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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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Neurological heterotopic ossification:novel mechanisms,prognostic biomarkers and prophylactic therapies

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Bone Research 2020年第4期8卷 379-392页

作者： Ker Rui Wong Richelle Mychasiuk Terence J.o’Brien Sandy R.Shultz Stuart J.mcdonald Rhys D.Brady Department of Neuroscience Central Clinical SchoolMonash UniversityMelbourneVICAustralia Department of Medicine Royal Melbourne HospitalThe University of MelbourneParkvilleVICAustralia Department of Physiology Anatomy and MicrobiologySchool of Life SciencesLa Trobe UniversityBundooraVICAustralia

Neurological heterotopic ossification(NHo)is a debilitating condition where bone forms in soft tissue,such as muscle surrounding the hip and knee,following an injury to the brain or spinal *** abnormal formation of bone can result in nerve impingement,pain,contractures and impaired *** are often diagnosed with NHo after the bone tissue has completely mineralised,leaving invasive surgical resection the only remaining treatment *** resection of NHo creates potential for added complications,particularly in patients with concomitant injury to the central nervous system(CNS).Although recent work has begun to shed light on the physiological mechanisms involved in NHo,there remains a significant knowledge gap related to the prognostic biomarkers and prophylactic treatments which are necessary to prevent NHo and optimise patient *** article reviews the current understanding pertaining to NHo epidemiology,pathobiology,biomarkers and treatment *** particular,we focus on how concomitant CNS injury may drive ectopic bone formation and discuss considerations for treating polytrauma patients with *** conclude that understanding of the pathogenesis of NHo is rapidly advancing,and as such,there is the strong potential for future research to unearth methods capable of identifying patients likely to develop NHo,and targeted treatments to prevent its manifestation.

关键词： such has likely

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Bone loss from Wnt inhibition mitigated by concurrent alendronate therapy

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Bone Research 2018年第2期6卷 167-176页

作者： Babita Madan Mitchell J.mcdonald Gabrielle E.Foxa Cassandra R.Diegel Bart o.Williams David M.Virshup Program in Cancer and Stem Cell Biology Duke-NUS Medical School Center for Cancer and Cell Biology and Program for Skeletal Disease and Tumor Microenvironment Van Andel Research Institute Department of Pediatrics Duke University

Dysregulated Wnt signaling is associated with the pathogenesis of cancers, fibrosis, and vascular diseases. Inhibition of Wnt signaling has shown efficacy in various pre-clinical models of these disorders. one of the key challenges in developing targeted anti-cancer drugs is to balance efficacy with on-target toxicity. Given the crucial role Wnts play in the differentiation of osteoblasts and osteoclasts, acute inhibition of Wnt signaling is likely to affect bone homeostasis. In this study, we evaluated the skeletal effect of small molecule inhibitor of an o-acyl transferase porcupine（PoRCN） that prevents Wnt signaling by blocking the secretion of all Wnts. Micro-computed tomography and histomorphometric evaluation revealed that the bones of mice treated with two structurally distinct PoRCN inhibitors LGK974 and ETC-1922159（ETC-159） had loss-of-bone volume and density within 4 weeks of exposure. This decreased bone mass was associated with a significant increase in adipocytes within the bone marrow. Notably,simultaneous administration of a clinically approved anti-resorptive, alendronate, a member of the bisphosphonate family,mitigated loss-of-bone mass seen upon ETC-159 treatment by regulating activity of osteoclasts and blocking accumulation of bone marrow adipocytes. our results support the addition of bone protective agents when treating patients with PoRCN *** of bone toxicity can extend the therapeutic utility of Wnt pathway inhibitors.

关键词： Wnt ETC Bone loss Wnt inhibition mitigated concurrent alendronate therapy

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one-Dimensionality, Reliability, Distribution, and Correlates of the Brief Interactive optimism Scale among University Teachers

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open Journal of Medical Psychology 2025年第1期14卷 41-70页

作者： José Moral de la Rubia Adrián Valle de la o Jesús Alfonso Beltran-Sanchez School of Psychology Universidad Autnoma de Nuevo Len Monterrey Mexico School of Medicine and Health Sciences Tecnolgico de Monterrey Monterrey Mexico

