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Investigation of HCAr2 antagonists as a potential strategy to modulate bovine leukocytes

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

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40-meter-long rEBCO tapes with critical current over 4,000 A/12 mm at 4.2 k and 13 T by advanced MOCVD

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Superconductivity 2024年第1期9卷 29-34页

作者： Mahesh Paidpilli Chirag Goel Bhabesh Sarangi Siwei Chen Eduard Galstyan Jan Jaroszynski Griffin bradford Dmytro Abraimov Venkat Selvamanickam Department of Mechanical Engineering Advanced Manufacturing InstituteTexas Center for SuperconductivityUniversity of HoustonHoustonTexasUSA AMPeers LLC HoustonTexasUSA National High Magnetic Field Laboratory TallahasseeFloridaUSA

rEBa_(2)Cu_(3)O_(7−δ)(rEBCO,rE=rare earth)tapes doped with 5%and 15%Zr have been scaled up to lengths more than 40 m in a pilot‐scale advanced metal organic chemical vapor deposition(A‐MOCVD)*** precursor compositions used for the long tapes were guided by a study of the influence of(Ba+dopant)/Cu content on the critical current density(Jc)of 5 and 15 mol.%Hf‐and Zr‐added tapes at 4.2 k and 13 *** 40‐mlong tapes exhibited a critical current(Ic)over 4,000 A/12 mm at 4.2 k and 13 T as well as over 1,400 A/12 mm at 20 k and 20 *** critical current densities of a 40‐m‐long tape doped with 5%Zr at 4.2 k measured at the National High Magnetic Field Laboratory(NHMFL)were>10 MAcm^(−2)and>5 MAcm^(−2)at 14 T and 30 T,respectively,which are over three times those of commercial rEBCO *** infield Jc of 5%Zradded 40‐m‐long tapes was similar to those of previously‐reported high‐performance short samples made with 15%Zr or *** results demonstrate the excellent potential of A‐MOCVD for manufacturing high Ic rEBCO tapes for use in ultrahigh‐field magnet applications.

关键词： High‐temperature superconductors MOCVD rEBCO Critical current

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虐待性头部外伤硬脊膜下出血:回顾性研究

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国际医学放射学杂志 2012年第2期 171-171页

作者： A.k.Choudhary r.k.bradford M.S.Dias G.J.Moore D.k.B.Boal 陈娟 Department of radiology Penn State University College of MedicineMilton S.Hershey Medical Center500 University DrHershey PA 17033

目的比较虐待性头部外伤患儿与意外创伤患儿硬脊膜下出血的相对发病率、分布及影像学特征。方法本研究得到了人类受试者保护办公室的事先批准。免除了知情同意。符合HIPAA要求。通过病例回顾收集到1997年—2009年间在

关键词：头部外伤患儿病人硬脊膜意外创伤

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Development of an in vitro macrophage screening system on the immunomodulating effects of feed components

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Journal of Animal Science and Biotechnology 2021年第2期12卷 639-648页

作者： S.E.Sivinski L.k.Mamedova r.A.rusk C.C.Elrod T.H.Swartz J.M.McGill B.J.bradford Department of Animal Sciences and Industry Kansas State UniversityManhattan 66506USA Department of Diagnostic Medicine/Pathobiology Kansas State UniversityManhattan 66506USA Natural Biologics NewfieldNY 14867USA 2265k Anthony Hall 474 S.Shaw LaneEast LansingMI 48824USA

Background:While feed components capable of modulating the immune system are highly sought after and marketed,often little evidence is available to support functional immune response ***,a high-throughput in vitro cell screening system was developed to test these compounds for innate immune signaling effects,using Saccharomyces cerevisiae and its cell wall components in addition to lauric acid and its esters as models in two separate *** screening system utilized rAW 264.7 murine macrophages to assess live *** cells and ***-derived cell wall componentsβ-glucan,mannan,and zymosan(a crude cell wall preparation containing bothβ-glucan and mannan).D-mannose was also evaluated as the monomer of *** also examined the effect of a saturated fatty acid(C12:0,lauric acid)and its esters(methyl laurate and glycerol monolaurate)on innate immune cell activation and cellular *** cells were transfected with a vector that drives expression of alkaline phosphatase upon promoter activation of nuclear factorκ-light-chain-enhancer of activated B cells(NFκB),a major inflammatory/immune transcription *** cells were incubated with 0.01,0.1 or 1 mg/mL of yeast compounds alone or rAW cells were challenged with LPS and then incubated with yeast *** a separate experiment,rAW cells were incubated with 0,0.5,2.5,12.5,62.5,and 312.5μmol/L of lauric acid,methyl laurate,or glycerol monolaurate alone,or rAW cells were challenged with LPS and then incubated with fatty acid ***:Treatment with zymosan orβ-glucan alone induced NFκB activation in a dose-dependent manner,whereas treatment with D-mannose,mannan,or live *** cells did ***-treatment with mannan after an LPS challenge decreased NFκB activation,suggesting that this treatment may ameliorate LPS-induced *** increases in NFκB activation were found when fatty acid treatments were applied in the absence of LPS,yet substantial reductio

