2,982 research outputs found

    Ultrasonic Imaging of Reproductive Events in Muskoxen

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    To our knowledge, this is the first detailed report of ovarian follicular dynamics in a wild species. It seems that the pattern in muskoxen, with major and minor waves and a short first cycle, is similar to that in goats. Insight of this kind is important in the design of appropriate artificial breeding systems and in this respect, the muskox may provide a useful model for the endangered takin {Budorcas taxicolor). A detailed knowledge of ovarian events may also be critical to the interpretation of the response of wild populations to environmental stress

    Protein Delivery of an Artificial Transcription Factor Restores Widespread Ube3a Expression in an Angelman Syndrome Mouse Brain.

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    Angelman syndrome (AS) is a neurological genetic disorder caused by loss of expression of the maternal copy of UBE3A in the brain. Due to brain-specific genetic imprinting at this locus, the paternal UBE3A is silenced by a long antisense transcript. Inhibition of the antisense transcript could lead to unsilencing of paternal UBE3A, thus providing a therapeutic approach for AS. However, widespread delivery of gene regulators to the brain remains challenging. Here, we report an engineered zinc finger-based artificial transcription factor (ATF) that, when injected i.p. or s.c., crossed the blood-brain barrier and increased Ube3a expression in the brain of an adult mouse model of AS. The factor displayed widespread distribution throughout the brain. Immunohistochemistry of both the hippocampus and cerebellum revealed an increase in Ube3a upon treatment. An ATF containing an alternative DNA-binding domain did not activate Ube3a. We believe this to be the first report of an injectable engineered zinc finger protein that can cause widespread activation of an endogenous gene in the brain. These observations have important implications for the study and treatment of AS and other neurological disorders

    Investigating inbreeding in the turkey (Meleagris gallopavo) genome

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    The detrimental effects of increased homozygosity due to inbreeding have prompted the development of methods to reduce inbreeding. The detection of runs of homozygosity (ROH), or contiguous stretches of homozygous marker genotypes, can be used to describe and quantify the level of inbreeding in an individual. The estimation of inbreeding coefficients can be calculated based on pedigree information, ROH, or the genomic relationship matrix. The aim of this study was to detect and describe ROH in the turkey genome and compare estimates of pedigree-based inbreeding coefficients (FPED) with genomic-based inbreeding coefficients estimated from ROH (FROH) and the genomic relationship matrix (FGRM). A total of 2,616,890 pedigree records were available. Of these records, 6,371 genotyped animals from three purebred turkey (Meleagris gallopavo) lines between 2013 and 2019 were available, and these were obtained using a dense single nucleotide polymorphism array (56,452 SNPs). The overall mean length of detected ROH was 2.87 ± 0.29 Mb with a mean number of 84.87 ± 8.79 ROH per animal. Short ROH with lengths of 1 to 2 Mb long were the most abundant throughout the genome. Mean ROH coverage differed greatly between chromosomes and lines. Considering inbreeding coefficient means across all lines, genomic derived inbreeding coefficients (FROH = 0.27; FGRM = 0.32) were higher than coefficients estimated from pedigree records (FPED = 0.14). Correlations between FROH and FPED, FROH and FGRM, and FPED and FGRM ranged between 0.19 to 0.31, 0.68 to 0.73, and 0.17 to 0.30, respectively. Additionally, correlations between FROH from different lengths and FPED substantially increased with ROH length from -0.06 to 0.33. Results of the current research, including the distribution of ROH throughout the genome and ROH-derived inbreeding estimates, can provide a more comprehensive description of inbreeding in the turkey genome. This knowledge can be used to evaluate genetic diversity, a requirement for genetic improvement, and develop methods to minimize inbreeding in turkey breeding programs

    Diversity and Keratin Degrading Ability of Fungi Isolated from Canadian Arctic Marine Bird Feathers