The Brief Interactive optimism Scale (BIoS-G), recently published, was developed to measure optimism based on the interactive personality styles theory in the general population of Mexican adults. It has been validated in both the general population in Mexico and other Latin American countries. This study aims to further consolidate the validity of the BIoS-G in a specific population. The objectives are to assess the psychometric properties of its items, validate its unidimensional structure, describe its distribution, verify its internal consistency, and examine its direct relationship with affective balance and positive affect, as well as its inverse relationship with emotional exhaustion and negative affect among Mexican university teachers. The BIoS-G, the CESQT emotional exhaustion subscale, and Scale of Positive and Negative Experience (SPANE) were administered to a non-probability sample of 213 Mexican university teachers. All items demonstrated discriminative power and internal consistency. The scale showed internal consistency (Green-Yang ordinal ω = 0.74 and mcdonald ordinal ω = 0.88). The one-factor model presented good to acceptable fit to the data, with an average variance extracted of 0.65. Its distribution was negatively skewed and mesokurtic. The BIoS-G correlated directly with SPANE’s affective balance and positive emotional experiences and inversely with negative emotional experiences and emotional exhaustion, with moderate strengths of association. Its mean score was higher in men than in women and correlated positively with age. It is concluded that the BIoS-G demonstrates internal consistency and validity evidence among Mexican university teachers, and its use in this specific population is recommended.

关键词： optimism Psychometric Properties Affective Balance Emotional Exhaustion University Teachers

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Performance and yield stability of maize hybrids in stress-prone environments in eastern Africa

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The Crop Journal 2020年第1期8卷 107-118页

作者： Wender Santos Rezende Yoseph Beyene Stephen Mugo Eric Ndou Manje Gowda Julius Pyton Sserumaga Godfrey Asea Ismail Ngolinda mcdonald Jumbo Sylvester o.oikeh Michael olsen Aluízio Borém Cosme Damião Cruz Boddupalli M.Prasanna Federal University of Viçosa(UFV) P.O.Box 36570000ViçosaBrazil International Maize and Wheat Improvement Center(CIMMYT) P.O.Box 1041-00621NairobiKenya Bayer Crop Science P.O.Box 1512PetitSouth Africa National Crops Resources Research Institute(NaCRRI) P.O.Box 7084KampalaUganda Ilonga Agricultural Research Institute(ARI-Ilonga) P.O.Box 66KilosaTanzania African Agricultural Technology Foundation(AATF) P.O.Box 30709-00100NairobiKenya

Identification and deployment of high-yielding and stress-tolerant maize hybrids adapted to stress-prone agro-ecologies is important for improving the food security and livelihoods of smallholder farmers in eastern *** objectives of this study were to(i)assess the performance of maize hybrids under well-watered and drought stress conditions;(ii)evaluate grain yield stability of 65 intermediate-maturing and 55 early-maturing hybrids in 24 well-watered locations and seven drought stress locations;and(iii)identify representative and/or discriminative testing locations for increasing genetic gains for the target *** were significant differences for grain yield among early-and intermediatematuring hybrids tested under well-watered and drought stress *** the early-maturing hybrids,the top 10 hybrids produced 46.8%–73.9%and 31.2%–42.1%higher mean grain yields than the best commercial check under drought and well-watered conditions,*** the intermediate-maturing hybrids,the top 10 hybrids produced 25.2%–47.7%and 8.5%–13.5%higher grain yield than commercial checks under drought stress and well-watered conditions,respectively,suggesting improvement in the levels of drought tolerance in both early-and intermediate-maturing *** biplot analysis and a bi-segmented regression linear method identified specific early-maturing and intermediate-maturing hybrids that performed well under both well-watered and drought stress *** hybrids could be recommended for commercial production in eastern *** in Kenya was found to be the most representative and highly discriminating site among well-watered testing locations,while Kabuku in Tanzania was the least representative of test *** testing under drought stress conditions,Kiboko in Kenya was identified as the most representative *** information could be useful for allocating resources and streamlining CIMMYT maize hybrid testing in eastern Africa

关键词： Drought stress Eastern Africa Genotype by environment interaction Yield stability Zea mays L.

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Characterization and catalytic behavior of EDTA modified silica nanosprings (NS)-supported cobalt catalyst for Fischer-Tropsch Co-hydrogenation

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燃料化学学报 2018年第8期46卷 957-966页

作者： Abdulbaset M.Alayat Elena Echeverria David N.Mcllroy Armando G.mcdonald Environmental Science University of IdahoMoscowID83844-3006United States Renewable Materials Program Department of Forest Rangeland and Fire Sciences University of IdahoMoscow ID 83844-1133 United States Department of Physics Oklahoma S

