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Modulation of the Nogo signaling pathway to overcome amyloid-β-mediated neurite inhibition in human pluripotent stem cell-derived neurites

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Neural Regeneration Research 2025年第9期20卷 2645-2654页

作者： Kirsty Goncalves stefan Przyborski Department of Biosciences Durham UniversityDurhamUK Reprocell Europe Ltd. GlasgowUK

Neuronal cell death and the loss of connectivity are two of the primary pathological mechanisms underlying Alzheimer's *** accumulation of amyloid-βpeptides,a key hallmark of Alzheimer's disease,is believed to induce neuritic abnormalities,including reduced growth,extension,and abnormal growth cone morphology,all of which contribute to decreased ***,the precise cellular and molecular mechanisms governing this response remain *** this study,we used an innovative approach to demonstrate the effect of amyloid-βon neurite dynamics in both two-dimensional and three-dimensional cultu re systems,in order to provide more physiologically relevant culture *** utilized various methodologies,including the addition of exogenous amyloid-βpeptides to the culture medium,growth substrate coating,and the utilization of human-induced pluripotent stem cell technology,to investigate the effect of endogenous amyloid-βsecretion on neurite outgrowth,thus paving the way for potential future applications in personalized ***,we also explore the involvement of the Nogo signaling cascade in amyloid-β-induced neurite *** demonstrate that inhibition of downstream ROCK and RhoA components of the Nogo signaling pathway,achieved through modulation with Y-27632(a ROCK inhibitor)and Ibuprofen(a Rho A inhibitor),respectively,can restore and even enhance neuronal connectivity in the presence of amyloid-β.In summary,this study not only presents a novel culture approach that offers insights into the biological process of neurite growth and inhibition,but also proposes a specific mechanism for reduced neural connectivity in the presence of amyloid-βpeptides,along with potential intervention points to restore neurite ***,we aim to establish a culture system that has the potential to serve as an assay for measuring preclinical,predictive outcomes of drugs and their ability to promote neurite outgrowth,both generally and in a patie

关键词： Alzheimer's disease induced pluripotent stem cell neurite outgrowth neuron Nogo Rho A ROCK stem cell three-dimensional culture

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Insulin and leptin enhance human sperm motility, acrosome reaction and nitric oxide production

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Asian Journal of Andrology 2008年第5期10卷 799-807页

作者： Fanuel Lampiao stefan s. du Plessis Division of Medical Physiology Department of Biomedical Sciences University of Stellenbosch Tygerberg 7505 South Africa

Aim： To investigate the in vitro effects of insulin and leptin on human sperm motility, viability, acrosome reaction and nitric oxide （NO） production. Methods： Washed human spermatozoa from normozoospermic donors were treated with insulin （10 μIU） and leptin （10 nmol）. Insulin and leptin effects were blocked by inhibition of their intracellular effector, phosphotidylinositol 3-kinase （PI3K）, by wortmannin （10 μmol） 30 min prior to insulin and leptin being given. Computer-assisted semen analysis was used to assess motility after 1, 2 and 3 h of incubation. Viability was assessed by fluorescence-activated cell sorting using propidium iodide as a fluorescent probe. Acrosome-reacted cells were observed under a fluorescent microscope using fluorescein-isothiocyanate-Pisum sativum agglutinin as a probe. NO was measured after treating the sperm with 4,5-diaminofluorescein-2/diacetate （DAF-2/DA） and analyzed by fluorescence-activated cell sorting. Results： Insulin and leptin significantly increased total motility, progressive motility and acrosome reaction, as well as NO production. Conclusion： This study showed the in vitro beneficial effects of insulin and leptin on human sperm function. These hormones could play a role in enhancing the fertilization capacity of human spermatozoa.

关键词： insulin leptin spermatozoa nitric oxide motility acrosome reaction

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small Directed strongly Regular Graphs

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Algebra Colloquium 2020年第1期27卷 11-30页

作者： stefan Gyurki Deparment of Mathematics and Descriptive Geometry Faculty of Civil Engineering Slovak University of Technology81005 BratislavaSlovakia

The goal of the present paper is to provide a gallery of small directed strongly regular *** each graph of order n≤12 and valency ks depicted,its relation to other small directed strongly regular graphs is revealed,the full group of automorphisms is described,and some other nice properties are *** each graph a list of interesting subgraphs is provided as well.

