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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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Hepatitis C virus core antigen testing: Role in diagnosis, disease monitoring and treatment

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World Journal of Gastroenterology 2014年第22期20卷 6701-6706页

作者： hans l Tillmann GI/Hepatology Duke Clinical Research Institute and Duke UniversityDurhamNC 27708United States

While hepatitis B virus(HBV)screening relies on hepatitis B surface antigen to confirm HBV infection since the early days of hepatitis B disease management,hepatitis C virus(HCV)infection screening is based on anti-HCV testing which does not discriminate active from past *** to confirm infection HCV RNA testing has been required;recently a HCV core antigen assay became widely commercially available which could serve to confirm *** assay is less sensitive than current HCV RNA assays,but as more than 50%of anti-HCV positive persons will be HCV core antigen positive,HCV core antigen testing can be a cost effective and reflex test to confirm HCV infection in anti-HCV positive individuals and will be easier as it can be applied on the same *** treatment monitoring,more data need to be generated,but the early data available at present suggest that HCV core antigen may be an alternative to HCV RNA *** direct antivirals,HCV core antigen could even be superior to HCV RNA testing,as direct antivirals might already prevent virus formation when HCV core antigen is still produced and thereby correlates better with eventual viral clearance.

关键词： Hepatitis C virus Hepatitis C Diagnostic assay Diagnostic accuracy Hepatitis C virus core antigen Treatment monitoring

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Towards engineering a portable platform for laparoscopic pre-training in virtual reality with haptic feedback

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虚拟现实与智能硬件（中英文） 2024年第2期6卷 83-99页

作者： hans-Georg ENKlER Wolfgang KUNERT Stefan PFEFFER Kai-Jonas bock Steffen AXT Jonas JOHANNINK Christoph REICH Furtwangen University 78120 FurtwangenGermany University Hospital and Faculty of Medicine Tuebingen 72076 TuebingenGermany

Background laparoscopic surgery is a surgical technique in which special instruments are inserted through small incision holes inside the *** some time,efforts have been made to improve surgical pre training through practical exercises on abstracted and reduced *** The authors strive for a portable,easy to use and cost-effective Virtual Reality-based(VR)laparoscopic pre-training platform and therefore address the question of how such a system has to be designed to achieve the quality of today's gold standard using real tissue *** VR controllers are limited regarding haptic *** haptic feedback is necessary or at least beneficial for laparoscopic surgery training,the platform to be developed consists of a newly designed prototype laparoscopic VR controller with haptic feedback,a commercially available head-mounted display,a VR environment for simulating a laparoscopic surgery,and a training *** To take full advantage of benefits such as repeatability and cost-effectiveness of VR-based training,the system shall not require a tissue sample for haptic *** is currently calculated and visually displayed to the user in the VR *** the prototype controller,a first axis was provided with perceptible feedback for test *** of the prototype VR controllers can be combined to simulate a typical both-handed use case,e.g.,laparoscopic suturing.A Unity based VR prototype allows the execution of simple standard *** The first prototype enables full operation of a virtual laparoscopic instrument in *** addition,the simulation can compute simple interaction *** challenges lie in a realistic real-time tissue simulation and calculation of forces for the haptic *** weaknesses were identified in the first hardware prototype,which will be improved in subsequent *** degrees of freedom of the controller are to be provided with haptic *** make forces t

关键词： laparoscopic surgery Training Virtual reality Controller Haptic feedback Kinesthetic skills

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Novel stable isotope concepts to track antibiotics in wetland systems

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Journal of Environmental Sciences 2024年第12期146卷 298-303页

作者： Xiao liu Junya Zhang hans Hermann Richnow Gwenaël Imfeld Institut Terre et Environnement de Strasbourg(ITES) Universitéde Strasbourg/EOST/ENGEESCNRS UMR 7063F-67084 StrasbourgFrance State Key Joint laboratory of Environmental Simulation and Pollution Control Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China Department of Technical Biogeochemistry Helmholtz Centre for Environmental Research-UFZPermoserstraße 1504318 LeipzigGermany Isodetect GmbH Deutscher Platz 5b04103 LeipzigGermany

