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Rbfox1 controls alternative splicing of focal adhesion genes in cardiac muscle cells

Journal of Molecular Cell Biology 2024年第1期16卷 54-65页

作者： Peter Zorn Jaime Calvo Sánchez Tala Alakhras Barbara Schreier Michael Gekle stefan hüttelmaier Marcel Köhn Junior Group‘Non-coding RNAs and RBPs in human Diseases’ Medical FacultyUniversity of Halle–Wittenberg06120 Halle(Saale)Germany Julius Bernstein Institute of Physiology Medical FacultyUniversity of Halle–Wittenberg06112 Halle(Saale)Germany Institute of Molecular Medicine Medical FacultyUniversity of Halle–Wittenberg06120 Halle(Saale)Germany

Alternative splicing is one of the major cellular processes that determine the tissue-specific expression of protein ***,it remains challenging to identify physiologically relevant and tissue-selective proteins that are generated by alternative ***,we investigated the target spectrum of the splicing factor Rbfox1 in the cardiac muscle context in more *** using a combination of in silico target prediction and in-cell validation,we identified several focal adhesion proteins as alternative splicing targets of *** focused on the alternative splicing patterns of vinculin(metavinculin isoform)and paxillin(extended paxillin isoform)and identified both as potential Rbfox1 *** analyses suggested that both isoforms are promoted by Rbfox1 due to binding in the *** adhesions play an important role in the cardiac muscle context,since they mainly influence cell shape,cytoskeletal organization,and cell–matrix *** data confirmed that depletion of Rbfox1 changed cardiomyoblast morphology,cytoskeletal organization,and multinuclearity after differentiation,which might be due to changes in alternative splicing of focal adhesion ***,our results indicate that Rbfox1 promotes alternative splicing of focal adhesion genes in cardiac muscle cells,which might contribute to heart disease progression,where downregulation of Rbfox1 is frequently observed.

关键词： Rbfox1 alternative splicing focal adhesion cardiac muscle cells

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POLIII-derived non-coding RNAs acting as scaffolds and decoys

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Journal of Molecular Cell Biology 2019年第10期11卷 880-885页

作者： hendrikTauber stefan huttelmaier Marcel Kohn Institute of Molecular Medicine Section for Molecular Cell BiologyFaculty of MedicineMartin Luther University Halle-WittenbergCharles Tan ford Protein CentreKurt-Mothes-Str.3a06120 HalleGermany Julius Bernstein Institute of Physiology Faculty of MedicineMartin Luther University Halle-WittenbergCharles Tan ford Protein CentreKurt-Mothes-Str.3a06120 HalleGermany

A large variety of eukaryotic small structured POLIII-derived non-coding RNAs(ncRNAs)have been described in the ***,for only few,e.g.7SL and h1/MRP families,cellular functions are well *** the vast majority of these transcripts,cellular functions remain *** findings on the role ofY RNAs and other POLIII-derived ncRNAs suggest an evolutionarily conserved function of these ncRNAs in the assembly and function of ribonucleoprotein complexes(RNPs).These RNPs provide cellular‘machineries’,which are essential for guiding the fate and function of a variety of *** this review,we summarize current knowledge on the role of POLIII-derived ncRNAs in the assembly and function of *** propose that these ncRNAs serve as scaffolding factors that‘chaperone’RNA-binding proteins(RBPs)to form functional *** addition or associated with this role,some small ncRNAs act as molecular decoys impairing the RBP-guided control of RNA fate by competing with other RNA *** suggests that POLIII-derived ncRNAs serve essential and conserved roles in the assembly of larger RNPs and thus the control of gene expression by indirectly guiding the fate of mRNAs and IncRNAs.

