Effects of injury to mice by microwave (2400 mHz) irradiation and subsequent recovery

Threshold values of power density (PD) and exposure at which the mortality did not exceed 0.1% were determined in experiments on 2200 mice. The rate of formation of the pathological changes and of repair reactions was found to be close to an exponential function of PD. The functional relations established describe the adaptive powers of mice to microwave irradiation quantitatively.Institute of Biophysics, Academy of Sciences of the USSR, Moscow (Presented by Academician of the Academy of Medical Sciences of the USSR N. N. Zhukov-Verezhnikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 7, pp. 55–57, July, 1979.     

In-vitro mutagenic potential and effect on permeability of co-administered drugs across Caco-2 cell monolayers of Rubus idaeus and its fortified fractions

This study investigated the mutagenic, anti-mutagenic and cytotoxic effects of acetone extract of raspberry, Rubus idaeus L. (v. Ottawa) Rosaceae, and the isolated and characterized ellagitannin and anthocyanin fractions thereof, suitable for food applications. The studied raspberry extract and fractions did not show any mutagenic effects determined in the miniaturized Ames test and were not cytotoxic to Caco-2 cells at the used concentrations. However, the anti-mutagenic properties were changed (i.e. decreased mutagenicity of 2-nitrofluorene in strain TA98, and slightly increased mutagenicity of 2-aminoanthracene in strain TA100) with metabolic activation. Further, their influence on the permeability of co-administered common drugs (ketoprofen, paracetamol, metoprolol and verapamil) across Caco-2 monolayers was evaluated. The apical-to-basolateral permeability of highly permeable verapamil was mostly affected (decreased) during co-administration of the raspberry extract or the ellagitannin fraction. Ketoprofen permeability was decreased by the ellagitannin fraction. Consumption of food rich in phytochemicals, as demonstrated here with chemically characterized raspberry extract and fractions, with well-absorbing drugs would seem to affect the permeability of some of these drugs depending on the components. Thus their effects on the absorption of drugs in-vivo cannot be excluded.     

Preparation of monoclonal antibodies to the Fc-fragment of human IgG and the use of their based immunoenzyme conjugates

An original kit containing 17 clones of hybridomas, the producers of monoclonal antibodies (MCAb) against the Fc-fragments of human IgG, has been obtained. The possibility of using horseradish peroxidase conjugates of obtained MCAb as a part of ELISA test systems (Diaproph-Med, Ukraine) was comparatively studied. The application of peroxidase conjugates of two monoclonal antibodies (156C10 and 153H11) as part of five diagnostic kits was shown to provide a high specificity and a high sensitivity.     

HLA gene and haplotype frequencies in a Nagaybaks population from the Chelyabinsk Region (Russian South Urals)

A total of 112 Nagaybaks, a Turkic ethnoconfessional group living mainly in the Nagaybak district of the Chelyabinsk Region of Russian South Urals, were genotyped for HLA-A, -B, -DRB1, -DQA1 and -DQB1 loci using PCR-SSP (low-resolution) and HLA-A29 (high-resolution). All loci were in Hardy-Weinberg equilibrium (all p values >0.1 thus showing no locus-level deviations. The genotype data are available in the Allele Frequencies Net Database under the population name ‘‘Russia, South Ural, Chelyabinsk Region, Nagaybaks” and the identifier AFND0003397.     

Osteotomie als Methode der operativen Behandlung der Spasmophilie und Tetanie

Zusammenfassung 3 Beobachtungen, welche die Beeinflu\barkeit tetanischer und spasmophiler Zust?nde durch einfache operative Knochentraumen zeigen sollen.      

