Appearance frequency modulated gene set enrichment testing

Abstract Background Gene set enrichment testing has helped bridge the gap from an individual gene to a systems biology interpretation of microarray data. Although gene sets are defined a priori based on biological knowledge, current methods for gene set enrichment testing treat all genes equal. It is well-known that some genes, such as those responsible for housekeeping functions, appear in many pathways, whereas other genes are more specialized and play a unique role in a single pathway. Drawing inspiration from the field of information retrieval, we have developed and present here an approach to incorporate gene appearance frequency (in KEGG pathways) into two current methods, Gene Set Enrichment Analysis (GSEA) and logistic regression-based LRpath framework, to generate more reproducible and biologically meaningful results. Results Two breast cancer microarray datasets were analyzed to identify gene sets differentially expressed between histological grade 1 and 3 breast cancer. The correlation of Normalized Enrichment Scores (NES) between gene sets, generated by the original GSEA and GSEA with the appearance frequency of genes incorporated (GSEA-AF), was compared. GSEA-AF resulted in higher correlation between experiments and more overlapping top gene sets. Several cancer related gene sets achieved higher NES in GSEA-AF as well. The same datasets were also analyzed by LRpath and LRpath with the appearance frequency of genes incorporated (LRpath-AF). Two well-studied lung cancer datasets were also analyzed in the same manner to demonstrate the validity of the method, and similar results were obtained. Conclusions We introduce an alternative way to integrate KEGG PATHWAY information into gene set enrichment testing. The performance of GSEA and LRpath can be enhanced with the integration of appearance frequency of genes. We conclude that, generally, gene set analysis methods with the integration of information from KEGG PATHWAY performs better both statistically and biologically.http://deepblue.lib.umich.edu/bitstream/2027.42/112430/1/12859_2010_Article_4457.pd

SEC24A deficiency lowers plasma cholesterol through reduced PCSK9 secretion.

The secretory pathway of eukaryotic cells packages cargo proteins into COPII-coated vesicles for transport from the endoplasmic reticulum (ER) to the Golgi. We now report that complete genetic deficiency for the COPII component SEC24A is compatible with normal survival and development in the mouse, despite the fundamental role of SEC24 in COPII vesicle formation and cargo recruitment. However, these animals exhibit markedly reduced plasma cholesterol, with mutations in Apoe and Ldlr epistatic to Sec24a, suggesting a receptor-mediated lipoprotein clearance mechanism. Consistent with these data, hepatic LDLR levels are up-regulated in SEC24A-deficient cells as a consequence of specific dependence of PCSK9, a negative regulator of LDLR, on SEC24A for efficient exit from the ER. Our findings also identify partial overlap in cargo selectivity between SEC24A and SEC24B, suggesting a previously unappreciated heterogeneity in the recruitment of secretory proteins to the COPII vesicles that extends to soluble as well as trans-membrane cargoes. DOI:http://dx.doi.org/10.7554/eLife.00444.001

THINK Back: KNowledge-based Interpretation of High Throughput data

Results of high throughput experiments can be challenging to interpret. Current approaches have relied on bulk processing the set of expression levels, in conjunction with easily obtained external evidence, such as co-occurrence. While such techniques can be used to reason probabilistically, they are not designed to shed light on what any individual gene, or a network of genes acting together, may be doing. Our belief is that today we have the information extraction ability and the computational power to perform more sophisticated analyses that consider the individual situation of each gene. The use of such techniques should lead to qualitatively superior results