The effect of ethylene diamine tetraacetic acid(EDTA) modification on the physico-chemical properties and catalytic performance of silica nanosprings(NS) supported cobalt(Co) catalyst was investigated in the conversion of syngas(H^(2+) Co) to hydrocarbons by Fischer-Tropsch synthesis(FTS). The unmodified Co/NS and modified Co/NS-EDTA catalysts were synthesized via an impregnation method. The prepared Co/NS and Co/NS-EDTA catalysts were characterized before the FTS reaction by BET surface area,X-ray diffraction(XRD),transmission electron microscopy(TEM),temperature programmed reduction(TPR),X-ray photoelectron spectroscopy(XPS),differential thermal analysis(DTA) and thermogravimetric analysis(TGA) in order to find correlations between physico-chemical properties of catalysts and catalytic performance. FTS was carried out in a quartz fixedbed microreactor(H_2/Co of 2 ∶1,230 ℃ and atmospheric pressure) and the products trapped and analyzed by GC-TCD and GC-MS to determine Co conversion and reaction selectivity. The experimental results indicated that the modified Co/NS-EDTA catalyst displayed a more-dispersed phase of Co_3o_4 nanoparticles(10.9%) and the Co_3o_4 average crystallite size was about 12.4 nm. The EDTA modified catalyst showed relatively higher Co conversion(70.3%) and selectivity toward C_(6-18)(JP-8,Jet A and diesel) than the Co/NS catalyst(C_(6-14))(JP-4).

关键词：化学分析煤矿燃烧

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Inhibiting WNT secretion reduces high bone mass caused by Sost loss-of-function or gain-of-function mutations in Lrp5

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Bone Research 2023年第3期11卷 595-606页

作者： Cassandra R.Diegel Ina Kramer Charles Moes Gabrielle E.Foxa Mitchell J.mcdonald Zachary B.Madaj Sabine Guth Jun Liu Jennifer L.Harris Michaela Kneissel Bart o.Williams Department of Cell Biology Van Andel Institute333 Bostwick Ave.NEGrand RapidsMI 49503USA Diseases of Aging and Regenerative Medicine Novartis Institutes for Biomedical ResearchCH-4002 BaselSwitzerland Bioinformatics and Biostatistics Core Van Andel Institute333 Bostwick Ave.NEGrand RapidsMI 49503USA oncology Novartis Institutes for Biomedical ResearchSan DiegoCA 92121USA

Proper regulation of Wnt signaling is critical for normal bone development and *** in several Wnt signaling components,which increase the activity of the pathway in the skeleton,cause high bone mass in human subjects and mouse *** bone mass is often accompanied by severe headaches from increased intracranial pressure,which can lead to fatality and loss of vision or hearing due to the entrapment of cranial *** addition,progressive forehead bossing and mandibular overgrowth occur in almost all *** that would provide symptomatic relief in these subjects are ***-mediated palmitoylation is necessary for Wnt secretion and binding to the frizzled *** inhibition of porcupine is a highly selective method of Wnt signaling *** treated three different mouse models of high bone mass caused by aberrant Wnt signaling,including homozygosity for loss-of-function in Sost,which models sclerosteosis,and two strains of mice carrying different point mutations in Lrp5(equivalent to human G171V and A214V),at 3 months of age with porcupine inhibitors for 5–6 *** significantly reduced both trabecular and cortical bone mass in all three *** demonstrates that porcupine inhibition is potentially therapeutic for symptomatic relief in subjects who suffer from these disorders and further establishes that the continued production of Wnts is necessary for sustaining high bone mass in these models.

关键词： homeostasis function mass

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Nano-additive manufacturing of multilevel strengthened aluminum matrix composites

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International Journal of Extreme Manufacturing 2023年第1期5卷 254-264页

作者： Chenwei Shao Haoyang Li Yankun Zhu Peng Li Haoyang Yu Zhefeng Zhang Herbert Gleiter Andrémcdonald James Hogan Department of Mechanical Engineering University of AlbertaEdmonton T6G 1H9Canada Shi-Changxu Innovation Center for Advanced Materials Institute of Metal ResearchChinese Academy of SciencesShenyang 110016People’s Republic of China School of Materials Science and Engineering University of Science and Technology of ChinaHefei 230026People’s Republic of China nanoFAB Fabrication and Characterization Centre University of AlbertaEdmonton T6G 1H9Canada Institute of Nanotechnology Karlsruhe Institute of TechnologyHermann-von-Helmholtz-Platz 1Eggenstein-Leopoldshafen 76344Germany

Nanostructured materials are being actively developed,while it remains an open question how to rapidly scale them up to bulk engineering materials for broad industrial *** study propose an industrial approach to rapidly fabricate high-strength large-size nanostructured metal matrix composites and attempts to investigate and optimize the deposition process and strengthening ***,advanced nanocrystalline aluminum matrix composites(nanoAMCs)were assembled for the first time by a novel nano-additive manufacturing method that was guided by numerical simulations(*** in-flight particle model and the porefree deposition model).The present nanoAMC with a mean grain sizeows the highest hardness among all Al–Al2o3 composites reported to date in the literature,which are the outcome of controlling multiscale strengthening mechanisms from tailoring solution atoms,dislocations,grain boundaries,precipitates,and externally introduced reinforcing *** present high-throughput strategy and method can be extended to design and architect advanced coatings or bulk materials in a highly efficient(synthesizing a nanostructured bulk with dimensions of 50×20×4 mm^(3) in 9 min)and highly flexible(regulating the gradient microstructures in bulk)way,which is conducive to industrial production and application.