ParA2, a Vibrio cholerae chromosome partitioning protein,forms left-handed helical filaments on DNA

Most bacterial chromosomes contain homologs of plasmid partitioning (par) loci. These loci encode ATPases called ParA that are thought to contribute to the mechanical force required for chromosome and plasmid segregation. In Vibrio cholerae, the chromosome II (chrII) par locus is essential for chrII segregation. Here, we found that purified ParA2 had ATPase activities comparable to other ParA homologs, but, unlike many other ParA homologs, did not form high molecular weight complexes in the presence of ATP alone. Instead, formation of high molecular weight ParA2 polymers required DNA. Electron microscopy and three-dimensional reconstruction revealed that ParA2 formed bipolar helical filaments on double-stranded DNA in a sequence-independent manner. These filaments had a distinct change in pitch when ParA2 was polymerized in the presence of ATP versus in the absence of a nucleotide cofactor. Fitting a crystal structure of a ParA protein into our filament reconstruction showed how a dimer of ParA2 binds the DNA. The filaments formed with ATP are left-handed, but surprisingly these filaments exert no topological changes on the right-handed B-DNA to which they are bound. The stoichiometry of binding is one dimer for every eight base pairs, and this determines the geometry of the ParA2 filaments with 4.4 dimers per 120 Å pitch left-handed turn. Our findings will be critical for understanding how ParA proteins function in plasmid and chromosome segregation.     

Remodeling of actin filaments by ADF/cofilin proteins

Cofilin/ADF proteins play key roles in the dynamics of actin, one of the most abundant and highly conserved eukaryotic proteins. We used cryoelectron microscopy to generate a 9-Å resolution three-dimensional reconstruction of cofilin-decorated actin filaments, the highest resolution achieved for a complex of F-actin with an actin-binding protein. We show that the cofilin-induced change in the filament twist is due to a unique conformation of the actin molecule unrelated to any previously observed state. The changes between the actin protomer in naked F-actin and in the actin-cofilin filament are greater than the conformational changes between G- and F-actin. Our results show the structural plasticity of actin, suggest that other actin-binding proteins may also induce large but different conformational changes, and show that F-actin cannot be described by a single molecular model.     

Cytotoxic T lymphocytes carrying a pattern recognition protein Tag7 can detect evasive, HLA-negative but Hsp70-exposing tumor cells, thereby ensuring FasL/Fas-mediated contact killing

Within the broad problem of host immune surveillance versus tumor immune evasion, a most intriguing question is how the cellular immunity can cope with cancerous cells that have gotten rid of the classical antigen-presenting machinery. One such option stems from (1) the fact that HLA loss is often attended with expression of Hsp70 on the tumor cell surface, and (2) our findings that human lymphocytes express a protein Tag7 (also known as PGRP-S) capable of tight and specific interaction with cognate Hsp70. Here we show that a subpopulation of human CD4(+)CD25(+) lymphocytes, obtained either in culture as lymphokine-activated killers or directly from healthy donors, carry Tag7 and FasL on their surface and can indeed kill the HLA-negative tumor-derived cells K562 and MOLT-4 that expose Hsp70 and Fas. The primary binding of lymphocyte Tag7 to target-cell Hsp70 is very specific (eg, it is blocked by preincubating either cell with minimal peptides from the "partner" protein), and secures cell contact indispensable for subsequent FasL/Fas-triggered apoptosis. Unrelated to natural killer cell action or the putative role of Hsp as an antigen-presenting substitute, this novel mechanism is rather a backup analog of orthodox (CD8(+)) target recognition (Tag7 acting as built-in T-cell receptor and Hsp70 itself as ligand).     

NSI+] determinant has a pleiotropic phenotypic manifestation that is modulated by SUP35, SUP45, and VTS1 genes

We recently discovered the novel non-chromosomal determinant in Saccharomyces cerevisiae [NSI ⁺] (nonsense suppression inducer), which causes omnipotent nonsense suppression in strains where the Sup35 N-terminal domain is deleted. [NSI ⁺] possesses yeast prion features and does not correspond to previously identified yeast prion determinants. Here, we show that [NSI ⁺ ] enhances nonsense codon read-through and inhibits vegetative growth in S. cerevisiae. Using a large-scale overexpression screen to identify genes that impact the phenotypic effects of [NSI ⁺], we found that the SUP35 and SUP45 genes encoding the translation termination factors eRF3 and eRF1, respectively, modulate nonsense suppression in [NSI ⁺] strains. The VTS1 gene encodes an NQ-enriched RNA-binding protein that enhances nonsense suppression in [NSI ⁺] and [nsi ⁻] strains. We demonstrate that VTS1 overexpression, like [NSI ⁺] induction, causes translational read-through and growth defects in S. cerevisiae.