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Made available in DSpace on 2022-05-01T15:46:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 Key message: Based on transcriptome and qPCR analysis, a phenotypic abnormality resulting from a Eucalyptus crossing is associated with overexpression of metabolic pathways related to defense responses against biotic and abiotic stress. Abstract: Genetic recombination by outcrossing, a strategy used in improvement programs, can present a low frequency of individuals within progeny with morphological and physiological abnormalities. An abnormality was identified in progeny from a controlled cross of Eucalyptus grandis. Applying RNA-Seq technology to leaf, stem, and root tissue of normal and abnormal seedlings grown under the same greenhouse conditions, we examined global gene expression changes and compared the transcriptional profiles of the two contrasting phenotypes. We also conducted functional enrichment and metabolic pathway analyses. Among the identified differentially expressed genes, most were upregulated in leaf and stem tissues of abnormal plants, with gene ontology (GO) terms associated with 'response to stress', 'response to stimulus', and 'immune system process' categories. Further, in differential gene expression and functional enrichment analyses, we observed overexpression of metabolic pathways related to defense response processes in abnormal plants. Our results suggest that the anomaly is associated with changes in the defense response to biotic and abiotic stresses. As all progeny were grown in a controlled environment and there was no evidence of pathogenic attacks, the defense response in abnormal plants may be due to an autoimmune mechanism caused by genetic incompatibility. Departamento de Ciências Químicas e Biológicas Instituto de Biociências Universidade Estadual Paulista (UNESP), SP Instituto de Biotecnologia Universidade Estadual Paulista (UNESP), SP Departamento de Biofísica e Farmacologia Instituto de Biociências Universidade Estadual Paulista (UNESP), SP Luxembourg Centre for Systems Biomedicine (LCSB) University of Luxembourg Empresa Suzano Papel e Celulose SA, Av. Dr. José Lembo 1010, SP Plant Pathology and Entomology Section Department of Agricultural Food Environmental and Forestry Science and Technology (DAGRI) University of Florence, Florence province School of Agriculture São Paulo State University (Unesp), SP Departamento de Ciências Químicas e Biológicas Instituto de Biociências Universidade Estadual Paulista (UNESP), SP Instituto de Biotecnologia Universidade Estadual Paulista (UNESP), SP Departamento de Biofísica e Farmacologia Instituto de Biociências Universidade Estadual Paulista (UNESP), SP School of Agriculture São Paulo State University (Unesp), SP

Made available in DSpace on 2021-07-14T10:46:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-04-16. Added 1 bitstream(s) on 2021-07-14T11:37:58Z : No. of bitstreams: 1 S1414-40772021000100197.pdf: 606620 bytes, checksum: a5b464489e1427d6bba9821bb49e9d98 (MD5) A evasão é um tema de interesse mundial na área da educação, contudo o entendimento atual sobre o fenômeno é ainda insuficiente, sobretudo quando o objetivo é avaliar políticas efetivas de evasão. Neste artigo o percentual anual de evasão da Unesp é avaliado com base na adoção da política de reserva de vagas. Existem três possibilidades de ingresso - sistema universal (SU), quota por ter estudado em escola pública (EP) e quota por ser PPI (pretos, pardos, indígenas). Os dados foram segmentados por curso e ano de ingresso. A Unesp tem campus em 24 cidades, que reúnem 34 unidades e abrigam 136 diferentes cursos de Graduação. O ingresso para estes cursos é realizado por meio de vestibular com 186 diferentes opções em 63 carreiras. Uma comparação das taxas de evasão permite observar que elas podem depender do modo de ingresso, mas isso ocorre de forma variada ao longo do tempo e depende da área do curso, não sendo significativo. Verificou-se um decréscimo consistente da taxa de evasão global e por categoria de ingresso. Student dropout is a topic of worldwide interest in the field of education research; however, current understanding of the phenomenon remains insufficient, particularly when the objective is to evaluate effective retention policies. The annual dropout rate at UNESP was evaluated based on the admission selection policy. There are three admission categories: the universal exam system; a selection quota for students who studied in public schools; and a selection quota for students who are Black, Brown or Indigenous. The data was classified by course and admittance year. UNESP has campuses in 24 towns, divided into 34 campuses that provide 136 different undergraduate courses. Admission to these courses is conducted by an entrance exam with 186 different options in 63 careers. A comparison of dropout rates shows that these may depend on the admission category, but it varies over time and depends on the course subject. The data also reveal a consistent decrease in the annual dropout rates, according to the admission category. Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Ciências e Letras Universidade Estadual Paulista Júlio de Mesquita Filho, Instituto de Biociências Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Medicina de Botucatu Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Ciências e Engenharias Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Filosofia e Ciências Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Ciências e Letras Universidade Estadual Paulista Júlio de Mesquita Filho, Instituto de Biociências Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Medicina de Botucatu Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Ciências e Engenharias Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Filosofia e Ciências

