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Structural basis for polyuridine tract recognition by SARS-CoV-2 Nsp15

Protein & Cell 2024年第7期15卷 547-552页

作者： Fumiaki Ito Hanjing Yang z.Hong zhou Xiaojiang S.Chen Molecular and Computational Biology Department of Biological SciencesUniversity of Southern CaliforniaLos AngelesCA 90089United States Department of Microbiology Immunology and Molecular GeneticsUniversity of CaliforniaLos AngelesCA 90095United States california NanoSystems Institute University of CaliforniaLos AngelesCA90095United States Genetic Molecular and Cellular Biology ProgramKeck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90089United States Norris Comprehensive cancer Center University of Southern CaliforniaLos AngelesCA 90089United States Center of Excellence in NanoBiophysics University of Southern CaliforniaLos AngelesCA 90089United States

Dear Editor,Coronaviruses have evolved a wide array of tactics to evade host antiviral *** host cells detect invading foreign nucleic acids including viral genome and viral replication intermediates,they activate interferon(IFN)signaling via cytoplasmic pattern recognition receptors(Kang et al.,2002;Kato et al.,2006).Remarkable stealth activities exhibited by coronaviruses are facilitated by a series of non-structural proteins(Nsps),such as Nsp15(Deng and Baker,2018;Deng et al.,2019;Hackbart et al.,2020),which is a uridine-specific endoribonuclease that mediates evasion of host detection of viral double-stranded RNA(dsRNA)(Bhardwaj et al.,2004;Deng et al.,2017;Frazier et al.,2021;Ivanov et al.,2004).Nsp15 targets a polyuridine[poly(U)]tract on the coronavirus negative strand RNA(Hackbart et al.,2020).Nsp15 limits the abundance and length of poly(U)within the negative strand RNA 5ʹ-extension by trimming down the initially synthesized poly(U)lead sequence to the optimal length that can suppress dsRNA formation but still serves as a template for poly(A)tail of the positive strand genome of the coronaviruses(Hofmann and Brian,1991).

关键词： p15 interferon template

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Size matters:the biochemical logic of ligand type in endocrine crosstalk

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Life Metabolism 2024年第1期3卷 10-20页

作者： Jameel Barkat Lone Jonathan z.Long Katrin J.Svensson Department of Pathology Stanford University School of MedicineStanfordCA 94305United States Department of Chemistry Stanford UniversityStanfordCA 94305United States Stanford Diabetes Research Center Stanford University School of MedicineStanfordCA 94305United States Sarafan ChEM-H Stanford UniversityStanfordCA 94305United States Wu Tsai Human Performance Alliance Stanford UniversityStanfordCA 94305United States Stanford cardiovascular Institute Stanford University School of MedicineCA 94305United States

The endocrine system is a fundamental type of long-range cell-cell communication that is important for maintaining metabolism,physiology,and other aspects of organismal *** signaling is mediated by diverse blood-borne ligands,also called hormones,including metabolites,lipids,steroids,peptides,and *** size and structure of these hormones are fine-tuned to make them bioactive,responsive,and adaptable to meet the demands of changing *** has nature selected such diverse ligand types to mediate communication in the endocrine system?What is the chemical,signaling,or physiologic logic of these ligands?What fundamental principles from our knowledge of endocrine communication can be applied as we continue as a field to uncover additional new circulating molecules that are claimed to mediate long-range cell and tissue crosstalk?This review provides a framework based on the biochemical logic behind this crosstalk with respect to their chemistry,temporal regulation in physiology,specificity,signaling actions,and evolutionary development.

