Influence of single amino acid substitutions in the hemagglutinin on the antigenic and receptor-binding properties of influenza virus B/Florida/04/2006 of Yamagata-like evolutionary lineage

Influenza A and B viruses use sialylated oligosaccharide chains expressed on the surface of a host cell as the cell entry receptors. The type of the bond between sialic acid (SA) and the neighboring galactose residue (Gal) is one of the main characteristics that define the type of receptor. Influenza viruses recognize SAα2-3Gal- or SAα2-6Gal-structures on the surface of the cells. Influenza A viruses of avian origin bind α2-3-sialylated glycans, while the human strains bind preferentially α2-6-sialylated ones. However, the receptor-binding specificity of influenza B viruses has not been characterized sufficiently so far. In this study, we selected the escape mutants of influenza B/Florida/04/2006 strain (Yamagata-like lineage) using monoclonal antibodies (mAb) to hemagglutinin (HA). The analysis of the amino acid sequences of mAb-induced escape mutants revealed the single amino acid substitutions 40Tyr→His, 85His→Tyr, 202Asn→Lys and 242Ser→Arg in 10F4-, 8Н11-, 8Н3- and 9А3-induced HA variants, correspondingly. It was shown that the single amino acid substitutions 202Asn→Lys and 242Ser→Arg alter the receptor-binding specificity of the influenza B virus. These findings are important for the understanding of the influence of individual amino acid residues in HA on the receptor-binding properties of influenza B Yamagata-like lineage viruses and allow us to predict the possible ways of their evolution.Influenza A and B viruses use sialylated oligosaccharide chains expressed on the surface of a host cell as the cell entry receptors. The type of the bond between sialic acid (SA) and the neighboring galactose residue (Gal) is one of the main characteristics that define the type of receptor. Influenza viruses recognize SAα2-3Gal- or SAα2-6Gal-structures on the surface of the cells. Influenza A viruses of avian origin bind α2-3-sialylated glycans, while the human strains bind preferentially α2-6-sialylated ones. However, the receptor-binding specificity of influenza B viruses has not been characterized sufficiently so far. In this study, we selected the escape mutants of influenza B/Florida/04/2006 strain (Yamagata-like lineage) using monoclonal antibodies (mAb) to hemagglutinin (HA). The analysis of the amino acid sequences of mAb-induced escape mutants revealed the single amino acid substitutions 40Tyr→His, 85His→Tyr, 202Asn→Lys and 242Ser→Arg in 10F4-, 8Н11-, 8Н3- and 9А3-induced HA variants, correspondingly. It was shown that the single amino acid substitutions 202Asn→Lys and 242Ser→Arg alter the receptor-binding specificity of the influenza B virus. These findings are important for the understanding of the influence of individual amino acid residues in HA on the receptor-binding properties of influenza B Yamagata-like lineage viruses and allow us to predict the possible ways of their evolution

The research of anxiety level of boys and girls, studying in the specialized classes of the Lyceum

The article deals with the problem of differences in the manifestation of anxiety in boys and girls, who are in tenth grade of specialized classes of Lyceum. The results of the pilot empirical study, which showed that the anxiety of girls is significantly higher than boys’, are discussedСтатья посвящена проблеме различий в проявлении тревожности юношей и девушек, обучающихся в десятых профильных классах лицея. Обсуждаются результаты пилотажного эмпирического исследования, показавшего, что тревожность девушек значительно выше, чем юноше

Effect of Solid Dispersions on the Dissolution of Ampicillin

© 2016, Springer Science+Business Media New York.In this work, we studied water solubility of ampicillin trihydrate and its solid dispersions (SD) with polyethylene glycol-1500, polyvinylpyrrolidone-10000, and β-cyclodextrin. It was found that SD formation increases the solubility by a factor of 1.34–1.73 and the rate of ampicillin dissolution by a factor of 3.43–7.40. The results of complex physicochemical studies suggest that the improved release of ampicillin from SD is due to its micronization and solubilization by the polymer

Безопасность и эффективность 23-валентной полисахаридной пневмококковой вакцины у больных системной красной волчанкой

