A role for eisosomes in maintenance of plasma membrane phosphoinositide levels

The plasma membrane delineates the cell and mediates its communication and material exchange with the environment. Many processes of the plasma membrane occur through interactions of proteins with phosphatidylinositol(4,5)-bisphosphate (PI(4,5)P2), which is highly enriched in this membrane and is a key determinant of its identity. Eisosomes function in lateral organization of the plasma membrane, but the molecular function of their major protein subunits, the BAR domain–containing proteins Pil1 and Lsp1, is poorly understood. Here we show that eisosomes interact with the PI(4,5)P2 phosphatase Inp51/Sjl1, thereby recruiting it to the plasma membrane. Pil1 is essential for plasma membrane localization and function of Inp51 but not for the homologous phosphatidylinositol bisphosphate phosphatases Inp52/Sjl2 and Inp53/Sjl3. Consistent with this, absence of Pil1 increases total and available PI(4,5)P2 levels at the plasma membrane. On the basis of these findings, we propose a model in which the eisosomes function in maintaining PI(4,5)P2 levels by Inp51/Sjl1 recruitment

Optimal simple rules and the lower bound on the nominal interest rate in the Christiano–Eichenbaum–Evans model of the US business cycle

Schmitt-Grohé and Uribe (NBER wp 10724, 2004b) analyzes the optimal, simple and implementable monetary policy rules in a medium-scale macromodel, as the one proposed by Christiano et al. (J Polit Econ 113:1–45, 2005). In doing so, they use a sensible, but somewhat arbitrary constraint to account for the lower bound condition on the nominal interest rate. In this work, we check the robustness of their main results to such a criteria. We find that the optimal policies are actually absolutely robust to the easing of this criterion for all the diff erent cases considered.info:eu-repo/semantics/publishedVersio

Regular Solar Radio Imaging at Arecibo: Space Weather Perspective of Evolution of Active Regions

The sudden release of magnetic energy on the Sun drives powerful solar flares and coronal mass ejections. The key issue is the difficulty in predicting the occurrence time and location of strong solar eruptions, i.e., those leading to the high impact space weather disturbances at the near-Earth environment. Solar radio imaging helps identify the magnetic field characteristics of active regions susceptible to intense flares and energetic coronal mass ejections. Mapping of the Sun at X-band (8.1 -- 9.3 GHz) with the 12-m radio telescope at the Arecibo Observatory allows monitoring of the evolution of the brightness temperature of active regions in association with the development of magnetic complexity, which can lead to strong eruptions. For a better forecasting strategy in the future, such ground-based radio observations of high-spatial and temporal resolution, along with a full polarization capability, would have tremendous potential not only to understand the magnetic activity of solar eruptions, but also for revealing the particle acceleration mechanism and additional exciting science.Comment: 11 pages and 3 figures (White Paper Submitted to `Decadal Survey for Solar and Space Physics (Heliophysics) 2024-2033'

Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci

Alopecia areata (AA) is a prevalent autoimmune disease with 10 known susceptibility loci. Here we perform the first meta-analysis of research on AA by combining data from two genome-wide association studies (GWAS), and replication with supplemented ImmunoChip data for a total of 3,253 cases and 7,543 controls. The strongest region of association is the major histocompatibility complex, where we fine-map four independent effects, all implicating human leukocyte antigen-DR as a key aetiologic driver. Outside the major histocompatibility complex, we identify two novel loci that exceed the threshold of statistical significance, containing ACOXL/BCL2L11(BIM) (2q13); GARP (LRRC32) (11q13.5), as well as a third nominally significant region SH2B3(LNK)/ATXN2 (12q24.12). Candidate susceptibility gene expression analysis in these regions demonstrates expression in relevant immune cells and the hair follicle. We integrate our results with data from seven other autoimmune diseases and provide insight into the alignment of AA within these disorders. Our findings uncover new molecular pathways disrupted in AA, including autophagy/apoptosis, transforming growth factor beta/Tregs and JAK kinase signalling, and support the causal role of aberrant immune processes in AA

The Moral Imperative: the case of the English education system

In England, social choice in education faces trade-offs between equity and efficiency. The scope of these trade-offs ranges from the introduction of choice to correcting 'market failures' to reduce inequalities and restrict social injustices. The article analyses the English school education system and its relationship with social preferences. The authors argue that the moral and legal need for non-discriminatory education supersedes perceptions of cost-effectiveness and utilitarianism. They consider that the current system has failed owing to inappropriate processes within social and public choice and that a reformed system based on a social democratic imperative will allow closer social integration on the basis of ability rather than privilege

Sources of pro-cyclicality in east Asian financial systems

Procyclicality is a normal feature of economic systems, but financial sector weaknesses can exacerbate it sufficiently to pose a threat to macroeconomic and financial stability. These include shortcomings in bank risk management and governance, in supervision and in terms of dependence on volatile sources of funds. The paper tests econometrically for the importance of such features leading to pro-cyclicality in the financial systems of 11 East Asian countries. This analysis makes it possible to identify specific policy measures for East Asian countries that could limit the extent to which financial systems exacerbate pro-cyclicality