Epizootiological-and-Epidemiological Situation in Natural Tularemia Foci of the Siberian and Far Eastern Federal Districts in 2011, and Prognosis for 2012

Presented is a piece of information about the situation in natural tularemia foci and human morbidity in the territory of Siberia and Far East in 2011. Outlined is the prognosis of epizootic situation for 2012. In 2011, sporadic morbidity was registered in the Novosibirsk, Tomsk, Kemerovo, and Omsk Regions. Isolated cases of the disease were identified in the Altai Territory, in the Khanty-Mansiisk autonomous district, and the Sakhalin Region. Specified is the fact that in 2011 epizooties were of a local scale, and the situation on tularemia on the whole was favorable. Nevertheless, the possibility of aggravation of the situation in some territories in 2012 is not ruled out completely

Pituitary tumor transforming gene-1 haplotypes and risk of pituitary adenoma: a case-control study

<p>Abstract</p> <p>Background</p> <p>It has been suggested that pituitary adenoma results from accumulation of multiple genetic and/or epigenetic aberrations, which may be identified through association studies. As pituitary tumor transforming gene-1 (<it>PTTG1</it>)/securin plays a critical role in promoting genomic instability in pituitary neoplasia, the present study explored the association of <it>PTTG1 </it>haplotypes with the risk of pituitary adenoma.</p> <p>Methods</p> <p>We genotyped five <it>PTTG1 </it>haplotype-tagging SNPs (htSNP) by PCR-RFLP assays in a case-control study, which included 280 Han Chinese patients diagnosed with pituitary adenoma and 280 age-, gender- and geographically matched Han Chinese controls. Haplotypes were reconstructed according to the genotyping data and linkage disequilibrium status of the htSNPs.</p> <p>Results</p> <p>No significant differences in allele and genotype frequencies of the htSNPs were observed between pituitary adenoma patients and controls, indicating that none of the individual <it>PTTG1 </it>SNPs examined in this study is associated with the risk of pituitary adenoma. In addition, no significant association was detected between the reconstructed <it>PTTG1 </it>haplotypes and pituitary adenoma cases or the controls.</p> <p>Conclusions</p> <p>Though no significant association was found between <it>PTTG1 </it>haplotypes and the risk of pituitary adenoma, this is the first report on the association of individual <it>PTTG1 </it>SNPs or <it>PTTG1 </it>haplotypes with the risk of pituitary adenoma based on a solid study; it will provide an important reference for future studies on the association between genetic alterations in <it>PTTG1 </it>and the risk of pituitary adenoma or other tumors.</p

Studying Humoral Immune Response at Mild and Asymptomatic COVID-19 Forms

Background. Currently, during the COVID-19 pandemic, one of the most pressing healthcare problems is to ensure the safety of the population of the Russian Federation. There is insufficient information on the duration and intensity of post-infectious immunity in relation to SARS-CoV-2, especially in case of inapparent (without clinical signs), mild or latent forms of infection.Materials and methods. The study involved 99 volunteers with a laboratory confirmed PCR diagnosis of COVID-19 who were residents of the Irkutsk Region and of other regions of the Russian Federation and arrived to work in Bodaybo on a rotational basis. Also the study included 50 conditionally healthy people living in Irkutsk who had negative PCR results for SARS-CoV-2 RNA presence.Specific IgG and IgM antibodies to SARS-CoV-2 were detected in blood serum by enzyme-linked immunosorbent assay (ELISA) using test systems “ELISA anti-SARS-CoV-2 IgG” (FBUN SSC PMB, Obolensk, Russian Federation), “SARS-CoV-2-IgG-IFA-BEST” and “SARS-CoV-2-IgM-IFA-BEST” (Vector-Best, Novosibirsk, Russian Federation).Results. The results of a study of the humoral immunity of patients with asymptomatic and clinical forms of COVID-19 are presented. The data indicate the production of specific IgG in the blood serum of people in 2–3 weeks after SARSCov-2 infection and reaching its maximum level on the 20–21st day. The seroconversion rate  was 94.9 %. It was shown that the geometric mean titer of antibodies in asymptomatic and mild forms of coronavirus infection did not differ statistically and amounted to 1:512 and 1:632, respectively. Higher titers of antibodies (1:1600) were detected in the moderate form.Conclusion. The research results can serve as a basis for studying the dynamics of changes in the indicators  of the humoral immune response in patients with COVID-19 and for clarifying the duration of their post- infectious immunity in order to predict the development of the epidemic situation and to ensure the planning of specific prevention

Population immunity to SARS-CoV-2 virus in residents of the Irkutsk Region in the dynamics of the epidemic

