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Cell-type resolved transcriptomic approaches for dissecting selective vulnerability in neurodgeneration

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Neural Regeneration Research 2024年第7期19卷 1411-1413页

作者： Caleb A.Wood Nicholas M.Tran Department of Neuroscience Baylor College of MedicineHoustonTXUSA Department of Molecular and human genetics Baylor College of MedicineHoustonTXUSA

A common feature among neurodegenerative conditions is that ce rtain neuronal populations are selectively vulnerable to loss(Fu et al.,2018).By corollary,other neurons are selectively resilient,suggesting they may possess unique features that support their survival.U nderstanding the basis of neuronal resilience or vulnerability would provide a logical strategy to identify factors that could be targeted therapeutically.

关键词： selective targeted

Decoding the Cellular Trafficking of Prion-like Proteins in Neurodegenerative Diseases

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Neuroscience Bulletin 2024年第2期40卷 241-254页

作者： Chenjun Hu Yiqun Yan Yanhong Jin Jun Yang Yongmei Xi Zhen Zhong Department of Neurology of the Second Afliated Hospital and Department of human Anatomy Histology and EmbryologyZhejiang University School of MedicineHangzhou 310058China Department of Physiology and Department of Cardiology of the Second Afliated Hospital Zhejiang University School of MedicineHangzhou 310058China Division of human Reproduction and Developmental genetics Women’s Hospital and Institute of GeneticsZhejiang University School of MedicineHangzhou 310006China

The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases(NDs)such as Alzheimer’s disease,Parkinson's disease,or Amyotrophic Lateral *** a process known as‘seeding’,prion-like proteins such as amyloid beta,microtubule-associated protein tau,α-synuclein,silence superoxide dismutase 1,or transactive response DNA-binding protein 43 kDa,propagate their misfolded conformations by transforming their respective soluble monomers into *** and molecular evidence of prion-like propagation in NDs,the clinical relevance of their‘seeding’capacities,and their levels of contribution towards disease progression have been intensively studied over recent *** review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization,endo-lysosomal leaking,aggregate degradation,and *** on the importance of the role of prion-like protein aggregates in NDs,whether causal or consequent,are also *** lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.

关键词： Neurodegenerative diseases Prion-like propagation Seeding Endocytosis Endolyosomal leaking Degradation

Suppression of mature TAU isoforms prevents Alzheimer's disease-like amyloid-beta oligomer-induced spine loss in rodent neurons

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Neural Regeneration Research 2024年第8期19卷 1655-1657页

作者： Sarah Buchholz Hans Zempel Institute of human genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Center for Molecular Medicine Cologne(CMMC) Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany

Introduction:TAU isoforms as disease mediators:The microtubule-associated protein TAU is predominantly present in the axons of neurons under physiological *** Alzheimer’s disease(AD)and related tauopathies,TAU also mislocalizes("TAU missorting")to the soma and the dendrites,where it eventually forms aggregates,the so-called neurofibrillary tangles(for review see Zimmer-Bensch and Zempel,2021;Zempel,2023).

关键词： Alzheimer Zimmer tau

New glucocerebrosidase antibodies can advance research in the field of neurodegenerative disorders

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Neural Regeneration Research 2025年第4期20卷 1085-1086页

作者： Charis Ma Krystyna Rytel Yu Chen Ellen Sidransky Medical genetics Branch National Human Genome Research InstituteNational Institutes of HealthBethesdaMDUSA

In medical research,there are times when the introduction of a new tool can launch scientific discovery in new *** antibody development may be considered mundane,in the field of glucocerebrosidase(GCase)research,the dearth of validated antibodies for different applications has impeded progress in studies of disease pathogenesis and therapeutic *** recent introduction of new,rigorously evaluated antibodies can now propel research into the link between glucocerebrosidase and Parkinson’s disease(PD)as well as aspects of the pathobiology of Gaucher disease(Jong et al.,2024).

关键词： antibodies cerebro

Impacts of Early Pleistocene glacial vicariance among refugial lineages and Mid-Late Pleistocene interglacial dispersal and expansion on forging population genetic structure of the giant clam Tridacna squamosa(Bivalvia:Cardiidae:Tridacninae) across the Red

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Acta Oceanologica Sinica 2024年第08期 111-127页

作者： Temim Deli Laboratory of human genetics (LR99ES10) Faculty of Medicine of Tunis University Tunis El Manar 1068

This study aims at identifying the microevolutionary processes responsible for the onset of the remarkable phylogeographic structure already recorded for the endangered giant clam Tridacna squamosa across its distribution range. For this purpose, the evolutionary, biogeographic and demographic histories of the species were comprehensively reconstructed in a mitochondrial dataset comprising nearly the whole available published cytochrome c oxidase 1 gene sequences of T. squamosa. Relatively higher level of genetic diversification was unveiled within T. squamosa, in comparison to earlier macro-geographic investigations, whereby five mitochondrial clusters were delineated. The resulting divergent gene pools in the Red Sea, western Indian Ocean,Indo-Malay Archipelago and western Pacific were found to be driven by Early Pleistocene glacial vicariance events among refugial lineages. Accentuated genetic diversification of the species across the Indo-Malay Archipelago was successively triggered by historical dispersal event during the Mid-Pleistocene MIS19c interglacial. This latter historical event might have also enabled genetically distinct giant clams from the IndoMalay Archipelago to subsequently colonize the western Pacific, accounting for the genetic diversity hotspot detected within this region(comprising three divergent mitochondrial clusters). Late Pleistocene demographic expansion of T. squamosa, during the Last Interglacial period, could have contributed to forging spatial distribution of the so far delineated genetic entities across the Indo-Western Pacific. Overall, being resilient to major climate shifts during the Pleistocene through adaptation and consequent diversification, T. squamosa could be used as a model species to track the impact of climate change on genetic variability and structure of marine species. In particular, the new information, provided in this investigation, may help with understanding and/or predicting the consequences of ongoing global

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Resident immune responses to spinal cord injury:role of astrocytes and microglia

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Neural Regeneration Research 2024年第8期19卷 1678-1685页

作者： Sydney Brockie Cindy Zhou Michael G.Fehlings Division of genetics and Development Krembil Research InstituteUniversity Health NetworkTorontoONCanada Institute of Medical Science University of TorontoTorontoONCanada Division of Neurosurgery and Spine program Department of SurgeryUniversity of TorontoTorontoONCanada

Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our *** r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal *** makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative *** these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory *** review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after ***,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural *** the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous *** advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are *** key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.

