PI4P-signaling pathway for the synthesis of a nascent membrane structure in selective autophagy

Phosphoinositides regulate a wide range of cellular activities, including membrane trafficking and biogenesis, via interaction with various effector proteins that contain phosphoinositide binding motifs. We show that in the yeast Pichia pastoris, phosphatidylinositol 4′-monophosphate (PI4P) initiates de novo membrane synthesis that is required for peroxisome degradation by selective autophagy and that this PI4P signaling is modulated by an ergosterol-converting PpAtg26 (autophagy-related) protein harboring a novel PI4P binding GRAM (glucosyltransferase, Rab-like GTPase activators, and myotubularins) domain. A phosphatidylinositol-4-OH kinase, PpPik1, is the primary source of PI4P. PI4P concentrated in a protein–lipid nucleation complex recruits PpAtg26 through an interaction with the GRAM domain. Sterol conversion by PpAtg26 at the nucleation complex is necessary for elongation and maturation of the membrane structure. This study reveals the role of the PI4P-signaling pathway in selective autophagy, a process comprising multistep molecular events that lead to the de novo membrane formation

TiO2/Si composites synthesized by sol-gel method and their improved electrode performance as Li-ion battery anodes

Composites of rutile-type TiO2 and Si were synthesized by a facile sol-gel method for a high-performance anode of Li-ion battery. We have investigated anode performance of binder-free thick-film electrodes prepared by a gas-deposition method using the TiO2/Si composites obtained. The composite electrode exhibited a remarkably improved cyclability and a good high-rate performance: a discharge capacity at the 900th cycle was 710 mA h g–1, and a specific capacity per Si weight was as large as 1870 mA h g(Si)–1 even at a high current rate of 4.8C. It is suggested that a fast Li-ion diffusion in TiO2 provides smooth insertion/extraction of Li-ion into/from the composite electrodes. The results offer a utility of rutile TiO2 as a Li-ion conductor in Si-based electrodes for the next-generation Li-ion battery

The Institutional Presidency from a Comparative Perspective: Argentina and Brazil since the 1980s

This paper focuses on the evolution of the institutional presidency - meaning the cluster of agencies that directly support the chief of the executive - in Argentina and Brazil since their redemocratization in the 1980s. It investigates what explains the changes that have come about regarding the size of the institutional presidency and the types of agency that form it. Following the specialized literature, we argue that the growth of the institutional presidency is connected to developments occurring in the larger political system - that is, to the political challenges that the various presidents of the two countries have faced. Presidents adjust the format and mandate of the different agencies under their authority so as to better manage their relations with the political environment. In particular, we argue that the type of government (coalition or single-party) has had consequences for the structure of the presidency or, in other words, that different cabinet structures pose different challenges to presidents. This factor has not played a significant role in presidency-related studies until now, which have hitherto mostly been based on the case of the United States. Our empirical references, the presidencies of Argentina and Brazil, typical cases of coalitional as well as single-party presidentialism respectively allow us to show the impact of the type of government on the number and type of presidential agencies

A1C but Not Serum Glycated Albumin Is Elevated in Late Pregnancy Owing to Iron Deficiency

OBJECTIVE—A1C levels have been shown to be elevated in relation to glycemia in late pregnancy, although the precise mechanisms remain undetermined. We hypothesized that iron deficiency is involved in the A1C increase in late pregnancy

The Ability of β-Cells to Compensate for Insulin Resistance is Restored with a Reduction in Excess Growth Hormone in Korean Acromegalic Patients

The aim of this study was to assess the prevalence of diabetes and to study the effects of excess growth hormone (GH) on insulin sensitivity and β-cell function in Korean acromegalic patients. One hundred and eighty-four acromegalic patients were analyzed to assess the prevalence of diabetes, and 52 naïve acromegalic patients were enrolled in order to analyze insulin sensitivity and insulin secretion. Patients underwent a 75 g oral glucose tolerance test with measurements of GH, glucose, insulin, and C-peptide levels. The insulin sensitivity index and β-cell function index were calculated and compared according to glucose status. Changes in the insulin sensitivity index and β-cell function index were evaluated one to two months after surgery. Of the 184 patients, 17.4% were in the normal glucose tolerance (NGT) group, 45.1% were in the pre-diabetic group and 37.5% were in the diabetic group. The insulin sensitivity index (ISI0,120) was significantly higher and the HOMA-IR was lower in the NGT compared to the diabetic group (P = 0.001 and P = 0.037, respectively). The ISI0,120 and disposition index were significantly improved after tumor resection. Our findings suggest that both insulin sensitivity and β-cell function are improved by tumor resection in acromegalic patients

Vascular endothelial growth factor: an angiogenic factor reflecting airway inflammation in healthy smokers and in patients with bronchitis type of chronic obstructive pulmonary disease?

<p>Abstract</p> <p>Background</p> <p>Patients with bronchitis type of chronic obstructive pulmonary disease (COPD) have raised vascular endothelial growth factor (VEGF) levels in induced sputum. This has been associated with the pathogenesis of COPD through apoptotic and oxidative stress mechanisms. Since, chronic airway inflammation is an important pathological feature of COPD mainly initiated by cigarette smoking, aim of this study was to assess smoking as a potential cause of raised airway VEGF levels in bronchitis type COPD and to test the association between VEGF levels in induced sputum and airway inflammation in these patients.</p> <p>Methods</p> <p>14 current smokers with bronchitis type COPD, 17 asymptomatic current smokers with normal spirometry and 16 non-smokers were included in the study. VEGF, IL-8, and TNF-α levels in induced sputum were measured and the correlations between these markers, as well as between VEGF levels and pulmonary function were assessed.</p> <p>Results</p> <p>The median concentrations of VEGF, IL-8, and TNF-α were significantly higher in induced sputum of COPD patients (1,070 pg/ml, 5.6 ng/ml and 50 pg/ml, respectively) compared to nonsmokers (260 pg/ml, 0.73 ng/ml, and 15.4 pg/ml, respectively, p < 0.05) and asymptomatic smokers (421 pg/ml, 1.27 ng/ml, p < 0.05, and 18.6 pg/ml, p > 0.05, respectively). Significant correlations were found between VEGF levels and pack years (r = 0.56, p = 0.046), IL-8 (r = 0.64, p = 0.026) and TNF-α (r = 0.62, p = 0.031) levels both in asymptomatic and COPD smokers (r = 0.66, p = 0.027, r = 0.67, p = 0.023, and r = 0.82, p = 0.002, respectively). No correlation was found between VEGF levels in sputum and pulmonary function parameters.</p> <p>Conclusion</p> <p>VEGF levels are raised in the airways of both asymptomatic and COPD smokers. The close correlation observed between VEGF levels in the airways and markers of airway inflammation in healthy smokers and in smokers with bronchitis type of COPD is suggestive of VEGF as a marker reflecting the inflammatory process that occurs in smoking subjects without alveolar destruction.</p

The Prediabetic Period: Review of Clinical Aspects

Hyperglycemia that does not satisfy the diagnostic criteria for diabetes mellitus (DM) is generally called prediabetes (preDM). The global prevalence of preDM has been increasing progressively in the past few decades, and it has been established that preDM status is a strong risk factor for DM and cardiovascular disease. Currently, preDM status is classified into two subtypes: impaired fasting glucose and impaired glucose tolerance. Currently, preDM is not regarded as an independent clinical entity, but only as a risk factor for others. In this article, we review various clinical aspects of preDM in terms of the working definition, changes in criteria over the years, epidemiology, and pathophysiological characteristics, and its clinical significance in current medicine