Genetic effects of sulfur-35 decay in Saccharomyces cerevisiae cells. V. Comparative study of the lethal and mutagenic effectiveness of the decay of 35S and 32P incorporated into cells of the radiosensitive mutant xrs2]

The lethal effect of 35S and 32P decays on cells of yeast radiation-sensitive mutant xrs2 was studied. The mutant is 7 times more sensitive than the wild type to transmutation of both isotopes. The survival curve for xrs2 was exponential. In spite of the lethal effect, mutant cells are not more mutable than the wild type under decays of both isotopes (the number of mutations in ade1 and ade2 genes was counted), xrs2 and wild type strains differ in kinds of mutations induced by the decay of incorporated 35S in ade2 locus. Namely, there are 82% of base substitutions and 18% of other types mutations induced in xrs2 strain despite 97% and 3% respectively for the wild type strain. Also it was shown that complete and mosaic mutants, induced by the the 35S decay in xrs2 strain, differ in a pattern of interallelic complementation.     

Two substrate-targeting sites in the Yersinia protein tyrosine phosphatase co-operate to promote bacterial virulence

YopH is a protein tyrosine phosphatase and an essential virulence determinant of the pathogenic bacterium Yersinia. Yersinia delivers YopH into infected host cells using a type III secretion mechanism. YopH dephosphorylates several focal adhesion proteins including p130Cas in human epithelial cells, resulting in disruption of focal adhesions and cell detachment from the extracellular matrix. How the C-terminal protein tyrosine phosphatase domain of YopH targets specific substrates such as p130Cas in the complex milieu of the host cell has not been fully elucidated. An N-terminal non-catalytic domain of YopH binds p130Cas in a phosphotyrosine-dependent manner and functions as a novel substrate-targeting site. The structure of the YopH protein tyrosine phosphatase domain bound to a model phosphopeptide substrate was solved and the resulting structure revealed a second substrate-targeting site ('site 2') within the catalytic domain. Site 2 binds to p130Cas in a phosphotyrosine-dependent manner, and co-operates with the N-terminal domain ('site 1') to promote efficient recognition of p130Cas by YopH in epithelial cells. The identification of two substrate-targeting sites in YopH that co-operate to promote epithelial cell detachment and bacterial virulence reinforces the importance of protein-protein interactions for determining protein tyrosine phosphatase specificity in vivo, and highlights the sophisticated nature of microbial pathogenicity factors.     

The influence of the exogenous melanin on the development of the second generation of the female Wistar rats exposed during the critical period of the pegnancy at the nonsterilizing doses of different rate means

The purpose of this study was to estimate the radio-protective activity of melanin for the reproductive status of Wistar rats. Wistar rats were exposed in utero either to the single gamma-irradiation on the tenth day of embryogenesis with the dose of 1 Gy or to the chronic gamma-irradiation with the total dose of 1 Gy during the first 10 days of embryogenesis. Such things like the ability of the rats to conceive, the embryogeny and early postnatal ontogeny of rat's posterity were studied. These doses of the radiation and the melanin did not produce the significant damages of the reproductive function of the survival offsprings of the first generation. The possible mechanisms of radio-protective effect of melanin on reproductive system of animals which have been exposed with the nonsterilizing doses at different mean dose rate were discussed.     

Alterations in some oxidative parameters in susceptible and resistant wheat plants infected with Puccinia recondita f.sp. tritici

We studied the systemic effects after infection of susceptible and resistant (expressing HSR) wheat plants with leaf rust (Puccinia recondita f.sp. tritici) on the amount of hydrogen peroxide and activity of some ROS scavenging enzymes. Measurements were performed 7 and 21 days after inoculation. In susceptible cultivar (Sadovo 1), an inhibition of activity of catatase and GST was found. By contrast, in resistant cultivar (Kristal), the infection caused an activation of these enzymes. Moreover, it was established that cv. Kristal plants possess constitutive higher levels of hydrogen peroxide, as well as higher superoxide dismutase activity.     

