المؤلفون: Aaron J. Brown, Gillian Scoley, Niamh O’Connell, Alan Gordon, Katie Lawther, Sharon A. Huws, Steven J. Morrison

المصدر: Animals, Vol 13, Iss 6, p 1109 (2023)

مصطلحات موضوعية: bedding, enteric disease, housing, feeding equipment, management, space allowance, Veterinary medicine, SF600-1100, Zoology, QL1-991

الوصف: Pre-weaned dairy calves are very susceptible to disease in the first months of life due to having a naïve immune system and because of the numerous physiological stressors they face. Hygiene management is a key element in minimizing enteric disease risk in calves by reducing their exposure to pathogens. Samples of milk, concentrate feed and drinking water, boot swabs of bedding and swabs of feed equipment were collected from 66 dairy farms as part of a survey of calf rearing practice and housing design. All the samples were cultured to determine total viable counts (TVC), total coliforms (TCC) and Escherichia coli as indicators of hygiene. Target ranges for levels of TVC, TCC and E. coli were defined from the literature and the sample results compared against them. The TVC targets in milk, MR and water were 10 CFU/mL. TCC and E. coli targets of 10 CFU/mL (the detection limit) were used for milk, MR, concentrate feed and feeding equipment. For water, the TCC and E. coli targets were 10 CFU/100 mL. The targets used for bedding boot swabs were 10 TVC CFU/mL and 10 TCC or E. coli CFU/mL. Farm management factors were included as fixed effects in a generalized linear mixed model to determine the probability of samples being within each hygiene indicator target range. Milk replacer samples obtained from automatic feeders were more likely to be within the TVC target range (0.63 probability) than those prepared manually (0.34) or milk samples taken from the bulk tank (0.23). Concentrate feed samples taken from buckets in single-calf pens were more likely to have E. coli detected (0.89) than samples taken from group pen troughs (0.97). A very small proportion of water samples were within the indicator targets (TVC 9.8%, TCC 6.0%, E. coli 10.2%). Water from self-fill drinkers had a lower likelihood of being within the TVC target (0.03) than manually filled buckets (0.14), and water samples from single pens were more likely to be within TCC target ranges (0.12) than those from group pens (0.03). However, all self-fill drinkers were located in group pens so these results are likely confounded. Where milk feeders were cleaned after every feed, there was a greater likelihood of being within the TVC target range (0.47, compared with 0.23 when not cleaned after every feed). Detection of coliforms in milk replacer mixing utensils was linked with reduced probability of TVC (0.17, compared with 0.43 when coliforms were not detected) and TCC (0.38, compared with 0.62), which was within target in feeders. Key factors related to increased probability of bedding samples being within TCC target range were use of group calf pens (0.96) rather than single-calf pens (0.80), use of solid floors (0.96, compared with 0.76 for permeable floors) and increased space allowance of calves (0.94 for pens with ≥2 m2/calf, compared with 0.79 for pens with 2/calf). Bedding TVC was more likely to be within the target range in group (0.84) rather than in single pens (0.66). The results show that hygiene levels in the calf rearing environment vary across farms and that management and housing design impact hygiene.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2076-2615/13/6/1109Test; https://doaj.org/toc/2076-2615Test

الوصول الحر: https://doaj.org/article/c1d6736ff813472e97760b03723dfcc1Test

المؤلفون: Aaron J. Brown, Krishna Mohan Sepuru, Kirti V. Sawant, Krishna Rajarathnam

المصدر: Frontiers in Immunology, Vol 8 (2017)

مصطلحات موضوعية: chemokine, glycosaminoglycan, heparin, NMR, CXCL7, NAP-2, Immunologic diseases. Allergy, RC581-607

الوصف: Platelet-derived chemokine CXCL7 (also known as NAP-2) plays a crucial role in orchestrating neutrophil recruitment in response to vascular injury. CXCL7 exerts its function by activating the CXC chemokine receptor 2 (CXCR2) receptor and binding sulfated glycosaminoglycans (GAGs) that regulate receptor activity. CXCL7 exists as monomers, dimers, and tetramers, and previous studies have shown that the monomer dominates at lower and the tetramer at higher concentrations. These observations then raise the question: what, if any, is the role of the dimer? In this study, we make a compelling observation that the dimer is actually the favored form in the GAG-bound state. Further, we successfully characterized the structural basis of dimer binding to GAG heparin using solution nuclear magnetic resonance (NMR) spectroscopy. The chemical shift assignments were obtained by exploiting heparin binding-induced NMR spectral changes in the WT monomer and dimer and also using a disulfide-linked obligate dimer. We observe that the receptor interactions of the dimer are similar to the monomer and that heparin-bound dimer is occluded from receptor interactions. Cellular assays also show that the heparin-bound CXCL7 is impaired for CXCR2 activity. We conclude that the dimer–GAG interactions play an important role in neutrophil–platelet crosstalk, and that these interactions regulate gradient formation and the availability of the free monomer for CXCR2 activation and intrathrombus neutrophil migration to the injury site.

