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Investigation of HCAR2 antagonists as a potential strategy to modulate bovine leukocytes

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journal of Animal Science and Biotechnology 2024年第4期15卷 1567-1577页

作者： Laman K.Mamedova Kirby C.Krogstad Paiton O.McDonald Laxman Pokhrel Duy H.Hua evan C.Titgemeyer Barry j.Bradford Department of Animal Science Michigan State UniversityEast LansingMichigan 48824USA Department of Animal Sciences and Industry Kansas State UniversityManhattanKS 66506USA Comparative Medicine and Integrative Biology East LansingMI 48824USA Department of Chemistry Kansas State UniversityManhattanKS 66506USA

Background Dairy cows experiencing ketosis after calving suffer greater disease incidence and are at greater risk of leaving the herd. In vitro administration of beta-hydroxybutyric acid(BHBA;the primary blood ketone) has inhibitory effects on the function of bovine leukocytes. BHBA is a ligand of HCAR2 and the activation of these receptors promotes an anti-inflammatory response which may be related with immunosuppression observed in transition dairy cattle. The objective of this study was to identify and test antagonists for HCAR2 in bovine immune cells cultured with *** We observed expression of HCAR2 at the protein level within lymphocytes, monocytes, and granulocytes. The proportion of cells expressing HCAR2 tended to be greater in mid-lactation compared to early lactation cows;the increase was a result of increased proportion of T and B cells expressing HCAR2. Stimulation of HCAR2 with niacin or BHBA promoted Ca^(2+) mobilization in neutrophils and mononuclear cells. Mononuclear cells treated with BHBA had diminished intracellular Ca^(2+) responses when HCAR2 was knocked down by si RNA silencing, indicating Ca^(2+) mobilization was mediated by HCAR2 signaling. Two candidate antagonists for HCAR2, synthesized from niacin(NA-1 and NA-5), were tested;monocytes and neutrophils pre-treated with NA-1 and NA-5 had reduced Ca^(2+) mobilization after incubation with BHBA. Furthermore, NA-5 but not NA-1 prevented BHBA-associated reductions in cyclic *** We demonstrated that HCAR2 is present on bovine leukocytes and has greater expression later in lactation. We confirmed that BHBA and niacin derived HCAR2 antagonists alter bovine leukocyte activity. Our results demonstrate that both BHBA and niacin affect bovine leukocyte Ca^(2+) mobilization in a HCAR2-dependent manner.

关键词： Flow cytometry GPR109A HM74A Ketosis

Opposite latitudinal gradients for species richness and phylogenetic diversity of endemic snakes in the Atlantic Forest

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Current Zoology 2024年第4期70卷 522-530页

作者： joséThales da Motta Portillo josuéanderson Rēgo Azevedo Fausto Erritto Barbo Ricardo j.Sawaya Programa de Pos-Graduacao em Biologia Animal Instituto de BiocienciasLetras e Ciencias ExatasUniversidade Estadual Paulista"Julio de Mesquita Filho"Rua Cristovao Colombo2265Sao Josédo Rio PretoSao Paulo 15054-000Brazil Programa de Colecoes Cientificas Biologicas Coordenagao de BiodiversidadeInstituto Nacional de Pesquisas da AmazoniaAvenida AndréAraujo2936ManausAmazonas 69067-375Brazil Gothenburg Global Biodiversity Centre University of GothenburgBox 461GothenburgVastra Gotaland SE-40530Sweden Instituto Federal de Educacao Ciencia e Tecnologia de Minas GeraisRodovia Machado-Paraguacukm 3MachadoMinas Gerais 37750-000Rraizil Centro de Ciencias Naturais e Humanas UniversidadeFederaldo ABCRua Arcturus03Sao Bernardo do CampoSao Paulo09606-070Brazil

