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Developmental regulation of neuronal gene expression by Elongator complex protein 1 dosage

Journal of Genetics and Genomics 2022年第7期49卷 654-665页

作者： Elisabetta morini Dadi Gao emily m.logan monica Salani Aram J.Krauson Anil Chekuri Yei-Tsung Chen Ashok Ragavendran Probir Chakravarty Serkan Erdin Alexei Stortchevoi Jesper Q.Svejstrup michael E.Talkowski Susan A.Slaugenhaupt Center for Genomic medicine Massachusetts General Hospital Research InstituteBostonMAUSA Department of Neurology Massachusetts General Hospital Research Institute and Harvard Medical SchoolBostonMAUSA Program in medical and Population Genetics and Stanley Center for Psychiatric Research Broad Institute of Harvard and MITCambridgeMAUSA Department of Life Sciences and Institute of Genome Sciences National Yang Ming Chiao Tung UniversityTaiwanChina Bioinformatics and Biostatistics The Francis Crick InstituteLondonUK mechanisms of Transcription Laboratory The Francis Crick InstituteLondonUK Department of Cellular and molecular medicine Panum InstituteUniversity of CopenhagenCopenhagenDenmark

Familial dysautonomia(FD), a hereditary sensory and autonomic neuropathy, is caused by a mutation in the Elongator complex protein 1(ELP1) gene that leads to a tissue-specific reduction of ELP1 protein. Our work to generate a phenotypic mouse model for FD headed to the discovery that homozygous deletion of the mouse Elp1 gene leads to embryonic lethality prior to mid-gestation. Given that FD is caused by a reduction, not loss, of ELP1, we generated two new mouse models by introducing different copy numbers of the human FD ELP1 transgene into the Elp1 knockout mouse(Elp1) and observed that human ELP1 expression rescues embryonic development in a dose-dependent manner. We then conducted a comprehensive transcriptome analysis in mouse embryos to identify genes and pathways whose expression correlates with the amount of ELP1. We found that ELP1 is essential for the expression of genes responsible for nervous system development. Further, gene length analysis of the differentially expressed genes showed that the loss of Elp1 mainly impacts the expression of long genes and that by gradually restoring Elongator, their expression is progressively rescued. Finally, through evaluation of co-expression modules, we identified gene sets with unique expression patterns that depended on ELP1 expression.

关键词： ELP1 Elongator Transcriptional elongation Familial dysautonomia Neurodevelopmental disease

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Global Change in Agricultural Flash Drought over the 21st Century

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Advances in Atmospheric Sciences 2024年第2期41卷 209-220,I0002-I0019页

作者： emily BLACK National Centre for Atmospheric Science Fairbairn House71-75 Clarendon RoadLeedsLS29PHU.K Department of meteorology Brian Hoskins BuildingUniversity of ReadingWhiteknights campusReadingRG66ETU.K.

Agricultural flash droughts are high-impact phenomena, characterized by rapid soil moisture dry down. The ensuing dry conditions can persist for weeks to months, with detrimental effects on natural ecosystems and crop cultivation. Increases in the frequency of these rare events in a future warmer climate would have significant societal impact. This study uses an ensemble of 10 Coupled model Intercomparison Project(CmIP) models to investigate the projected change in agricultural flash drought during the 21st century. Comparison across geographical regions and climatic zones indicates that individual events are preceded by anomalously low relative humidity and precipitation, with long-term trends governed by changes in temperature, relative humidity, and soil moisture. As a result of these processes, the frequency of both upperlevel and root-zone flash drought is projected to more than double in the mid-and high latitudes over the 21st century, with hot spots developing in the temperate regions of Europe, and humid regions of South America, Europe, and southern Africa.

