Geoscientists now live in a world rich with digital data and methods, and their computational research cannot be fully captured in traditional publications. The Geoscience Paper of the Future (GPF) presents an approach to fully document, share, and cite all their research products including data, software, and computational provenance. This article proposes best practices for GPF authors to make data, software, and methods openly accessible, citable, and well documented. The publication of digital objects empowers scientists to manage their research products as valuable scientific assets in an open and transparent way that enables broader access by other scientists, students, decision makers, and the public. Improving documentation and dissemination of research will accelerate the pace of scientific discovery by improving the ability of others to build upon published work.
The regulation of protein synthesis by the availability of heme in reticulocytes is well established. However, the mechanism by which heme regulates translational initiation is not clear. In this study, we have examined the heme regulation directly on the homogeneous heme-regulated eIF-2A kinase (HRI), which is activated during heme deficiency. We found that HRI purified as a hemoprotein with the characteristic Soret band of hemoprotein at 424 nm. This HRI was an active autokinase and eIF-2A kinase, and its kinase activities were inhibited by submicromolar concentrations of hemin with an apparent K i of 0.5 µM. Homogeneous HRI was a homodimer, and its activities could not be inhibited by incubation with purified inactive K199R HRI in vitro. Our results suggest that there are two distinct types of hemebinding sites in the HRI homodimer. The binding of heme to the first site is stable, while the binding of heme to the second site is responsible for the rapid downregulation of HRI activity by heme. These results indicate that HRI binds heme and serves as a sensor of the availability of heme to coordinate the balanced synthesis of globins and heme in erythroid cells.Keywords : protein kinase ; heme ; hemoprotein ; translation ; initiation.Protein synthesis in reticulocytes is regulated by the availability of heme. During heme deficiency, protein synthesis is inhibited at the level of initiation, as a result of the activation of the heme-regulated eukaryotic initiation factor 2A (eIF-2A) kinase (HRI) (reviewed in [1Ϫ3]). Phosphorylation of the A subunit of eIF-2 at the Ser51 residue by activated HRI results in the formation of the eIF-2(AP)/eIF-2B complex and renders eIF-2B non-functional. eIF-2B is required for the exchange of GTP for GDP bound to eIF-2 in the recycling of eIF-2 for another round of initiation. Since eIF-2B is limiting, phosphorylation of a fraction of eIF-2 is sufficient to shut-off protein synthesis.In addition to HRI, there are two other eIF-2A kinases that have been studied extensively (reviewed in [4]); these are human and mouse double-stranded RNA-dependent eIF-2A kinase (PKR), and yeast and Drosophila [5] GCN2 protein kinase. These three eIF-2A kinases share extensive homology in the kinase catalytic domains [5Ϫ8], and phosphorylate eIF-2A at Ser51 [9,10]. However, the regulatory mechanisms of these three eIF-2A kinases are very different, involving heme for HRI, dsRNA for PKR and the condition of amino acid starvation for GCN2. Both HRI and PKR can functionally substitute for GCN2 in the GCN4 translational control in yeast [11]. The autophosphorylation, eIF-2A phosphorylation and the inhibition of protein synthesis by purified HRI is inhibited by incubation with hemin [28]. In addition, the binding of hemin to a highly purified HRI has been demonstrated [29]. We have shown that hemin promotes intersubunit disulfide-bond formation in HRI [30], and that this disulfide-bond formation in HRI correlates with the maintenance of protein synthesis, the reversal of the inhibition of protein synthesi...
Cyanobacteria are unique eubacteria with an organized subcellular compartmentalization of highly differentiated internal thylakoid membranes (TM), in addition to the outer and plasma membranes (PM). This leads to a complicated system for transport and sorting of proteins into the different membranes and compartments. By shotgun and gel-based proteomics of plasma and thylakoid membranes from the cyanobacterium Synechocystis sp. PCC 6803, a large number of membrane proteins were identified. Proteins localized uniquely in each membrane were used as a platform describing a model for cellular membrane organization and protein intermembrane sorting and were analyzed by multivariate sequence analyses to trace potential differences in sequence properties important for insertion and sorting to the correct membrane. Sequence traits in the C-terminal region, but not in the N-terminal nor in any individual transmembrane segments, were discriminatory between the TM and PM classes. The results are consistent with a contact zone between plasma and thylakoid membranes, which may contain short-lived "hemifusion" protein traffic connection assemblies. Insertion of both integral and peripheral membrane proteins is suggested to occur through common translocons in these subdomains, followed by a potential translation arrest and structure-based sorting into the correct membrane compartment.
Yerba Mate, derived from the leaves of the tree, Ilex paraguariensis, is widely-used as a tea or as an ingredient in formulated foods. The aim of the present study was to evaluate the effects of Yerba Mate extract on weight loss, obesity-related biochemical parameters, and diabetes in high-fat diet-fed mice.To this end, by using in vivo animal models of dietary-induced obesity, we have made the interesting observations that Yerba Mate has the ability to decrease the differentiation of pre-adipocytes and to reduce the accumulation of lipids in adipocytes, both of which contribute to a lower growth rate of adipose tissue, lower body weight gain, and obesity. Our data from in vivo studies revealed that Yerba Mate treatment affects food intake, resulting in higher energy expenditure, likely as a result of higher basal metabolism in Yerba Mate-treated mice. Furthermore, in vivo effects of Yerba Mate on lipid metabolism included reductions in serum cholesterol, serum triglycerides, and glucose concentrations in mice that were fed a high fat diet. In conclusion, Yerba Mate can potentially be used to treat obesity and diabetes.
This cross-sectional study aimed to explore the relationships among sociodemographics, health literacy, self-efficacy, social support, health-promoting behavior, and health-related quality of life (HRQOL) in older adults. A total of 240 older adults aged >65 years were recruited from three community senior welfare centers in South Korea. Standardized self-administered questionnaires measuring sociodemographic characteristics, health literacy, social support, self-efficacy, health-promoting behavior, and health-related quality of life were distributed to older adults. Multiple regression analyses with stepwise selection was used to determine the factors affecting health-related quality of life. Factors affecting a higher physical component score of HRQOL were a higher comprehension level of and numeracy in health literacy, physical health-promoting behavior, perceived emotional–informational support, and a lesser number of comorbidities. Factors affecting a higher mental component score of HRQOL were a higher comprehension level of and numeracy in health literacy, self-efficacy, physical health-promoting behavior, perceived emotional–informational support, and a lesser number of comorbidities. To improve HRQOL among older adults, nursing interventions are required to measure health literacy, empower physical health-promoting behavior and self-efficacy, and enhance emotional–informational support from family or other resources.
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