Characterization of a new mouse model for human apolipoprotein A-I/C-III/A-IV deficiency

Human data raised the possibility that coronary heart disease is associated with mutations in the apolipoprotein gene cluste

In vivo anti-tumor activity of the organometallic ruthenium(II)-arene complex [Ru(eta(6)-p-cymene)-Cl-2(pta)] (RAPTA-C) in human ovarian and colorectal carcinomas

Based on the clinical success of platinum-based anti-cancer drugs such as cisplatin, carboplatin and oxaliplatin, a variety of other metal-based anti-cancer compounds are being investigated. In particular, a number of ruthenium-based compounds have been identified which exhibit unique biochemical properties and reduced toxicity profiles compared to the clinically used platinum-based drugs. We have developed a series of organometallic ruthenium(II)-arene complexes that were shown to exert anti-metastatic activity with relatively minor activity on primary tumor growth. Here, we show that the prototype compound, [Ru(eta(6)-p-cymene)Cl-2(pta)], where pta = 1,3,5-triaza-7-phosphaadamantane (RAPTA-C), reduces the growth of primary tumors in preclinical models for ovarian and colorectal carcinomas. When administered daily at relatively low doses (0.2 mg kg(-1)), RAPTA-C was shown to significantly reduce the growth of the A2780 ovarian carcinoma transplanted onto the chicken chorioallantoic membrane model. Similar activity was observed in LS174T colorectal carcinoma in athymic mice, albeit at a higher dose. In both models, a clear inhibition of microvessel density was observed, confirming the previously discovered anti-angiogenic mechanism of RAPTA-C. Biodistribution studies with radiolabeled (Ru-103) RAPTA-C indicate that the compound is rapidly cleared from the organs and the bloodstream through excretion by the kidneys. As such, RAPTA-C is a promising compound for translation to clinical evaluation

Glucose Regulates the Expression of the Apolipoprotein A5 Gene

The apolipoprotein A5 gene (APOA5) is a key player in determining triglyceride concentrations in humans and mice. Since diabetes is often associated with hypertriglyceridemia, this study explores whether APOA5 gene expression is regulated by alteration in glucose homeostasis and the related pathways. D-glucose activates APOA5 gene expression in a time- and dose-dependent manner in hepatocytes, and the glycolytic pathway involved was determined using D-glucose analogs and metabolites. Together, transient transfections, electrophoretic mobility shift assays and chromatin immunoprecipitation assays show that this regulation occurs at the transcriptional level through an increase of USF1/2 binding to an E-box in the APOA5 promoter. We show that this phenomenon is not due to an increase of mRNA or protein expression levels of USF. Using protein phosphatases 1 and 2A inhibitor, we demonstrate that D-glucose regulates APOA5 gene via a dephosphorylation mechanism, thereby resulting in an enhanced USF1/2-promoter binding. Last, subsequent suppressions of USF1/2 and phosphatases mRNA through siRNA gene silencing abolished the regulation. We demonstrate that APOA5 gene is up regulated by D-glucose and USF through phosphatase activation. These findings may provide a new cross talk between glucose and lipid metabolism

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good