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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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In Vitro assessment of the nutritive value of expanded soybean meal for dairy cattle

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Journal of Animal Science and Biotechnology 2012年第2期3卷 93-99页

作者： Eman A Elwakeel evan c titgemeyer Zongjia J cheng Abdelaziz M Nour Mohamed EA Nasser Department of Animal & Fish Production Faculty of Agriculture Alexandria University Department of Animal Sciences and Industry Kansas State University American Soybean Association-International Marketing

Little information is available about the nutritive value of expanded soybean meal, which is produced by expansion of soybeans prior to solvent extraction of the oil. During processing, expanded soybean meal is subjected to additional heat, which might increase the concentration of ruminally undegraded protein. Processing of soybeans with heat during oil extraction could affect lysine availability by increasing ruminally undegraded protein or by impairing intestinal digestion. Our objective was to compare solvent and expanded soybeans with regard to chemical composition and nutritive value for dairy cattle. Samples of expanded soybean meal （n = 14） and solventextracted soybean meal （n = 5） were obtained from People＇s Republic of china to study effects of the expansion process on nutritive value for dairy cattle. Solvent-extracted soybean meal （n = 2） and mechanically extracted （heated） soybean meal （n = 2） from the United States served as references for comparison. Samples were analyzed for crude fat, long-chain fatty acids, crude protein, amino acids, chemically available lysine, in situ ruminal protein degradation, and in vitro intestinal digestibility. No differences were found between solvent-extracted soybean meals from china and expanded soybean meals from china for crude fat, crude protein, amino acids, or chemically available lysine. In situ disappearance of nitrogen, ruminally undegraded protein content, and in vitro intestinal digestion of the ruminally undegraded protein were generally similar between solvent-extracted soybean meals made in china and expanded soybean meals made in china; variation among soybean meals was small. Results indicate that the additional heat from the expansion process was not great enough to affect the nutritive value of soybean meal protein for ruminants. Although expansion may improve the oil extraction process, the impact on the resulting soybean meal is minimal and does not require consideration when formulating ruminant di

关键词： Digestibility Escape Lysine Protein Rumen

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Description of two new species of Hemiphyllodactylus(Reptilia: Gekkonidae) from karst landscapes in Yunnan, china, highlights complex conservation needs

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Zoological Research 2022年第5期43卷 767-786页

作者： Ade Prasetyo Agung Ada chornelia L.Lee Grismer Jesse L.Grismer evan S.H.Quah Jian-Mei Lu Kyle W.Tomlinson Alice c.Hughes Landscape Ecology Group Center for Integrative ConservationXishuangbanna Tropical Botanical GardenChinese Academy of SciencesMenglunMenglaYunnan 666303China University of chinese Academy of Sciences Beijing 101408China Herpetology Laboratory Department of BiologyLa Sierra UniversityRiversideCalifornia 92515USA Institute for Tropical Biology and conservation Universiti Malaysia SabahJalan UMSKota KinabaluSabah 88400Malaysia Lee Kong chian Natural History Museum National University of SingaporeSingapore 117377Singapore community Ecology and conservation Group Center for Integrative ConservationXishuangbanna Tropical Botanical GardenChinese Academy of SciencesMenglunMenglaYunnan 666303China School of Biological Sciences University of Hong KongPokfulamHong Kong SARChina

Karst habitats are hotspots of diversity and endemism. Their naturally fragmented distributions across broad geographic landscapes have led to the complex array of smaller evolutionary ecosystems that present unique challenges from a conservation *** assessments of karst habitats have revealed that these ecosystems contain an almost unparalleled level of endemism, and many site-restricted species remain undescribed, thus posing considerable challenges for effective conservation *** rock-dwelling species, such as geckos, may be particularly prone to such isolation. In this paper, we discuss one such genus, i.e.,Hemiphyllodactylus, and explore its diversity across karst landforms in Yunnan Province, southwestern china. Based on morphological and genetic data, we describe two new species of Hemiphyllodactylus from karst habitats in Simao District and Yanshan county. A phylogenetic tree for Hemiphyllodactylus was constructed using 1?039 base pairs(bp) of the mitochondrial NADH dehydrogenase subunit 2 gene(ND2). The Simao and Yanshan specimens can be distinguished from all other congeners within their respective subclades based on uncorrected genetic pairwise distances greater than 6.3% and 4.3%respectively, as well as significant morphological differences. The discovery and description of these two new species brings the total number of described Hemiphyllodactylus species in china to 14and indicates many more undescribed species from unsurveyed karst regions await *** findings suggest that karst ecosystems in Yunnan support a higher diversity of Hemiphyllodactylus than previously *** study also highlights the importance of karst ecosystems as refugia for sitespecific endemic species and the need for heightened conservation efforts.