Made available in DSpace on 2021-06-25T10:55:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-12-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Background: During vertebrate evolution, the heart has undergone remarkable changes that lead to morphophysiological differences in the fully formed heart of these species, such as chamber septation, heart rate frequency, blood pressure, and cardiac output volume. Despite these differences, the heart developmental process is guided by a core gene set conserved across vertebrates. Nonetheless, the regulatory mechanisms controlling the expression of genes involved in heart development and maintenance are largely uncharted. MicroRNAs (miRNAs) have been described as important regulatory elements in several biological processes, including heart biology. These small RNA molecules are broadly conserved in sequence and genomic context in metazoans. Mutations may occur in miRNAs and/or genes that contribute to the establishment of distinct repertoires of miRNA-target interactions, thereby favoring the differential control of gene expression and, consequently, the origin of novel phenotypes. In fact, several studies showed that miRNAs are integrated into genetic regulatory networks (GRNs) governing specific developmental programs and diseases. However, studies integrating miRNAs in vertebrate heart GRNs under an evolutionary perspective are still scarce. Results: We comprehensively examined and compared the heart miRNome of 20 species representatives of the five major vertebrate groups. We found 54 miRNA families with conserved expression and a variable number of miRNA families with group-specific expression in fishes, amphibians, reptiles, birds, and mammals. We also detected that conserved miRNAs present higher expression levels and a higher number of targets, whereas the group-specific miRNAs present lower expression levels and few targets. Conclusions: Both the conserved and group-specific miRNAs can be considered modulators orchestrating the core and peripheral genes of heart GRNs of vertebrates, which can be related to the morphophysiological differences and similarities existing in the heart of distinct vertebrate groups. We propose a hypothesis to explain evolutionary differences in the putative functional roles of miRNAs in the heart GRNs analyzed. Furthermore, we present new insights into the molecular mechanisms that could be helping modulate the diversity of morphophysiology in the heart organ of vertebrate species. Laboratório Especial de Toxinologia Aplicada (LETA) CeTICS Instituto Butantan Department of Chemical and Biological Sciences Institute of Biosciences of Botucatu São Paulo State University (UNESP) Department of Biophysics and Pharmacology Institute of Biosciences of Botucatu São Paulo State University (UNESP) Department of Biological Sciences Vanderbilt University Department of Molecular Biosciences The Wenner-Gren Institute (MBW) Stockholm University Department of Chemical and Biological Sciences Institute of Biosciences of Botucatu São Paulo State University (UNESP) Department of Biophysics and Pharmacology Institute of Biosciences of Botucatu São Paulo State University (UNESP) FAPESP: 2012/15589-7 FAPESP: 2013/06864-7

Additional file 7 Supplementary data in pdf format.

Additional file 5 Supplementary data in xls format.

Additional file 3 Supplementary data in pdf format.

Nile tilapia is the third most cultivated fish worldwide and a novel model species for evolutionary studies. Aiming to improve productivity and contribute to the selection of traits of economic impact, biotechnological approaches have been intensively applied to species enhancement. In this sense, recent studies have focused on the multiple roles played by microRNAs (miRNAs) in the post-transcriptional regulation of protein-coding genes involved in the emergence of phenotypes with relevance for aquaculture. However, there is still a growing demand for a reference resource dedicated to integrating Nile Tilapia miRNA information, obtained from both experimental and in silico approaches, and facilitating the analysis and interpretation of RNA sequencing data. Here, we present an open repository dedicated to Nile Tilapia miRNAs: the &ldquo, miRTil database&rdquo, The database stores data on 734 mature miRNAs identified in 11 distinct tissues and five key developmental stages. The database provides detailed information about miRNA structure, genomic context, predicted targets, expression profiles, and relative 5p/3p arm usage. Additionally, miRTil also includes a comprehensive pre-computed miRNA-target interaction network containing 4936 targets and 19,580 interactions.

