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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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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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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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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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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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用改进逆境萌发的滲透引发来熟练掌握种子水分关系

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种子 1987年第6期 68-74页

作者： Kent j.bradford ,陈暖

对许多一年生作物来讲,从种植到定植这段时间,是生产的关键时期。直播作物的出苗和齐苗,对最终产量和质量有很大影响,特别是蔬菜。为获得理想植物群体,精耕细作保证种植的粒粒种子都能定植。此外,价格昂贵的

关键词：种子含水量发根等式 MPa 膨压渗透调节种子含水率紧张压相对紧涨度 RWC PEG 种子引发逆境

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被忽视的经济增长机遇——中美商业服务贸易

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新金融评论 2013年第3期 136-155页

作者： j.bradford jensen 本刊编辑乔治敦大学商学院

当前中美之间有一项重要的商贸机会——商业服务贸易一直被忽视。美国已经连续多年存在大量贸易逆差,亟需扩大出口,尤其是对那些经济增长较快的发展中国家的出口。对中国来说,提高制造业的价值链就需要获得工程、设计、开发、检验、市... 详细信息

当前中美之间有一项重要的商贸机会——商业服务贸易一直被忽视。美国已经连续多年存在大量贸易逆差,亟需扩大出口,尤其是对那些经济增长较快的发展中国家的出口。对中国来说,提高制造业的价值链就需要获得工程、设计、开发、检验、市场营销、广告推广、物流和配送等多方面的高效尖端服务。目前中国的商业服务业规模还比较小,收费也比较高。虽然长期来看,教育可以解决这个问题,但短期来看,进口服务是一个合适的选择。很多服务都是可交易的,但中国对服务业贸易设置的壁垒还是较多。中美之间的商业服务贸易可开发的潜力很大,这也将给两个国家带来好处。当然,抓住这个机遇就必须要减少政策障碍。

关键词：商业服务服务业贸易政策障碍

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论美中双边投资协定的重要性:潜在经济效益

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新金融评论 2017年第3期 97-112页

作者： Lee Branstetter Britta Glennon j.bradford jensen 卡内基梅隆大学乔治城大学

虽然中国在经济开放方面已经取得了重大进展,包括允许私营企业、国际贸易和外商投资等进入市场,但这一进程还远未结束。外商直接投资中国服务性行业的壁垒相对较高,从而降低了服务行业生产力,抬高了价格,限制了中国消费者和企业的选择,... 详细信息

虽然中国在经济开放方面已经取得了重大进展,包括允许私营企业、国际贸易和外商投资等进入市场,但这一进程还远未结束。外商直接投资中国服务性行业的壁垒相对较高,从而降低了服务行业生产力,抬高了价格,限制了中国消费者和企业的选择,最终抑制了经济增长。美中双边投资协定(BIT)则能在消除外商直接投资壁垒、促进两国经济发展上发挥重要作用。一个高标准的BIT将对深化开放外资以及提高中国服务性行业的竞争与发展水平产生重大影响。加大外商直接投资或将成为缩小中国第三产业和国际先进标准间生产力鸿沟的契机。若放开本土竞争与实施BIT同时进行,那么一个高标准的BIT将在极大程度上提升中国经济增长潜力。尽管评估BIT的影响较为困难,我们参考了一系列最新研究报告估算潜在收益范围。我们的研究表明签订BIT可能带来巨大收益。

关键词：美中双边投资协定服务业外商直接投资

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Multi-Institutional US Experience of the Occlutech AFR Device in Congenital and Acquired Heart Disease

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Congenital Heart Disease 2022年第1期17卷 107-116页

作者： barry O’Callaghan jenny Zablah joseph Vettukattil Daniel Levi Morris Salem Allison Cabalka jason Anderson Makram Ebeid Ryan Alexy Gareth j.Morgan The Heart Institute Children’s Hospital ColoradoAuroraUSA Pediatric Cardiology Helen DeVos Children’s HospitalGrand RapidsUSA Pediatric Cardiology UCLA HealthMattel Children’s HospitalLos AngelesUSA Pediatric Cardiology UCLA Medical CentreLos AngelesUSA Pediatric Cardiology Mayo ClinicRochesterUSA Pediatric Cardiology University of Mississippi Medical CenterJacksonUSA Pediatric Cardiology Riley Hospital for Children at Indiana University HealthIndianapolisUSA

Objectives:To detail the US multi-institutional experience with the Occlutech©(Occlutech International AB,Helsingborg,Sweden)atrial flow regulator(AFR)in children and adults with acquired or congenital heart ***:The creation of a long-term atrial communication is desirable in several cardiovascular disease phenotypes,most notably pulmonary arterial hypertension,disorders of increased left ventricular filling and increased cavopulmonary pressures in patients with a Fontan type ***:Patients were identified for inclusion from the AFR device manufacturer *** was collected using a RedCap database following IRB approval.8 weeks of follow up data was sought for each patient based on available *** was analyzed and summarized using ***:We report the experience of 6 US centers in the implantation of AFR devices in 15 patients,across a wide age range,with different disease phenotypes and a variety of *** was technically successful in all patients and improvement was noted in both clinical and hemodynamic *** were no immediate or intermediate term complications reported.3 patients died remote from *** deaths were not felt to be related to the AFR device or related procedural ***:Compassionate use of the AFR device in children and adults with congenital&acquired heart disease is technically feasible and produces beneficial short term hemodynamic and symptomatic *** uptake of this technique and treatment at specialist centers has the potential to provide significant benefits to a variety of complex patients with currently limited treatment options and indeterminate prognosis.

关键词： Congenital heart disease pulmonary hypertension left atrial hypertension single ventricle palliation diastolic heart failure

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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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