Background. Currently, the COVID-19 pandemic in the world and in Russia remains the main event. In this regard, the study of the manifestations of the epidemic process of the new coronavirus infection COVID-19 and the patterns of its development are an urgent area of research. In the fight against this viral disease, an important role is assigned to the study of the development of population immunity to the SARSCoV-2 virus, which will make it possible to assess the dynamics of seroprevalence and the formation of post-infectious humoral immunity, forecasting the development of the epidemiological situation, elucidating the characteristics of the epidemic process, and will also contribute to planning activities for specific and non-specific prevention of the disease.The aim: to determine the dynamics of population immunity to SARS-CoV-2 among the population of the Irkutsk region during the COVID-19 pandemic.Materials and methods. As a part of the Rospotrebnadzor project of assessing population immunity to SARS-CoV-2 in the population of the Russian Federation, the research has being conducted among the population of the Irkutsk region in the periods from June 23, 2020 to July 19, 2020 (Stage 1), from September 16, 2020 to September 25, 2020 (Stage 2), from December 7, 2020 to December 18, 2020 (Stage 3) and from March 8, 2021 to March 14, 2021(Stage 4), taking into account the reacted one recommended by the WHO. The content of antibodies to SARS-CoV-2 was determined by ELISA using a set of tests for human serum or plasma for specific immunoglobulins of class G to the proteins of the SARS-CoV-2 coronavirus.The results. The research of the humoral immunity of volunteers shows that during the period of an epidemic rise in the incidence of COVID-19 in the Irkutsk region, a low level of seroprevalence was formed (Stage 1 – 5.8 ± 0.5 %, Stage 2 – 12.1 ± 0.7 %), and in conditions of a long-term maximum increase in the incidence rate – 25.9 ± 1.0 % (Stage 3) and 46.2 ± 1.2 % (Stage 4). A significant proportion (Stage 1 – 82.2 ± 3.2 %, Stage 2 – 86.1 ± 2.3 %) of asymptomatic forms of infection characterizes the high intensity of the latently developing epidemic process in the first two stages. High levels of IgG in reconvalescents of COVID-19 persisted for an average of 3 to 5 months.Conclusion. The results of assessing the population immunity to the SARS-CoV-2 virus in the population of the Irkutsk region indicate that the seroprevalence level at Stage 4 of the research was 46.2 %. After the disease, on average, 49.5 % of persons did not detect antibodies. The results obtained should be taken into account when organizing preventive measures, including vaccination, and predicting morbidity

HCMV Spread and Cell Tropism are Determined by Distinct Virus Populations

Human cytomegalovirus (HCMV) can infect many different cell types in vivo. Two gH/gL complexes are used for entry into cells. gH/gL/pUL(128,130,131A) shows no selectivity for its host cell, whereas formation of a gH/gL/gO complex only restricts the tropism mainly to fibroblasts. Here, we describe that depending on the cell type in which virus replication takes place, virus carrying the gH/gL/pUL(128,130,131A) complex is either released or retained cell-associated. We observed that virus spread in fibroblast cultures was predominantly supernatant-driven, whereas spread in endothelial cell (EC) cultures was predominantly focal. This was due to properties of virus released from fibroblasts and EC. Fibroblasts released virus which could infect both fibroblasts and EC. In contrast, EC released virus which readily infected fibroblasts, but was barely able to infect EC. The EC infection capacities of virus released from fibroblasts or EC correlated with respectively high or low amounts of gH/gL/pUL(128,130,131A) in virus particles. Moreover, we found that focal spread in EC cultures could be attributed to EC-tropic virus tightly associated with EC and not released into the supernatant. Preincubation of fibroblast-derived virus progeny with EC or beads coated with pUL131A-specific antibodies depleted the fraction that could infect EC, and left a fraction that could predominantly infect fibroblasts. These data strongly suggest that HCMV progeny is composed of distinct virus populations. EC specifically retain the EC-tropic population, whereas fibroblasts release EC-tropic and non EC-tropic virus. Our findings offer completely new views on how HCMV spread may be controlled by its host cells

The Lid Domain of Caenorhabditis elegans Hsc70 Influences ATP Turnover, Cofactor Binding and Protein Folding Activity

Hsc70 is a conserved ATP-dependent molecular chaperone, which utilizes the energy of ATP hydrolysis to alter the folding state of its client proteins. In contrast to the Hsc70 systems of bacteria, yeast and humans, the Hsc70 system of C. elegans (CeHsc70) has not been studied to date

