Effect of Thermal Exposure on Structure of the Ultrafine-GrainedZr-1Nb Alloy

Effect of annealing at temperature range of 573–823 K on stability of the ultrafine-grained structure of the Zr-1wt.%Nb alloy was studied by methods of transmission electron microscopy. Growth kinetics of grain–subgrain structure elements of alloy was investigated

Allosteric Modulators of Steroid Hormone Receptors : Structural Dynamics and Gene Regulation

Peer reviewedPublisher PD

Cystatin D locates in the nucleus at sites of active transcription and modulates gene and protein expression

Cystatin D is an inhibitor of lysosomal and secreted cysteine proteases. Strikingly, cystatin D has been found to inhibit proliferation, migration, and invasion of colon carcinoma cells indicating tumor suppressor activity that is unrelated to protease inhibition. Here, we demonstrate that a proportion of cystatin D locates within the cell nucleus at specific transcriptionally active chromatin sites. Consistently, transcriptomic analysis show that cystatin D alters gene expression, including that of genes encoding transcription factors such as RUNX1, RUNX2, and MEF2C in HCT116 cells. In concordance with transcriptomic data, quantitative proteomic analysis identified 292 proteins differentially expressed in cystatin D-expressing cells involved in cell adhesion, cytoskeleton, and RNA synthesis and processing. Furthermore, using cytokine arrays we found that cystatin D reduces the secretion of several protumor cytokines such as fibroblast growth factor-4, CX3CL1/fractalkine, neurotrophin 4 oncostatin-M, pulmonary and activation-regulated chemokine/CCL18, and transforming growth factor B3. These results support an unanticipated role of cystatin D in the cell nucleus, controlling the transcription of specific genes involved in crucial cellular functions, which may mediate its protective action in colon cancer

Coexpression of Nuclear Receptors and Histone Methylation Modifying Genes in the Testis: Implications for Endocrine Disruptor Modes of Action

BACKGROUND: Endocrine disruptor chemicals elicit adverse health effects by perturbing nuclear receptor signalling systems. It has been speculated that these compounds may also perturb epigenetic mechanisms and thus contribute to the early origin of adult onset disease. We hypothesised that histone methylation may be a component of the epigenome that is susceptible to perturbation. We used coexpression analysis of publicly available data to investigate the combinatorial actions of nuclear receptors and genes involved in histone methylation in normal testis and when faced with endocrine disruptor compounds. METHODOLOGY/PRINCIPAL FINDINGS: The expression patterns of a set of genes were profiled across testis tissue in human, rat and mouse, plus control and exposed samples from four toxicity experiments in the rat. Our results indicate that histone methylation events are a more general component of nuclear receptor mediated transcriptional regulation in the testis than previously appreciated. Coexpression patterns support the role of a gatekeeper mechanism involving the histone methylation modifiers Kdm1, Prdm2, and Ehmt1 and indicate that this mechanism is a common determinant of transcriptional integrity for genes critical to diverse physiological endpoints relevant to endocrine disruption. Coexpression patterns following exposure to vinclozolin and dibutyl phthalate suggest that coactivity of the demethylase Kdm1 in particular warrants further investigation in relation to endocrine disruptor mode of action. CONCLUSIONS/SIGNIFICANCE: This study provides proof of concept that a bioinformatics approach that profiles genes related to a specific hypothesis across multiple biological settings can provide powerful insight into coregulatory activity that would be difficult to discern at an individual experiment level or by traditional differential expression analysis methods

Structural basis for the recognition and cleavage of histone H3 by cathepsin L

Proteolysis of eukaryotic histone tails has emerged as an important factor in the modulation of cell-cycle progression and cellular differentiation. The recruitment of lysosomal cathepsin L to the nucleus where it mediates proteolysis of the mouse histone H3 tail has been described recently. Here, we report the three-dimensional crystal structures of a mature, inactive mutant of human cathepsin L alone and in complex with a peptide derived from histone H3. Canonical substrate–cathepsin L interactions are observed in the complex between the protease and the histone H3 peptide. Systematic analysis of the impact of posttranslational modifications at histone H3 on substrate selectivity suggests cathepsin L to be highly accommodating of all modified peptides. This is the first report of cathepsin L–histone H3 interaction and the first structural description of cathepsin L in complex with a substrate

Информационные технологи в диагностике и прогнозировании функциональной надежности водителей автотранспортных средств

Предметом данной статьи является информационная система диагностики оценки надежности водителей автотранспортных средств в условиях сложных транспортных ситуаций. Данная система диагностики может рассматриваться как основа для разработки информационной технологии мониторинга, комплексной системы оценки надежности операторов автотранспортных и других человекомашинных систем в различных сферах профессиональной деятельности. The subject of this article is information system reliability assessment of motor vehicle drivers under conditions of difficult traffic situations. This diagnostic system can be considered as the basis for the development of information technology monitoring, an integrated system for assessing the reliability of operators, vehicles and other man-machine systems in various fields of professional activity

STORAGE CAPACITY OF SNOW COVER

Snow cover well accumulates various chemical compounds and is an indicator of their content in the atmosphere. Due to the sorption capacity, snow serves as an assistant in identifying the anthropogenic impact on the natural environment

Differential diagnosis of parapharyngeal abscess with multisystem inflammatory syndrome in children associated with COVID-19

The pandemic of the new coronavirus infection (COVID-19) has identified new diagnostic and medical tasks before different doc-tors. As observations show, children have the flow of infection easier than adults. However, in some cases, COVID-19 in children proceeds extremely difficult, with fever and multisystem inflammation, possibly requiring treatment in the resuscitation depart-ment. In domestic practice, the term “Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19” is used to indicate the disease. Among the local symptoms of MIS are inflammations of the skin and mucous membranes, as well as var-ious lymphadenopathy. The article presents the results of our clinic’s observation of 205 patients with MIS for the period from May 2020 to May 2021. In some patients, the clinical manifestations of MIS-C required differential diagnosis with parapharyngeal abscesses (PPA). For this purpose, the children were consulted by an otorhinolaryngologist and a CT scan of the neck with contrast enhancement was performed. Despite the striking clinical manifestations similar to PPA, in no case was a pharyngeal abscess re-vealed. Both of these diseases are potentially fatal if treatment is not started on time, and therefore we believe that the awareness of otorhinolaryngologists about the manifestations of MIS-C will be useful in modern clinical practice. © 2022, Media Sphera Publishing Group. All rights reserved