Feedback modulation of cholesterol metabolism by the lipid-responsive non-coding RNA LeXis.

Liver X receptors (LXRs) are transcriptional regulators of cellular and systemic cholesterol homeostasis. Under conditions of excess cholesterol, LXR activation induces the expression of several genes involved in cholesterol efflux, facilitates cholesterol esterification by promoting fatty acid synthesis, and inhibits cholesterol uptake by the low-density lipoprotein receptor. The fact that sterol content is maintained in a narrow range in most cell types and in the organism as a whole suggests that extensive crosstalk between regulatory pathways must exist. However, the molecular mechanisms that integrate LXRs with other lipid metabolic pathways are incompletely understood. Here we show that ligand activation of LXRs in mouse liver not only promotes cholesterol efflux, but also simultaneously inhibits cholesterol biosynthesis. We further identify the long non-coding RNA LeXis as a mediator of this effect. Hepatic LeXis expression is robustly induced in response to a Western diet (high in fat and cholesterol) or to pharmacological LXR activation. Raising or lowering LeXis levels in the liver affects the expression of genes involved in cholesterol biosynthesis and alters the cholesterol levels in the liver and plasma. LeXis interacts with and affects the DNA interactions of RALY, a heterogeneous ribonucleoprotein that acts as a transcriptional cofactor for cholesterol biosynthetic genes in the mouse liver. These findings outline a regulatory role for a non-coding RNA in lipid metabolism and advance our understanding of the mechanisms that coordinate sterol homeostasis

Bankenpools beeinflussen Sanierung positiv : über Einflüsse des Insolvenzrechts auf das Verhalten der Gläubiger

Die Pleitewelle in Deutschland steuert nach Angaben des Bundesverbandes Deutscher Inkasso-Unternehmen (BDIU) auf einen neuen Höchststand zu. Für 2003 erwartet der Verband bereits zum vierten Mal in Folge sowohl bei Unternehmens- als auch Verbraucherinsolvenzen Rekordmarken: Die für 2003 geschätzten 40 000 Unternehmenspleiten (zuzüglich weiterer 58 000 Pleiten von Selbstständigen und Privaten) mit einem zu erwartenden volkswirtschaftlichen Gesamtschaden von über 50 Milliarden Euro tragen erheblich zur schlechten Stimmung in Deutschland bei. Diese Zahlen verdeutlichen auch, wie außerordentlich wichtig ein modernes Insolvenzrecht ist, das neben dem Gläubigerschutz auch der möglichen Sanierung eines Unternehmens Rechnung trägt

Mehr Markt für mehr soziale Sicherheit : Starökonom Robert J. Shiller stellt neue Ideen in Frankfurt vor

Die neue Finanzordnung / Robert J. Shiller. - Frankfurt : Campus Verlag, 2003 450 S., ISBN 3-593-37327-0. 34,90 Euro

Using Lexis Objects for Multi-State Models in R

The Lexis class in the R package Epi provides tools for creation, manipulation and display of data from multi-state models. Transitions between states are described by rates (intensities); Lexis objects represent this kind of data and provide tools to show states and transitions annotated by relevant summary numbers. Data can be transformed to a form that allows modelling of several transition rates with common parameters.

The Big Match - Lexis v Westlaw

Lexis and Westlaw are the biggest names in subscription legal database provision. The author provides a comparative critical examination from his experience is of academic subscriptions to the services - including their American academic contentPreprint of an article by Paul Norman, former Reference and Online Services Librarian at the Institute of Advanced Legal Studies, published in Legal Information Management, the journal of the British and Irish Association of Law Librarian

Metformin for non-diabetic patients with coronary heart disease (the CAMERA study): a randomised controlled trial

