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Ca^(2+) binding to the C_(2)E domain of otoferlin is required for hair cell exocytosis and hearing

Protein & Cell 2024年第4期15卷 305-312页

作者： Han Chen Mehar Monga Qinghua Fang Loujin Slitin Jakob Neef Shashank S.Chepurwar Regina Célia Mingroni Netto Karina Lezirovitz Alfredo Tabith,Jr. Fritz Benseler Nils Brose Kathrin Kusch Carolin Wichmann Nicola Strenzke Barbara Vona Julia Preobraschenski Tobias Moser Institute for Auditory Neuroscience and InnerEarLab University Medical Center Göttingen37075 GöttingenGermany Collaborative Research Center 889 University of Göttingen37075 GöttingenGermany Auditory Neuroscience and Synaptic Nanophysiology Group Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Göttingen Graduate Center for Neurosciences Biophysics and Molecular BiosciencesUniversity of Göttingen37075 GöttingenGermany Biochemistry of Membrane Dynamics Group Institute for Auditory NeuroscienceUniversity Medical Center Göttingen37075 GöttingenGermany Molecular Architecture of Synapses Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Center for Biostructural Imaging of Neurodegeneration University Medical Center Göttingen37075 GöttingenGermany Auditory Systems Physiology Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Departamento de Genética e Biologia Evolutiva Centro de Pesquisas sobre o Genoma Humano e Células-TroncoInstituto de BiociênciasUniversidade de São PauloSão Paulo 05508-220Brazil Laboratório de Otorrinolaringologia/LIM32 Faculdade de MedicinaHospital das ClínicasUniversidade de São PauloSão PauloSP 05508-220Brazil DERDIC Pontifícia Universidade Católica de São PauloSão Paulo 05508-220Brazil Department of Molecular Neurobiology Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Multiscale Bioimaging Cluster of Excellence(MBExC) University of Göttingen37075 GöttingenGermany Functional Auditory Genomics Group Auditory Neuroscience and Optogenetics LaboratoryGerman Primate Center37077 GöttingenGermany Hearing Genomics Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Institute of Human Genetics University Medical Center Göttingen37075 GöttingenGermany

Dear Editor,Afferent synapses of cochlear inner hair cells(IHCs)employ a unique molecular machinery(see extended background in Supplementary Materials).Otoferlin is a key player in this machinery and its defects cause human auditory synaptopathy(Moser and Starr,2016).Otoferlin,a tail-anchored(Vogl et al.,2016)multi-C_(2)-domain protein(Fig.1Ai)specific to hair cells(Roux et al.,2006),is a member of the ferlin protein family involved in membrane trafficking and repair that are of major disease relevance(Pangršičet al.,2012),also see Supplementary *** is distributed broadly within IHCs(Fig.2Ai-Aiii;Pangrsic et al.,2010;Roux et al.,2006).

关键词： auditory hair

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Spatial analysis of Dengue through the reproduction numbers relating to socioeconomic features:Case studies on two Brazilian urban centers

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Infectious Disease Modelling 2024年第1期9卷 142-157页

作者： Ana T.C.Silva Rejane C.Dorn Lívia R.Tomás Leonardo B.L.Santos Lacita M.Skalinski Suani T.R.Pinho Departamento de Física Universidade Estadual de Feira de SantanaAv.Transnordestinas/n.Novo HorizonteFeira de Santana44036-900BABrazil Instituto de Física Universidade Federal da BahiaRua Barão de Jeremoabo s/nCampus Universitário de OndinaSalvador40170-115BABrazil Centro Nacional de Monitoramento e Alertas de Desastres Naturais(CEMADEN) Estrada Dr.Altino Bondensan500São Josédos Campos12247-016SPBrazil Universidade Estadual de Santa Cruz Campus Soane Nazaréde AndradeRodovia Jorge AmadoKm 16SalobrinhoIlhéus45662-900BABrazil Instituto de Saúde Coletiva Universidade Federal da BahiaR.Basílio da Gamas/n-CanelaSalvador40110-140BABrazil Instituto Nacional de Ciência e Tecnologia-Sistemas Complexos Virtual InstitutionBrazil

The study of the propagation of infectious diseases in urban centers finds a close connection with their population's social characteristics and *** work performs a spatial analysis of dengue cases in urban centers based on the basic reproduction numbers,R0,and incidence by planning areas(PAs),as well as their correlations with the Human Development Index(HDI)and the number of *** analyzed dengue epidemics in 2002 at two Brazilian urban centers,Belo Horizonte(BH)and Rio de Janeiro(RJ),using PAs as spatial *** results reveal heterogeneous spatial scenarios for both cities,with very weak correlations between R0 and both the number of trips and the HDI;in BH,the values of R0 show a less spatial heterogeneous pattern than in *** BH,there are moderate correlations between incidence and both the number of trips and the HDI;meanwhile,they weakly correlate for ***,the absence of strong correlations between the considered measures indicates that the transmission process should be treated considering the city as a whole.

