GOLD.db: genomics of lipid-associated disorders database

BACKGROUND: The GOLD.db (Genomics of Lipid-Associated Disorders Database) was developed to address the need for integrating disparate information on the function and properties of genes and their products that are particularly relevant to the biology, diagnosis management, treatment, and prevention of lipid-associated disorders. DESCRIPTION: The GOLD.db provides a reference for pathways and information about the relevant genes and proteins in an efficiently organized way. The main focus was to provide biological pathways with image maps and visual pathway information for lipid metabolism and obesity-related research. This database provides also the possibility to map gene expression data individually to each pathway. Gene expression at different experimental conditions can be viewed sequentially in context of the pathway. Related large scale gene expression data sets were provided and can be searched for specific genes to integrate information regarding their expression levels in different studies and conditions. Analytic and data mining tools, reagents, protocols, references, and links to relevant genomic resources were included in the database. Finally, the usability of the database was demonstrated using an example about the regulation of Pten mRNA during adipocyte differentiation in the context of relevant pathways. CONCLUSIONS: The GOLD.db will be a valuable tool that allow researchers to efficiently analyze patterns of gene expression and to display them in a variety of useful and informative ways, allowing outside researchers to perform queries pertaining to gene expression results in the context of biological processes and pathways

The complement of protein kinases of the microsporidium Encephalitozoon cuniculi in relation to those of Saccharomyces cerevisiae and Schizosaccharomyces pombe.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Microsporidia, parasitic fungi-related eukaryotes infecting many cell types in a wide range of animals (including humans), represent a serious health threat in immunocompromised patients. The 2.9 Mb genome of the microsporidium Encephalitozoon cuniculi is the smallest known of any eukaryote. Eukaryotic protein kinases are a large superfamily of enzymes with crucial roles in most cellular processes, and therefore represent potential drug targets. We report here an exhaustive analysis of the E. cuniculi genomic database aimed at identifying and classifying all protein kinases of this organism with reference to the kinomes of two highly-divergent yeast species, Saccharomyces cerevisiae and Schizosaccharomyces pombe. RESULTS: A database search with a multi-level protein kinase family hidden Markov model library led to the identification of 29 conventional protein kinase sequences in the E. cuniculi genome, as well as 3 genes encoding atypical protein kinases. The microsporidian kinome presents striking differences from those of other eukaryotes, and this minimal kinome underscores the importance of conserved protein kinases involved in essential cellular processes. Approximately 30% of its kinases are predicted to regulate cell cycle progression while another approximately 28% have no identifiable homologues in model eukaryotes and are likely to reflect parasitic adaptations. E. cuniculi lacks MAP kinase cascades and almost all protein kinases that are involved in stress responses, ion homeostasis and nutrient signalling in the model fungi S. cerevisiae and S. pombe, including AMPactivated protein kinase (Snf1), previously thought to be ubiquitous in eukaryotes. A detailed database search and phylogenetic analysis of the kinomes of the two model fungi showed that the degree of homology between their kinomes of approximately 85% is much higher than that previously reported. CONCLUSION: The E. cuniculi kinome is by far the smallest eukaryotic kinome characterised to date. The difficulty in assigning clear homology relationships for nine out of the twentynine microsporidian conventional protein kinases despite its compact genome reflects the phylogenetic distance between microsporidia and other eukaryotes. Indeed, the E. cuniculi genome presents a high proportion of genes in which evolution has been accelerated by up to four-fold. There are no orthologues of the protein kinases that constitute MAP kinase pathways and many other protein kinases with roles in nutrient signalling are absent from the E. cuniculi kinome. However, orthologous kinases can nonetheless be identified that correspond to members of the yeast kinomes with roles in some of the most fundamental cellular processes. For example, E. cuniculi has clear orthologues of virtually all the major conserved protein kinases that regulate the core cell cycle machinery (Aurora, Polo, DDK, CDK and Chk1). A comprehensive comparison of the homology relationships between the budding and fission yeast kinomes indicates that, despite an estimated 800 million years of independent evolution, the two model fungi share approximately 85% of their protein kinases. This will facilitate the annotation of many of the as yet uncharacterised fission yeast kinases, and also those of novel fungal genomes.Published versio

Hard-wired heterogeneity in blood stem cells revealed using a dynamic regulatory network model

