Cellular immune response in infected mice to NSP protein encoded by the negative strand NS RNA of influenza A virus

Influenza A virus belongs to a family of enveloped viruses with an RNA genome of negative polarity consisting of 8 RNA segments. The transcription of this RNA genome results in the synthesis of positive-sense mRNAs that translate up to 16 unique viral proteins with the help of splicing and translational shift mechanisms. The 8th NS segment encodes the NS1 protein (27 kDa), which is an active interferon antagonist, and the nuclear export protein NEP (14 kDa) through the standard negative polarity pathway. In addition, an alternative open reading frame for the synthesis of a third viral protein (NSP, negative-strand protein) by means of a direct translation of genome polarity RNA (the so-called positive polarity genome strategy) was identified in the NS segment. Since it is unknown as to whether the NSP protein can be synthesized in the infected organism post viral infection, the generation of spleen leucocytes specific to this protein was studied in mice after two sequential infections with influenza A viruses of H1N1 and H3N2 subtypes. It was found that leucocyte clones specifically recognizing a peptide domain in the central region of the NSP protein (amino acid positions 82-119) were generated in mice infected with influenza A viruses. In silico prediction has shown strong major histocompatibility complex-1 (MHC-I) and MHC-II specific epitopes in this central domain of the NSP. Comparative analysis of the influenza H3N2 viruses circulating in humans during 1968-2018 has shown high NSP variability, which was similar to that shown for the hemagglutinin (HA) and neuraminidase (NA) proteins. The highest variability was found to be in the N- and C-terminal parts of the NSP. These observations suggest that synthesis of the NSP protein occurs in infected animals and further support a bipolar (ambisense) strategy of the RNA genome of human influenza A virus.Influenza A virus belongs to a family of enveloped viruses with an RNA genome of negative polarity consisting of 8 RNA segments. The transcription of this RNA genome results in the synthesis of positive-sense mRNAs that translate up to 16 unique viral proteins with the help of splicing and translational shift mechanisms. The 8th NS segment encodes the NS1 protein (27 kDa), which is an active interferon antagonist, and the nuclear export protein NEP (14 kDa) through the standard negative polarity pathway. In addition, an alternative open reading frame for the synthesis of a third viral protein (NSP, negative-strand protein) by means of a direct translation of genome polarity RNA (the so-called positive polarity genome strategy) was identified in the NS segment. Since it is unknown as to whether the NSP protein can be synthesized in the infected organism post viral infection, the generation of spleen leucocytes specific to this protein was studied in mice after two sequential infections with influenza A viruses of H1N1 and H3N2 subtypes. It was found that leucocyte clones specifically recognizing a peptide domain in the central region of the NSP protein (amino acid positions 82-119) were generated in mice infected with influenza A viruses. In silico prediction has shown strong major histocompatibility complex-1 (MHC-I) and MHC-II specific epitopes in this central domain of the NSP. Comparative analysis of the influenza H3N2 viruses circulating in humans during 1968-2018 has shown high NSP variability, which was similar to that shown for the hemagglutinin (HA) and neuraminidase (NA) proteins. The highest variability was found to be in the N- and C-terminal parts of the NSP. These observations suggest that synthesis of the NSP protein occurs in infected animals and further support a bipolar (ambisense) strategy of the RNA genome of human influenza A virus

Atypical reactive center Kunitz-type inhibitor from the sea anemone <i>Heteractis crispa</i>

The primary structure of a new Kunitz-type protease inhibitor InhVJ from the sea anemone Heteractis crispa (Radianthus macrodactylus) was determined by protein sequencing and cDNA cloning. InhVJ amino acid sequence was shown to share high sequence identity (up to 98%) with the other known Kunitz-type sea anemones sequences. It was determined that the P1 Thr at the reactive site resulted in a decrease of the Ki of InhVJ to trypsin and a-chymotrypsin (7.38 × 10-8 M and 9.93 × 10-7 M, respectively). By structure modeling the functional importance of amino acids at the reactive site as well as at the weak contact site were determined. The significant role of Glu45 for the orientation and stabilization of the InhVJ-trypsin complex was elucidated. We can suggest that there has been an adaptive evolution of the P1 residue at the inhibitor reactive site providing specialization or functional diversification of the paralogs. The appearance of a key so-called P1 Thr residue instead of Lys might lead to refinement of inhibitor specificity in the direction of subfamilies of serine proteases. The absence of Kv channel and TRPV1-receptor modulation activity was confirmed by electrophysiological screening tests

The use of nanosecond electron beam for the eggs surface disinfection in industrial poultry