Antibiotics,their transformation products,and the translocation of antibiotic-resistant genes in the environment pose significant health risks to humans,animals,and ecosystems,aligning with the One Health *** wetlands hold substantial yet underutilized potential for treating wastewater from agricultural,domestic sewage,or contaminated effluents from wastewater treatment plants,with the goal of eliminating ***,the comprehensive understanding of the distribution,persistence,and dissipation processes of antibiotics within constructed wetlands remains largely *** this context,we provide an overview of the current application of stable isotope analysis at natural abundance to *** explore the opportunities of an advanced multiple stable isotope approach,where isotope concepts could be effectively applied to examine the fate of antibiotics in *** development of a conceptual framework to study antibiotics in wetlands using multi-element stable isotopes introduces a new paradigm,offering enhanced insights into the identification and quantification of natural attenuation of antibiotics within wetland *** perspective has the potential to inspire the general public,governmental bodies,and the broader research community,fostering an emphasis on the utilization of stable isotope analysis for studying antibiotics and other emerging micropollutants in wetland systems.

关键词： Constructed wetlands Micropolluants Antibiotics Degradation,CSIA

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Intestinal organoids as tools for enriching and studying specific and rare cell types:advances and future directions

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Journal of Molecular Cell Biology 2020年第8期12卷 562-568页

作者： Kim E.Boonekamp Talya l.Dayton hans Clevers Oncode Institute Hubrecht InstituteRoyal Netherlands Academy of Arts and Sciences(KNAW)and University Medical Centre(UMC)Utrecht358A CT UtrechtThe Netherlands Princess Maxima Centre for Paediatric Oncology 358A CS UtrechtThe Netherlands

Adult tissue-derived organoids allow for the expansion and maintenance of primary epithelial cells in a near-native *** 3D and self-organizing organotypic cultures derived from adult tissues have been increasingly used in fundamental and translational research.A key feature of this organoid system is that it recapitulates the stem cell lineage and thus,the differentiated cell-type heterogeneity of the in vivo tissue of origin.

关键词： directions organo rare

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Community-based cross-sectional seroprevalence study of hepatitis A in Bangladesh

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World Journal of Gastroenterology 2009年第39期15卷 4932-4937页

作者： Samir K Saha Setarunnahar Saha Salim Shakur Mohammed Hanif Md Ahsan Habib Sanjoy K Datta hans l bock Bangladesh Institute of Child Health Dhaka Shishu Hospital Institute of Public Health Glaxo-SmithKline Biologicals 89 Rue de l'Institut

AIM： TO elucidate the age-distribution of anti-hepatitis A virus （HAY） seroprevalence across different socioeconomic status （SES） categories in Bangladesh which, despite scarce data, is generally deemed to have high endemicity. METHODS： Blood samples of 818 subjects from a stratified samp#e of schools and hospitals, comprising different age categories and SES were collected. They were assayed for total anti-HAV antibodies. Social and medical history data were obtained using a questionnaire. RESUlTS： Overall anti-HAV seroprevalence was 69.6%, increasing with age from 1-5 years （40.4%） to 〉 30 years （98.4%）. Seroprevalence was lowest （49.8%） in the high SES group and highest （96.5%） in the rural lower-middle SES group. Among subjects aged 6-20 years, anti-HAV seroprevalence was lowest in urban private school children （43.0%）, followed by urban government school children （76.2%） and rural school children （96.5%）（P 〈 0.01）. Within the high SESgroup, anti-HAV seroprevalence was 32.3% in subjects 〈 10 years and 51.7% in those aged 11-20 years. Until now Bangladesh has been deemed to have high endemicity for HAV. CONClUSION： The transition from high to intermediate HAV endemicity may be underway; high SES adolescents and adults remain particularly at risk of symptomatic illness. Preventive measures need consideration.

关键词： Age groups Hepatitis A virus Hepatitis A virus seroprevalence Anti-hepatitis A virus antibodies Socioeconomic groups

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Factors affecting trace element content in periurban market garden subsoil in Yunnan Province,China

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Journal of Environmental Sciences 2011年第3期23卷 488-496页

作者： Yanqun zu laurent bock Christian Schvartz Gilles Colinet Yuan li College of Resources and Environment Yunnan Agricultural University Kunming 650201 China laboratory of Soil Science Gembloux Agro-bio Technology University Liege University Gembloux Belgium laboratory of Soil and Environment Institute of Advanced Agriculture Catholic University Lille France