Motivation: Combinatorial interactions of transcription factors with cis-regulatory elements control the dynamic progression through successive cellular states and thus underpin all metazoan development. The construction of network models of cis-regulatory elements, therefore, has the potential to generate fundamental insights into cellular fate and differentiation. Haematopoiesis has long served as a model system to study mammalian differentiation, yet modelling based on experimentally informed cis-regulatory interactions has so far been restricted to pairs of interacting factors. Here, we have generated a Boolean network model based on detailed cis-regulatory functional data connecting 11 haematopoietic stem/progenitor cell (HSPC) regulator genes. Results: Despite its apparent simplicity, the model exhibits surprisingly complex behaviour that we charted using strongly connected components and shortest-path analysis in its Boolean state space. This analysis of our model predicts that HSPCs display heterogeneous expression patterns and possess many intermediate states that can act as ‘stepping stones' for the HSPC to achieve a final differentiated state. Importantly, an external perturbation or ‘trigger' is required to exit the stem cell state, with distinct triggers characterizing maturation into the various different lineages. By focusing on intermediate states occurring during erythrocyte differentiation, from our model we predicted a novel negative regulation of Fli1 by Gata1, which we confirmed experimentally thus validating our model. In conclusion, we demonstrate that an advanced mammalian regulatory network model based on experimentally validated cis-regulatory interactions has allowed us to make novel, experimentally testable hypotheses about transcriptional mechanisms that control differentiation of mammalian stem cells. Contact: [email protected] or [email protected] or [email protected] Supplementary information: Supplementary data are available at Bioinformatics onlin

Parents' Perceptions about Salt Consumption in Urban Areas of Peru: Formative Research for a Social Marketing Strategy.

BACKGROUND: Salt intakes in Latin America currently double the World Health Organization's recommendation of 5 g/day. Various strategies to reduce the population's salt consumption, such as raising awareness using social marketing, have been recommended. This study identified parents' perceptions of salt consumption to inform a social marketing strategy focused on urban areas in Peru. METHODS: Using a sequential exploratory methods design, parents of pre-school children, of high and low socioeconomic status, provided qualitative data in the form of interviews and focus groups. Following this, quantitative data was obtained via questionnaires, which were sent to all parents. The information was analyzed jointly. RESULTS: 296 people (mean age 35.4, 82% women) participated, 64 in the qualitative and 232 in the quantitative phase of the study. Qualitative data from the first phase revealed that the majority of mothers were in charge of cooking, and female participants expressed that cooking was "their duty" as housewives. The qualitative phase also revealed that despite the majority of the participants considered their salt intake as adequate, half of them mentioned that they have tried to reduce salt consumption, and the change in the flavor of the food was stated as the most difficult challenge to continue with such practice. Quantitative data showed that 67% of participants would be willing to reduce their salt intake, and 79.7% recognized that high salt intake causes hypertension. In total, 84% of participants reaffirmed that mothers were in charge of cooking. There were no salient differences in terms of responses provided by participants from high versus low socioeconomic groups. CONCLUSIONS: The results point towards the identification of women as a potential target-audience of a social marketing strategy to promote reductions in salt intake in their families and, therefore, a gender-responsive social marketing intervention is recommended

Plan de negocios para la creación de una frutícola sostenible

El bajo aprovechamiento agrícola en la región La Libertad, ha originado que exista una economía desigual, que no ha favorecido a las comunidades locales; sistemas de comercio no sostenibles, que han generado impactos negativos al cuidado del medio ambiente; poca valoración a su biodiversidad, que ha originado una falta de identidad cultural en la región, y poca promoción al consumo local, que ha provocado que se frene la competitividad en la producción, distribución y comercialización de frutas en la región. El consumo local de frutas ha sido desplazado por la producción de alimentos a escala industrial, teniendo como consecuencia que el seguimiento de parámetros de calidad de los productos quede en manos de los intermediarios comerciales. Ante esta problemática, se plantea la creación del proyecto empresarial FRUTAGRO S.A.C, que se origina con el fin de explotar el máximo potencial agrícola de frutas que existen en la región La Libertad, con cadenas de suministros cortas e inclusivas que contará con la participación activa de los pequeños productores de frutas de la zona, con el fin de promover el consumo de frutas locales o de proximidad y de esa manera revalorar su biodiversidad, y asimismo contribuir a un consumo más responsable y sostenible. La unidad empresarial se dedicará al acopio, procesamiento y comercialización de frutas locales o de proximidad de alta calidad. Para diferenciarse de sus principales competidores y garantizar la calidad de sus productos, la empresa desarrollará una cadena de suministro corta e inclusiva con fruticultores de la región, a fin de asegurar el abastecimiento de la materia prima y el mejoramiento de la misma, en línea con la mejora en la calidad de vida de los fruticultores locales. Esta asociación, y el impacto positivo sobre la sociedad y el medio ambiente permitirán la estabilidad de la oferta de FRUTAGRO, vital para el posicionamiento de sus productos y fidelización de sus clientes. El horizonte de evaluación del proyecto es de 5 años. Este, considera una inversión inicial por un monto equivalente a S/ 91,387.00, financiado 60% a través de aportes de accionistas y 40% mediante deuda bancaria de largo plazo con una TCEA del 8%, respectivamente. El Valor Presente Neto Económico resultante asciende a S/ 231,411.03, con un periodo de recupero de la inversión de 3.17 años, un ratio de beneficio-costo de 2.99, finalmente una TIR de 37.90%.The low level of agricultural use in the region of La Libertad has led to an unequal economy that has not favored local communities; unsustainable trade systems that have had a negative impact on the environment; a lack of appreciation for its biodiversity, which has led to a lack of cultural identity in the region; and little promotion of local consumption, which has slowed competitiveness in the production, distribution, and marketing of fruit in the region. Local fruit consumption has been displaced by industrial-scale food production, with the result that the monitoring of product quality parameters is left in the hands of commercial intermediaries. Faced with this problem, the FRUTAGRO S.A.C. business project was created to exploit the maximum agricultural potential of fruits that exist in the region of La Libertad, with short and inclusive supply chains that will have the active participation of small fruit producers in the area, in order to promote the consumption of local fruits or from a proximity and thus revalue their biodiversity, and also contribute to a more responsible and sustainable consumption. The business unit will be dedicated to the collection, processing, and marketing of high quality local fruit or from a proximity. To differentiate itself from its main competitors and guarantee the quality of its products, the company will develop a short and inclusive supply chain with fruit growers in the region to ensure the supply of raw materials and their improvement, in line with the improvement in the quality of life of local fruit growers. This partnership, and the positive impact on society and the environment, will allow FRUTAGRO's supply stability, which is vital for the positioning of its products and customer loyalty. The project evaluation horizon is 5 years. It considers an initial investment for an amount equivalent to S/ 91,387.00, 60% of the amount is financed through shareholder contributions and 40% through long-term bank debt with an TCEA of 8 %, respectively. The resulting Economic Net Present Value amounts to S/ 231,411.03, with a payback period of 3.17 years, a benefit-cost ratio of 2.99, and finally a TIR of 37.90%

