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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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A novel homozygous missense variant in ARSk causes MPS X,a new subtype of mucopolysaccharidosis

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Genes & Diseases 2024年第3期11卷 87-90页

作者： Miao Sun Cornelia k.kaminsky Philip Deppe Mai-Brittllse Frederic M.Vaz barbara Plecko Torben Lubke Linda M.Randolph Division of Genomic Medicine Department of Pathology and Laboratory MedicineChildren's Hospital Los Angeles/Keck School of Medicine of USCLos AngelesCA 90027USA Department of Radiology Children's Hospital Los Angeles/Keck School of Medicine of USCLos AngelesCA 90027USA Department of Chemistry BiochemistryBielefeld UniversityBielefeld 33615Germany Amsterdam UMC Location University of Amsterdam Department of Clinical Chemistry and PediatricsLaboratory Genetic Metabolic DiseasesEmma Children's HospitalMeibergdreef 9Amsterdam 1100 DEthe Netherlands Amsterdam Gastroenterology Endocrinology Metabolism Inborn Errors of MetabolismAmsterdam 1105 BKthe Netherlands Core Facility Metabolomics Amsterdam UMC Location University of AmsterdamAmsterdam 1100DDthe Netherlands Department of Pediatrics Division of General PediatricsMedical Universityof GrazGraz8036Austria Division of Medical Genetics Department of PediatricsChildren's Hospital Los Angeles/Keck School of Medicine of USCLos AngelesCA 90027USA

Mucopolysaccharidoses(MPS)are a group of rare inborn errors of metabolism caused by defective lysosomal enzymes which prevent cells from degrading and recycling certain carbohydrates and fats,resulting in the storage of glycosaminoglycans in cells throughout the *** leads to multisystem abnormalities involving bone,connective tissues,brain,blood,spinal cord,skin,and other tissues.

关键词： metabolism doses polys

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Segmented trust assessment in autonomous vehicles via eye-tracking

Journal of Intelligent and Connected Vehicles

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Journal of Intelligent and Connected Vehicles 2024年第2期7卷 151-161页

作者： Miklós Lukovics Szabolcs Prónay barbara Nagy Faculty of Economics and Business Administration University of SzegedSzeged H-6726Hungary

Previous studies have identified trust as one of the key factors in the technology acceptance of autonomousvehicles. As these studies mostly investigated the population in general, little is known about segment-specific ***, the widely used survey methods are less able to capture the deeper forms of trust—which neuroscientificmethods are much better suited to capture. The main objective of our research is to study trust as one of the key factors oftechnology acceptance related to autonomous vehicles by using neuroscientific methods for specific consumer ***-time eye-tracking tests were applied to a sample of 113 participants, combined with a posttest self-report. The testswere carried out under laboratory conditions during which our subjects watched videos recorded with the internal camerasof autonomous vehicles. Based on the fixation count, total fixation duration, and pupil dilation, we empirically verified thatthe trust level of all five identified segments is relatively low, while the trust level of the “traditional rejecting” segment is thelowest. An increase in trust level can be shown if the subjects receive extra information about the journey. Anotherimportant finding is that the self-reported trust level is not always congruent with the eye-tracking analysis results;therefore,combined approaches can lead to greater measurement validity.

关键词： autonomous vehicles(AVs) technology acceptance trust eye-tracking

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Taxonomic dependency and spatial heterogeneity in assembly mechanisms of bacteria across complex coastal waters

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Ecological Processes 2024年第1期13卷 80-97页

作者： Huizhen Yan Dandan Lin Gaoke Gu Yujie Huang Xuya Hu Zhenhao Yu Dandi Hou Demin Zhang barbara J.Campbell kai Wang State key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products School of Marine SciencesNingbo University key Laboratory of Marine Biotechnology of Zhejiang Province School of Marine Sciences Ningbo University Department of Biological Sciences Clemson University

