26 research outputs found
Reflection of the status and role of social structure in agentive impersonal sentences in german
The article is devoted to the implicit representation of status and role groups in society on the material of impersonal sentences in the german language. The focus is set on the types of the implicit semantic subject, characterized by varying degrees of determination in context: indefinite-personal, generalizedpersonal and definite-personal semantic subject. The authors propose a tripartite paradigm of types of the implicit semantic subject on the basis of its social and role affiliatio
Phosphorylation of Puma modulates its apoptotic function by regulating protein stability
Puma is a potent BH3-only protein that antagonises anti-apoptotic Bcl-2 proteins, promotes Bax/Bak activation and has an essential role in multiple apoptotic models. Puma expression is normally kept very low, but can be induced by several transcription factors including p53, p73, E2F1 and FOXO3a, whereby it can induce an apoptotic response. As Puma can to bind and inactivate all anti-apoptotic members of the Bcl-2 family, its activity must be tightly controlled. We report here, for the first time, evidence that Puma is subject to post-translational control through phosphorylation. We show that Puma is phosphorylated at multiple sites, with the major site of phosphorylation being serine 10. Replacing serine 10 with alanine causes reduced Puma turnover and enhanced cell death. Interestingly, Puma turnover occurs through the proteasome, and substitution of serine 10 causes elevated Puma levels independently of macroautophagy, Bcl-2 family member binding, caspase activity and apoptotic death. We conclude, therefore, that phosphorylation of Puma at serine 10 promotes Puma turnover, represses Puma's cell death potential and promotes cell survival. Owing to the highly pro-apoptotic nature of Puma, these studies highlight an important additional regulatory step in the determination of cellular life or death
Physical and Functional Interaction of NCX1 and EAAC1 Transporters Leading to Glutamate-Enhanced ATP Production in Brain Mitochondria
Glutamate is emerging as a major factor stimulating energy production in CNS. Brain mitochondria can utilize this neurotransmitter as respiratory substrate and specific transporters are required to mediate the glutamate entry into the mitochondrial matrix. Glutamate transporters of the Excitatory Amino Acid Transporters (EAATs) family have been previously well characterized on the cell surface of neuronal and glial cells, representing the primary players for glutamate uptake in mammalian brain. Here, by using western blot, confocal microscopy and immunoelectron microscopy, we report for the first time that the Excitatory Amino Acid Carrier 1 (EAAC1), an EAATs member, is expressed in neuronal and glial mitochondria where it participates in glutamate-stimulated ATP production, evaluated by a luciferase-luciferin system. Mitochondrial metabolic response is counteracted when different EAATs pharmacological blockers or selective EAAC1 antisense oligonucleotides were used. Since EAATs are Na+-dependent proteins, this raised the possibility that other transporters regulating ion gradients across mitochondrial membrane were required for glutamate response. We describe colocalization, mutual activity dependency, physical interaction between EAAC1 and the sodium/calcium exchanger 1 (NCX1) both in neuronal and glial mitochondria, and that NCX1 is an essential modulator of this glutamate transporter. Only NCX1 activity is crucial for such glutamate-stimulated ATP synthesis, as demonstrated by pharmacological blockade and selective knock-down with antisense oligonucleotides. The EAAC1/NCX1-dependent mitochondrial response to glutamate may be a general and alternative mechanism whereby this neurotransmitter sustains ATP production, since we have documented such metabolic response also in mitochondria isolated from heart. The data reported here disclose a new physiological role for mitochondrial NCX1 as the key player in glutamate-induced energy production
Популяционный иммунитет к SARS-COV-2 населения Калиниградской области в эпидемический сезон COVID-19
