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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.che.urwar 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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Applicability of unique scarf joint configuration in friction stir welding of AA6061-T6:Analysis of torque,force,microstructure and mechanical properties

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Defence Technology（防务技术） 2022年第4期18卷 567-582页

作者： Durjyodhan sethi Uttam Acharya shashank shekhar Barnik saha Roy Department of Mechanical Engineering National Institute of Technology AgartalaBarjalaJiraniaWest TripuraPin-799046India Department of Materials science and Engineering Indian Institute of Technology KanpurKanpur208016India

The present research introduces a unique concept of scarf joint technique in friction stir welding(FsW) of aluminum alloy AA 6061-T6 plates and an investigation on weld quality.A new joint configuration with two distinct scarf angles(75°and 60°) was considered in this *** various aspects of welding were compared with contemporary simple square butt(ssB) joint *** was carried out at a constant tool rotation speed(TRs),tool traverse speed(TTs) and tool tilt angle of 1100 rpm,2 mm/s and2°,*** results are analyzed in terms of force and torque distribution,microstructure,macrostructure,and mechanical property perspective for different joint *** study reveals the minimum amount of force and torque at 60°scarf angle joint configuration compared to that of square butt joint *** study shows that all the joints were defect-free,and a prominent onion ring was present in the lower portion of the weld nugget(WN).Fine equiaxed grains with a minimum average grain size diameter of 6.82 μm were obtained in the WN of scarf joint configuration(sJC).The maximum ultimate tensile strength(UTs) and maximum average NZ hardness of 267 MPa and83.82 HV0.1were obtained in sJC3 at a scarf angle of 60°.It has been observed from the investigation that the joint efficiency increases from 72.5%(ssB) to 86%(sJC3) at a 60° scarf *** unique characteristic may lay an impetus on probable joint strength enhancement technique without increasing the production cost.

关键词： Friction stir welding Joint configuration Al alloys Force and torque Microstructure Mechanical property

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China's treatment regimen for fulminant myocarditis is bringing wonderful achievement to the world

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science China(Life sciences) 2019年第2期62卷 282-284页

作者： Jing Zhang Weijian Hang Rutai Hui Qiong Zhao shashank s.Desai Cardiovascalar Intensive Care Unit Fuwai Huazhong Cardiovascular Hospital Division of Cardiology Department of Internal Medicine Tongji Hospital Tongji Medical College Huazhong University of Science & Technology Fuwai Hospital National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Advanced Heart Failure/Transplant Program Inova Heart and Vascular Institute Inova Fairfax Hospital

Fulminant myocarditis is characterized by acute and severe inflammation with injury of myocardium globally. It has a fulminant course and high in-hospital mortality rate of up to50%-70%. It onsets rapidly after viral ... 详细信息

关键词： China’s treatment regimen for fulminant myocarditis is bringing wonderful achievement to the world

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Decay rates of charmonia within a quark-antiquark confining potential

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Chinese Physics C 2016年第5期40卷 14-23页

作者： smruti Patel P.C.Vinodkumar shashank Bhatnagar Department of Physics Sardar Patel University Department of Physics Addis Ababa University

In this work, we investigate the spectroscopy and decay rates of charmonia within the framework of the non-relativistic schrsdinger equation by employing an approximate inter quark-antiquark potential. The spin hyperfine, spin-orbit and tensor components of the one gluon exchange interaction are employed to compute the spectroscopy of the excited s states and a few low-lying P and D waves. The resultant wave functions at zero inter- quark separation as well as some finite separations are employed to predict the di-gamma, di-leptonic and di-gluon decay rates of charmonia states using the conventional Van Royen-Weisskopf formula. The di-gamma and di-leptonic decay widths are also computed by incorporating the relativistic corrections of order v4 within the NRQCD formalism. We have observed that the NRQCD predictions with their matrix elements computed at finite radial separation yield results which are found to be in better agreement with experimentM values for both di-gamma and di-leptonic decays. The same scenario is seen in the case when di-gamma and di-leptonic decay widths are computed with the Van Royen- Weisskopf formula. It is also observed that the di-gluon decay width with the inclusion of binding energy effects are in better agreement with the experimental data available for 1s-2s and 1P. The di-gluon decay width of 3s and 2P waves waves are Mso predicted. Thus, the present study of decay rates clearly indicates the importance of binding energy effects.