关键词： high-throughput fabrication bulk nanoAMC low-temperature additive manufacturing multi-level strengthening

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Ankle Arthroscopy: A Complimentary Adjunct in the Diagnosis and Management of Ankle Fractures

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open Journal of orthopedics 2020年第12期10卷 403-411页

作者： Ciaran mcdonald Conor o’Dwyer Peter McLoughlin Rebecca Jeanne Bermingham Thomas Bayer Department of orthopaedics and Trauma Midlands Regional Hospital Tullamore Tullamore Ireland

Ankle fractures are one of the most common injuries treated by orthopaedic surgeons. A minority of patients with ankle fractures go on to develop persistent pain following anatomical reduction. These sequelae may arise as a result of untreated ligamentous or chondral injuries. This study aims to correlate acute arthroscopic ankle findings with the Lauge-Hansen fracture pattern classification. We further aim to compare subjective functional outcomes at least one year following surgery between patients who have received Open Reduction and Internal Fixation (ORIF) alone, versus ORIF plus arthroscopy. This is a retrospective case series of patients who have undergone ankle fracture ORIF +/- arthroscopy from July 2014 to July 2017 inclusive. Each patient’s presenting radiograph was classified according to the Lauge-Hansen ankle fracture classification with subsequent correlation to intra-operative arthroscopic findings. Functional outcome at a minimum of one year was evaluated with the American Academy of Orthopaedic Surgeons (AAOS) metric. Twenty two patients underwent ankle ORIF plus arthroscopy (Group A) with a further 26 patients receiving ORIF alone (Group B). 1 in 3 supination-external-rotation type II (SER II) injuries possessed a concomitant syndesmosis injury or osteochondral lesion (OCL) on arthroscopy. 1 in 3 patients with an SER IV injury had an osteochondral lesion. The mean AAOS score achieved for Group A was 89.6 (±7.9) with the mean score for Group B being 82.0 (±13.7). In conclusion, ankle arthroscopy aids the diagnosis and treatment of ligamentous and osteochondral injuries not evident on plain film with subsequent superior short-term outcomes.

关键词： Ankle Fracture Arthroscopy osteochondral Injury Syndesmosis Lauge-Hansen oRIF Ligamentous Injury Syndesmosis Disruption Persistent Ankle Pain Post-Traumatic Arthritis

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Elimination of antibiotic resistance genes and control of horizontal transfer risk by UV-based treatment of drinking water: A mini review

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Frontiers of Environmental Science & Engineering 2019年第3期13卷 3-11页

作者： Virender K.Sharma Xin Yu Thomas J.mcdonald Chetan Jinadatha Dionysios D.Dionysiou Mingbao Feng Department of Environmental and occupational Health School of Public Health Texas A&M University College Station TX 77843 USA Institute of Urban Environment Chinese Academy of Sciences Xiamen 361021 China Central Texas Veterans Health Care System Temple TX 76504 USA College of Medicine Texas A&M Health Science Center Bryan TX 77807 USA Environmental Engineering and Science Program Department of Chemical and Environmental Engineering (DChEE) 705 Engineering Research Center University of Cincinnati Cincinnati OH 45221 USA

Antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) have been recognized as one of the biggest public health issues of the 21 st century. Both ARB and ARGs have been determined in water after treatment with conventional disinfectants. Ultraviolet (UV) technology has been seen growth in application to disinfect the water. However, UV method alone is not adequate to degrade ARGs in water. Researchers are investigating the combination of UV with other oxidants (chlorine, hydrogen peroxide (H2o2), peroxymonosulfate (PMS), and photocatalysts) to harness the high reactivity of produced reactive species (C1-, C1o -, Cl2-,-oH, and So4-_) in such processes with constituents of cell (e.g., deoxyribonucleic acid (DNA) and its components) in order to increase the degradation efficiency of ARGs. This paper briefly reviews the current status of different UV-based treatments (UV/chlorination, UV/H2o2, UV/PMS, and UV-photocatalysis) to degrade ARGs and to control horizontal gene transfer (HGT) in water. The review also provides discussion on the mechanism of degradation of ARGs and application of q-PCR and gel electrophoresis to obtain insights of the fate of ARGs during UV-based treatment processes.

关键词： Antibiotic resistance bacteria Advanced oxidation processes Disinfection Reactive chlorine species Sulfate radicals Reactive oxygen species

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