Microbiome&ndash, host interactions play significant roles in health and in various diseases including autoimmune disorders. Uncovering these inter-kingdom cross-talks propels our understanding of disease pathogenesis and provides useful leads on potential therapeutic targets. Despite the biological significance of microbe&ndash, host interactions, there is a big gap in understanding the downstream effects of these interactions on host processes. Computational methods are expected to fill this gap by generating, integrating, and prioritizing predictions&mdash, as experimental detection remains challenging due to feasibility issues. Here, we present MicrobioLink, a computational pipeline to integrate predicted interactions between microbial and host proteins together with host molecular networks. Using the concept of network diffusion, MicrobioLink can analyse how microbial proteins in a certain context are influencing cellular processes by modulating gene or protein expression. We demonstrated the applicability of the pipeline using a case study. We used gut metaproteomic data from Crohn&rsquo, s disease patients and healthy controls to uncover the mechanisms by which the microbial proteins can modulate host genes which belong to biological processes implicated in disease pathogenesis. MicrobioLink, which is agnostic of the microbial protein sources (bacterial, viral, etc.), is freely available on GitHub.

Made available in DSpace on 2020-12-12T02:09:43Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-09-18 MicroRNAs (miRNAs) are non-coding RNAs that regulate a wide range of biological pathways by post-transcriptionally modulating gene expression levels. Given that even a single miRNA may simultaneously control several genes enrolled in multiple biological functions, one would expect that these tiny RNAs have the ability to properly sort among distinctive cellular processes to drive protein production. To test this hypothesis, we scrutinized previously published microarray datasets and clustered protein-coding gene expression profiles according to the intensity of fold-change levels caused by the exogenous transfection of 10 miRNAs (miR-1, miR-7, miR-9, miR-124, miR-128a, miR-132, miR-133a, miR-142, miR-148b, miR-181a) in a human cell line. Through an in silico functional enrichment analysis, we discovered non-randomic regulatory patterns, proper of each cluster identified. We demonstrated that miRNAs are capable of equivalently modulate the expression signatures of target genes in regulatory clusters according to the biological function they are assigned to. Moreover, target prediction analysis applied to ten vertebrate species, suggest that such miRNA regulatory modus operandi is evolutionarily conserved within vertebrates. Overall, we discovered a complex regulatory cluster-module strategy driven by miRNAs, which relies on the controlled intensity of the repression over distinct targets under specific biological contexts. Our discovery helps to clarify the mechanisms underlying the functional activity of miRNAs and makes it easier to take the fastest and most accurate path in the search for the functions of miRNAs in any distinct biological process of interest. Institute of Biosciences of Botucatu Department of Genetics Sao Paulo State University (UNESP) Department of Physics and Biophysics Sao Paulo State University (UNESP) Laboratory of Structural Genomics (GenEstrut) Technology Developmental Center Graduate Program of Biotechnology Federal University of Pelotas Institute of Biosciences of Botucatu Department of Genetics Sao Paulo State University (UNESP) Department of Physics and Biophysics Sao Paulo State University (UNESP)

