function of the increase in RH, yet, under our experimental conditions, we observed（40 ± 4）% toluene removal at supersaturation for Fe3O4 NPs, and toluene removal of（83 ± 4）% to（59 ± 6）%, for OA-Fe3O4 NPs. In the presence of SO2, the toluene uptake was reduced under dry conditions to（89 ± 2）% and（75 ± 1）% for the uncoated and coated NPs, respectively, depicting competitive adsorption. At RH 〉 100%,competitive adsorption reduced the removal efficiency to（27 ± 1）% for uncoated NPs whereas OA-Fe3O4 NPs exhibited moderate efficiency loss of（55 ± 2）% at *** point to heterogeneous water coverage on the NP surface. The magnetic property of magnetite facilitated the recovery of both types of NPs, without the loss in efficiency when recycled and reused.

关键词： Fe3O4 nanoparticles Co-adsorption Competitive adsorption BTEX removal SO2 removal

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TOWARDS A HUMAN DIGNITY BASED APPROACH TO FOOD SECURITY： LESSONS FROM CHINA AND INDIA

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Frontiers of Law in China-Selected Publications from Chinese Universities 2016年第2期11卷 243-265页

作者： Nandini Ramanujam Stephanie Chow Faculty of Law McGill University centre of Human Rights and Legal Pluralism at mcgill university MontrealCanada

Despite almost halving the proportion of the world＇s undernourished over the past two and half decades, the number of undernourished people in the world remains staggeringly high. Efforts to address the global state of food insecurity must target China and India, which are home to the world＇s highest and second highest number of undernourished people. This article analyzes the comparative experiences of tackling food security in China and India and adopts an inter-disciplinary approach, which melds legal, economic, and human perspectives to food security. Both China and India have made concerted efforts to improve food security of vulnerable populations in the past three decades. These efforts have historically focused on actively promoting grain production, which has been largely successful in achieving grain self-sufficiency and securing adequate availability of food for their populations. However, the contemporary challenges to food security are now increasingly driven by unsustainable dietary patterns and are exacerbated by growing populations, increasing wealth, and the globalization of food supply chains. As a result, the cause of food insecurity is no longer fundamentally about food supply, but rather about the extent to which marginalized populations are empowered with the rights, freedoms, and capabilities that enable them to attain healthy and productive lives. China and India apply markedly different approaches to address the issue of people＇s access to food. In India, the right to food movement has gained momentum through the work of civil society actors and there is now a legal right to food. In contrast, in China the right to food is neither stipulated in Chinese law nor referenced to in the official policy rhetoric as the country seeks to ensure access to food by focusing on poverty alleviation more generally through an income transfer program and a non-food based, social safety net to help the poor. At the same time, the Chinese population＇s high edu

关键词： food security human dignity human capabilities right to food

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The coronavirus disease-19 pandemic and acute coronary syndrome:a specific impact in the elderly

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Journal of Geriatric Cardiology 2022年第5期19卷 325-334页

作者： ViktorČulić Ahmed AlTurki Riccardo Proietti Department of Cardiology and Angiology University Hospital Centre SplitSplitCroatia university of Split School of Medicine SplitCroatia Division of Cardiology McGill University Health CentreMontrealQuebecCanada Liverpool centre for Cardiovascular Science University of LiverpoolLiverpoolUnited Kingdom

The coronavirus disease-19(COVID-19)pandemic has dramatically burdened healthcare systems worldwide by creating new public health *** addition to the most prevalent presentation of COVID-19 with mild to moderate respiratory symptoms,which occasionally progresses to acute respiratory distress syndrome,cardiovascular complications of COVID-19 include arterial and venous thromboembolic events(pulmonary embolism,acute myocardial infarction(MI)and ischemic stroke),myocarditis/myocardial injury.

关键词： acute respiratory distress

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