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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

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AAV-based gene therapy approaches for genetic forms of tauopathies and related neurogenetic disorders

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BIOCELL 2022年第4期46卷 847-853页

作者： MOHAMED AGHYAD AL kABBANI GILBERT WUNDERLICH christoph köhler HANS ZEMPEL Faculty of Medicine and University Hospital Cologne Institute of Human GeneticsUniversity of CologneCologne50931Germany Faculty of Medicine and University Hospital Cologne Center for Molecular Medicine Cologne(CMMC)University of CologneCologne50931Germany Faculty of Medicine and University Hospital Cologne Department of NeurologyUniversity of CologneCologne50937Germany Faculty of Medicine and University Hospital Cologne Center for Rare DiseasesUniversity of CologneCologne50937Germany Faculty of Medicine and University Hospital Cologne Center AnatomyDepartment of Molecular and Translational NeuroscienceUniversity of CologneCologne50931Germany

Tauopathies comprise a spectrum of genetic and sporadic neurodegenerative diseases mainly characterized by the presence of hyperphosphorylated TAU protein aggregations in neurons or *** therapy,in particular adeno-associated virus(AAV)-based,is an effective medical approach for difficult-to-treat genetic diseases for which there are no convincing traditional therapies,such as *** AAV-based gene therapy to treat,in particular,genetic tauopathies has many potential therapeutic benefits,but also drawbacks which need to be addressed in order to successfully and efficiently adapt this still unconventional therapy for the various types of *** this Viewpoint,we briefly introduce some potentially treatable tauopathies,classify them according to their etiology,and discuss the potential advantages and possible problems of AAV-based gene ***,we outline a future vision for the application of this promising therapeutic approach for genetic and sporadic tauopathies.

关键词： Tauopathies Neurogenetic diseases AAV-based gene therapy Neurodegeneration Alzheimer disease TAU

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Achievements and Challenges in European Energy Markets

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Journal of Modern Power Systems and Clean Energy 2023年第3期11卷 698-704页

作者： christoph Weber University of Duisburg-Essen EssenGermany IEEE

The European electricity and gas markets have been deregulated more than two decades *** rather diverse starting points,they have continuously evolved over the years to accommodate with new challenges and to improve *** 2005,these markets have been complemented by the market for emission certificates established by the European Union(EU)emission trading *** partly competing paradigms have thereby shaped the markets and continue to drive their on-going transformation:effective competition,subsidiarity and sustainability.

关键词： Electricity marker Europe carbon pricing market design deregulation decarbonization sustainable energy system

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The evolutionary ecology of symbiont-conferred resistance to parasitoids in aphids

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Insect Science 2014年第3期21卷 251-264页

作者： christoph Vorburger Institute of Integrative Biology ETH Zǖrich Universitātstrasse 16 8092 Zǖdch EAWAG Swiss Federal Institute of Aquatic Science and Technology Uberlandstrasse 133 8600 Dǖbendoàf Switzerland

Aphids may harbor a wide variety of facultative bacterial endosymbionts. These symbionts are transmitted maternally with high fidelity and they show horizontal trans-mission as well, albeit at rates too low to enable infectious spread. Such symbionts need to provide a net fitness benefit to their hosts to persist and spread. Several symbionts haveachieved this by evolving the ability to protect their hosts against parasitoids. Reviewing empirical work and some models, I explore the evolutionary ecology of symbiont-conferredresistance to parasitoids in order to understand how defensive symbiont frequencies are maintained at the intermediate levels observed in aphid populations. I further show thatdefensive symbionts alter the reciprocal selection between aphids and parasitoids by augmenting the heritable variation for resistance, by increasing the genetic specificity of thehost-parasitoid interaction, and by inducing environment-dependent trade-offs. These effects are conducive to very dynamic, symbiont-mediated coevolution that is driven by frequency-dependent selection. Finally I argue that defensive symbionts represent a problem for biological control of pest aphids, and I propose to mitigate this problem byexploiting the parasitoids＇ demonstrated ability to rapidly evolve counteradaptations to symbiont-conferred resistance.