关键词： Inflammation In vitro screening system NFκB

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restricted nutrient intake does not alter serum-mediated measures of implant response in cell culture

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Journal of Animal Science and Biotechnology 2014年第1期5卷 80-87页

作者： Christopher D reinhardt Tiffany L Lee Daniel U Thomson Laman k Mamedova Barry J bradford Department of Animal Sciences and Industry 232 Weber Hall Kansas State University Department of Clinical Sciences A-111 Mosier Hall Kansas State University

Background： During nutritional stress, reduced intake may reduce the efficacy of anabolic implants. This study was conducted to evaluate basic cellular responses to a growth promotant implant at two intake levels. Methods： Sixteen crossbred steers （293 ± 19.3 kg） were used to evaluate the impact of anabolic implants in either an adequate or a restricted nutritional state. Steers were trained to individual Calan gates, and then randomly assigned to 1 of 4 treatments in a 2 × 2 factorial arrangement. Treatments consisted off presence or absence of an anabolic growth implant （revalor-XS, 200 mg TBA and 40 mg estradiol; IMPLANT or CONTrOL） and a moderate energy, pelleted, starting cattle diet fed at either 2.0 × or 1.0 × maintenance energy （NEM） requirements （HIGH or LOW）. Serum （d O, 14, and 28） was used for application to bovine muscle satellite cells. After treatment with the serum （20% of total media） from the trial cattle, the satellite cells were incubated for 72 h. Protein abundance of myosin heavy chain （MHC）, phosphorylated extracellular signal-related kinase （phospho-Erk）, and phosphorylated mammalian target of rapamycin （phospho-mTOr） were analyzed to determine the effects of implant, intake, and their interaction （applied via the serum）. results： Intake had no effect on MHC （P = 0.85） but IMPLANT increased （P 〈 0.01） MHC abundance vs. CONTrOL. Implant status, intake status, and the interaction had no effect on the abundance of phospho-Erk （P〉0.23）. Implanting increased phospho-mTOr （P 〈 0.01） but there was no effect （P 〉 0.51） of intake or intake x implant. Conclusions： The nearly complete lack of interaction between implant and nutritional status indicates that the signaling molecules measured herein respond to implants and nutritional status independently. Furthermore, results suggest that the muscle hypertrophic effects of anabolic implants may not be mediated by circulating IGF-1.

关键词： Beef cattle Implant Muscle Myosin heavy chain Nutrient restriction Satellite cells

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The diagnostic conundrum in necrotizing otitis externa

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第1期10卷 59-65页

作者： Abiya A.Ahmed Shaan rashid Vinay k.Gupta Neil C.Molony keshav k.Gupta bradford royal Infirmary Bradford Teaching Hospitals NHS Foundation TrustWest BromwichWest YorkshireUK Sandwell and West Birmingham Hospitals NHS Trust West BromwichUK russells Hall Hospital DudleyUK

Necrotizing otitis externa(NOE)is an aggressive and fast‐evolving infection of the external auditory *** diagnoses and untreated cases can lead to severe,even fatal consequences and so early diagnosis and treatment are *** is a notoriously challenging diagnosis to *** is therefore important to understand what diagnostic modalities are available and how otolaryngologists can use them to accurately treat such an aggressive *** review aims to evaluate the different diagnostic options available in NOE and discuss their advantages and limitations,thus,providing an up‐to‐date picture of the multimodal approach required in the diagnosis of this disease.

关键词： diagnostic malignant otitis externa necrotizing osteomyelitis skull base osteomyelitis temporal bone osteomyelitis

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Postpartum meloxicam administration alters plasma haptoglobin, polyunsaturated fatty acid, and oxylipid concentrations in postpartum ewes

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Journal of Animal Science and Biotechnology 2020年第4期11卷 1047-1060页

作者： katie EOlagaray Barry J.bradford Lorraine M.Sordillo Jeffery C.Gandy Laman k.Mamedova Turner H.Swartz Trey D.Jackson Emma k.Persoon Caitlin S.Shugart Curtis r.Youngs Department of Animal Sciences and Industry Kansas State UniversityManhattan 66506USA College of Veterinary Medicine Michigan State University2265K Anthony HallEast LansingMI 48824-1225USA Department of Animal Science Iowa State UniversityAmesIAUSA.