关键词： potential models heavy quarkonia radiative decays non relativistic quark model

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A Micro-structure Dependent Buckling Analysis of Partially-Cracked Generally Orthotropic Plate under Thermal Domain

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Advances in Applied Mathematics and Mechanics 2023年第1期15卷 244-266页

作者： Ankur Gupta shashank soni N.K.Jain Department of Mechanical Engineering National Institute of TechnologyRaipurChhattisgarh 492010India

In this work,a non-classical analytical approach for buckling analysis of partially cracked generally orthotropic plate is proposed under the thermal *** derivation for the governing equation is based on the non-classical approach using Kirchhoff’s thin plate theory and the modified couple stress *** effect of fibre orientation on critical buckling temperature is incorporated by considering the coefficients of mutual *** spring model is applied with some modifications to formulate all the crack terms while the thermal effects are introduced in form of thermal in-plane moments and *** final governing equation is solved using Galerkin’s method and the relation for critical buckling temperature as affected by fibre orientation is *** variation of critical buckling temperature as affected by fibre orientation for different values of crack length,crack location and length scale parameter is ***,the effect of fibre orientation on fundamental frequency under the thermal domain is analysed.

关键词： Orthotropic plate fibre orientation crack microstructure thermal domain

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Bilateral sequential femoral neck stress fractures in young adult with HIV infection on antiretroviral therapy: A case report

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World Journal of Orthopedics 2019年第6期10卷 247-254页

作者： saisunder shashank Chaganty Deeptiman James Faculty of Medicine and Dentistry University of PlymouthPlymouth PL6 8BUUnited Kingdom Assistant Professor Department of OrthopedicsChristian Medical CollegeVelloreVellore 632004Tamil NaduIndia

BACKGROUND Femoral neck stress fractures are rarely encountered among young adults and are often associated with either repetitive excessive loading or underlying bone *** research has indicated human immunodeficiency virus(HIV)/antiretroviral therapy(ART)as predisposing agents to osteopenia and osteoporosis related *** report a case of HIV/ART induced insufficiency fracture in a resource limited setting in Central *** aim is to increase awareness and promote screening of HIV/ART related osteopenia and osteoporosis in order to prevent catastrophic orthopaedic *** sUMMARY A 35-year-old HIV positive male presented with a stress fracture of left femoral *** patient was on ART and reported no *** went on to be successfully managed ***,during work-up osteopenia of the contralateral proximal femur was recognised using singh’s *** months post-op the patient presented with right-sided femoral-neck stress *** this stage the patient was nonconcordant with ART and denied surgical *** In the absence of co-morbidities,several mechanisms of HIV/antiretroviral therapy may have played a role in predisposing our patient towards such a *** recommend routine screening all HIV-infected patients for osteopenia,especially in younger *** low resource settings and district hospitals,pelvis radiograph&singh’s index can be used for screening.

关键词： Bilateral femoral neck stress fracture Human immunodeficiency virusantiretroviral therapy related osteopenia Osteoporosis in resource limited setting Human immunodeficiency virus related fragility fractures

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Additive friction stir deposition of AZ31B magnesium alloy

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Journal of Magnesium and Alloys 2022年第9期10卷 2404-2420页

作者： sameehan s.Joshi shreyash M.Patil sangram Mazumder shashank sharma Daniel A.Riley shelden Dowden Rajarshi Banerjee Narendra B.Dahotre Department of Materials science and Engineering University of North Texas3940 N Elm StDentonTX 76207USA Center for Agile and Adaptive Additive Manufacturing University of North Texas3940 N Elm StDentonTX 76207USA

The current work explored additive friction stir deposition of AZ31B magnesium alloy with the aid of MELD?***31B magnesium bar stock was fed through a hollow friction stir tool rotating at constant velocity of 400 rpm and translating at linear velocity varied from 4.2 to 6.3 mm/s.A single wall consisting of five layers with each layer of 140×40×1 mm^(3)dimensions was deposited under each processing ***,phase,and crystallographic texture evolutions as a function of additive friction stir deposition parameters were studied with the aid of scanning electron microscopy including electron back scatter diffraction and X-ray *** feed material and additively produced samples consisted of theα-Mg *** additively produced samples exhibited a refined grain structure compared to the feed *** feed material appeared to have a weak basal texture,while the additively produced samples experienced a strengthening of this basal *** additively produced samples showed a marginally higher hardness compared to the feed *** current work provided a pathway for solid state additive manufacturing of Mg suitable for structural applications such as automotive components and consumable biomedical implants.

