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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...

sleep-based neuronal oscillations as a physiological biomarker for Alzheimer's disease:is night time the right time?

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 2024年第7期19卷 1417-1418页

作者： Jonathan Witton Erica s.Brady michael T.Craig Department of Clinical and Biomedical sciences Faculty of Health and Life SciencesUniversity of ExeterExeterEnglandUK Gladstone Institute for Neurological Disease San FranciscoCAUSA school of Psychology and Neuroscience College of MedicalVeterinary and Life SciencesUniversity of GlasgowGlasgowScotlandUK

Dementia is a devastating syndrome characterized by memory problems,confusion,and behavior changes that prevent people from performing everyday *** is the leading cause of dependency and disability amongst older people,resulting in a global economic cost of ~$1.3 *** 58 million people are currently afflicted by dementia worldwide,with Alzheimer s disease(AD) causing most(60-70%) of these cases.

关键词： Alzheimer everyday performing

Application of a simplified ADM1 for full-scale anaerobic co-digestion of cattle slurry and grass silage:assessment of input variability

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Frontiers of Environmental science & Engineering 2024年第4期18卷 125-139页

作者： sofia Tisocco sören Weinrich Gary Lyons michael Wills Xinmin Zhan Paul Crosson Civil Engineering College of Science and EngineeringUniversity of GalwayGalwayH91 TK33Ireland Teagasc Animal and Bioscience Research Department Animal and Grassland Research and Innovation CentreDunsanyC15 PW93Ireland Biochemical Conversion Department Deutsches Biomasseforschungszentrum gemeinnützige GmbHLeipzig 04347Germany Faculty of Energy·Building services·Environmental Engineering Münster University of Applied SciencesSteinfurt 48565Germany Agri-Food and Biosciences Institute HillsboroughBT266DRUK Ryan Institute University of GalwayGalwayH91 TK33Ireland MaREI Research Centre for Energy Climate and MarineRyan InstituteUniversity of GalwayGalwayH91 TK33Ireland

Mathematical modeling of anaerobic digestion is a powerful tool to predict gas yields and optimize the *** Anaerobic Digestion Model No.1(ADM1)is a widely implemented model for this ***,modeling full-scale biogas plants is challenging due to the extensive substrate and parameter characterization *** study describes the modification of the ADM1 through a simplification of individual process phases,characteristic components and required ***,the ability of the simplified model to simulate the co-digestion of grass silage and cattle slurry was evaluated using data from a full-scale biogas *** impacts of substrate composition(crude carbohydrate,protein and lipid concentration)and variability of carbohydrate degradability on simulation results were assessed to identify the most influential *** indicated that the simplified version was able to depict biogas and biomethane production with average model efficiencies,according to the Nash-sutcliffe efficiency(NsE)coefficient,of 0.70 and 0.67,respectively,and was comparable to the original ADM1(average model efficiencies of 0.71 and 0.63,respectively).The variability of crude carbohydrate,protein and lipid concentration did not significantly impact biogas and biomethane output for the data sets *** contrast,carbohydrate degradability seemed to explain much more of the variability in the biogas and methane ***,the application of simplified models provides a reliable basis for the process simulation and optimization of full-scale agricultural biogas plants.

关键词： ADM1 Agricultural feedstocks Biogas technology Input variability Parameter estimation

A review of control strategies used for morphing aircraft applications

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Chinese Journal of Aeronautics 2024年第4期37卷 436-463页

作者： Muhammed s.PARANCHEERIVILAKKATHIL Jafar s.PILAKKADAN Rafic M.AJAJ Mohammadreza AMOOZGAR Davood AsADI yahya ZWEIRI michael I.FRIsWELL Department of Aerospace Engineering Khalifa University of Science and TechnologyAbu DhabiUnited Arab Emirates Department of Aerospace Engineering Advanced Research and Innovation Center(ARIC)Khalifa University of Science and TechnologyAbu DhabiUnited Arab Emirates Department of Mechanical Materials&Manufacturing EngineeringUniversity of NottinghamNottingham NG72RDUK Department of Aerospace Engineering Adana Alparslan Turkes Science and Technology UniversityTurkey College of Engineering Swansea UniversitySwansea SA18ENUK

This paper reviews the various control algorithms and strategies used for fixed-wing morphing aircraft applications. It is evident from the literature that the development of control algorithms for morphing aircraft technologies focused on three main areas. The first area is related to precise control of the shape of morphing concepts for various flight conditions. The second area is mainly related to the flight dynamics, stability, and control aspects of morphing aircraft. The third area deals mainly with aeroelastic control using morphing concepts either for load alleviation purposes and/or to control the instability boundaries. The design of controllers for morphing aircraft/wings is very challenging due to the large changes that can occur in the structural, aerodynamic, and inertial characteristics. In addition, the type of actuation system and actuation rate/speed can have a significant effect on the design of such controllers. The aerospace community is in strong need of such a critical review especially as morphing aircraft technologies move from fundamental research at a low Technology Readiness Level(TRL) to real-life applications. This critical review aims to identify research gaps and propose future directions. In this paper, research activities/papers are categorized according to the control strategy used. This ranges from simple Proportional Integral Derivative(PID) controllers at one end to complex robust adaptive controllers and deep learning algorithms at the other end. This includes analytical, computational, and experimental studies. In addition, the various dynamic models used and their fidelities are highlighted and discussed.