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    We present the first records of fungi associated with feathers from seabirds and sea ducks in the Canadian Arctic and sub-Arctic. Birds sampled in Nunavut and Newfoundland (Canada) included the Common Eider (Somateria mollissima), King Eider (S. spectabilis), Black-legged Kittiwake (Rissa tridactyla), Northern Fulmar (Fulmarus glacialis), Glaucous Gull (Larus hyperboreus), Black Guillemot (Cepphus grylle), and Thick-billed Murre (Uria lomvia). In total 19 fungal species were cultured from feathers, identified using ITS rDNA barcoding, and screened for their ability to degrade keratin using a keratin azure assay. Our results indicate that 1) of the 19 isolates, 74% were ascomycetes, while the remaining 26% were basidiomycetes (yeasts); 2) 21% of the ascomycete isolates demonstrated keratinolytic activity (a known pathogenicity factor for fungi that may potentially be harmful to birds); 3) the largest number of fungi were cultured from the sampled Thick-billed Murre; and 4) based on a multiple correspondence analysis, there is some indication that both the King Eider and the Thick-billed Murre collected in the low Arctic had distinct fungal communities that were different from each other and from the other birds sampled. Although our sample sizes were small, initial trends in point (4) do demonstrate that additional study is merited to assess whether the fungal community differences are influenced by variation in the known ecologies of the avian hosts and fungi identified.Nous présentons les premiers enregistrements de champignons se rapportant aux plumes d’oiseaux et de canards de mer dans l’Arctique et la région subarctique du Canada. Parmi les oiseaux échantillonnés au Nunavut et à Terre-Neuve (Canada), notons l’eider à duvet (Somateria mollissima), l’eider à tête grise (S. spectabilis), la mouette tridactyle (Rissa tridactyla), le fulmar boréal (Fulmarus glacialis), le goéland bourgmestre (Larus hyperboreus), le guillemot à miroir (Cepphus grylle) et le guillemot de Brünnich (Uria lomvia). En tout, 19 espèces de champignons ont été prélevées à partir de plumes. Elles ont été identifiées au moyen de codes à barres ITS ADNr et examinées afin de déterminer si elles sont capables de dégrader la kératine, et ce, à l’aide d’une épreuve de dégradation de la kératine au bleu azur. Nos résultats indiquent : 1) que parmi les 19 isolats, 74 % étaient des ascomycètes et que les 26 % restants étaient des basidiomycètes (levures); 2) que 21 % des isolats d’ascomycètes ont affiché une activité kératinolytique (un facteur de pathogénicité pour les champignons, facteur susceptible de nuire aux oiseaux); 3) que le plus grand nombre de cultures de champignons a été prélevé chez le guillemot de Brünnich; et 4) que d’après une analyse de correspondance multiple, il y a une certaine indication que les échantillons de l’eider à tête grise et du guillemot de Brünnich recueillis dans le Bas-Arctique comprenaient des communautés fongiques distinctes qui différaient les unes des autres ainsi que des autres oiseaux échantillonnés. Même si la taille de nos échantillons était petite, les premières tendances ressortant du point (4) démontrent qu’il y a lieu de faire des études plus poussées afin de déterminer si les différences entre les communautés fongiques sont influencées par la variation des écologies connues des hôtes aviaires et des champignons identifiés

    Deep learning for accurately recognizing common causes of shoulder pain on radiographs

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    Objective: Training a convolutional neural network (CNN) to detect the most common causes of shoulder pain on plain radiographs and to assess its potential value in serving as an assistive device to physicians. Materials and methods: We used a CNN of the ResNet-50 architecture which was trained on 2700 shoulder radiographs from clinical practice of multiple institutions. All radiographs were reviewed and labeled for six findings: proximal humeral fractures, joint dislocation, periarticular calcification, osteoarthritis, osteosynthesis, and joint endoprosthesis. The trained model was then evaluated on a separate test dataset, which was previously annotated by three independent expert radiologists. Both the training and the test datasets included radiographs of highly variable image quality to reflect the clinical situation and to foster robustness of the CNN. Performance of the model was evaluated using receiver operating characteristic (ROC) curves, the thereof derived AUC as well as sensitivity and specificity. Results: The developed CNN demonstrated a high accuracy with an area under the curve (AUC) of 0.871 for detecting fractures, 0.896 for joint dislocation, 0.945 for osteoarthritis, and 0.800 for periarticular calcifications. It also detected osteosynthesis and endoprosthesis with near perfect accuracy (AUC 0.998 and 1.0, respectively). Sensitivity and specificity were 0.75 and 0.86 for fractures, 0.95 and 0.65 for joint dislocation, 0.90 and 0.86 for osteoarthrosis, and 0.60 and 0.89 for calcification. Conclusion: CNNs have the potential to serve as an assistive device by providing clinicians a means to prioritize worklists or providing additional safety in situations of increased workload

    Describing the relationships among meat quality traits in domestic turkey (Meleagris gallopavo) populations.