The decrease in species richness toward higher latitudes is an expected biogeographical *** pattern could be related to particular envi-ronmental constraints and the evolutionary history of ***,species richness does not fully represent the evolutionary history of the clades behind their *** diversity better clarifies the role of historical factors in biogeographical *** analyzed envi-ronmental and historical drivers related to latitudinal variation in species richness and phylogenetic diversity of Atlantic Forest endemic *** implemented species distribution models,from voucherbased locality points,to map the snake ranges and *** used generalized additive mixed models to evaluate the relationships among the diversity metrics and area,topographical roughness,and past climate change velocity since the Last Maximum Glacial in the Atlantic Forest latitudinal *** to the expected general pattern,species richness was higher toward higher latitudes,being positively related to past climatic *** richness also increased with total area and higher topographical *** diversity,on the other hand,showed opposite relationships related to the same *** diversity increased with lower climatic stability in lower ***,dimensions of diversity were affected in different ways by historical and environmental constraints in this unique and threatened biodiversity hotspot.

关键词： biodiversity latitudinal gradient neotropical region phylogenetic diversity serpents species richness.

Advancing Evaluation of Microplastics Thresholds to Inform Water Treatment Needs and Risks

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Environment & Health 2024年第7期2卷 441-452页

作者： Omar S.Chowdhury Philip j.Schmidt William B.anderson Monica B.Emelko Department of Civil and Environmental Engineering University of Waterloo200 University Avenue WestWaterlooON N2L 3G1Canada

Although human health impacts of microplastics are not well understood,concern regarding chemical contaminants retained on or within them is *** water providers are increasingly asked about these risks,but strategies for evaluating them and the extent of treatment needed to manage them are currently *** can potentially induce health effects if the concentration of contaminants adsorbed to them exceeds predetermined drinking water guidelines(e.g.,Maximum Contaminant Levels).The risk posed by microplastics due to adsorbed contaminants is difficult to determine,but a worst-case scenario can be evaluated by using adsorption ***,a“Threshold Microplastics Concentration”(TMC)framework is developed to evaluate whether waterborne microplastic concentrations can potentially result in the intake of regulated contaminants on/in microplastics at levels of human health concern and identify treatment targets for managing associated health *** the TMC does not indicate an immediate health risk;it informs the need for detailed risk assessment or further treatment evaluation to ensure particle removal targets are ***,the TMC concept and framework provide an updateable,science-based screening tool to determine if there is a need for detailed risk assessment or treatment modification due to waterborne microplastics in supplies used for potable water production.

关键词： drinking water treatment chemical contaminants adsorption capacity risk management maximum contaminant level

Error field penetration in j-TEXT tokamak based on two-fluid drift-MHD model

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Chinese Physics B 2024年第4期33卷 545-551页

作者：王文徐涛张仪 the j-TEXT team State Key Laboratory of Advanced Electromagnetic Technology International Joint Research Laboratory of Magnetic Confinement Fusion and Plasma PhysicsSchool of Electrical and Electronic EngineeringHuazhong University of Science and TechnologyWuhan 430074China

An externally generated resonant magnetic perturbation can induce complex non-ideal MHD responses in their resonant *** have studied the plasma responses using Fitzpatrick's improved two-fluid model and program *** calculated the error field penetration threshold for *** addition,we find that the island width increases slightly as the error field amplitude increases when the error field amplitude is below the critical penetration ***,the island width suddenly jumps to a large value because the shielding effect of the plasma against the error field disappears after the *** scanning the natural mode frequency,we find that the shielding effect of the plasma decreases as the natural mode frequency ***,we obtain the m/n=2/1 penetration threshold scaling on density and temperature.

关键词： plasma responses drift-MHD model error field penetration

Prehospital transdermal glyceryl trinitrate for ultra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- controlled ambulance trial

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Stroke & Vascular Neurology 2024年第1期9卷 38-49,I0035-I0046页