关键词： Dengue Mathematical mode lBasic reproduction number Urban mobility Urban indices

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Dysregulated microRNAs in type 2 diabetes and breast cancer:Potential associated molecular mechanisms

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World Journal of Diabetes 2024年第6期15卷 1187-1198页

作者： Alex Cleber Improta-Caria Filipe Ferrari João Lucas Penteado Gomes Paloma Brasilio Villalta Úrsula Paula RenóSoci Ricardo Stein Edilamar M Oliveira Laboratory of Biochemistry and Molecular Biology of the Exercise Physical Education and Sport SchoolUniversity of São PauloSão Paulo 05508-030Brazil Graduate Program in Cardiology and Cardiovascular Sciences Federal University of Rio Grande do SulHospital de Clínicas de Porto AlegrePorto Alegre 90035003Brazil Laboratory of Metabolic Disorders(Labdime) School of Applied SciencesUniversity of Campinas-UNICAMPCampinas 13484-350Brazil Departments of Internal Medicine Molecular Pharmacology and PhysiologyCenter for Regenerative MedicineUSF Health Heart InstituteMorsani College of MedicineUniversity of South FloridaTampaFL 33602United States

Type 2 diabetes(T2D)is a multifaceted and heterogeneous syndrome associated with complications such as hypertension,coronary artery disease,and notably,breast cancer(BC).The connection between T2D and BC is established through processes that involve insulin resistance,inflammation and other *** this comprehension the specific cellular and molecular mechanisms linking T2D to BC,especially through microRNAs(miRNAs),remain *** are regulators of gene expression at the post-transcriptional level and have the function of regulating target genes by modulating various signaling pathways and biological ***,the signaling pathways and biological processes regulated by miRNAs that are associated with T2D and BC have not yet been *** review aims to identify dysregulated miRNAs in both T2D and BC,exploring potential signaling pathways and biological processes that collectively contribute to the development of BC.

关键词： Type 2 diabetes Breast cancer MicroRNAs Molecular mechanisms

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Olympic Games and 24-hour movement behaviors:A match worth making

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Journal of Sport and Health Science 2024年第6期13卷 728-731页

作者： Mark S.Tremblay Nicholas Kuzik Markus J.Duncan Diego Augusto Santos Silva CHEO Research Institute OttawaON K1H 8L1Canada Department of Pediatrics University of OttawaOttawaON K1H 8L1Canada Federal University of Santa Catarina FlorianopolisSanta Catarina 88040-900Brazil

*** The Olympic motto,"Faster,Higher,Stronger-Together",represents the pursuit of athletic excellence,united as a global community."Excellence,respect and friendship"are the Olympic *** the motto and values are multifaceted and holistic in nature,and all-encompassing in their reach while recognizing no single entity rises above the ***,these foundational statements anchor the Olympic movement in its quest to build a better world through sport.

关键词： movement Together pursuit

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淋巴浆细胞淋巴瘤华氏巨球蛋白血症的研究进展

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临床检验杂志 2024年第7期42卷 514-518页

作者：李卫滨陈娅张胜行联勤保障部队第900医院检验科福州350025 福建医科大学福总临床学院&第900医院检验科福州350025 福建中医药大学福总教学医院&第900医院检验科福州350025

淋巴浆细胞淋巴瘤/华氏巨球蛋白血症(lymphoplasmacytic lymphoma/Waldenström macroglobulinemia,LPL/WM)是一种以血液中出现大量单克隆丙种球蛋白(IgM)为特征的、少见的惰性成熟B细胞淋巴瘤。其诊断标准包括血清中检测到单克隆性IgM,... 详细信息

