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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

REAL COdEd GENETIC ALGORITHM FOR sTOCHAsTIC HYdROTHERMAL GENERATION sCHEdULING

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Journal of systems science and systems Engineering 2011年第1期20卷 87-109页

作者： Jarnail s.dHILLON J.s.dHILLON d.p.KOTHARI G.Z.s.College of Engineering and Technology sant Longowal Institute of Engineering and Technology Vindhya Institute of Technology and science

The intent of this paper is to schedule short-term hydrothermal system probabilistically considering stochastic operating cost curves for thermal power generation units and uncertainties in load demand and reservoir water inflows. Therefore, the stochastic multi-objective hydrothermal generation scheduling problem is formulated with explicit recognition of uncertainties in the system production cost coefficients and system load, which are treated as random variable. Fuzzy methodology has been exploited for solving a decision making problem involving multiplicity of objectives and selection criterion for best compromised solution. A real-coded genetic algorithm with arithmetic-average-bound-blend crossover and wavelet mutation operator is applied to solve short-term variable-head hydrothermal scheduling problem. Initial feasible solution has been obtained by implementing the random heuristic search. The search is performed within the operating generation limits. Equality constraints that satisfy the demand during each time interval are considered by introducing a slack thermal generating unit for each time interval. Whereas the equality constraint which satisfies the consumption of available water to its full extent for the whole scheduling period is considered by introducing slack hydro generating unit for a particular time interval. Operating limit violation by slack hydro and slack thermal generating unit is taken care using exterior penalty method. The effectiveness of the proposed method is demonstrated on two sample systems.

关键词： stochastic multi-objective optimization real-coded genetic algorithm fuzzy set economicload dispatch

Effect of Zn Concentration on Microstructural,Optical,and Hyperfine properties of Nanocrystalline a-Fe_(2)O_(3)

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Acta Metallurgica sinica(English Letters) 2014年第4期27卷 563-568页

作者： N.R.panda d.sahu B.s.Acharya p.Nayak s.p.pati d.das school of Basic science Indian Institute of Technology BhubaneswarBhubaneswar 751013OdishaIndia school of physics Sambalpur UniversitySambalpur 768019OdishaIndia school of Chemistry Sambalpur UniversitySambalpur 768019OdishaIndia C.V.Raman College of Engineering Bhubaneswar 752054OdishaIndia department of Electronic Engineering Tohoku UniversitySendai 980-8579Japan UGC-dAE CsR Sector IIILB-8Bidhan NagarKolkata 700098India

Efforts have been made to prepare nanocomposites of a-Fe2O3-ZnO by wet chemical route with varying concentrations of the *** microstructural properties of the samples are investigated by powder X-ray diffractometry（pXRd） and Transmission electron *** concentration of Zn ions（up to 20 at%） leads to the formation of nanocomposites of a-Fe2O3 and *** of ZnFe2O4 phase is detected by the substitution of higher concentration of Zn2？（30 at%） in the *** average size of the nanoparticles remains in the range of 22–27 nm as obtained from XRd *** results obtained from electron microscopic studies are also close to these *** measurement shows the excitonic peak of ZnO around 390 nm which gets strengthened with Zn *** spectra show the metal–oxygen band below 700 *** temperature Mssbauer studies of the samples show the transition of iron oxide form antiferromagnetic state to paramagnetic state with increasing concentration of Zn2？.sharp quenching of hyperfine field with Zn concentration is observed as the Hintvalue reduced to zero from 51 T.

关键词： Iron oxide ZnO Electron microscopy Mssbauer study

Nucleus-acoustic solitary waves in self-gravitating degenerate quantum plasmas

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Chinese physics B 2018年第4期27卷 191-197页

作者： d M s Zaman M Amina p R dip A A Mamun department of physics Jahangirnagar University department of EEE Bangladesh University of Business and Technology(BUBT)

Nucleus-acoustic（NA） solitary waves（sWs） propagating in a self-gravitating degenerate quantum plasma（sdQp）system（containing non-relativistically degenerate heavy and light nuclei,and non-/ultra-relativistically degenerate electrons） have been theoretically *** modified Korteweg–de Vries（m K-d V） equation has been derived for both planar and non-planar geometry by employing the reductive perturbation *** is shown that the NA sWs exist with positive（negative） electrostatic（self-gravitational） *** is also observed that the effects of non-/ultra-relativistically degenerate electron pressure,dynamics of non-relativistically light nuclei,spherical geometry,*** modify the basic features（e.g.,amplitude,width,speed,etc.） of the NA *** applications of our results,which are relevant to astrophysical compact objects,like white dwarfs and neutron stars,are briefly discussed.