Development of the technology bases of egg disinfection using surface irradiation is executed by the nanosecond electron beam. Experiments on shell eggs irradiation using the frequency nanosecond URT-0.5 accelerator were made. Determination of absorbed dose distributionwas executed. In case of irradiation by the electron beam with absorbed dose level 5 kGy, it is enough for the full disinfection of the surface and pores of egg shell. The absorbed dose in the egg at the expense of bremsstrahlung will not exceed 0.08 Gy which can't have essential action on protein. Irradiation of shell eggs batch in plastic package of 100 pieces pledged in an incubator together with an inspection lot of not irradiated egg was made. The percent of eggs deductibility and chickens survival of pilot and control batches were identical, indicating that there was no significant radio biological effect from irradiation of egg internal structures. The received chickens were grown up within the 5 weeks. It is established that the chickens who are grown up from the irradiated egg have no essential differences in development. © Published under licence by IOP Publishing Ltd.This work was performed within a support of the Russian Science No. 16-16-04038)

ПСИХОЛОГИЧЕСКИЕ ОСОБЕННОСТИ И ОТНОШЕНИЕ К ЗДОРОВЬЮ У ПАЦИЕНТОВ С АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИЕЙ

This work is dedicated to the study of psychological characteristics and attitude to health among patients with arterial hypertension. We hypothesized that it was important to study the picture of health not only for healthy individuals, but also for people with chronic somatic diseases for whom category «health» may be of particular significance. It was also important to study correlation between attitude to health and compliance to treatment.Работа посвящена исследованию психологических особенностей и отношения к здоровью у пациентов с психосоматическими заболеваниями на примере пациентов с артериальной гипертензией. В основу исследования легло предположение о том, что важно изучать картину здоровья не только у здоровых лиц, но и у людей, страдающих хроническими соматическими заболеваниями, для которых категория «здоровье» может иметь особое значение. Вместе с этим интересно проследить соотношение параметров отношения к здоровью с уровнем комплаентности к лечению

Features of the natural course of subclinical hypothyroidism in young athletes

Objective: to assess the natural course of subclinical hypothyroidism in young athletes.Methods: In the prospective single-center uncontrolled study, data from 3,062 outpatient records of young athletes (members of the Russian national team) of both sexes (middle age — 15 [14; 16] years) and underwent medical examination in the period from January 2021 to September 2022 were studied. All athletes were divided into 2 groups according to the presence of subclinical hypothyroidism (an increase in the level of thyroid-stimulating hormone from 5 to 10 mUn/l with a normal level of T4 free). During a dynamic follow-up (1 year), athletes with subclinical hypothyroidism underwent a repeated study of the concentration of thyroid-stimulating hormone, free thyroxine and antibodies to thyroperoxidase.Results: Signs of subclinical hyperthyroidism were found in 58 young athletes (30 boys (51.7 %) and 28 (48.3 %) girls). During dynamic observation with continued habitual physical activity, spontaneous normalization of the level of thyroid-stimulating hormone was observed in 74 % of young athletes. At the same time, normalization of thyroid-stimulating hormone in girls was observed less often compared to boys (p = 0,272). In no case did clinically pronounced hypothyroidism develop.Conclusion: The majority of young male and female athletes with subclinical hypothyroidism have spontaneous normalization of hormonal profile against the background of persistent physical and psycho-emotional stress. The data obtained make it possible, subject to the possibility of dynamic observation, to recommend doctors working with young elite athletes not to prescribe hormonal replacement therapy and not to modify the usual lifestyle

COMPARATIVE PHARMACOKINETICS AND EFFECT ON THE HEMODYNAMICS OF ORIGINAL AND GENERIC NEBIVOLOL IN HEALTHY VOLUNTEERS

Beta-blockers are an important part of modern pharmacotherapy in cardiology. The introduction of generics into clinical practice requires clear evidence of bioequivalence to the original drug.Aim. To study the pharmacokinetics and effect on hemodynamic parameters of the original and a generic nebivolol in healthy volunteers in the fasting state. Material and methods. 18 healthy volunteers were included into the randomized open study on cross-balanced design. They received single dose (5 mg) of two compared preparations of nebivolol under fasting condition. The concentration of unchanged nebivolol in blood plasma was determined by gas chromatography-tandem mass spectrometry. Calculation of pharmacokinetic parameters and assessment of the hemodynamic were performed.Results. The concentrations of nebivolol after the original and generic drugs intake did not differ significantly in any time point (AUC0-∞ 41.09±46.82 vs 47.16±66.58 ng•hr/mL and T1/2 30.84±10.78 vs 29.59±12.08 hours, respectively). Blood pressure reduction was slightly more pronounced when taking generic nebivolol, while the reduction in heart rate at 2 and 4 hours – after original nebivolol intake.Conclusion. A comparative pharmacokinetic study of the genetic nebivolol showed its bioequivalence to the original drug. The effect on hemodynamic parameters with single dose (5 mg) of generic and original nebivolol in healthy volunteers was comparable

