187 resultados para Hundred (Political Division)
Resumo:
This paper reviews the policy learning literature in political science. In recent years, the number of publications on learning in the political realm increased dramatically. Researchers have focused on how policymakers and administrators adapt policies based on learning processes or experiences. Thereby, learning has been discussed in very different ways. Authors have referred to learning in the context of ideas, understood as deeply held beliefs, and, as change and adaptation of policy instruments. Two other strands of literature have taken into consideration learning, namely the diffusion literature and research on transfer, which put forward learning to understand who learns from whom and what. Opposed to these views, political learning emphasizes the adaptation of new strategies by policymakers over the transfer of knowledge or broad ideas. In this approach, learning occurs due to the failure of existing policies, increasing problem pressure, scientific innovations, or a combination of these elements.
Resumo:
Division site positioning is critical for both symmetric and asymmetric cell divisions. In many organisms, positive and negative signals cooperate to position the contractile actin ring for cytokinesis. In rod-shaped fission yeast Schizosaccharomyces pombe cells, division at midcell is achieved through positive Mid1/anillin-dependent signaling emanating from the central nucleus and negative signals from the dual-specificity tyrosine phosphorylation-regulated kinase family kinase Pom1 at the cell poles. In this study, we show that Pom1 directly phosphorylates the F-BAR protein Cdc15, a central component of the cytokinetic ring. Pom1-dependent phosphorylation blocks Cdc15 binding to paxillin Pxl1 and C2 domain protein Fic1 and enhances Cdc15 dynamics. This promotes ring sliding from cell poles, which prevents septum assembly at the ends of cells with a displaced nucleus or lacking Mid1. Pom1 also slows down ring constriction. These results indicate that a strong negative signal from the Pom1 kinase at cell poles converts Cdc15 to its closed state, destabilizes the actomyosin ring, and thus promotes medial septation.
Resumo:
Ever since the inception of economics over two hundred years ago, the tools at the discipline's disposal have grown more and more more sophisticated. This book provides a historical introduction to the methodology of economics through the eyes of economists. The story begins with John Stuart Mill's seminal essay from 1836 on the definition and method of political economy, which is then followed by an examination of how the actual practices of economists changed over time to such an extent that they not only altered their methods of enquiry, but also their self-perception as economists. Beginning as intellectuals and journalists operating to a large extent in the public sphere, they then transformed into experts who developed their tools of research increasingly behind the scenes. No longer did they try to influence policy agendas through public discourse; rather they targeted policymakers directly and with instruments that showed them as independent and objective policy advisors, the tools of the trade changing all the while. In order to shed light on this evolution of economic methodology, this book takes carefully selected snapshots from the discipline's history. It tracks the process of development through the nineteenth and twentieth centuries, analysing the growth of empirical and mathematical modelling. It also looks at the emergence of the experiment in economics, in addition to the similarities and differences between modelling and experimentation. This book will be relevant reading for students and academics in the fields of economic methodology, history of economics, and history and philosophy of the social sciences.
Resumo:
Chlamydiales possess a minimal but functional peptidoglycan precursor biosynthetic and remodeling pathway involved in the assembly of the division septum by an atypical cytokinetic machine and cryptic or modified peptidoglycan-like structure (PGLS). How this reduced cytokinetic machine collectively coordinates the invagination of the envelope has not yet been explored in Chlamydiales. In other Gram-negative bacteria, peptidoglycan provides anchor points that connect the outer membrane to the peptidoglycan during constriction using the Pal-Tol complex. Purifying PGLS and associated proteins from the chlamydial pathogen Waddlia chondrophila, we unearthed the Pal protein as a peptidoglycan-binding protein that localizes to the chlamydial division septum along with other components of the Pal-Tol complex. Together, our PGLS characterization and peptidoglycan-binding assays support the notion that diaminopimelic acid is an important determinant recruiting Pal to the division plane to coordinate the invagination of all envelope layers with the conserved Pal-Tol complex, even during osmotically protected intracellular growth.
Resumo:
Mutations of the huntingtin protein (HTT) gene underlie both adult-onset and juvenile forms of Huntington's disease (HD). HTT modulates mitotic spindle orientation and cell fate in mouse cortical progenitors from the ventricular zone. Using human embryonic stem cells (hESC) characterized as carrying mutations associated with adult-onset disease during pre-implantation genetic diagnosis, we investigated the influence of human HTT and of an adult-onset HD mutation on mitotic spindle orientation in human neural stem cells (NSCs) derived from hESCs. The RNAi-mediated silencing of both HTT alleles in neural stem cells derived from hESCs disrupted spindle orientation and led to the mislocalization of dynein, the p150Glued subunit of dynactin and the large nuclear mitotic apparatus (NuMA) protein. We also investigated the effect of the adult-onset HD mutation on the role of HTT during spindle orientation in NSCs derived from HD-hESCs. By combining SNP-targeting allele-specific silencing and gain-of-function approaches, we showed that a 46-glutamine expansion in human HTT was sufficient for a dominant-negative effect on spindle orientation and changes in the distribution within the spindle pole and the cell cortex of dynein, p150Glued and NuMA in neural cells. Thus, neural derivatives of disease-specific human pluripotent stem cells constitute a relevant biological resource for exploring the impact of adult-onset HD mutations of the HTT gene on the division of neural progenitors, with potential applications in HD drug discovery targeting HTT-dynein-p150Glued complex interactions.