关键词： Control strategies Morphing aircraft shape morphing Flight dynamics Aeroelasticity

The energetics of cellular life transitions

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Life Metabolism 2024年第3期3卷 12-20页

作者： Anna s.Monzel michael Levin Martin Picard Department of Psychiatry Division of Behavioral MedicineCollege of Physicians and SurgeonsColumbia University Irving Medical CenterNew YorkNY 10032United States Department of Biology Tufts UniversityMedfordMA 02155United States Allen Discovery Center at Tufts University MedfordMA 02155United States Wyss Institute for Biologically Inspired Engineering Harvard UniversityBostonMA 02115United States Department of Neurology H.Houston Merritt CenterColumbia Translational Neuroscience InitiativeCollege of Physicians and SurgeonsColumbia University Irving Medical CenterNew YorkNY 10032United States New york state Psychiatric Institute New YorkNY 10032United States Robert N Butler Columbia Aging Center Columbia University Mailman School of Public HealthNew YorkNY 10032United States

Major life transitions are always difficult because change costs *** findings have demonstrated how mitochondrial oxidative phosphorylation(OxPhos)defects increase the energetic cost of living and that excessive integrated stress response(IsR)signaling may prevent cellular identity transitions during *** this perspective,we discuss general bioenergetic principles of life transitions and the costly molecular processes involved in reprograming the cellular hardware/software as cells shift *** energetic cost of cellular differentiation has not been directly quantified,representing a gap in *** propose that the IsR is an energetic checkpoint evolved to(i)prevent OxPhos-deficient cells from engaging in excessively costly transitions and(ii)allow IsR-positive cells to recruit systemic energetic resources by signaling via GDF15 and the brain.

关键词： energy mitochondria signaling pathway growth differentiation factor 15 energy balance development

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

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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

Rbfox1 controls alternative splicing of focal adhesion genes in cardiac muscle cells

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Journal of Molecular Cell Biology 2024年第1期16卷 54-65页

作者： Peter Zorn Jaime Calvo sánchez Tala Alakhras Barbara schreier michael Gekle stefan Hüttelmaier Marcel Köhn Junior Group‘Non-coding RNAs and RBPs in Human Diseases’ Medical FacultyUniversity of Halle–Wittenberg06120 Halle(Saale)Germany Julius Bernstein Institute of Physiology Medical FacultyUniversity of Halle–Wittenberg06112 Halle(Saale)Germany Institute of Molecular Medicine Medical FacultyUniversity of Halle–Wittenberg06120 Halle(Saale)Germany

Alternative splicing is one of the major cellular processes that determine the tissue-specific expression of protein ***,it remains challenging to identify physiologically relevant and tissue-selective proteins that are generated by alternative ***,we investigated the target spectrum of the splicing factor Rbfox1 in the cardiac muscle context in more *** using a combination of in silico target prediction and in-cell validation,we identified several focal adhesion proteins as alternative splicing targets of *** focused on the alternative splicing patterns of vinculin(metavinculin isoform)and paxillin(extended paxillin isoform)and identified both as potential Rbfox1 *** analyses suggested that both isoforms are promoted by Rbfox1 due to binding in the *** adhesions play an important role in the cardiac muscle context,since they mainly influence cell shape,cytoskeletal organization,and cell–matrix *** data confirmed that depletion of Rbfox1 changed cardiomyoblast morphology,cytoskeletal organization,and multinuclearity after differentiation,which might be due to changes in alternative splicing of focal adhesion ***,our results indicate that Rbfox1 promotes alternative splicing of focal adhesion genes in cardiac muscle cells,which might contribute to heart disease progression,where downregulation of Rbfox1 is frequently observed.

关键词： Rbfox1 alternative splicing focal adhesion cardiac muscle cells

Transcranial photobiomodulation for the brain: a wide range of clinical applications

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Neural Regeneration Research 2024年第3期19卷 483-484页

作者： michael R.Hamblin Laser Research Centre Faculty of Health ScienceUniversity of Johannesburg-Doornfontein CampusDoornfonteinSouth Africa

Photobiomodulation therapy(PBMT)is a rapidly growing approach to the healing,stimulation,protection,and regeneration of many human organs and tissue *** started in the 1960s as low-level laser therapy for wound healing,but since then the introduction of light-emitting diodes(LEDs)has dramatically increased the number of applications and reports of positive *** generally uses red(620-700 nm)and/or near-infrared(780-1270 nm)wavelengths of light at an intensity that causes no tissue heating,and its activity is based on well-established biological and cellular mechanisms(de Freitas and Hamblin,2016).While laser therapists continue to use various types of laser in their office practice,LEDs are ideally suited for home use devices because they are completely safe and without any known significant adverse *** the various body parts on which PBMT has been shown to exert beneficial effects,the brain stands out as perhaps the most promising *** has been shown to reduce neuroinflammation,while increasing mitochondrial function,oxygen consumption,and blood flow within the brain(Hamblin,2016).Moreover,PBMT can stimulate the processes of synaptogenesis,neurogenesis,and neuroplasticity thus helping the brain to heal itself.

关键词： healing stimulation wound