关键词： endocrine ligand size metabolites signaling evolution

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Effects of friction stir processing and nano-hydroxyapatite on the microstructure,hardness,degradation rate and in-vitro bioactivity of WE43 alloy for biomedical applications

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Journal of Magnesium and Alloys 2024年第1期12卷 209-224页

作者： Bo Wu Farazila Yusof Fuguo Li Huan Miao A.R.Bushroa Mohd Ridha Bin Muhamad Irfan Anjum Badruddin Mahmoud z.Ibrahim Department of Mechanical Engineering Faculty of EngineeringUniversiti MalayaKuala Lumpur 50603Malaysia Centre of Advanced Manufacturing and Material Processing(AMMP Centre) Universiti MalayaKuala Lumpur 50603Malaysia Center of Foundation studies in Science Universiti MalayaKuala Lumpur 50603Malaysia State Key Laboratory of Solidification Processing School of Materials Science and EngineeringNorthwestern Polytechnical UniversityXi’an 710072China Mechanical Engineering Department College of EngineeringKing Khalid UniversityAbha 61421Saudi Arabia Design and Production Engineering Faculty of EngineeringAin Shams UniversityCairo 11517Egypt

Nowadays,magnesium alloys are emerging in biomedical implants for their similar properties to natural ***,the rapid degradation of magnesium alloys in biological media hinders successful *** of microstructure,as well as reinforcement particles can significantly improve the degradation *** this work,multi-pass friction stir processing(FSP)was proposed to synthesize WE43/nano-hydroxyapatite(n HA)surface composite,the microstructure,reinforced particle distribution,micro-hardness,corrosion behavior and in-vitro bioactivity were *** subsequent FSP passes of WE43 alloy and WE43/n HA composite refined the grain size which was reduced by 94.29%and 95.92%(2.63 and 1.88μm,respectively)compared to base metal after three *** resulted in increasing the microhardness by 120%(90.86 HV0.1)and 135%(105.59 HV0.1)for the WE43 and WE43-n HA,*** is found that increasing FSP passes improved the uniform distribution of n HA particles within the composite matrix which led to improved corrosion resistance and less degradation *** corrosion rate of the FSPed WE43/n HA composite after three passes was reduced by 38.2%(4.13 mm/year)and the degradation rate was reduced by 69.7%(2.87 mm/y).This is attributed to secondary phase(Mg24Y5and Mg41Nd5)particle fragmentation and redistribution,as well as a homogeneous distribution of n ***,the growing ca-P and Mg(OH)2layer formed on the surface represented a protective layer that reduced the degradation *** wettability test revealed a relatively hydrophilic surface with water contact angle of 49.1±2.2°compared to 71.2±2.1°for base ***,biomineralization test showed that apatite layer grew after immersion 7d in simulated body fluid with atomic ratio of ca/P 1.60 approaching the stoichiometric ratio(1.67)indicating superior bioactivity of FSPed WE43/n HA composite after three *** results raise that the grain refinement by FSP and introduction of n HA partic

关键词： Friction stir processing Magnesium-based composite Nano-hydroxyapatite Corrosion behavior In-vitro bioactivity

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Exploiting open source omics data to advance pancreas research

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Journal of Pancreatology 2024年第1期7卷 21-27页

作者： Gayathri Swaminathan Toshie Saito Sohail z.Husain Division of Gastroenterology Hepatology and NutritionDepartment of PediatricsStanford University School of MedicineStanfordCA

The"omics"revolution has transformed the biomedical research landscape by equipping scientists with the ability to interrogate complex biological phenomenon and disease processes at an unprecedented *** volume of"big"data generated by the different omics studies such as genomics,transcriptomics,proteomics,and metabolomics has led to the concurrent development of computational tools to enable in silico analysis and aid data *** the intensive resources and high costs required to generate and analyze big data,there has been centralized,collaborative efforts to make the data and analysis tools freely available as"Open Source,"to benefit the wider research *** research studies have contributed to this"big data rush"and have additionally benefitted from utilizing the open source data as evidenced by the increasing number of new research findings and publications that stem from such *** this review,we briefly introduce the evolution of open source omics data,data types,the"FAIR"guiding principles for data management and reuse,and centralized platforms that enable free and fair data accessibility,availability,and provide tools for omics data *** illustrate,through the case study of our own experience in mining pancreatitis omics data,the power of repurposing open source data to answer translationally relevant questions in pancreas research.