淋巴浆细胞淋巴瘤/华氏巨球蛋白血症(lymphoplasmacytic lymphoma/Waldenström macroglobulinemia,LPL/WM)是一种以血液中出现大量单克隆丙种球蛋白(IgM)为特征的、少见的惰性成熟B细胞淋巴瘤。其诊断标准包括血清中检测到单克隆性IgM,骨髓中浆细胞样或浆细胞分化的小淋巴细胞呈小梁间隙侵犯,特征性的免疫表型,除外其他已知类型的淋巴瘤以及90%以上的MYD88 L265P突变。其发病机制与家族易感性、丙型肝炎、自身免疫病、意义未明的单克隆免疫球蛋白病(MGUS)以及MYD88基因突变相关。实验室检查主要涵盖骨髓细胞学、血清学、组织学、免疫表型和基因突变。LPL/WM需要与IgM-MGUS、冒烟型WM(SWM)及其他淋巴增殖性疾病(LPD)进行鉴别诊断。LPL/WM治疗的优选方案包括BR[苯达莫司汀+利妥昔单抗(R)]、BDR(硼替佐米+地塞米松+R)、伊布替尼单药或伊布替尼+R(1类推荐)、RCD(R+环磷酰胺+地塞米松)、泽布替尼单药(1类推荐)等。

关键词：淋巴浆细胞淋巴瘤/华氏巨球蛋白血症成熟B细胞淋巴瘤实验室检测

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燃料电池式反应器中Pt和Pd中加入Bi用于催化乙醇发电并选择性联产醋酸盐

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燃料化学学报 2021年第10期49卷 1540-1548页

作者： Lima F.S. Fontes E.H. Nandenha J. de Souza R.F.B. Neto A.O. Instituto de Pesquisas Energéticas e Nucleares IPEN/CNEN-SPCEP 05508-900 São PauloSPBrazil

直接乙醇燃料电池作为便携式移动电源受到越来越多的关注,如乙醇能量密度高、可再生、无毒、清洁、便于储存和运输等优点。然而,乙醇燃料电池的研究也面临一些严重问题,其中C−C键断裂是最为挑战的问题之一。近年来有报道表明,乙醇的完... 详细信息

直接乙醇燃料电池作为便携式移动电源受到越来越多的关注,如乙醇能量密度高、可再生、无毒、清洁、便于储存和运输等优点。然而,乙醇燃料电池的研究也面临一些严重问题,其中C−C键断裂是最为挑战的问题之一。近年来有报道表明,乙醇的完全氧化(包含C−C键断裂过程)并没有显示出燃料电池效率的增加,相反乙醇不完全氧化的催化剂会导致更明显的催化电流增加。同时金属Bi掺杂会对催化剂产生电子效应和几何效应并有效增加碱性体系中催化剂的活性位中心和抗CO中毒能力。因此,本工作将铋掺杂在铂和钯中制备出PtBi/C和PdBi/C作为乙醇燃料电池催化剂,同时研究Bi掺杂催化剂对乙醇燃料电池性能以及乙醇的不完全氧化产物醋酸盐的影响,为乙醇燃料电池电-化学品联产提供一定的依据。以硼氢化钠为还原剂,Vulcan XC-72(Cabot)导电炭为载体制备了Pt/C、Pd/C、PtBi/C和PdBi/C(20%质量比)炭载催化剂,其中PtBi和PdBi原子比均为95∶5。首先将金属前驱体溶于H_(2)O/异丙醇溶液(50/50,体积比)中,加入Vulcan XC-72导电炭黑充分混合,然后加入硼氢化钠在常温常压下充分反应,过滤洗涤干燥备用。其次,对所制备的催化剂进行TEM、XRD、XPS、电化学以及光谱电化学进行表征和测试。电化学、光谱电化学在三电极电解池中进行,将所制备的催化剂分散在超薄多孔电极上制备成工作电极,对电极为Pt片电极,参比电极为Ag/AgCl电极。电解液为碱性1 mol/L KOH的乙醇溶液,在电化学工作站上进行CV、LSV扫描以及在不同电位下测试溶液的ATR-FTIR谱。最后,燃料电池测试在一个面积为5 cm2的单电池上进行,阳极为2 mol/L乙醇+3 mol/L KOH溶液,流量为2 mL/min,阴极通入氧气,并研究催化剂的构成及性能对电池性能的影响。采用硼氢化钠还原法合成Pt/C、PtBi(95∶5)/C、Pd/C和PdBi(95∶5)/C。Pd/C和PdBi/C的晶体结构呈现FCC特征,Pt/C和PtBi/C的晶体结构也呈现FCC特征。XRD也揭示了铋原子对Pt晶体结构的影响。在1 mol/L KOH溶液中,异位XPS和循环伏安法显示这些金属具有较高的氧化态。透射电镜显示Pd/C有一定的纳米粒子聚集,PdBi/C有一定的有序结构。红外光谱(ATR-FTIR)结果表明,Bi效应由于吸附能力较弱,抑制了碳酸盐的生成,增加了醋酸盐的生成。由于醋酸盐优先生成,且不被碳酸盐离子毒害,PtBi/C具有最佳的电化学和DEFC性能。通过在Pt和Pd掺杂金属Bi制备具有电子调控的双金属炭载PtBi(95∶5)/C和PdBi(95∶5)/C催化剂,以增强乙醇氧化反应催化氧化过程。透射电镜(TEM)和X射线光电子能谱(XPS)结果表明,Bi含量不影响PdBi纳米颗粒的尺寸,但会影响PtBi纳米颗粒的尺寸。X射线衍射分析表明,Bi掺杂改变了Pt晶体结构中的晶格参数。此外,ATR-FTIR结果表明,碳酸盐的形成受到抑制,乙酸盐产量增加。极化曲线和功率密度曲线结果表明,PtBi/C催化剂具有更高的功率密度,几乎是Pt/C的6倍。在线性扫描伏安实验中,PtBi/C具有最高的电流密度(44 mW/cm2)和最低的起始电位(−0.6 V)。在电流-时间实验中,它也具有最高的最终电流密度。因此,在Pt和Pd中掺杂铋催化剂被证明是一种很有前途的燃料电池发电和醋酸盐的联产方法。