关键词： ncRNA POLIII RBP scaffold RBP decoy

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Experimental investigation on slip conditions during thread rolling with flat dies

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Friction 2024年第1期12卷 136-143页

作者： stefan VOLZ Peter GROChE Institute for Production Engineering and Forming Machines Technical University DarmstadtOtto-Berndt Straße 2Darmstadt 64287Germany

The process design of flat die rolling operations can be a tedious and costly process due to the challenges posed by small process *** this work,an effort is made to closely investigate and understand the process limits caused by excessive slippage of the *** measurements are carried out to capture the characteristics of excessive slippage and the influence of the stroke rate and the tribological system on this process *** differences in slippage were observed,depending on the tribological *** systems with polymer based lubricants showed excessive slippage at low stroke rates,systems using oil or no lubricant endured higher stroke rates before process limits were *** optical measurements revealed three major forms of slippage:successful rolling without slippage,failure due to excessive slippage at process start,and failure due to excessive slippage at around one workpiece rotation.

关键词： rolling incremental forming thread rolling slippage profile rolling

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Deformable microlaser force sensing

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Light(Science & Applications) 2024年第6期13卷 1196-1209页

作者： Eleni Dalaka Joseph Shill Jonathan h.h.Booth Anna Popczyk stefan R.Pulver Malte C.Gather Marcel Schubert Centre of Biophotonics SUPASchool of Physics and AstronomyUniversity of St AndrewsNorth HaughSt AndrewsUK humboldt Centre for Nano-and Biophotonics Department of ChemistryUniversity of CologneKölnGermany School of Psychology and Neuroscience University of St AndrewsSt Mary’s QuadSouth StreetSt AndrewsUK Institute for Bioengineering of Catalonia BarcelonaSpain

Mechanical forces are key regulators of cellular behavior and function,affecting many fundamental biological processes such as cell migration,embryogenesis,immunological responses,and pathological *** force sensors and imaging techniques have been developed to quantify these otherwise invisible forces in single cells and in ***,current techniques rely heavily on high-resolution microscopy and do not allow interrogation of optically dense tissue,reducing their application to 2D cell cultures and highly transparent biological ***,we introduce DEFORM,deformable microlaser force sensing,a spectroscopic technique that detects sub-nanonewton forces with unprecedented spatio-temporal *** is based on the spectral analysis of laser emission from dye-doped oil microdroplets and uses the force-induced lifting of laser mode degeneracy in these droplets to detect nanometer *** validation by atomic force microscopy and development of a model that links changes in laser spectrum to applied force,DEFORM is used to measure forces in 3D and at depths of hundreds of microns within tumor spheroids and late-stage Drosophila *** furthermore show continuous force sensing with single-cell spatial and millisecond temporal resolution,thus paving the way for non-invasive studies of biomechanical forces in advanced stages of embryogenesis,tissue remodeling,and tumor invasion.

关键词： invasion otherwise hundreds

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The big data challenge-and how polypharmacology supports the translation from pre-clinical research into clinical use against neurodegenerative diseases and beyond

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Neural Regeneration Research 2024年第8期19卷 1647-1648页

作者： Sven Marcel stefan Muhammad Rafehi Drug Development and Chemical Biology Lübeck Institute of Experimental Dermatology(LIED)University of Lübeck and University Medical Center Schleswig-HolsteinLübeckGermany Department of Pathology Section of NeuropathologyTranslational Neurodegeneration Research and Neuropathology LabUniversity of Oslo and Oslo University HospitalOsloNorway School of Medical Sciences Faculty of Medicine and HealthUniversity of SydneySydneyNSWAustralia Institute of Clinical Pharmacology University Medical Center GöttingenGöttingenGermany Department of Medical Education Augsburg University MedicineAugsburgGermany

Introductory comments:The identification and validation of disease-modifying proteins are fundamental aspects in drug ***,the m ultifactority of n eurodegen era tive diseases poses a real challenge for targeted ***,the behavior of individually(over-)expressed to rget proteins in vitro is likely to differ from their actual functional behavior when embedded in cascades and pathways in vivo.

