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Population-scale genetic control of alternative polyadenylation and its association with human diseases

Quantitative Biology 2022年第1期10卷 44-54页

作者： Lei Li Yumei Li Xudong Zou Fuduan Peng Ya Cui eric j.wagner Wei Li Institute of Systems and Physical Biology Shenzhen Bay LaboratoryShenzhen 518055China Division of Computational Biomedicine Department of Biological ChemistrySchool of MedicineUniversity of CaliforniaIrvineCA 92697USA Department of Biochemistry&Molecular Biology University of Texas Medical BranchGalvestonTX 77555USA

Background:Genome-wide association studies(GWAS)have identified thousands of genomic non-coding variants statistically associated with many human traits and diseases,including cancer.However,the functional interpretation of these non-coding variants remains a significant challenge in the post-GWAS era.Alternative polyadenylation(APA)plays an essential role in post-transcriptional regulation for most human genes.By employing different poly(A)sites,genes can either shorten or extend the 3'-UTRs that contain cu-regulatory elements such as miRNAs or RNA-binding protein binding sites.Therefore,APA can affect the mRNA stability,translation,and cellular localization of proteins.Population-scale studies have revealed many inherited genetic variants that potentially impact APA to further influence disease susceptibility and phenotypic diversity,but systematic computational investigations to delineate the connections are in their earliest states.Results:Here,we discuss the evolving definitions of the genetic basis of APA and the modern genomics tools to identify,characterize,and validate the genetic influences of APA events in human populations.We also explore the emerging and surprisingly complex molecular mechanisms that regulate APA and summarize the genetic control of APA that is associated with complex human diseases and traits.Conclusion:APA is an intermediate molecular phenotype that can translate human common non-coding variants to individual phenotypic variability and disease susceptibility.

关键词： GWAS eQTL disease alternative polyadenylation

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Alternative polyadenylation of mRNA and its role in cancer

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Genes & Diseases 2021年第1期8卷 61-72页

作者： Fuwen Yuan William Hankey eric j.wagner Wei Li Qianben Wang Department of Pathology Duke University School of MedicineDurhamNC27710USA Department of Biochemistry and Molecular Biology University of Texas Medical Branch at GalvestonGalvestonTX77555USA Department of Biological Chemistry University of CaliforniaIrvineCA92697USA Duke Cancer Institute Center for Prostate and Urologic Cancers Duke University School of MedicineDurhamNC27710USA

Alternative polyadenylation(APA)is a molecular process that generates diversity at the 3′end of RNA polymeraseⅡtranscripts from over 60%of human genes.APA is derived from the existence of multiple polyadenylation signals(PAS)within the same transcript,and results in the differential inclusion of sequence information at the 3′end.While APA can occur between two PASs allowing for generation of transcripts with distinct coding potential from a single gene,most APA occurs within the untranslated region(3′UTR)and changes the length and content of these non-coding sequences.APA within the 3′UTR can have tremendous impact on its regulatory potential of the mRNA through a variety of mechanisms,and indeed this layer of gene expression regulation has profound impact on processes vital to cell growth and development.Recent studies have particularly highlighted the importance of APA dysregulation in cancer onset and progression.Here,we review the current knowledge of APA and its impacts on mRNA stability,translation,localization and protein localization.We also discuss the implications of APA dysregulation in cancer research and therapy.

关键词： 3′untranslated region Alternative polyadenylation Cancer Gene regulation Polyadenylation signals

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Physiological phenotypes differ among color morphs in introduced common wall lizards(Podarcis muralis)

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Integrative Zoology 2024年第3期19卷 505-523页

作者： Ali AMER Sierra SPEARS Princeton L.VAUGHN Cece COLWELL Ethan H.LIVINGSTON Wyatt MCQUEEN Anna SCHILL Dustin G.REICHARD eric j.GANGLOFF Kinsey M.BROCK Department of Biological Sciences Ohio Wesleyan UniversityDelawareOhioUSA Department of Ecology and Evolutionary Biology Princeton UniversityPrincetonNew JerseyUSA Department of Biology Idaho State UniversityPocatelloIdahoUSA Department of Environmental Science Policyand ManagementCollege of Natural ResourcesUniversity of CaliforniaBerkeleyUSA Museum of Vertebrate Zoology University of CaliforniaBerkeleyUSA

