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Berry-Esseen bounds and moderate deviations for the norm, entries and spectral radius of products of positive random matrices

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Science China Mathematics 2024年第3期67卷 627-646页

作者： Hui Xiao Ion Grama Quansheng Liu Institut fur Mathematik und Angewandte Informatik Universitat HildesheimHildesheim 31141Germany Academy of Mathematics and Systems Science Chinese Academy of SciencesBeijing 100190China LMBA Universite Bretagne SudCNRS UMR 6205Vannes F-56000France

Let(g_(n))_(n≥1) be a sequence of independent and identically distributed positive random d×d matrices and consider the matrix product G_(n)=g_(n)…g_*** suitable conditions,we establish the Berry-Esseen bounds on the rate of convergence in the central limit theorem and Cramer-type moderate deviation expansions,for any matrix norm ‖G_(n)‖ of G_(n),its entries G_(n)^(i,j) and its spectral radius ρ(G_(n)).Extended versions of their joint law with the direction of the random walk G_(n)x are also established,where x is a starting point in the unit sphere of R~d.

关键词： Berry-Esseen bound Cramér-type moderate deviation product of random matrices operator norm entry spectral radius

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

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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

Dysfunction of the adhesion G protein-coupled receptor latrophilin 1(ADGRL1/LPHN1)increases the risk of obesity

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2298-2311页

作者： Heba ZabriTorsten Schöneberg AndréNguyen Dietzsch Hadi Al-Hasani Joachim Altschmied Katharina Bottermann Jana Brendler Judith Haendeler Susanne Horn Isabell Kaczmarek Antje Körner Kerstin Krause Kathrin Landgraf Diana Le Duc Laura Lehmann Stefan Lehr Stephanie Pick Albert Ricken Rene Schnorr Angela Schulz Martina Strnadová Akhil Velluva Heba Zabri Torsten Schöneberg Doreen Thor Simone Prömel Rudolf Schönheimer Institute of Biochemistry Medical FacultyLeipzig UniversityLeipzigGermany Institute for Clinical Biochemistry and Pathobiochemistry Medical FacultyGerman Diabetes CenterLeibniz Center for Diabetes Research at Heinrich Heine University DüsseldorfDüsseldorfGermany German Center for Diabetes Research(DZD e.V.) Munich-NeuherbergGermany Cardiovascular Degeneration Clinical Chemistry and Laboratory DiagnosticsMedical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Cardiovascular Research Institute(CARID) Medical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Institute of Pharmacology Medical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Institute of Anatomy Medical FacultyLeipzig UniversityLeipzigGermany Center for Pediatric Research Hospital for Children and AdolescentsMedical FacultyLeipzig UniversityLeipzigGermany Helmholtz Institute for Metabolic Obesity and Vascular Research(HI-MAG)of the Helmholtz Zentrum München at the University of Leipzig and University Hospital LeipzigLeipzigGermany Department of Endocrinology NephrologyRheumatologyLeipzig University Medical CenterLeipzigGermany Institute of Human Genetics Leipzig University Medical CenterLeipzigGermany Institute of Cell Biology Department of BiologyHeinrich Heine University DüsseldorfDüsseldorfGermany School of Medicine University of Global Health EquityKigaliRwanda

Obesity is one of the diseases with severe health consequences and rapidly increasing worldwide *** the complex network of food intake and energy balance regulation is an essential prerequisite for pharmacological intervention with obesity.G protein-coupled receptors(GPCRs)are among the main modulators of metabolism and energy ***,for instance,regulate appetite and satiety in certain hypothalamic neurons,as well as glucose and lipid metabolism and hormone secretion from *** in some GPCRs,such as the melanocortin receptor type 4(MC4R),have been associated with early-onset ***,we identified the adhesion GPCR latrophilin 1(ADGRL1/LPHN1)as a member of the regulating network governing food intake and the maintenance of energy *** of the highly conserved receptor in mice results in increased food consumption and severe obesity,accompanied by dysregulation of glucose ***,we identified a partially inactivating mutation in human ADGRL1/LPHN1 in a patient suffering from ***,we propose that LPHN1 dysfunction is a risk factor for obesity development.