Androgen Receptor Drives Cellular Senescence

The accepted androgen receptor (AR) role is to promote proliferation and survival of prostate epithelium and thus prostate cancer progression. While growth-inhibitory, tumor-suppressive AR effects have also been documented, the underlying mechanisms are poorly understood. Here, we for the first time link AR anti-cancer action with cell senescence in vitro and in vivo. First, AR-driven senescence was p53-independent. Instead, AR induced p21, which subsequently reduced ΔN isoform of p63. Second, AR activation increased reactive oxygen species (ROS) and thereby suppressed Rb phosphorylation. Both pathways were critical for senescence as was proven by p21 and Rb knock-down and by quenching ROS with N-Acetyl cysteine and p63 silencing also mimicked AR-induced senescence. The two pathways engaged in a cross-talk, likely via PML tumor suppressor, whose localization to senescence-associated chromatin foci was increased by AR activation. All these pathways contributed to growth arrest, which resolved in senescence due to concomitant lack of p53 and high mTOR activity. This is the first demonstration of senescence response caused by a nuclear hormone receptor

Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor

Antidepressants increase adult hippocampal neurogenesis in animal models, but the underlying molecular mechanisms are unknown. In this study, we used human hippocampal progenitor cells to investigate the molecular pathways involved in the antidepressant-induced modulation of neurogenesis. Because our previous studies have shown that antidepressants regulate glucocorticoid receptor (GR) function, we specifically tested whether the GR may be involved in the effects of these drugs on neurogenesis. We found that treatment (for 3–10 days) with the antidepressant, sertraline, increased neuronal differentiation via a GR-dependent mechanism. Specifically, sertraline increased both immature, doublecortin (Dcx)-positive neuroblasts (+16%) and mature, microtubulin-associated protein-2 (MAP2)-positive neurons (+26%). This effect was abolished by the GR-antagonist, RU486. Interestingly, progenitor cell proliferation, as investigated by 5′-bromodeoxyuridine (BrdU) incorporation, was only increased when cells were co-treated with sertraline and the GR-agonist, dexamethasone, (+14%) an effect which was also abolished by RU486. Furthermore, the phosphodiesterase type 4 (PDE4)-inhibitor, rolipram, enhanced the effects of sertraline, whereas the protein kinase A (PKA)-inhibitor, H89, suppressed the effects of sertraline. Indeed, sertraline increased GR transactivation, modified GR phosphorylation and increased expression of the GR-regulated cyclin-dependent kinase-2 (CDK2) inhibitors, p27Kip1 and p57Kip2. In conclusion, our data suggest that the antidepressant, sertraline, increases human hippocampal neurogenesis via a GR-dependent mechanism that requires PKA signaling, GR phosphorylation and activation of a specific set of genes. Our data point toward an important role for the GR in the antidepressant-induced modulation of neurogenesis in humans

Re-cycling paradigms: cell cycle regulation in adult hippocampal neurogenesis and implications for depression

Since adult neurogenesis became a widely accepted phenomenon, much effort has been put in trying to understand the mechanisms involved in its regulation. In addition, the pathophysiology of several neuropsychiatric disorders, such as depression, has been associated with imbalances in adult hippocampal neurogenesis. These imbalances may ultimately reflect alterations at the cell cycle level, as a common mechanism through which intrinsic and extrinsic stimuli interact with the neurogenic niche properties. Thus, the comprehension of these regulatory mechanisms has become of major importance to disclose novel therapeutic targets. In this review, we first present a comprehensive view on the cell cycle components and mechanisms that were identified in the context of the homeostatic adult hippocampal neurogenic niche. Then, we focus on recent work regarding the cell cycle changes and signaling pathways that are responsible for the neurogenesis imbalances observed in neuropathological conditions, with a particular emphasis on depression

Aneuploidy and chromosomal instability in cancer: a jackpot to chaos

Genomic instability (GIN) is a hallmark of cancer cells that facilitates the acquisition of mutations conferring aggressive or drug-resistant phenotypes during cancer evolution. Chromosomal instability (CIN) is a form of GIN that involves frequent cytogenetic changes leading to changes in chromosome copy number (aneuploidy). While both CIN and aneuploidy are common characteristics of cancer cells, their roles in tumor initiation and progression are unclear. On the one hand, CIN and aneuploidy are known to provide genetic variation to allow cells to adapt in changing environments such as nutrient fluctuations and hypoxia. Patients with constitutive aneuploidies are more susceptible to certain types of cancers, suggesting that changes in chromosome copy number could positively contribute to cancer evolution. On the other hand, chromosomal imbalances have been observed to have detrimental effects on cellular fitness and might trigger cell cycle arrest or apoptosis. Furthermore, mouse models for CIN have led to conflicting results. Taken together these findings suggest that the relationship between CIN, aneuploidy and cancer is more complex than what was previously anticipated. Here we review what is known about this complex ménage à trois, discuss recent evidence suggesting that aneuploidy, CIN and GIN together promote a vicious cycle of genome chaos. Lastly, we propose a working hypothesis to reconcile the conflicting observations regarding the role of aneuploidy and CIN in tumorigenesis