وصف الملف: electronic resource

العلاقة: http://journal.frontiersin.org/article/10.3389/fimmu.2017.01248/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/5ccc58a30a744d99a02ec781ccb4a591Test

المؤلفون: Aaron J. Brown, Krishna Mohan Sepuru, Krishna Rajarathnam

المصدر: International Journal of Molecular Sciences, Vol 18, Iss 3, p 508 (2017)

مصطلحات موضوعية: chemokine, CXCL7, NAP-2, CXCR2, glycosaminoglycan, heparin, NMR, monomer, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: CXCL7, a chemokine highly expressed in platelets, orchestrates neutrophil recruitment during thrombosis and related pathophysiological processes by interacting with CXCR2 receptor and sulfated glycosaminoglycans (GAG). CXCL7 exists as monomers and dimers, and dimerization (~50 μM) and CXCR2 binding (~10 nM) constants indicate that CXCL7 is a potent agonist as a monomer. Currently, nothing is known regarding the structural basis by which receptor and GAG interactions mediate CXCL7 function. Using solution nuclear magnetic resonance (NMR) spectroscopy, we characterized the binding of CXCL7 monomer to the CXCR2 N-terminal domain (CXCR2Nd) that constitutes a critical docking site and to GAG heparin. We found that CXCR2Nd binds a hydrophobic groove and that ionic interactions also play a role in mediating binding. Heparin binds a set of contiguous basic residues indicating a prominent role for ionic interactions. Modeling studies reveal that the binding interface is dynamic and that GAG adopts different binding geometries. Most importantly, several residues involved in GAG binding are also involved in receptor interactions, suggesting that GAG-bound monomer cannot activate the receptor. Further, this is the first study that describes the structural basis of receptor and GAG interactions of a native monomer of the neutrophil-activating chemokine family.

وصف الملف: electronic resource

العلاقة: http://www.mdpi.com/1422-0067/18/3/508Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/47df4aafb3b74bbd824f23287df18da9Test

المؤلفون: Aaron J Brown, Gillian Scoley, Niamh O’Connell, Jamie Robertson, Amanda Browne, Steven Morrison

المصدر: Animals; Volume 11; Issue 7; Pages: 1954

مصطلحات موضوعية: dairy calf, health, performance, survey, calf housing, hygiene

جغرافية الموضوع: agris

الوصف: The first few months of life are of great importance to the longevity and lifetime performance of dairy cows. The nutrition, environment and healthcare management of heifer calves must be sufficient to minimise exposure to stress and disease and enable them to perform to their genetic potential. Lack of reporting of farm management practices in Northern Ireland (NI) makes it difficult to understand where issues impacting health, welfare and performance may occur in the rearing process. The objective of this study was to investigate housing design and management practices of calves on 66 dairy farms across NI over a 3-month period and also identify areas that may cause high risk of poor health and performance in dairy calves. An initial survey was used to detail housing and management practices, with two subsequent visits to each farm used to collect animal and housing-based measurements linked to hygiene management, animal health and performance. Large variations in key elements such as weaning criteria and method, calf grouping method used, nutritional feed plane, and routine hygiene management were identified. The specification of housing, in particular ventilation and stocking density, was highlighted as a potential limiting factor for calf health and performance. Lack of measurement of nutritional inputs, hygiene management practices and calf performance was observed. This poses a risk to farmers’ ability to ensure the effectiveness of key management strategies and recognise poor calf performance and health.

