The role of microRNAs in neural stem cell-supported endothelial morphogenesis

Functional signaling between neural stem/progenitor cells (NSPCs) and brain endothelial cells (ECs) is essential to the coordination of organized responses during initial embryonic development and also during tissue repair, which occurs following brain injury. In this study, we investigated the molecular mechanisms underlying this functional signaling, using primary mouse brain ECs and NSPCs from embryonic mouse brain. EC/NSPC co-culture experiments have revealed that neural progenitors secrete factors supporting angiogenesis, which induce noticeable changes in endothelial morphology. We demonstrate that NSPCs influence the expression of mTOR and TGF-β signaling pathway components implicated in the regulation of angiogenesis. Endothelial morphogenesis, an essential component of vascular development, is a complex process involving gene activation and the upregulation of specific cell signaling pathways. Recently identified small molecules, called microRNAs (miRNAs), regulate the expression of genes and proteins in many tissues, including brain and vasculature. We found that NSPCs induced considerable changes in the expression of at least 24 miRNAs and 13 genes in ECs. Three NSPC-regulated EC miRNAs were identified as the potential primary mediators of this NSPC/EC interaction. We found that the specific inhibition, or overexpression, of miRNAs miR-155, miR-100, and miR-let-7i subsequently altered the expression of major components of the mTOR, TGF-β and IGF-1R signaling pathways in ECs. Overexpression of these miRNAs in ECs suppressed, while inhibition activated, the in vitro formation of capillary-like structures, a process representative of EC morphogenesis. In addition, we demonstrate that inhibition of FGF, VEGF, and TGF-β receptor signaling abolished NSPC-promoted changes in the endothelial miRNA profiles. Our findings demonstrate that NSPCs induce changes in the miRNA expression of ECs, which are capable of activating angiogenesis by modulating distinct cell signaling pathways

Identification of microsatellite loci according to BAC sequencing data and their physical mapping to the bread wheat 5B chromosome

The shortage of polymorphic markers for the regions of wheat chromosomes that encode commercially valuable traits determined the need for studying wheat microsatellite loci. In this work, SSR markers for individual regions in the short arm of bread wheat chromosome 5B (5BS) were designed based on sequencing data for BAC clones, and the regions of the corresponding chromosome were saturated with these markers. Totally, 130 randomly selected BAC clones from the 5BS library were sequenced on the Ion Torrent platform and assembled in contigs using MIRA software. The assembly characteristics (N50 = 4 136 bp) are comparable to the recently obtained data for wheat and relative species and acceptable for identification of microsatellite loci. An algorithm utilizing the properties of complexity decompositions in  he sliding-window mode was used to detect DNA sequences with a repeat unit of 2–4 bp. Analysis of 17 770 contigs with the total length of 25 879 921 bp allowed for designing 113, 79, and 67 microsatellite (SSR) loci with a repeat unit of 2, 3, and 4 bp, respectively. The SSR markers with a motif of 3 bp were tested using nullitetrasomic lines of Chinese Spring wheat homoeologous group 5. Thus, 21 markers specific for chromosome 5B were detected. Eight of these markers were mapped to the distal region of this chromosome (bin 5BS6) using a set of Chinese Spring deletion lines for 5BS. Eight and four markers were mapped to the interstitial region (bins 5BS5 and 5BS4, respectively). One marker was mapped to a pericentromeric bin. A comparative analysis of the distribution of trinucleotide microsatellites over wheat chromosome 5B and in different cereal species suggests that the (AAG)n repeat has proliferated and has been maintained during the evolution of cereals

Geochemistry of Vein Calcites Hosted in the Troodos Pillow Lavas and Their Implications for the Timing and Physicochemical Environment of Fracturing, Fluid Circulation, and Vein Mineral Growth

