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Effects of P301L-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice

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Neural Regeneration Research 2025年第8期20卷 2348-2360页

作者： Mohamed Aghyad Al kabbani Christoph köhler Hans Zempel Institute of Human Genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Center for Molecular Medicine Cologne(CMMC) University of CologneCologneGermany Center Anatomy Department ⅡMedical FacultyUniversity of CologneCologneGermany

TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the *** is missorted and aggregated in an array of diseases known as *** are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing *** impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule *** therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to *** investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-kO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic *** sum,P301L-TAU results in changes in micr

关键词： human induced pluripotent stem cell microtubules P301L pR5 mice TAU tauopathy tubulin code

Microglia:a promising therapeutic target in spinal cord injury

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Neural Regeneration Research 2025年第2期20卷 454-463页

作者： Xiaowei Zha Guoli Zheng Thomas Skutella karl kiening Andreas Unterberg Alexander Younsi Department of Neurosurgery Heidelberg University HospitalHeidelbergGermany Department of Neuroanatomy Institute for Anatomy and Cell BiologyHeidelberg UniversityHeidelbergGermany

Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal *** a healthy spinal cord,microglia are accountable for immune surveillance,however,when a spinal cord injury occurs,the microenvironment drastically changes,leading to glial scars and failed axonal *** this context,microglia vary their gene and protein expression during activation,and proliferation in reaction to the injury,influencing injury responses both favorably and unfavorably.A dynamic and multifaceted injury response is mediated by microglia,which interact directly with neurons,astrocytes,oligodendrocytes,and neural stem/progenitor *** a clear understanding of their essential nature and origin,the mechanisms of action and new functions of microglia in spinal cord injury require extensive *** review summarizes current studies on microglial genesis,physiological function,and pathological state,highlights their crucial roles in spinal cord injury,and proposes microglia as a therapeutic target.

关键词： astrocytes cytokines functional recovery immune regulation M1/M2 activation macrophages microglia neuroinflammation spinal cord injury therapy

Dedicated to Professor Dr.-Ing. ***.h.c. Jurgen Zierep for his 80^(th) birthday Pattern Formation in Rotating Fluids

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Journal of Thermal Science 2009年第2期18卷 109-118页

作者： karl Bühler Department of Mechanical and Process Engineering University of Applied Sciences

Flows in nature and technology are often associated with specific structures and pattern. This paper deals with thedevelopment and behaviour of such flow pattern. Flow structures are important for the mass, momentum and energytransport. The behaviour of different flow pattern is used by engineers to obtain an efficient mass and energyconsumption. Mechanical power is transmitted via the momentum of rotating machine parts. Therefore thephysical and mathematical knowledge of these basic concepts is important. Theoretical and experimental investigationsof principle experiments are described in the following. We start with the classical problem of the flowbetween two concentric cylinders where the inner cylinder rotates. Periodic instabilities occur which are calledTaylor vortices. The analogy between the cylindrical gap flow, the heat transfer in a horizontal fluid layer exposedto the gravity field and the boundary layer flow along concave boundaries concerning their stability behaviour isaddressed. The vortex breakdown phenomenon in a cylinder with rotating cover is also described. A generalizationto spherical sectors leads then to investigations with different boundary conditions. The spherical gap flowexhibits interesting phenomena concerning the nonlinear character of the Navier-Stokes equations. Multiple solutionsin the nonlinear regime give rise to different routes during the laminar-turbulent transition. The interactionof two rotating spheres results in flow structures with separation and stagnation lines. Experimental results areconfirmed by numerical simulations.

关键词： Rotating Fluids Stability Behaviour Bifurcation Vortices Laminar-turbulent Transition

Pattern Formation Around Interacting Bodies in Rotating Fluids

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Journal of Thermal Science 2006年第2期15卷 132-134页

作者： karl Bhler University of Applied Sciences Badstrasse 24 D-77652 Offenburg Germany

The interaction of bodies like spheres and disks in rotating fluids leads to novel flow structures. The primary swirling flow in circumferential direction is superimposed by a secondary motion in the meridional plane. The flow is visualized by introducing ink through a hole in the center of the axes and distributed radially in the central plane between the interacting bodies. The flow structure depends on the shape of the bodies, their geometrical arrangement and the Reynolds number given by the rotational speed. The observed flow structures gave rise to further investigations with PIV-measurcments and numerical simulations.

关键词： Rotating fluids pattern formation recirculation zones interacting bodies flow visualization

Boundary behavior of Gleason's problem in hyperbolic harmonic Bergman spaces

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Science China Mathematics 2005年第2期48卷 145-154页

作者： Uwe khler Department of Mathematics

Necessary and sufficient conditions are obtained for the boundedness of Berezin transformation on Lebesgue space Lp(B,dVβ) in the real unit ball B in Rn. As an application, we prove that Gleason type problem is solvable in hyperbolic harmonic Bergman spaces. Furthermore we investigate the boundary behavior of the solutions of Gleason type problem.

关键词： hyperbolic harmonic functions Berezin transformation Gleason’s problem.