关键词： Gene expression Omics Open source data Pancreatitis

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Exploring a targeted approach for public health capacity restrictions during COVID-19 using a new computational model

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Infectious Disease Modelling 2024年第1期9卷 234-244页

作者： Ashley N.Micuda Mark R.Anderson Irina Babayan Erin Bolger Logan cantin Gillian Groth Ry Pressman-Cyna Charlotte z.Reed Noah J.Rowe Mehdi Shafiee Benjamin Tam Marie C.Vidal Tianai Ye Ryan D.Martin Department of Physics Engineering Physics&AstronomyQueen's UniversityKingstonONCanada Department of Medical Biophysics Western UniversityLondonONCanada Department of Mathematics and Statistics Queen's UniversityKingstonONCanada Department of Biology Queen's UniversityKingstonONCanada Department of Electrical and Computer Engineering Nazarbayev UniversityNur-SultanKazakhstan Energetic Cosmos Laboratory Nazarbayev UniversityNur-SultanKazakhstan School of Computing Queen's UniversityKingstonONCanada Department of Biomedical and Molecular Sciences Queen's UniversityKingstonONCanada Department of Physics University of OxfordOxfordUnited Kingdom Department of Physics Stanford UniversityStanfordCAUnited States

This work introduces the Queen's University Agent-Based Outbreak Outcome Model(QUABOOM).This tool is an agent-based Monte carlo simulation for modelling epidemics and informing public health *** illustrate the use of the model by examining capacity restrictions during a *** find that public health measures should focus on the few locations where many people interact,such as grocery stores,rather than the many locations where few people interact,such as small *** also discuss a case where the results of the simulation can be scaled to larger population sizes,thereby improving computational efficiency.

关键词： Monte-carlo Agent-based epidemic modelling COVID-19 Small business capacity restrictions Public health Basic reproductive number

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Development,validation,and transportability of several machine-learned,non-exercise-based VO_(2max)prediction models for older adults

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Journal of Sport and Health Science 2024年第5期13卷 611-620页

作者： Benjamin T.Schumacher Michael J.LaMonte Andrea z.LaCroix Eleanor M.Simonsick Steven P.Hooker Humberto Parada Jr. John Bellettiere Arun Kumar Herbert Wertheim School of Public Health and Human Longevity Science University of California San DiegoLa JollaCA 92093USA Department of Epidemiology and Environmental Health School of Public Health and Health ProfessionsUniversity at BuffaloState University of New YorkBuffaloNY 14214USA Translational Gerontology Branch Intramural Research ProgramNational Institute on AgingNational Institutes of HealthBaltimoreMD 21225USA College of Health and Human Services San Diego State UniversitySan DiegoCA 92182USA Division of Epidemiology and Biostatistics School of Public HealthSan Diego State UniversitySan DiegoCA 92182USA University of california San Diego Moores cancer Center La JollaCA 92093USA Computer Science and Engineering and Halicioglu Data Science Institute University of California San DiegoLa JollaCA 92093USA

Background:There exist few maximal oxygen uptake(VO_(2max))non-exercise-based prediction equations,fewer using machine learning(ML),and none specifically for older *** direct measurement of VO_(2max)is infeasible in large epidemiologic cohort studies,we sought to develop,validate,compare,and assess the transportability of several ML VO_(2max)prediction ***:The Baltimore Longitudinal Study of Aging(BLSA)participants with valid VO2_(max)tests were included(n=1080).Least absolute shrinkage and selection operator,linear-and tree-boosted extreme gradient boosting,random forest,and support vector machine(SVM)algorithms were trained to predict VO_(2max)*** developed these algorithms for:(a)the overall BLSA,(b)by sex,(c)using all BLSA variables,and(d)variables common in aging ***,we quantified the associations between measured and predicted VO_(2max)and ***:The age was 69.0±10.4 years(mean±SD)and the measured VO_(2max)was 21.6±5.9 mL/kg/*** absolute shrinkage and selection operator,linear-and tree-boosted extreme gradient boosting,random forest,and support vector machine yielded root mean squared errors of 3.4 mL/kg/min,3.6 mL/kg/min,3.4 mL/kg/min,3.6 mL/kg/min,and 3.5 mL/kg/min,*** quartiles of measured VO_(2max)showed an inverse gradient in mortality *** VO_(2max)variables yielded similar effect estimates but were not robust to ***:Measured VO_(2max)is a strong predictor of *** ML can improve the accuracy of prediction as compared to simpler approaches but estimates of association with mortality remain sensitive to *** studies should seek to reproduce these results so that VO_(2max),an important vital sign,can be more broadly studied as a modifiable target for promoting functional resiliency and healthy aging.

