Channel noise in nerve membranes and lipid bilayers

The basic principles underlying fluctuation phenomena in thermodynamics have long been understood (for reviews see Kubo, 1957; Kubo, Matsuo & Kazuhiro 1973 Lax, 1960). Classical examples of how fluctuation analysis can provide an insight into the corpuscular nature of matter are the determination of Avogadro's number according to Einstein's theory of Brownian motion (see, e.g. Uhlenbeck & Ornstein, 1930; Kac, 1947) and the evaluation of the electronic charge from the shot noise in vacuum tubes (see Van der Ziel, 1970

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

Novel modulatory effects of neurosteroids and benzodiazepines on excitatory and inhibitory neurons excitability: a multi-electrode array (MEA) recording study.

The dynamic equilibrium between glutamate- and GABA-mediated synaptic neurotransmission in the brain is fundamental to the control of nervous system function. Such a balance is regulated by the \u2018tonic\u2019 release of a variety of neurotransmitters and endogenous factors that influence synaptic function. One such important group of modulatory molecules are the neurosteroids (NSs) which, similarly to benzodiazepines (BDZs), enhance GABAergic neurotransmission. The purpose of our work was to investigate, at in-vivo physiologically relevant concentrations, the effects of these two classes of GABA modulators on dissociated neocortical neuron networks grown in long-term culture. We used a multi-electrode array (MEA) recording technique and a novel method of analysis that was able to both identify the action potentials of engaged excitatory and inhibitory neurons and to detect novel drug-induced network up-states (burst). We found that the NSs tetrahydrodeoxycorticosterone (THDOC) and allopregnanolone (ALLO) applied at low nanomolar concentrations, produced different modulatory effects on the two neuronal clusters. Conversely, at high concentrations (1 \ub5M), both NSs, decreased excitatory and inhibitory neuron cluster excitability; however, even several hours after washout, the excitability of inhibitory neurons continued to be depressed, leading to a network long term depression (LTD). The BDZs clonazepam (CLZ) and midazolam (MDZ) also decreased the network excitability, but only MDZ caused LTD of inhibitory neuron cluster. To investigate the origin of the LTD after MDZ application, we tested finasteride (FIN), an inhibitor of endogenous NSs synthesis. FIN did not prevent the LTD induced by MDZ, but surprisingly induced it after application of CLZ. The significance and possible mechanisms underlying these LTD effects of NSs and BDZs are discussed. Taken together, our results not only demonstrate that ex-vivo neuronal networks show a sensitivity to drugs comparable to that expressed in vivo, but also provide a new global in-vitro description of the physiological mode of action of NSs and BDZs that can help in understanding their activity in more complex systems

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

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

Terahertz photoconductivity and plasmon modes in double-quantum-well field-effect transistors

Double-quantum-well field-effect transistors with a grating gate exhibit a sharply resonant, voltage tuned terahertz photoconductivity. The voltage tuned resonance is determined by the plasma oscillations of the composite structure. The resonant photoconductivity requires a double-quantum well but the mechanism whereby plasma oscillations produce changes in device conductance is not understood. The phenomenon is potentially important for fast, tunable terahertz detectors

Os isotopes in SNC meteorites and their implications to the early evolution of Mars and Earth

A new development on the measurement of the Os isotopic composition by mass spectrometry using negative ions opened a new field of applications. The Re-Os systematic provides time information on the differentiation of the nobel metals. The nobel metals are strongly partitioned into metal and sulphide phases, but also the generation of silicate melts might fractionate the Re-Os system. Compared to the other isotopic systems which are mainly dating the fractionation of the alkalis and alkali-earth elements, the Re-Os system is expected to disclose entirely new information about the geochemistry. Especially the differentiation and early evolution of the planets such as the formation of the core will be elucidated with this method

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

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

Urinary eicosanoid metabolites in HIV-infected women with central obesity switching to raltegravir: an analysis from the women, integrase, and fat accumulation trial.

Chronic inflammation is a hallmark of HIV infection. Eicosanoids reflect inflammation, oxidant stress, and vascular health and vary by sex and metabolic parameters. Raltegravir (RAL) is an HIV-1 integrase inhibitor that may have limited metabolic effects. We assessed urinary F2-isoprostanes (F2-IsoPs), prostaglandin E2 (PGE-M), prostacyclin (PGI-M), and thromboxane B2 (TxB2) in HIV-infected women switching to RAL-containing antiretroviral therapy (ART). Thirty-seven women (RAL = 17; PI/NNRTI = 20) with a median age of 43 years and BMI 32 kg/m(2) completed week 24. TxB2 increased in the RAL versus PI/NNRTI arm (+0.09 versus -0.02; P = 0.06). Baseline PGI-M was lower in the RAL arm (P = 0.005); no other between-arm cross-sectional differences were observed. In the PI/NNRTI arm, 24-week visceral adipose tissue change correlated with PGI-M (rho = 0.45; P = 0.04) and TxB2 (rho = 0.44; P = 0.005) changes, with a trend seen for PGE-M (rho = 0.41; P = 0.07). In an adjusted model, age ≥ 50 years (N = 8) was associated with increased PGE-M (P = 0.04). In this randomized trial, a switch to RAL did not significantly affect urinary eicosanoids over 24 weeks. In women continuing PI/NNRTI, increased visceral adipose tissue correlated with increased PGI-M and PGE-M. Older age (≥ 50) was associated with increased PGE-M. Relationships between aging, adiposity, ART, and eicosanoids during HIV-infection require further study