关键词： obesity metabolism intake

Classical and non-classical MHC I molecule manipulation by human cytomegalovirus： so many targets--but how many arrows in the quiver？

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Cellular & Molecular Immunology 2015年第2期12卷 139-153页

作者： Anne Halenius Carolin Gerke Hartmut Hengel Institute of Virology University Medical Center Albert-Ludwig-University Freiburg Freiburg Germany

Major mechanisms for the recognition of pathogens by immune cells have evolved to employ classical and non-classical major histocompatibility complex class I （MHC I） molecules. Classical MHC I molecules present antigenic peptide ligands on infected cells to CD8＋ T cells, whereas a key function for non-classical MHC I molecules is to mediate inhibitory or activating stimuli in natural killer （NK） cells. The structural diversity of MHC I puts immense pressure on persisting viruses, including cytomegaloviruses. The very large coding capacity of the human cytomegalovirus allows it to express a whole arsenal of immunoevasive factors assigned to individual MHC class I targets. This review summarizes achievements from more than two decades of intense research on how human cytomegalovirus manipulates MHC I molecules and escapes elimination by the immune system.

关键词： antigen presentation CD8+ T cells NK cells human cytomegalovirus immune evasion KIR

Contribution of Toll-like receptors to the control of hepatitis B virus infection by initiating antiviral innate responses and promoting specific adaptive immune responses

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Cellular & Molecular Immunology 2015年第3期12卷 273-282页

作者： Zhiyong Ma Ejuan Zhang Dongliang Yang Mengji Lu Institute of Virology University Hospital Essen University of Duisburg-Essen Essen Germany Department of Infectious Diseases Zhongnan Hospital ofWuhan University Wuhan China Wuhan Institute of Virology Chinese Academy of Sciences Wuhan China Department of Infectious Diseases Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China

It is well accepted that adaptive immunity plays a key role in the control of hepatitis B virus （HBV） infection. In contrast, the contribution of innate immunity has only received attention in recent years. Toll-like receptors （TLRs） sense pathogen-associated molecule patterns and activate antiviral mechanisms, including intracellular antiviral pathways and the production of antiviral effector interferons （IFNs） and pro-inflammatory cytokines. Experimental results from in vitroand in vivo models have demonstrated that TLRs mediate the activation of cellular signaling pathways and the production of antiviral cytokines, resulting in a suppression of HBV replication. However, HBV infection is associated with downregulation of TLR expression on host cells and blockade of the activation of downstream signaling pathways. In primary HBV infection, TLRs may slow down HBV infection, but contribute only indirectly to viral clearance. Importantly, TLRs may modulate HBV-specific T- and B-cell responses in vivo, which are essential for the termination of HBV infection. Thus, TLR agonists are promising candidates to act as immunomodulators for the treatment of chronic HBV infection. Antiviral treatment may recover TLR expression and function in chronic HBV infection and may increase the efficacy of therapeutic approaches based on TLR activation. A combined therapeutic strategy with antiviral treatment and TLR activation could facilitate the restoration of HBV-specific immune responses and thereby, achieve viral clearance in chronically infected HBV patients.

关键词： Hepatitis B virus Toll like receptor Innate immune response Adaptive immune response

Nucleus-Encoded Light-Harvesting Chlorophyll a/b Proteins are Imported Normally into Chlorophyll b-Free Chloroplasts of Arabidopsis

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Molecular Plant 2013年第3期6卷 860-871页

作者： Sabine Nick Jorg Meurer Jurgen Soil Elisabeth Ankele Dept Biologie I-Botanik Biozentrum LMU Munchen Grosshadernerstrasse 2-4 D-82152 Planegg-Martinsried Germany Munich Center for Integrated Protein Science ClPSM Ludwig-Maximilians-Universitat Munchen Feodor-Lynen-Strasse 25 D-81377 Munich Germany

Chloroplast-located proteins which are encoded by the nuclear genome have to be imported from the cytosol into the organelle in a posttranslational manner. Among these nuclear-encoded chloroplast proteins are the light- harvesting chlorophyll a/b-binding proteins （LHCPs）. After translation in the cytosol, precursor proteins of LHCPs are imported via the TOC/TIC translocase, processed to their mature size to insert into thylakoid membranes where they recruit chlorophylls a and b to form pigment-protein complexes. The translocation of proteins is a highly regulated process which employs several regulators. To analyze whether CAO （chlorophyll a oxigenase） which converts chlorophyll a to chlorophyll b at the inner chloroplast membrane, is one of these regulators, we performed import reactions utilizing a homozygous loss-of-function mutant （cao-1）. We imported in vitro translated and 35S-labeled precursor proteins of light- harvesting proteins of photosystem II LHCB1, LHCB4, and LHCB5 into chloroplasts isolated from cao-1 and show that import of precursor proteins and their processing to mature forms are not impaired in the mutant. Therefore, regulation of the import machinery cannot be responsible for the decreased steady-state levels of light-harvesting complex （LHC） proteins. Regulation does not take place at the transcriptional level either, because Lhcb mRNAs are not down-regulated. Additionally, reduced steady-state levels of LHCPs also do not occur due to posttranslational turnover of non-functional LHCPs in chloroplasts. Taken together, our data show that plants in the absence of CAO and therefore devoid of chlorophyll b are not influenced in their import behavior of LHC proteins.

