The DNA fragments obtained from the culture media exposed to adaptive doses of the ionizing radiation as factors of stress signaling between lymphocytes and bystander cells

At the initial stages of an adaptive response the transposition of the homologous chromosome loci from the peripheral parts of the nucleus and their approach happens. It is necessary for the repair of DNA double strand breaks in the process of the homologous recombination. Was shown that the chromosome loci transposition and accompanied by the nucleolus activities took place first in the irradiated (X-rays, 10 cGy) G0-lymphocytes, and then in the intact (bystander) cells incubated in the growth medium of irradiated lymphocytes. If there is a bystander effect the quantity of irradiated cells may be three order less than the bystander cells that affirms the great capacity of stress-signalization system. Moreover, the DNA fragments (the factors of stress signaling) were obtained from the growth medium supernatant of the irradiated and of the intact lymphocytes. In other independent experiments they were inoculated into the growth medium of recipient cells. Was demonstrated that there is loci transposition of homologous chromosomes loci and of nucleus activity after introducing the DNA fragments of irradiated cells. After introducing the DNA fragments of non-irradiated cells the both effects were not observed. In the work the characteristics of the obtained factors and the possible ways of stress signaling between the irradiated and the bystander lymphocytes were discussed.     

Stress signaling between human lymphocytes after induction of bystander effect by exposure to ionizing radiation in adaptive doses

We previously reported that the consequence of human lymphocytes irradiation by the adaptive doses (X-rays, 10 cGy) was a transposition of the homologous chromosome loci in the cell nucleus (FISH method); this phenomenon was mediated by the increase of nucleolus activity. They both are transmited to non-irradiated cells by the bystander effect (BE). We shown that the reaction of stress signaling is induced by the DNA fragments of irradiated lymphocytes. The study shows that after the inhibition of caspase 3 activity in irradiating lymphocytes or the blockade TLR9 in bystander cells the transposition was not observed. A signaling way of BE from irradiated lymphocytes apoptosis to bystander cells receptors is discussing.     

Strategies for analyzing highly enriched IP-chip datasets

Background  

Chromatin immunoprecipitation on tiling arrays (ChIP-chip) has been employed to examine features such as protein binding and histone modifications on a genome-wide scale in a variety of cell types. Array data from the latter studies typically have a high proportion of enriched probes whose signals vary considerably (due to heterogeneity in the cell population), and this makes their normalization and downstream analysis difficult.     

Abrupt and altered cell-type specific DNA methylation profiles in blood during acute HIV infection persists despite prompt initiation of ART

HIV-1 disrupts the host epigenetic landscape with consequences for disease pathogenesis, viral persistence, and HIV-associated comorbidities. Here, we examined how soon after infection HIV-associated epigenetic changes may occur in blood and whether early initiation of antiretroviral therapy (ART) impacts epigenetic modifications. We profiled longitudinal genome-wide DNA methylation in monocytes and CD4⁺ T lymphocytes from 22 participants in the RV254/SEARCH010 acute HIV infection (AHI) cohort that diagnoses infection within weeks after estimated exposure and immediately initiates ART. We identified monocytes harbored 22,697 differentially methylated CpGs associated with AHI compared to 294 in CD4⁺ T lymphocytes. ART minimally restored less than 1% of these changes in monocytes and had no effect upon T cells. Monocyte DNA methylation patterns associated with viral load, CD4 count, CD4/CD8 ratio, and longitudinal clinical phenotypes. Our findings suggest HIV-1 rapidly embeds an epigenetic memory not mitigated by ART and support determining epigenetic signatures in precision HIV medicine.Trial Registration:{"type":"clinical-trial","attrs":{"text":"NCT00782808","term_id":"NCT00782808"}}NCT00782808 and {"type":"clinical-trial","attrs":{"text":"NCT00796146","term_id":"NCT00796146"}}NCT00796146.     

Investigations of calcium homeostasis mechanisms in nerve cells and their alterations during brain pathology

The paper summarises new data about the molecular mechanisms of calcium homeostasis maintenance in nerve cells and generation of intracellular calcium transients--the most general secondary messenger triggering or modulating all steps of neuronal life cycle and its main functions. It describes the low- and high-voltage activated plasmalemmal ion channels injecting Ca2+ into the cell, cytosolic buffering systems which rapidly bind the main part of injected ions, properties of intracellular stores accumulating Ca2+ ions due to the activity of CERCA-pumps and releasing them back into the cytosol via the CICR mechanism, possible participation of mitochondria in this process, extrusion of Ca2+ from the cell by PMCA-pumps. By introducing new techniques, quantitative characteristics are obtained of these mechanisms and of their participation in determining the amplitude and kinetics of calcium signals in different neurons, as well as their changes during ageing and some forms of brain pathology.     

The intraorganic lymphatic bed of the mucous membrane of the tongue

The intraorganic lymphatic bed of the canine tongue mucous membrane is presented by the superficial and deep capillary networks and by the plexuses of the intraorganic lymphatic vessels. The capillaries of the superficial network in the thickness of the mucous membrane of the dorsal surface of the lingual tip, body and root form the lymphatic bed of the mechanical and gustatory papillas. The diameter of the capillaries in the both networks and in the intraorganic lymphatic vessels is greater in the mucous membrane of the ventral surface of the tip and of the lateral surfaces of the lingual body, and density of their arrangement is higher in the mucous membrane on the dorsal surface of the lingual tip, body and root. The capillaries of the superficial network in all areas of the lingual mucous membrane are thinner than those of the deep network, and the loops formed by the capillaries of the superficial network are less than the loops of the deep network.