Examining c-di-GMP and possible quorum sensing regulation in Pseudomonas fluorescens SBW25:links between intra and inter-cellular regulation benefits community cooperative activities such as biofilm formation

Bacterial success in colonizing complex environments requires individual response to micro-scale conditions as well as community-level cooperation to produce large-scale structures such as biofilms. Connecting individual and community responses could be achieved by linking the intracellular sensory and regulatory systems mediated by bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) and other compounds of individuals with intercellular quorum sensing (QS) regulation controlling populations. There is growing evidence to suggest that biofilm formation by many pseudomonads is regulated by both intra and intercellular systems, though in the case of the model Pseudomonas fluorescens SBW25 Wrinkly Spreader in which mutations increasing c-di-GMP levels result in the production of a robust cellulose-based air-liquid interface biofilm, no evidence for the involvement of QS regulation has been reported. However, our recent review of the P. fluorescens SBW25 genome has identified a potential QS regulatory pathway and other QS–associated genes linked to c-di-GMP homeostasis, and QS signal molecules have also been identified in culture supernatants. These findings suggest a possible link between c-di-GMP and QS regulation in P. fluorescens SBW25 which might allow a more sophisticated and responsive control of cellulose production and biofilm formation when colonising the soil and plant-associated environments P. fluorescens SBW25 normally inhabits.Анализ ц-ди-ГМФ и возможного чувства кворума у Pseudomonas fluorescens SBW 25: связь между внутри и межклеточной регуляцией способствует кооперативному поведению в сообществе и формированию биоплёнкиУспешность бактериальной колонизации сложных экониш требует индивидуального ответа на изменения условий на микроуровне равно как и кооперации на уровне сообщества для продукции таких крупно масштабных структур как биоплёнки. Координация индивидуальных ответ ов и ответов сообщества может быть достигнута путем связывания внутриклеточных сенсорных и регуляторных систем, опосредуемых бис-(3',5')-циклическим димерным гуанозинмонофосфатом (ц-ди-ГМФ) и другими соединениями индивидуумов с межклеточной регуляцией - чувством кворума (ЧК), контролирующем популяци ю. Накапливается всё больше доказательств того, что формирование биопленки многими псевдомонадами регулируется как внутри клеточными, так и меж клеточными регуляторными системами, хотя в случае модельной Pseudomonas fluorescens SBW25 Wrinkly Spreader, у которой мутации, повышающ ие уровни ц-ди-ГМФ, приводят к созданию прочной целлюлозной биоплёнки на границе раздела фаз воздух-жидкость, не было обнаружено ни ка кого свидетельства вовлечения кворум-зависимой регуляции. Однако наш недавний обзор генома P. fluorescens SBW25 выявил потенциальный ЧК-зависимый регуляторный пу ть и другие ЧК-зависимые гены, связанные с гомеостазом ц-ди-ГМФ, а молекулы ЧК-сигналинга были идентифицированы в культуре. Эти данные свидетельствуют о возможной связи между ц-ди-ГМФ-регуляцией и ЧК у P. fluorescens SBW25, что позволяет более сложный и гибкий контроль над продукцией целлюлозы и образовани ем биопленки при колонизации почв и экониш, aссоциированных с растениям и, - естественными средами обитания P. fluorescens SBW25

eDNA inactivation and biofilm inhibition by the polymeric biocide polyhexamethylene guanidine hydrochloride (PHMG-Cl)