Activation of IKK by thymosin alpha1 requires the TRAF6 signalling pathway

Thymosin alpha1 (T(alpha)1) is noted for its immunomodulatory activities and therapeutic potential in treatment of infectious diseases and cancer. However, the molecular mechanism of its effectiveness is not completely understood. Here, we report that T(alpha)1 induces interleukin (IL)-6 expression through the I(kappa)B kinase (IKK) and nuclear factor-(kappa)B (NF-(kappa)B) pathway. Using IKK(beta)-deficient bone-marrow-derived macrophages and mouse embryo fibroblasts (MEFs), we show that IKK(beta) is essential for IKK and NF-(kappa)B activation as well as efficient IL-6 induction. Further analysis using tumour necrosis factor receptor-associated factor 6 (TRAF6)-deficient MEFs shows that TRAF6 is crucial for activation of IKK and induction of IL-6 by Talpha1. Intriguingly, T(alpha)1 triggers protein kinase C (PKC)iota/zeta activation, which is TRAF6 dependent and involves IKK. In addition, T(alpha)1 induces the formation of a signalsome composed of TRAF6, p62 and PKC(iota)/zeta as well as IKK. Thus, our study identifies T(alpha)1 as a unique activator of the TRAF6 signal pathway and provides a cohesive interpretation of the molecular basis of the therapeutic utility of T(alpha)1.     

Removal of power-line interference from the ECG: a review of the subtraction procedure

Background  

Modern biomedical amplifiers have a very high common mode rejection ratio. Nevertheless, recordings are often contaminated by residual power-line interference. Traditional analogue and digital filters are known to suppress ECG components near to the power-line frequency. Different types of digital notch filters are widely used despite their inherent contradiction: tolerable signal distortion needs a narrow frequency band, which leads to ineffective filtering in cases of larger frequency deviation of the interference. Adaptive filtering introduces unacceptable transient response time, especially after steep and large QRS complexes. Other available techniques such as Fourier transform do not work in real time. The subtraction procedure is found to cope better with this problem.     

Peptidomics: a logical sequel to proteomics

Rapid progress of separation techniques as well as methods of structural analysis provided conditions in the past decade for total screening of complex biologic mixtures for any given class of biomolecules. The present review updates the reader with the modern state of peptidomics, a chapter of chemical biology that deals with structure and biologic properties of sets of peptides present in biologic tissues, cells or fluids. Scope and limitations of currently employed experimental techniques are considered and the main results are outlined. Considerable attention will be afforded to the biologic role of peptides formed in vivo by proteolysis of nonspecialized precursor proteins with other well-defined functions. In conclusion, the connection is discussed between peptidomics and the much more mature and still closely related field of proteomics.     

Effect of SWF-radiation on thrombocytes and erythrocyte functions of albino rats upon stress condition

With the help of a specially designed generator, we have investigated the effect of electromagnetic SWF-oscillation, at nitric oxide molecular spectrum of radiation and absorption, on the function of thrombocytes and erythrocytes of albino rats in the state of immobilizing stress. 5, 15 and 30 min long SWF-radiation treatments were demonstrated to foster various degrees of restoration of thrombocyte and erythrocyte function, the efficiency depending on the period of radiation. It was after a 30 min radiation of rats that a most expressed restoration of thrombocyte and erythrocyte functional activity was observed.     

A PHD finger motif in the C terminus of RAG2 modulates recombination activity

The RAG1 and RAG2 proteins catalyze V(D)J recombination and are essential for generation of the diverse repertoire of antigen receptor genes and effective immune responses. RAG2 is composed of a "core" domain that is required for the recombination reaction and a C-terminal nonessential or "non-core" region. Recent evidence has emerged arguing that the non-core region plays a critical regulatory role in the recombination reaction, and mutations in this region have been identified in patients with immunodeficiencies. Here we present the first structural data for the RAG2 protein, using NMR spectroscopy to demonstrate that the C terminus of RAG2 contains a noncanonical PHD finger. All of the non-core mutations of RAG2 that are implicated in the development of immunodeficiencies are located within the PHD finger, at either zinc-coordinating residues or residues adjacent to an alpha-helix on the surface of the domain that participates in binding to the signaling molecules, phosphoinositides. Functional analysis of disease and phosphoinositide-binding mutations reveals novel intramolecular interactions within the non-core region and suggests that the PHD finger adopts two distinct states. We propose a model in which the equilibrium between these states modulates recombination activity. Together, these data identify the PHD finger as a novel and functionally important domain of RAG2.