وصف الملف: application/pdf

العلاقة: Cattle; https://dx.doi.org/10.3390/ani11071954Test

الإتاحة: https://doi.org/10.3390/ani11071954Test

المؤلفون: Jeffrey R. Livezey, Thomas Oliver, Daniel J. Selig, Elaine D. Por, Jesse P. DeLuca, Adrian T. Kress, Rosenie Thelus Jean, Aaron J. Brown

المصدر: Pharmacoepidemiology and Drug Safety. 29:1605-1615

مصطلحات موضوعية: Adult, medicine.medical_specialty, endocrine system diseases, Epidemiology, Military Health Services, Population, Muscarinic Antagonists, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Fesoterodine, Darifenacin, Humans, Pharmacology (medical), 030212 general & internal medicine, Risk factor, Oxybutynin, education, Aged, Retrospective Studies, Aged, 80 and over, education.field_of_study, Solifenacin, Antimuscarinic Agent, Urinary Bladder, Overactive, business.industry, Middle Aged, Diabetes Mellitus, Type 2, Female, Tolterodine, business, medicine.drug

الوصف: PURPOSE To explore patterns of antimuscarinic medication as a risk factor for type 2 diabetes mellitus (T2DM). METHODS This is a retrospective cohort study of females 18 years or older within the Military Health System from 2006 to 2016. Administrative and claims data were used to select patients who initiated therapy with tolterodine, fesoterodine, oxybutynin, darifenacin, solifenacin, or trospium. Patients with no documented history of T2DM were followed for the occurrence of T2DM, the end of the study or loss of eligibility. Rates of T2DM were calculated for the overall population, by duration of therapy and by individual drugs. Crude and adjusted Cox proportional hazards were calculated to assess differences by duration of use and specific muscarinic antagonist. RESULTS Over 2.6 million antimuscarinic prescriptions were dispensed to 241 829 females (mean age/SD, 62 ± 18 years). Patients exposed to M3 selective antagonists had highest risk of developing T2DM compared to those exposed to nonselective antagonists. Using oxybutynin, a nonselective antagonist as a comparator, adjusted rate ratios of T2DM were 57% (HR 1.57, 95%CI 1.48-1.67) and 29% (HR 1.29, 95%CI 1.24-1.35) significantly higher for darifenacin and solifenacin, respectively (both M3 selective). CONCLUSIONS We found exposure to M3 selective antagonists darifenacin and solifenacin had the highest risk of developing T2DM compared to nonselective antagonist oxybutynin. This is supported by well described physiologic mechanisms and may allow for more informed prescribing decisions, particularly if minimizing risk of T2DM is a priority.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::036bcf70642bdadfd60f2bb0c5bd3df2Test
https://doi.org/10.1002/pds.5090Test

المؤلفون: Aaron J. Brown, Andrew E. Newhouse, Dylan Parry, William A. Powell

المصدر: Insect Science. 27:1067-1078

مصطلحات موضوعية: Genotype, Bacillus thuringiensis, Castanea dentata, Moths, General Biochemistry, Genetics and Molecular Biology, Lepidoptera genitalia, food, Ascomycota, Lymantria dispar, Botany, Fagus, Animals, Blight, Herbivory, Cryphonectria, Ecology, Evolution, Behavior and Systematics, Plant Diseases, biology, fungi, Plants, Genetically Modified, biology.organism_classification, Nucleopolyhedroviruses, food.food, Fagaceae, Plant Leaves, Transformation (genetics), Larva, Insect Science, Agronomy and Crop Science

الوصف: American chestnut (Castanea dentata [Marsh.] Borkh.) was once the dominant hardwood species in Eastern North America before an exotic fungal pathogen, Cryphonectria parasitica (Murrill) Barr, functionally eliminated it across its range. One promising approach toward restoring American chestnut to natural forests is development of blight-tolerant trees using genetic transformation. However, transformation and related processes can result in unexpected and unintended phenotypic changes, potentially altering ecological interactions. To assess unintended tritrophic impacts of transgenic American chestnut on plant-herbivore interactions, gypsy moth (Lymantria dispar L.) caterpillars were fed leaf disks excised from two transgenic events, Darling 54 and Darling 58, and four control American chestnut lines. Leaf disks were previously treated with an LD50 dose of either the species-specific Lymantria dispar multiple nucleopolyhedrovirus (LdMNPV) or the generalist pathogen Bacillus thuringiensis subsp. kurstaki (Btk). Mortality was quantified and compared to water blank controls. Tree genotype had a strong effect on the efficacies of both pathogens. Larval mortality from Btk-treated foliage from only one transgenic event, Darling 54, differed from its isogenic progenitor, Ellis 1, but was similar to an unrelated wild-type American chestnut control. LdMNPV efficacy was unaffected by genetic transformation. Results suggest that although genetic modification of trees may affect interactions with other nontarget organisms, this may be due to insertion effects, and variation among different genotypes (whether transgenic or wild-type) imparts a greater change in response than transgene presence.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2a91b45797f1bbb4456a4dcb0e04d310Test
https://doi.org/10.1111/1744-7917.12713Test

