1,057 research outputs found

    The β€˜Blueprint’ framework for career management skills: a critical exploration

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    This article examines the Blueprint framework for career management skills as it has been revealed across sequential implementations in the USA, Canada and Australia. It is argued that despite its lack of an empirical basis, the framework forms a useful and innovative means through which career theory, practice and policy can be connected. The framework comprises both core elements (learning areas, learning model and levels) and contextual elements (resources, community of practice, service delivery approach and policy connection). Each of these elements is explored

    Sustained methane emissions from China after 2012 despite declining coal production and rice-cultivated area

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    China’s anthropogenic methane emissions are the largest of any country in the world. A recent study using atmospheric observations suggested that recent policies aimed at reducing emissions of methane due to coal production in China after 2010 had been largely ineffective. Here, based on a longer observational record and an updated modelling approach, we find a statistically significant positive linear trend (0.36 Β± 0.04 ( Β±1Οƒ\pm1\sigma ) Tg CH _4 yr ^βˆ’2 ) in China’s methane emissions for 2010–2017. This trend was slowing down at a statistically significant rate of -0.1 Β± 0.04 Tg CH _4 yr ^βˆ’3 . We find that this decrease in growth rate can in part be attributed to a decline in China’s coal production. However, coal mine methane emissions have not declined as rapidly as production, implying that there may be substantial fugitive emissions from abandoned coal mines that have previously been overlooked. We also find that emissions over rice-growing and aquaculture-farming regions show a positive trend (0.13 Β± 0.05 Tg CH _4 yr ^βˆ’2 for 2010–2017) despite reports of shrinking rice paddy areas, implying potentially significant emissions from new aquaculture activities, which are thought to be primarily located on converted rice paddies

    Clinical and biochemical characterization of four patients with mutations in ECHS1

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    Short-chain enoyl-CoA hydratase (SCEH, encoded by ECHS1) catalyzes hydration of 2-trans-enoyl-CoAs to 3(S)-hydroxy-acyl-CoAs. SCEH has a broad substrate specificity and is believed to play an important role in mitochondrial fatty acid oxidation and in the metabolism of branched-chain amino acids. Recently, the first patients with SCEH deficiency have been reported revealing only a defect in valine catabolism. We investigated the role of SCEH in fatty acid and branched-chain amino acid metabolism in four newly identified patients. In addition, because of the Leigh-like presentation, we studied enzymes involved in bioenergetics. Metabolite, enzymatic, protein and genetic analyses were performed in four patients, including two siblings. Palmitate loading studies in fibroblasts were performed to study mitochondrial Ξ²-oxidation. In addition, enoyl-CoA hydratase activity was measured with crotonyl-CoA, methacrylyl-CoA, tiglyl-CoA and 3-methylcrotonyl-CoA both in fibroblasts and liver to further study the role of SCEH in different metabolic pathways. Analyses of pyruvate dehydrogenase and respiratory chain complexes were performed in multiple tissues of two patients. All patients were either homozygous or compound heterozygous for mutations in the ECHS1 gene, had markedly reduced SCEH enzymatic activity and protein level in fibroblasts. All patients presented with lactic acidosis. The first two patients presented with vacuolating leukoencephalopathy and basal ganglia abnormalities. The third patient showed a slow neurodegenerative condition with global brain atrophy and the fourth patient showed Leigh-like lesions with a single episode of metabolic acidosis. Clinical picture and metabolite analysis were not consistent with a mitochondrial fatty acid oxidation disorder, which was supported by the normal palmitate loading test in fibroblasts. Patient fibroblasts displayed deficient hydratase activity with different substrates tested. Pyruvate dehydrogenase activity was markedly reduced in particular in muscle from the most severely affected patients, which was caused by reduced expression of E2 protein, whereas E2 mRNA was increased. Despite its activity towards substrates from different metabolic pathways, SCEH appears to be only crucial in valine metabolism, but not in isoleucine metabolism, and only of limited importance for mitochondrial fatty acid oxidation. In severely affected patients SCEH deficiency can cause a secondary pyruvate dehydrogenase deficiency contributing to the clinical presentatio

    The Theory/Applications Balance in Management Pedagogy: Where Do We Stand?