Introduction. The COVID-19 pandemic was announced by WHO in February 2020. In the Kaliningrad region, the first case (imported) was registered in early March 2020, the beginning of the epidemic increase fell on the 14th week. 2020, and the peak incidence was reached in the 22nd week of the year, after which there was a steady decrease in the number of cases. The study of population immunity was carried out at the 32nd week during the period of the lowest level of intensity of the epidemic process.Purpose of the study. Assessment of the assessment of the level of population immunity to the SARS-CoV-2 virus among the population of the Kaliningrad region during the period of the epidemic incidence of the population of COVID-19.Materials and methods. The study was carried out as part of the first stage of the Rospotrebnadzor program to assess population immunity to SARS-CoV-2 among the population of the Russian Federation. The selection of volunteers for the study was carried out by a questionnaire survey and subsequent randomization. The analysis includes the results of a survey of 2675 people. The number of volunteers in age groups ranged from 314 to 493 people. The results obtained were processed by the methods of variation statistics.Results. The results obtained showed that the average seroprevalence in the population was 50.2%, while the highest seroprevalence was found in the child age group 1-17 years (66.9%) and among persons aged 18-29 (57.0). No significant gender differences were found (men – 48,3 ± 1,6%, women – 51,1 ± 1,1%). The distribution of the proportion of seropositive people in the settlements of the region varied from 33,9% to 59.6%. The largest share of seroprevalence in the representative samples was found among people engaged in art / creativity (55,3%), the smallest – among educational workers (42,0%). Among COVID-19 convalescents, the level of humoral immunity reached 94,6%. Most of the seropositive volunteers (95,2%) did not have any symptoms of COVID-19, that is, they belonged to the category of asymptomatic carriers.Output. The results of a survey of a representative cohort of volunteers in the Kaliningrad region showed that they are characterized by a high level of population immunity, which makes it possible to expect a decrease in.Введение. Пандемия COVID-19 была объявлена Всемирная организация здравоохранения в феврале 2020 г. В Калининградской области первый случай (завозной) зарегистрировали в начале марта 2020 г., начало эпидемического нарастания пришлось на 14-ю неделю 2020 г., а пик заболеваемости был достигнут на 22-й неделе года, после чего отмечалось устойчивое снижение количества заболевший. Исследование популяционного иммунитета было проведено на 32-й неделе в период самого низкого уровня напряженности эпидемического процесса.Цель. Оценка уровня популяционного иммунитета к вирусу SARS-CoV-2 среди населения Калининградской области в период эпидемической заболеваемости населения COVID-19.Материалы и методы. Исследование проведено в рамках первого этапа программы Роспотребнадзора по оценке популяционного иммунитета к SARS-CoV-2 среди населения Российской Федерации. Отбор волонтеров для исследования проводили методом анкетирования и последующей рандомизации. В анализ включены результаты обследования 2675 человек. Количество волонтеров в возрастных группах варьировало от 314 до 493 человек. Полученные результаты обрабатывали методами вариационной статистики.Результаты. Полученные результаты показали, что средняя серопревалентность по популяции составила 50,2%, при этом набольшая серопревалентность была выявлена в детской возрастной группе 1–17 лет (66,9%) и среди лиц в возрасте 18–29 лет (57,0). Достоверных половых различий не установлено (мужчины – 48,3±1,6%, женщины – 51,1±1,1%). Распределение доли серопозитивных по населенным пунктам области варьировало от 33,9% до 59,6%. Наибольшая доля серопревалентных в репрезентативных выборках выявлена среди лиц, занятых искусством/творчеством (55,3%), наименьшая – среди работников образования (42,0%). Среди реконвалесцентов COVID-19 уровень гуморального иммунитета достиг 94,6%. Большая часть серопозитивных волонтеров (95,2%) не имела каких-либо симптомов COVID-19, то есть относилась к категории бессимптомных носителей.Выводы. Результаты обследования репрезентативной когорты волонтеров Калининградской области показали, что для них характерен высокий уровень популяционного иммунитета, позволяющий ожидать снижения напряженности эпидемического процесса.