المؤلفون: Amanda Browne, Gillian Scoley, Jamie Robertson, Niamh O'Connell, Aaron J Brown, Steven Morrison

المصدر: Animals, Vol 11, Iss 1954, p 1954 (2021)
Animals : an Open Access Journal from MDPI
Brown, A J, Scoley, G, O’Connell, N, Robertson, J, Browne, A & Morrison, S 2021, ' Pre-Weaned Calf Rearing on Northern Irish Dairy Farms: Part 1. A Description of Calf Management and Housing Design ', ANIMALS, vol. 11, no. 7, e1954 . https://doi.org/10.3390/ani11071954Test
Animals
Volume 11
Issue 7

مصطلحات موضوعية: media_common.quotation_subject, Veterinary medicine, Article, Health administration, hygiene, Stocking, Irish, Calf rearing, Hygiene, Environmental health, SF600-1100, survey, Management practices, Housing design, media_common, General Veterinary, dairy calf, health, language.human_language, QL1-991, calf housing, language, Animal Science and Zoology, Business, Welfare, Zoology, performance

الوصف: Simple Summary Calf health, welfare and performance in the first few months of life are important for the lifetime productivity of dairy cows. Therefore, all aspects of management, including nutrition, hygiene, housing and health, should be optimal to maintain productive calves. As there is little information surrounding these areas on Northern Irish dairy farms, this study investigated 66 farms with the objective of describing common trends and identifying factors which have the potential to compromise calf health, welfare and performance. A large degree of variation was seen in calf housing and other management practices across the farms. The majority of housing, in terms of building design and functionality, was identified as sub-optimal and is likely a contributing factor for selection of particular management practices. Regular monitoring of management practices such as measuring quantity of feedstuffs provided and animal live weight allows farmers to assess the effectiveness of their rearing system. However, this study highlighted a lack of appropriate monitoring and measuring in several key areas that present a risk for calf health and performance. Abstract The first few months of life are of great importance to the longevity and lifetime performance of dairy cows. The nutrition, environment and healthcare management of heifer calves must be sufficient to minimise exposure to stress and disease and enable them to perform to their genetic potential. Lack of reporting of farm management practices in Northern Ireland (NI) makes it difficult to understand where issues impacting health, welfare and performance may occur in the rearing process. The objective of this study was to investigate housing design and management practices of calves on 66 dairy farms across NI over a 3-month period and also identify areas that may cause high risk of poor health and performance in dairy calves. An initial survey was used to detail housing and management practices, with two subsequent visits to each farm used to collect animal and housing-based measurements linked to hygiene management, animal health and performance. Large variations in key elements such as weaning criteria and method, calf grouping method used, nutritional feed plane, and routine hygiene management were identified. The specification of housing, in particular ventilation and stocking density, was highlighted as a potential limiting factor for calf health and performance. Lack of measurement of nutritional inputs, hygiene management practices and calf performance was observed. This poses a risk to farmers’ ability to ensure the effectiveness of key management strategies and recognise poor calf performance and health.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7727068fb25ffac61cca9f2e411723afTest
https://www.mdpi.com/2076-2615/11/7/1954Test

المؤلفون: Aaron J. Brown, Brandon A. Jones

المصدر: Journal of Spacecraft and Rockets. 56:823-835

مصطلحات موضوعية: Physics, Mathematical optimization, SIMPLE (military communications protocol), Space and Planetary Science, Trajectory planning, International Space Station, Aerospace Engineering, Atmospheric drag, Translation (geometry), Simulation, Rule of thumb

الوصف: Long-term trajectory planning for the International Space Station (ISS) uses simple rules of thumb embedded in a manual framework to target translation burns. This approach is limited by coarse kno...

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::20368aa6f7f79de57b21a15dbde2832cTest
https://doi.org/10.2514/1.a34292Test

المؤلفون: Kirti V. Sawant, Krishna Rajarathnam, Krishna Mohan Sepuru, Aaron J. Brown, Prem Raj B. Joseph

المصدر: Journal of Histochemistry & Cytochemistry. 66:229-239

مصطلحات موضوعية: Models, Molecular, 0301 basic medicine, Chemokine, Histology, Neutrophils, Reviews, Inflammation, Extracellular matrix, 03 medical and health sciences, chemistry.chemical_compound, Cell Movement, In vivo, medicine, Animals, Humans, Amino Acid Sequence, CXC chemokine receptors, Receptor, Glycosaminoglycans, Innate immune system, biology, Heparan sulfate, Immunity, Innate, Cell biology, 030104 developmental biology, Neutrophil Infiltration, chemistry, biology.protein, Chemokines, Anatomy, medicine.symptom, Sequence Alignment