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    The presence of meat quality defects is increasing in the turkey industry. While the main strategy for mitigating these issues is through improved housing, management, and slaughter conditions, it may be possible to incorporate meat quality into a turkey breeding strategy with the intent to improve meat quality. Before this can occur, it is important to describe the current state of turkey meat quality as well as the correlations among the different meat quality traits and important production traits. The main objective of the present study was to provide a descriptive analysis of 8 different meat quality traits for turkey breast meat from 3 different purebred lines (A, B, and C), and their correlation with a selection of production traits. Using a total of 7,781 images, the breast meat (N = 590-3,892 birds depending on trait) was evaluated at 24 h postmortem for color (L*, a*, b*), pH, and physiochemical characteristics (drip loss, cooking loss, shear force). Descriptive statistics (mean and standard deviation) and Pearson correlations were computed to describe the relationships among traits within each genetic line. A one-factor ANOVA and post hoc t-test were conducted for each trait and between each of the genetic lines. We found significant differences between genetic lines for some color traits (L* and a*), pHinitial, drip loss, and cooking loss. The lightest line in weight (line B) had meat that was the lightest (L*) in color. The heaviest line (line C) had meat that was less red (a*) with a higher pHinitial and greater cooking loss. Unfavorable correlations between production traits and meat quality were also found for each of the genetic lines where increases in production (e.g., body weight, growth rate) resulted in meat that was lighter and redder in color and in some cases (line B and C), with an increased moisture loss. The results of this study provide an important benchmark for turkey meat quality in purebred lines and provide an updated account of the relationships between key production traits and meat quality. Although the magnitude of these correlations is low, their cumulative effect on meat quality can be more significant especially with continued selection pressure on growth and yield

    Rac1 as a therapeutic target in ovarian cancer

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    Rac1 is a high value therapeutic target for cancer based on its tumor promoting activities, yet clinical applications targeting Rac1 are in their infancy. High expression and hyperactivation of Rac1 in ovarian cancer, along with our identification of R-ketorolac as a novel Rac1 and Cdc42 selective inhibitor with translational potential, prompt us to test the hypothesis that targeting Rac1 has therapeutic utility for ovarian cancer. Ascites tumor cell samples from ovarian cancer patients in a prospective study receiving racemic ketorolac for clinically indicated use in pain relief were previously reported to show time dependent reduction of Rac1 and Cdc42 activities post-treatment. New RNA seq data of these patient samples reveals significant changes of genes involved in cell adhesion, cytokine-mediated signaling and cytokine production pathways. Conversely, the identified downregulated genes were overexpressed and associated with worse survival in ovarian cancer patients analyzed through The Cancer Genome Atlas (TCGA). Among the downregulated genes in the NOD pathway are chemokines and pro-inflammatory cytokines. Follow-up cytokine panels from patients confirm that racemic ketorolac treatment reduces the levels of immunosuppressive cytokines IL-6, IL-10 and RANTES in ascites fluids. Together, these data indicate there may be a benefit to the anti-inflammatory activity of the S- enantiomer, as well as the GTPase inhibitory activity of the R- enantiomer of ketorolac for ovarian cancer treatment

    Effectiveness and cost-effectiveness of a physical activity loyalty scheme for behaviour change maintenance: a cluster randomised controlled trial

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    Abstract Background Increasing physical activity in the workplace can provide employee physical and mental health benefits, and employer economic benefits through reduced absenteeism and increased productivity. The workplace is an opportune setting to encourage habitual activity. However, there is limited evidence on effective behaviour change interventions that lead to maintained physical activity. This study aims to address this gap and help build the necessary evidence base for effective, and cost-effective, workplace interventions. Methods/design This cluster randomised control trial will recruit 776 office-based employees from public sector organisations in Belfast and Lisburn city centres, Northern Ireland. Participants will be randomly allocated by cluster to either the Intervention Group or Control Group (waiting list control). The 6-month intervention consists of rewards (retail vouchers, based on similar principles to high street loyalty cards), feedback and other evidence-based behaviour change techniques. Sensors situated in the vicinity of participating workplaces will promote and monitor minutes of physical activity undertaken by participants. Both groups will complete all outcome measures. The primary outcome is steps per day recorded using a pedometer (Yamax Digiwalker CW-701) for 7 consecutive days at baseline, 6, 12 and 18 months. Secondary outcomes include health, mental wellbeing, quality of life, work absenteeism and presenteeism, and use of healthcare resources. Process measures will assess intervention “dose”, website usage, and intervention fidelity. An economic evaluation will be conducted from the National Health Service, employer and retailer perspective using both a cost-utility and cost-effectiveness framework. The inclusion of a discrete choice experiment will further generate values for a cost-benefit analysis. Participant focus groups will explore who the intervention worked for and why, and interviews with retailers will elucidate their views on the sustainability of a public health focused loyalty card scheme. Discussion The study is designed to maximise the potential for roll-out in similar settings, by engaging the public sector and business community in designing and delivering the intervention. We have developed a sustainable business model using a ‘points’ based loyalty platform, whereby local businesses ‘sponsor’ the incentive (retail vouchers) in return for increased footfall to their business. Trial registration ISRCTN17975376 (Registered 19/09/2014)
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