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The novel male meiosis recombination regulator coordinates the progression of meiosis prophase Ⅰ

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Journal of Genetics and Genomics 2020年第8期47卷 449-464页

作者： Miao Li Haiwei Feng Zexiong Lin Jiahuan Zheng Dongteng Liu Rui Guo Junshi Li Raymond H.W.Li Ernest H.y.Ng michael s.y.huen P.Jeremy Wang William s.B.yeung Kui Liu shenzhen Key Laboratory of Fertility Regulation Center of Assisted Reproduction and EmbryologyThe University of Hong Kong-Shenzhen HospitalShenzhen518000China Department of Obstetrics and Gynecology Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong999077China Department of Biomedical sciences University of Pennsylvania School of Veterinary MedicinePhiladelphiaPA19104USA school of Biomedical sciences Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong999077China

Meiosis is a specialized cell division for producing haploid gametes in sexually reproducing *** this study,we have independently identified a novel meiosis protein male meiosis recombination regulator(MAMERR)/4930432 K21 Rik and showed that it is indispensable for meiosis prophase I progression in male *** super-resolution structured illumination microscopy,we found that MAMERR functions at the same double-strand breaks as the replication protein A and meiosis-specific with OB domains/spermatogenesis associated 22 *** generated a Mamerr-deficient mouse model by deleting exons 3 e6 and found that most of Mamerrà/àspermatocytes were arrested at pachynema and failed to progress to diplonema,although they exhibited almost intact synapsis and progression to the pachytene stage along with Xy body *** mechanistic studies revealed that the recruitment of DMC1/RAD51 and heat shock factor 2 ebinding protein in Mamerrà/àspermatocytes was only mildly impaired with a partial reduction in double-strand break repair,whereas a substantial reduction in ubiquitination on the autosomal axes and on the Xy body appeared as a major phenotype in Mamerrà/à*** propose that MAMERR may participate in meiotic prophase I progression by regulating the ubiquitination of key meiotic proteins on autosomes and Xy chromosomes,and in the absence of MAMERR,the repressed ubiquitination of key meiotic proteins leads to pachytene arrest and cell death.

关键词： Meiosis 4930432K21Rik Recombination Ubiquitination

RNF169 drives high-fidelity DNA repair via a bifunctional NLs

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RNF169 drives high-fidelity DNA repair via a bifunctional NL...

Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

中国晶体学会第六届学术年会暨会员代表大会（大分子晶体学分会）

作者： Liwei An yiyang Jiang Howin H.W.Ng Jie Chen Qingguo Gong michael s.y.huen school of Biomedical sciences LKS Faculty of MedicineThe University of Hong Kong school of Life sciences University of Science and Technology of China state Key Laboratory of Brain and Cognitive sciences The University of Hong Kong

Loading of 53BP1 and RAP80 at DNA double-strand breaks(DsBs)drives cell cycle checkpoint activation but is counterproductive to high-fidelity DNA ***169 maintains the balance by limiting the deposition of DNA damage mediator proteins at the damaged *** report here that this is accomplished,in part,by a predicted NLs that not only shuttles

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Neural Regeneration Research 2025年第1期20卷 174-180页

作者： yinglong Miao michael s.Wolfe Computational Medicine Program and Department of Pharmacology University of North Carolina–Chapel HillChapel HillNCUSA Department of Medicinal Chemistry University of KansasLawrenceKSUSA

γ-secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-stay-Trim,”“sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics Notch

Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease

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Neural Regeneration Research 2025年第7期20卷 1981-1988页

作者： shan Ping yu Emily Choi michael QJiang Ling Wei Department of Anesthesiology Emory University School of MedicineAtlantaGAUSA Center for Visual and Neurocognitive Rehabilitation Atlanta Veterans Affairs Medical CenterDecaturGAUSA

stroke and Alzheimer's disease are common neurological disorders and often occur in the same *** comorbidity of the two neurological disorders represents a grave health threat to older *** review presents a brief background of the development of novel concepts and their clinical *** activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal *** ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic *** Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute ***,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death *** on the Ca^(2+)hypothesis of Alzheimer's disease and recent advances,this Ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic *** N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic *** stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time *** is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related

