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Emerging structur.s.and dynamic mechanisms ofγ-secretase for Alzheimer.s.disease

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Neural regeneration r.s.arch 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.s.bstrate 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 micr.s.opy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a r.s.lved 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

Complementary roles of glial cells in generating region-specific neuroinflammatory r.s.onses and phagocytosis in Parkinson’s disease

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Neural regeneration r.s.arch 2025年第10期20卷 2917-2918页

作者： Leyre Ayerra Maria s.Aymerich Universidad de Navarra Facultad de CienciasDepartamento de Bioquímica y GenéticaPamplonaSpain CIMA-Universidad de Navarra PamplonaSpain IdisNA Instituto de Investigación Sanitaria de NavarraPamplonaSpain

Neuroinflammation is associated with Parkinson’s disease:reactive gliosis and neuroinflammation are hallmar.s.of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progr.s.ive loss of dopaminergic *** has long been considered a mere consequence of neuronal loss,but whether it promotes PD or is a key player in disease progr.s.ion remains to be *** leukocyte antigen.

关键词： inflammation leukocyte generating

A comprehensive investigation on nonlinear vibration and bending character.s.ics of bio-inspired helicoidal laminated composite structures

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Applied Mathematics and Mechanics(English Edition) 2025年第1期46卷 81-100页

作者： s.sAUrABH r.KIrAN D.sINGH r.VAIsH V.s.CHAUHAN school of Mechanical and Materials Engineering Indian Institute of Technology Mandi

Bio-inspired helicoidal composite laminates, inspired by the intricate helical structur.s.found in nature, pr.s.nt a promising frontier for enhancing the mechanical properties of structural designs. Hence, this study provides a comprehensive investigation into the nonlinear free vibration and nonlinear bending behavior of bio-inspired composite plates. The inverse hyperbolic shear deformation theory(IHsDT) of plates is employed to characterize the displacement field, with the incorporation of Green-Lagrange nonlinearity. The problem is modeled using the C0finite element method(FEM), and an in-house code is developed in the MATLAB environment to solve it numerically. Various helicoidal layup configurations including helicoidal recursive(Hr), helicoidal exponential(HE), helicoidal semi-circular(Hs), linear helicoidal(LH), and Fibonacci helicoidal(FH)with different layup sequences and quasi-isotropic configurations are studied. The model is validated, and parametric studies are conducted. These studies investigate the effects of layup configurations, side-to-thickness ratio, modulus ratios, boundary conditions, and loading conditions at different load amplitudes on the nonlinear vibration and nonlinear bending behaviors of bio-inspired composite plates. The r.s.lts show that the laminate sequence exer.s.a substantial impact on both nonlinear natural frequencies and nonlinear bending behaviors. Moreover, this influence varies acr.s. different side-to-thickness ratios and boundary conditions of the bio-inspired composite plate.

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DOUBLE s-BrEAKING CUBIC TUrNING POINTs AND THEIr COMPUTATION

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Journal of Computational Mathematics 1996年第1期14卷 8-22页

作者： r.s. Ye Z.H. Yang(Department of Mathematics, shanghai University of science and Technology, shanghai,China) 上海大学数学系上海

In the paper we are concerned with double s-breaking cubic turning points of two-parameter nonlinear problems in the pr.s.nce of Z(2)-symmetry. Three extended systems are proposed to determine double s-breaking cubic turning points. We show that there exist two kinds of singular point path passing through double s-breaking cubic turning point, One is the simple quadratic turning point path, the other is the pitchfork bifurcation point path.

关键词： DOUBLE s-BrEAKING CUBIC TUrNING POINTs AND THEIr COMPUTATION Pro

Effect of adrenalectomy on rat epididymidis

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Asian Journal of Andrology 2002年第4期4卷 273-279页

作者： Neena Nair r.s. Bedwal r.s. Mathur Cell Biology Laboratory Department of Zoology University of Rajasthan Jaipur-302 004 IndiaCell Biology Laboratory Department of Zoology University of Rajasthan Jaipur-302 004 IndiaCell Biology Laboratory Department of Zoology University of Rajasthan Jaipur-302 004 India