A Glimpse into the Natural History of Leiolepis rubritaeniata Mertens,1961(Squamata:Leiolepididae)

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Asian Herpetological Research 2023年第2期14卷 147-155页

作者： Gunther kÖhler Panupong THAMMACHOTI Senckenberg Forschungsinstitut und Naturmuseum Senckenberganlage 25Frankfurt a.M.60325Germany Department of Biology Faculty of ScienceChulalongkorn UniversityBangkok 10330Thailand

During the months of April through July 2020 we studied aspects of the natural history of Leiolepis rubritaeniata,a species of butterfly lizard that occurs on the khorat Plateau in Thailand and adjacent regions of Laos and Cambodia as well as in south-central *** present data on population size and structure,as well as location,size,compass orientation,and structure of the lizard’s ***,we present climatic data(ambient air temperature and precipitation)at the study site for the duration of our field work as well as temperature data for the complete year ***,we provide data on egg laying,incubation conditions and characteristics of the ***,we present an easy to use and reliable non-invasive method for the long-term recognition of individual butterfly lizards based on their unique dorsal *** lizards are utilized as a food source for the local human *** far,there are no farming projects in Thailand involving this species and all individuals are collected from the wild *** data are available on the population dynamics of *** but it can be assumed that habitat destruction due to land use change as well as its utilization for human consumption have negative effects on the long-term survival of the local populations of this lizard *** baseline data presented here are essential for any meaningful conservation strategy for these lizards.

关键词： Burrow structure butterfly lizard ecology khorat Plateau Southeast Asia Squamata

Intrumer:A Multi Module Distributed Explainable IDS/IPS for Securing Cloud Environment

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Computers, Materials & Continua 2025年第1期82卷 579-607页

作者： Nazreen Banu A S.k.B.Sangeetha Department of Computer Science and Engineering SRM Institute of Science and TechnologyVadapalani CampusChennai600026Tamil NaduIndia

The increasing use of cloud-based devices has reached the critical point of cybersecurity and unwanted network *** environments pose significant challenges in maintaining privacy and *** approaches,such as IDS,have been developed to tackle these ***,most conventional Intrusion Detection System(IDS)models struggle with unseen cyberattacks and complex high-dimensional *** fact,this paper introduces the idea of a novel distributed explainable and heterogeneous transformer-based intrusion detection system,named INTRUMER,which offers balanced accuracy,reliability,and security in cloud settings bymultiplemodulesworking together within *** traffic captured from cloud devices is first passed to the TC&TM module in which the Falcon Optimization Algorithm optimizes the feature selection process,and Naie Bayes algorithm performs the classification of *** selected features are classified further and are forwarded to the Heterogeneous Attention Transformer(HAT)*** this module,the contextual interactions of the network traffic are taken into account to classify them as normal or malicious *** classified results are further analyzed by the Explainable Prevention Module(XPM)to ensure trustworthiness by providing interpretable *** the explanations fromthe classifier,emergency alarms are transmitted to nearby IDSmodules,servers,and underlying cloud devices for the enhancement of preventive *** experiments on benchmark IDS datasets CICIDS 2017,Honeypots,and NSL-kDD were conducted to demonstrate the efficiency of the INTRUMER model in detecting network trafficwith high accuracy for different *** outperforms state-of-the-art approaches,obtaining better performance metrics:98.7%accuracy,97.5%precision,96.3%recall,and 97.8%*** results validate the robustness and effectiveness of INTRUMER in securing diverse cloud environments against sophisticated cyber threats.

关键词： Cloud computing intrusion detection system transformers and explainable artificial intelligence(XAI)

Recycling of magnesium drive train components

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Science China(Technological Sciences) 2009年第1期52卷 148-154页

作者： Daniel FECHNER Carsten BLAWERT Norbert HORT karl ulrich kAINER MagIC-Magnesium Innovation Centre GKSS Research Centre Max-Planck-Straβe 1

With the development of new heat resistant magnesium alloys, the automotive industry has introduced several parts to the drive train. The rising number of large magnesium components will result in a higher quantity of automotive post consumer scrap. It was the aim of this work to find a reasonable alloy system for the recycling of these magnesium drive train components. A matrix of potential recy-cling alloys based on the magnesium alloy AM50 was prepared via permanent mould casting. The materials were investigated via tensile testing, creep tests and salt spray tests. Three alloys were selected for processing via high pressure die casting and the tests were repeated on the new materials. A promising system for recycling has been isolated and will be investigated more deeply for the influence of impurities.

关键词： magnesium recycling end-of-life vehicles recycling alloy post consumer scrap

PSEUDOHYPERBOLIC METRIC AND UNIFORMLY DISCRETE SEQUENCES IN THE REAL UNIT BALL

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Acta Mathematica Scientia 2014年第3期34卷 629-638页

作者：任广斌 Uwe khler Department of Mathematics University of Science and Technology of China CIDMA-Center of R &D in Mathematics and Applications University of AveiroP-3810-193 AveiroPortugal

We present an overview of the properties of the pseudohyperbolic metric in several real dimensions and study uniformly discrete sequences for the real unit ball in R^n.

关键词： Uniformly discrete sequences harmonic functions Bergman spaces pseudohy-perbolic metric