关键词： directed strongly regular graphs Cayley graphs voltage assignments

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Polymodal roles of transient receptor potential channels in the control of ocular function

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Eye and Vision 2015年第1期2卷 53-62页

作者： Peter s Reinach Weiwei Chen stefan Mergler school of Ophthalmology and Optometry Wenzhou Medical UniversityWenzhouZhejiang 325027P.R.China Charité-Universitätsmedizin Berlin Campus Virchow-KlinikumKlinik für AugenheilkundeAugustenburger Platz 1D-13353 BerlinGermany

Maintenance of intracellular Ca^(2+)levels at orders of magnitude below those in the extracellular environment is a requisite for preserving cell *** channels contribute to such control through modulating their time-dependent opening and closing *** regulation requires Ca^(2+)to serve as a second messenger mediating receptor control of numerous life-sustaining *** receptor potential(TRP)channels signal transduce a wide variety of different sensory stimuli to induce responses modulating cellular *** channels are non-selective cation channels with variable Ca^(2+)selectivity having extensive sequence *** constitute a superfamily made up of 28 different members that are subdivided into 7 different subfamilies based on differences in sequence *** of these TRP channel isotypes are expressed in the eye and localized to both neuronal and non-neuronal cell *** activation generates intracellular Ca^(2+)transients and other downstream-linked signalling events that affect numerous responses required for visual *** there is an association between changes in functional TRP expression in various ocular diseases,there are efforts underway to determine if these channels can be used as drug targets to reverse declines in ocular *** review here our current knowledge about the expression,function and regulation of TRPs in different eye tissues in health and ***,some of the remaining hurdles are described to developing safe and efficacious TRP channel modulators for use in a clinical setting.

关键词： Transient receptor potential ion channels Calcium Retina Cornea Uvea Lens

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Beyond the Expected-Residual Risk and Cases of Overload in the Context of Managing Alpine Natural Hazards

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International Journal of Disaster Risk science 2021年第2期12卷 205-219页

作者： sönke Hartmann Lydia Pedoth Cristina Dalla Torre stefan schneiderbauer Eurac Research Institute for Earth Observation39100BolzanoSouth TyrolItaly Eurac Research Institute for Regional Development39100BolzanoSouth TyrolItaly Institute for Environment and Human security United Nations University53113BonnGermany

structural protection measures are designed to protect the population and infrastructure against natural hazards up to a specific predefined protection *** events with intensities that exceed the capacity of these protection structures are called“cases of overload”and are associated with“residual risks”that remain after the implementation of protection *** order to address residual risks and to reduce the damages from overload events,a combination of structural protection measures with additional,nonstructural measures is *** on data collected through a literature review,a questionnaire survey,expert interviews,and an expert workshop we highlight the status quo as well as key challenges of dealing with residual risks and cases of overload in Alpine countries in the context of geohydrological hazards and gravitational mass *** present a holistic conceptual framework that describes the relationships of residual risks,cases of overload,and protection goals in the context of both risk governance and integrated risk *** framework is valuable for decision makers aiming at an improved management of natural hazards that takes adequate account of residual risk and cases of overload in Alpine countries and mountain areas worldwide.

关键词： Alpine countries Cases of overload Integrated risk management Natural hazards Residual risk Risk governance

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Generalized sampling in shift Invariant spaces with Frames

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Acta Mathematica sinica,English series 2012年第9期28卷 1823-1844页

作者： stefan ERICssON Department of Engineering sciences and Mathematics Lule University of Technology

Generalized sampling in a shift invariant subspace V of L2（R） is considered. A function f in V is processed with different filters Lm and then one tries to reconstruct f from the samples L^mf（j＇k）. We develop a theory of how to do this in the case when V possesses a shift invariant frame. special attention is paid to the question： How to obtain dual frames with compact support？

关键词： Generalized sampling frames Riesz basis reproducing kernel shift invariant spaces

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Radiative suppression of exciton-exciton annihilation in a two-dimensional semiconductor

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Light(science & Applications) 2023年第9期12卷 1911-1920页

作者： Luca sortino Merve Gülmüs Benjamin Tilmann Leonardo de s.Menezes stefan A.Maier Chair in Hybrid Nanosystems Nanoinstitute MunichFaculty of PhysicsLudwig-Maximilians-Universität München80539 MunichGermany Center for Nanoscience Faculty of PhysicsLudwig-Maximilians-Universität München80539 MunichGermany Departamento de Física Universidade Federal de Pernambuco50670-901 Recife-PEBrazil school of Physics and Astronomy Monash UniversityClaytonVIC 3800Australia The Blackett Laboratory Department of PhysicsImperial College LondonLondon SW72BWUK

Two-dimensional(2D)semiconductors possess strongly bound excitons,opening novel opportunities for engineering light-matter interaction at the ***,their in-plane confinement leads to large non-radiative exciton–exciton annihilation(EEA)processes,setting a fundamental limit for their photonic *** this work,we demonstrate suppression of EEA via enhancement of light-matter interaction in hybrid 2D semiconductor-dielectric nanophotonic platforms,by coupling excitons in Ws2 monolayers with optical Mie resonances in dielectric *** hybrid system reaches an intermediate light-matter coupling regime,with photoluminescence enhancement factors up to *** the exciton ultrafast dynamics reveal suppressed EEA for coupled excitons,even under high exciton densities>10^(12)cm^(−2).We extract EEA coefficients in the order of 10^(−3),compared to 10^(−2)for uncoupled monolayers,as well as a Purcell factor of *** results highlight engineering the photonic environment as a route to achieve higher quantum efficiencies,for low-power hybrid devices,and larger exciton densities,towards strongly correlated excitonic phases in 2D semiconductors.