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Abstract:  Health professionals have a caregiver and promoter profile, and they must contribute with new theories of sustainable human development that seek to consolidate better opportunities for people on their social, economic and environmental dimensions, and an intergenerational perspective. We wonder if nutritional health care professionals in the future are in favor of environmental protection practices. Objective: to determine if environmental protection practices are considered when handling foods and its connection with nutritional status in advanced health services students. Descriptive, observational, correlational, cross-sectional study. Universe: students of the last course of careers of FCM, UNC (2020). Non-probabilistic convenience sample (N = 270): students of the last year of Bachelor\u27s degrees in Speech Therapy, Nursing and Production in Bioimaging who participated voluntarily. A semi-structured, online survey form and informed consent were used. Descriptive statistics: measures of frequency, central tendency and dispersion. Inferential statistics: Chi Square test (α = 0.05) Survey responses were in a 88.52% from the female gender. The nutritional status according to BMI showed a predominance of students in normal weight condition (60.74%), mean of 25.23 ± 6.03. In relation to environmental protection behaviors: 50% referred to habitually control food waste and 58,2% practice the reuse of food waste. Energy sources control (54.07%) and measured use of water for food preparation (60.74%) was majority adhesion. The selection of foods produced with less environmental impact showed highly dispersed behaviors. About farming for self-consumption, 46.67% claimed not to practice. An association was observed between nutritional status (NS) and consciousness about food waste levels, such as between NS and farming for self-consumption. Conclusion: Frequent monitoring in the use of water, energy sources and food waste were contributory practices to safeguard the environment, and most of students adhered to that. The nutritional status of the students, though, was not related to all these assessed practices. It is still necessary to continue working on the value of different practices for the protection of the environment as a health factor for students.Desde las nuevas teorías del desarrollo humano sostenible que procuran consolidar mejores oportunidades para las personas en su dimensión social, económica y ambiental, en perspectiva intergeneracional, los profesionales de la salud desde su rol de cuidadores y promotores deben contribuir.  Nos preguntamos si el cuidado de la salud alimentaria nutricional encuentra activados a los futuros profesionales en favor de conductas de protección al medio ambiente. Objetivo: determinar la inclusión de conductas de resguardo al medio ambiente en el manejo de la alimentación y su relación con el estado nutricional en estudiantes avanzados en ciencias de la salud. Estudio descriptivo, observacional, correlacional, corte transversal. Universo: estudiantes del último curso de carreras de FCM, UNC (2020). Muestra no probabilística por conveniencia(N= 270): estudiantes del último curso de  Licenciaturas en Fonoaudiología, Enfermería y Producción en Bioimágenes que participaron voluntariamente. Se empleó formulario de encuesta semiestructurada, on line y consentimiento informado.  Estadística descriptiva: medidas de frecuencia, tendencia central y dispersión. Estadística inferencial: Test de Chi Cuadrado (α=0,05) Los encuestados representaron  88, 52% al género femenino. El estado nutricional según IMC mostró predominio de estudiantes en condición normopeso (60,74%), media de 25,23 ± 6, 03. En relación a conductas de resguardo al medio ambiente: el 50% refirió controlar habitualmente desperdicios alimentarios y el 58,2% practicar la reutilización de sobrantes alimentarios. El control del uso de fuentes energéticas (54,07%) y del agua para la preparación de alimentos (60,74%) fue de adhesión mayoritaria. La selección de alimentos  producidos con menor impacto ambiental mostró conductas de alta dispersión. Al cultivo para autoconsumo, el  46,67% refirió no practicarlo.  Se observó asociación entre estado nutricional (EN) y cuidado del nivel de desperdicios alimentarios, como entre EN y el cultivo para autoconsumo. Conclusión: El control habitual en el manejo del agua, fuentes energéticas y sobrantes alimentarios fueron prácticas contributivas al resguardo del medio ambiente a las que mayoritariamente adhirieron los estudiantes. El estado nutricional de los estudiantes no guardó relación con todas las prácticas valoradas. Es necesario continuar trabajando el valor de distintas prácticas para la protección del medio ambiente como factor de salud en los estudiantes.

Mechanisms involved in acquisition of bla<inf>NDM</inf> genes by IncA/C<inf>2</inf> and IncFII<inf>Y</inf> plasmids