Background Understanding community assembly mechanisms across taxa and space is fundamental for microbial ecology. However, the variability and determinants of assembly processes over taxa and space remain unclear. Here, we investigated taxonomic dependency and spatial heterogeneity in bacterial assembly mechanisms across coastal waters in the East China Sea using neutral and null models with customized visualization *** Overall, bacterial assembly mechanisms varied across broad taxonomic groups(phyla and proteobacterial classes) and space at the regional scale. A determinism–stochasticity balanced mechanism governed total bacterial assembly, while taxonomic dependency existed in assembly mechanisms and ecological processes. Among community ecological features, niche breadth and negative-to-positive cohesion ratio were strongly associated with the determinism-to-stochasticity ratio of bacterial groups. Bacterial assembly mechanisms commonly exhibited spatial heterogeneity, the extent and determinants of which varied across taxonomic groups. Spatial assembly of total bacteria was directly driven by many environmental factors and potential interactions between taxa, but not directly by geographic factors. Overall, the bacterial groups with higher spatial heterogeneity in assembly mechanisms were more related to environmental and/or geographic factors(except Bacteroidetes), while those with lower heterogeneity were more related to ecological *** Our results confirm the pervasiveness of taxonomic dependency and spatial heterogeneity in bacterial assembly, providing a finer understanding about regulation across complex coastal waters.

关键词： Bacterioplankton Assembly mechanism Niche breadth Null model Environmental gradient Biogeography

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CDC7 inhibition impairs neuroendocrine transformation in lung and prostate tumors through MYC degradation

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3519-3532页

作者： Alvaro Quintanal-Villalonga kenta kawasaki Esther Redin Fathema Uddin Swanand Rakhade Vidushi Durani Amin Sabet Moniquetta Shafer Wouter R.karthaus Samir Zaidi Yingqian A.Zhan Parvathy Manoj Harsha Sridhar Dennis kinyua Hong Zhong barbara P.Mello Metamia Ciampricotti Umesh k.Bhanot Irina Linkov Juan Qiu Radhika A.Patel Colm Morrsey Sanjoy Mehta Jesse Barnes Michael C.Haffner Nichlas D.Socci Richard P.koche Elisa de Stanchina Sonia Molina-Pinelo Sohrab Salehi Helena A.Yu Joseph M.Chan Charles M.Rudin Department of Medicine Thoracic Oncology ServiceMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Cancer Biology and Genetics Program Sloan Kettering InstituteMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Vagelos College of Physicians and Surgeons Columbia UniversityNew YorkNYUSA Weill Cornell Graduate School of Medical Sciences Weill Cornell MedicineNew YorkNYUA Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Center for Epigenetics Research Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Pathology Core Facilty Department of Pathology and Laboratory MedicineMSKCCNew YorkNYUSA Antitumor Assessment Core Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Divisionsof Human Biology and Clinical Research Fred Hutchinon Cancer CenterSeattleWAUSA Deparmentof Urology University of WashingtonSeattleWAUSA Gene Editing&Screening Core Facility Memorial Sloan kettering Cancer Center New YorkNYUSA Department of Laboratory Medicine and Pathology University of WashingtonSeattleWAUSA Bioinfomatics CoreFacility Memorial Soan Kettering Cancer CenterNew YorkNYUSA Institute of Biomedicine of Seille(Bis) HURCSCUniversidad de SevillaSevilleSpain Computational Oncology Department of Epidemiology and BiostatisticsMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Well Cornell Medical College New York NYUSA Present address:Swiss Institute for Experimental Cancer Research(ISREC) School of Life SciencesEPFLLausanneSwitzerland

Neuroendocrine(NE)transformation is a mechanism of resistance to targeted therapy in lung and prostate adenocarcinomas leading to poor *** to date,even if patients at high risk of transformation can be identified by the occurrence of Tumor Protein P53(TP53)and Retinoblastoma Transcriptional Corepressor 1(RB1)mutations in their tumors,no therapeutic strategies are available to prevent or delay histological *** of the cell cycle kinase Cell Division Cycle 7(CDC7)occurred in tumors during the initial steps of NE transformation,already after TP53/RB1 co-inactivation,leading to induced sensitivity to the CDC7 inhibitor ***7 inhibition suppressed NE transdifferentiation and extended response to targeted therapy in in vivo models of NE transformation by inducing the proteasome-mediated degradation of the MYC Proto-Oncogen(MYC),implicated in stemness and histological *** overexpression of a degradation-resistant MYC isoform reestablished the NE transformation phenotype observed on targeted therapy,even in the presence of ***7 inhibition also markedly extended response to standard cytotoxics(cisplatin,irinotecan)in lung and prostate small cell carcinoma *** results nominate CDC7 inhibition as a therapeutic strategy to constrain lineage plasticity,as well as to effectively treat NE tumors de novo or after *** simurosertib clinical efficacy trials are ongoing,this concept could be readily translated for patients at risk oftransformation.