Field investigations were conducted to measure subsoil trace element content and factors influencing content in an intensive periurban market garden in Chenggong County, Yunnan Province, South-West China. The area was divided into three different geomorphological units： specifically, mountain （M）, transition （T） and lacustrine （l）. Mean trace element content in subsoil were determined for Pb （58.2 mg/kg）, Cd （0.89 mg/kg）, Cu （129.2 mg/kg）, and Zn （97.0 mg/kg）. Strong significant relationships between trace element content in topsoil and subsoil were observed. Both Pb and Zn were accumulated in topsoil （RTS （ratio of mean trace element in topsoil to subsoil） of Pb and Zn ≥1.0） and Cd and Cu in subsoil （RTS of Cd and Cu≤1.0）. Subsoil trace element content was related to relief, stoniness, soil color, clay content, and cation exchange capacity. Except for 7.5 YR （yellow-red） color, trace element content increased with color intensity from brown to reddish brown. Significant positive relationships were observed between Fe content and that of Pb and Cu. Trace element content in mountain unit subsoil was higher than in transition and lacustrine units （M 〉 T 〉 l）, except for Cu （T 〉 M 〉 l）. Mean trace element content in calcareous subsoil was higher than in sandstone and shale. Mean trace element content in clay texture subsoil was higher than in sandy and sandy loam subsoil, and higher Cu and Zn content in subsoil with few mottles. It is possible to model Pb, Cd, Cu, and Zn distribution in subsoil physico-chemical characteristics to help improve agricultural practice.

关键词： trace elements subsoil topsoil relationships

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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

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Near-infrared-reflection spectroscopy as measuring method to determine the state of the process for automatic control of anaerobic digestion

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International Journal of Agricultural and Biological Engineering 2013年第2期6卷 63-72页

作者： Andrea Stockl Daniel löffler hans Oechsner Thomas Jungbluth Klaus Fischer Martin Kranert State Institute of Agricultural Engineering and Bioenergy University of Hohenheim70593 Stuttgart-PlieningenGermany Institute for Sanitary Engineering Water Quality and Solid Waste ManagementUniversity of StuttgartBandtäle 270569 StuttgartGermany State Institute of Agricultural Engineering Livestock System EngineeringUniversity of Hohenheim70593 Stuttgart-PlieningenGermany

A recently developed control strategy for the anaerobic digestion process requires secure knowledge about the state of the *** near infrared reflection spectroscopy(NIRS),provides the possibility to determine process parameters of the anaerobic digestion process online and directly at the *** investigate if the NIRS measurements can successfully be used for the characterization of the state of the process within the control strategy the control was operated on two experimental *** NIR spectra were recorded during the *** values of the process parameters(mainly concentrations of organic acids)obtained by NIRS differ from the values of the chemical analyses during the *** the state of the process is categorized equally on the basis of both measurement *** can consequently be stated that NIRS is expected to meet the requirements of the control strategy.

关键词： near-infrared-reflection spectroscopy(NIRS) state of the process automatic process control anaerobic digestion biogas

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Antiviral therapy and resistance with hepatitis B virus infection

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World Journal of Gastroenterology 2007年第1期13卷 125-140页

作者： hans l Tillmann University of leipzig Philipp-Rosenthal Street 27 Leipzig 04103 Germany

Hepatitis B virus （HBV） infection is still the most common cause of hepatocellular carcinoma and liver drrhosis world wide. Recently, however, there has been quite dramatic improvement in the understanding of HBV assodated liver disease and its treatment. It has become dear that high viral replication is a major risk factor for the development of both cirrhosis and hepatocellular carcinoma. Early studies have shown lamivudine lowers the risk of HBV associated complications. There are currently three nucleos（t）ides licensed, in addition to interferon, and there are more drugs coming to the market soon. Interferon or its pegylated counterpart are still the only options for treatment with defined end points, while nudeos（t）ides therapy is used mostly for long term treatment. Combination therapies have not been shown to be superior to monotherapy in naive patients, however, the outcome depends on how the end point is defined. Interferon plus lamivudine achieves a higher viral suppression than either treatment alone, even though Hbe-seroconversion was not different after a one year treatment. HBV-genotypes emerge as relevant factors, with genotypes ＂A＂ and ＂B＂ responding relatively well to interferon, achieving up to 20% HBsAg clearance in the case of genotype ＂A＂. In addition to having a defined treatment duration, interferon has the advantage of lack- ing resistance selection, which is a major drawback for lamivudine and the other nucleos（t）ides. The emergence of resistance against adefovir and entecavir is some- what slower in na＇fve compared to lamivudine resistant patients. Adefovir has a low resistance profile with 3%, 9%, 18%, and 28% after 2, 3, 4, and 5 years, respectively, while entecavir has rarely produced resistance in naive patients for up to 3 years.

关键词： Hepatitis B Antiviral therapy Resistance Interferon Nucleosides Nucleotides

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