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    Business schools are expected to be "professional" in the sense that their mission is primarily to prepare people to practice their skills in the business world. Various critics, however, claim that management professors overemphasize theory and research and neglect the practice and applications students need to transfer classroom theory to the world of practice. This study compared an earlier sample with a more recent sample of Academy of Management members concerning the relative emphasis they believed should be placed on theory and applications in management pedagogy and the techniques they used to bring applications into the classroom. Current respondents believed that more emphasis should be placed on applications than the earlier respondents. An unexpected finding, however, was that the more recent respondents reported a lower mean usage of pedagogical techniques that are appropriate for developing students' ability to apply course concepts than the previous group. Possible reasons for these incongruent findings are discussed as well as the implications for management pedagogy.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

    Gene Promoter Evolution Targets the Center of the Human Protein Interaction Network

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    Assessing the contribution of promoters and coding sequences to gene evolution is an important step toward discovering the major genetic determinants of human evolution. Many specific examples have revealed the evolutionary importance of cis-regulatory regions. However, the relative contribution of regulatory and coding regions to the evolutionary process and whether systemic factors differentially influence their evolution remains unclear. To address these questions, we carried out an analysis at the genome scale to identify signatures of positive selection in human proximal promoters. Next, we examined whether genes with positively selected promoters (Prom+ genes) show systemic differences with respect to a set of genes with positively selected protein-coding regions (Cod+ genes). We found that the number of genes in each set was not significantly different (8.1% and 8.5%, respectively). Furthermore, a functional analysis showed that, in both cases, positive selection affects almost all biological processes and only a few genes of each group are located in enriched categories, indicating that promoters and coding regions are not evolutionarily specialized with respect to gene function. On the other hand, we show that the topology of the human protein network has a different influence on the molecular evolution of proximal promoters and coding regions. Notably, Prom+ genes have an unexpectedly high centrality when compared with a reference distribution (Pβ€Š=β€Š0.008, for Eigenvalue centrality). Moreover, the frequency of Prom+ genes increases from the periphery to the center of the protein network (Pβ€Š=β€Š0.02, for the logistic regression coefficient). This means that gene centrality does not constrain the evolution of proximal promoters, unlike the case with coding regions, and further indicates that the evolution of proximal promoters is more efficient in the center of the protein network than in the periphery. These results show that proximal promoters have had a systemic contribution to human evolution by increasing the participation of central genes in the evolutionary process

    Isolation and Characterization of Intestinal Epithelial Cells from Normal and SIV-Infected Rhesus Macaques

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    Impairment of intestinal epithelial barriers contributes to the progression of HIV/SIV infection and leads to generalized HIV-induced immune-cell activation during chronic infection. Rhesus macaques are the major animal model for studying HIV pathogenesis. However, detailed characterization of isolated rhesus epithelial cells (ECs) from intestinal tissues is not well defined. It is also not well documented whether isolated ECs had any other cell contaminants from intestinal tissues during the time of processing that might hamper interpretation of EC preparations or cultures. In this study, we identify and characterize ECs based on flow cytometry and immunohistochemistry methods using various enzymatic and mechanical isolation techniques to enrich ECs from intestinal tissues. This study shows that normal healthy ECs differentially express HLA-DR, CD23, CD27, CD90, CD95 and IL-10R markers. Early apoptosis and upregulation of ICAM-1 and HLA-DR in intestinal ECs are thought to be the key features in SIV mediated enteropathy. The data suggest that intestinal ECs might be playing an important role in mucosal immune responses by regulating the expression of different important regulatory and adhesion molecules and their function

    Mutations in Zebrafish lrp2 Result in Adult-Onset Ocular Pathogenesis That Models Myopia and Other Risk Factors for Glaucoma

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    The glaucomas comprise a genetically complex group of retinal neuropathies that typically occur late in life and are characterized by progressive pathology of the optic nerve head and degeneration of retinal ganglion cells. In addition to age and family history, other significant risk factors for glaucoma include elevated intraocular pressure (IOP) and myopia. The complexity of glaucoma has made it difficult to model in animals, but also challenging to identify responsible genes. We have used zebrafish to identify a genetically complex, recessive mutant that shows risk factors for glaucoma including adult onset severe myopia, elevated IOP, and progressive retinal ganglion cell pathology. Positional cloning and analysis of a non-complementing allele indicated that non-sense mutations in low density lipoprotein receptor-related protein 2 (lrp2) underlie the mutant phenotype. Lrp2, previously named Megalin, functions as an endocytic receptor for a wide-variety of bioactive molecules including Sonic hedgehog, Bone morphogenic protein 4, retinol-binding protein, vitamin D-binding protein, and apolipoprotein E, among others. Detailed phenotype analyses indicated that as lrp2 mutant fish age, many individualsβ€”but not allβ€”develop high IOP and severe myopia with obviously enlarged eye globes. This results in retinal stretch and prolonged stress to retinal ganglion cells, which ultimately show signs of pathogenesis. Our studies implicate altered Lrp2-mediated homeostasis as important for myopia and other risk factors for glaucoma in humans and establish a new genetic model for further study of phenotypes associated with this disease
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