Project description:Leadership plays an important role in employee well-being. In light of a growing research interest in leaders' resources as determinants of healthy leadership, it is not yet clear how leaders' behavior regarding their own health (self-care) may trickle down to employees. Drawing on Conservation of Resources Theory and the model of Health-Oriented Leadership, this study tests two mechanisms through which employees may benefit from self-caring leaders: (a) through staff care, that is, concern for their employees' health (improved leadership hypothesis); and (b) through a direct relationship between leaders' and employees' self-care (role-modeling hypothesis). In turn, both staff care and employee self-care would relate positively to employee health. Multilevel path models based on a sample of N = 46 supervisors and 437 employees revealed that leader self-care was positively related to leader-rated staff care at Level 2, which was positively related to employee-rated staff care at Level 1. In turn, employee-rated staff care was positively related to employee health. The findings support the improved leadership hypothesis and underline the importance of leader self-care as a determinant of healthy leadership.
Project description:Currently, several ?-synuclein immunotherapies are being tested in experimental Parkinson's disease models and in clinical trials. Recent research has revealed that ?-synuclein is not just an intracellular synaptic protein but also exists extracellularly. Moreover, the transfer of misfolded ?-synuclein between cells might be a crucial step in the process leading to a progressive increase in deposition of ?-synuclein aggregates throughout the Parkinson's disease brain. The revelation that ?-synuclein is present outside cells has increased the interest in antibody-based therapies and opens up for the notion that microglia might play a key role in retarding Parkinson's disease progression. The objectives of this review are to describe and contrast the use of active and passive immunotherapy in treating ?-synucleinopathies and highlight the likely important role of microglia in clearing misfolded ?-synuclein from the extracellular space.
Project description:BackgroundCancer cells possess a common metabolic phenotype, rewiring their metabolic pathways from mitochondrial oxidative phosphorylation to aerobic glycolysis and anabolic circuits, to support the energetic and biosynthetic requirements of continuous proliferation and migration. While, over the past decade, molecular and cellular studies have clearly highlighted the association of oncogenes and tumor suppressors with cancer-associated glycolysis, more recent attention has focused on the role of microRNAs (miRNAs) in mediating this metabolic shift. Accumulating studies have connected aberrant expression of miRNAs with direct and indirect regulation of aerobic glycolysis and associated pathways.Scope of reviewThis review discusses the underlying mechanisms of metabolic reprogramming in cancer cells and provides arguments that the earlier paradigm of cancer glycolysis needs to be updated to a broader concept, which involves interconnecting biological pathways that include miRNA-mediated regulation of metabolism. For these reasons and in light of recent knowledge, we illustrate the relationships between metabolic pathways in cancer cells. We further summarize our current understanding of the interplay between miRNAs and these metabolic pathways. This review aims to highlight important metabolism-associated molecular components in the hunt for selective preventive and therapeutic treatments.Major conclusionsMetabolism in cancer cells is influenced by driver mutations but is also regulated by posttranscriptional gene silencing. Understanding the nuanced regulation of gene expression in these cells and distinguishing rapid cellular responses from chronic adaptive mechanisms provides a basis for rational drug design and novel therapeutic strategies.
Project description:MicroRNAs (miRNAs) are short, non-protein-encoding RNAs that effect post-transcriptional gene regulation by targeting messenger RNAs. miRNAs are associated with specific human diseases and help regulate development. Here we review recent advances in understanding the roles of miRNAs in skeletal malformations, including cleft palate, and in the evolution of skeletal morphologies. We propose the hypothesis that evolutionary variation in miRNA expression patterns or structural variation in miRNA binding sites in messenger RNAs can help explain the evolution of craniofacial variation among species, the development of human craniofacial disease and physiological changes leading to osteopenia that increases with ageing.
Project description:The unconventional mRNA capping enzyme (GDP polyribonucleotidyltransferase, PRNTase) domain of the vesicular stomatitis virus (VSV) L protein possesses a dual-functional "priming-capping loop" that governs terminal de novo initiation for leader RNA synthesis and capping of monocistronic mRNAs during the unique stop-start transcription cycle. Here, we investigated the roles of basic amino acid residues on a helix structure directly connected to the priming-capping loop in viral RNA synthesis and identified single point mutations that cause previously unreported defective phenotypes at different steps of stop-start transcription. Mutations of residue R1183 (R1183A and R1183K) dramatically reduced the leader RNA synthesis activity by hampering early elongation, but not terminal de novo initiation or productive elongation, suggesting that the mutations negatively affect escape from the leader promoter. On the other hand, mutations of residue R1178 (R1178A and R1178K) decreased the efficiency of polyadenylation-coupled termination of mRNA synthesis at the gene junctions, but not termination of leader RNA synthesis at the leader-to-N-gene junction, resulting in the generation of larger amounts of aberrant polycistronic mRNAs. In contrast, both the R1183 and R1178 residues are not essential for cap-forming activities. The R1183K mutation was lethal to VSV, whereas the R1178K mutation attenuated VSV and triggered the production of the polycistronic mRNAs in infected cells. These observations suggest that the PRNTase domain plays multiple roles in conducting accurate stop-start transcription beyond its known role in pre-mRNA capping.
Project description:MicroRNAs are implicated in many biological and pathological processes and are emerging as key actors in lung health and disease. Specific patterns of dysregulated microRNAs have been found in idiopathic pulmonary fibrosis (IPF), an untreatable interstitial lung disease of unknown etiology. IPF is characterized by dramatic and extensive phenotypic changes in the lung that include alveolar cell hyperplasia, fibroblast proliferation and formation of myofibroblast foci, deposition of extracellular matrix, and changes in lung transcriptional programming. Here, we discuss the latest insights about the role of microRNAs in lung fibrosis with a focus on the contribution of animal models of disease to the derivation of these insights.
Project description:What will be the role of the intensivist when computer-assisted decision support reaches maturity? Celi's group reports that Bayesian theory can predict a patient's fluid requirement on day 2 in 78% of cases, based on data collected on day 1 and the known associations between those data, based on observations in previous patients in their unit. There are both advantages and limitations to the Bayesian approach, and this test study identifies areas for improvement in future models. Although such models have the potential to improve diagnostic and therapeutic accuracy, they must be introduced judiciously and locally to maximize their effect on patient outcome. Efficacy is thus far undetermined, and these novel approaches to patient management raise new challenges, not least medicolegal ones.