Signal transduction mechanism of interleukin 6 in cultured rat mesangial cells

AbstractInterleukin 6 (IL-6) is one of the potent autocrine growth factors for mesangial cells. We investigated the signal transduction mechanism or IL-6 in cultured rat mesangial cells. IL-6 induced a transient increase of inositol 1,4,5-trisphosphate (Ins 1,4,5-P3) followed by a transient and sustained increase of intracellular calcium concentration, suggesting that IL-6 stimulates phosphoinositide turnover. IL-6 also stimulated prostaglandin E2 (PGE2) production. The IL-6-concentration dependency in PGE2 production was similar to that in Ins 1,4,5-P3 production. We concluded that the action of IL-6 on mesangial cells is exerted at least partially through the enhancement of phosphoinositide turnover and PGE2 production

The Hydrogen Burning Turn-off of RS Ophiuchi 2006

We report a coordinated multi-band photometry of the RS Oph 2006 outburst and highlight the emission line free y-band photometry that shows a mid-plateau phase at y ~ 10.2 mag from day 40 to day 75 after the discovery followed by a sharp drop of the final decline. Such mid-plateau phases are observed in other two recurrent novae, U Sco and CI Aql, and are interpreted as a bright disk irradiated by the white dwarf. We have calculated theoretical light curves based on the optically thick wind theory and have reproduced the observed light curves including the mid-plateau phase and the final sharp decline. This final decline is identified with the end of steady hydrogen shell-burning, which turned out the day ~80. This turnoff date is consistent with the end of a supersoft X-ray phase observed with Swift. Our model suggests a white dwarf mass of 1.35 \pm 0.01 M_\sun, which indicates that RS Oph is a progenitor of Type Ia supernovae. We strongly recommend the y-filter observation of novae to detect both the presence of a disk and the hydrogen burning turn-off.Comment: to appear in ApJL, 4 pages including 4 figure

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Kyara-play and the fluid self

This thesis examines how identity-formation in the context of contemporary Japan can be understood in terms of “kyara-play,” a pervasive and performative practice in which the subject circumstantially defines and enacts multiple-selves mediated by history, language, and technology. Challenging existent nihonjinron readings of Japanese identity, we open an understanding of kyara-play drawing on James Gibson’s concept of ecological psychology (Gibson, 1950/1966/1986). The concept will be further developed in terms of post-Gibsonian thinking (Fuller, 2005; Hodges, 2009; Norman, 2013), to discuss the media-cultural configuration of the subject, with a specific focus on the performative nature of the concept of Gibson’s theory of “affordance.” This focus allows the thesis to examine the generality and specificity of cultural identities, and will argue for the pragmatic interdependence between subject and environment. This thesis will also draw on the concepts of “assemblage” and “meme” to underpin its analysis of the fluid self as a vehicle for kyara-play, and focus on the prevalence of “seken,” understood as a normative governing power which opens up the production of the ambiguous self through kyara-play. Continuing an ecological psychologist perspective, we trace how Japanese language functions relationally as an equivocal determinant, which has an equally pervasive influence on the ways the subject thinks, perceives and references circumstantially-defined multiple-selves in relation to the mediated environment. Drawing on Gibson further, I will use his theories of perception to discuss how manga and the subject inter-relate, inspiring multi-form, media-mix transformations, traceable through the case studies of artists Murakami Takashi and Aida Makoto. Through their performative engagement with multiple kyara-play in multiple-dimensional spaces, we can analyse the ecological view of perception as central to an understanding of cultural formations, and appreciate how the subject perceives “the self” as a reflection of one’s surrounding environment: the ecology of self, fluidly enacted through kyara-play

The Potential Application of Heavy Ion Beams in the Treatment of Arrhythmia: The Role of Radiation-Induced Modulation of Connexin43 and the Sympathetic Nervous System.