关键词： translation beyond likely

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Implementation and validation of a bonded particle model to predict rheological properties of viscoelastic materials

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Particuology 2024年第6期89卷 198-210页

作者： Michael Mascara Arno Mayrhofer stefan Radl Christoph Kloss Institute of Process and Particle Engineering Graz University of TechnologyInffeldgasse 13Graz8010Austria DCS Computing Gmbh Industriezeile 35Linz4020Austria

This work focuses on implementing a particle-based method able to characterize viscoelastic materials whose rheological properties,such as storage modulus G′and loss modulus G″,are *** is based on the bonded particle model,with the elastic constitutive relation here substituted with a viscoelastic one to capture time-scale *** Burgers model,vastly used in literature to model viscoelastic systems,is discretized and *** test case used for calibration comprises of a cubic lattice,sheared with a periodic motion,to mimic the effect of a shear *** appropriate filtering of the stress response,the rheological properties are obtained,highlighting the effect of the lattice geometry,as well as the particle size,on the accuracy of the ***,the Burgers parameters are calibrated by analytically fitting the experimental dataset,showing the limitation of the Burgers *** micro-contact parameters are obtained from the macro parameters through appropriate *** completing a frequency sweep,the simulated G′and G″show a relatively large error,around 25%for G’for *** this reason,a more robust model,namely the generalized Maxwell model,has been *** calibration procedure is performed in the same fashion as for the Burgers ***,the tangential micro-contact parameters are scaled *** normal *** scaling parameter,calledα,is calibrated by minimizing the root mean square error between simulation and experimental data,giving errors below 10%in both G′and G″for a large ***,a full ring plate-plate rheometer setup is simulated,and the simulation is compared with the given experimental dataset,again finding a good agreement.

关键词： DEM Rheology Numerical modeling Viscoelasticity

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In situ characterization of particle formation in spray flame synthesis using wide-angle light scattering

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Particuology 2024年第3期86卷 304-312页

作者： Simon Aβmann Franz J.T.huber stefan Will Lehrstuhl für Technische Thermodynamik(LTT) Friedrich-Alexander-Universitat Erlangen-Nürnberg(FAU)Erlangen91058Germany Erlangen Graduate Schoolin Advanced Optical Technologies(SAOT) Friedrich-Alexander-Universitat Erlangen-Nurnberg(FAU)Erlangen91052Germany Competence Unit Engineering of Advanced Materials(EAM) Friedrich-Alexander-Universitat Erlangen-Nürnberg(FAU)Erlangen91052Germany

Wide-angle light scattering(WALS)was used for in situ measurements of droplet and nanoparticle size distributions during the synthesis of titania and iron oxide particles from liquid precursor solutions in the standardized SpraySyn burner for spray flame *** was synthesized from titanium tetraisopropoxide(TTIP)and iron oxide from iron(II)nitrate nonahydrate(INN)using ethanol(EtOh)as *** images were taken at heights up to 120 mm above the burner surface and classified into droplet and particle *** size distributions were derived from a sequential analysis of scattering data containing the oscillating Mie pattern,the lognormal size distribution parameters for spherical and fractal particle fractions from a multivariate approach on averaged particle scattering *** results show that the precursor addition leads to altered evaporation behavior and even droplet disruption probably induced by puffing or micro-explosions compared to pure *** the case of TTIP(a hygroscopic alkoxide),the synthesis of a large fraction of spheres was observed,while the nitrate INN leads to the formation of mostly fractal aggregates.