关键词： astrocytes glial signaling microglia spinal cord injury synaptic transmission

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Acta Oceanologica Sinica 2024年第8期43卷 111-127页

作者： Temim Deli Laboratory of human genetics(LR99ES10) Faculty of Medicine of TunisUniversity Tunis El Manar 1068Tunisia

This study aims at identifying the microevolutionary processes responsible for the onset of the remarkable phylogeographic structure already recorded for the endangered giant clam Tridacna squamosa across its distribution *** this purpose,the evolutionary,biogeographic and demographic histories of the species were comprehensively reconstructed in a mitochondrial dataset comprising nearly the whole available published cytochrome c oxidase 1 gene sequences of *** higher level of genetic diversification was unveiled within ***,in comparison to earlier macro-geographic investigations,whereby five mitochondrial clusters were *** resulting divergent gene pools in the Red Sea,western Indian Ocean,Indo-Malay Archipelago and western Pacific were found to be driven by Early Pleistocene glacial vicariance events among refugial *** genetic diversification of the species across the Indo-Malay Archipelago was successively triggered by historical dispersal event during the Mid-Pleistocene MIS19c *** latter historical event might have also enabled genetically distinct giant clams from the Indo-Malay Archipelago to subsequently colonize the western Pacific,accounting for the genetic diversity hotspot detected within this region(comprising three divergent mitochondrial clusters).Late Pleistocene demographic expansion of ***,during the Last Interglacial period,could have contributed to forging spatial distribution of the so far delineated genetic entities across the Indo-Western ***,being resilient to major climate shifts during the Pleistocene through adaptation and consequent diversification,*** could be used as a model species to track the impact of climate change on genetic variability and structure of marine *** particular,the new information,provided in this investigation,may help with understanding and/or predicting the consequences of ongoing global warming on genetic poly

关键词： Mollusks Red Sea and Indo-Pacific evolutionary and biogeographic histories mitochondrial DNA Pleistocene glacial refugia interglacial dispersal and expansion

Identific tion of quantitative trait loci and associated candidate genes for pregnancy success in Angus–Brahman crossbred heifers

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Journal of Animal Science and Biotechnology 2024年第1期15卷 162-170页

作者： Quinn A.Hoorn Gabriel A.Zayas Eduardo E.Rodriguez Laura M.Jensen Raluca G.Mateescu Peter J.Hansen Department of Animal Sciences Donald Henry Barron Reproductive and Perinatal Biology Research Programand the Genetics InstituteUniversity of FloridaGainesvilleFLUSA School of Applied Systems Biology La Trobe UniversityBundooraVIC 3083Australia

Background In beef cattle, more than 50% of the energy input to produce a unit of beef is consumed by the female that produced the calf. Development of genomic tools to identify females with high genetic merit for reproductive function could increase the profitability and sustainability of beef *** Genome-wide association studies(GWAS) were performed using a single-step genomic best linear unbiased prediction approach on pregnancy outcome traits from a population of Angus–Brahman crossbred heifers. Furthermore, a validation GWAS was performed using data from another farm. Heifers were genotyped with the Bovine GGP F250 array that contains 221,077 SNPs. In the discovery population, heifers were bred in winter breeding seasons involving a single round of timed artificial insemination(AI) followed by natural mating for 3 months. Two phenotypes were analyzed: pregnancy outcome to first-service AI(PAI;n = 1,481) and pregnancy status at the end of the breeding season(PEBS;n = 1,725). The heritability was estimated as 0.149 and 0.122 for PAI and PEBS, respectively. In the PAI model, one quantitative trait locus(QTL), located between 52.3 and 52.5 Mb on BTA7, explained about 3% of the genetic variation, in a region containing a cluster of γ-protocadherin genes and SLC25A2. Other QTLs explaining between 0.5% and 1% of the genetic variation were found on BTA12 and 25. In the PEBS model, a large QTL on BTA7 was synonymous with the QTL for PAI, with minor QTLs located on BTA5, 9, 10, 11, 19, and 20. The validation population for pregnancy status at the end of the breeding season were Angus–Brahman crossbred heifers bred by natural mating. In concordance with the discovery population, the large QTL on BTA7 and QTLs on BTA10 and 12 were *** In summary, QTLs and candidate SNPs identified were associated with pregnancy outcomes in beef heifers, including a large QTL associated with a group of protocadherin genes. Confirmation of these associations

关键词： Beef cattle Fertility GWAS QTL

Proximity-dependent protein (de)stabilization: screening the human ORFeome for protein degraders and stabilizers

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3161-3162页

作者： Thomas Hermanns Kay Hofmann Institute for genetics University of CologneCologneGermany

In a recent study published in Nature,Poirson et *** an unbiased screen for proteins that can either bring about-or prevent-the destruction of proteinaceous model substrates in a proximity-dependent *** of such protein degraders and stabilizers will be instrumental in the development of new drug classes that specifically regulate the abundance of their target proteins.

关键词： al. stabilization stabilizers