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How do neurons age?A focused review on the aging of the microtubular cytoskeleton

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Neural Regeneration Research 2024年第9期19卷 1899-1907页

作者： brad.Richardson Thomas Goedert Shmma Quraishe Katrin Deinhardt Amritpal Mudher School of Biological Sciences University of SouthamptonSouthamptonUK Institute of Developmental and Regenerative Medicine University of OxfordOxfordUK

Aging is the leading risk factor for Alzheimer’s disease and other neurodegenerative diseases. We now understand that a breakdown in the neuronal cytoskeleton, mainly underpinned by protein modifications leading to the destabilization of microtubules, is central to the pathogenesis of Alzheimer’s disease. This is accompanied by morphological defects across the somatodendritic compartment, axon, and synapse. However, knowledge of what occurs to the microtubule cytoskeleton and morphology of the neuron during physiological aging is comparatively poor. Several recent studies have suggested that there is an age-related increase in the phosphorylation of the key microtubule stabilizing protein tau, a modification, which is known to destabilize the cytoskeleton in Alzheimer’s disease. This indicates that the cytoskeleton and potentially other neuronal structures reliant on the cytoskeleton become functionally compromised during normal physiological aging. The current literature shows age-related reductions in synaptic spine density and shifts in synaptic spine conformation which might explain age-related synaptic functional deficits. However, knowledge of what occurs to the microtubular and actin cytoskeleton, with increasing age is extremely limited. When considering the somatodendritic compartment, a regression in dendrites and loss of dendritic length and volume is reported whilst a reduction in soma volume/size is often seen. However, research into cytoskeletal change is limited to a handful of studies demonstrating reductions in and mislocalizations of microtubule-associated proteins with just one study directly exploring the integrity of the microtubules. In the axon, an increase in axonal diameter and age-related appearance of swellings is reported but like the dendrites, just one study investigates the microtubules directly with others reporting loss or mislocalization of microtubule-associated proteins. Though these are the general trends reported, there are clea

关键词： age-related changes aging cytoskeleton microtubules neuronal morphology

The influence of resistance exercise training prescription variables on skeletal muscle mass,strength,and physical function in healthy adults:An umbrella review

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Journal of Sport and Health Science 2024年第1期13卷 47-60页

作者： Jonathan C.Mcleod brad.S.Currier Caroline V.Lowisz Stuart M.Phillips Department of Kinesiology Faculty of ScienceMcMaster UniversityHamilton L8S4L8Canada

Purpose:The aim of this umbrella review was to determine the impact of resistance training(RT)and individual RT prescription variables on muscle mass,strength,and physical function in healthy ***:Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines,we systematically searched and screened eligible systematic reviews reporting the effects of differing RT prescription variables on muscle mass(or its proxies),strength,and/or physical function in healthy adults aged>18 ***:We identified 44 systematic reviews that met our inclusion *** methodological quality of these reviews was assessed using A Measurement Tool to Assess Systematic Reviews;standardized effectiveness statements were *** found that RT was consistently a potent stimulus for increasing skeletal muscle mass(4/4 reviews provide some or sufficient evidence),strength(4/6 reviews provided some or sufficient evidence),and physical function(1/1 review provided some evidence).RT load(6/8 reviews provided some or sufficient evidence),weekly frequency(2/4 reviews provided some or sufficient evidence),volume(3/7 reviews provided some or sufficient evidence),and exercise order(1/1 review provided some evidence)impacted RT-induced increases in muscular *** discovered that 2/3 reviews provided some or sufficient evidence that RT volume and contraction velocity influenced skeletal muscle mass,while 4/7 reviews provided insufficient evidence in favor of RT load impacting skeletal muscle *** was insufficient evidence to conclude that time of day,periodization,inter-set rest,set configuration,set end point,contraction velocity/time under tension,or exercise order(only pertaining to hypertrophy)influenced skeletal muscle adaptations.A paucity of data limited insights into the impact of RT prescription variables on physical ***:Overall,RT increased muscle mass,strength,and physical function compared to no ***

关键词： Hypertrophy Resistance training Resistance training prescription variables Strength Umbrella review

Telomeric DNA breaks in human induced pluripotent stem cells trigger ATR-mediated arrest and telomerase-independent telomere damage repair