Calcite veins hosted in pillow lavas of the Late Cretaceous Troodos suprasubduction zone ophiolite provide insights into the timing and physicochemical environment of postmagmatic fracturing and fluid circulation through oceanic crust. This study presents rare earth element and yttrium (REE+Y) concentrations, δ13C, δ18O, 87Sr/86Sr, and clumped isotopic (Δ47) compositions of vein calcites in order to investigate their fluid sources, formation temperatures, and precipitation ages. These geochemical data are combined with microtextural analyses. Intersections of 87Sr/86Sr ratios of vein calcites with the Sr isotope seawater curve suggest two distinct calcite veining phases. Major calcite veining within an interval of ~10 Myr after crust formation is characterized by microtextures that point to extensional fracturing related to crack and sealing, host rock brecciation, and advective fluid flow. These vein calcites show REE+Y characteristics, 87Sr/86Sr ratios, and clumped isotopic compositions indicative of precipitation from seawater at <50 °C. Extended fluid residence times intensified fluid‐rock interactions and lowered Y/Ho ratios of some blocky vein calcites, whereas crack and sealing resulted in pristine seawater signatures. Low 87Sr/86Sr ratios of localized high‐temperature blocky vein calcites point to the involvement of hydrothermal fluids. These calcites show Mn‐controlled oscillatory growth zonations that probably developed in a closed system out of equilibrium. Later calcite veining (<75 Ma) may have coincided with rotation and/or uplift of the Troodos ophiolite. Microtextures of these vein calcites indicate fluid diffusion and fracture‐independent crystallization pressure‐driven veining. Their variably modified seawater signatures resulted from diffusion‐related fluid interaction with hydrothermal sediments

Изменение функционального профиля моноцитов крови при раке молочной железы

The purpose of the study was to identify functional features of circulation monocytes in patients with nonmetastatic breast cancer.Material and Methods. The study cohort consisted of 10 breast cancer patients treated at Tomsk Cancer Research Institute. 7 healthy female volunteers were enrolled as a control group. CD14+16-, CD14+16+ and CD14-16+ monocytes subsets were obtained from blood by sorting. Whole transcriptome profling was provided in monocytes from patients and healthy females. Macrophages were differentiated from the obtained monocytes under in vitro conditions. The ability of conditioned media obtained from macrophages to infuence apoptosis and proliferation of MDA-MB 231 cell line was evaluated.Results. Transcriptomic profling revealed signifcant changes in monocytes of breast cancer patients. CD14+16- subset showed higher expression of transporters ABCA1 and ABCG1; chemokines CCR1, CRRL2, CXCR4; maturation and differentiation factors Mafb and Jun; endocytosis mediating factors CD163 and Siglec1; proteases and tetrasponins ADAM9, CD151, CD82, and growth factor HBEGF in patient group. Macrophages derived from monocytes of breast cancer patients produced factors that supported proliferation of the MDA-MB 231 cell line, which was not observed for monocytes from healthy volunteers.Conclusion. Thus, breast carcinoma has a systemic effect on peripheral blood monocytes, programming them to differentiate into macrophages with tumor supporting capacity. Цель исследования ‒ оценить особенности функционального профиля моноцитов периферической крови у больных неметастатической формой рака молочной железы.Материал и методы. В исследование вошли 10 больных раком молочной железы II–III стадии (T1–3N0–2M0). В качестве контроля была обследована группа из 7 здоровых женщин. Моноциты были получены из периферической крови путем сортировки популяций с фенотипом CD14+16-, CD14+16+ и CD14-16+. Проведено полнотранскриптомное профилирование полученных моноцитов от больных раком молочной железы и здоровых женщин. Из полученных моноцитов in vitro были дифференцированы макрофаги. Проведена оценка способности полученных от макрофагов кондиционных сред влиять на апоптоз и пролиферацию клеток линии MDA-MB 231.Результаты. Показано, что транскриптомный профиль моноцитов больных РЖЖ имеет выраженные отличия по сравнению со здоровыми женщинами. Моноциты пациенток с раком молочной железы отличаются повышенной экспрессией мРНК белков-транспортеров ABCA1, ABCG1; хемокинов CCR1, CRRL2, CXCR4; факторов созревания и дифференцировки моноцитов Mafb и Jun; факторов, опосредующих эндоцитоз CD163, Siglec1; протеаз и тетраспонинов ADAM9, CD151, CD82 и ростового фактора HBEGF. Макрофаги, полученные в результате культивирования моноцитов больных раком молочной железы в условиях in vitro, продуцировали факторы, которые позволили поддерживать пролиферацию клеточной линии опухолевых клеток, чего не наблюдалось для моноцитов здоровых доноров.Заключение. Опухоль молочной железы оказывает системное влияние на моноциты периферической крови, программируя их к дифференцировке в макрофаги с проопухолевой функциональной активностью.

