CONSTRUCTION OF ISOCOMFORTABLE MICROCLIMATE PARAMETERS VALUES MATRIX

Abstract. In the article is considered the modern approach to the assessment of climate parameters on the basis of the thermal comfort indices in accordance with the requirements of GOST R ISO 7730-2009. For the first time is introduced the concept of isocomfortable values of microclimate parameters, representing a set providing a predetermined thermal comfort level. Are calculated and presented the examples of three-dimensional arrays of given parameters as the convection temperature function from relative humidity and mobility of air. Microclimate parameters ensuring a specified level of thermal comfort were calculated by the method of successive approximations.Proposed in this article matrixes of isocomfortable values of microclimate parameters can be formulated for different combinations of source parameters

LEA4 Protein Is Likely to Be Involved in Direct Protection of DNA Against External Damage

© 2016, Springer Science+Business Media New York.Anhydrobiotic larvae of an African chironomid Polypedilum vanderplanki are known to be highly resistant to various abiotic stress factors, including ultraviolet radiation. The comparison of survival rates after different doses of UV irradiation between P. vanderplanki larvae and closely related non-anhydrobiotic Polypedilum nubifer larvae showed strongly enhanced resistance of P. vanderplanki to UV irradiation, especially in completely desiccated state. Plasmid-based assay showed an evidence of contribution of LEA4 protein to the protection of the larvae’s DNA against UV damage

Twenty-year changes in the clinical and echocardiographic characteristics of patients with early postinfarction remodeling after primary ST-segment elevation myocardial infarction

Aim. To compare structural and functional left ventricular (LV) changes in the early period of myocardial infarction (MI) within 20 years on the basis of the Emergency Cardiology Department of the Cardiology Research Institute (Tomsk).Material and methods. The study included two groups of patients who were treated at different periods of time with an interval of 20 years. Group 1 included 83 patients who had ST-segment elevation MI (STEMI) in 1997-1999, while group 2 — 83 patients with STEMI from 2019-2020. Echocardiography was performed during the first 72 hours from hospitalization and on the 7-10th day. Depending on the increase in LV end-diastolic volume (EDV) by >15% by the 7-10th day, the patients were divided into 2 subgroups: with remodeling (LVR+) and without remodeling (LVR-).Results. Patients of the 2nd group were older, with a larger proportion of females and with a high incidence of risk factors for coronary artery disease compared with patients of the 1st group. In the early postinfarction period among patients of the 2nd group, acute LV aneurysm, early postinfarction angina and Dressler syndrome developed less frequently. The proportion of adverse LV remodeling in patients of the 1st group was higher (32,8% vs 17%), and while the percentage of reverse remodeling was lower (10% vs 24%), p<0,05. Comparison of the absolute values of LV EDV, end-systolic volume (ESV) and ejection fraction (EF) at baseline and after 7 days, as well as their increase showed higher intensity of post-infarction remodeling in group 1 patients. In patients of the 1st group, there was a progression of LV remodeling (Me ΔEDV — 12,2%) with a deterioration in LV contractility by the 7th day (Me ΔESV — 14%), while in patients of the 2nd group during the first 7 days of MI, there were more stable LV EDV and ESV (p>0,05) and an increase in LVEF (p=0,03) before discharge.Conclusion. In the present era of primary percutaneous coronary intervention and pharmacological treatment of MI, early adverse LV remodeling develops less frequently and is characterized by less pronounced left heart dilatation

Short ORF-Dependent Ribosome Shunting Operates in an RNA Picorna-Like Virus and a DNA Pararetrovirus that Cause Rice Tungro Disease

Rice tungro disease is caused by synergistic interaction of an RNA picorna-like virus Rice tungro spherical virus (RTSV) and a DNA pararetrovirus Rice tungro bacilliform virus (RTBV). It is spread by insects owing to an RTSV-encoded transmission factor. RTBV has evolved a ribosome shunt mechanism to initiate translation of its pregenomic RNA having a long and highly structured leader. We found that a long leader of RTSV genomic RNA remarkably resembles the RTBV leader: both contain several short ORFs (sORFs) and potentially fold into a large stem-loop structure with the first sORF terminating in front of the stem basal helix. Using translation assays in rice protoplasts and wheat germ extracts, we show that, like in RTBV, both initiation and proper termination of the first sORF translation in front of the stem are required for shunt-mediated translation of a reporter ORF placed downstream of the RTSV leader. The base pairing that forms the basal helix is required for shunting, but its sequence can be varied. Shunt efficiency in RTSV is lower than in RTBV. But in addition to shunting the RTSV leader sequence allows relatively efficient linear ribosome migration, which also contributes to translation initiation downstream of the leader. We conclude that RTSV and RTBV have developed a similar, sORF-dependent shunt mechanism possibly to adapt to the host translation system and/or coordinate their life cycles. Given that sORF-dependent shunting also operates in a pararetrovirus Cauliflower mosaic virus and likely in other pararetroviruses that possess a conserved shunt configuration in their leaders it is tempting to propose that RTSV may have acquired shunt cis-elements from RTBV during their co-existence