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Journal of Molecular Cell Biology 2024年第3期16卷 46-60页

作者： Katrina N.Estep John W.Tobias Rafael J.Fernandez Brinley M.Beveridge F.brad.Johnson Department of Pathology and Laboratory Medicine University of PennsylvaniaPhiladelphiaPA 19104USA Quantiative Biosciences Merck&Co.Inc.West PointPA 19486USA Penn Genomic Analysis Core University of PennsylvaniaPhiladelphiaPA 19104USA

Although mechanisms of telomere protection are well-defined in differentiated cells,how stem cells sense and respond to telomere dysfunction,in particular telomeric double-strand breaks(DSBs),is poorly ***,we report the DNA damage signaling,cell cycle,and transcriptome changes in human induced pluripotent stem cells(iPSCs)in response to telomere-internal *** engineer human iPSCs with an inducible TRF1-FokI fusion protein to acutely induce DSBs at *** this model,we demonstrate that TRF1-FokI DSBs activate an ATR-dependent DNA damage response,which leads to p53-independent cell cycle arrest in *** CRISPR–Cas9 to cripple the catalytic domain of telomerase reverse transcriptase,we show that telomerase is largely dispensable for survival and lengthening of TRF1-FokI-cleaved telomeres,which instead are effectively repaired by robust homologous recombination(HR).In contrast to HR-based telomere maintenance in mouse embryonic stem cells,where HR causes ZSCAN4-dependent extension of telomeres beyond their initial lengths,HR-based repair of telomeric breaks is sufficient to maintain iPSC telomeres at a normal length,which is compatible with sustained survival of the cells over several days of TRF1-FokI *** findings suggest a previously unappreciated role for HR in telomere maintenance in telomerase-positive iPSCs and reveal distinct iPSC-specific responses to targeted telomeric DNA damage.

关键词： telomeres telomerase alternative lengthening of telomeres pluripotent stem cells DNA damage double-strand breaks

Item-Level Analysis of the Revised Occupational Therapy Fieldwork Performance Evaluation Applied in Practice

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Open Journal of Therapy and Rehabilitation 2024年第2期12卷 145-159页

作者： Cynthia L. Sears brad.E. Egan Patricia F. Tomsic Craig A. Velozo Graduate College of Health Professions Occupational Therapy Program Hawai&#8217i Pacific University Honolulu HI USA College of Science and Health Occupational Therapy Program DePaul University Chicago IL USA Department of Occupational Therapy Wingate University Wingate NC USA College of Health Professions Department of Rehabilitation Sciences Division of Occupational Therapy Medical University of South Carolina Charleston SC USA

Competency-based assessments for healthcare professionals are critical for safe and effective client outcomes. Rehabilitation clinical skill competency assessments must be validated and revised to produce safe and skilled practitioners. The revised American Occupational Therapy Association (AOTA) Fieldwork Performance Evaluation (FWPE) instrument measures occupational therapy student performance to determine readiness for practice. The assessment includes thirty-seven competencies that address both profession specific clinical skills and general professional behavior skills. The objective of this study was to use Rasch methods to explore the use of the revised FWPE in actual fieldwork practice and to determine the instrument’s psychometric properties when separating the item components into two distinct subdomains: General Health Professions Competences and Occupational Therapy-Specific Competencies. Internal construct validity and test reliability were analyzed using data from 149 occupational therapy students after completing their initial Level II A fieldwork clinical internship. This study examined the item difficulty hierarchy, item fit, person-fit to model, person separation index, person separation reliability coefficient, strata, ceiling and floor effect, and unidimensionality of the FWPE instrument as a whole and as two separate domains. With the exception of not meeting the criteria for unidimensionality, the full FWPE instrument and the Occupational Therapy-Specific Competencies subdomain showed acceptable item-level psychometrics for reliability and precision. While the General Health Professions Competencies subdomain showed good item-level psychometrics, it was below the criterion for reliability and only separated the sample into two strata. Results support the validity, reliability, and clinical use of the revised FWPE full instrument and the Occupational Therapy-Specific Competencies subdomain to measure entry-level clinical skill competencies in pr

