Меры снижения потерь от риска в процессе реализации инвестиционного проекта

Материалы XVI Междунар. науч.-техн. конф. студентов, аспирантов и молодых ученых, Гомель, 28–29 апр. 2016 г

Identification of NCAN as a candidate gene for developmental dyslexia

A whole-genome linkage analysis in a Finnish pedigree of eight cases with developmental dyslexia (DD) revealed several regions shared by the affected individuals. Analysis of coding variants from two affected individuals identified rs146011974G >A (Ala1039Thr), a rare variant within the NCAN gene co-segregating with DD in the pedigree. This variant prompted us to consider this gene as a putative candidate for DD. The RNA expression pattern of the NCAN gene in human tissues was highly correlated (R > 0.8) with that of the previously suggested DD susceptibility genes KIAA0319, CTNND2, CNTNAP2 and GRIN2B. We investigated the association of common variation in NCAN to brain structures in two data sets: young adults (Brainchild study, Sweden) and infants (FinnBrain study, Finland). In young adults, we found associations between a common genetic variant in NCAN, rs1064395, and white matter volume in the left and right temporoparietal as well as the left inferior frontal brain regions. In infants, this same variant was found to be associated with cingulate and prefrontal grey matter volumes. Our results suggest NCAN as a new candidate gene for DD and indicate that NCAN variants affect brain structure.Peer reviewe

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

Prokaryotic protein subcellular localization prediction and genome-scale comparative analysis

Identifying protein subcellular localization (SCL) is important for deducing protein function, annotating newly sequenced genomes, and guiding experimental designs. Identification of cell surface-bound and secreted proteins from pathogenic bacteria may lead to the discovery of biomarkers, novel vaccine components and therapeutic targets. Characterizing such proteins for non-pathogenic bacteria and archaea can have industrial uses, or play a role in environmental detection. Previously, the Brinkman lab has developed PSORTb, the most precise SCL prediction software tool for bacteria. However, as we increasingly appreciate the diversity of prokaryotic species and their cellular structures, it became clear that there was a need to more accurately make predictions for more diverse microbes. For my thesis research, I developed a new version of PSORTb that now provides SCL prediction capability for more prokaryotes, including Archaea and Bacteria with atypical cell wall and membrane structures. The new PSORTb also has significantly increased proteome prediction coverage for all bacterial species. The software is the first of its kind to predict subcategory localizations for bacterial organelles such as the flagellum as well as host cell destinations. Using both computational validations and a new proteomic dataset I produced, I established that PSORTb 3.0 outperforms all other published prokaryotic SCL prediction tools in terms of both precision and recall. Furthermore, I have developed a semi-automated version of a comprehensive prokaryotic SCL database (PSORTdb) that provides access to experimentally verified and pre-computed SCL predictions for all sequenced prokaryotic genomes. I developed an ‘outer membrane prediction method’ which allows auto-detection of bacterial structure, distinguishing bacteria with one vs. two membranes. This method allows the database to be automatically updated as newly sequenced genomes are released. In addition, the method can aid more general analysis of a bacterial genome for which the bacteria’s associated cellular structure is not initially clear. Finally, I performed a global analysis of SCL proportions for over 1000 sequenced bacterial and archaeal genomes. This is the most comprehensive SCL analysis of prokaryotes to date. My findings provide insights into prokaryotic protein network evolution, elucidate relationships between SCL proportions and genome size, and provide directions for future SCL prediction research

Motor Function Deficits in the Estrogen Receptor Beta Knockout Mouse : Role on Excitatory Neurotransmission and Myelination in the Motor Cortex