It has been known that heart disease—such as myocardial infarction (MI), cardiac hypertrophy, or heart failure—alters the molecular structure and function of the gap junction, which can lead to an abnormal heart rhythm. Radiation has been shown to modulate intercellular communication in the skin and lungs by increasing connexin43 (Cx43) expression. Understanding how Cx43 upregulation is induced in a diseased heart can help provide a new perspective to radiation therapy for arrhythmias. In a recent study with rabbits after MI, carbon ions were accelerated to 290 MeV/u and extracted in the air; a biologically (cell kill) uniform 6-cm spread-out Bragg peak beam was generated, and beam tissue depth was set to 30 mm with energy degraders to the depth position. Targeted heavy ion irradiation (THIR) with 15 Gy to the left ventricle increased Cx43 expression, improved conductivity, decreased the spatial heterogeneity of repolarization, and reduced the vulnerability of rabbit hearts to ventricular arrhythmias after MI. In clinically normal rabbits, THIR (>10 Gy) caused a significant dose-dependent increase of Cx43 protein and messenger RNA 2 weeks after irradiation. The left (irradiated) and right (non-irradiated) ventricles exhibited circumferential upregulation of Cx43 lasting for at least 1 year. There were no significant changes in electrocardiograms and echocardiograms, indicating no apparent injury for 1 year. A single exposure of 135 MeV/u THIR with 15 Gy to a dog heart attenuated vulnerability to ventricular arrhythmia after the induction of MI for at least 1 year through the modulation of Cx43 expression. This long-lasting remodeling effect on gap junctions may lay the groundwork to novel therapies against life-threatening ventricular arrhythmias in structural heart disease. To date, there have been few investigations into the effects of carbon-ion irradiation on electrophysiological properties in the human heart. Patients with mediastinum cancer were investigated for 5 years after treatment that included irradiation to the heart, and investigators found that carbon-ion beam irradiation to the heart is not immediately cardiotoxic and demonstrates consistent signals of arrhythmia reduction. Its practical application in non–cancer treatment, such as in arrhythmia treatment, is highly anticipated

Arrhythmia Treatment Using Carbon Ion Beams

We found that carbon beam irradiation to a part of heart induces Cx43 protein in the whole heart, and antiarrhythmic effect by improve stimulating conduction. Arrhythmia reduced to be 1 from 4 cases in 5 myocardial infarction rabbits after the irradiation, and the expression of Cx43 in mRNA, Immunostaining, and Western Blotting continued for one year. Myocardial infarction dogs also showed increased expression of Cx43 and decreased arrhythmia, and no myocardial injury was observed at one year later the irradiation. Electrophysiological heart studies were conducted in 8 mediastinum cancer patients treated with carbon and follow-up for 5 years. Tendency of arrhythmia observed in 5 cases decreased in 4 cases but 1 case was unchanged, and no side-effects were observed.International Symposium on Ion Therapy 201

A Single-Arm, Prospective, Exploratory Study to Preliminarily Test Effectiveness and Safety of Skin Electrical Stimulation for Leber Hereditary Optic Neuropathy

Leber hereditary optic neuropathy (LHON) is an intractable disease associated with mitochondrial DNA (mtDNA) mutations. In this preliminary, single-arm, prospective, open-label exploratory trial, we investigated the effectiveness and safety of skin electrical stimulation (SES) for cases of LHON harboring the mtDNA 11,778 mutation. Of the 11 enrolled patients, 10 completed six sessions of SES once every two weeks over a 10-week period. The primary outcome measure was the change in logarithm of the minimum angle of resolution (logMAR)-converted best-corrected visual acuity (BCVA) at one week after the last session of SES. The main secondary outcome measures were the logMAR BCVA at four and eight weeks and Humphrey visual field test sensitivities at one, four, and eight weeks. At all follow-up points, the logMAR BCVA had improved significantly from baseline, [1.80 (1.70-1.80) at baseline, 1.75 (1.52-1.80) at one week, 1.75 (1.50-1.80) at four weeks, and 1.75 (1.52-1.80) at eight weeks; p 2-fold increase in the summed sensitivity at 52 measurement points from baseline. No adverse effects were observed. In conclusion, SES could be a viable treatment option for patients with LHON in the chronic phase harboring the mtDNA 11,778 mutation