关键词： flash drought climate change soil moisture agricultural drought CmIP

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Advancing respirable coal mine dust source apportionment:a preliminary laboratory exploration of optical microscopy as a novel monitoring tool

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International Journal of Coal Science & Technology 2024年第2期11卷 222-233页

作者： Nestor Santa emily Sarver Department of mining and minerals Engineering Virginia TechBlacksburgVA 24061USA

Exposure to respirable coal mine dust(RCmD)can cause chronic and debilitating lung ***-time monitoring capabilities are sought which can enable a better understanding of dust components and *** many underground mines,RCmD includes three primary components which can be loosely associated with three major dust sources:coal dust from the coal seam itself,silicates from the surrounding rock strata,and carbonates from the inert‘rock dust’products that are applied to mitigate explosion hazards.A monitor which can reliably partition RCmD between these three components could thus allow source *** tracking silicates,specifically,could be valuable since the most serious health risks are typically associated with this component-particularly if abundant in crystalline *** a monitoring concept based on field microscopy,and following up on prior research using polarized light,the aim of the current study was to build and test a model to classify respirable-sized particles as either coal,silicates,or *** model development,composite dust samples were generated in the laboratory by successively depositing dust from high-purity materials onto a sticky transparent substrate,and imaging after each deposition event such that the identity of each particle was known a *** testing followed a similar approach,except that real geologic materials were used as the source for each dust *** showed that the model had an overall accuracy of 86.5%,indicating that a field-microscopy based moni-tor could support RCmD source apportionment and silicates tracking in some coal mines.

关键词： Polarized light microscopy Image processing Dust monitoring Respirable silica Coal mining

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A review of public health guidelines for postpartum physical activity and sedentary behavior from around the world

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Journal of Sport and Health Science 2024年第4期13卷 472-483,F0003页

作者： Kelly R.Evenson Wendy J.Brown Alison K.Brinson emily Budzynski-Seymour melanie Hayman Department of Epidemiology Gillings School of Global Public HealthUniversity of North Carolina at Chapel HillChapel HillNC 27599-8050USA Faculty of Health Sciences and medicine Bond UniversityGold CoastQLD 4226Australia School of Human movement and Nutrition Sciences The University of QueenslandBrisbaneQLD 4072Australia Department of Anthropology University of North Carolina at Chapel HillChapel HillNC 27599-3115USA Carolina Population Center University of North Carolina at Chapel HillChapel HillNC 27599-8120USA Faculty of Sport Health and Social SciencesSolent UniversitySouthamptonSO140YNUK Appleton Institute School of HealthMedical and Applied SciencesCentral Queensland UniversityRockhamptonQLD 4701Australia

Background:The period following pregnancy is a critical time window when future habits with respect to physical activity(PA) and sedentary behavior(SB) are established;therefore,it warrants *** purpose of this scoping review was to summarize public health-oriented country-specific postpartum PA and SB guidelines ***:To identity guidelines published since 2010,we performed a(a) systematic search of 4 databases(CINAHL,Global Health,Pubmed,and SPORTDiscus),(b) structured repeatable web-based search separately for 194 countries,and(c) separate web-based *** the most recent guideline was included for each ***:We identified 22 countries with public health-oriented postpartum guidelines for PA and 11 countries with SB *** continents with guidelines included Europe(n=12),Asia(n=5),Oceania(n=2),Africa(n=1),North America(n=1),and South America(n=1).The most common benefits recorded for PA included weight control/management(n=10),reducing the risk of postpartum depression or depressive symptoms(n=9),and improving mood/well-being(n=8).Postpartum guidelines specified exercises to engage in,including pelvic floor exercises(n=17);muscle strengthening,weight training,or resistance exercises(n=13);aerobics/general aerobic activity(n=13);walking(n=11);cycling(n=9);and swimming(n=9).Eleven guidelines remarked on the interaction between PA and breastfeeding;several guidelines stated that PA did not impact breast milk quantity(n=7),breast milk quality(n=6),or infant growth(n=3).For SB,suggestions included limiting long-term sitting and interrupting sitting with ***:Country-specific postpartum guidelines for PA and SB can help promote healthy behaviors using a culturally appropriate context while providing specific guidance to public health practitioners.