Many species exhibit color polymorphisms which have distinct physiological and behavioral characteristics.However,the consistency of morph trait covariation patterns across species,time,and ecological contexts remains unclear.This trait covariation is especially relevant in the context of invasion biology and urban adaptation.Specifically,physiological traits pertaining to energy maintenance are crucial to fitness,given their immediate ties to individual reproduction,growth,and population establishment.We investigated the physiological traits of Podarcis muralis,a versatile color polymorphic species that thrives in urban environments(including invasive populations in Ohio,USA).We measured five physiological traits(plasma corticosterone and triglycerides,hematocrit,body condition,and field body temperature),which compose an integrated multivariate phenotype.We then tested variation among co-occurring color morphs in the context of establishment in an urban environment.We found that the traits describing physiological status and strategy shifted across the active season in a morph-dependent manner—the white and yellow morphs exhibited clearly different multivariate physiological phenotypes,characterized primarily by differences in plasma corticosterone.This suggests that morphs have different strategies in physiological regulation,the flexibility of which is crucial to urban adaptation.The white-yellow morph exhibited an intermediate phenotype,suggesting an intermediary energy maintenance strategy.Orange morphs also exhibited distinct phenotypes,but the low prevalence of this morph in our study populations precludes clear interpretation.Our work provides insight into how differences among stable polymorphisms exist across axes of the phenotype and how this variation may aid in establishment within novel environments.

关键词： color polymorphism physiological status seasonal variation thermoregulation urban habitat

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A One Health approach to fight antimicrobial resistance in Uganda: Implementation experience, results, and lessons learned

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Biosafety and Health 2024年第2期6卷 125-132页

作者： Reuben Kiggundu j.P.Waswa Niranjan Konduri Hassan Kasuja Marion Murungi Patrick Vudriko Harriet Akello eric Lugada Cecilia Muiva Esther Were Dinah Tjipura Henry Kajumbula Kate Kikule Emmanuel Nfor Mohan P.joshi USAID Medicines Technologiesand Pharmaceutical Services ProgramManagement Sciences for HealthKampala 256Uganda USAID Medicines Technologiesand Pharmaceutical Services ProgramManagement Sciences for HealthArlingtonVA 22203USA College of Veterinary Medicine Animal Resources and BiosecurityMakerere UniversityKampala 256Uganda Ministry of Health Uganda Kampala 256Uganda USAID Strengthening Supply Chain Systems Activity Management Sciences for HealthKampala 256Uganda USAID Medicines Technologiesand Pharmaceutical Services ProgramManagement Sciences for HealthNairobi 254Kenya Department of Microbiology College of Health SciencesMakerere UniversityKampala 256Uganda

Uganda has been implementing the Global Health Security Agenda(GHSA)since 2015 to build its capacity according to World Health Organization(WHO)Benchmarks on International Health Regulations Capacities.The country remains prone to outbreaks,with more than 20 disease outbreaks reported in the past five years,including Ebola virus disease,Crimean-Congo haemorrhagic fever,Marburg haemorrhagic fever,measles,yellow fever,coronavirus disease 2019(COVID-19),and cholera.Antimicrobial resistance(AMR)is an ongoing challenge.Uganda scored capacity level 3 on infection prevention and control(IPC)and antimicrobial stewardship(AMS)in the 2017 joint External Evaluation(jEE)assessment.Identified gaps were being addressed after a self-assessment in 2021.This paper describes the technical assistance approaches provided to Uganda by the Medicines,Technologies,and Pharmaceutical Services Program,funded by the United States(U.S.)Agency for International Development,and implemented by Management Sciences for Health.The program,through a One Health approach,supported systematic capacity strengthening based on the jEE's capacity advancement framework for global health security,specifically relating to AMR.The program's interventions impacted 32 WHO benchmark actions(7 for AMR multisectoral coordination,16 for IPC,and 9 for AMS),contributing to Uganda's strengthened GHSA capacity.Leveraging success built on the AMR platform,the program trained 745 health workers in IPC for the Ebola virus and provided support for simulation exercises by eight district IPC teams.The program also worked with the Ministry of Health to coordinate IPC for the COVID-19 response in five health regions,covering 45 districts and reaching 5,452 health workers at 858 health facilities.