关键词： Discovery Endemism Geckos Reptiles South china

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Leaching of lanthanide and yttrium from a central Appalachian coal and the ashes obtained at 550-950℃

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Journal of Rare Earths 2022年第5期40卷 807-814,I0005页

作者： Ronghong Lin Yee Soong Bret H.Howard Murphy J.Keller Elliot A.Roth Ping Wang evan J.Granite U.S.Department of Energy National Energy Technology Laboratory626 Cochrans Mill RoadP.O.Box 10940PittsburghPA15236United States Keylogic Systems.Pittsburgh PA15236United States

In this work,we investigated leaching of lanthanide and yttrium(REY) from a central Appalachian coal and its ashes obtained at 550-950℃ with the main purpose of understanding the impact of ashing temperature on REY leachability in water,ammonium sulfate,and hydrochloric *** is found that the coal contains a negligible amount of water-soluble REY,less than 1% ion-exchangeable REY,and about 28% of Hcl-soluble *** leads to dramatic changes in REY leachability in both ammonium sulfate and hydrochloric acid solutions,which is believed to be related to transformation and redistribution of organically-associated REY in coal during the ashing *** temperature significantly affects REY leaching from coal ashes;higher ashing temperature results in lower REY leachability in both *** minerals may play a significant role in changing the leachability of REY after *** addition,the results also suggest that the organic matter in the coal is relatively enriched in heavy REY.

关键词： Acid leaching cation exchange coal coal ash Rare earth elements Yttrium

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A quiet place:The impact of the word"quiet"on clinical workload

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2023年第1期9卷 91-96页

作者： Beatrice c.Go Kevin chorath Amy Schettino Vincent Anagnos Ivy Maina Laura Henry Lukas Dumberger Neel Sangal Vasiliki Triantafillou Solomon Husain chad Sudoko evan cretney Karthik Rajasekaran Department of Otorhinolaryngology University of PennsylvaniaPhiladelphiaPennsylvaniaUSA Department of Otorhinolaryngology Leonard Davis Institute of Health EconomicsUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA

Purpose:This study aimed to determine the impact of uttering the word"quiet"on clinical workload during the overnight otolaryngology call shift and understand the factors contributing to resident *** and Methods:A multicenter,single-blind,randomized-controlled trial was conducted.A total of 80 overnight call shifts covered by a pool of 10 residents were randomized to the quiet or to the control *** the start of shift,residents were asked to state aloud,"Today will be a quiet night"(quiet group)or"Today will be a good night"(control group).clinical workload,as measured by number of consults,was the primary *** measures included number of sign-out tasks,unplanned inpatient and operating room visits,number of phone calls and hours of sleep,and self-perceived ***:There was no difference in the number of total(P=0.23),nonurgent(P=0.18),and urgent(P=0.18)*** at signout,total phone calls,unplanned inpatient visits,and unplanned operating room visits did not differ between the control and quiet *** there were more unplanned operating room visits in the quiet group(29,80.6%)compared to the control group(34,94.4%),this was not found to be significant(P=0.07).The majority of residents reported feeling"not busy"during control nights(18,50.0%)compared to feeling"somewhat busy"during quiet nights(17,47.2%;P=0.42).conclusion:contrary to popular belief,there is no clear evidence that uttering the word"quiet"significantly increases clinical workload.