关键词： Breastfeeding Caesarean section Guidelines Postnatal Recommendations

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Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease

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Neural Regeneration Research 2025年第7期20卷 1981-1988页

作者： Shan Ping Yu emily Choi michael QJiang Ling Wei Department of Anesthesiology Emory University School of MedicineAtlantaGAUSA Center for Visual and Neurocognitive Rehabilitation Atlanta Veterans Affairs Medical CenterDecaturGAUSA

Stroke and Alzheimer's disease are common neurological disorders and often occur in the same *** comorbidity of the two neurological disorders represents a grave health threat to older *** review presents a brief background of the development of novel concepts and their clinical *** activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal *** ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic *** Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute ***,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death *** on the Ca^(2+)hypothesis of Alzheimer's disease and recent advances,this Ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic *** N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic *** stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time *** is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related

关键词： Ca^(2+)hypothesis cognitive deficits hyperactivity late-onset Alzheimer's disease neurodegeneration N-methyl-D-aspartate receptors N-methyl-D-aspartate receptor subunits pathogenesis preventive treatment

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A review of complications after ureteral reconstruction

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Asian Journal of Urology 2024年第3期11卷 348-356页

作者： Jonathan Rosenfeld Devin Boehm Aidan Raikar Devyn Coskey matthew Lee emily Ji Ziho Lee Department of Urology Northwestern UniversityFeinberg School of MedicineChicagoILUSA Department of Urology Temple UniversityLewis Katz School of MedicinePhiladelphiaPAUSA

Objective:This study aimed to provide a comprehensive overview of the complications unique to ureteral reconstruction in adults,emphasizing their presentation,diagnosis,and management in the treatment of ureteral structure ***:This review involves an in-depth analysis of existing literature and case studies pertaining to ureteral reconstruction,with a focus on examining the range of complications that can arise *** attention is given to the presentation of each complication,the diagnostic process involved,and the subsequent management ***:Ureteral reconstruction can treat ureteral stricture disease with low morbidity;however,complications,although uncommon,can have severe *** most notable complications include urinary extravasation,stricture recurrence,urinary tract infections,compartment syndrome,symptomatic vesicoureteral reflux,and Boari flap *** complication presents unique diagnostic challenges and requires specific management ***:Ureteral reconstruction is a highly effective treatment for ureteral stricture *** a strong understanding of the potential complications that patients may experience following ureteral reconstruction is not only critical to adequately counsel patients but also facilitate prompt diagnosis and management of complications when they arise.

关键词： Ureteral reconstruction Postoperative complication Urinary extravasation Stricturerecurrence Urinary tract infection

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Female Infertility and Obesity across the United States—A Geographic Cross-Sectional Analysis

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Advances in Reproductive Sciences 2024年第3期12卷 179-189页

作者： Raegan Abadie emily m. Dantes Jennifer H. Shaw Dani Zoorob Health Sciences Center in Shreveport Louisiana State University Shreveport LA USA Department of Biomedical Sciences Philadelphia College of Osteopathic Medicine South Georgia Moultrie GA USA Health Sciences Center in Shreveport Department of Obstetrics and Gynecology Louisiana State University Shreveport LA USA

This cross-sectional study investigates a connection between female infertility and obesity across various regions of the United States, utilizing data from the NIH’s “All of Us” Researcher Workbench. Analysis suggested that the Southern region exhibited the highest percentage of concurrently infertile and obese females at 32.3%, in contrast to the lowest in the Western region at 28.7%. The findings underscore the significant regional disparities in obesity-related infertility, particularly in medically underserved areas where healthcare access is limited. The study highlights the urgent need for targeted public health interventions, particularly in the Southern United States, to address the rising prevalence of obesity and its impact on infertility. Further, these results advocate for enhanced public health education and policies aimed at improving healthcare accessibility, with the goal of mitigating the adverse effects of obesity on reproductive health.

关键词： Female Infertility medical Deserts Obesity South

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Neuroprotection by resveratrol-glucuronide and quercetin-glucuronide via binding to polyphenol-and glycosaminoglycan-binding sites in the laminin receptor

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Neural Regeneration Research 2025年第3期20卷 819-820页

作者： Rayudu Gopalakrishna Jennifer Aguilar emily Lee William J.mack Department of Integrative Anatomical Sciences Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA Department of Neurological Surgery Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA

The dietary polyphenolic compounds resveratrol and quercetin prevent neurodegenerative diseases in experimental models;however, they reach the brain only in nanomolar concentrations in the glucuronidated and sulfated ... 详细信息

关键词： resveratrol molar dated

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Synthesis and Characterization of Naproxen-Salicylate Derivatives as Potential Dual-Targeted Inhibitors of Dihydrofolate Reductase

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Advances in Biological Chemistry 2024年第4期14卷 87-102页