关键词： chloroplast import LHCPs cao-1 protein complex assembly thylakoid membranes photosynthesis.

Current Injection Provokes Rapid Expansion of the Guard Cell Cytosolic Volume and Triggers Ca^2＋ Signals

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Molecular Plant 2016年第3期9卷 471-480页

作者： Lena J. Voss Rainer Hedrich M. Rob G. Roelfsema Molecular Plant Physiology and Biophysics Julius-von-Sachs Institute for Biosciences Biocenter Werzburg University Julius-von-Sachs-Platz 2 97082 Werzburg Germany

High-resolution microscopy opens the door for detailed single-cell studies with fluorescent reporter dyes and proteins. We used a confocal spinning disc microscope to monitor fluorescent dyes and the fluorescent protein Venus in tobacco and Arabidopsis guard cells. Multi-barreled microelectrodes were used to inject dyes and apply voltage pulses, which provoke transient rises in the cytosolic Ca^2＋ level. Voltage pulses also caused changes in the distribution of Lucifer Yellow and Venus, which pointed to a reversible increase of guard cell cytosolic volume. The dynamic cytosolic volume changes turned out to be provoked by current injection of ions. A reduction of the clamp current, by blocking K^＋ uptake channels with Cs^＋, strongly suppressed the cytosolic volume changes. Cs^＋ not only inhibited the expansion of the cytosol, but also inhibited hyperpolarization-induced elevations of the cytosolic Ca^2＋ concentration. A complete loss of voltage-induced Ca^2＋ signals occurred when Ca^2＋-permeable plasma membrane channels were simultaneously blocked with La^3＋. This shows that two mechanisms cause hyperpolarization-induced elevation of the cytosolic Ca^2＋-concentration：（i） activation of voltage-dependent Ca^2＋-permeable channels, （ii） osmotically induced expansion of the cytosol, which leads to a release of Ca^2＋ from intracellular stores.

关键词： guard cell cytosolic Ca^2+ cytosolic volume voltage clamp current injection ion channel

Zinc Fingers, TAL Effectors, or Cas9-Based DNA Binding Proteins： What＇s Best for Targeting Desired Genome Loci？

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Molecular Plant 2013年第5期6卷 1384-1387页

作者： Annett Strauβ Thomas Lahaye Faculty of Biology Institute of Genetics Ludwig-Maximilians-University Munich Grolβhaderner Straβe 2-4 D-82152 Martinsried Germany

ZINC FINGER- AND TAL EFFECTOR- BASED DNA BINDING PROTEINSProgrammable DNA binding proteins （PDPs） that selectively bind user-defined nucleotide sequences can navigate protein domains to any desired target within the genome. Different functional domains can be fused to PDPs to achieve （1） acti- vation or repression of transcription, （2） nicking or cleavage of DNA, or （3） modification or removal of epigenetic marks at the targeted genome spot. Given their broad applicabil- ity, the development of highly specific, easy-to-use PDPs has been a holy grail of biotechnology since the determination of the 3-D structure of zinc fingers （ZFs） bound to DNA in 1991 （Pavletich and Pabo, 1991）. This structure suggested that tandemly arranged ZFs act as functionally independ- ent modules with each finger binding three bases. However, the combination of fingers with experimentally defined base specificities into arrays revealed that ZFs are not function- ally independent. Instead, they were found to behave in a context-dependent, and often unpredictable fashion requir- ing iterative cycles of selection to get ZF arrays with desired specificity （Joung and Sander, 2013）.

关键词： DNA结合蛋白基因组 TAL 锌指期望基础蛋白质结构域用户自定义

Hepatitis B virus is degraded by autophagosome-lysosome fusion mediated by Rab7 and related components

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Protein & Cell 2019年第1期10卷 60-66页

作者： Yong Lin Chunchen Wu Xueyu Wang Thekla Kemper Anthony Squire Matthias Gunzer Jiming Zhang Xinwen Chen Mengji Lu Institute of Virology University Hospital EssenUniversity of Duisburg-Essen45117 EssenGermany State Key Laboratory of Virology Wuhan Institute of VirologyChinese Academy of ScienceWuhan 430071China Institute for Experimental Immunology and Imaging University Hospital EssenUniversity Duisburg-Essen45117 EssenGermany Department of Infectious Diseases Huashan HospitalFudan UniversityShanghai 200040China

Dear Editor,With an estimated 240 million chronically infected people worldwide,hepatitis B virus(HBV)infection is a major public health problem(Schweitzer et al.,2015).Despite more than 30 years of in tense research,... 详细信息

关键词： Editor people HBV