The choice of effective biocides used for routine hospital practice should consider the role of disinfectants in the maintenance and development of local resistome and how they might affect antibiotic resistance gene transfer within the hospital microbial population. Currently, there is little understanding of how different biocides contribute to eDNA release that may contribute to gene transfer and subsequent environmental retention. Here, we investigated how different biocides affect the release of eDNA from mature biofilms of two opportunistic model strains Pseudomonas aeruginosa ATCC 27853 (PA) and Staphylococcus aureus ATCC 25923 (SA) and contribute to the hospital resistome in the form of surface and water contaminants and dust particles. The effect of four groups of biocides, alcohols, hydrogen peroxide, quaternary ammonium compounds, and the polymeric biocide polyhexamethylene guanidine hydrochloride (PHMG-Cl), was evaluated using PA and SA biofilms. Most biocides, except for PHMG-Cl and 70% ethanol, caused substantial eDNA release, and PHMG-Cl was found to block biofilm development when used at concentrations of 0.5% and 0.1%. This might be associated with the formation of DNA–PHMG-Cl complexes as PHMG-Cl is predicted to bind to AT base pairs by molecular docking assays. PHMG-Cl was found to bind high-molecular DNA and plasmid DNA and continued to inactivate DNA on surfaces even after 4 weeks. PHMG-Cl also effectively inactivated biofilm-associated antibiotic resistance gene eDNA released by a pan-drug-resistant Klebsiella strain, which demonstrates the potential of a polymeric biocide as a new surface-active agent to combat the spread of antibiotic resistance in hospital settings

Половозрастные особенности распространенности метаболически здорового фенотипа ожирения

Aim. The study objective was to assess the age and gender characteristics of the metabolically healthy obesity phenotype (MHO) prevalence, taking into account various classifications.Materials and methods. The materials used are the cross-sectional studies of the population cohort (Health, Alcohol and Psychosocial factors in Eastern Europe (HAPIEE) project, Novosibirsk), with the total of 3,197 people, among them 857 men (26.8%) and 2,340 women (73.2%), with BMI ≥30 kg/m². The MHO is defined according to different classifications: 1. IDF (International Diabetes Federation, 2005) – Waist circumference (WC) ≥ 94 cm in men and ≥80 cm in women and one or none of the components of metabolic syndrome (MS); 2. NCEP ATP III (the National Cholesterol Education Program Adult Treatment Panel III, 2001) in the presence of 2 and / or less components of the metabolic syndrome and 3. RSC (The Royal Society of Chemistry) – the index of waist circumference / hip circumference (WC / HC) ≤0.9 in men and ≤0.85 in women.Results. According to IDF the frequency of MHO in the group was 23.2%; NCEP ATP III – 41.8; RSC criteria – 27.1%. The frequency of MHO was higher in women than in men, and it significantly decreased with the age in women population. In all classifications, increased average blood pressure (BP) level, with normal average values of the level of triglycerides (TG) and high-density lipoprotein (HDL) is typical for persons with MHO. The surveyed according to the RSC criteria people with MHO demonstrate higher frequency levels of all cardio metabolic risk factors than those surveyed with the use of other criteria of MHO.Conclusion. The frequency of MHO varies depending on the used classification. In women, the frequency of MHO is reliably higher than in men. With the age, a significant reduction of the frequency of MHO in women is manifested. The frequency of arterial hypertension and abdominal obesity, the level of fasting blood glucose and LDL (low density lipoprotein), hypertriglyceridemia is higher in persons with MHO according to the criteria RSC.Цель. Изучить половозрастные особенности метаболически здорового фенотипа ожирения (МЗФО).Материалы и методы. Использованы материалы кросс-секционного исследования популяционной когорты (проект HAPIEE, г. Новосибирск) (n = 3 197 человек, среди них 857 (26,8%) мужчин и 2 340 (73,2%) женщин, с индексом массы тела (ИМТ) ≥30 кг/м²). МЗФО определен в соответствии с различными классификациями: 1) IDF (2005) – окружность талии (ОТ) ≥94 см у мужчин и ≥80 см у женщин и любой компонент метаболического синдрома (МС) по IDF или без него; 2) NCEP ATP III (2001) при наличии 2 и (или) менее компонентов МС; 3) критерии РКО (2017) – индекс окружность талии / окружность бедер (ОТ / ОБ) ≤0,9 у мужчин и ОТ / ОБ ≤ 0,85 у женщин.Результаты. Среди лиц с ожирением частота МЗФО по критериям IDF – 23,2%; NCEP ATP III – 41,8%; РКО – 27,1%. Частота МЗФО выше у женщин, чем у мужчин, и она значимо снижается с возрастом в женской популяции. Для лиц с МЗФО по всем классификациям характерно повышенное среднее значение артериального давления при нормальных средних значениях уровня триглицеридов и холестерина липопротеидов высокой плотности. Обследованные с МЗФО по критериям РКО демонстрируют более высокие показатели частоты всех изучаемых кардиометаболических факторов риска, чем при использовании других критериев МЗФО.Выводы. Частота МЗФО варьирует в зависимости от используемой классификации. У женщин частота МЗФО достоверно выше, чем у мужчин. С возрастом отмечается значимое снижение частоты МЗФО у женщин. Частота артериальной гипертонии, абдоминального ожирения, уровень глюкозы крови натощак, холестерина липопротеидов низкой плотности и гипертриглицеридемия выше у лиц с наличием МЗФО по критериям РКО