关键词： Rehabilitation Competency-Based Assessments Occupational Therapy Measurement Rasch Analysis

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美国富豪对特朗普热情高涨

商业周刊（中文版） 2024年第6期 4-5页

作者： brad.Stone 易语(译) 不详

乔·拜登(Joe Biden)与唐纳德·特朗普(Donald Trump)在2024年美国总统大选中的再度对决,给人的感觉或许是早该退休的两个老家伙之间以自由世界未来为赌注的一场令人乏味的复赛。不过这一次,有些东西感觉有点不一样,而且很难解释。特朗... 详细信息

乔·拜登(Joe Biden)与唐纳德·特朗普(Donald Trump)在2024年美国总统大选中的再度对决,给人的感觉或许是早该退休的两个老家伙之间以自由世界未来为赌注的一场令人乏味的复赛。不过这一次,有些东西感觉有点不一样,而且很难解释。特朗普最明显的支持者不再是来自红州那些戴着印有MAGA标识的帽子、在集会上挥舞着“抽干沼泽”标语的愤怒蓝领工人,反倒变成了国内一些最成功的商界精英,他们不断在网上发帖表达心中的不满,大力秤击移民问题和乌克兰战争,并不断对拜登的表现和老迈提出质疑。

关键词：美国总统大选特朗普商界精英乌克兰提出质疑

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成功传承之路

商业周刊（中文版） 2024年第12期 4-5页

作者： brad.Stone 易语(译) 不详

最近的研究显示,家族控股不但在上市公司中司空见惯,也具有一定的优势雅各布·萨皮尔斯坦(Jacob Sapirstein)是波兰瓦索什(Wasosz)一位拉比的儿子,他于1905年移民到美国,辗转芝加哥最终在克利夫兰落下了脚。他投奔亲戚找到了一份工作,... 详细信息

最近的研究显示,家族控股不但在上市公司中司空见惯,也具有一定的优势雅各布·萨皮尔斯坦(Jacob Sapirstein)是波兰瓦索什(Wasosz)一位拉比的儿子,他于1905年移民到美国,辗转芝加哥最终在克利夫兰落下了脚。他投奔亲戚找到了一份工作,在市中心一家酒店的大堂里卖明信片,后来靠着50美元银行贷款开始自己创业,驾着一辆马车向糖果店、新奇物品商店和药店兜售从德国进口的精美明信片。

关键词：银行贷款拉比上市公司克利夫兰德国进口明信片雅各布萨皮尔

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雾里看花的AI时代

商业周刊（中文版） 2024年第8期 4-6页

作者： brad.Stone Rachel Metz 易语(译) 不详

●从技术、经济到动力,这一新兴产业还有许多有待梳理的方方面面旧金山初创公司AtmoInc.的25名员工有一万条理由感到志志。这家已经成立四年的公司从气象传感器中获取大气数据,使用人工智能(AI)进行天气预测,并将预测结果出售给美国空... 详细信息

●从技术、经济到动力,这一新兴产业还有许多有待梳理的方方面面旧金山初创公司AtmoInc.的25名员工有一万条理由感到志志。这家已经成立四年的公司从气象传感器中获取大气数据,使用人工智能(AI)进行天气预测,并将预测结果出售给美国空军和菲律宾政府等对之有需求的客户。Atmo表示,其AI生成的预测比超级计算机处理大量数据后作出的预测更加准确,使用成本也低得多,而且还能从以往的错误中吸取教训。

关键词：初创公司新兴产业气象传感器菲律宾政府超级计算机天气预测美国空军 AI

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设计可移植的用户接口

微型计算机 1993年第6期13卷 52-55页

作者： brad.,JL 闵珍晖

Single-cell multi-cohort dissection of the schizophrenia transcriptome

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四川生理科学杂志 2024年第5期46卷 1114-1114页

作者： W brad.Ruzicka 不详

The complexity and heterogeneity of schizophrenia have hindered mechanistic elucidation and the development of more effective ***,we performed single-cell dissection of schizophrenia-associated transcriptomic changes in the human prefrontal cortex across 140 individuals in two independent *** neurons were the most affected cell group,with transcriptional changes converging on neurodevelopment and synapse-related molecular pathways.

关键词： transcriptional schizophrenia elucidation