РЕКУРРЕНТНЫЕ ИНФЕКЦИИ ОРГАНОВ ДЫХАНИЯ У ДЕТЕЙ И ПРОГРАММЫ ИММУНОРЕАБИЛИТАЦИИ

The paper proposed a modern rehabilitation program for children with recurrent infections of the respiratory tract. As a result, it is shown interferon and immunotherapy is an important component of an integrated approach to the rehabilitation of children with recurrent respiratory infections, positively influencing to the nature of the immunological abnormalities. Using this scheme can reduce the frequency of episodes of ARI and increase the duration of clinically successful period after the experimentation. В статье предложена современная программа реабилитации детей с рекуррентными инфекциями респираторного тракта. В результате показано, что интерферонои иммунотерапия является важным компонентом комплексного подхода к реабилитации детей с рекуррентными инфекциями органов дыхания, положительно влияющим на характер иммунологических отклонений. Использование указанной схемы позволяет сократить частоту эпизодов ОРИ и увеличить продолжительность клинически благополучного периода после ее проведения.

Enhanced tonic GABAA inhibition in typical absence epilepsy

The cellular mechanisms underlying typical absence seizures, which characterize various idiopathic generalized epilepsies, are not fully understood, but impaired GABAergic inhibition remains an attractive hypothesis. In contrast, we show here that extrasynaptic GABAA receptor–dependent ‘tonic’ inhibition is increased in thalamocortical neurons from diverse genetic and pharmacological models of absence seizures. Increased tonic inhibition is due to compromised GABA uptake by the GABA transporter GAT–1 in the genetic models tested, and GAT–1 is critical in governing seizure genesis. Extrasynaptic GABAA receptors are a requirement for seizures in two of the best characterized models of absence epilepsy, and the selective activation of thalamic extrasynaptic GABAA receptors is sufficient to elicit both electrographic and behavioural correlates of seizures in normal animals. These results identify an apparently common cellular pathology in typical absence seizures that may have epileptogenic significance, and highlight novel therapeutic targets for the treatment of absence epilepsy.peer-reviewe

Adult onset asthma and interaction between genes and active tobacco smoking: The GABRIEL consortium.

BACKGROUND: Genome-wide association studies have identified novel genetic associations for asthma, but without taking into account the role of active tobacco smoking. This study aimed to identify novel genes that interact with ever active tobacco smoking in adult onset asthma. METHODS: We performed a genome-wide interaction analysis in six studies participating in the GABRIEL consortium following two meta-analyses approaches based on 1) the overall interaction effect and 2) the genetic effect in subjects with and without smoking exposure. We performed a discovery meta-analysis including 4,057 subjects of European descent and replicated our findings in an independent cohort (LifeLines Cohort Study), including 12,475 subjects. RESULTS: First approach: 50 SNPs were selected based on an overall interaction effect at p<10-4. The most pronounced interaction effect was observed for rs9969775 on chromosome 9 (discovery meta-analysis: ORint = 0.50, p = 7.63*10-5, replication: ORint = 0.65, p = 0.02). Second approach: 35 SNPs were selected based on the overall genetic effect in exposed subjects (p <10-4). The most pronounced genetic effect was observed for rs5011804 on chromosome 12 (discovery meta-analysis ORint = 1.50, p = 1.21*10-4; replication: ORint = 1.40, p = 0.03). CONCLUSIONS: Using two genome-wide interaction approaches, we identified novel polymorphisms in non-annotated intergenic regions on chromosomes 9 and 12, that showed suggestive evidence for interaction with active tobacco smoking in the onset of adult asthma

Management of Work and Procedure for the Laboratory Diagnostics of Infectious Diseases during the Winter XXII Olympics and XI Paralympics, 2014

Analyzed is the management system for laboratory diagnostics of infectious diseases during the XXII Olympics and XI Paralympics, 2014 in Sochi. Reviewed is piece of work, executed in the pre-Olympic period as regards provision of laboratory facilities deployed for clinical material investigation, development of normative and regulatory documentation which considers peculiarities of the situation, identification of diagnostic capacities of the laboratories, and forecasting of the probable volume of laboratory studies by reference to various groups of infections. Put forward is the procedure for arrangement of work at the different stages of laboratory diagnostics, cooperation and response in case of emergency situation in the sphere of sanitary-epidemiological welfare of the population. Discussed is the role of geo-information system and current means of monitoring over epidemiological situation in the participating states and in the region of the Olympics in laboratory support organization