751 research outputs found

    An Investigation of the Metabolic Response to Cardiopulmonary Bypass and the Effects of Two Levels of Intraoperative Hypothermia on the Response

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    The metabolic response to trauma has been an area of intense clinical research since Studley's identification of an increase in postoperative mortality and morbidity in patients with preoperative weight loss. Consequently, considerable efforts have been made to modify the response, including the use of nutritional, pharmacologic and environmental manipulations, and have met with varying degrees of success. The concept of using intraoperative hypothermia to reduce the "stress response to surgery" was first postulated in the 1950s but there has been little evidence to support this premise. Recently, however, a reduction in "post-traumatic proteolysis" following open-heart surgery, using a combination of moderate hypothermia (2

    Seasonal changes in the ejaculate of the male tammar wallaby, Macropus eugenii: implications for fertility and assisted breeding

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    The tammar wallaby, Macropus eugenii is a seasonally breeding macropodid marsupial. The seasonality observed in males is known to be driven by the reproductive state of the females. There is a significant increase in male prostate and Cowper's gland weights and testosterone concentration during the breeding season in January/February and again in October when the young females leave their i;nothers pouches and enter puberty. The dynamics of sperm production in the male tammar wallaby was assessed using changes in ejaculatory and sperm characteristics in and out of the breeding season in order to determine more accurately true seasonality in the male. Semen was collected from wild-caught adult males by electro-ejaculation at four times during the year (January, February, June/July and October). Ejaculates were assessed for semen volume, plug formation, sperm index, percentage and rating of motility, sperm and motile sperm concentration, and total sperm count. Increases were observed during the two breeding seasons in all traits assessed. Semen volume showed a steady increase from June/July (0.7 ml) to reach a peak in February (10.25 ml). In conclusion, we found a significant decrease in the size and coagulation properties of the ejaculate, and in sperm quality out of season. Implications for captive and assisted breeding programs are discussed

    FAK promotes stromal PD-L2 expression associated with poor survival in pancreatic cancer

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    BACKGROUND: Pancreatic Cancer is one of the most lethal cancers, with less than 8% of patients surviving 5 years following diagnosis. The last 40 years have seen only small incremental improvements in treatment options, highlighting the continued need to better define the cellular and molecular pathways contributing to therapy response and patient prognosis. METHODS: We combined CRISPR, shRNA and flow cytometry with mechanistic experiments using a Kras(G12D)p53(R172H) mouse model of pancreatic cancer and analysis of publicly available human PDAC transcriptomic datasets. RESULTS: Here, we identify that expression of the immune checkpoint, Programmed Death Ligand 2 (PD-L2), is associated with poor prognosis, tumour grade, clinical stage and molecular subtype in patients with Pancreatic Ductal Adenocarcinoma (PDAC). We further show that PD-L2 is predominantly expressed in the stroma and, using an orthotopic murine model of PDAC, identify cancer cell-intrinsic Focal Adhesion Kinase (FAK) signalling as a regulator of PD-L2 stromal expression. Mechanistically, we find that FAK regulates interleukin-6, which can act in concert with interleukin-4 secreted by CD4 T-cells to drive elevated expression of PD-L2 on tumour-associated macrophages, dendritic cells and endothelial cells. CONCLUSIONS: These findings identify further complex heterocellular signalling networks contributing to FAK-mediated immune suppression in pancreatic cancer

    Differential Survival among Batches of Atlantic Cod (Gadus morhua L.) from Fertilisation through to Post-Metamorphosis

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    Aquaculture production of cod has decreased from over 20,000 tonnes in 2009 to less than 2,000 tonnes in 2014 and the industry faces many challenges, one of which is high and unpredictably variable mortality rates in the early life stages. Hence, full-cycle farming with hatchery produced juveniles is still considered unprofitable compared to fisheries and on-growing of wild cod. In the present study, potential batch differences in progeny survival of wild-caught, hatchery-spawned Faroe Bank cod (Gadus morhuaL.) were investigated at two defined periods during early life history; i) the embryo stage (60 day degrees post fertilisation) and ii) the fry stage (110 days post hatch), post metamorphosis. The fry stage experiment was conducted in three replicates (N= 300 per replicate), and a panel of three polymorphic microsatellite markers was used for parental analysis. Mean survival rate at the embryo stage was 69% (± 20% SD). Survival was positively associated with egg diameter (P< 0.01), explaining 90% of the variation in egg survival rates. The data were too scarce to conclude either way concerning a possible correlation between survival rates between the two periods (P< 0.10). Offspring from three batches (from a total of eight) dominated in the fry stage, contributing over 90% of the progeny, and results were consistent over all three replicate tanks. The skewed batch representation observed may be of relevance to the effective management of selective breeding programmes for cod

    Integrated Airframe Technology: The Future of Advanced Composites

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    The challenge for advanced composites in integrated airframe technology is that: airframes must provide ever increasing performance at an affordable cost; reduce costs as compared to current airframe technology; and integration of design and manufacturing. The trend in technology is that a gap exists between the potential of advanced composites and our ability to effectively utilize them (cost/weight)
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