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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

Body Building on Diamonds

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Journal of Bionic Engineering 2009年第1期6卷 14-17页

作者： Andrei p. Sommer Tim Scharnweber hans-Joerg Fecht Institute of Micro and Nanomaterials University of UlmUlm 89081Germany Institute for Biological Interfaces Research Center KarlsruheKarlsruhe 76021Germany Institute for Nanotechnology Research Center Karlsruhe Karlsruhe 76021Germany

Whereas conservative therapies aim to stall the advance of disease,regenerative medicine strives to reverse *** capacity of most tissues to regenerate derives from stem cells,but there are a number of barriers which have to be circumvented before it will be possible to use stem-cell-based *** therapies,however,are expected to improve human health enormously, and knowledge gained from studying stem cells in culture and in model organisms is now laying the groundwork for a new era of regenerative *** of the most prominent methods to study stem cell differentiation is to let them to form embryoid *** favourable conditions any stem cell line will form embryoid ***,the mechanism of the formation of embryoid bodies is not very well understood,and to produce them in the laboratory is in no way trivial-an important technical barrier in stem cell ***,the embryoid body cultivation step has been successfully circumvented for the derivation of osteogenic cultures of embryonic stem *** we report on a simple and reusable system to cultivate embryoid bodies in extremely short *** method is inspired by the principles that lead to the establishment of the biomimetic triangle.

关键词： biomimetic triangle stem cells embryoid bodies nanobionics nanocrystalline diamond

Microstructure, mechanical properties and wear resistance of an Al–Mg–Si alloy produced by equal channel angular pressing

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progress in Natural Science:Materials International 2020年第4期30卷 485-493页

作者： Manping liu Jian Chen Yaojun lin Zhoulei Xue hans J.Roven p?l C.Skaret School of Materials Science and Engineering Jiangsu University School of Materials Science and Engineering Wuhan University of Technology Department of Materials Science and Engineering Norwegian University of Science and Technology (NTNU)

Microstructure, mechanical properties and wear resistance in an ultrafine-grained Al–Mg–Si alloy fabricated utilizing a combination of equal channel angular pressing(ECAp) and dynamic aging were investigated in this paper. The results indicated that the grain size of the ECAp alloy was significantly refined, i.e., to ～239 nm after three ECAp passes. Meanwhile, the yield and tensile strength of the ECAped material reached 340 Mpa and445 Mpa, respectively, while maintaining a significant uniform elongation of 14%. Wear resistance results demonstrated that the wear rate, wear depth and width of the ECAped material decreased in comparison with the solution-treated(SST) and peak-aged(T6) conditions under a load range of 5–25 N. The adhesive wear that occurs in the undeformed specimens at 10 N does not appear in the ECAped specimen at the same load, indicating that the ECAped specimen delay the appearance of more serious wear mechanisms under certain *** cooperative interaction of high density nano-scale β" precipitates and dislocations resulted in a combination of super-high strength and good work hardening ability which suppressed the extension of cracks between the friction layer and the plastic deformation zone. As a consequence, the combination of ECAp and dynamic aging brings a significant improvement for antifriction performance of the 6061 aluminum alloy.

关键词： Al–Mg–Si aluminum Alloy Equal channel angular pressing Dynamic aging Mechanical properties Wear resistance Wear mechanism Work hardening rate

AtGGM2014, an Arabidopsis gene co-expression network for functional studies

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Science China(life Sciences) 2015年第3期58卷 276-286页

作者： MA ShiSong BOHNERT hans J DINESH-KUMAR Savithramma p Department of plant Biology and the Genome Center College of Biological Sciences University of California Departments of plant Biology and of Crop Sciences University of Illinois at Urbana-Champaign