关键词： Spray flame synthesis Metal oxide particles Elastic light scattering Droplet size distribution Nanoparticle morphology Particle size distribution

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Artificial intelligence analysis of videos to augment clinical assessment:an overview

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Neural Regeneration Research 2024年第4期19卷 717-718页

作者： David C.Wong stefan Williams University of Leeds Leeds Teaching hospitals Trust LeedsUK

Observation is a fundamental part of the practice of clinical *** of movement is particularly important for the *** such as Parkinson’s disease,multiple sclerosis,stroke,epilepsy,and many others affect a person’s movement in characteristic *** some conditions,changes in the patient’s voice can be included in this-changes in sound caused by changes in the movements of *** clinician’s detection of a characteristic abnormality,and their judgment of its severity,plays a central role in both diagnosis and the assessment of prognosis or response to ***,that practice depends upon a limited resource of experienced *** addition,these experts are limited by human visual judgment,which cannot reliably or precisely detect and measure small or subtle changes in movement(Williams et al.,2023).

关键词： clinical epilepsy diagnosis

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Modulation of the Nogo signaling pathway to overcome amyloid-β-mediated neurite inhibition in human pluripotent stem cell-derived neurites

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Neural Regeneration Research 2025年第9期20卷 2645-2654页

作者： Kirsty Goncalves stefan Przyborski Department of Biosciences Durham UniversityDurhamUK Reprocell Europe Ltd. GlasgowUK

Neuronal cell death and the loss of connectivity are two of the primary pathological mechanisms underlying Alzheimer's *** accumulation of amyloid-βpeptides,a key hallmark of Alzheimer's disease,is believed to induce neuritic abnormalities,including reduced growth,extension,and abnormal growth cone morphology,all of which contribute to decreased ***,the precise cellular and molecular mechanisms governing this response remain *** this study,we used an innovative approach to demonstrate the effect of amyloid-βon neurite dynamics in both two-dimensional and three-dimensional cultu re systems,in order to provide more physiologically relevant culture *** utilized various methodologies,including the addition of exogenous amyloid-βpeptides to the culture medium,growth substrate coating,and the utilization of human-induced pluripotent stem cell technology,to investigate the effect of endogenous amyloid-βsecretion on neurite outgrowth,thus paving the way for potential future applications in personalized ***,we also explore the involvement of the Nogo signaling cascade in amyloid-β-induced neurite *** demonstrate that inhibition of downstream ROCK and RhoA components of the Nogo signaling pathway,achieved through modulation with Y-27632(a ROCK inhibitor)and Ibuprofen(a Rho A inhibitor),respectively,can restore and even enhance neuronal connectivity in the presence of amyloid-β.In summary,this study not only presents a novel culture approach that offers insights into the biological process of neurite growth and inhibition,but also proposes a specific mechanism for reduced neural connectivity in the presence of amyloid-βpeptides,along with potential intervention points to restore neurite ***,we aim to establish a culture system that has the potential to serve as an assay for measuring preclinical,predictive outcomes of drugs and their ability to promote neurite outgrowth,both generally and in a patie

关键词： Alzheimer's disease induced pluripotent stem cell neurite outgrowth neuron Nogo Rho A ROCK stem cell three-dimensional culture

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A theoretical framework for improved fire suppression by linking management models with smart early fire detection and suppression technologies

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Journal of Forestry Research 2024年第5期35卷 1-13页

作者： Li Meng Jim O’hehir Jing Gao stefan Peters Anthony hay University of South Australia AdelaideSAAustralia Esk Spatial InvermayTASAustralia

Bushfires are devastating to forest managers,owners,residents,and the natural *** tech-nological advances indicate a potential for faster response times in terms of detecting and suppressing ***,to date,all these technologies have been applied in *** paper introduces the latest fire detection and sup-pression technologies from ground to *** operations research method was used to assemble these technologies into a theoretical framework for fire detection and *** framework harnesses the advantages of satellite-based,drone,sensor,and human reporting technologies as well as image processing and artificial intelligence machine *** study concludes that,if a system is designed to maximise the use of available technologies and carefully adopts them through complementary arrangements,a fire detection and resource suppression system can achieve the ultimate aim:to reduce the risk of fire hazards and the dam-age they may cause.

关键词： Forest fire Resource suppression Smart fire detection and suppression system Forest fire management holistic system

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