关键词： tumors markedly transformation

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Long-term overlap of social and genetic structure in free-ranging house mice reveals dynamic seasonal and group size effects

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Current Zoology 2021年第1期67卷 59-69页

作者： Julian C.EVANS Anna k.LINDHOLM barbara köNIG Department of Evolutionary Biology and Environmental Studies University of ZurichWinterthurerstrasse 190Zurich8057Switzerland

Associating with relatives in social groups can bring benefits such as reduced risk of aggression and increased likelihood of *** among relatives over limited resources,on the other hand,can induce individuals to alter their patterns of *** density might further affect the costs and benefits of associating with relatives by altering resource competition or by changing the structure of social groups;preventing easy association with ***,the overlap between genetic and social structure is expected to decrease with increasing population size,as well as during times of increased breeding ***,we use multi-layer network techniques to quantify the similarity between long-term,high resolution genetic,and behavioral data from a large population of free-ranging house mice(Mus musculus domesticus),studied over *** infer how the benefit of associating with genetically similar individuals might fluctuate in relation to breeding behavior and environmental *** found a clear seasonal effect,with decreased overlap between social and genetic structure during summer months,characterized by high temperatures and high breeding *** the effect of overall population size was relatively weak,we found a clear decrease in the overlap between genetic similarity and social associations within larger *** well as longer-term within-group changes,these results reveal population-wide short-term shifts in how individuals associate with *** study suggests that resource competition modifies the trade-off between the costs and benefits of interacting with relatives.

关键词： genetic relatedness long-term data multilayer networks seasonal social behavior

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A porous puckered V_(2)O_(5) polymorph as new high performance cathode material for aqueous rechargeable zinc batteries

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Journal of Energy Chemistry 2021年第10期30卷 459-468,I0012页

作者： Dauren Batyrbekuly barbara Laïk Jean-Pierre Pereira-Ramos Zhumabay Bakenov Rita Baddour-Hadjean Institut de Chimie et des Matériaux Paris Est(ICMPE) UMR 7182 CNRS et UniversitéParis Est Créteil2 rue Henri Dunant94320 ThiaisFrance School of Engineering National Laboratory AstanaNazarbayev University53 Kabanbay Batyr AvenueAstana 010000Kazakhstan

Aqueous rechargeable zinc batteries are getting increasing attention for large-scale energy storage owing to their advantages in terms of cost,environmental friendliness and ***,the layered puckeredγ’-V_(2)O_(5) polymorph with a porous morphology is firstly introduced as cathode for an aqueous zinc battery system in a binary Zn^(2+)/Li^(+)*** Zn‖γ’-V_(2)O_(5) cell delivers high capacities of 240 and190 mAh g^(-1) at current densities of 29 and 147 mA g^(-1),respectively,and remarkable cycling stability in the 1.6 V-0.7 V voltage window(97%retention after 100 cycles at 0.15 A g^(-1)).The detailed structural evolution during first discharge-charge and subsequent cycling is investigated using X-ray diffraction and Raman *** demonstrate a reaction mechanism based on a selective Li insertion in the1.6 V-1.0 V voltage *** involves a reversible exchange of 0.8 Li^(+)in γ’-V_(2)O_(5) and the same structural response as the one reported in lithiated organic ***,in the extended 1.6 V-0.7 V voltage range,this work puts forward a concomitant and gradual phase transformation from γ’-V_(2)O_(5) to zinc pyrovanadate Zn_(3)V_(2)O_(7)(OH)2.2 H_(2)O(ZVO)during *** mechanism involving the in-situ formation of ZVO,known as an efficient Zn and Li intercalation material,explains the high electrochemical performance here reported for the Zn‖γ’-V_(2)O_(5) *** work highlights the peculiar layered-puckeredγ’-V_(2)O_(5) polymorph outperforms the conventionalα-V_(2)O_(5) with a huge improvement of capacity of 240 mAh g^(-1)vs 80 mAh g^(-1) in the same electrolyte and voltage window.