关键词： cardiorespiratory fitness Prediction algorithms Epidemiology Mortality

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Geomorphic impacts of timber harvesting

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Chinese Science Bulletin 2001年第S1期46卷 1-4页

作者： Olav SlaymakerDepartment of Geography, The University of British Columbia, Vancouver, B. C. V6T 1z2, canada (e-mail: olav@geog.ubc.ca) Department of Geography The University of British Columbia Vancouver Canada

Timber harvesting influences (a) forest hydrology; (b) fluvial geomorphology; (c) terrain stability; and (d) integrated watershed behavior. Impacts on forest hydrology are well understood and include increased average runoff, total water yield, increased storm runoff and advances in timing of floods. Stream channels and valley floors are impacted differently by fine sediment, coarse sediment and large woody debris transport. Terrain stability is influenced through gully and mass movement processes that are accelerated by timber harvesting. Impacts on integrated watershed behavior are assessed through disturbed sediment budgets and lake sediments.

关键词： timber harvesting forest hydrology stream channel hillslope stability.

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Geochemical elements in suspended particulate matter of Ensenada de La Paz Lagoon,Baja california Peninsula,Mexico:Sources,distribution,mass balance and ecotoxicological risks

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Journal of Environmental Sciences 2024年第2期136卷 422-436页

作者： Sandra Soledad Morales-García Pilar de Acacia Pérez-Escamilla Suresh Babu Sujitha Pichaimani Godwyn-Paulson Andrés Felipe zuniga-cabezas Muthuswamy Ponniah Jonathan Instituto Politécnico Nacional(IPN) Centro Mexicano para la Producción más Limpia(CMPL)Av.Acueducto s/nCol.Barrio la Laguna TicománDel Gustavo A.MaderoC.P.07340Ciudad de MéxicoMexico Instituto Politécnico Nacional(IPN) Escuela Superior de Ingeniería y Arquitectura(ESIA)Unidad Ticomán***án 600Delg.Gustavo A.MaderoC.P.07340Ciudad de México(CDMX)Mexico Instituto Politécnico Nacional(IPN) Centro Interdisciplinario de Investigaciones y Estudios sobre Medio Ambiente y Desarrollo(CIIEMAD)Calle 30 de Junio de 1520Barrio la Laguna TicománDel.Gustavo A.MaderoC.P.07340Ciudad de MéxicoMéxico

The present study aimed to evaluate multi-element concentrations(Al,As,ca,Cd,Co,Cr,Cu,Fe,Mg,Mn,Mo,Ni,Pb,Sr)in suspended particulate material(SPM)collected from Ensenada de La Paz(ELP)lagoon,Baja california Sur,Mexico in two different periods(September and May)to comprehend their origin,geochemical behavior,mass transfer and associated ecotoxicological *** 24 hr variation coefficient of volumetric SPM levels were found to be 51.7%in September and 40.5%in May,signifying the effects of oceanic *** calculated enrichment factor(EF)values for all the studied elements were of higher magnitude because of the high surface area and oxide nature of SPM,and in this study,Mo had the highest EF of 46.77 probably due to its origin from continental *** the ecotoxicological perspective,the integrated toxic risk index revealed low toxic risk to the benthic ***,the mean-ERM-Quotient calculated using the particulate concentrations of As,Cd,Cr,Cu,Ni,Pb indicated 9%probability of toxicity to *** comprehensive geochemical and ecotoxicological assessment of particulate metal concentrations in the ELP lagoon signify low to moderate contamination.