关键词： burnout call schedule quiet resident workload wellness

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Dupilumab in Adults and Adolescents with Eosinophilic Esophagitis

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四川生理科学杂志 2022年第12期44卷 2116-2116页

作者： evan S Dellon From the center for Esophageal Diseases and Swallowing University of North Carolina School of Medicine Chapel Hill (E.S.D.) cincinnati children's Hospital Medical center and University of cincinnati college of Medicine Cincinnati (M.E.R. M.H.C.) Northwestern University Feinberg School of Medicine Chicago (I.H.) Mount Sinai center for Eosinophilic Disorders Icahn School of Medicine at Mount Sinai New York (M.C.) and Regeneron Pharmaceuticals Tarrytown (X.S. M.P.K. M.A.K. J.D.H. B.B. E.M. B.A. N.A. W.K.L. M.F.W. M.R. D.R.W. G.D.Y. B.S. J.M. A.G. A.S.) - both in New York Amsterdam University Medical center Amsterdam (A.J.B.) Hospital General de Tomelloso Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas Madrid and Instituto de Investigación Sanitaria de Castilla-La Mancha Toledo - both in Spain (A.J.L.) children's Hospital of Philadelphia Philadelphia (J.M.S.) University of california San Diego La Jolla and Rady Children's Hospital San Diego - both in California (S.A.) Sanofi Bridgewater NJ (K.P. E.L.) Sanofi Chilly-Mazarin France (L.P.M.) and Sanofi Cambridge MA (N.P.).

Background:Dupilumab,a fully human monoclonal antibody,blocks interleukin-4 and interleukin-13 signaling,which have key roles in eosinophilic ***:We conducted a three-part,phase 3 trial in which patients 12 years of age or older underwent randomization in a 1:1 ratio to receive subcutaneous dupilumab at a weekly dose of 300 mg or placebo(Part A)or in a 1:1:1 ratio to receive 300 mg of dupilumab either weekly or every 2 weeks or weekly placebo(Part B)up to week 24.

关键词： monoclonal placebo weekly

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A Revised checklist of Amphibians and Reptiles in camiguin Sur,Misamis Oriental,Mindaanao,Philippines

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Asian Herpetological Research 2020年第1期11卷 28-43页

作者： Russell evan L·VENTURINA Ynigo Luis c·DEL PRADO Rhim Ayyah c·KAMIR Marlon N·BALMORES Arvin c·DIESMOS Department of Biology College of ScienceDe La Salle UniversityTaft AvenueManila The Graduate School University of Santo TomasEsparaManila Mindanao State Uniersity-ligan Institute of Technology Iligan CityMindanao Herpetology Section Zoology DivisionNational Museum of Natural HistoryPhilippines

The Philippines is listed as one of the world's megadiverse countries despite its small ***,it is also on the list of global biodiversity conservation *** the threat of extinction at an all-time high,better understa nding of the archipelago's biodiversity will provide invalua ble baseline information for proper conservation *** we provide an upda ted checklist on the herpetological biodiversity of ca miguin Sur,Misa mis Oriental,Minda nao,*** surveys and specimen collection from the municipality of Mambajao resulted in a total of 28 species(13 anurans,11 lizards,and four snakes)-all well represented by voucher *** data provides seven additional species records,upda ting the island's total amphibian and reptile species count to 57,with about half Philippine *** in the new records are three invasive alien species of amphibians:The cane Toad Rhinella marina,the Greenhouse Frog Eleutherodatylus planirstris,and the Asiatic Painted Narrowmouth Toad Kaloula pulchra.

关键词： camiguin Sur amphibians and reptiles biodiversity conservation

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Targeting Tyrosyl-DNA phosphodiesterase I to enhance toxicity of phosphodiester linked DNA-adducts

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cancer Drug Resistance 2019年第4期2卷 1153-1163页

作者： evan J.Brettrager Robert c.A.M.van Waardenburg Department of Pharmacology and Toxicology University of Alabama at BirminghamBirminghamAL 35294-0019USA

Our genomic DNA is under constant assault from endogenous and exogenous sources,which needs to be resolved to maintain cellular *** eukaryotic DNA repair enzyme Tyrosyl-DNA phosphodiesterase I(Tdp1)catalyzes the hydrolysis of phosphodiester bonds that covalently link adducts to ***1 utilizes two catalytic histidines to resolve a growing list of *** DNA-adducts can be divided into two groups:small adducts,including oxidized nucleotides,RNA,and non-canonical nucleoside analogs,and large adducts,such as(drug-stabilized)topoisomerase-DNA covalent complexes or failed Schiff base reactions as occur between PARP1 and *** Tdp1 substrates are generated by chemotherapeutics linking Tdp1 to cancer drug resistance,making a compelling argument to develop small molecules that target Tdp1 as potential novel therapeutic ***1’s unique catalytic cycle,which is centered on the formation of Tdp1-DNA covalent reaction intermediate,allows for two principally different targeting strategies:(1)catalytic inhibition of Tdp1 catalysis to prevent Tdp1-mediated repair of DNA-adducts that enhances the effectivity of chemotherapeutics;and(2)poisoning of Tdp1 by stabilization of the Tdp1-DNA covalent reaction intermediate,which would increase the half-life of a potentially toxic DNA-adduct by preventing its resolution,analogous to topoisomerase targeted poisons such as topotecan or *** catalytic Tdp1 mutant that forms the molecular basis of the autosomal recessive neurodegenerative disease spinocerebellar ataxia with axonal neuropathy best illustrates this concept;however,no small molecules have been reported for this ***,we concisely discuss the development of Tdp1 catalytic inhibitors and their results.