关键词： aphids biological control coevolution genotype × genotype interaction Hamiltonella defensa parasitoid resistance symbiosis

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Tuning the translational freedom of DNA for high speed AFM

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Nano Research 2015年第6期8卷 1811-1821页

作者： Andrew J. Lee Michal Szymonik Jamie k. Hobbs christoph Walti Bioelectronics School of Electronic and Electrical Engineering University of Leeds Leeds LS2 9JT UK Department of Physics and Astronomy University of Sheffield Sheffield 53 7RH UK

Direct observation is arguably the preferred way to investigate the interactions between two molecular complexes. With the development of high speed atomic force microscopy （AFM）, it is becoming possible to observe directly DNA-protein interactions with relevant spatial and temporal resolutions. These interactions are of central importance to biology, bionanotechnology, and functional biologically inspired materials. As in all microscopy studies, sample preparation plays a central role in AFM observation and minimal perturbation of the sample is desired. Here, we demonstrate the ability to tune the interactions between DNA molecules and the surface to create an association strong enough to enable high-resolution AFM imaging while also providing sufficient translational freedom to allow the relevant protein-DNA interactions to take place. Furthermore, we describe a quantitative method for measuring DNA mobility, while also determining the individual forces contributing to DNA movement. We found that for a weak surface association, a significant contribution to the movement arises from the interaction of the AFM tip with the DNA. In combination, these methods enable the tuning of the surface translational freedom of DNA molecules to allow the direct study of a wide range of nucleo-protein interactions by high speed atomic force microscopy.

关键词： high speed atomic forcemicroscopy (HS-AFM) DNA protein bionanotechnology

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The effects of 12 weeks of functional strength training on muscle strength,volume and activity upon exposure to elevated Gz forces in high-performance aircraft personnel

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Military Medical Research 2021年第4期8卷 481-489页

作者： Monika Rausch Frank Weber Sven kühn Carla Ledderhos christoph Zinner Billy Sperlich Multinational Medical Coordination Centre/European Medical Command Andernacher Strasse 10056070 KoblenzGermany. German Air Force Center of Aerospace Medicine 82256 FuerstenfeldbruckGermany. Department of Radiology Bundeswehr Central Hospital56072 KoblenzGermany. Department of Sport University of Applied Sciences for Police and Administration of Hesse65199 WiesbadenGermany. Integrative&Experimental Exercise Science&Training Institute of Sport ScienceUniversity of Wuerzburg97082 WuerzburgGermany

Background:Technological advancements in modern military and acrobatic jet planes have resulted in extraordinary psychophysiological loads being exerted upon flying personnel,including inducing neck and back *** purpose of this study was to examine the effects of 12 weeks of functional strength training on 1)the volume and strength of the neck and shoulder muscles and 2)muscular activity upon exposure to helmets of different masses and elevated Gz forces in a long-arm centrifuge in high-performance aircraft ***:Eighteen participants underwent 12 weeks of functional strength training(n=12)or the control protocol(n=6)without additional strength ***-and post-intervention tests included evaluations of isometric strength of the head extensor muscles,flexion,and lateral flexion and rotation,as well as magnetic resonance imaging(MRI)to measure the volume of the ***,***,and deep neck ***,during a long-arm centrifuge(+1.4 and+3Gz)protocol,the muscular activity levels of the ***,*** and *** spinae muscles were assessed without a flight helmet,with a helmet,and with a helmet and night vision *** participant’s perception of muscular strain was noted immediately after the long-arm centrifuge ***:The maximal isometric strength in all exercises and muscle volumes increased in the training group but not the control group(Pk muscles induced by the long-arm centrifuge did not differ between the ***:Twelve weeks of functional strength training improves the maximal isometric strength and volume of neck and shoulder m

关键词： Fighter pilots Long-arm centrifuge Muscular strain Strength training Neck muscle High-performance aircraft Gz forces

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Convergent patterns in multitrophic biodiversity effects on yield across ecosystems

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Science China(Life Sciences) 2023年第11期66卷 2697-2699页

作者： christoph Scherber Leibniz Institute for the Analysis of Biodiversity Change(LIB) Museum KoenigCentre for Biodiversity Monitoring and Conservation ScienceBonn 53113Germany Institute of Evolutionary Biology and Ecology University of BonnBonn 53113Germany

In ecosystems managed for food or fiber production,there is often no space for *** example,intensive cereal monocultures are usually managed towards optimized yields using herbicides,fungicides and *** such systems,biodiversity is essentially unwanted,except maybe when it improves soil health or carbon ***,it has been difficult to convincingly show if and where biodiversity is economically important in intensive production systems.