关键词：甲醇氧化反应 Bi掺杂电-化学品联产

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Numerical modeling of adhesion and adhesive failure during unidirectional contact between metallic surfaces

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Friction 2016年第3期4卷 217-227页

作者： Eleir M.BORTOLETO Erika F.PRADOS Vanessa SERIACOPI Newton K.FUKUMASU Luiz G.D.B.da S.LIMA Izabel F.MACHADO Roberto M.SOUZA Surface Phenomena Laboratory Department of Mechanical Engineering Polytechnic School of the University of S(a)o Paulo Av.Prof.Mello Moraes 2231 S(a)o Paulo 05508-900 Brazil Federal University of ABC-UFABC Santo André 09210-170 Brazil

In this work, we developed a finite element modeling approach to study adhesion during unidirectional contact between a two-dimensional plane-strain square and a flat slab. The surfaces were metallic or ceramic, and we analyzed different pairs of materials and their adhesion intensity using a FORTRAN subroutine (DLOAD) connected to a commercial finite element code Abaqus, which provided the surface attractive forces based on the Lennard-Jones interatomic potential using Hamaker constants. We considered adhesive loads during both the approach and separation of the surfaces. During the separation step, we modeled the material transfer between surfaces due to adhesion with respect to damage initiation and propagation at the flat slab. The parameters considered in the simulations include normal load, chemical affinity, and system size, and we analyzed different conditions by comparing the interaction forces during approach and withdrawal. This work also presents: (i) a description of the evolution of energy dissipation due to adhesion hysteresis, (ii) the formation–growth–breakage process of the adhesive junctions and the material transfer between surfaces, and (iii) an adhesive wear map based on a proposed novel equation that correlates the material parameters and material loss due to adhesion. The results indicate that the chemical affinity between bodies in contact is more related to adhesion than the applied load. In addition, the ratio between the material strength and elastic modulus seems to be an important factor in reducing adhesive wear.

关键词： adhesion adhesive failure finite element model interatomic potentials Hamaker constants

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P2X7 receptor antagonist recovers ileum myenteric neurons after experimental ulcerative colitis

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World Journal of Gastrointestinal Pathophysiology 2020年第4期11卷 84-103页

作者： Roberta Figueiroa Souza Mariá Munhoz Evangelinellis Cristina Eusébio Mendes Marta Righetti Múcio Cevulla Silva Lourenco Patricia Castelucci Department of Anatomy University of Sao PauloSao Paulo 05508-900Brazil Department of Surgery Faculty of Veterinary Medicine and Animal ScienceUniversity of Sao PauloSao Paulo 05508-900Brazil

