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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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我的宏大叙事

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中国改革 2024年第4期 81-86页

作者：布拉德福德·德龙美国加州大学伯克利分校

1870-2010年之间的140年加长版20世纪是人类全部历史中最具深远意义的阶段,它也是我们可以把经济作为最主要历史发展线索的第一个世纪,因为正是在这个时期,我们终结了几乎普遍存在的物质贫困。我要介绍的“加长版20世纪”始于1870年前后... 详细信息

1870-2010年之间的140年加长版20世纪是人类全部历史中最具深远意义的阶段,它也是我们可以把经济作为最主要历史发展线索的第一个世纪,因为正是在这个时期,我们终结了几乎普遍存在的物质贫困。我要介绍的“加长版20世纪”始于1870年前后:当时发生了若干分水岭性质的事件,即全球化、工业实验室与现代公司这三件大事,它们带来的变革将使人类逐渐摆脱自发展农业以来的上万年贫困苦难。

关键词：物质贫困工业实验室加长版宏大叙事分水岭全球化深远意义 20世纪

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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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Degree One Loading by Pressure Variations at the CMB

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journal of Earth Science 2013年第5期24卷 736-749页

作者： Ming Fang bradford H Hager Weijia Kuang Department of Earth Atmospheric & Planetary Sciences Massachusetts Institute of Technology Planetary Geodynamics Laboratory NASA Goddard Space Flight Center

Hemispherical asymmetry in core dynamics induces degree-1 pressure variations at the core mantle boundary （CMB）, which in turn deforms the overlaying elastic mantle, at the same time keeps center of mass of the whole Earth stationary in space. We develop a systematic procedure to deal with the degree-1 CMB pressure loading. We find by direct calculation a surprisingly negative load Love number h1=-1.425 for vertical displacement. Further analysis indicates that the negative hi corre- sponds to thickening above the positive load that defies intuition that pressure inflation pushes over- laying material up and thins the enveloping shell. We also redefine the pressure load Love numbers in general to enable comparison between the surface mass load and the CMB pressure load for the whole spectrum of harmonic degrees. We find that the gravitational perturbations from the two kinds of loads at degrees n〉l are very similar in amplitude but opposite in sign. In particular, if the CMB pressure variation at degree 2 is at the level of -1 hpa/yr （1 cm water height per year）, it would perturb the variation of Earth＇s oblateness, known as the j2, at the observed level.

关键词： Degree One Loading by Pressure Variations at the CMB MRSP

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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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