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Calcium channels caught in peripheral glia’s tug-of-war on axon regeneration in Drosophila

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Neural Regeneration Research 2025年第2期20卷 475-476页

作者： Jackson Powell tobias Steinschaden Rose Horowitz Yuanquan Song Raymond G.Perelman Center for Cellular and Molecular Therapeutics The Children’s Hospital of PhiladelphiaPhiladelphiaPAUSA The Neuroscience Graduate Group University of PennsylvaniaPhiladelphiaPAUSA Department of Pathology and Laboratory Medicine University of PennsylvaniaPhiladelphiaPAUSA Medical University of Vienna Center for Brain ResearchDepartment of NeuroimmunologyViennaAustria

Neural damage or degeneration is at the crux of many diseases,and treatment of these diseases will require the development of therapeutics to enhance and guide neural *** intrinsic and extrinsic factors dictate a neuron’s ability to regenerate,and the combination of these factors results in the great regenerative capacity of the peripheral nervous system(PNS)and the poor regenerative capacity of the central nervous system(CNS)following *** the core of a neuron’s function is its ability to relay electrochemical signals,and a neuron’s excitability is a key factor in its ability to *** works have focused on the changes in neuronal electrophysiological properties,firing patterns,and ion flux after injury,which differentially activate signaling pathways at the core of *** role of glia in neuron regeneration has long been studied.

关键词： degeneration firing system

Regression analysis of squeezing-induced hybrid nanofluid flow in Darcy-Forchheimer porous medium

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Applied Mathematics and Mechanics(English Edition) 2025年第1期46卷 193-208页

作者： k.MUHAMMAD M.SARFRAZ Department of Humanities and Sciences School of Electrical Engineering and Computer Science National University of Sciences and Technology Department of Mathematics Quaid-i-Azam University

This article presents a mathematical model addressing a scenario involving a hybrid nanofluid flow between two infinite parallel plates. One plate remains stationary, while the other moves downward at a squeezing velocity. The space between these plates contains a Darcy-Forchheimer porous medium. A mixture of water-based fluid with gold(Au) and silicon dioxide(Si O2) nanoparticles is formulated. In contrast to the conventional Fourier's heat flux equation, this study employs the Cattaneo-Christov heat flux equation. A uniform magnetic field is applied perpendicular to the flow direction, invoking magnetohydrodynamic(MHD) effects. Further, the model accounts for Joule heating, which is the heat generated when an electric current passes through the fluid. The problem is solved via NDSolve in MATHEMATICA. Numerical and statistical analyses are conducted to provide insights into the behavior of the nanomaterials between the parallel plates with respect to the flow, energy transport, and skin *** findings of this study have potential applications in enhancing cooling systems and optimizing thermal management strategies. It is observed that the squeezing motion generates additional pressure gradients within the fluid, which enhances the flow rate but reduces the frictional drag. Consequently, the fluid is pushed more vigorously between the plates, increasing the flow velocity. As the fluid experiences higher flow rates due to the increased squeezing effect, it spends less time in the region between the plates. The thermal relaxation, however, abruptly changes the temperature, leading to a decrease in the temperature fluctuations.

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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

Modularization of adhesion G protein-coupled receptor(aGPCR)structure:how alternative splicing regulates synaptogenesis

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1793-1795页

作者： tobias Langenhan Rudolf Schönheimer Institute of Biochemistry Division of General BiochemistryMedical FacultyLeipzig UniversityLeipzigGermany Comprehensive Cancer Center Central Germany(CCCG) Leipzig UniversityLeipzigGermany Institute of Biology Faculty of Life SciencesLeipzig UniversityLeipzigGermany

A recent report has uncovered a fascinating aspect of how neurons utilize alternative splicing of transcripts of an adhesion G protein-coupled receptor(aGPCR)gene to serve specific functions in the life of a synapse.1 The work provides significant insight into the ability of cells to support distinct biochemical and physiological operations through post-transcriptional processing of genetic information that is encoded in a single aGPCR locus.

关键词： GPCR utilize operations

Targeting the EGF receptor family in non-small cell lung cancerincreased complexity and future perspectives

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Cancer Biology & Medicine 2022年第11期19卷 1543-1564页

作者： tobias Boch Jens kohler Melanie Janning Sonja Loges DkFZ-Hector Cancer Institute at the University Medical Center Mannheim Mannheim 68135Germany Division of Personalized Medical Oncology(A420) German Cancer Research Center(DKFZ)Heidelberg 69120Germany Department of Personalized Oncology University Medical Center MannheimMedical Faculty MannheimHeidelberg UniversityMannheim 68135Germany

Lung cancer remains the leading cause of cancer-associated mortality worldwide,but with the emergence of oncogene targeted therapies,treatment options have tremendously *** to their biological relevance,members of the ERBB receptor family,including the EGF receptor(EGFR),HER2,HER3 and HER4,are among the best studied oncogenic *** EGFR mutations are frequently observed in non-small cell lung cancer(NSCLC),and small molecule tyrosine kinase inhibitors(TkIs)are the established first line treatment option for patients whose tumors bear"typical/classical"EGFR mutations(exon 19 deletions,L858R point mutations).Additionally,new TkIs are rapidly evolving with better efficacy to overcome primary and secondary treatment resistance(e.g.,that due to T790M or C797S resistance mutations).Some atypical EGFR mutations,such as the most frequent exon 20 insertions,exhibit relative resistance to earlier generation TkIs through steric *** this subgroup,newer TkIs,such as mobocertinib and the bi-specific antibody amivantamab have recently been approved,whereas less frequent atypical EGFR mutations remain *** contrast to EGFR,HER2 has long remained a challenging target,but better structural understanding has led to the development of newer generations of *** recent FDA approval of the antibody-drug conjugate trastuzumab-deruxtecan for pretreated patients with HER2 mutant NSCLC has been an important therapeutic ***3 and HER4 also exert oncogenic potential,and targeted treatment approaches are being developed,particularly for ***,strategies to inhibit the oncogenic function of ERBB receptors in NSCLC are currently evolving at an unprecedented pace;therefore,this review summarizes current treatment standards and discusses the outlook for future developments.