Copyright © 2016, American Society for Microbiology. All Rights Reserved. blaNDM genes confer carbapenem resistance and have been identified on transferable plasmids belonging to different incompatibility (Inc) groups. Here we present the complete sequences of four plasmids carrying a blaNDM gene, pKP1-NDM-1, pEC2-NDM-3, pECL3-NDM-1, and pEC4-NDM-6, from four clinical samples originating from four different patients. Different plasmids carry segments that align to different parts of the blaNDM region found on Acinetobacter plasmids. pKP1-NDM-1 and pEC2-NDM-3, from Klebsiella pneumoniae and Escherichia coli, respectively, were identified as type 1 IncA/C2 plasmids with almost identical backbones. Different regions carrying blaNDM are inserted in different locations in the antibiotic resistance island known as ARI-A, and ISCR1 may have been involved in the acquisition of blaNDM-3 by pEC2-NDM-3. pECL3-NDM-1 and pEC4-NDM-6, from Enterobacter cloacae and E. coli, respectively, have similar IncFIIY backbones, but different regions carrying blaNDM are found in different locations. Tn3-derived inverted-repeat transposable elements (TIME) appear to have been involved in the acquisition of blaNDM-6 by pEC4-NDM-6 and the rmtC 16S rRNA methylase gene by IncFIIY plasmids. Characterization of these plasmids further demonstrates that even very closely related plasmids may have acquired blaNDM genes by different mechanisms. These findings also illustrate the complex relationships between antimicrobial resistance genes, transposable elements, and plasmids and provide insights into the possible routes for transmission of blaNDM genes among species of the Enterobacteriaceae family

Inflammatory-mediated repression of the rat ileal sodium-dependent bile acid transporter by c-fos nuclear translocation

AbstractBackground & Aims: Ileal malabsorption of bile salts is observed in Crohn's ileitis. We define the transcriptional mechanisms involved in cytokine-mediated repression of the rat apical sodium-dependent bile acid transporter (ASBT). Methods: ASBT regulation was studied in IL-1β–treated IEC-6 and Caco-2 cells and in indomethacin-treated rats. Results: Indomethacin-induced ileitis in Lewis rats leads to specific reductions in ileal ASBT messenger RNA and protein levels, whereas c-jun and c-fos are induced. The proinflammatory cytokines interleukin-1β and tumor necrosis factor repress the activity of the ASBT promoter in Caco-2 and intestinal epithelial cell-6 cells. This effect is blocked by the proteasome inhibitor, MG-132, or by the phosphatidyl inositol 3-kinase inhibitor, wortmannin. Indomethacin (in vivo) or proinflammatory cytokine (in vitro) treatment leads to serine phosphorylation and nuclear translocation of c-fos. Mutation of a 5' activated protein (AP)-1 site inactivates the ASBT promoter, whereas mutation of the 3' site abrogates the proinflammatory cytokine–mediated repression. The 5' site binds a c-jun homodimer, whereas the 3' site binds a c-jun/c-fos heterodimer. c-Jun overexpression enhances ASBT promoter activity, whereas a dominant negative c-jun construct inactivates the promoter. c-Fos overexpression represses promoter activity. A 27 base pair cis-element from the 3' site in the ASBT promoter imparts cytokine-mediated down-regulation to a heterologous SV40 promoter construct. Conclusions: The ASBT promoter contains 2 distinct cis AP-1 elements; the 5' element binds homodimeric c-jun and mediates basal transcription. Inflammation is associated with up-regulation, phosphorylation, and nuclear translocation of c-fos, which then represses ASBT promoter activity via binding of the 3' AP-1 element by a c-fos/c-jun heterodimer.GASTROENTEROLOGY 2002;123:2005-201

WordCloud: a Cytoscape plugin to create a visual semantic summary of networks

<p>Abstract</p> <p>Background</p> <p>When biological networks are studied, it is common to look for clusters, i.e. sets of nodes that are highly inter-connected. To understand the biological meaning of a cluster, the user usually has to sift through many textual annotations that are associated with biological entities.</p> <p>Findings</p> <p>The WordCloud Cytoscape plugin generates a visual summary of these annotations by displaying them as a tag cloud, where more frequent words are displayed using a larger font size. Word co-occurrence in a phrase can be visualized by arranging words in clusters or as a network.</p> <p>Conclusions</p> <p>WordCloud provides a concise visual summary of annotations which is helpful for network analysis and interpretation. WordCloud is freely available at <url>http://baderlab.org/Software/WordCloudPlugin</url></p

Gitools: Analysis and Visualisation of Genomic Data Using Interactive Heat-Maps

Intuitive visualization of data and results is very important in genomics, especially when many conditions are to be analyzed and compared. Heat-maps have proven very useful for the representation of biological data. Here we present Gitools (http://www.gitools.org), an open-source tool to perform analyses and visualize data and results as interactive heat-maps. Gitools contains data import systems from several sources (i.e. IntOGen, Biomart, KEGG, Gene Ontology), which facilitate the integration of novel data with previous knowledge