Objective: to study the safety and efficacy of the 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with systemic lupus erythematosus (SLE).Patients and methods. The study included 75 patients with definite diagnosis of SLE at the age of 19–68 years, 10 (13%) of them had high SLE activity, 18 (24%) – moderate, 42 (56%) – low, in 5 (7%) patients the disease was in remission. PPV-23 was injected subcutaneously in a single dose of 0.5 ml. In 60 patients the follow-up period was ≥12 months, in 15 – from 2 to 6 months. Patients were examined before and 1, 3 and 12 months after immunization.Results and discussion. In 38 (50.7%) patients, standard local vaccination reactions of mild and moderate severity were noted, in 1 (1.3%) – a general reaction of mild severity, in 2 (2.7%) – mild diarrhea during 1 day, in 1 (1.3%) – a hyperergic reaction of the Artyus phenomenon type, the symptoms were relieved within 7 days. During 12 months of follow-up, neither exacerbations of SLE, reliably associated with vaccination, nor new autoimmune phenomena, were detected. After 1 year of observation, the number of responders to vaccination was 58%, non-responders – 42%. The duration and activity of the disease, age over 50 years, glucocorticoid therapy > 10 mg per day, did not significantly affect the vaccine response. There was a decrease in the immune response in patients on biologic DMARDs (bDMARDs) therapy compared to patients without such treatment (43 and 68% of cases, respectively), p=0.058. There was no difference between rituximab and belimumab treated subjects. There was a tendency for the prevalence of vaccination responses among patients, who received bDMARDs <1 year before immunization, as well as among patients in whom this therapy was initiated after the administration of PPV-23. There was a positive trend in decrease of pneumonia, acute and exacerbations of chronic bronchitis episodes and sinusitis.Conclusion. Sufficient immunogenicity, good tolerability and clinical efficacy of PPV-23 in patients with SLE, including those who received combined immunosuppressive therapy, have been shown. The use of bDMARDs reduces the number of patients with a vaccine response. The number of responders to vaccination increases when immunization is carried out before the initiation of therapy with bDMARDs or when this therapy is initiated <1 year before immunization. Further long-term prospective studies in large patient cohorts are required.Цель исследования – изучение безопасности и эффективности 23-валентной полисахаридной пневмококковой вакцины (ППВ-23) у больных системной красной волчанкой (СКВ).Пациенты и методы. В исследование включено 75 пациентов с достоверным диагнозом СКВ в возрасте 19–68 лет, 10 (13%) из них имели высокую активность СКВ, 18 (24%) – среднюю, 42 (56%) – низкую, у 5 (7%) – выявлена ремиссия заболевания. ППВ-23 вводили подкожно в разовой дозе 0,5 мл. У 60 пациентов срок наблюдения составлял ≥12 мес, у 15 – от 2 до 6 мес. Больных обследовали до и через 1, 3 и 12 мес после иммунизации.Результаты и обсуждение. У 38 (50,7%) пациентов отмечались стандартные местные вакцинальные реакции легкой и средней степени выраженности, у 1 (1,3%) – общая реакция легкой степени выраженности, у 2 (2,7%) – легкая диарея в течение 1 сут, у 1 (1,3%) – гиперергическая реакция по типу феномена Артюса, симптомы которой были купированы за 7 дней. На протяжении 12 мес наблюдения не выявлено ни одного случая обострения СКВ, достоверно связанного с вакцинацией, а также новых аутоиммунных феноменов. Через 1 год наблюдения число ответивших на вакцинацию составило 58%, не ответивших – 42%. Длительность и активность заболевания, возраст старше 50 лет, прием глюкокортикоидов в дозе >10 мг/сут значимо не влияли на вакцинальный ответ. Отмечено снижение иммунного ответа на фоне терапии генно-инженерными биологическими препаратами (ГИБП) по сравнению с отсутствием данного лечения (43 и 68% случаев соответственно), р=0,058. Различий на фоне применения ритуксимаба и белимумаба не установлено. Обнаружена тенденция к преобладанию ответивших на вакцинацию среди больных, получавших ГИБП <1 года до иммунизации, а также среди пациентов, которым эта терапия была инициирована после введения ППВ-23. Наблюдалась положительная динамика в виде уменьшения эпизодов пневмоний, острого и обострения хронического бронхита, синуситов.Заключение. Показаны достаточная иммуногенность, хорошая переносимость и клиническая эффективность ППВ-23 у больных СКВ, в том числе получавших комбинированную иммуносупрессивную терапию. Применение ГИБП уменьшает число пациентов с вакцинальным ответом. Если иммунизацию проводить до начала терапии ГИБП или на фоне такого лечения длительностью <1 года, то число ответивших на вакцинацию возрастает. Необходимы дальнейшие длительные проспективные исследования на больших выборках пациентов

ОПТИМИЗАЦИЯ ГЕОМЕТРИИ ТЕХНОЛОГИЧЕСКОГО ИНСТРУМЕНТА ПРИ ПРЕССОВАНИИ ТРИМЕТАЛЛИЧЕСКОЙ ЗАГОТОВКИ

A procedure of determining the optimum angles of process tools for trimetal work-piece pressing is proposed. The pressing stress providing the minimum power consumption is taken as the basis of optimization.Предложена методика определения оптимальных углов технологического инструмента при прессовании триметаллической заготовки. В основу оптимизации положено напряжение прессования, обеспечивающее минимальные энергозатраты при прессовании

Changes in the antigenic and genetic structure of influenza viruses: analysis of surveillance data of influenza A and B in Russia in 2006-2013