Germination of the coffee (Coffea arabica L.) seed is the result of events that occur simultaneously in the embryo and endosperm. To understand the molecular mechanisms responsible for these events, we undertook a transcriptome analysis of embryo, micropylar and lateral endosperms from 10-day-imbibed seeds. The sequencing yielded contigs coding for 16,813 proteins. From those, 14,005 (~ 83%) were highly similar to at least one protein sequence in the nr database. 162 genes were significantly expressed in the embryo, 36 in the micropylar endosperm and 72 in the lateral endosperm. The tissue specificity analysis of the significantly expressed genes showed that the embryo had the highest proportion of specific genes (113/162, ~70%), while 11 were expressed in the micropylar and lateral endosperms. In the embryo, genes were mainly associated with abiotic stress, cell growth, and intercellular communication. In the micropylar and lateral endosperms, they were associated with abiotic stress and cell wall degradation. The accuracy of RNA-seq data was confirmed by RT-qPCR. This work adds new information about the molecular mechanism involved in coffee seed germination. Resumo: A germinação da semente do café (Coffea arabica L.) é resultado de eventos que ocorrem simultaneamente no embrião e endosperma. Para entender os mecanismos moleculares responsáveis por estes eventos, nós realizamos uma análise transcricional do embrião e dos endospermas micropilar e lateral de sementes embebidas por 10 dias. O sequenciamento obteve contigs que codificam 16.813 proteínas. Destas, 14.005 (~ 83%) foram altamente similares a pelo menos uma sequência de proteína na base de dados nr. 162 genes foram significativamente expressos em embrião, 36 em endosperma micropilar e 72 em endosperma lateral. A análise de tecido-especificidade dos genes significativamente expressos mostrou que a maior proporção de genes específicos está no embrião (113/162, ~70%), enquanto 11 genes foram expressos nos endospermas lateral e micropilar. No embrião, os genes foram associados principalmente com estresse abiótico, crescimento celular e comunicação intercelular. Nos endospermas micropilar e lateral, eles foram associados com estresse abiótico e degradação da parede celular. A acurácia da análise de RNA-seq foi confirmada por RT-qPCR. Este trabalho acrescenta novas informações sobre os mecanismos moleculares envolvidos na germinação de sementes de café.

O Workshop da Pós-Graduação é um evento anual e tem como objetivo discutir temas pertinentes aos Pós-Graduandos, Docentes e Administração do Instituto deBiociências de Botucatu, promovendo o amadurecimento político-científico, análise do mercado atual para os egressos, aperfeiçoamento e conhecimento científico. Busca-se apresentar experiências externas e mostrar possibilidades diferentes da carreira acadêmica.Na oportunidade, facilita-se a formação de novas redes de trabalho e cooperação. Os contatos e experiências vivenciados durante o evento são de plena importância para vida profissional dos participantes. A organização do evento inclui a participação de docentes e de discentes que elaboraram a programação e participaram ativamente da revisão dos trabalhos aqui apresentados.A oitava edição do evento ocorreu no Instituto de Biociências durante os dias 23, 24 e 25 de abril no Instituto de Biociências de Botucatu e contou com a participação de 200 inscritos.A natureza do evento é interdisciplinar pois congrega os diferentes programas de pós-graduação do Instituto de Biociências de Botucatu: Farmacologia, Botânica, Genética, Zoologia, Biologia Geral e Aplicada e Biometria. O programa inclui mini-cursos ministrados pelos pós-graduandos tratando de temas atuais de pesquisa, estes eventos incluem além de exposições orais e oficinas, a produção de material de apoio que compõe este volume.Entre os temas tratados neste volume destacamos a biodiversidade, toxicologia aplicada a reprodução humana, biodiversidade, restauração ecológica, biologia floral, embriologia e farmacocinética aplicada a testes clínicos. A diversidade dos tópicos tratados ilustra a riqueza das atividades de pesquisa realizada no Instituto de Biociências de Botucatu.

Metalloproteases play a fundamental role in snake venom envenomation inducing hemorrhagic, fibrigen(ogen)olytic and myotoxic effects in their victims. Several snake venoms, such as those from the Bothrops genus, present important local effects which are not efficiently neutralized by conventional serum therapy. Consequently, these accidents may result in permanent sequelae and disability, creating economic and social problems, especially in developing countries, leading the attention of the World Health Organization that considered ophidic envenomations a neglected tropical disease. Aiming to produce an efficient inhibitor against bothropic venoms, we synthesized different molecules classified as quinolinones – a group of low-toxic chemical compounds widely used as antibacterial and antimycobacterial drugs – and tested their inhibitory properties against hemorrhage caused by bothropic venoms. The results from this initial screening indicated the molecule 2-hydroxymethyl-6-methoxy-1,4-dihydro-4-quinolinone (Q8) was the most effective antihemorrhagic compound among all of the assayed synthetic quinolinones. Other in vitro and in vivo experiments showed this novel compound was able to inhibit significantly the hemorrhagic and/or proteolytic activities of bothropic crude venoms and isolated snake venom metalloproteases (SVMPs) even at lower concentrations. Docking and molecular dynamic simulations were also performed to get insights into the structural basis of Q8 inhibitory mechanism against proteolytic and hemorrhagic SVMPs. These structural studies demonstrated that Q8 may form a stable complex with SVMPs, impairing the access of substrates to the active sites of these toxins. Therefore, both experimental and structural data indicate that Q8 compound is an interesting candidate for antiophidic therapy, particularly for the treatment of the hemorrhagic and necrotic effects induced by bothropic venoms.