<br>Background: Metformin reduces cardiovascular risk in patients with type 2 diabetes seemingly independent of lowering blood glucose concentration. We assessed the cardiovascular effects of metformin in individuals without type 2 diabetes.</br> <br>Methods: We did a single-centre, double-blind, placebo-controlled trial at the Glasgow Clinical Research Facility (Glasgow, UK). We enrolled patients taking statins who did not have type 2 diabetes but who did have coronary heart disease and large waist circumferences. Participants were randomly assigned (1:1) by computer to either metformin (850 mg twice daily) or matching placebo in block sizes of four. Patients, investigators, trial staff, and statisticians were masked to treatment allocation. The primary endpoint was progression of mean distal carotid intima-media thickness (cIMT) over 18 months in the modified intention-to-treat population. Secondary endpoints were changes in carotid plaque score (in six regions), measures of glycaemia (HbA1c, fasting glucose, and insulin concentrations, and Homeostasis Model Assessment of Insulin Resistance [HOMA-IR]), and concentrations of lipids, high sensitivity C-reactive protein, and tissue plasminogen activator. The trial was registered at ClinicalTrials.gov, number NCT00723307.</br> <br>Findings: We screened 356 patients, of whom we enrolled 173 (86 in the metformin group, 87 in the placebo group). Average age was 63 years. At baseline, mean cIMT was 0·717 mm (SD 0·129) and mean carotid plaque score was 2·43 (SD 1·55). cIMT progression did not differ significantly between groups (slope difference 0·007 mm per year, 95% CI −0·006 to 0·020; p=0·29). Change of carotid plaque score did not differ significantly between groups (0·01 per year, 95% CI −0·23 to 0·26; p=0·92). Patients taking metformin had lower HbA1c, insulin, HOMA-IR, and tissue plasminogen activator compared with those taking placebo, but there were no significant differences for total cholesterol, HDL-cholesterol, non-HDL-cholesterol, triglycerides, high sensitivity C-reactive protein, or fasting glucose. 138 adverse events occurred in 64 patients in the metformin group versus 120 in 60 patients in the placebo group. Diarrhoea and nausea or vomiting were more common in the metformin group than in the placebo group (28 vs 5).</br> <br>Interpretation: Metformin had no effect on cIMT and little or no effect on several surrogate markers of cardiovascular disease in non-diabetic patients with high cardiovascular risk, taking statins. Further evidence is needed before metformin can be recommended for cardiovascular benefit in this population.</br&gt

Lexis as most local context: towards an SFL approach to lexicology

The world of lexis is vast and complex and it is generally accepted in psycholinguistics that it is represented as part of a large complex network. However, in systemic functional linguistics (SFL) modelling lexis has remained a relatively underdeveloped area of the theory. The ideas underpinning this paper stem from exploring the interface of context and lexicology, asking how SFL does and could handle lexis within the theory. Here the SFL concept of context is used to develop a similar account of lexis. The argumentation is based on the assumption that ‘knowing about’ context and 'knowing about’ lexis is contained and maintained within a networked cognitive system. The common view of the relationship between context and lexis is generally one of disambiguation, frequently through collocation. However, I argue that there is more involved than that. In this paper, I use the SFL approach to context to establish the first steps towards an analogous approach to lexicology. The conclusion offered here is that it is theoretically plausible to draw on the dimension of instantiation, in a complementary way to delicacy, in order to model lexis as most local context, where the lexeme (or lemma) is modelled as meaning potential

Case Study: Deutsche Telekom and "Schools Online" (SaN). Connecting German Schools to the internet

The CEO of Deutsche Telekom, Ron Sommer, and Jürgen Rüttgers, current prime minister of North Rhine-Westphalia, founded “schools online” (in German: “Schulen ans Netz”, and short: SaN) in 1996 with the goal of connecting German schools to the internet. In his opening speech, Ron Sommer said the commitment of Deutsche Telekom was made on the grounds of its responsibility towards society. Deutsche Telekom wanted to display good corporate citizenship in an area that was close to its business and expertise. He also claimed the money spent was an investment into the future rather than a sponsoring activity. An early employee, Nikolaus Huss, responsible for public relations at SaN said: “There never was any clear indication as to what the goal was. It was never really made clear whether there was more to it than corporate citizenship. It was understood among us that somehow Telekom felt responsible for electronic alphabetisation and on the other hand was sure to profit from this later on, although nobody really felt it necessary to plan the future outcome.