作者： Syon Schlecht emily Gunderson Ruthie Fowler Takara Aguilar Biotechnology Research and Development Empower College and Career Center Jefferson Georgia

Dihydrofolate reductase (DHFR) is an enzyme that catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate (THF). Chemotherapy drugs such as methotrexate help to slow the progression of cancer by limiting the ability of dividing cells to make nucleotides by competitively inhibiting DHFR. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been previously reported to exhibit competitive inhibition of DHFR, in addition to their primary action on cyclooxygenase enzymes. This interaction interferes with the enzymatic reduction of dihydrofolate to tetrahydrofolate, thereby impeding the folate metabolism pathway essential for nucleotide synthesis and cell proliferation. This activity stems from their structural resemblance to the p-aminobenzoyl-l-glutamate (pABG) moiety of folate, a substrate of DHFR. It has been established that NSAIDs containing a salicylate group (which has structural similarities to pABG), such as diflunisal, exhibit stronger DHFR-binding activity. In this study, we synthesized salicylate derivatives of naproxen with the aim of exploring their potential as inhibitors of DHFR. The interactions between these derivatives and human DHFR were characterized using a combination of biochemical, biophysical, and structural methods. Through polyacrylamide gel electrophoresis (PAGE) analysis, enzymatic assays, and quantitative ELISA, we investigated the binding affinity and inhibitory potency of the synthesized salicylate derivatives towards DHFR. The findings of this study suggest the potential of salicylate derivatives of naproxen as promising candidates for the inhibition of DHFR, thereby offering novel therapeutic opportunities for modulating the inflammatory process through multiple pathways. Further optimization of these derivatives could lead to the development of more efficacious dual-targeted analogs with enhanced therapeutic benefits.

关键词： Dihydrofolate Reductase DHFR Chemotherapy Nonsteroidal Anti-Inflammatory Drugs NSAIDs Folate metabolism Pathway Anti-Folate Novel Therapeutic Development

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Long-term follow-up of kidney transplant recipients admitted to a tertiary care transplant center with SARS-CoV-2

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World Journal of Virology 2024年第2期13卷 87-95页

作者： emily E Zona mina L Gibes Asha S Jain Jeannina A Smith Jacqueline m Garonzik-Wang Didier A mandelbrot Sandesh Parajuli Division of Nephrology Department of MedicineUniversity of Wisconsin School of Medicine and Public HealthMadisonWI 53705United States Department of Infectious Disease University of Wisconsin Hospital and ClinicsMadisonWI 53705United States Department of Surgery University of WisconsinMadisonWI 53705United States Department of medicine University of Wisconsin School of Medicine and Public HealthMadisonWI 53705United States Department of medicine University of Wisconsin School of Medicine and Public HealthUniversity of Wisconsin MadisonMadisonWI 53705United States

BACKGROUND Kidney transplant recipients(KTR)are at risk of severe coronavirus disease 2019(COVID-19)disease and mortality after severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** predicted that hospitalization for COVID-19 and subsequent admission to the intensive care unit(ICU)would yield worse outcomes in *** was stratified by ICU *** of interest included risk factors for ICU admission and mortality,length of stay(LOS),respiratory symptoms at admission,all-cause graft failure at the last follow-up,and death related to *** 96 KTRs were hospitalized for SARS-COV-2 infection.21(22%)required ICU *** ICU group had longer hospital LOS(21.8 vs 8.6 days,Pmore likely to experience graft failure(81%vs 31%,Pmitted to the ICU,76%had death at last-follow up,and 71%had death related to *** factors for ICU admission included male sex(aHR:3.11,95%CI:1.04-9.34;P=0.04).Risk factors for all-cause mortality and COVID-19-related mortality included ICU admission and advanced age at SARS-CoV-2 *** was highest within a month of COVID-19 diagnosis,with the ICU group having increased risk of all-cause(aHR:11.2,95%CI:5.11-24.5;Pmortality(aHR:27.2,95%CI:8.69-84.9;Pmission conferred an increased risk of mortality,graft failure,and longer ***-fifth of those hospit-alized died of COVID-19,reflecting the impact of COVID-19-related morbidity and mortality among KTRs.

关键词： Kidney transplants SARS-CoV-2 Intensive care unit admission Outcomes Graft failure

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