The goal of this research project was to study the natural variability of human influenza A and B viruses based on the analysis of the population structure of influenza viruses, circulating in Russia in 2006-2013, in order to determine the direction of their genetic and antigenic drift by comparison to the WHO reference strains. Our results proved that during that period significant changes occurred in the genetic structure of influenza viruses, their phylogenetic affiliation, as well as their sensitivity to antiviral drugs. According to the surveillance data, the percentage of influenza A(H1N1) viruses among patients with influenza-like illness or acute respiratory infection gradually decreased from 42% of the total number of influenza viruses in 2006-2007 to 19% in 2008- 2009. Influenza A(H1N1) viruses are characterized by «silent» variability that manifests in the gradual accumulation of amino acid substitutions in the minor undetectable group of viruses.The share of influenza A(H3N2) viruses varied from 10% in the 1st post pandemic year to approx. 60% in 2008-2009 and 2011- 2012 epidemic seasons. All of the influenza A strains isolated during the last years of the period, covered in this study, were found to be susceptible to neuraminidase inhibitors and resistant to adamantane antivirals.Influenza B viruses of both Yamagata and Victoria lineages circulated in Russia in the period from 2006 to 2013. The vast majority of these influenza B viruses belonged to the Victoria lineage. Phylogenetic and antigenic analyses of influenza B viruses have demonstrated a gradual drift of Russian isolates from the reference strains. No changes leading to resistance to oseltamivir or zanamivir were found in influenza B strains isolated until 2013.The goal of this research project was to study the natural variability of human influenza A and B viruses based on the analysis of the population structure of influenza viruses, circulating in Russia in 2006-2013, in order to determine the direction of their genetic and antigenic drift by comparison to the WHO reference strains. Our results proved that during that period significant changes occurred in the genetic structure of influenza viruses, their phylogenetic affiliation, as well as their sensitivity to antiviral drugs. According to the surveillance data, the percentage of influenza A(H1N1) viruses among patients with influenza-like illness or acute respiratory infection gradually decreased from 42% of the total number of influenza viruses in 2006-2007 to 19% in 2008- 2009. Influenza A(H1N1) viruses are characterized by «silent» variability that manifests in the gradual accumulation of amino acid substitutions in the minor undetectable group of viruses. The share of influenza A(H3N2) viruses varied from 10% in the 1st post pandemic year to approx. 60% in 2008-2009 and 2011- 2012 epidemic seasons. All of the influenza A strains isolated during the last years of the period, covered in this study, were found to be susceptible to neuraminidase inhibitors and resistant to adamantane antivirals. Influenza B viruses of both Yamagata and Victoria lineages circulated in Russia in the period from 2006 to 2013. The vast majority of these influenza B viruses belonged to the Victoria lineage. Phylogenetic and antigenic analyses of influenza B viruses have demonstrated a gradual drift of Russian isolates from the reference strains. No changes leading to resistance to oseltamivir or zanamivir were found in influenza B strains isolated until 2013

Exposing Racial Discrimination: Implicit & Explicit Measures–The My Body, My Story Study of 1005 US-Born Black & White Community Health Center Members

Background To date, research on racial discrimination and health typically has employed explicit self-report measures, despite their potentially being affected by what people are able and willing to say. We accordingly employed an Implicit Association Test (IAT) for racial discrimination, first developed and used in two recent published studies, and measured associations of the explicit and implicit discrimination measures with each other, socioeconomic and psychosocial variables, and smoking. Methodology/Principal Findings Among the 504 black and 501 white US-born participants, age 35–64, randomly recruited in 2008–2010 from 4 community health centers in Boston, MA, black participants were over 1.5 times more likely (p<0.05) to be worse off economically (e.g., for poverty and low education) and have higher social desirability scores (43.8 vs. 28.2); their explicit discrimination exposure was also 2.5 to 3.7 times higher (p<0.05) depending on the measure used, with over 60% reporting exposure in 3 or more domains and within the last year. Higher IAT scores for target vs. perpetrator of discrimination occurred for the black versus white participants: for “black person vs. white person”: 0.26 vs. 0.13; and for “me vs. them”: 0.24 vs. 0.19. In both groups, only low non-significant correlations existed between the implicit and explicit discrimination measures; social desirability was significantly associated with the explicit but not implicit measures. Although neither the explicit nor implicit discrimination measures were associated with odds of being a current smoker, the excess risk for black participants (controlling for age and gender) rose in models that also controlled for the racial discrimination and psychosocial variables; additional control for socioeconomic position sharply reduced and rendered the association null. Conclusions Implicit and explicit measures of racial discrimination are not equivalent and both warrant use in research on racial discrimination and health, along with data on socioeconomic position and social desirability

ОПТИМИЗАЦИЯ ГЕОМЕТРИИ ТЕХНОЛОГИЧЕСКОГО ИНСТРУМЕНТА ПРИ ПРЕССОВАНИИ БИМЕТАЛЛИЧЕСКОЙ ЗАГОТОВКИ

A technique to determine optimum taper angles of the technological tool in press forming a bimetallic piece part is proposed. The forming stress ensuring the minimum power consumption is taken in the basis of the optimization.Предложена методика определения оптимальных углов технологического инструмента при прессовании биметаллической заготовки. В основу оптимизации положено напряжение прессования, обеспечивающее минимальные энергозатраты в ходе процесса