关键词： self-gravitational potential solitary waves

Effects of variable viscosity and temperature modulation on linear Rayleigh-Bénard convection in Newtonian dielectric liquid

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Applied Mathematics and Mechanics(English Edition) 2019年第11期40卷 1601-1614页

作者： p.G.sIddHEsHWAR d.UMA s.BHAVYA department of Mathematics Bangalore UniversityBengaluru 560056India department of Computer science and Engineering PES UniversityBengaluru 560085India department of Mathematics Atria Institute of TechnologyBengaluru 560024India

The linear Rayleigh-Bénard electro-convective stability of the Newtonian dielectric liquid is determined theoretically subject to the temperature modulation with time.A perturbation method is used to compute the critical Rayleigh number and the wave *** critical Rayleigh number is calculated as a function of the frequency of modulation,the temperature-dependent variable viscosity,the electric field dependent variable viscosity,the prandtl number,and the electric Rayleigh *** effects of all three cases of modulations are established to delay or advance the onset of the convection *** addition,how the effect of variable viscosity controls the onset of convection is studied.

关键词： dielectric liquid temperature dependent variable viscosity electric field dependent variable viscosity electric Rayleigh number temperature modulation

Can rainfall seasonality trigger soil water repellency in a tropical riparian forest?

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Journal of Forestry Research 2023年第3期34卷 773-780页

作者： Gleicon Queiroz de brito Johnny Rodrigues de Melo Murta sérgio Fernandes Mendonca Filho Luiz Felippe salemi Núcleo de Estudos e pesquisas Ambientais e Limnológicas(NEpAL) Faculdade UnB de Planaltina(FUP)Universidade de Brasília(UnB)DFVila Nossa Senhora de FátimaÁrea Universitária 1Planaltina 73345-010Brazil

Though riparian areas generally have a shallow water table and higher soil moisture compared to up slope areas,climatic seasonality may trigger water repellency in tropical riparian forests,which,if persistent,could negatively affect essential ecosystem functions related to water resources protection such as reduced overland-flow,sediment transport,and nutrient *** objective of this study was to answer the following:can tropical riparian forests develop water repellency?If so,does water repellency affect infiltration on a seasonal basis?For this,water repellency and infiltration were measured in a grid of 72points during a dry and a wet month of a tropical riparian forest with a shallow water table in a region with highly marked climatic *** repellency and infiltration were significantly different between the wet and dry *** repellency affected negatively infiltration in the dry month,its effect in the wet month was *** a result,a higher infiltration capacity was observed over the wet *** research has claimed that the development and persistence of repellency in soils could promote other hydrological processes such as overland *** findings shown here demonstrate that such phenomenon does not persist longer than the dry season.

关键词： Hydrophobicity Gallery forest Aquifer recharge Climate change Erosion

Analytical solution of the Blast Wave problem in a Non-Ideal Gas

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Chinese physics Letters 2011年第11期28卷 152-154页

作者： L.p.singh s.d.Ram d.B.singh department of Applied Mathematics Institute of TechnologyBanaras Hindu UniversityVaranasi-221005India

An analytical approach is used to construct the exact solution of the blast wave problem with generalized geometries in a non-ideal *** is assumed that the density ahead of the shock front varies according to a power of distance from the source of the blast ***,an analytical expression for the total energy in a non-ideal medium is derived.

关键词： wave analytical assumed

small molecule inhibitor ddQ-treated hippocampal neuronal cells show improved neurite outgrowth and synaptic branching

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Neural Regeneration Research 2025年第9期20卷 2624-2632页

作者： Jangampalli Adi pradeepkiran priyanka Rawat Arubala p.Reddy Erika Orlov pHemachandra Reddy department of Internal Medicine Texas Tech University Health Sciences CenterLubbockTXUSA department of Nutritional sciences College of Human SciencesTexas Tech UniversityLubbockTXUSA department of pharmacology&Neuroscience Texas Tech University Health Sciences CenterLubbockTXUSA department of Neurology Texas Tech University Health Sciences CenterLubbockTXUSA department of speech Language and Hearing SciencesTexas Tech University Health Sciences CenterLubbockTXUSA department of public Health Texas Tech University Health Sciences CenterLubbockTXUSA

The process of neurite outgrowth and branching is a crucial aspect of neuronal development and *** and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start *** we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(ddQ)on neurite developmental features in HT22 neuronal *** this work,we examined the protective effects of ddQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)*** investigate ddQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were *** outgrowth is evaluated through the segmentation and measurement of neural *** neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite *** neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal ***-treated mTau-HT22 cells(HT22 cells transfected with cdNA mutant Tau)were seen to display increased levels of synaptophysin,MAp-2,andβ-***,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed ddQ enhanced the neurite characteristics and improved neurite development through increased synaptic *** findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with ddQ have functional neurite developmental chara *** key finding is that,in mTa u-HT22 cells,ddQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.

关键词： diethyl(3 4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(ddQ) hippocampal neuronal cells HT22 neurite outgrowth neuronal development small molecule

Complementary roles of glial cells in generating region-specific neuroinflammatory responses and phagocytosis in parkinson’s disease

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Neural Regeneration Research 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 hallmarks of parkinson’s disease(pd),a multisystem neurodegenerative disorder characterized by a progressive 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 progression remains to be *** leukocyte antigen.

关键词： inflammation leukocyte generating