关键词： Suspended particulate material Heavy metals Risk assessment Mass transfer Ensenada de La Paz

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Preliminary performance analysis and optimization based on 1D neutronics model for Indian DEMO HCCB blanket

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Plasma Science and Technology 2020年第8期22卷 184-191页

作者： D AGGARWAL C DANANI M z YOUSSEF Institute for Plasma Research GandhinagarGujarat 382428India Homi Bhabha National Institute(HBNI) AnushaktinagarMumbai 400094India University of california-Los Angeles Los AngelesCA 90095United States of America

India,under its breeding blanket R&D program for DEMO,is focusing on the development of two tritium breeding blanket concepts;namely the lead-lithium-cooled ceramic breeder and the helium-cooled ceramic breeder(HCCB).The study presented in this paper focuses on the neutronic design analysis and optimization from the tritium breeding perspective of the HCCB *** Indian concept has an edge-on configuration and is one of the variants of the helium-cooled solid breeder blanket concepts proposed by several partner countries in *** Indian HCCB blanket having lithium titanate(Li2TiO3)as the tritium breeder and beryllium(Be)as the neutron multiplier with reduced-activation ferritic/martensitic steel structure aims at utilizing the low-energy neutrons at the rear part of the *** aim of the optimization study is to minimize the radial blanket thickness while ensuring tritium self-sufficiency and provide data for further neutronic design and thermal-hydraulic layout of the HCCB *** is found that inboard and outboard blanket thicknesses of 40 cm and 60 cm,respectively,can give a tritium breeding ratio(TBR)>1.3,with 60%6Li enrichment,which is assumed to be sufficient to cover potential tritium losses and associated *** results also demonstrated that the Be packing fraction(PF)has a more profound impact on the TBR as compared to 6Li enrichment and the PF of Li2TiO3.

关键词： DEMO helium-cooled ceramic breeder blanket neutronic optimization study tritium breeding ratio

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Optical redox imaging of ANT1-de-cient muscles

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Journal of Innovative Optical Health Sciences 2024年第1期17卷 135-140页

作者： He N.Xu Ryan M.Morrow Min Feng Huaqing zhao Douglas Wallace Lin z.Li Britton Chance Laboratory of Redox Imaging Department of Radiology Perelman School of Medicine University of Pennsylvania PhiladelphiaPA 19104USA Center for Mitochondrial and Epigenomic Medicine Children's Hospital of Philadelphia Research Institute Philadelphia PA 19104USA Center for Biostatistics and Epidemiology Lewis Katz School of Medicine at Temple University Philadelphia PA 19140USA

Adenine nucleotide translocator(ANT)is a mitochondrial protein involved in the exchange of ADP and ATP across the mitochondrial inner *** plays a crucial role in cellular energy metabolism by facilitating the transport of ATP synthesized within the mitochondria to the *** isoform ANT1 predominately expresses in cardiac and skeletal *** or dysregulation in ANT1 have been implicated in various mitochondrial disorders and neuromuscular *** aimed to examine whether ANT1 deletion may affect mitochondrial redox state in our established ANT1-de-cient *** and quadriceps resected from age-matched wild type(WT)and ANT1-de-cient mice were snap-frozen in liquid *** Chance redox scanner was utilized to perform 3D optical redox *** sample underwent scanning across 3–5 *** averaging analysis showed no signi-cant differences in the redox indices(NADH,flavin adenine dinucleotide containing-flavoproteins Fp,and the redox ratio Fp/(NADH+Fp)between WT and ANT1-de-cient ***,quadriceps had higher Fp than hearts in both groups(p¼0:0004 and 0.01,respectively).Furthermore,the quadriceps were also more oxidized(a higher redox ratio)than hearts in WT group(p¼0:004).NADH levels were similar in all *** data suggest that under non-stressful physical condition,the ANT1-de-cient muscle cells were in the same mitochondrial state as WT ones and that the signi-cant difference in the mitochondrial redox state between quadriceps and hearts found in WT might be diminished in ANT1-de-cient *** imaging of muscles under physical stress can be conducted in future.

关键词： ANT1 redox ratio flavoproteins

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