Background: Male estrogen receptor beta (ER beta) knockout (BERKO) mice display anxiety and aggression linked to, among others, altered serotonergic signaling in the basolateral amygdala and dorsal raphe, impaired cortical radial glia migration, and reduced GABAergic signaling. The effects on primary motor cortex (M1 cortex) and locomotor activity as a consequence of ER beta loss have not been investigated. Objective: The aim of this study was to determine whether locomotor activity is altered as a consequence of the changes in the M1 cortex. Methods: The locomotor activity of male wild-type (WT) and BERKO mice was evaluated using the open-field and rotarod tests. Molecular changes in the M1 cortex were analyzed by RNA sequencing, electron microscopy, electrophysiology, and immunohistological techniques. In addition, we established oligodendrocyte (OL) cultures from WT and BERKO mouse embryonic stem cells to evaluate OL function. Results: Locomotor profiling revealed that BERKO mice were more active than WT mice but had impaired motor coordination. Analysis of the M1 cortex pointed out differences in synapse function and myelination. There was a reduction in GABAergic signaling resulting in imbalanced excitatory and inhibitory neurotransmission as well as a defective OL differentiation accompanied by myelin defects. The effects of ER beta loss on OL differentiation were confirmed in vitro. Conclusion: ER beta is an important regulator of GABAergic interneurons and OL differentiation, which impacts on adult M1 cortex function and may be linked to increased locomotor activity and decreased motor coordination in BERKO mice.Peer reviewe

MANF protects human pancreatic beta cells against stress-induced cell death

There is a great need to identify factors that could protect pancreatic beta cells against apoptosis or stimulate their replication and thus prevent or reverse the development of diabetes. One potential candidate is mesencephalic astrocyte-derived neurotrophic factor (MANF), an endoplasmic reticulum (ER) stress inducible protein. Manf knockout mice used as a model of diabetes develop the condition because of increased apoptosis and reduced proliferation of beta cells, apparently related to ER stress. Given this novel association between MANF and beta cell death, we studied the potential of MANF to protect human beta cells against experimentally induced ER stress. Primary human islets were challenged with proinflammatory cytokines, with or without MANF. Cell viability was analysed and global transcriptomic analysis performed. Results were further validated using the human beta cell line EndoC-beta H1. There was increased expression and secretion of MANF in human beta cells in response to cytokines. Addition of recombinant human MANF reduced cytokine-induced cell death by 38% in human islets (p <0.05). MANF knockdown in EndoC-beta H1 cells led to increased ER stress after cytokine challenge. Mechanistic studies showed that the protective effect of MANF was associated with repression of the NF-kappa B signalling pathway and amelioration of ER stress. MANF also increased the proliferation of primary human beta cells twofold when TGF-beta signalling was inhibited (p <0.01). Our studies show that exogenous MANF protein can provide protection to human beta cells against death induced by inflammatory stress. The antiapoptotic and mitogenic properties of MANF make it a potential therapeutic agent for beta cell protection.Peer reviewe

Complementing tissue characterization by integrating transcriptome profiling from the Human Protein Atlas and from the FANTOM5 consortium

Understanding the normal state of human tissue transcriptome profiles is essential for recognizing tissue disease states and identifying disease markers. Recently, the Human Protein Atlas and the FANTOM5 consortium have each published extensive transcriptome data for human samples using Illumina-sequenced RNA-Seq and Heliscope-sequenced CAGE. Here, we report on the first large-scale complex tissue transcriptome comparison between full-length versus 5'-capped mRNA sequencing data. Overall gene expression correlation was high between the 22 corresponding tissues analyzed (R &gt; 0.8). For genes ubiquitously expressed across all tissues, the two data sets showed high genome-wide correlation (91% agreement), with differences observed for a small number of individual genes indicating the need to update their gene models. Among the identified single-tissue enriched genes, up to 75% showed consensus of 7-fold enrichment in the same tissue in both methods, while another 17% exhibited multiple tissue enrichment and/or high expression variety in the other data set, likely dependent on the cell type proportions included in each tissue sample. Our results show that RNA-Seq and CAGE tissue transcriptome data sets are highly complementary for improving gene model annotations and highlight biological complexities within tissue transcriptomes. Furthermore, integration with image-based protein expression data is highly advantageous for understanding expression specificities for many genes