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Intracellular compartmentation of cAMP promotes neuroprotection and regeneration of CNs neurons

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Neural Regeneration Research 2017年第2期12卷 201-202页

作者： Evan G.Cameron michael s.kapiloff Byers Eye Institute Stanford University Departments of Pediatrics and Medicine Leonard M.Miller School of MedicineUniversity of Miami

In the central nervous system（CNs）,cyclic adenosine monophosphate（cAMP）plays a critical role in numerous,often concurrent,neuronal functions including survival,growth,differentiation and synaptogenesis.

关键词： AMP PDEs CNs

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

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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

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

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

Anatomic location of the first dorsal extensor compartment for surgical De-Quervain’s tenosynovitis release:A cadaveric study

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World Journal of Orthopedics 2024年第4期15卷 379-385页

作者： Aditya Thandoni William Nicholas Yetter steven michael Regal Department of Orthopaedic surgery Allegheny Health NetworkPittsburghPA 15212United States

BACKGROUND De-Quervain’s tenosynovitis is a disorder arising from the compression and irritation of the first dorsal extensor compartment of the *** who fail conservative treatment modalities are candidates for surgical ***,risks with surgery include damage to the superficial radial nerve and an incomplete release due to inadequate ***,there is a paucity of literature demonstrating the exact anatomic location of the first dorsal extensor compartment in reference to surface ***,this cadaveric study was performed to determine the exact location of the first extensor compartment and to devise a reliable surgical incision to prevent *** To describe the location of the first dorsal compartment in relation to bony surface landmarks to create replicable surgical *** six cadaveric forearms,including four left and two right forearm specimens were *** were performed by a single fellowship trained upper extremity orthopaedic *** of the first dorsal compartment from landmarks such as Lister’s tubercle,the wrist crease,and the radial styloid were *** variables studied included the presence of the superficial radial nerve overlying the first dorsal compartment,additional compartment subsheaths,number of abductor pollicis longus(APL)tendon slips,and the presence of a *** Distance from the radial most aspect of the wrist crease to the extensor retinaculum was 5.14 mm±0.80 *** distance from Lister’s tubercle to the distal aspect of the extensor retinaculum was 13.37 mm±2.94 ***’s tubercle to the start of the first dorsal compartment was 18.43 mm±2.01 *** radial styloid to the initial aspect of the extensor retinaculum measured 2.98 mm±0.99 *** retinaculum length longitudinally on average was 26.82 mm±3.34 *** cadaveric forearms had separate extensor pollicis brevis *** average number of APL tendon slips was th

关键词： De-Quervain’s tenosynovitis First extensor compartment Cadaveric study superficial radial nerve Radial styloid Lister’s tubercle

Detection and clearance in Alzheimer’s disease: leading with illusive chemical, structural and morphological features of the targets

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Neural Regeneration Research 2024年第3期19卷 497-498页

作者： Luís Gales i3s−Instituto de Investigação e Inovação em saúde Rua Alfredo AllenPortoPortugal(Gales L)IBMC−Instituto de Biologia Molecular e CelularUniversidade do PortoRua Alfredo AllenPortoPortugal ICBAs−Instituto de Ciências Biomédicas Abel salazar Rua de Jorge Viterbo FerreiraPortoPortugal

Highly specific interactions between biomolecules,such as antigen-antibody,protein-ligand,or nucleic acid base pair complementary are on the basis of the organization of complex *** same principles may be tentatively used in molecular medicine for diagnosis and therapeutics.A molecule can be designed to selectively bind a protease and thereby inhibit the production of a peptide that forms toxic aggregates in the brain or an antibody may be produced to bind specifically to that peptide for detection or clearance ***,interference in biological systems is not that *** a start there is the inhibition of the physiological role of the protease;moreover,several cleavage fragments may be produced,which may continue to diverge due to putative post-translational modification and self-assembly processes,hiding the toxic target in a“soup”of peptide species varying in size,structure and chemical composition.A perspective of the current status and challenges in targeting peptide species for diagnosis and treatment in the context of Alzheimer’s disease is given.

关键词： Alzheimer diagnosis thereby

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 Topic:cardiac myocytesalternative splicingfocal adhesionsgenesintronsprotein isoformsrna splicing