关键词： Ca^(2+)hypothesis cognitive deficits hyperactivity late-onset Alzheimer's disease neurodegeneration N-methyl-D-aspartate receptors N-methyl-D-aspartate receptor subunits pathogenesis preventive treatment

Poststroke seizure:optimising its management

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stroke & Vascular Neurology 2019年第1期4卷 48-56页

作者： michael y Xu Department of Neurology OSF Illinois Neurological InstituteUniversity of Illinois College of MedicinePeoriaIllinoisUSA

seizure after stroke or poststroke seizure (Pss) is a common and very important complication of stroke. It can be divided into early seizure and late seizure, depending on seizure onset time after the stroke. It has been reported that ischaemic and haemorrhagic stroke accounts for about 11% of all adult epilepsy cases and 45% of epilepsy cases over 60 years of age. However, there are no reliable guidelines in clinical practice regarding most of the fundamental issues of Pss management. In recent years there has been an increased interest in the study of Pss which may give clinical practitioners a better picture of how to optimise Pss management. studies have indicated two peaks in Pss occurrence-the first day and 6-12 months after a stroke. Haemorrhagic stroke, cortical involvement, severity of initial neurological deficit, younger patients (years of age), family history of seizures and certain genetic factors carry a higher risk of Pss. The use of continuous electroencephalogram has demonstrated significant benefits in capturing interictal or ictal abnormalities, especially in cases of non-convulsive seizures and non-convulsive status epilepticus. Current available data indicated that there was no significant difference in antiepileptic efficacy among most of the antiepileptic drugs (AEDs) in Pss. Levetiracetam and lamotrigine are the most studied newer generation AEDs and have the best drug tolerance. The purpose of this review is to summarise the recent advances in Pss research and focus on the most important practice issues of Pss management.

关键词： seizure epilepsy involvement

A systematic review of progenitor survival and maturation in Parkinsonian models

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Neural Regeneration Research 2025年第11期20卷 3172-3178页

作者： Giulia Comini Eilís Dowd Pharmacology&Therapeutics and Galway Neuroscience Center University of GalwayGalwayIreland

stem cell-based brain repair is a promising emergent therapy for Parkinson's disease based on years of foundational research using human fetal donors as a cell *** current therapeutic options for patients,this approach has the potential to provide longterm stem cell–derived reconstruction and restoration of the dopaminergic input to denervated regions of the brain allowing for restoration of certain functions to *** ultimate clinical success of stem cell–derived brain repair will depend on both the safety and efficacy of the approach and the latter is dependent on the ability of the transplanted cells to survive and differentiate into functional dopaminergic neurons in the Parkinsonian *** the pre-clinical literature suggests that there is considerable variability in survival and differentiation between studies,the aim of this systematic review was to assess these parameters in human stem cell-derived dopaminergic progenitor transplant studies in animal models of Parkinson's disease.A defined systematic search of the PubMed database was completed to identify relevant studies published up to March *** screening,76 articles were included in the analysis from which 178 separate transplant studies were *** these,graft survival could be assessed in 52 studies and differentiation in 129 ***,we found that graft survival ranged froms transplanted,with a median of 51%of transplanted cells surviving in the brain;while dopaminergic differentiation of the cells ranged from 0% to 46% of cells transplanted with a median of 3%.This systematic review suggests that there is considerable scope for improvement in the differentiation of stem cell-derived dopaminergic progenitors to maximize the therapeutic potential of this approach for patients.