关键词： Vanadium pentoxide γ-V_(2)O_(5) Cathode Aqueous zinc battery High performance Layered structure Energy storage Renewable energy

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Carbon-Supported Silver Catalysts for CO Selective Oxidation in Excess Hydrogen

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Journal of Natural Gas Chemistry 2006年第3期15卷 181-190页

作者： barbara Pietruszka State key Laboratory of Catalysis Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China

Carbon materials were used as supports for Ag catalysts that are prepared using the conventional wet impregnation method, and their catalytic properties for CO selective oxidation in excess hydrogen at temperatures below 483 k were tested. A variety of techniques, e.g. N2 adsorption, XPS, TPD, UV-Vis DRS, TEM and SEM, were used to determine the influence of physical and chemical properties of the carbon on the properties of Ag catalyst. It was found that defects on the carbon surface served as nucleation sites for silver ions, while functional groups on carbon surface induced their reduction to the metallic form. The formation of silver particles on carbon was governed by homogeneous and/or heterogeneous nucleation during the impregnation and subsequent activation processes. The best catalytic performance was obtained with a Ag/carbon black catalyst with a uniform size distribution of silver nanoparticles （about 12 nm）, moderate BET surface area （with a mesoporous structure）, and a limited amount of carbon-oxygen groups. The research indicates that carbon materials are potentially good supports for silver catalysts for preferential oxidation of CO in excess hydrogen.

关键词： carbon support catalytic property defect functional group

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Metal and organo-catalysed asymmetric hydroaminomethylation of styrenes

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催化学报 2015年第1期36卷 106-112页

作者： barbara Villa-Marcos Jianliang Xiao Department of Chemistry University of Liverpool

A new protocol that enables asymmetric hydroaminomethylation of styrenes to afford chiral amines has been developed. Catalysed by an Rh-phosphine species and a chiral phosphoric acid, styrenes are converted into β-chiral amines with good enantioselectivities under syngas in the presence of an amine and Hantzsch ester. The reaction involves two key steps, hydroformylation and reductive amination, with the former catalysed by the Rh species whilst the latter by the phosphoric acid.

关键词：苯乙烯不对称有机催化金属对映选择性加氢甲酰化手性胺酸催化

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乳腺癌预防的三期临床试验:雌激素靶向药物,选择性雌激素受体调控剂和芳香酶抑制剂(英文)

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化学进展 2013年第9期25卷 1429-1449页

作者： barbara k. Dunn (Medical Officer National Cancer Institute Division of Cancer Prevention)

据估计,2008年全世界有138万新诊断的乳腺癌,占女性所有癌症的23%,是世界范围内女性中最常见的癌症。尽管早期诊断和治疗技术的进步已经降低了乳腺癌的发病率和死亡率,但乳腺癌仍然是女性中死亡率最高的癌症。因此,探索预防乳腺癌的途... 详细信息

据估计,2008年全世界有138万新诊断的乳腺癌,占女性所有癌症的23%,是世界范围内女性中最常见的癌症。尽管早期诊断和治疗技术的进步已经降低了乳腺癌的发病率和死亡率,但乳腺癌仍然是女性中死亡率最高的癌症。因此,探索预防乳腺癌的途径和开发风险评估模型以确定最可能从预防性干预中受益的女性具有重要意义。大规模临床试验是评估乳腺癌预防药物功效的金标准,同时也是这些药物获得正式批准的基础。因此,本文重点讨论了已经进入三期临床试验或已获正式批准用于降低乳腺癌风险的药物,尤其是针对雌激素受体阳性乳腺癌的预防药物如选择性雌激素受体调控剂和芳香酶抑制剂等;此外也对乳腺癌风险评估模型进行了简单评述。

关键词：乳腺癌预防选择性雌激素受体调控剂芳香酶抑制剂三期临床试验风险评估模型

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