Significance of Input Correlations in Striatal Function

The striatum is the main input station of the basal ganglia and is strongly associated with motor and cognitive functions. Anatomical evidence suggests that individual striatal neurons are unlikely to share their inputs from the cortex. Using a biologically realistic large-scale network model of striatum and cortico-striatal projections, we provide a functional interpretation of the special anatomical structure of these projections. Specifically, we show that weak pairwise correlation within the pool of inputs to individual striatal neurons enhances the saliency of signal representation in the striatum. By contrast, correlations among the input pools of different striatal neurons render the signal representation less distinct from background activity. We suggest that for the network architecture of the striatum, there is a preferred cortico-striatal input configuration for optimal signal representation. It is further enhanced by the low-rate asynchronous background activity in striatum, supported by the balance between feedforward and feedback inhibitions in the striatal network. Thus, an appropriate combination of rates and correlations in the striatal input sets the stage for action selection presumably implemented in the basal ganglia

Retinoic Acid Functions as a Key GABAergic Differentiation Signal in the Basal Ganglia

Retinoic acid (RA) is essential for the generation of GABAergic inhibitory neurons in the mouse forebrain, and RA treatment of embryonic stem cells induces the production of GABAergic neurons

Gender and age related features of metabolically healthy obesity phenotype prevalence

Aim. The study objective was to assess the age and gender characteristics of the metabolically healthy obesity phenotype (MHO) prevalence, taking into account various classifications.Materials and methods. The materials used are the cross-sectional studies of the population cohort (Health, Alcohol and Psychosocial factors in Eastern Europe (HAPIEE) project, Novosibirsk), with the total of 3,197 people, among them 857 men (26.8%) and 2,340 women (73.2%), with BMI ≥30 kg/m². The MHO is defined according to different classifications: 1. IDF (International Diabetes Federation, 2005) – Waist circumference (WC) ≥ 94 cm in men and ≥80 cm in women and one or none of the components of metabolic syndrome (MS); 2. NCEP ATP III (the National Cholesterol Education Program Adult Treatment Panel III, 2001) in the presence of 2 and / or less components of the metabolic syndrome and 3. RSC (The Royal Society of Chemistry) – the index of waist circumference / hip circumference (WC / HC) ≤0.9 in men and ≤0.85 in women.Results. According to IDF the frequency of MHO in the group was 23.2%; NCEP ATP III – 41.8; RSC criteria – 27.1%. The frequency of MHO was higher in women than in men, and it significantly decreased with the age in women population. In all classifications, increased average blood pressure (BP) level, with normal average values of the level of triglycerides (TG) and high-density lipoprotein (HDL) is typical for persons with MHO. The surveyed according to the RSC criteria people with MHO demonstrate higher frequency levels of all cardio metabolic risk factors than those surveyed with the use of other criteria of MHO.Conclusion. The frequency of MHO varies depending on the used classification. In women, the frequency of MHO is reliably higher than in men. With the age, a significant reduction of the frequency of MHO in women is manifested. The frequency of arterial hypertension and abdominal obesity, the level of fasting blood glucose and LDL (low density lipoprotein), hypertriglyceridemia is higher in persons with MHO according to the criteria RSC