关键词： Oncology NSCLC EGFR HER2 HER3 HER4

Human endogenous retrovirus type-W and multiple sclerosis–related smoldering neuroinflammation

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Neural Regeneration Research 2025年第3期20卷 813-814页

作者： Joel Gruchot Laura Reiche Andrew Chan Robert Hoepner Patrick küry Department of Neurology Medical Faculty and University Hospital DüsseldorfHeinrich Heine University DüsseldorfDüsseldorfGermany Department of Neurology InselspitalBern University Hospital and University of BernBernSwitzerland

Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.

关键词： endogenous inflammation Human

Nucleoside modified mRNA-lipid nanoparticles as a new delivery platform for the repair of the injured spinal cord

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Neural Regeneration Research 2025年第8期20卷 2311-2312页

作者： krisztián Pajer Tamás Bellák Antal Nógrádi Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary

Spinal cord injury and treatment opportunities:The adult mammalian spinal cord has a very limited capacity for spontaneous regeneration due to various intrinsic molecular and cellular *** the spinal cord neurons have the capacity to regenerate their axons,the expression of growth inhibitory factors,lack or suppression of proper guidance cues,and profound inflammatory responses do not permit successful regeneration(khyeam et al.,2021).

关键词： injured capacity modified

Second-generation trabecular micro-bypass stent implantation: Retrospective analysis after 12- and 24-month follow-up

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Eye and Vision 2020年第1期7卷 1-10页

作者： Raphael Neuhann tobias Neuhann Neuhann Augentagesklinik MarienplatzMarienplatz 18-1980331 MunichGermany

Background:The study aimed to investigate the 24-month safety and efficacy of implantation of two secondgeneration iStent inject trabecular micro-bypass stents with concomitant cataract ***:This consecutive case series included 164 eyes of 109 patients implanted with the iStent inject®device with concomitant cataract *** series was comprised of eyes with primary open-angle glaucoma(n=84),pseudoexfoliation glaucoma(n=42),normal-tension glaucoma(n=18),and ocular hypertension(n=20).All 164 eyes reached 9–14 months of follow-up(“12-month consistent cohort”),with a subset of 88 eyes reaching 21–26 months of follow-up(“24-month consistent cohort”).Performance outcome measures included intraocular pressure(IOP)and number of glaucoma *** outcomes included intra-or postoperative complications,the need for secondary procedures and corrected distance visual *** of change in continuous(e.g.,IOP)and categorical(e.g.,proportions of eyes on zero medications)measures between baseline and postoperative times were made with the paired t-test and McNemar’s chi-squared test,***:At 12 months postoperatively,IOP was reduced by 25.5%(from 20.0±5.5 mmHg to 14.9±2.0 mmHg;p<0.001);at 24 months postoperatively,IOP was reduced by 26.6%(from 20.3±6.1 mmHg to 14.9±1.9 mmHg;p<0.001).At 12 months postoperatively,mean number of glaucoma medications was reduced by 85.0%(from 2.0±1.0 to 0.3±0.8 medications;p<0.001);at 24 months postoperatively,mean number of medications was reduced by 81.0%(from 2.1±1.1 to 0.4±0.8 medications;p<0.001).After 12 months,96.3%of eyes had an IOP≤18 mmHg and 58.5%of eyes had an IOP≤15 mmHg,with 81.1%of eyes free of any medication,compared to 1.8%of eyes medication-free in the 12-month cohort at *** 24 months,98.9%of eyes had an IOP≤18 mmHg and 53.4%of eyes had an IOP≤15 mmHg,with 72.7%free of medication compared to 1.1%of eyes medication-free in the 24-month cohort at ***,a high safe

关键词： Glaucoma MIGS IStent inject Trabecular Safety Stent Bypass

Large-scale Data Collection and Analysis via a Gamified Intelligent Crowdsourcing Platform

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International Journal of Automation and computing 2019年第4期16卷 427-436页

作者： Simone Hantke tobias Olenyi Christoph Hausner tobias Appel Bjorn Schuller ZD.B Chair of Embedded Intelligence for Health Care and Wellbeing University of Augsburg Germany Machine Intelligence & Signal Processing Group Technische Universitat München München Germany audEERING GmbH Gilching Germany Group on Language Audio & Music (GLAM) Department of Computing Imperial College London SW7 2AZ UK

In this contribution, we present iHEARu-PLAY, an online, multi-player platform for crowdsourced database collection and labelling, including the voice analysis application (VoiLA), a free web-based speech classification tool designed to educate iHEARu-PLAY users about state-of-the-art speech analysis paradigms. Via this associated speech analysis web interface, in addition, VoiLA encourages users to take an active role in improving the service by providing labelled speech data. The platform allows users to record and upload voice samples directly from their browser, which are then analysed in a state-of-the-art classification pipeline. A set of pre-trained models targeting a range of speaker states and traits such as gender, valence, arousal, dominance, and 24 different discrete emotions is employed. The analysis results are visualised in a way that they are easily interpretable by laymen, giving users unique insights into how their voice sounds. We assess the effectiveness of iHEARu-PLAY and its integrated VoiLA feature via a series of user evaluations which indicate that it is fun and easy to use, and that it provides accurate and informative results.

关键词： Human computation speech analysis crowdsourcing gamified data collection survey