Gene co-expression networks provide an important tool for systems biology studies. Using microarray data from the Array Express database, we constructed an Arabidopsis gene co-expression network, termed At GGM2014, based on the graphical Gaussian model, which contains 102,644 co-expression gene pairs among 18,068 genes. The network was grouped into 622 gene co-expression modules. These modules function in diverse house-keeping, cell cycle, development, hormone response, metabolism, and stress response pathways. We developed a tool to facilitate easy visualization of the expression patterns of these modules either in a tissue context or their regulation under different treatment conditions. The results indicate that at least six modules with tissue-specific expression pattern failed to record modular regulation under various stress conditions. this discrepancy could be best explained by the fact that experiments to study plant stress responses focused mainly on leaves and less on roots, and thus failed to recover specific regulation pattern in other tissues. Overall, the modular structures revealed by our network provide extensive information to generate testable hypotheses about diverse plant signaling pathways. At GGM2014 offers a constructive tool for plant systems biology studies.

关键词： Arabidopsis gene co-expression network graphical Gaussian model plant development stress response hormone response

DSC analyses of static and dynamic precipitation of an Al–Mg–Si–Cu aluminum alloy

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progress in Natural Science:Materials International 2015年第2期25卷 153-158页

作者： Manping liu Zhenjie Wu Rui Yang Jiangtao Wei Yingda Yu p?l C. Skaret hans J. Roven School of Materials Science and Engineering Jiangsu Province Key Laboratory of Materials Tribology Jiangsu University Department of Materials Science and Engineering Norwegian University of Science and Technology (NTNU)

In the present investigation, both static and dynamic precipitations of an Al–Mg–Si–Cu aluminum alloy after solid-solution treatment(SST)were comparatively analyzed using differential scanning calorimetry(DSC). Dynamic aging was performed in the SST alloy through equal channel angular pressing(ECAp) at different temperatures of room temperature, 110, 170, 191 and 300 1C. For comparison, static artificial aging was conducted in the SST alloy at 191 1C with two aging times of 4 and 10 h. The DSC analyses reveal that the dynamic precipitation has occurred in the ECAped samples, while the activation energies associated with the strengthening precipitates in the dynamic samples are considerably higher than the energies in the SST and static aged samples. The higher activation energies are probably attributed to the smaller grains and higher dislocation density developed after ECAp. The results in the present investigation allow the prediction of the type of the dynamic precipitates to influence the strength of the ultrafine grained alloy during ECAp at various temperatures.

关键词： Differential scanning calorimetry Al–Mg–Si–Cu aluminum alloy Dynamic aging precipitation behaviors Equal channel angular pressing Severe plastic deformation

It is Time for a Change： opetri Dishes Weaken Cells

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Journal of Bionic Engineering 2012年第3期9卷 353-357页

作者： Andrei p. Sommer Mike Kh. Haddad hans-Joerg Fecht Institute of Micro and Nanomaterials University of Ulm 89081 Ulm Germany Institute for Nanotechnology Karlsruhe Institute for Technology 76344 Eggenstein-Leopoldshafen Germany

We wish to draw the attention to a potential deficiency in the biocompatibility of polystyrene cell culture dishes which is caused by a softening of the material under relevant culture conditions. The finding confirms the central hypothesis of our previous model study. In it we assumed a local increase in pH at the interface between the hydrophilic polymer and liquid. The finding is of considerable biological interest. polystyrene tissue culture dishes are now in use for 50 years. To the best of our knowledge their biocompatibility has never been challenged. Here we report the first experimental proof that exposure to water softens the surface of polystyrene petri dishes. We expect that our results will stimulate the development of a new generation of cell culture devices, including petri dishes and culture flasks, and the establishment of improved biomimetic settings for tissue engineering and stem cell research. New non-swelling biomaterials or nanocoatings designed to reduce the swelling of polymer ct, lture dishes could improve cell performance. The need for further study is clear.