Made available in DSpace on 2018-12-11T17:20:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-12-01 MicroRNAs (miRNAs) are key regulators of gene expression in multicellular organisms. The elucidation of miRNA function and evolution depends on the identification and characterization of miRNA repertoire of strategic organisms, as the fast-evolving cichlid fishes. Using RNA-seq and comparative genomics we carried out an in-depth report of miRNAs in Nile tilapia (Oreochromis niloticus), an emergent model organism to investigate evo-devo mechanisms. Five hundred known miRNAs and almost one hundred putative novel vertebrate miRNAs have been identified, many of which seem to be teleost-specific, cichlid-specific or tilapia-specific. Abundant miRNA isoforms (isomiRs) were identified with modifications in both 5p and 3p miRNA transcripts. Changes in arm usage (arm switching) of nine miRNAs were detected in early development, adult stage and even between male and female samples. We found an increasing complexity of miRNA expression during ontogenetic development, revealing a remarkable synchronism between the rate of new miRNAs recruitment and morphological changes. Overall, our results enlarge vertebrate miRNA collection and reveal a notable differential ratio of miRNA arms and isoforms influenced by sex and developmental life stage, providing a better picture of the evolutionary and spatiotemporal dynamics of miRNAs. Department of Genetics Institute of Biosciences of Botucatu Sao Paulo State University (UNESP) Department of Physics and Biophysics Institute of Biosciences of Botucatu Sao Paulo State University (UNESP) School of Biological Sciences University of East Anglia (UEA), Norwich Research Park Department of Clinical and Molecular Medicine Norwegian University of Science and Technology (NTNU) Stevenson Center Vanderbilt University Unit of Biotechnology University of Mogi das Cruzes Department of Morphology Institute of Biosciences of Botucatu Sao Paulo State University (UNESP) Department of Genetics Institute of Biosciences of Botucatu Sao Paulo State University (UNESP) Department of Physics and Biophysics Institute of Biosciences of Botucatu Sao Paulo State University (UNESP) Department of Morphology Institute of Biosciences of Botucatu Sao Paulo State University (UNESP)

Made available in DSpace on 2020-12-12T02:32:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-03-07 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Escherichia coli ribosomal genes are a well-established experimental model used to investigate the transcription process. These genes are essential to cell physiology and are therefore strongly expressed. Multiple transcription units collaborate in rrn expression. Experiments involving electron microscopy have shown the non-uniform density of the RNA polymerases transcribing these ribosomal operons. Here, we investigate RNAP collaborative transcription in E. coli ribosomal genes using a stochastic sequence-dependent model that included interactions among the RNAPs. We achieved results consistent with experimental data using a model with variable parametrization for genic and intergenic regions, compared with previous attempts that used uniform parameters for genic and intergenic regions. Our model also showed that cooperative behaviour reduced the dwell times in pause sites predicted by the single-round approach but induced a new pausing event at an upstream position. This work may stimulate new experimental research and provide other scenarios to test our model predictions. Institute of Biosciences UNESP - Univ Estadual Paulista Department of Physics and Biophysics Institute of Biosciences UNESP - Univ Estadual Paulista Department of Physics and Biophysics CNPq: 152838/2012-0 FAPESP: 2012/19377-4 FAPESP: 2013/06683-2