关键词： Additive friction stir deposition Magnesium alloys Additive manufacturing Thermomechanical processing Materials processing solid state additive manufacturing

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A rare case of infectious colitis

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Gastroenterology Report 2016年第4期4卷 328-330,I0003页

作者： Aditya Kalakonda shashank Garg suraj Tandon Rakesh Vinayak sudhir Dutta state University of New York(sUNY)Upstate Medical University SyracuseNYUSA Department of Gastroenterology Sinai Hospital of BaltimoreBaltimoreMDUSA

Methicillin-resistant staphylococcus aureus(MRsA)is responsible for numerous infectious *** tract involvement is rather rare and only a handful of cases of MRsA colitis have been reported in North *** present a case of MRsA colitis in an adult without apparent risk *** computed tomography(CT)showed thickening of the sigmoid colon,indicative of colitis,and empiric therapy with ciprofloxacin and metronidazole was *** work-up for infection-including blood and stool cultures,and stool Clostridium difficile toxin assay-was *** patient’s clinical status improved but his diarrhea did not *** of stool culture demonstrated luxuriant growth of MRsA sensitive to *** vancomycin was administered and the patient’s symptoms promptly ceased.

关键词： methicillin-resistant staphylococcus aureus infectious colitis stool culture

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Emerging targets in cancer drug resistance

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Cancer Drug Resistance 2019年第2期2卷 161-177页

作者： shashank Kumar Prem Prakash Kushwaha sanjay Gupta school of Basic and Applied sciences Department of Biochemistry and Microbial SciencesCentral University of PunjabBathinda 151001India Department of Urology Case Western Reserve UniversityClevelandOhio 44106USA The Urology Institute University Hospitals Cleveland Medical CenterClevelandOhio 44106USA Department of Nutrition Case Western Reserve UniversityClevelandOhio 44106USA Divison of General Medical sciences Case Comprehensive Cancer CenterClevelandOhio 44106USA Department of Urology Louis Stokes Cleveland Veterans Affairs Medical CenterClevelandOhio 44106USA.

Drug resistance is a complex phenomenon that frequently develops as a failure to chemotherapy during cancer *** cells increasingly generate resistance to various chemotherapeutic drugs through distinct mechanisms and *** the molecular mechanisms involved in drug resistance remains an important area of research for identification of precise targets and drug discovery to improve therapeutic *** review highlights the role of some recent emerging targets and pathways which play critical role in driving drug resistance.

关键词： Drug resistance transforming growth factor-β Keap1-Nrf2 PI3K-Akt FOXO transcription factors focal adhesion kinases annexins MIEN1 gene splicing sphingolipids microRNA

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An Improved Methodology to Overcome Key Issues in Human Fecal Metagenomic DNA Extraction

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Genomics, Proteomics & Bioinformatics 2016年第6期14卷 371-378页

作者： Jitendra Kumar Manoj Kumar shashank Gupta Vasim Ahmed Manu Bhambi Rajesh Pandey Nat singh Chauhan Department of Biochemistry Maharshi Dayanand UniversityRohtak 124001India Ayurgenomics Unit Translational Research and Innovative Science Through AyurgeomicsCouncil of Scientific and Industrial ResearchInstitute of Genomics and Integrative BiologyNew Delhi 110020India

Microbes are ubiquitously distributed in nature, and recent culture-independent studies have highlighted the significance of gut microbiota in human health and disease. Fecal DNA is the primary source for the majority of human gut microbiome studies. However, further improvement is needed to obtain fecal metagenomic DNA with sufficient amount and good quality but low host genomic DNA contamination. In the current study, we demonstrate a quick, robust, unbiased, and cost-effective method for the isolation of high molecular weight （〉 23 kb） metagenomic DNA （260/280 ratio 〉 1.8） with a good yield （55.8 ± 3.8 ng/mg of feces）. We also confirm that there is very low human genomic DNA contamination （eubacterial： human genomic DNA marker genes = 227.9：1） in the human feces. The newly-developed method robustly performs for fresh as well as stored fecal samples as demonstrated by 16s rRNA gene sequencing using 454 FLX＋. Moreover, 16s rRNA gene analysis indicated that compared to other DNA extraction methods tested, the fecal metagenomic DNA isolated with current methodology retains species richness and does not show microbial diversity biases, which is further confirmed by qPCR with a known quantity of spike-in genomes. Overall, our data highlight a protocol with a balance between quality, amount, user-friendliness, and cost effectiveness for its suitability toward usage for cultureindependent analysis of the human gut microbiome, which provides a robust solution to overcome key issues associated with fecal metagenomic DNA isolation in human gut microbiome studies.

关键词： Metagenomic DNAextraction Gut microbiome Human feces 16s rRNA

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