关键词： annihilation dielectric coupling

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Cholesterol crystal binding of biliary immunoglobulin A: visualization by fluorescence light microscopy

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World Journal of Gastroenterology 2001年第2期7卷 198-202页

作者： Frank Lammert stefan südfeld Norbert Busch siegfried Matern Department of Medicine III University of Technology (RWTH) AachenGermany

AIM: To assess potential contributions of biliary IgA for crystal agglomeration into gallstones, we visualized cholesterol crystal binding of biliary IgA. METHODs: Crystal binding biliary proteins were extracted from human gallbladder bile using lectin affinity *** IgA was isolated from the bound protein fraction by immunoaffinity chromatography. Pure cholesterol monohydrate crystals were incubated with biliary IgA and fluoresceine isothiocyanate (FITC)conjugated anti IgA at 37 degree. samples were examined under polarizing and fluorescence light microscopy with digital image processing. REsULTs: Binding of biliary IgA to cholesterol monohydrate crystals could be visualized with FITC conjugated anti IgA *** fluorescence occurred at crystal edges and dislocations. Controls without biliary IgA or with biliary IgG showed no significant fluorescence. CONCLUsION: Fluorescence light microscopy provided evidence for cholesterol crystal binding of biliary IgA. Cholesterol crystal binding proteins like IgA might be important mediators of crystal agglomeration and growth of cholesterol gallstones by modifying the evolving crystal structures in vivo.

关键词： Crystallization Bile Cholelithiasis Cholesterol Chromatography, Affinity Fluorescent Antibody Technique Humans Image Processing, Computer-Assisted Immunoglobulin A, secretory Microscopy, Fluorescence Research support, Non-U.s. Gov't

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Constitutive relations for the shear band evolution in granular matter under large strain

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Particuology 2008年第6期6卷 501-505页

作者： stefan Luding Multi scale Mechanics TS CTW UTwente P.O. Box 217 7500 AE Enschede Netherlands

A so-called ＂split-bottom ring shear cell＂ leads to wide shear bands under slow, quasi-static deformation. Unlike normal cylindrical Couette shear cells or rheometers, the bottom plate is split such that the outer part of it can move with the outer wall, while the other part （inner disk） is immobile. From discrete element simulations （DEM）, several continuum fields like the density, velocity, deformation gradient and stress are computed and evaluated with the goal to formulate objective constitutive relations for the powder flow behavior. From a single simulation, by applying time- and （local） space-averaging, a non-linear yield surface is obtained with peculiar stress dependence. The anisotropy is always smaller than the macroscopic friction coefficient. However, the lower bound of anisotropy increases with the strain rate, approaching the maximum according to a stretched exponential with a specific rate that is consistent with a shear path of about one particle diameter.

关键词： Ring shear cell shear bands DEM simulation Micro-macro transition Objective constitutive relations Yield stress fluid

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Diabetes mellitus and male infertility

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Asian pacific Journal of Reproduction 2018年第1期7卷 6-14页

作者： Omolaoye Temidayo s du Plessis stefan s Division of Medical Physiology Faculty of Medicine and Health SciencesStellenbosch UniversityTygerbergSouth Africa

Infertility is prevalent in about 10%-25% of couples in their reproductive age, analogous to 60-80 million infertile couples globally. Of these infertility cases, 10%-30% are exclusively attributed to a problem of the male. several diseases have been implicated as contributors to deteriorating male fertility and diabetes mellitus (DM) is included. DM, a chronic non-communicable disease, has been considered as one of the most appreciable health threats, as it affects 9% (422 million) of the world's population as of 2014. It is characterised by hyperglycaemia, which can result from the inability of the pancreaticβ-cells to secrete insulin or from the target tissue becoming insensitive to insulin. DM has been reported to influence male reproductive function through diverse pathways and mechanisms. The adverse effects of reactive oxygen species and successive development of oxidative stress that occur due to DM have been investigated and implicated by several studies. The products of non-enzymatic glycosylation are reported to be widely distributed in the reproductive tract of diabetic men. Additionally, DM has been implicated to impair the processes of male sexual acts. Data reported in this review were extracted from PubMed, Google scholar, science Direct and scopus with diabetes and male infertility as the key search words. In light of the aforementioned, the aim of this review is to provide brief background information on DM as well highlight and explain the likely mechanisms of male fertility which DM impacts.

关键词： Diabetes mellitus Male infertility Diabetic neuropathy Oxidative stress Reactive oxygen species Advanced glycated end products

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