Made available in DSpace on 2018-12-11T17:34:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-12-01 Phospholipase A2-like (PLA2-like) proteins contribute to the development of muscle necrosis in Viperidae snake bites and are not efficiently neutralized by current antivenom treatments. The toxic mechanisms of PLA2-like proteins are devoid of catalytic activity and not yet fully understood, although structural and functional experiments suggest a dimeric assembly and that the C-terminal residues are essential to myotoxicity. Herein, we characterized the functional mechanism of bothropic PLA2-like structures related to global and local measurements using the available models in the Protein Data Bank and normal mode molecular dynamics (NM-MD). Those measurements include: (i) new geometric descriptions between their monomers, based on Euler angles; (ii) characterizations of canonical and non-canonical conformations of the C-terminal residues; (iii) accessibility of the hydrophobic channel; (iv) inspection of ligands; and (v) distance of clustered residues to toxin interface of interaction. Thus, we described the allosteric activation of PLA2-like proteins and hypothesized that the natural movement between monomers, calculated from NM-MD, is related to their membrane disruption mechanism, which is important for future studies of the inhibition process. These methods and strategies can be applied to other proteins to help understand their mechanisms of action. Departamento de Física e Biofísica Instituto de Biociências Universidade Estadual Paulista (UNESP) Departamento de Física e Biofísica Instituto de Biociências Universidade Estadual Paulista (UNESP)

Made available in DSpace on 2018-12-11T17:12:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-05-09 Target prediction is generally the first step toward recognition of bona fide microRNA (miRNA)-target interactions in living cells. Several target prediction tools are now available, which use distinct criteria and stringency to provide the best set of candidate targets for a single miRNA or a subset of miRNAs. However, there are many false-negative predictions, and consensus about the optimum strategy to select and use the output information provided by the target prediction tools is lacking. We compared the performance of four tools cited in literature-TargetScan (TS), miRanda-mirSVR (MR), Pita, and RNA22 (R22), and we determined the most effective approach for analyzing target prediction data (individual, union, or intersection). For this purpose, we calculated the sensitivity, specificity, precision, and correlation of these approaches using 10 miRNAs (miR-1-3p, miR-17-5p, miR-21-5p, miR-24-3p, miR-29a-3p, miR-34a-5p, miR-124-3p, miR-125b-5p, miR-145-5p, and miR-155-5p) and 1,400 genes (700 validated and 700 non-validated) as targets of these miRNAs. The four tools provided a subset of high-quality predictions and returned few false-positive predictions; however, they could not identify several known true targets. We demonstrate that union of TS/MR and TS/MR/R22 enhanced the quality of in silico prediction analysis of miRNA targets. We conclude that the union rather than the intersection of the aforementioned tools is the best strategy for maximizing performance while minimizing the loss of time and resources in subsequent in vivo and in vitro experiments for functional validation of miRNA-target interactions. Laboratory of Genomics and Molecular Evolution Department of Genetics Institute of Biosciences of Botucatu São Paulo State Univesity (UNESP) Laboratory of Bioinformatics and Computational Biophysics Department of Physics and Biophysics Institute of Biosciences of Botucatu São Paulo State Univesity (UNESP) Laboratory of Genomics and Molecular Evolution Department of Genetics Institute of Biosciences of Botucatu São Paulo State Univesity (UNESP) Laboratory of Bioinformatics and Computational Biophysics Department of Physics and Biophysics Institute of Biosciences of Botucatu São Paulo State Univesity (UNESP)

Objective Sleep spindles have been suggested as surrogates of thalamo-cortical activity. Internal frequency modulation within a spindle's time frame has been demonstrated in healthy subjects, showing that spindles tend to decelerate their frequency before termination. We investigated internal frequency modulation of slow and fast spindles according to Obstructive Sleep Apnea (OSA) severity and brain topography. Methods Seven non-OSA subjects and 21 patients with OSA contributed with 30min of Non-REM sleep stage 2, subjected to a Matching pursuit procedure with Gabor chirplet functions for automatic detection of sleep spindles and quantification of sleep spindle internal frequency modulation (chirp rate). Results Moderate OSA patients showed an inferior percentage of slow spindles with deceleration when compared to Mild and Non-OSA groups in frontal and parietal regions. In parietal regions, the percentage of slow spindles with deceleration was negatively correlated with global apnea-hypopnea index ( r s =−0.519, p =0.005). Discussion Loss of physiological sleep spindle deceleration may either represent a disruption of thalamo-cortical loops generating spindle oscillations or some compensatory mechanism, an interesting venue for future research in the context of cognitive dysfunction in OSA. Significance Quantification of internal frequency modulation (chirp rate) is proposed as a promising approach to advance description of sleep spindle dynamics in brain pathology.