作者： jason Philip Appleton Lisa j Woodhouse Craig S anderson Sandeep Ankolekar Lesley Cala Mark Dixon Timothy j England Kailash Krishnan Grant Mair Keith W Muir john Potter Christopher I Price Marc Randall Thompson G Robinson Christine Roffe Else C Sandset jeffrey L Saver Angela Shone Aloysius Niroshan Siriwardena joanna M Wardlaw Nikola Sprigg Philip M Bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Applied HealthResearch University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trials Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Faculty of Medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University Health Science Center BeijingChina Neurology Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia Department of Neurology King's College Hospital NHS Foundation TrustLondonUK Faculty of Health and Medical Sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East Midlands Ambulance Service NHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK Centre for Clinical Brain Sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurology and Psychology University of GlasgowGlasgowUK Bob Champion Research and Education Building University of East AngliaNorwichUK Institute of Neuroscience Newcastle UniversityNewcastle upon TyneUK Department of Neurology Leeds Teaching Hospitals NHS TrustLeedsUK Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre University of LeicesterLeicesterUK Stroke Research in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK Department of Neurology Oslo University HospitalOsloNorway Research and Development Norwegian Air Ambulance FoundationOsloNorway Department of Neurology and Comprehensive Stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA Research and Graduate Services University of NottinghamNottinghamUK Community and Health Research Unit University of LincolnLincolnUK

Background The effect of transdermal glyceryl trinitrate(GTN,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is ***,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).Methods RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4hours of *** primary outcome was a shift in scores on the modified Rankin scale(mRS)at day *** outcomes included death;a global analysis(Wei-Lachin test)containing Barthel Index,EuroQol-5D,mRS,telephone interview for cognitive status-modified and Zung depression scale;and neuroimaging-determined‘brain frailty’*** were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWD)with 95%*** 597 of 1149(52%)patients had a final diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Glasgow Coma Scale 14(2)and time from onset to randomisation 67[45,108]***‘brain frailty’was common:median score 2[2,3](range 0–3).At day 90,GTN did not influence the primary outcome(acOR for increased disability 1.15,95%CI 0.85 to 1.54),death or global analysis(MWD 0.00,95%CI-0.10 to 0.09).In subgroup analyses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe *** In patients who had an ischaemic stroke,ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital *** IS ALREADY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those w

关键词： Glasgow nitrate random

Storing Freshwater Versus Storing Electricity in Power Systems with High Freshwater Electric Demand

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journal of Modern Power Systems and Clean Energy 2024年第2期12卷 323-333页

作者： Mubarak j.Al-Mubarak Antonio j.Conejo Department of Electrical and Computer Engineering The Ohio State UniversityColumbusOHUSA Department of Electrical Engineering Kuwait UniversityP.O.Box 5969Safat 13060Kuwait Department of Integrated Systems Engineering and the Department of Electrical and Computer Engineering The Ohio State UniversityColumbusOH 43210USA IEEE

We consider a power system whose electric demand pertaining to freshwater production is high(high freshwater electric demand),as in the Middle East,and investigate the tradeoff of storing freshwater in tanks versus storing electricity in batteries at the day-ahead operation *** storing freshwater and storing electricity increase the actual electric demand at valley hours and decrease it at peak hours,which is generally beneficial in term of cost and ***,to what extent?We analyze this question considering three power systems with different generation-mix configurations,i.e.,a thermal-dominated mix,a renewable-dominated one,and a fully renewable *** generation-mix configurations are inspired by how power systems may evolve in different countries in the Middle *** production uncertainty is compactly modeled using chance *** draw conclusions on how both storage facilities(freshwater and electricity)complement each other to render an optimal operation of the power system.

关键词： Power system operation freshwater production and transportation coordination day-ahead scheduling

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

Analysis of ancient mass extinction recoveries in marine environments: generating strategies for managing outcomes of the current mass extinction

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National Science Review 2024年第1期11卷 8-10页

作者： David j.Bottjer Department of Earth Sciences University of Southern California

The defining feature of a mass extinction and its associated recovery is the global amount of extinction that occurred[1]. However, there is finer-scale detail to the story, as seen in the ongoing modern mass extinction(the sixth mass extinction), which exhibits variable effects among marine ecosystems and environments, and hence geographic areas [1].

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Global weirding at mass extinction horizons

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National Science Review 2024年第1期11卷 10-12页

作者： Gregory j.Retallack Department of Earth Sciences University of Oregon

A strong motivation for studying mass extinctions is understanding how current climatic and biodiversity crises will affect creatures living on land such as ourselves. Perhaps the question is: how bad can it get? In that case, terrestrial Permian-Triassic mass extinctions are an irresistible worst-case scenario [1].

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