Genetic background of enhanced radioresistance in an anhydrobiotic insect: transcriptional response to ionizing radiations and desiccation

© 2016, Springer Japan.It is assumed that resistance to ionizing radiation, as well as cross-resistance to other abiotic stresses, is a side effect of the evolutionary-based adaptation of anhydrobiotic animals to dehydration stress. Larvae of Polypedilum vanderplanki can withstand prolonged desiccation as well as high doses of ionizing radiation exposure. For a further understanding of the mechanisms of cross-tolerance to both types of stress exposure, we profiled genome-wide mRNA expression patterns using microarray techniques on the chironomid larvae collected at different stages of desiccation and after exposure to two types of ionizing radiation—70 Gy of high-linear energy transfer (LET) ions (4He) and the same dose of low-LET radiation (gamma rays). In expression profiles, a wide transcriptional response to desiccation stress that much exceeded the amount of up-regulated transcripts to irradiation exposure was observed. An extensive group of coincidently up-regulated overlapped transcripts in response to desiccation and ionizing radiation was found. Among this, overlapped set of transcripts was indicated anhydrobiosis-related genes: antioxidants, late embryogenesis abundant (LEA) proteins, and heat-shock proteins. The most overexpressed group was that of protein-L-isoaspartate/D-aspartate O-methyltransferase (PIMT), while probes, corresponding to LEA proteins, were the most represented. Performed functional analysis showed strongly enriched gene ontology terms associated with protein methylation. In addition, active processes of DNA repair were detected. We assume that the cross-tolerance of the sleeping chironomid to both desiccation and irradiation exposure comes from a complex mechanism of adaptation to anhydrobiosis

Features of heart failure with preserved ejection fraction (HFpEF) in diabetic patients with resistant hypertension

BACKGROUND: It is expected that a steady increase in the incidence of diabetes and resistant hypertension (RHTN), along with an increase in life expectancy, will lead to a noticeable increase in the proportion of patients with heart failure with preserved ejection fraction (HFpEF). At the same time, data on the frequency of HFpEF in a selective group of patients with RHTN in combination with diabetes are still lacking, and the pathophysiological and molecular mechanisms of its formation have not been yet studied sufficiently.AIM: To assess the features of the development HFpEF in diabetic and non-diabetic patients with RHTN, as well as to determine the factors associated with HFpEF.MATERIALS AND METHODS: In the study were included 36 patients with RHTN and type 2 diabetes mellitus (DM) (mean age 61.4 ± 6.4 years, 14 men) and 33 patients with RHTN without diabetes, matched by sex, age and level of systolic blood pressure (BP). All patients underwent baseline office and 24-hour BP measurement, echocardiography with assess diastolic function, lab tests (basal glycemia, HbA1c, creatinine, aldosterone, TNF-alpha, hsCRP, brain naturetic peptide, metalloproteinases of types 2, 9 (MMP-2, MMP-9) and tissue inhibitor of MMP type 1 (TIMP-1)). HFpEF was diagnosed according to the 2019 AHA/ESC guidelines.RESULTS: The frequency of HFpEF was significantly higher in patients with RHTN with DM than those without DM (89% and 70%, respectively, p=0.045). This difference was due to a higher frequency of such major functional criterion of HFpEF as E/e’≥15 (p=0.042), as well as a tendency towards a higher frequency of an increase in left atrial volumes (p=0.081) and an increase in BNP (p=0.110). Despite the comparable frequency of diastolic dysfunction in patients with and without diabetes (100% and 97%, respectively), disturbance of the transmitral blood flow in patients with DM were more pronounced than in those without diabetes. Deterioration of transmitral blood flow and pseudo-normalization of diastolic function in diabetic patients with RHTN have relationship not only with signs of carbohydrate metabolism disturbance, but also with level of pulse blood pressure, TNF-alfa, TIMP-1 and TIMP-1 / MMP-2 ratio, which, along with the incidence of atherosclerosis, were higher in patients with DM than in those without diabetes.CONCLUSIONS: Thus, HFpEF occurs in the majority of diabetic patients with RHTN. The frequency of HFpEF in patients with DN is significantly higher than in patients without it, which is associated with more pronounced impairments of diastolic function. The progressive development of diastolic dysfunction in patients with diabetes mellitus is associated not only with metabolic disorders, but also with increased activity of chronic subclinical inflammation, profibrotic state and high severity of vascular changes

Facilitated leaky scanning and atypical ribosome shunting direct downstream translation initiation on the tricistronic S1 mRNA of avian reovirus