Automated and efficient methods that map ortholog interactions from several organisms and public databases (pDB) are needed to identify new interactions in an organism of interest (interolog mapping). When computational methods are applied to predict interactions, it is important that these methods be validated and their efficiency proven. In this study, we compare six Blast+ metrics over three datasets to identify the best metric for protein-protein interaction predictions. Using Blast+ to align the protein pairs, the ortholog interactions from DIP were mapped to String, Intact and Psibase pDBs. For each interaction mapped to each pDBs, we retrieved the alignment score, e-value, bitscore, similarity, identity and coverage. We evaluated these Blast+ values, and combinations thereof, with the Receiver Operating Characteristic (ROC) curves and computed the Area Under Curve (AUC). To validate these predictions, we used a subset of the Database of Interacting Proteins (DIP) composed of experimental interactions curated by the International Molecular Exchange (IMEx). The cut-off point for each metric/pDB was computed aiming to identify the best one that separates the true and false predicted interactions. In contrast to other methods that only compute the first Blast hit, we considered the first 20 hits, thus increasing the number of predicted interaction pairs. In addition, we identified the contribution of each individual pDB, as well as their combined contribution to the prediction. The best metric had an AUC of 0.96 for a single pDB and AUC of 0.93 for combined pDBs. Compared to other studies, with a cut-off point of 0.70 representing a specificity of 0.95 and a sensitivity of 0.90 for individual pDB, our method efficiently predicts protein-protein interactions.

Made available in DSpace on 2018-12-11T17:05:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-08-25 National Natural Science Foundation of China Background: Many centrality measures have been proposed to mine and characterize the correlations between network topological properties and protein essentiality. However, most of them show limited prediction accuracy, and the number of common predicted essential proteins by different methods is very small. Results: In this paper, an ensemble framework is proposed which integrates gene expression data and protein-protein interaction networks (PINs). It aims to improve the prediction accuracy of basic centrality measures. The idea behind this ensemble framework is that different protein-protein interactions (PPIs) may show different contributions to protein essentiality. Five standard centrality measures (degree centrality, betweenness centrality, closeness centrality, eigenvector centrality, and subgraph centrality) are integrated into the ensemble framework respectively. We evaluated the performance of the proposed ensemble framework using yeast PINs and gene expression data. The results show that it can considerably improve the prediction accuracy of the five centrality measures individually. It can also remarkably increase the number of common predicted essential proteins among those predicted by each centrality measure individually and enable each centrality measure to find more low-degree essential proteins. Conclusions: This paper demonstrates that it is valuable to differentiate the contributions of different PPIs for identifying essential proteins based on network topological characteristics. The proposed ensemble framework is a successful paradigm to this end. Systems Biology Core NHLBI NIH, 9000 Rockville Pike XiangNan University Department of Computer Science, Eastern Wangxian Park UNESP-S�o Paulo State University Department of Physics and Biophysics Institute of Biosciences of Botucatu Norwegian University of Science and Technology (NTNU) Department of Cancer Research and Molecular Medicine, P.B. 8905 UNESP-S�o Paulo State University Department of Physics and Biophysics Institute of Biosciences of Botucatu National Natural Science Foundation of China: 51378243 National Natural Science Foundation of China: 61402423 National Natural Science Foundation of China: 61502343

This study aimed to investigate the association between twelve gene polymorphisms and body weight loss, 12 months after Roux-en-Y gastric bypass (RYGB) surgery. Three hundred and fifty-one obese women participated in this study. The statistical software WEKA was used to identify which gene polymorphisms were potential predictors of postoperative percentage of excess weight loss (%EWL). Our results indicate that the only gene polymorphism that predicted %EWL was rs3813929, which is related to the serotonin receptor gene (5-HT2C). Therefore, the 5-HT2C gene polymorphism rs3813929 (more specifically, the TT genotype) predicted greater %EWL 12 months after RYGB surgery among female patients.