Background: Postpartum inflammation is a natural and necessary response;however, a dysfunctional inflammatory response can be detrimental to animal productivity. The objective of this study was to determine the effects of a non-steroidal anti-inflammatory drug(meloxicam) on ewe postpartum inflammatory response, ewe plasma polyunsaturated fatty acid and oxylipid concentrations, and lamb ***: After lambing, 36 Hampshire and Hampshire × Suffolk ewes were sequentially assigned within type of birth to control(n = 17) or meloxicam orally administered on d 1 and 4 of lactation(MEL;90 mg, n = 19). Milk and blood samples were collected on d 1(prior to treatment) and d 4. Milk glucose-6-phosphate was not affected by MEL. Plasma haptoglobin(Hp) concentrations were less for MEL ewes;control ewes with greater d 1 Hp concentrations had elevated Hp on d 4, but this was not the case for MEL-treated ewes. Treatment with MEL increased plasma arachidonic acid concentration by more than 4-fold in ewes rearing singles but decreased concentrations of 9,10-dihydroxyoctadecenoic acid, prostaglandin F2α, 8-iso-prostaglandin E2, and 8,9-dihydroxyeicosatetraenoic acid. Nine oxylipids in plasma had interactions of treatment with d 1 Hp concentration,all of which revealed positive associations between d 1 Hp and d 4 oxylipid concentrations for CON, but neutral or negative relationships for MEL. MEL decreased 13-hydroxyoctadecadienoic acid:13-oxooctadecadienoic acid ratio and tended to increase 9-hydroxyoctadecadienoic acid:9-oxooctadecadienoic acid ratio(both dependent on d 1 values), indicating progressive metabolism of linoleic acid-derived oxylipids occurred by enzymatic oxidation after MEL treatment. Meloxicam reduced oxylipids generated across oxygenation pathways, potentially due to an improved redox ***: Postpartum MEL treatment of ewes decreased plasma concentrations of Hp and several oxylipids,with the greatest impact in ewes with biomarkers reflecting a greate

关键词： Eicosanoid Inflammation Lactation Nonsteroidal anti-inflammatory drug Sheep

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Investigation of HCAr2 antagonists as a potential strategy to modulate bovine leukocytes.

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畜牧与生物技术杂志(英文版) 2024年第4期 1567页

作者： Laman k.Mamedova kirby C.krogstad Paiton O.McDonald Laxman Pokhrel Duy H.Hua Evan C.Titgemeyer Barry J.bradford

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提升影响力-成为可信赖的领导者(第3版)

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2020年

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Differential expression of pancreatic protein and chemosensing receptor m rNAs in NkCC1-null intestine

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World Journal of Gastrointestinal Pathophysiology 2016年第1期7卷 138-149页

作者： Emily M bradford kanimozhi Vairamani Gary E Shull Department of Internal Medicine Division of GastroenterologyUniversity of Kentucky Department of Molecular Genetics Biochemistry and MicrobiologyUniversity of Cincinnati College of Medicine

AIM: To investigate the intestinal functions of the NkCC1 Na^+-k^+-2Cl cotransporter(SLC12a2 gene), differential m rNA expression changes in NkCC1-null intestine were ***: Microarray analysis of m rNA from intestines of adult wild-type mice and gene-targeted NkCC1-null mice(n = 6 of each genotype) was performed to identify patterns of differential gene expression changes. Differential expression patterns were further examined by Gene Ontology analysis using the online Gorilla program, and expression changes of selected genes were verified using northern blot analysis and quantitative real time-polymerase chain reaction. Histological staining and immunofluorescence were performed to identify cell types in which upregulated pancreatic digestive enzymes were ***: Genes typically associated with pancreatic function were upregulated. These included lipase, amylase, elastase, and serine proteases indicative of pancreatic exocrine function, as well as insulin and regenerating islet genes, representative of endocrine function. Northern blot analysis and immunohistochemistry showed that differential expression of exocrine pancreas m rNAs was specific to the duodenum and localized to a subset of goblet cells. In addition, a major pattern of changes involving differential expression of olfactory receptors that function in chemical sensing, as well as other chemosensing G-protein coupled receptors, was observed. These changes in chemosensory receptor expression may be related to the failure of intestinal function and dependency on parenteral nutrition observed in humans with SLC12a2 mutations. CONCLUSION: The results suggest that loss of NkCC1 affects not only secretion, but also goblet cell function and chemosensing of intestinal contents via G-protein coupled chemosensory receptors.

关键词： SLC12a2 Chemosensory Chemosensitivity Gastrointestinal Dyspepsia

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