BACKGROUND The P2X7 receptor is expressed by enteric neurons and enteric glial *** have demonstrated that administration of a P2X7 receptor antagonist,brilliant blue G(BBG),prevents neuronal *** To report the effects of BBG in ileum enteric neurons immunoreactive(ir)following experimental ulcerative colitis in Rattus norvegicus *** 2,4,6-trinitrobenzene sulfonic acid(TNBS group,n=5)was injected into the distal ***(50 mg/kg,BBG group,n=5)or vehicle(sham group,n=5)was given subcutaneously 1 h after *** animals were euthanized after 24 h,and the ileum was *** was performed on the myenteric plexus to evaluate immunoreactivity for P2X7 receptor,neuronal nitric oxide synthase(nNOS),choline acetyltransferase(ChAT),HuC/D and glial fibrillary acidic *** The numbers of nNOS-,ChAT-,HuC/D-ir neurons and glial fibrillary acidic protein-ir glial cells were decreased in the TNBS group and recovered in the BBG *** neuronal profile area(μm^2)demonstrated that nNOS-ir neurons decreased in the TNBS group and recovered in the BBG *** were no differences in the profile areas of ChAT-and HuC/D-ir *** Our data conclude that ileum myenteric neurons and glial cells were affected by ulcerative colitis and that treatment with BBG had a neuroprotective ***,these results demonstrate that the P2X7 receptor may be an important target in therapeutic strategies.

关键词： P2X7 receptor Brilliant blue G Myenteric plexus Experimental ulcerative colitis Ileum Chemical coding

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Characterization of Arroyo Verde Epithermal Deposit:Paragenesis,Mineral Geochemistry,Geochronology and Fluid Inclusions in Lower Chon Aike Volcanism,Argentina

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Journal of Earth Science 2024年第1期35卷 62-84页

作者： Cecilia Pavón Pivetta Leonardo Benedini Paulo Marcos Ma.Agustina Cócola Mercedes Virginia Barros Daniel Gregori Leonardo Strazzere Anderson Costa dos Santos Mauro C.Geraldes Instituto Geologico del Sur(INGEOSUR) Universidad Nacional del Sur(UNS)-Consejo Nacional de Investigaciones Cientificas y Tecnicas(CONICET)Bahia Blanca 8000Argentina Dpto.de Geologia Universidad Nacional del Sur(UNS)Bahia Blanca 8000Argentina Universidad Nacional de Rio Negro Instituto de Investigacion en Paleobiologia y GeologiaGeneral Roca 8332Argentina Universidade do Estado do Rio de Janeiro Faculdade de GeologiaDepartamento de Mineralogia e Petrologia igneaRiodeJaneiro20559-900Brazil Geobiotec Departamento de GeocienciasUniversidade de AveiroAveiro 3800-002Portuga

Arroyo Verde epithermal deposit,in the North Patagonia region of Argentina,is located within the Lower Chon Aike volcanism and is developed between 192.6±2.5 Ma(mineralization host rock)and 189.5±2.6 Ma(overlying lava).Marifil volcanic complex is the host rock for these veins,veinlets and *** particular small deposit has developed low to intermediate sulphidation characteristics,with gangue mineral textures associated with several ore *** probe microanalysis determines electrum,silver minerals such as acanthite,and tetrahedrite,related Ag-Cu minerals like jalpaite,mckinstryite,stromeyerite,and base metals like chalcopyrite,sphalerite,galena and *** inclusions in quartz of two out of five events indicate that these Low Jurassic veins were formed due to subtle boiling and dilution mechanisms and by low-salinity(3.4 wt.%to 6.7 wt.%NaCl Eq)magmatic-hydrothermal fluid at 225 to 310℃.The fluid inclusion measurements that indicate boiling(Event 3)were plotted,and based on this data,we interpret that the Arroyo Verde deposit has been eroded between 550 and 700 *** particular character has not been previously recorded for other sectors of the eastern north Patagonian region.

关键词： epithermal deposit Ag minerals mineral geochemistry fluid inclusions Chon Aike geochronology

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Effluent Zero Release Concept-The Brazilian Experience

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过程工程学报 2006年第4期6卷 691-696页

作者： José Carlos Mierzwa Sandra Mara Garcia Bello Ivanildo Hespanhol Hydraulic and Sanitation Eng.Dept. Univ.Sao PauloAv.Prof.Almeida Prado83 SoPauloBrazil CEP:05508-900 Navy Technologic Center in Sao Paulo Av.Prof.Lineu Prestes2468 SoPauloBrazilCEP:05508-900

Water scarcity is pushing the government,industries and researchers to the development of new strategies for water and wastewater *** approach aimed at the optimization of the water use and minimization of effluent generation was developed at the Centro Experimental ARAMAR(CEA),a nuclear research facility,located in the State of Sao Paulo,*** scale tests followed by a pilot plant treating effluents from some nuclear research facilities have shown the results leading to the conclusion that the effluent zero release concept is *** on the gathered data,a project of an integrated effluent treatment system focusing on water recovery and environmental effluent release reduction has been developed.

关键词： effluent wastewater treatment zero release

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