关键词： One health Antimicrobial resistance Antibiotic resistance jointexternal evaluation Global health security Uganda Africa WHO Benchmarks for International Health Regulations Capacities

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Confirmation of a Sub-Saturn-size Transiting Exoplanet Orbiting a G Dwarf:TOI-1194 b and a Very Low Mass Companion Star: TOI-1251 B from TESS

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Research in Astronomy and Astrophysics 2024年第3期24卷 129-143页

作者： jia-Qi Wang Xiao-jun jiang jie Zheng Hanna Kellermann Arno Riffeser Liang Wang Karen A.Collins Allyson Bieryla Lars A.Buchhave Steve B.Howell Elise Furlan eric Girardin joao Gregorio eric jensen Felipe Murgas Mesut Yilmaz Sam Quinn Xing Gao Ruo-Yu Zhou Frank Grupp Hui-juan Wang CAS Key Laboratory of Optical Astronomy National Astronomical ObservatoriesChinese Academy Of SciencesBeijing 10010China University of Chinese Academy of Sciences Beijing 100049China University Observatory Munich Scheinertrsse 1.D-81679 MunichGemany Max Planck Institute for Extraterrestrial Physics Giessenbachstr.1D-85748 GarchingGermany National Astronomical Observatories/Nanjing Institute of Astronomical Optics&Technology Chinese Academy of SciencesNanjing210042China CAS Key Laboratory of Astronomical Optics&Technology Nanjing Institute of Astronomical Optics&TechnologyNanjing 210042China Center for Astrophysics Harvard&Smithsonian60 Garden Street.CambridgeMA 02138USA National Space Institute Technical University of DenmarkElektrovejDK-2800 KgsLyngbyDenmark NASA Ames Research Center Moffett FieldCA 94035USA NASA Exoplanet Science Institute Caltech/IPACMail Code 100-221200 E.California Blvd.PasadenaCA91125USA Grand Pra Observatory Switzerland Department of Physics Washington UniversitySt.LouisMO 63130.USA Department of Physics and Astronomy Swarthmore CollegeSwarthmorePA 19081USA Instituto de Astrofísica de Canarias(IAC) E-38205 La Laguna.TenerifeSpain Departamento de Astrofísica Universidad de La LagunaSpain Dept.of Astronomy and Space Sciences Ankara UniversityTandogan 06100AnkaraTurkey Xinjiang Astronomical Observatory Chinese Academy of SciencesUrumqi 830011China Urumqi No.1 Senior High School Urumqi 830002China Lijiang Gemini Observatory Lijiang 674199China

We report the confirmation of a sub-Saturn-size exoplanet,TOI-1194 b,with a mass of about 0.456+0.055-0.051M_(j),and a very low mass companion star with a mass of about 96.5±1.5 Mj,TOI-1251 *** candidates provided by the Transiting Exoplanet Survey Satellite(TESS)are suitable for further follow-up observations by ground-based telescopes with small and medium apertures.The analysis is performed based on data from several telescopes worldwide,including telescopes in the Sino-German multiband photometric campaign,which aimed at confirming TESS Objects of Interest(TOIs)using ground-based small-aperture and medium-aperture telescopes,especially for long-period targets.TOI-1194 b is confirmed based on the consistent periodic transit depths from the multiband photometric data.We measure an orbital period of 2.310644±0.000001 days,the radius is 0.767+0.045-0.041Rj and the amplitude of the RV curve is 69.4_(-7.3)^(+7.9)m s^(-1).TOI-1251 B is confirmed based on the multiband photometric and high-resolution spectroscopic data,whose orbital period is 5.963054+0.000002-0.000001days,radius is 0.947+0.035-0.033 R_(j) and amplitude of the RV curve is 9849_(-40)^(+42)ms^(-1).

关键词： planets and satellites fundamental parameters-planets and satellites gaseous planets-stars fundamental parameters-stars low-mass-methods data analysis-techniques photometric-techniques spectroscopic

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Obstructive sleep apnea:Overlooked comorbidity in patients with diabetes

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World journal of Diabetes 2024年第7期15卷 1448-1460页

作者： eric D Tenda joshua Henrina jin H Cha Muhammad R Triono Ersananda A Putri Dahliana j Aristy Dicky L Tahapary Division of Respirology and Critical Care Department of Internal MedicineFaculty of Medicine Universitas Indonesia-Cipto Mangunkusumo HospitalDKI JakartaJakarta Pusat 10430Indonesia Head of Research Group Artificial Intelligence and Digital Health Indonesian Medical Education and Research InstituteFaculty of Medicine University of IndonesiaDKI JakartaJakarta Pusat 10430Indonesia Division of Endocrinology Metabolism and DiabetesDepartment of Internal MedicineFaculty of Medicine Universitas Indonesia-Cipto Mangunkusumo HospitalDKI JakartaJakarta Pusat 10430Indonesia