Heterogeneity symptoms of urgency in patients with benign prostatic hyperplasia

Background One of the relevant tasks of modern urology is the correct understanding of symptoms of the lower urinary tract (LUTS). The social aspect of overactive bladder syndrome (OAB) and the lack of objective ways for non-invasive diagnostics make it necessary to search for new study methods. There is increasing evidence that urination diary can be a clinically powerful tool for assessing bladder sensation, especially in cases of obtaining information not only about the volume of micturition, but also about the degree of urgency with each individual urination. To date, several tools have been developed to assess the severity of OAB, including the international scale of Overactive Bladder Symptom Score (OABSS), proposed by Y. Homma and J. G. Blaivas in 2006–2007.Objective Тo identify the most significant signs of urgency in men with benign prostatic hyperplasia and overactive bladder with and without detrusor hyperactivity (DH).Material and Methods To assess the OAB, patients completed the OABSS, visual analogue scale (VAS), and also kept urination diaries. After the results were obtained, the severity of symptoms was evaluated, considering the data of the urination diary. All patients underwent a complex urodynamic study (CUDI), the results of which were compared with subjective criteria for the severity of urgency and the most significant clinical signs of detrusor hyperactivity.Results Against the background of the analysis of the data obtained, it was possible to classify nocturia by type in 93 patients. One patient (1.07%) had diurnal polyuria. Nocturnal polyuria was in 39 (41.9%) people. Decreased bladder capacity was found in 43 (46.2%) men. Ten (10.7%) patients had various sleep disorders. The IPSS was 24 ± 0.91, the mean score was 14 ± 0.7 points for irritative symptoms according to IPSS (questions 2, 4 and 7) and 13 ± 0.8 points for obstructive symptoms. From the data reported by CUDI, spontaneous detrusor activity was detected in 49 (43.7%) patients, in 63 (56.2%) it was not registered. When analyzing the VAS, it was found that the urgency in patients with BPH and DH, reflecting the initiation of the urge to urinate, is 31 ± 0.6 mm (p &lt; 0.05). On average the indices of the difficulty of holding the urge are higher by 2.9 ± 0.2 points (p &lt; 0.05) in those patients who have DH. When answering the question "How often cannot you retain urine with a strong sudden urge?", the indicators were recorded higher by 3.1 ± 0.3 points (p &lt; 0.05), in patients with detrusor hyperactivity.Conclusions In patients with BPH and the presence of urgency, the frequency of the urge to urinate is 32% higher, and the difficulty of maintaining the urge is 46% more pronounced, compared with the examined men who do not have detrusive hyperactivity

The role of active herpesvirus infection in the formation of atopic dermatitis and psoriasis

The results of previous studies suggest the involvement of herpes viruses in the development of atopic dermatitis and psoriasis, but there is no convincing evidence. Aim of the study was to evaluate the role of active herpesvirus infection in exacerbation of atopic dermatitis and psoriasis. Material and methods. The analysis of the incidence of infectious mononucleosis, genital herpes, cytomegalovirus infection, skin and subcutaneous tissue diseases, atopic dermatitis, psoriasis in Russia in 2000–2020 was carried out. 92 blood donors and 97 patients with skin and subcutaneous tissue diseases (44 with atopic dermatitis and 53 with psoriasis) were examined for the presence of immunoglobulins M and G to herpes simplex viruses (HSV1,2), Epstein-Barr (EBV), cytomegalovirus (CMV), human herpes type 6 (HНV6). Results and discussion. A significant strong direct correlation was revealed between the incidence of genital herpes and diseases of the skin and subcutaneous tissue (p = 0.85), atopic dermatitis (p = 0.85); infectious mononucleosis and psoriasis (p = 0.85). The frequency of detection of IgM to HSV1,2, in total, IgG EA and IgM VCA EBV in the group of patients is significantly higher than in donors (p &lt; 0.05). In patients with atopic dermatitis, IgM to HSV1 were detected significantly more often than in individuals with psoriasis, and markers of active EBV infection were significantly less common. The presence of IgM HSV-1 statistically significantly increases the incidence of atopic dermatitis (relative risk (RR) = 2.3, 95 % confidence interval (95 % CI) 1.6–3.3)), IgM VCA and IgG EA EBV – the incidence of psoriasis (RR = 2.3, 95 % CI 1.5–3.3). Conclusions. It has been shown for the first time that active HSV1,2 infection is a trigger factor for the development of atopic dermatitis, EBV infection is psoriasis

Surface states and Rashba-type spin polarization in antiferromagnetic MnBi2_2Te4_4

The layered van der Waals antiferromagnet MnBi$_2$Te$_4$ has been predicted to combine the band ordering of archetypical topological insulators such as Bi$_2$Te$_3$ with the magnetism of Mn, making this material a viable candidate for the realization of various magnetic topological states. We have systematically investigated the surface electronic structure of MnBi$_2$Te$_4$(0001) single crystals by use of spin- and angle-resolved photoelectron spectroscopy experiments. In line with theoretical predictions, the results reveal a surface state in the bulk band gap and they provide evidence for the influence of exchange interaction and spin-orbit coupling on the surface electronic structure.Comment: Revised versio