21 research outputs found

    Genetic Parameters of Austrian Fleckvieh Cattle in Organic and Conventional Production Systems with Different Levels of Management Intensity

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    Improvement of breeding and management has resulted in a considerable improvement of production and many fitness traits in Austrian dairy cattle. Apart from that, a variety of different dairy production systems, comprising organic, extensive to intensive systems can be observed in Austria. It can be assumed that different breeding goals exist in different production systems which would cause differences in genetic parameters and would imply the necessity of adapted breeding objectives. Therefore, the aim of the study was to estimate genetic parameters of three different production systems (organic, conventional low and high level of farm intensity) for three productions (milk kg, fat kg, protein kg) and six fitness traits (persistency, somatic cell score, functional longevity, milking speed, udder health index and fertility index) using an approximate multivariate two-step approach. In general, heritabilities and genetic correlations were similar in all three production systems. Heritabilities ranged from 0.04 for fertility index for the farms with a low level of farm intensity to 0.65 for milk kg for farms with a high level of farm intensity. Almost no deviations were found between the genetic correlations across the defined production systems. Due to the similar results it can be concluded that breeding objectives are similar in different production systems and currently breeding objectives do not need to be adjusted

    Genetic Parameters of Austrian Fleckvieh Cattle in Organic and Conventional Production Systems with Different Levels of Management Intensity

    Get PDF
    Improvement of breeding and management has resulted in a considerable improvement of production and many fitness traits in Austrian dairy cattle. Apart from that, a variety of different dairy production systems, comprising organic, extensive to intensive systems can be observed in Austria. It can be assumed that different breeding goals exist in different production systems which would cause differences in genetic parameters and would imply the necessity of adapted breeding objectives. Therefore, the aim of the study was to estimate genetic parameters of three different production systems (organic, conventional low and high level of farm intensity) for three productions (milk kg, fat kg, protein kg) and six fitness traits (persistency, somatic cell score, functional longevity, milking speed, udder health index and fertility index) using an approximate multivariate two-step approach. In general, heritabilities and genetic correlations were similar in all three production systems. Heritabilities ranged from 0.04 for fertility index for the farms with a low level of farm intensity to 0.65 for milk kg for farms with a high level of farm intensity. Almost no deviations were found between the genetic correlations across the defined production systems. Due to the similar results it can be concluded that breeding objectives are similar in different production systems and currently breeding objectives do not need to be adjusted

    Ca<sup>2+</sup> mobilization assays in GPCR drug discovery

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    FLIPR Calcium Mobilization Assays in GPCR Drug Discovery

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    Characterisation of P2Y12 Receptor Responsiveness to Cysteinyl Leukotrienes

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    Leukotriene E4 (LTE4), the most stable of the cysteinyl leukotrienes (cysLTs), binds poorly to classical type 1 and 2 cysLT receptors although in asthmatic individuals it may potently induce bronchial constriction, airway hyperresponsiveness and inflammatory cell influx to the lung. A recent study has suggested that the purinergic receptor P2Y12 is required for LTE4 mediated pulmonary inflammation in a mouse model of asthma and signals in response to cysLTs. The aim of the study was to characterise the responsiveness of human P2Y12 to cysteinyl leukotrienes. Models of human CysLT1, CysLT2 and P2Y12 overexpressed in HEK293, CHO cells and human platelets were used and responsiveness to different agonists was measured using intracellular calcium, cAMP and β-arrestin recruitment assays. CysLTs induced concentration dependent calcium mobilisation in cells overexpressing CysLT1 and CysLT2 but failed to induce any calcium response in cells expressing P2Y12 or P2Y12+ Gα16. In contrast, selective P2Y12 agonists ADP and 2-MeS-ADP induced specific calcium flux in cells expressing P2Y12+ Gα16. Similarly, specific response to 2-MeS-ADP, but not to cysLTs was also observed in cells expressing P2Y12 when intracellular cAMP and β-arrestin signalling were analysed. Platelets were used as a model of human primary cells expressing P2Y12 to analyse potential signalling and cell activation through P2Y12 receptor or receptor heterodimers but no specific LTE4 responses were observed. These results show that LTE4 as well as other cysLTs do not activate intracellular signalling acting through P2Y12 and suggest that another LTE4 specific receptor has yet to be identified

    Sphingosine-1-phosphate induces pro-remodelling response in airway smooth muscle cells

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    Background : Increased proliferation of airway smooth muscle (ASM) cells leading to hyperplasia and increased ASM mass is one of the most characteristic features of airway remodelling in asthma. A bioactive lipid, sphingosine-1-phosphate (S1P), has been suggested to affect airway remodelling by stimulation of human ASM cell proliferation. Objective : To investigate the effect of S1P on signalling and regulation of gene expression in ASM cells from healthy and asthmatic individuals. Methods : ASM cells grown from bronchial biopsies of healthy and asthmatic individuals were exposed to S1P. Gene expression was analysed using microarray, real-time PCR and western blotting. Receptor signalling and function was determined by mRNA knockdown and intracellular calcium mobilisation experiments. Results : S1P potently regulated the expression of more than 80 genes in human ASM cells, including several genes known to be involved in the regulation of cell proliferation and airway remodelling (HBEGF, TGFB3, TXNIP, PLAUR, SERPINE1, RGS4). S1P acting through S1P[subscript 2] and S1P[subscript 3] receptors activated intracellular calcium mobilisation and extracellular signal-regulated and Rho-associated kinases to regulate gene expression. S1P-induced responses were not inhibited by corticosteroids and did not differ significantly between ASM cells from healthy and asthmatic individuals. Conclusion : S1P induces a steroid-resistant, pro-remodelling pathway in ASM cells. Targeting S1P or its receptors could be a novel treatment strategy for inhibiting airway remodelling in asthma

    Ponsin interacts with Nck adapter proteins: implications for a role in cytoskeletal remodelling during differentiation of skeletal muscle cells

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    Skeletal muscle differentiation is a complex process: It is characterised by changes in gene expression and protein composition. Simultaneously, a dramatic remodelling of the cytoskeleton and associated cell-matrix contacts, the costameres, occurs. The expression and localisation of the protein ponsin at cell-matrix contacts marks the establishment of costameres. In this report we show that skeletal muscle cells are characterised by a novel ponsin isoform, which contains a large insertion in its carboxy-terminus. This skeletal muscle-specific module binds the adapter proteins Nck1 and Nck2, and increased co-localisation of ponsin with Nck2 is observed at remodelling cell-matrix contacts of differentiating skeletal muscle cells. Since this ponsin insertion can be phosphorylated, it may adjust the interaction affinity with Nck adapter proteins. The novel ponsin isoform and its interaction with Nck1/2 provide exciting insight into the convergence of signalling pathways at the costameres, and its crucial role for skeletal muscle differentiation and re-generation

    Effect of LTE<sub>4</sub> stimulation on calcium and β-arrestin signalling pathways in mouse P2Y<sub>12</sub> transfectants.

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    <p>HEK293 cells were transiently transfected with indicated vectors and intracellular calcium responses recorded. (A) [m-P2Y<sub>12</sub>+ G<sub>α16</sub>] and [Empty+G<sub>α16</sub>] transfectants were stimulated with LTE<sub>4</sub> and 2-MeS-ADP, N = 9, 2-way ANOVA between 2-MeS-ADP responses p = 0.0101. (B) CHO cells stably expressing m-P2Y<sub>12</sub> and β-arrestin were stimulated with either 2-MeS-ADP or LTE<sub>4</sub>, N = 9. Data presented as mean ± S.E.M.</p
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