Colours associated to non simply-laced Lie algebras and exact S-matrices

A new set of exact scattering matrices in 1+1 dimensions is proposed by solving the bootstrap equations. Extending earlier constructions of colour valued scattering matrices this new set has its colour structure associated to non simply-laced Lie algebras. This in particular leads to a coupling of different affine Toda models whose fusing structure has to be matched in a suitable manner. The definition of the new S-matrices is motivated by the semi-classical particle spectrum of the non simply-laced Homogeneous Sine-Gordon (HSG) models, which are integrable perturbations of WZNW cosets. In particular, the S-matrices of the simply-laced HSG models are recovered as a special case.Comment: 10 pages, TCI LaTeX (revised version to be published in PLB, Title changed and 2nd paragraph in the introduction rewritten.

A computational approach to microRNA detection

During the last few years more and more functionalities of RNA have been discovered that were previously thought of being carried out by proteins alone. One of the most striking discoveries was the de tection of microRNAs, a class of noncoding RNAs that play an important role in post-transcriptional gene regulation. Large-scale analyses are needed for the still increasingly growing amount of sequen ce data derived from new experimental technologies. In this paper we present a framework for the detection of the distinctive precursor structure of microRNAS that is based on the well-known Smith-Wat erman algorithm and various filtering steps. We conducted experiments on real genomic data and we found several new putative hits for microRNA precursor structures

Comparison of Plasma and Urine Biomarker Performance in Acute Kidney Injury.

New renal biomarkers measured in urine promise to increase specificity for risk stratification and early diagnosis of acute kidney injury (AKI) but concomitantly may be altered by urine concentration effects and chronic renal insufficiency. This study therefore directly compared the performance of AKI biomarkers in urine and plasma.This single-center, prospective cohort study included 110 unselected adults undergoing cardiac surgery with cardiopulmonary bypass between 2009 and 2010. Plasma and/or urine concentrations of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), liver fatty acid-binding protein (L-FABP), kidney injury molecule 1 (KIM1), and albumin as well as 15 additional biomarkers in plasma and urine were measured during the perioperative period. The primary outcome was AKI defined by AKIN serum creatinine criteria within 72 hours after surgery.Biomarkers in plasma showed markedly better discriminative performance for preoperative risk stratification and early postoperative (within 24h after surgery) detection of AKI than urine biomarkers. Discriminative power of urine biomarkers improved when concentrations were normalized to urinary creatinine, but urine biomarkers had still lower AUC values than plasma biomarkers. Best diagnostic performance 4h after surgery had plasma NGAL (AUC 0.83), cystatin C (0.76), MIG (0.74), and L-FAPB (0.73). Combinations of multiple biomarkers did not improve their diagnostic power. Preoperative clinical scoring systems (EuroSCORE and Cleveland Clinic Foundation Score) predicted the risk for AKI (AUC 0.76 and 0.71) and were not inferior to biomarkers. Preexisting chronic kidney disease limited the diagnostic performance of both plasma and urine biomarkers.In our cohort plasma biomarkers had higher discriminative power for risk stratification and early diagnosis of AKI than urine biomarkers. For preoperative risk stratification of AKI clinical models showed similar discriminative performance to biomarkers. The discriminative performance of both plasma and urine biomarkers was reduced by preexisting chronic kidney disease

Differential stability of cell-free circulating microRNAs : implications for their utilization as biomarkers

Background: MicroRNAs circulating in the blood, stabilized by complexation with proteins and/or additionally by encapsulation in lipid vesicles, are currently being evaluated as biomarkers. The consequences of their differential association with lipids/vesicles for their stability and use as biomarkers are largely unexplored and are subject of the present study. Methods: The levels of a set of selected microRNAs were determined by quantitative reverse-transcription PCR after extraction from sera or vesicle- and non-vesicle fractions prepared from sera. The stability of these microRNAs after incubation with RNase A or RNase inhibitor, an inhibitor of RNase A family enzymes was studied. Results: The levels of microRNA-1 and microRNA-122, but not those of microRNA-16, microRNA-21 and microRNA-142-3p, declined significantly during a 5-h incubation of the sera. RNase inhibitor prevented the loss of microRNAs in serum as well as the degradation of microRNA-122, a microRNA not expressed in blood cells, in whole blood. Stabilization of microRNA-122 was also achieved by hemolysis. Prolonged incubation of the sera led to enrichment of vesicle-associated relative to non-vesicle-associated microRNAs. Vesicle-associated microRNAs were more resistant to RNase A treatment than the respective microRNAs not associated with vesicles. Conclusions: Serum microRNAs showed differential stability upon prolonged incubation. RNase inhibitor might be useful to robustly preserve the pattern of cell-free circulating microRNAs. In the case of microRNAs not expressed in blood cells this can also be achieved by hemolysis. Vesicle-associated microRNAs appeared to be more stable than those not associated with vesicles, which might be useful to disclose additional biomarker properties of miRNAs