Type 2 diabetes: basic clinical and laboratory parameters and risk of cardiovascular death

Aim. To evaluate the basic clinical and laboratory parameters and their relationship with the 14-year risk of cardiovascular death in individuals with type 2 diabetes (T2D).Material and methods. A prospective case-control study of a sample of Novosibirsk residents with T2D was performed. An initial examination was conducted as part of the HAPIEE project in 2003-2005. The follow-up period lasted until 2017 and amounted to 13,7±0,7 years. The case group consisted of 145 people (mean age — 62,0±5,7 years) with recorded cardiovascular death. Control group — 272 people (mean age — 57,9±6,6 years) without recorded death as of December 31, 2017. Persons with a history of non-fatal myocardial infarction and/or stroke at the initial examination were excluded. Blood pressure (BP), biochemical, anthropometric and socio-demographic data were determined. Logistic regression models were used to analyze the association of clinical and laboratory parameters with the risk of cardiovascular death.Results. T2D subjects with recorded cardiovascular death at the initial examination had a longer duration of the disease, higher fasting plasma glucose (FPG) and anthropometric parameters (body mass index (BMI), waist circumference (WC) (in  women)), systolic blood pressure (SBP) and diastolic blood pressure (DBP). In individuals of both sexes, the risk of cardiovascular death increased 2,2 times with WC >95 cm, 2,3 times with an increased WC/HC ratio, 2,2 times with a BMI ≥30 kg/m2, 1,9 times with physical activity <3 hours/week, 2 times for smokers and those with a single marital status, 3,5 times for hypertensive people, 2 times with FPG ≥7,5 mmol/L and longer duration of diabetes.Conclusion. Fourteen-year follow-up revealed that individuals with T2D have associations of cardiovascular death with both conventional risk factors such as hypertension, abdominal obesity, low level of physical activity, smoking, single marital status, and diabetes-related ones — FPG and the duration of diabetes

10-year fracture risk (FRAX®), mineral bone density and trabecular bone index in women with type 2 diabetes mellitus

The aim of the study was to assess the 10-year risk of fractures (FRAX®), taking into account the values of bone mineral density (BMD) and trabecular bone index (TBI) in a population sample of women over 55 years of age with type 2 diabetes mellitus (DM2).Materials and methods. The study was carried out on the material of the population cohort of the international project HAPIEE (Novosibirsk). The design of the study is «case-control». Random groups of women aged 55-84 with and without DM2 were formed in combination with the presence or absence of fractures in the history (n = 103, group 4). Standardized questionnaires, anthropometry, densitometry (dual energy X-ray absorptiometry, DEXA), TBI and FRAX® fracture risk determination were performed on all people.Results. Women with DM2 who reported a history fracture (group 1) had lower T-criteria in the femoral neck than women with DM2 without fracture (group 2), p = 0.039. However, the history of fracture in women with DM2 was accompanied by higher T-criteria values (by 0.3-0.5 SD) in the vertebrae and hips compared to women without DM (group 3). We did not get a significant difference in the TBI parameter between all 4 groups studied. We also found no difference in the risk of repeated fracture among women with and without DM2 using FRAX® without densitometry and TBI-adjusted FRAX® (p = 0.841, p = 0.094, respectively). In group 1 with DM2 and fractures, the risk for FRAX with T-test was lower than in group 3 without DM with fractures (p = 0.034 for the main fractures, p = 0.002 for the hip).Conclusion. In the studied population groups «case-control» of women aged 55-84 years with diabetes mellitus and fractures in their history, the risk of FRAX® fractures is lower with regard to DEXA and does not differ significantly in terms of TBI in comparison with women without DM2 fractures. The data obtained reflect the difficulties in diagnostics and the need to search for additional methods of early diagnosis of increased risk of fractures in patients with DM2