ADP ribosylation adapts an ER chaperone response to short-term fluctuations in unfolded protein load

Gene expression programs that regulate the abundance of the chaperone BiP adapt the endoplasmic reticulum (ER) to unfolded protein load. However, such programs are slow compared with physiological fluctuations in secreted protein synthesis. While searching for mechanisms that fill this temporal gap in coping with ER stress, we found elevated levels of adenosine diphosphate (ADP)-ribosylated BiP in the inactive pancreas of fasted mice and a rapid decline in this modification in the active fed state. ADP ribosylation mapped to Arg470 and Arg492 in the substrate-binding domain of hamster BiP. Mutations that mimic the negative charge of ADP-ribose destabilized substrate binding and interfered with interdomain allosteric coupling, marking ADP ribosylation as a rapid posttranslational mechanism for reversible inactivation of BiP. A kinetic model showed that buffering fluctuations in unfolded protein load with a recruitable pool of inactive chaperone is an efficient strategy to minimize both aggregation and costly degradation of unfolded proteins.     

Separation and characteristics of the components of the antibiotic virenomycin

The composition of virenomycin, a new antitumor antibiotic was studied. Two components V and M were detected with high resolution liquid chromatography and thin layer chromatography on siluphol (Czechoslovakia) and silica gel (Merk, BRD). A preparative method for separation of the antibiotic components with the use of chromatography on columns with silica gel was developed. Biological and physicochemical properties of separate components were studied to show that they significantly differed by their antibacterial action in vitro: virenomycin V was 2 to 4 times more active than virenomycin M against a number of microbes. The physicochemical properties of the components are similar. It was shown with mass spectrometry that the molecular weight of virenomycin is 12 units higher than that of virenomycin M. The PMR spectra showed that this difference is due to the presence of a vinyl group in the chromophore moiety of the virenomycin V molecule and a methyl group at the similar site of the virenomycin M molecule.     

A study of the catalytic properties of the nitrile hydratase immobilized on aluminum oxides and carbon-containing adsorbents

The nitrile hydratase isolated from Rhodococcus ruber strain gt1, displaying a high nitrile hydratase activity, was immobilized on unmodified aluminum oxides and carbon-containing adsorbents, including the carbon support Sibunit. The activity and operational stability of the immobilized nitrile hydratase were studied in the reaction of acrylonitrile transformation into acrylamide. It was demonstrated that an increase in the carbon content in the support led to an increase in the amount of adsorbed enzyme and, concurrently, to a decrease in its activity. The nitrile hydratase immobilized on Sibunit and carbon-containing aluminum α-oxide having a “crust” structure displayed the highest operational stability in acrylonitrile hydration. It was shown that the thermostability of adsorbed nitrile hydratase increased by one order of magnitude.     

The association between EAE development in mice and the production of autoantibodies and abzymes after immunization of mice with different antigens

We have previously shown that immunization of C57BL/6 mice, prone to spontaneous development of experimental autoimmune encephalomyelitis (EAE), with three antigens (MOG_35-55, DNA-histone complex or DNA-methylated BSA complex), alters the differentiation profiles of bone marrow haematopoietic stem cells (HSCs). These are associated with the production of autoantibodies (auto-Abs) against these antigens and the formation of abzymes hydrolysing DNA, MOG, myelin basic protein (MBP) and histones. Immunization of mice with antigens accelerates the development of EAE. This work is the first to analyse the ratio of auto-Abs without and with catalytic activities at different stages of EAE development (onset, acute and remission phases) after immunization of mice with the three specific antigens. Prior to immunization and during spontaneous in-time development of EAE, the concentration of auto-Abs against MBP, MOG, histones and DNA and activities of IgG antibodies in the hydrolysis of substrates increased in parallel; correlation coefficients = +0.69-0.94. After immunization with MOG, DNA-histone complex or DNA-met-BSA complex, both positive (from +0.13 to +0.98) and negative correlations (from −0.09 to −0.69) were found between these values. Our study is the first showing that depending on the antigen, the relative amount of harmful auto-Abs without and abzymes with low or high catalytic activities may be produced only at onset and in acute or remission phases of EAE. The antigen governs the EAE development rate, whereby the ratio of auto-Abs without catalytic activity and with enzymatic activities of harmful abzymes hydrolysing MBP, MOG, histones and DNA varies strongly between different disease phases.     

Synthesis and Cytotoxic Activity of a Number of Functionalized 2,3-Allenoates

Russian Journal of Bioorganic Chemistry - A series of new functionalized allenoates has been synthesized, and their cytotoxic effect has been studied against the tumor cell line (HepG2 and Jurkat)...     

Effect of Pristine Multi-Walled Carbon Nanotubes on Formation and Degradation of Bacterial Biofilms

Microbiology - The effect of pristine multi-walled carbon nanotubes (MWCNT) on the biofilms of gram-negative bacteria, typical members of the activated sludge community, and gram-positive...     

Regulation of 3-desoxy-D-arabino-heptulosonate-7-phosphate synthetase in the bacteria Pseudomonas aurantiaca B-162

The regulation of activity and synthesis of DAHP-synthase in Pseudomonas aurantiaca B-162 was studied. Analysis of partially purified preparations of the enzyme revealed two isoenzymes: DAHP-synthase [tyr] and DAHP-synthase [phe], each of them being regulated by a corresponding amino acid. DAHP-synthase [tyr] is a dominant isoenzyme presenting 78 % of the enzyme activity, 50 % inhibition of which is possible by 1,3 x 10(-5) M of tyrosine. DAHP-synthase [phe] is minor isoenzyme (sharing 22 % of enzyme activity) and is controlled by phenylalanine. In this case, 50% of inhibition of activity is possible by adding 5,5 10(-6) M of corresponding amino acid. Synthesis of DAHP-synthase is constitutive.     

Response of microbial communities of Lake Baikal to extreme temperatures

The survival rate, metabolic activity, and ability for growth of microbial communities of Lake Baikal after exposure to extremely low temperatures (freeze-thawing) for different lengths of time have been first studied. It has been shown that short-term freezing (1-3 days) inhibits the growth and activity of microbial communities. The quantity of microorganisms increased after 7- and 15-day freezing. In the periods of maximums, the total number of microorganisms in the test samples was twice as high as in the control. It was established that after more prolonged freezing the microorganisms required more time after thawing to adapt to new conditions. In the variants with 7- and 15-day freezing, the activities of defrosted microbial communities were three or more times higher than in the control. The survival rate and activity of Baikal microorganisms after freeze-thawing confirms the fact that the Baikal microbial communities are highly resistant to this type of stress impact.