AIM: To investigate the effect of adrenalectomy (ADX) on the epididymidis of sprague-Dawley rats. METHODs: The histological, biochemical (cholesterol protein, zinc, copper, alkaline and acid phosphatase aryl sulphatase, lactic dehydrogenase and leucine amino peptidase) and hormonal (FsH, LH and testosterone) changes of caput and cauda epididymis in ADX rats were observed. r.s.LTs: Organ wet weight, histological studies and morphometric measurements indicated a cellular degeneration in caput and cauda epididymis of ADX rats. serum testosterone level was significantly lower in ADX than in sham-operated rats, while the serum FsH and LH were below the detection limit of 1 mIU/mL. The enzymatic activity was higher in ADX than in sham-operated rats. Epididymal zinc level increased whereas copper level decreased in ADX rats compared to the sham-operated. CONCLUsION: Adrenalectomy leads to degeneration of caput and cauda epididymidis epithelial cells as a r.s.lt of decreased supply of testosterone.

关键词： Adrenalectomy Acid Phosphatase Alkaline Phosphatase Animals Arylsulfatases Cholesterol Comparative study Copper Epididymis Follicle stimulating Hormone L-Lactate Dehydrogenase Leucyl Aminopeptidase Luteinizing Hormone Male Organ size rats rats, sprague-Dawley reference Values r.s.arch support, Non-U.s. Gov't Testosterone Time Factors Zinc

A systematic review of progenitor.s.rvival and maturation in Parkinsonian models

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Neural regeneration r.s.arch 2025年第11期20卷 3172-3178页

作者： Giulia Comini Eilís Dowd Pharmacology&Therapeutics and Galway Neur.s.ience Center University of GalwayGalwayIreland

stem cell-based brain repair is a promising emergent therapy for Parkinson's disease based on years of foundational r.s.arch 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 r.s.oration of the dopaminergic input to denervated regions of the brain allowing for r.s.oration 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

Deciphering the mechanobiology of microglia in traumatic brain injury with advanced micr.s.stems

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Neural regeneration r.s.arch 2025年第8期20卷 2304-2306页

作者： Anthony Procès sylvain Gabriele Univ.Grenoble Alpes InsermU1216Grenoble Institut des NeurosciencesGrenobleFrance Mechanobiology&Biomaterials Group CIRMAPResearch Institute for BiosciencesUniversity of MonsMonsBelgium

Advanced micr.s.stems in traumatic brain injury r.s.arch:Traumatic brain injury(TBI)r.s.lts from a mechanical insult to the brain,leading to neuronal and axonal damage and subsequently causing a secondary *** minutes ... 详细信息

关键词： traumatic injury damage

Free vibration and transient r.s.onse of double curved beams connected by intermediate straight beams

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Applied Mathematics and Mechanics(English Edition) 2025年第1期46卷 37-62页

作者： r.A.JAFArI-TALOOKOLAEI H.GHANDVAr E.JUMAEV s.KHATIr T.CUONG-LE school of Mechanical Engineering Babol Noshirvani University of Technology Department of Mechanical Engineering Faculty of Engineering New Uzbekistan University University of Business and science Center for Engineering Application and Technology solutions Ho Chi Minh City Open University

This paper investigates the free vibration and transient r.s.onse of interconnected structur.s.including double curved beams and intermediate straight beams,which are all constructed from functionally graded porous(FGP) materials. The strain potential and kinetic energies of each beam along with the work done by the external force are calculated. Additionally, a higher-order beam element is introduced to derive stiffness and mass matrices, along with the force vector. The curved and straight beams are discretized, and their assembled stiffness, mass matrices, and force vectors, are *** conditions at the joints are used to derive the total matrices of the entire structure. subsequently, the natural frequencies and transient r.s.onse of the system are determined. The accuracy of the mathematical model and the self-developed computer program is validated through the compar.s.n of the obtained r.s.lts with those of the existing literature and commercial software ANsYs, demonstrating excellent ***, a comprehensive study is conducted to investigate the effects of various parameters on the free vibration and transient r.s.onse of the considered structure.

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Understanding activity of butyrate at a cellular level

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Neural regeneration r.s.arch 2025年第8期20卷 2323-2324页

作者： Prapti Chakraborty Angela s.Laird Macquarie University Motor Neuron Disease r.s.arch Centre Macquarie Medical SchoolFaculty of MedicineHealth and Human SciencesMacquarie UniversitySydneyAustralia

Butyrate is a short-chain fatty acid of four carbons in length that is a by-product produced by the microbial fermentation of dietary fiber and undigested carbohydrates within the *** the years,butyrate has attracted ... 详细信息

关键词： carbons butyrate fiber