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

Detection of Escherichia coli and harmful enteric bacterial pathogens in domestic hand-dug wells in the Cuvelai Etosha Basin of Namibia

The Cuvelai Etosha Basin of Namibia is characterised by complex aquifer systems with multi-layered aquifers and various water qualities. Some parts of the basin have been covered with a pipeline system that supplies purified surface water from the Kunene River. Locations that lack a pipeline system utilisehand-dug wells as a source of drinking water. These wells draw water from shallow perched aquifers and are not protected from surface contamination nor is the water quality monitored. Sanitised water supply is relevant for the growth and development of societies and is a priority of the United Nations Millennium Development Goals. A bacteriological water quality study aimed at investigating the presence and seasonal variation of; Citrobacter, Escherichia, Klebsiella, Enterobacter, Proteus, Salmonella, Shigella, and Pseudomonasspecies was conducted on 44 hand-dug wells in the Ohangwena and Omusati regions of the Cuvelai Etosha Basin. Samples were collected from both the wet and dry seasons. Results disclosed the presence of Salmonella, Shigella, Citrobacter, Escherichia, Klebsiella, Enterobacter, Proteus, and Pseudomonas species.Chi-square confirmed a significant seasonal variation in Salmonella (P 0.05), Escherichia (P > 0.05), Klebsiella (P > 0.05), Enterobacter(P > 0.05), Proteus (P > 0.05) and Pseudomonas (P > 0.05) species.Water from these hand-dug wells is not safe for drinking unless it is subjected to appropriate treatment. It is recommended that hand-dug wells should be properly constructed at safe distances from contaminating structures such a pit latrines and routinely assessed for pathogens, and the water should be sanitized prior to consumption

A terahertz grid frequency doubler

We present a 144-element terahertz quasi-optical grid frequency doubler. The grid is a planar structure with bow-tie antennas as a unit cell, each loaded with a planar Schottky diode. The maximum output power measured for this grid is 24 mW at 1 THz for 3.1-μs 500-GHz input pulses with a peak input power of 47 W. An efficiency of 0.17% for an input power of 6.3 W and output power of 10.8 mW is measured. To date, this is the largest recorded output power for a multiplier at terahertz frequencies. Input and output tuning curves are presented and an output pattern is measured and compared to theory

Resurgent Current and Voltage Sensor Trapping Enhanced Activation by a β-Scorpion Toxin Solely in Nav1.6 Channel SIGNIFICANCE IN MICE PURKINJE NEURONS

Abstract Resurgent currents are functionally crucial in sustaining the high frequency firing of cerebellar Purkinje neurons expressing Nav1.6 channels. β-Scorpion toxins, such as CssIV, induce a left shift in the voltage-dependent activation of Nav1.2 channels by "trapping" the IIS4 voltage sensor segment. We found that the dangerous Cn2 β-scorpion peptide induces both the left shift voltage-dependent activation and a transient resurgent current only in human Nav1.6 channels (among 1.1-1.7), whereas CssIV did not induce the resurgent current. Cn2 also produced both actions in mouse Purkinje cells. These findings suggest that only distinct β-toxins produce resurgent currents. We suggest that the novel and unique selectivity of Cn2 could make it a model drug to replace deep brain stimulation of the subthalamic nucleus in patients with Parkinson disease

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

NLC-2 graph recognition and isomorphism

NLC-width is a variant of clique-width with many application in graph algorithmic. This paper is devoted to graphs of NLC-width two. After giving new structural properties of the class, we propose a $O(n^2 m)$-time algorithm, improving Johansson's algorithm \cite{Johansson00}. Moreover, our alogrithm is simple to understand. The above properties and algorithm allow us to propose a robust $O(n^2 m)$-time isomorphism algorithm for NLC-2 graphs. As far as we know, it is the first polynomial-time algorithm.Comment: soumis \`{a} WG 2007; 12

Plant Polyphenols and Exendin-4 Prevent Hyperactivity and TNF-alpha Release in LPS-Treated In vitro Neuron/Astrocyte/Microglial Networks

Increasing evidence supports a decisive role for neuroinflammation in the neurodegenerative process of several central nervous system (CNS) disorders. Microglia are essential mediators of neuroinflammation and can regulate a broad spectrum of cellular responses by releasing reactive oxygen intermediates, nitric oxide, proteases, excitatory amino acids, and cytokines. We have recently shown that also in ex-vivo cortical networks of neurons, astrocytes and microglia, an increased level of tumor necrosis factor-alpha (TNF-α) was detected a few hours after exposure to the bacterial endotoxin lipopolysaccharide (LPS). Simultaneously, an atypical “seizure-like” neuronal network activity was recorded by multi-electrode array (MEA) electrophysiology. These effects were prevented by minocycline, an established anti-inflammatory antibiotic. We show here that the same inhibitory effect against LPS-induced neuroinflammation is exerted also by natural plant compounds, polyphenols, such as curcumin (CU, curcuma longa), crocin (CR, saffron), and resveratrol (RE, grape), as well as by the glucagon like peptide-1 receptor (GLP-1R) agonist exendin-4 (EX-4). The drugs tested also caused per-se early transient (variable) changes of network activity. Since it has been reported that LPS-induced neuroinflammation causes rearrangements of glutamate transporters in astrocytes and microglia, we suggest that neural activity could be putatively increased by an imbalance of glial glutamate transporter activity, leading to prolonged synaptic glutamatergic dysregulation

Light Meson Dynamics Workshop. Mini proceedings

The mini-proceedings of the Light Meson Dynamics Workshop held in Mainz from February 10th to 12th, 2014, are presented. The web page of the conference, which contains all talks, can be found at https://indico.cern.ch/event/287442/overview .Comment: 46 pages, 17 contributions. Editors: W. Gradl, P. Masjuan, M. Ostrick, and S. Schere

Thermionic Energy Conversion in the Twenty-First Century: Advances and Opportunities for Space and Terrestrial Applications

Thermionic energy conversion (TEC) is the direct conversion of heat into electricity by the mechanism of thermionic emission, the spontaneous ejection of hot electrons from a surface. Although the physical mechanism has been known for over a century, it has yet to be consistently realized in a manner practical for large-scale deployment. This perspective article provides an assessment of the potential of TEC systems for space and terrestrial applications in the twenty-first century, overviewing recent advances in the field and identifying key research challenges. Recent developments as well as persisting research needs in materials, device design, fundamental understanding, and testing and validation are discussed