In this review article,we explore the interplay between obstructive sleep apnea(OSA)and type 2 diabetes mellitus(T2DM),highlighting a significant yet often overlooked comorbidity.We delve into the pathophysiological links between OSA and diabetes,specifically how OSA exacerbates insulin resistance and disrupts glucose metabolism.The research examines the prevalence of OSA in diabetic patients and its role in worsening diabetes-related complications.Emphasizing the importance of comprehensive management,including weight control and positive airway pressure therapy,the study advocates integrated approaches to improve outcomes for patients with T2DM and OSA.This review underscores the necessity of recognizing and addressing OSA in diabetes care to ensure more effective treatment and better patient outcomes.

关键词： Obstructive sleep apnea Type 2 diabetes mellitus Macrovascular Microvascular Weight loss Positive airway pressure

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Pre-operative visceral adipose tissue radiodensity is a potentially novel prognostic biomarker for early endoscopic post-operative recurrence in Crohn’s disease

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World journal of Gastrointestinal Surgery 2024年第3期16卷 740-750页

作者： Phillip Gu Shishir Dube Norman Gellada So Yung Choi Susan Win Yoo jin Lee Shaohong Yang Talin Haritunians Gil Y Melmed eric A Vasiliauskas Niru Bonthala Gaurav Syal Andres j Yarur David Ziring Shervin Rabizadeh Phillip Fleshner Cindy Kallman Suzanne Devkota Stephan R Targan Dalin Li Dermot PB McGovern Department of Medicine Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Imaging Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Biostatistics Shared Resource Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Internal Medicine Keimyung University School of MedicineDaegu 42601South Korea Department of Medicine University of California at Los AngelesLos AngelesCA 90095United States Department of Medicine University of California at San DiegoSan DiegoCA 92093United States Department of Pediatrics Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Surgery Cedars-Sinai Medical CenterLos AngelesCA 90048United States

BACKGROUND Evidence suggests inflammatory mesenteric fat is involved in post-operative recurrence(POR)of Crohn’s disease(CD).However,its prognostic value is INTRODUCTION Crohn’s disease(CD)is a debilitating chronic immune-mediated inflammatory disease(IMID)of the gastrointestinal tract that is increasing in incidence and prevalence globally[1].CD patients often undergo surgery for disease-related complic-ations and/or medically refractory disease.Unfortunately,surgery is not curative,and many patients develop post-operative recurrence(POR)of CD with a significant proportion eventually requiring additional surgeries.With advances in early detection and therapeutics,the contemporary 10-year risk of surgery has improved from 50%to 26%,but the risk of recurrent surgery has remained unchanged at 30%,suggesting a need to improve post-operative management strategies[2].Presently,there are two accepted strategies to mitigate POR,but each have potential limitations.Firstly,patients start early post-operative pharmacologic prophylaxis within 4-6 wk after surgery.This strategy can potentially overtreat a subset of patient who may not develop long-term disease recurrence off therapy.Consequently,these patients are at risk of medication-related adverse events and the direct and indirect costs associated with therapy with little or no benefit[3].The second strategy is performing early colonoscopy within 6-12 months after surgery and escalating therapy based on FOOTNOTES Author contributions:Gu P is the guarantor of the article and was involved in concept and design,data collection,statistical analysis,drafting of manuscript,and final approval of manuscript;Dube S and Choi SY were involved in statistical analysis,drafting of the manuscript,and final approval of manuscript;Gellada N,Win S,Lee Yj and Yang S were involved in the data collection,drafting of the manuscript,and final approval of manuscript;Haritunians T and Li D were involved in data analysis and interpretation,drafting of manuscript and final approval of manuscript;

关键词： Crohn’s disease Surgery Visceral adipose tissue Mesenteric adipose tissue Creeping fat Computed tomography

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Rare etiology of colonic intussusception involving an adult with emphysematous cystic enteropathy:A case report and review of literature

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World journal of Clinical Cases 2024年第17期12卷 3161-3167页

作者： eric Bergeron Maude Pichette Geneviève Boisvert Thibaut Manière Étienne Désilets Department of Surgery Charles LeMoyne HospitalGreenfield Park J4V 2H1QuebecCanada Department of Medical Imaging Charles LeMoyne HospitalGreenfield Park J4V 2H1QuebecCanada Department of Gastroenterology Charles LeMoyne HospitalGreenfield Park J4V 2H1QuebecCanada