关键词： Tdp1 small molecules DNA topoisomerases camptothecins oxidative DNA damage DNA adducts Etoposide chain terminating nucleotides/nucleoside analogs DNA metabolism drug development

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cascade of care for children and adolescents with chronic hepatitis c

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World Journal of Gastroenterology 2021年第12期27卷 1117-1131页

作者： Michael evan Rogers William F Balistreri Department of Pediatrics Cincinnati Children's Hospital Medical CenterCincinnatiOH 45229United States

chronic hepatitis c virus(HcV)infection presents a significant global public health *** 2015,over 400000 deaths worldwide were attributed to HcV *** led the World Health Organization(WHO)in 2016 to set the ambitious goal of eliminating HcV by ***-centered guidelines have been established in order to provide direction for healthcare professionals,allowing integration of the newest screening policies and therapeutic strategies into their ***,for children and adolescents,HcV is a significant,unrecognized public health *** infection rates in the United States in women of childbearing age and those who are pregnant have increased in parallel with the rising opioid *** estimated 29000 women with HcV infection gave birth each year from 2011 to 2014 in the United States,with approximately 1700 of their infants being infected with *** HcV-specific therapeutics,namely direct acting antivirals(DAA),has brought a new and highly successful approach to treatment of hepatitis *** studies have confirmed similar levels of effectiveness and safety of DAA therapies in the pediatric ***,an enhanced cascade of care,which should include the population under 18 years of age,can help achieve the WHO goal by focusing on elimination in the youngest *** review will present an overview of the natural history,clinical features,and management of HcV in children and adolescents.

关键词： Hepatitis c virus Hepatitis c education Hepatitis c elimination

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Extensive Spinal Epidural Abscess: cord compression with Permanent Neurological Defects

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Surgical Science 2023年第8期14卷 557-564页

作者： evan cohen Melissa Zahl Lindsay Hock Michael Olshansky Montefiore St. Luke’s cornwall Hospital Newburgh NY USA Touro college of Medicine Middletown NY USA

Spinal epidural abscesses (SEA) are considerably rare and tend to present over two to five vertebral segments. Occasionally, there will be two or more noncontiguous areas of pyogenic collections [1]. Minimal cases have been reported to span the entire vertebral column;a meta-analysis estimates that 1% of all SEA are holospinal [2]. The triad of presenting symptoms includes fever, back pain (often midline), and neurologic defects [1] [2] [3]. Early detection is identified as a critical aspect of improved outcomes. cases that do not present in this manner or with other masking symptoms can lead to delayed diagnosis, thus delaying treatment. In the event of cord compression, the occurrence of neurologic defects increases. Time from the onset of clinical manifestations to the operating room is crucial in reversing symptoms [2]. This article seeks to review a case of a 65-year-old male that presented to the emergency department (ED) due to a falling second to weakness and thigh pain. On presentation, he was also noted to have rhabdomyolysis causing acute kidney injury (AKI) with tubular necrosis. The patient was admitted to the hospital with a complex history of progressive leg weakness, pain in the lower back, incontinence, and elevated white blood cell count. Days into the admission, a magnetic resonance imaging (MRI) study was performed, which revealed a continuous posterior SEA from c4 to S2 with anterior mass effect causing spinal cord compression. Emergency neurosurgery was scheduled for laminectomies in the cervical, thoracic and lumbar spine to drain the abscess. Evaluation of this complex medical course, surgical approach to drainage of an incessant spinal column abscess, and sustained neurologic defects will be discussed.

关键词： Spinal Epidural Abscess Holospinal Abscess cauda Equina Spinal compression

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