关键词： ecosystems soil biodiversity

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The pH of the Apoplast： Dynamic Factor with =unctional Impact Under Stress

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Molecular Plant 2017年第11期10卷 1371-1386页

作者： christoph-Martin Geilfus Division of Controlled Environment Horticulture Faculty of Life Sciences Albrecht Daniel Thaer-Institute of Agricultural and Horticultural Sciences Humboldt-University of Berlin Albrecht-Thaer-Weg 1 14195 Berlin Germany

The apoplast is an interconnected compartment with a thin water-film that alkalinizes under stress. This systemic pH increase may be a secondary effect without functional implications, arising from ion movements or proton-pump regulations. On the other hand, there are increasing indications that it is part of a mechanism to withstand stress. Regardless of this controversy, alkalinization of the apoplast has received little attention. The apoplastic pH （PHapo） increases not only during plant-pathogen interactions but also in response to salinity or drought. Not much is known about the mechanisms that cause the leaf apoplast to alkalinize, nor whether, and if so, how functional impact is conveyed. Controversial explanations have been given, and the unusual complexity of pHapo regulation is considered as the primary reason behind this lack of knowledge. A gathering of scattered information revealed that changes in PHapo convey functionality by regulating stomatal aperture via the effects exerted on abscisic acid. Moreover, apoplastic alkalinization may regulate growth under stress, whereas this needs to be verified. In this review, a comprehensive survey about several physiological mechanisms that alkalize the apoplast under stress is given, and the suitability of apoplastic alkalinization as transducing element for the transmission of sensory information is discussed.

关键词： apoplastic fluid alkalinization abscisic acid PM-H^+-ATPase S-Type anion channel malate

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Which species discovers novel food sources first?A camera trap study in a natural environment

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Avian Research 2021年第3期12卷 421-424页

作者： christoph Randler Department of Biology Eberhard Karls University TuebingenAuf der Morgenstelle 2472070 TuebingenGermany

Birds underlie a predation-starvation risk,and foraging should show a diurnal/circadian *** traps were used to study visitation patterns and discovery of a novel food source in woodland birds in SW Germany.A total of 18 species occurred at feeders with nine of them being exploratory *** Tits(Parus major)discovered novel food sources first in most instances,and first discoveries occurred on average at 10:38,while it took 97 h for the first detection of the food *** size was correlated with *** study supports the predation-starva-tion risk hypothesis with discovery of food sources in the morning.

关键词： Camera trap Explorative behaviour Foraging behaviour Novel food source Starvation predation trade-off

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CO_(2)Plume Geothermal(CPG)Systems for Combined Heat and Power Production:an Evaluation of Various Plant Configurations

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Journal of Thermal Science 2022年第5期31卷 1266-1278页

作者： SCHIFFLECHNER christopher WIELAND christoph SPLIETHOFF Hartmut Chair of Energy Systems TUM School of Engineering and DesignTechnical University of Munich85747 GarchingGermany

CO_(2) Plume Geothermal(CPG)systems are a promising concept for utilising petrothermal resources in the context of a future carbon capture utilisation and sequestration *** geothermal energy has a tremendous worldwide potential for decarbonising both the power and heating *** paper investigates three potential CPG configurations for combined heating and power generation(CHP).The present work examines scenarios with reservoir depths of 4 km and 5 km,as well as required district heating system(DHS)supply temperatures of 70℃ and 90℃.The results reveal that a two-staged serial CHP concept eventuates in the highest achievable net power *** a thermosiphon system,the relative net power reduction by the CHP option compared with a sole power generation system is significantly lower than for a pumped *** net power reduction for pumped systems lies between 62.6%and 22.9%.For a thermosiphon system with a depth of 5 km and a required DHS supply temperature of 70℃,the achievable net power by the most beneficial CHP option is even 9.2%higher than for sole power generation *** second law efficiency for the sole power generation concepts are in a range between 33.0%and 43.0%.The second law efficiency can increase up to 63.0%in the case of a CHP ***,the combined heat and power generation can significantly increase the overall second law efficiency of a CPG *** evaluation of the achievable revenues demonstrates that a CHP application might improve the economic performance of both thermosiphon and pumped CPG ***,the minimum heat revenue required for compensating the power reduction increases with higher electricity *** summary,the results of this work provide valuable insights for the potential development of CPG systems for CHP applications and their economic feasibility.

关键词： deep geothermal energy combined heat and power generation CO_(2)plume geothermal systems petrothermal resources carbon capture utilisation and storage

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