Characteristics of the Herd Immunity to SARS-CoV-2 in Residents of the Saratov Region under COVID-19 Epidemic
The global community is experiencing one of the largest infectious disease outbreaks in the 21st century. In the Saratov Region, the first case of new coronavirus infection was confirmed on March 19, 2020.The maximum increase in cases was noted between May 15 and June 30, during that time the total number of infected people in the region increased from 1526 to 6444. Since July 2020, a stable incidence level of new coronavirus infection has been observed in the Saratov Region, without a steady decline.The aim of the study was to assess the status of population immunity to the SARS-CoV-2 virus among residents of Saratov and the Saratov Region under the COVID-19 epidemic.Materials and methods. In the period from June 23 to July 26, 2020, a serological study of blood samples from 3372 volunteers of different age groups was conducted. The content of antibodies to SARS-CoV-2 was determined by ELISA using a set of reagents “ELISA anti-SARS-CoV-2 IgG” produced by the State Scientific Center of Applied Microbiology and Biotechnology of the Rospotrebnadzor (Russia).Results and discussion. In general, the incidence of COVID-19 in the Saratov Region is taking place against the background of moderate seroprevalence to the SARS-CoV-2 virus, accompanied by a high incidence of non-apparent (asymptomatic) forms of the infectious process. The absence of clinical symptoms of the disease, in the context of the limited use of methods for determining the RNA of the SARS-CoV-2 virus in PCR (11 % of the region’s population) makes it difficult to assess the real spread of the virus in the population and to establish the timing of the formation of persistent herd immunity. A low rate of antibody response among individuals with a positive result of PCR analysis, as well as among volunteers who had an infection in May, June 2020, indicates a weak formation of the immune response, or the prevalence of individuals reacting mainly by activating the cellular link of the immune system in the population. The obtained results, although they need to be explained in a number of respects, can be applied to the organization of preventive measures, including vaccination, in the region
Experience in Studying Seroprevalence to SARS-CoV-2 Virus in the Population of the Irkutsk Region during COVID-19 Outbreak
Objective of the seroepidemiological study was to determine the level and structure of herd immunity to SARS-CoV-2 among the population of the Irkutsk Region during the period of an increase in the incidence of COVID-19.Materials and methods. The content of antibodies to SARS-CoV-2 was determined by ELISA applying a reagent panel “ELISA anti-SARS-Cov-2 IgG” produced by the State Scientific Center of Applied Microbiology and Biotechnology (Obolensk).Results and discussion. The investigation has revealed that the herd immunity of the total population of Irkutsk Region amounted to 5.8 %. The greatest share of seropositive persons was among the children aged 14–17 (13.8 %) and 1–6 (11.8 %). It has been established that the risk of infection increases by 3.1 times in case of contact with COVID-19 patients. After exposure to COVID-19, antibodies were produced in 56.5 % of the cases. The share of asymptomatic forms among seropositive residents of the Irkutsk Region reached 81.2 %. Consequently, during the chosen period of increased COVID-19 incidence among the population of Irkutsk Region low level of seroprevalence was formed. A significant proportion of asymptomatic forms of infection characterize high intensity of the latently developing epidemic process. The results obtained can be used when organizing preventive measures, including vaccination, and for forecasting morbidity rates
Herd Immunity to SARS-CoV-2 among the Population in Saint-Petersburg during the COVID-19 Epidemic
The first case of COVID-19 was diagnosed in St. Petersburg on March 2, 2020; the period of increase in the incidence lasted for 10 weeks, the maximum rates were recorded in mid-May, and subsequently there was a statistically significant decrease in the incidence.Objective: to determine the level and structure of community immunity to SARS-CoV-2 among the population of St. Petersburg during the period of intensive spread of COVID-19.Materials and methods. Selection of volunteers for the study was carried out through interviewing and randomization. The exclusion criterion was active COVID-19 infection at the time of the survey. 2713 people aged 1 to 70 years and above were examined for the presence of specific antibodies to SARS-CoV-2. Antibodies were detected by enzyme immunoassay.Results and discussion. Studies have shown that in St. Petersburg, in the active phase of COVID-19 epidemic, there was a moderate seroprevalence to SARS-CoV-2, which amounted to 26 %, against the background of a high frequency (84.5 %) of asymptomatic infection in seropositive individuals who did not have a history of COVID-19 disease, positive PCR result and ARI symptoms on the day of examination. The maximum indicators of herd immunity were established in children 1–6 years old (31.1 %), 7–13 years old (37.7 %) and people over 70 years old (30.4 %). Differences in the level of seroprevalence in the age groups of 18–49 years are statistically significant. The highest level of seroprevalence was found among the unemployed (29.7 %), healthcare workers (27.1 %), education sector (26.4 %) and business sector personnel (25 %). In convalescents, COVID-19 antibodies are produced in 75 % of cases. In individuals with positive result of PCR analysis carried out earlier, antibodies are detected in 70 % of the cases. The results of the study of herd immunity to SARS-CoV-2 are essential to forecast the development of the epidemiological situation, as well as to plan measures for specific and non-specific prevention of COVID-19