الوصف: Circulating neutrophils, rapidly recruited in response to microbial infection, form the first line in host defense. Humans express ~50 chemokines, of which a subset of seven chemokines, characterized by the conserved “Glu-Leu-Arg” motif, mediate neutrophil recruitment. Neutrophil-activating chemokines (NACs) share similar structures, exist as monomers and dimers, activate the CXCR2 receptor on neutrophils, and interact with tissue glycosaminoglycans (GAGs). Considering cellular assays have shown that NACs have similar CXCR2 activity, the question has been and remains, why do humans express so many NACs? In this review, we make the case that NACs are not redundant and that distinct GAG interactions determine chemokine-specific in vivo functions. Structural studies have shown that the GAG-binding interactions of NACs are distinctly different, and that conserved and specific residues in the context of structure determine geometries that could not have been predicted from sequences alone. Animal studies indicate recruitment profiles of monomers and dimers are distinctly different, monomer–dimer equilibrium regulates recruitment, and that recruitment profiles vary between chemokines and between tissues, providing evidence that GAG interactions orchestrate neutrophil recruitment. We propose in vivo GAG interactions impact several chemokine properties including gradients and lifetime, and that these interactions fine-tune and define the functional response of each chemokine that can vary between different cell and tissue types for successful resolution of inflammation.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::272d077a18b077e703ff39672e14bb70Test
https://doi.org/10.1369/0022155417739864Test

المؤلفون: Kirti V. Sawant, Krishna Rajarathnam, Aaron J. Brown, Prem Raj B. Joseph

المصدر: International Journal of Molecular Sciences; Volume 18; Issue 4; Pages: 748
International Journal of Molecular Sciences

مصطلحات موضوعية: 0301 basic medicine, Chemokine, Magnetic Resonance Spectroscopy, Chemokine CXCL1, Oligosaccharides, heparin, Platelet Factor 4, heterodimer, CXC chemokine receptors, Receptor, Spectroscopy, Glycosaminoglycans, biology, Chemistry, General Medicine, beta-Thromboglobulin, Computer Science Applications, Cell biology, CXCL1, Biochemistry, CXCL7, Small heterodimer partner, Protein Binding, HL-60 Cells, Molecular Dynamics Simulation, Catalysis, Article, Inorganic Chemistry, 03 medical and health sciences, Protein Domains, glycosaminoglycan, Humans, Interleukin 8, Amino Acid Sequence, Physical and Theoretical Chemistry, chemokine, CXCR2, NMR, Molecular Biology, Binding Sites, 030102 biochemistry & molecular biology, Sequence Homology, Amino Acid, Organic Chemistry, Interleukin-8, Kinetics, 030104 developmental biology, biology.protein, Calcium, Protein Multimerization, Function (biology)

الوصف: Chemokines mediate diverse fundamental biological processes, including combating infection. Multiple chemokines are expressed at the site of infection; thus chemokine synergy by heterodimer formation may play a role in determining function. Chemokine function involves interactions with G-protein-coupled receptors and sulfated glycosaminoglycans (GAG). However, very little is known regarding heterodimer structural features and receptor and GAG interactions. Solution nuclear magnetic resonance (NMR) and molecular dynamics characterization of platelet-derived chemokine CXCL7 heterodimerization with chemokines CXCL1, CXCL4, and CXCL8 indicated that packing interactions promote CXCL7-CXCL1 and CXCL7-CXCL4 heterodimers, and electrostatic repulsive interactions disfavor the CXCL7-CXCL8 heterodimer. As characterizing the native heterodimer is challenging due to interference from monomers and homodimers, we engineered a "trapped" disulfide-linked CXCL7-CXCL1 heterodimer. NMR and modeling studies indicated that GAG heparin binding to the heterodimer is distinctly different from the CXCL7 monomer and that the GAG-bound heterodimer is unlikely to bind the receptor. Interestingly, the trapped heterodimer was highly active in a Ca2+ release assay. These data collectively suggest that GAG interactions play a prominent role in determining heterodimer function in vivo. Further, this study provides proof-of-concept that the disulfide trapping strategy can serve as a valuable tool for characterizing the structural and functional features of a chemokine heterodimer.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5fe752cc84c0cfdbf0bb01ccd04e54a5Test