关键词： cell replacement therapy differentiation embryonic stem cells graft induced pluripotent stem cells Parkinson's disease survival transplant

Economic impact of minimally invasive lumbar surgery

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World Journal of Orthopedics 2015年第2期6卷 190-201页

作者： Christoph P Hofstetter Anna s Hofer michael y Wang Department of Neurological surgery University of Washington Department of Neurological surgery University of Miami MILLER School of Medicine

Cost effectiveness has been demonstrated for traditional lumbar discectomy, lumbar laminectomy as well as for instrumented and noninstrumented arthrodesis. While emerging evidence suggests that minimally invasive spine surgery reduces morbidity, duration of hospitalization, and accelerates return to activites of daily living, data regarding cost effectiveness of these novel techniques is limited. The current study analyzes all available data on minimally invasive techniques for lumbar discectomy, decompression, short-segment fusion and deformity surgery. In general, minimallyinvasive spine procedures appear to hold promise in quicker patient recovery times and earlier return to work. Thus, minimally invasive lumbar spine surgery appears to have the potential to be a cost-effective intervention. Moreover, novel less invasive procedures are less destabilizing and may therefore be utilized in certain indications that traditionally required arthrodesis procedures. However, there is a lack of studies analyzing the economic impact of minimally invasive spine surgery. Future studies are necessary to confirm the durability and further define indications for minimally invasive lumbar spine procedures.

关键词： Value-based medicine Cost efficiency Minimally invasive spine surgery Arthrodesis Outcomes

A rare case of staphylococcus lugdunensis septicemia associated with myocarditis and atrioventricular block

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Journal of Geriatric Cardiology 2019年第1期16卷 63-66页

作者： Alex Tsz Lai Nganh sharen Lee Tong LIU Mark Tam Ka Hou Christien Li Michelle Vangi Wong michael huen sum Lam Gary Tse Ishan Lakhani Department of Medicine and Therapeutics Faculty of MedicineChinese University of Hong KongHong KongChina Li Ka shing Institute of Health sciences Faculty of MedicineChinese University of Hong KongHong KongChina Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease Department of CardiologyTianjin Institute oj CardiologySecond Hospital of Tianjin Medical UniversityTianjinChina Faculty of Medicine Newcastle University.United Kingdom Faculty of Health and Wellbeing Sheffield Hallam UniversityUnited Kingdom

Myocarditis is a relatively rare,possibly life-threatening disease characterized by the inflammation of the myocardium.111 The disease pathogenesis is primarily initiated by acute injury and necrosis of cardiomyocytes,leading to an inflammatory response mediated by the immune system that can potentially cause further aggravation of myocardial damage and organ *** in patients with myocarditis depends on the clinical presentation,which ranges from an asymptomatic disease course to the concomitant development of cardiac arrhythmias,heart failure,cardiogenic shock and even the occurrence of death in extreme cases[1].

关键词： Atrioventricular block Conduction Inflammation Myocarditis staphylococcus lugdunensis

Cogon grass biochar amendment and Panicum coloratum planting improve selected properties of sandy soil under humid lowland tropical climatic conditions

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Biochar 2020年第4期2卷 489-502页

作者： Patrick s.michael Department of Agriculture Papua New Guinea University of TechnologyPMBLae 411MPPapua New Guinea

Biochar amendment improves the physical,chemical and biological characteristics of different soil types under different climatic and environmental *** this study,effects of biochar or live pasture plants existing alone or co-existing on selected soil properties of sandy loam soil under humid lowland tropical climatic conditions were *** changes measured in the amended soil,with or without plants,were compared to the unamended and unplanted *** amendment with or without pasture improved moisture retention,lowered bulk density,increased pH and kept the electrical conductivity within ranges conducive for pasture ***,contents of all the nutrients increased following biochar amendment,however pasture establishment without amendment resulted in depletion of available potassium and *** all treatment conditions,soil organic carbon and soil organic matter were significantly *** grass is invasive under all land use systems and contributes to greenhouse gas emissions through *** biomass from the grass instead of burning would mitigate CO2 emissions from the tropics.

关键词： Biochar Effect Pasture sandy loam soil PNG