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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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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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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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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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Fetal Head Compression: Its Possible Role in Neurologic Injury

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Open journal of Obstetrics and Gynecology 2024年第1期14卷 124-143页

作者： barry S. Schifrin Brian j. Koos Wayne R. Cohen Department of Obstetrics and Gynecology The Western University of Health Sciences Pomona USA The David Geffen School of Medicine at UCLA Los Angeles USA The University of Arizona College of Medicine Tucson USA

It is widely assumed that fetal ischemic brain injury during labor derives almost exclusively from severe, systemic hypoxemia with marked neonatal depression and acidemia. Severe asphyxia, however, is one of several causes of perinatal neurological injury and may not be the most common;most neonates diagnosed with hypoxic-ischemic encephalopathy do not have evidence of severe asphyxia. Sepsis, direct brain trauma, and drug or toxin exposure account for some cases, while mechanical forces of labor and delivery that increase fetal intracranial pressure sufficiently to impair brain perfusion may also contribute. Because of bony compliance and mobile suture lines, the fetal skull changes shape and redistributes cerebrospinal fluid during labor according to constraints imposed by contractions, and bony and soft tissue elements of the birth canal as the head descends. These accommodations, including the increase in intracranial pressure, are adaptive and necessary for efficient descent of the head while safeguarding cerebral blood flow. Autonomic reflexes mediated through central receptors normally provide ample protection of the brain from the considerable pressure exerted on the skull. On occasion, those forces, which are transmitted intracranially, may overcome the various adaptive anatomical, cardiovascular, metabolic, and neurological mechanisms that maintain cerebral perfusion and oxygen availability, resulting in ischemic brain injury. Accepting the notion of a potentially adverse impact of fetal head compression suggests that avoidance of excessive uterine activity and of relentless pushing without steady progress in descent may offer protection for the fetal brain during parturition. Excessive head compression should be considered in the differential diagnosis of ischemic encephalopathy.

关键词： Fetal Brain Injury Fetal Head Compression Ischemic Encephalopathy Neonatal Encephalopathy

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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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Robustness Assessment and Adaptive FDI for Car Engine

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International journal of Automation and computing 2008年第2期5卷 109-118页

作者： Mahavir Singh Sangha j.barry Gomm Control Systems Research Group School of EngineeringLiverpool John Moores University

A new on-line fault detection and isolation （FDI） scheme proposed for engines using an adaptive neural network classifier is evaluated for a wide range of operational modes to check the robustness of the scheme in this paper. The neural classifier is adaptive to cope with the significant parameter uncertainty, disturbances, and environment changes. The developed scheme is capable of diagnosing faults in on-line mode and the FDI for the closed-loop system with can be directly implemented in an on-board crankshaft speed feedback is investigated by diagnosis system （hardware）. The robustness of testing it for a wide range of operational modes including robustness against fixed and sinusoidal throttle angle inputs, change in load, change in an engine parameter, and all these changes occurring at the same time. The evaluations are performed using a mean value engine model （MVEM）, which is a widely used benchmark model for engine control system and FDI system design. The simulation results confirm the robustness of the proposed method for various uncertainties and disturbances.

关键词： On-board fault diagnosis automotive engines adaptive neural networks (ANNs) fault classification robustness assessment

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Fetal Head Compression: Its Possible Role in Neurologic Injury

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Open journal of Obstetrics and Gynecology（妇产科期刊） 2024年第1期

作者： barry S.Schifrin Brian j.Koos Wayne R.Cohen

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Escherichia coli-host macrophage interactions in the pathogenesis of inflammatory bowel disease

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World journal of Gastroenterology 2014年第27期20卷 8751-8763页

作者： Ahmed Tawfik Paul K Flanagan barry j Campbell Department of Gastroenterology Institute of Translational Medicine University of Liverpool

Multiple studies have demonstrated alterations in the intestinal microbial community (termed the microbiome) in Crohn’s disease (CD) and several lines of evidence suggest these changes may have a significant role in disease pathogenesis. In active and quiescent disease, both the faecal and mucosa-associated microbiome are discordant with matched controls with reduced biodiversity, changes in dominant organisms and increased temporal variation described. Mucosa-associated adherent, invasive Escherichia coli (E. coli) (AIEC), pro-inflammatory and resistant to killing by mucosal macrophages, appear to be particularly important. AIEC possess several virulence factors which may confer pathogenic potential in CD. Type-1 pili (FimH) allow adherence to intestinal cells via cell-surface carcinoembryonic antigen-related cell adhesion molecules and possession of long polar fimbrae promotes translocation across the intestinal mucosa via microfold (M)-cells of the follicle-associated epithelium. Resistance to stress genes (htrA, dsbA and hfq) and tolerance of an acidic pH may contribute to survival within the phagolysosomal environment. Here we review the current understanding of the role of mucosa-associated E. coli in Crohn’s pathogenesis, the role of the innate immune system, factors which may contribute to prolonged bacterial survival and therapeutic strategies to target intracellular E. coli.

关键词： Crohn's disease Inflammatory bowel disease Escherichia coli Intra-macrophage survival and replication Phagolysosome Autophagy

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COVID-19 has triggered a new century of vaccination and infection control for the benefit of all mankind

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Precision Clinical Medicine 2021年第2期4卷 77-79页

作者： barry j.Marshall Helicobacter pylori Research Laboratory School of Biomedical SciencesMarshall Centre for Infectious Disease Research and TrainingUniversity of Western AustraliaNedlands 6009Australia

Modern safe vaccinations were pioneered in 1796 by Edward jenner in England,when he noticed that milkmaids had beautiful complexions,clear of the blemishes from smallpox *** was attributed to their exposure to‘cowpox... 详细信息

关键词： vaccination infection attributed

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