The S1 mRNA of avian reovirus is functionally tricistronic, encoding three unrelated proteins, p10, p17 and σC, from three sequential, partially overlapping open reading frames (ORFs). The mechanism of translation initiation at the 3′-proximal σC ORF is currently unknown. Transient RNA transfections using Renilla luciferase reporter constructs revealed only a modest reduction in reporter expression upon optimization of either the p10 or p17 start sites. Insertion of multiple upstream AUG (uAUG) codons in a preferred start codon sequence context resulted in a substantial retention of downstream translation initiation on the S1 mRNA, but not on a heterologous mRNA. The S1 mRNA therefore facilitates leaky scanning to promote ribosome access to the σC start codon. Evidence also indicates that σC translation is mediated by a second scanning-independent mechanism capable of bypassing upstream ORFs. This alternate mechanism is cap-dependent and requires a sequence-dependent translation enhancer element that is complementary to 18S rRNA. Downstream translation initiation of the tricistronic S1 mRNA is therefore made possible by two alternate mechanisms, facilitated leaky scanning and an atypical form of ribosome shunting. This dual mechanism of downstream translation initiation ensures sufficient expression of the σC cell attachment protein that is essential for infectious progeny virus production

Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis

New drugs are required to counter the tuberculosis (TB) pandemic. Here, we describe the synthesis and characterization of 1,3-benzothiazin-4-ones (BTZs), a new class of antimycobacterial agents that kill Mycobacterium tuberculosis in vitro, ex vivo, and in mouse models of TB. Using genetics and biochemistry, we identified the enzyme decaprenylphosphoryl-beta-d-ribose 2'-epimerase as a major BTZ target. Inhibition of this enzymatic activity abolishes the formation of decaprenylphosphoryl arabinose, a key precursor that is required for the synthesis of the cell-wall arabinans, thus provoking cell lysis and bacterial death. The most advanced compound, BTZ043, is a candidate for inclusion in combination therapies for both drug-sensitive and extensively drug-resistant TB

Features of the response to subchronic low-dose exposure to copper oxide nanoparticles in rats

Copper is an essential trace element for human health and, at the same time, a major industrial metal widely used both in its elemental form and in compounds. We conducted a dose-dependent assessment of the response of outbred albino male rats to subchronic low-dose exposure to copper oxide nanoparticles administered intraperitoneally at cumulative doses of 18 and 36 mg/kg during 6 weeks to exposure groups 1 and 2, respectively. We observed disorders at different levels of organization of the body in the exposed animals, from molecular to organismal. The observed decrease in the activity of succinate dehydrogenase in nucleated blood cells gave evidence of impaired bioenergetics processes. In view of the results of the metabolomics analysis, we assume mitochondrial damage and contribution of apoptotic processes to the pathology induced by copper poisoning. We also assume neurodegenerative effects based on the assessed morphological parameters of the nervous system, results of behavioral tests, and a decreased level of expression of genes encoding NMDA receptor subunits in the hippocampus. The hepatotoxic effect noted by a number of metabolomics-based, biochemical, and cytological indicators was manifested by the impaired protein-synthesizing function of the liver and enhanced degenerative processes in its cells. We also observed a nephrotoxic effect of nanosized copper oxide with a predominant lesion of proximal kidney tubules. At the same time, both doses tested demonstrated such positive health effects as a statistically significant decrease in the activity of alkaline phosphatase and the nucleated blood cell DNA fragmentation factor. Judging by the changes observed, the cumulative dose of copper oxide nanoparticles of 18 mg/kg body weight administered intraperitoneally approximates the threshold one for rats. The established markers of health impairments may serve as a starting point in the development of techniques of early diagnosis of copper poisoning. © 2023, The Author(s).Friedrich-Schiller-Universität Jena, FSU; Ministry of Education and Science of the Russian Federation, Minobrnauka; Ministry of Science and Higher Education of the Russian Federation: Priority – 2030Open Access funding enabled and organized by Projekt DEAL. The research funding from Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers for funding the experimental materials and facilities is gratefully acknowledged. The research funding from the Ministry of Science and Higher Education of the Russian Federation (Ural Federal University Program of Development within the Priority–2030 Program) for experiment implementation and analysis of its results is gratefully acknowledged. The authors would like to express their deepest gratitude to the staff of the Ural Center for Shared Use “Modern Nanotechnologies” of the Ural Federal University named after the First Russian President Boris Yeltsin and personally to Professor Vladimir Ya. Shur, Director of the Center, for invaluable support in conducting this study by synthesizing suspensions of the nanoparticles studied. We are also grateful to the staff of the Central Research Laboratory of the Ural State Medical University and personally to Professor Oleg G. Makeyev for establishing genomic DNA fragmentation