BACKGROUND Pneumatosis cystoides intestinalis(PCI),characterized by a collection of gas-filled cysts in the intestinal wall,is an uncommon but well-known condition in gastroenterology.Abdominal pain is the most frequent symptom associated with PCI.Intussusception represents a potential cause of recurrent abdominal pain or emergency presentation.However,the occurrence of colonic intussusception secondary to PCI is very unusual in adulthood.CASE SUMMARY A 52-year-old male,known with idiopathic PCI,presented seventeen months after initial diagnosis with a new right upper quadrant pain.A computed tomographyscan demonstrated a colonic intussusception at the hepatic flexure.PCI did not progress compared with initial investigation.The patient underwent an emergency right hemicolectomy.CONCLUSION Resection was recommended in this case because PCI proved to be persisting with no identified curable cause.Surgery allowed to address the underlying pathology,the potential relapse of intussusception,and the likely cause of recurrent abdominal pain,either invagination or PCI itself.

关键词： Pneumatosis cystoides intestinalis Colonic intussusception Colonic obstruction Colonoscopy Case report

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Penicillin-G: Efficacy against <i>Flavobacterium psychrophilum</i>and evaluation of lethal dose limits for rainbow trout

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Open journal of Animal Sciences 2012年第3期2卷 150-158页

作者： eric j. wagner Randall W. Oplinger Matthew Bartley G Fisheries Experiment Station Utah Division of Wildlife Resources Logan USA

The effect of penicillin-G on Flavobacterium psychrophilum, the cause of bacterial coldwater disease, was evaluated in 15 min and overnight exposures. Separate tests evaluated the effect of increasing doses of penicillin-G to rainbow trout Oncorhynchus mykiss eggs, fingerlings, and adults. Rainbow trout eggs were exposed for 1 h to penicillin doses of 0, 250, 500, 1,000, 10,000, 50,000, or 100,000 IU/mL. Mean percent hatch ranged from 64.6% to 75.1%, and did not significantly differ among the treatments. Fingerlings were injected intraperitoneally (i.p.) with 200 μL of 0, 1, 10, 100, 1,000, 10,000, 100,000, or 500,000 IU/mL. Probit analysis resulted in a LD10 (lethal dose for 10% of injected fish) of 52,868 IU/mL (95% confidence limits: 31,522 - 69,490 IU/mL) and a LD50 of 131,466 IU/mL (113,095 - 157,878 IU/mL). Brood stock were injected (i.p.) with 200 μL of penicillin at concentrations of 0 (control), 10,000, 50,000, 100,000, 200,000, 400,000, or 800,000 IU/mL. Mortality ranged from 0% to 7% (50,000 IU/mL treatment) and did not significantly differ among treatments. In 28 h exposure tests, penicillin concentrations of ≥ 333 IU/mL were required to completely suppress growth of F. psychrophilum. In 15 min exposures, ≥ 10,000 IU/mL were needed to achieve the same result. Tests indicated that rainbow trout eggs can tolerate 1 h exposures to penicillin-G concentrations as high as 100,000 IU/mL, and that brood fish can tolerate injections of at least 800,000 IU/mL. Fingerling data however, suggested that injection of doses greater than 10,000 IU/mL can be toxic. The data suggests rainbow trout eggs or brood can tolerate high doses of penicillin-G that could be used for controlling the transfer of F. psychrophilum to hatcheries receiving eggs.

关键词： Flavobacterium psychrophilum Penicillin Antibiotics Toxicity Drug Safety

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美股科技双杰崛起

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商业周刊（中文版） 2024年第5期 48-49页

作者： eric j.Weiner jeran Wittenstein Mark Gurman 孟洁冰(译) 不详

十多年来,少数几家科技巨头推动美国股市一路向前,带来了超高速增长的希望。你熟知这些家喻户晓的名字:比如谷歌的母公司Alphabet、亚马逊公司(***)、苹果公司、Facebook的母公司Meta、微软公司和特斯拉公司。这些公司的名号组成了各种... 详细信息

十多年来,少数几家科技巨头推动美国股市一路向前,带来了超高速增长的希望。你熟知这些家喻户晓的名字:比如谷歌的母公司Alphabet、亚马逊公司(***)、苹果公司、Facebook的母公司Meta、微软公司和特斯拉公司。这些公司的名号组成了各种首字母缩略词——FANG、FAANG、MAMAA——几乎成为每个投资组合的主要配置。

关键词：投资组合母公司 Amazon 苹果公司亚马逊公司美国股市 .com

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