Tax1BP1 limits hepatic inflammation and reduces experimental hepatocarcinogenesis

The nuclear factor kappa beta (NFκB) signaling pathway plays an important role in liver homeostasis and cancer development. Tax1-binding protein 1 (Tax1BP1) is a regulator of the NFκB signaling pathway, but its role in the liver and hepatocellular carcinoma (HCC) is presently unknown. Here we investigated the role of Tax1BP1 in liver cells and murine models of HCC and liver fibrosis. We applied the diethylnitrosamine (DEN) model of experimental hepatocarcinogenesis in Tax1BP1+/+ and Tax1BP1−/− mice. The amount and subsets of non-parenchymal liver cells in in Tax1BP1+/+ and Tax1BP1−/− mice were determined and activation of NFκB and stress induced signaling pathways were assessed. Differential expression of mRNA and miRNA was determined. Tax1BP1−/− mice showed increased numbers of inflammatory cells in the liver. Furthermore, a sustained activation of the NFκB signaling pathway was found in hepatocytes as well as increased transcription of proinflammatory cytokines in isolated Kupffer cells from Tax1BP1−/− mice. Several differentially expressed mRNAs and miRNAs in livers of Tax1BP1−/− mice were found, which are regulators of inflammation or are involved in cancer development or progression. Furthermore, Tax1BP1−/− mice developed more HCCs than their Tax1BP1+/+ littermates. We conclude that Tax1BP1 protects from liver cancer development by limiting proinflammatory signaling

Diagnostic performance of biomarkers in urine.

<p>Receiver operating characteristic curves (AUC-ROC) show discriminative abilities for preoperative risk stratification (pre-OP) and postoperative diagnosis of AKI (at 2h, 4h and 24h after CPB) for all patients (solid thick line) and separately for patients with (sold thin line) and without (dashed line) preexisting CKD. Indicated are AUC (p-value).</p

An Allosteric Inhibitor Scaffold Targeting the PIF-Pocket of Atypical Protein Kinase C Isoforms

There is a current and pressing need for improved cancer therapies. The use of small molecule kinase inhibitors and their application in combinatorial regimens represent an approach to personalized targeted cancer therapy. A number of AGC kinases, including atypical Protein Kinase C enzymes (PKCs), are validated drug targets for cancer treatment. Most drug development programs for protein kinases focus on the development of drugs that bind at the ATP-binding site. Alternatively, allosteric drugs have great potential for the development of future innovative drugs. However, the rational development of allosteric drugs poses important challenges because the compounds not only must bind to a given site but also must stabilize forms of the protein with a desired effect at a distant site. Here we describe the development of a new class of compounds targeting a regulatory site (PIF-pocket) present in the kinase domain and provide biochemical and crystallographic data showing that these compounds allosterically inhibit the activity of atypical PKCs. PS432, a representative compound, decreased the rate of proliferation of non-small cell lung cancer cells more potently than aurothiomalate, an atypical PKC inhibitor currently under evaluation in clinical trials, and significantly reduced tumor growth without side effects in a mouse xenograft model. The druglike chemical class provides ample possibilities for the synthesis of derivative compounds, with the potential to allosterically modulate the activity of atypical PKCs and other kinases.Fil: Arencibia, Jose M.. Universitätsklinikum Frankfurt; AlemaniaFil: Fröhner, Wolfgang. Universitat Saarland; AlemaniaFil: Krupa, Magdalena. Universitätsklinikum Frankfurt; AlemaniaFil: Pastor Flores, Daniel. Universitätsklinikum Frankfurt; AlemaniaFil: Merker, Piotr. Universitätsklinikum Frankfurt; AlemaniaFil: Oellerich, Thomas. Goethe Universitat Frankfurt; AlemaniaFil: Neimanis, Sonja. Universitätsklinikum Frankfurt; AlemaniaFil: Schmithals, Christian. Universitätsklinikum Frankfurt; AlemaniaFil: Köberle, Verena. Universitätsklinikum Frankfurt; AlemaniaFil: Süß, Evelyn. Universitätsklinikum Frankfurt; AlemaniaFil: Zeuzem, Stefan. Universitätsklinikum Frankfurt; AlemaniaFil: Stark, Holger. Goethe Universitat Frankfurt; AlemaniaFil: Piiper, Albrecht. Universitätsklinikum Frankfurt; AlemaniaFil: Odadzic, Dalibor. Goethe Universitat Frankfurt; AlemaniaFil: Schulze, Jörg O.. Universitätsklinikum Frankfurt; AlemaniaFil: Biondi, Ricardo Miguel. Universitätsklinikum Frankfurt; Alemania. German Cancer Consortium; Alemania. German Cancer Research Center ; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin