Large-scale albuminuria screen for nephropathy models in chemically induced mouse mutants

Background/Aim: Phenotype-driven screening of a great pool of randomly mutant mice and subsequent selection of animals showing symptoms equivalent to human kidney diseases may result in the generation of novel suitable models for the study of the pathomechanisms and the identification of genes involved in kidney dysfunction. Methods: We carried out a large-scale analysis of ethylnitrosourea (ENU)-induced mouse mutants for albuminuria by using qualitative SDS-polyacrylamide gel electrophoresis. Results: The primary albuminuria screen preceded the comprehensive phenotypic mutation analysis in a part of the mice of the Munich ENU project to avoid loss of mutant animals as a consequence of prolonged suffering from severe nephropathy. The primary screen detected six confirmed phenotypic variants in 2,011 G1 animals screened for dominant mutations and no variant in 48 G3 pedigrees screened for recessive mutations. Further breeding experiments resulted in two lines showing a low phenotypic penetrance of albuminuria. The secondary albuminuria screen was carried out in mutant lines which were established in the Munich ENU project without preceding primary albuminuria analysis. Two lines showing increased plasma urea levels were chosen to clarify if severe kidney lesions are involved in the abnormal phenotype. This analysis revealed severe albuminuria in mice which are affected by a recessive mutation leading to increased plasma urea and cholesterol levels. Conclusion: Thus, the phenotypic selection of ENU-induced mutants according to the parameter proteinuria in principle demonstrates the feasibility to identify nephropathy phenotypes in ENU-mutagenized mice. Copyright (C) 2005 S. Karger AG, Basel

An analysis of precipitation isotope distributions across Namibia using historical data

Global precipitation isoscapes based on the Global Network for Isotopes in Precipitation (GNIP) network are an important toolset that aid our understanding of global hydrologiccycles. Although the GNIP database is instrumental in developing global isoscapes, data coverage in some regions of hydrological interest (e.g., drylands) is low or non-existent thus the accuracy and relevance of global isoscapes to these regions is debatable. Capitalizing on existing literature isotope data, we generated rainfall isoscapes for Namibia (dryland) using the cokriging method and compared it to a globally fitted isoscape (GFI) downscaled to country level. Results showed weak correlation between observed and predicted isotope values in the GFI model (r2 < 0.20) while the cokriging isoscape showed stronger correlation (r2 = 0.67). The general trend of the local cokriging isoscape is consistent with synoptic weather systems (i.e., influences from Atlantic Ocean maritime vapour, Indian Ocean maritime vapour, Zaire Air Boundary, the Intertropical Convergence Zone and Tropical Temperate Troughs) and topography affecting the region. However, because we used the unweighted approach in this method, due to data scarcity, the absolute values could beimproved in future studies. A comparison of local meteoric water lines (LMWL) constructed from the cokriging and GFI suggested that the GFI model still reflects the global averageeven when downscaled. The cokriging LMWL was however more consistent with expectations for an arid environment. The results indicate that although not ideal, for data deficientregions such as many drylands, the unweighted cokriging approach using historical local data can be an alternative approach to modelling rainfall isoscapes that are more relevantto the local conditions compared to using downscaled global isoscapes

An evaluation of |Vus| and precise tests of the Standard Model from world data on leptonic and semileptonic kaon decays

We present a global analysis of leptonic and semileptonic kaon decay data, including all recent results published by the BNL-E865, KLOE, KTeV, ISTRA+ and NA48 experiments. This analysis, in conjunction with precise lattice calculations of the hadronic matrix elements now available, leads to a very precise determination of |Vus| and allows us to perform several stringent tests of the Standard Model.Comment: LaTeX, 25 pages, 12 figures, 16 tables. Submitted to EPJC. v2: Minor changes for accepted version. No numerical results change

Precision tests of the Standard Model with leptonic and semileptonic kaon decays

We present a global analysis of leptonic and semileptonic kaon decays data, including all recent results by BNL-E865, KLOE, KTeV, ISTRA+, and NA48. Experimental results are critically reviewed and combined, taking into account theoretical (both analytical and numerical) constraints on the semileptonic kaon form factors. This analysis leads to a very accurate determination of Vus and allows us to perform several stringent tests of the Standard Model

Reactivity of bulky tris(Phenylpyrazolyl) methanesulfonate copper(I) complexes towards small unsaturated molecules

Reaction of the tris(3-phenylpyrazolyl)methane sulfonate species (Tpms(Ph))Li with the copper(I) complex [Cu(MeCN)(4)][PF6] affords [Cu(Tpms(Ph))(MeCN)] 1. The latter, upon reaction with equimolar amounts of cyclohexyl-(CyNC) or 2,6-dimethylphenyl (XylNC) isocyanides, or excess CO, furnishes the corresponding Cu(I)complexes [Cu(Tpms(Ph))(CNR)] (R = Cy 2, Xyl 3) or [Cu(Tpms(Ph))(CO)] 4. The ligated isocyanide in 2 or 3 (or the acetonitrile ligand in 1)is displaced by 3-iminoisoindolin-1-one to afford 5, the first copper(I) complex containing an 3-iminoisoindolin-1-one ligand. The ligated acetonitrile in 1 undergoes nucleophilic attack by methylamine to give the amidine complex [Cu(Tpms(Ph)){MeC(NH)NHMe}] 6, whereas only the starting materials were recovered from the attempted corresponding reactions of 2 and 3 with methylamine. Complexes 1 or 6 form the trinuclear hydroxo-copper(II)species [(mu-Cu){Cu(mu-OH) (2)(Tpms(Ph))}(2)] 7 upon air oxidation in moist methanol. In all the complexes the scorpionate ligand facially caps the metal in the N,N,O-coordination mode

Chemical Diversity along the Traverse of the Rover Spirit at Gusev Crater

The Alpha-Particle-X-ray Spectrometer (APXS) is part of the in situ payload of the Mars Exploration Rovers. It has determined the chemical composition of soils and rocks along the nearly 6 km long traverse of the rover Spirit. The measuring method a combination of PIXE and XRF using Cm244 sources - allowed the unambiguous identification of elemental compositions with high precision. Besides sample triage and quantification of saltforming elements as indicators for aqueous alteration, the APXS also delivered important constraints to mineralogy intruments (i.e., Mossbauer (MB), MiniTES, Pancam) on minerals and rock types. The mineralogy instruments on the other hand provided constraints on minerals used for APXS normative calculations and, e.g. allowed the attribution of S to sulfate, instead of sulfide or elemental sulfur. This abstract gives an updated overview of the data obtained up to our current rover position on sol 720 at the eastern base of the Columbia Hills. We will emphasize elemental correlations that imply the presence of certain minerals that can not be identified by the MER mineralogy instruments

Prospects for K+→π+ννˉK^+ \to \pi^+ \nu \bar{ \nu } at CERN in NA62

The NA62 experiment will begin taking data in 2015. Its primary purpose is a 10% measurement of the branching ratio of the ultrarare kaon decay $K^+ \to \pi^+ \nu \bar{ \nu }$, using the decay in flight of kaons in an unseparated beam with momentum 75 GeV/c.The detector and analysis technique are described here.Comment: 8 pages for proceedings of 50 Years of CP

Gene Expression Profiling in the Type 1 Diabetes Rat Diaphragm

BACKGROUND:Respiratory muscle contractile performance is impaired by diabetes, mechanisms of which included altered carbohydrate and lipid metabolism, oxidative stress and changes in membrane electrophysiology. The present study examined to what extent these cellular perturbations involve changes in gene expression. METHODOLOGY/PRINCIPAL FINDINGS:Diaphragm muscle from streptozotocin-diabetic rats was analyzed with Affymetrix gene expression arrays. Diaphragm from diabetic rats had 105 genes with at least +/-2-fold significantly changed expression (55 increased, 50 decreased), and these were assigned to gene ontology groups based on over-representation analysis using DAVID software. There was increased expression of genes involved in palmitoyl-CoA hydrolase activity (a component of lipid metabolism) (P = 0.037, n = 2 genes, fold change 4.2 to 27.5) and reduced expression of genes related to carbohydrate metabolism (P = 0.000061, n = 8 genes, fold change -2.0 to -8.5). Other gene ontology groups among upregulated genes were protein ubiquitination (P = 0.0053, n = 4, fold change 2.2 to 3.4), oxidoreductase activity (P = 0.024, n = 8, fold change 2.1 to 6.0), and morphogenesis (P = 0.012, n = 10, fold change 2.1 to 4.3). Other downregulated gene groups were extracellular region (including extracellular matrix and collagen) (P = 0.00032, n = 13, fold change -2.2 to -3.7) and organogenesis (P = 0.032, n = 7, fold change -2.1 to -3.7). Real-time PCR confirmed the directionality of changes in gene expression for 30 of 31 genes tested. CONCLUSIONS/SIGNIFICANCE:These data indicate that in diaphragm muscle type 1 diabetes increases expression of genes involved in lipid energetics, oxidative stress and protein ubiquitination, decreases expression of genes involved in carbohydrate metabolism, and has little effect on expression of ion channel genes. Reciprocal changes in expression of genes involved in carbohydrate and lipid metabolism may change the availability of energetic substrates and thereby directly modulate fatigue resistance, an important issue for a muscle like the diaphragm which needs to contract without rest for the entire lifetime of the organism

ChPT tests at the NA48 and NA62 experiments at CERN

The NA48/2 Collaboration at CERN has accumulated unprecedented statistics of rare kaon decays in the Ke4 modes: Ke4(+-) ($K^\pm \to \pi^+ \pi^- e^\pm \nu$) and Ke4(00) ($K^\pm \to \pi^0 \pi^0 e^\pm \nu$) with nearly one percent background contamination. The detailed study of form factors and branching rates, based on these data, has been completed recently. The results brings new inputs to low energy strong interactions description and tests of Chiral Perturbation Theory (ChPT) and lattice QCD calculations. In particular, new data support the ChPT prediction for a cusp in the $\pi^0\pi^0$ invariant mass spectrum at the two charged pions threshold for Ke4(00) decay. New final results from an analysis of about 400 $K^\pm \to \pi^\pm \gamma \gamma$ rare decay candidates collected by the NA48/2 and NA62 experiments at CERN during low intensity runs with minimum bias trigger configurations are presented. The results include a model-independent decay rate measurement and fits to ChPT description.Comment: XIIth International Conference on Heavy Quarks and Leptons 2014, Mainz, German

Recent NA48/2 and NA62 results

The NA48/2 Collaboration at CERN has accumulated and analysed unprecedented statistics of rare kaon decays in the $K_{e4}$ modes: $K_{e4}(+-)$ ($K^\pm \to \pi^+ \pi^- e^\pm \nu$) and $K_{e4}(00)$ ($K^\pm \to \pi^0 \pi^0 e^\pm \nu$) with nearly one percent background contamination. It leads to the improved measurement of branching fractions and detailed form factor studies. New final results from the analysis of 381 $K^\pm \to \pi^\pm \gamma \gamma$ rare decay candidates collected by the NA48/2 and NA62 experiments at CERN are presented. The results include a decay rate measurement and fits to Chiral Perturbation Theory (ChPT) description.Comment: Prepared for the Proceedings of "Moriond QCD and High Energy Interactions. March 22-29 2014." conferenc