关键词： petri dish polystyrene biomimetic triangle nanoindentation stem cells diamond

The Top of the Biomimetic Triangle

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Journal of Bionic Engineering 2008年第2期5卷 91-94页

作者： Andrei p. Sommer Dan Zhu Matthias Wiora hans-Joerg Fecht Institute of Micro and Nanomaterials University of Ulm Ulm 89081 Germany Institute for Nanotechnology Forschungszentrum Karlsruhe Karlsruhe 76021 Germany

There is increasing observational evidence indicating that crystalline interfacial water layers play a central role in evolution and biology. For instance in cellular recognition processes, in particular during first contact events, where cells decide upon survival or entering apoptosis. Understanding water layers is thus crucial in biomedical engineering, specifically in the design of biomaterials inspired by biomimetic principles. Whereas there is ample experimental evidence for crystalline interfacial water layers on surfaces in air, their subaquatic presence could not be verified directly, so far. Analysing a polarity dependent asym- metry in the surface conductivity on hydrogenated nanocrystalline diamond, we show that crystalline interfacial water layers persist subaquatically. Nanoscopic interfacial water layers with an order different from that of bulk water have been identified at room temperature on both hydrophilic and hydrophobic model surfaces - in air and subaquatically. Their generalization and systematic inclusion into the catalogue of physical and chemical determinants of biocompatibility complete the biomimetic triangle.

关键词： biomimetic triangle crystalline interfacial water layers nanobionics diamond

Evidence for the polyphyly of Encoelia and Encoelioideae with reconsideration of respective families in leotiomycetes

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Fungal Diversity 2017年第1期82卷 183-219页

作者： Kadri pärtel hans-Otto Baral Heidi Tamm Kadri põldmaa Institute of Ecology and Earth Sciences University of TartuLai 40EE-51005 TartuEstonia Mycological Collections Institute of Agricultural and Environmental SciencesEstonian University of Life SciencesTartuEstonia Blaihofstraße 42 72074 TübingenGermany

this study focuses on the genus Encoelia and the subfamily Encoelioideae in the morphologically and ecologically diverse *** 28S and 18S rDNA as well as tef1,rpb1 and rpb2 were sequenced for 70 *** analyses revealed Encoelia and Encoelioideae to be highly polyphyletic,with species distributed among eight major *** fascicularis and *** belonged to Sclerotiniaceae and were combined in a new genus,*** comprised *** and Dencoeliopsis johnstonii,both accepted in *** type of Encoelia,***,was closely related to species of Velutarina,Cenangiopsis and *** species together with members of Hemiphacidiaceae formed a clade conforming to the emended concept of Cenangiaceae,introduced *** resurrected family,Cordieritidaceae,comprised ***,*** and species of Ameghiniella,Cordierites,Diplocarpa and Ionomidotis,characterised by inamyloid asci and a positive ionomidotic *** glauca showed closest affinities with Chlorociboria species in Chlorociboriaceae.A new genus,Xeropilidium,with sporodochial and pycnidial synanamorphs,was described for the distinct encoelioid member of the Chaetomellaceae,previously known as *** and ecological synapomorphies were distinguished from convergent characters to delimit monophyletic taxa including encoelioid *** of public sequences from various biological samples in ITS rDNA analyses allowed identification of sequenced organisms at species,genus,or family level and added information on the ecology of seversal *** of Cenangiaceae appeared to be widespread as *** of encoelioid genera in Chaetomellaceae and Sclerotiniaceae added xylicolous saprotrophs to these families.

关键词： Environmental sequencing Fungicolous ascomycetes Helotiaceae lichenicolous fungi Forest pathogens Taxonomy

A solution to the hydrodynamic lubrication of a circular point contact sliding over a flat surface with cavitation

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Theoretical & Applied Mechanics letters 2012年第3期2卷 62-64页

作者： hans B.lfgren Functional Surfaces Research Group School of Business and EngineeringUniversity of HalmstadP.O.Box 823SE-301 18 HalmstadSweden

this letter presents an analytical solution to the hydrodynamic lubrication of a circular point contact sliding over a flat surface with *** solution is found by solving the Reynolds equation with Reynolds boundary condition for *** cavitation boundary is shown to be straight lines directed 108.4°against the sliding *** result is experimentally verified in the limit of large values of viscosity,sliding velocity and radius of a spherical *** solution raises questions about the coupling between cavitation and film rupture and can be used as an independent check on the validity of numerical solutions.

关键词： Reynolds equation analytical solution cavitation point contact