Antarctic research at a time of crisis: The impact of COVID-19 on the Antarctic research community

This presentation will share the results of a survey that aimed at understandingthe impact of COVID-19 on the Antarctic research community. Primarilydesigned to identify the most adversely affected Antarctic researchers andgauge what kind of assistance they might need, the survey, which forms partof an interdisciplinary international research programme on the impact of COVID-19 for the Antarctic community more broadly, also examined the longtermimplications of COVID-19 for National Antarctic Programmes.Over 300 Antarctic research community members, most of them academics,participated in the survey. Preliminary results show that the careers of earlycareerresearchers and those heavily reliant on fieldwork are most adverselyaffected by COVID-19. As expected, relief funds and free access to data,especially for those whose field campaigns were cancelled, would moderatethe impact the pandemic has had on researchers to a certain extent. The survey also reveals that COVID-19 resulted in significant adverse impacts onmental health for Antarctic researchers, with the majority of survey participants noting extreme or moderate dissatisfaction with their mental health and significant increases in anxiety and stress levels, all of which needs to be considered when designing strategies for addressing the impact of COVID-19 in the Antarctic community.Fil: Ligget, Daniela. University of Canterbury; Nueva ZelandaFil: Herbert, Andrea. University of Canterbury; Nueva ZelandaFil: Badhe, Renuka. European Polar Board; Países BajosFil: Hudson, Katelyn. Bond University; AustraliaFil: Kelman, Ilan. University College London; Estados UnidosFil: Sang Lee, Won. Korea Polar Research Institute; Corea del SurFil: Lorenzo, Cristian A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; Argentina. Universidad Nacional de Tierra del Fuego; ArgentinaFil: Marques Quinteiro, Pedro. Instituto Universitário; PortugalFil: Nash, Meredith. University of Tasmania; AustraliaFil: Navarro, Diego. Korea Polar Research Institute; Corea del SurFil: Nieboer, Miranda. University of Tasmania; AustraliaFil: Pickett, Jennifer. Vrije Unviversiteit Brussel; BélgicaFil: Estenssoro Saavedra, Fernando. Universidad de Santiago de Chile; ChileFil: Yermakova, Yelena. University of Oslo; NoruegaNew Zealand Antarctic Science ConferenceNueva ZelandaUniversity of CanterburyAntarctic Research CentreThe University of WaikatoInternational Centre for Terrestrial Antartic ResearchBodeker ScientficVictoria University of Wellingto

Genome-wide enhancer prediction from epigenetic signatures using genetic algorithm-optimized support vector machines

The chemical modification of histones at specific DNA regulatory elements is linked to the activation, inactivation and poising of genes. A number of tools exist to predict enhancers from chromatin modification maps, but their practical application is limited because they either (i) consider a smaller number of marks than those necessary to define the various enhancer classes or (ii) work with an excessive number of marks, which is experimentally unviable. We have developed a method for chromatin state detection using support vector machines in combination with genetic algorithm optimization, called ChromaGenSVM. ChromaGenSVM selects optimum combinations of specific histone epigenetic marks to predict enhancers. In an independent test, ChromaGenSVM recovered 88% of the experimentally supported enhancers in the pilot ENCODE region of interferon gamma-treated HeLa cells. Furthermore, ChromaGenSVM successfully combined the profiles of only five distinct methylation and acetylation marks from ChIP-seq libraries done in human CD4+ T cells to predict ∼21 000 experimentally supported enhancers within 1.0 kb regions and with a precision of ∼90%, thereby improving previous predictions on the same dataset by 21%. The combined results indicate that ChromaGenSVM comfortably outperforms previously published methods and that enhancers are best predicted by specific combinations of histone methylation and acetylation marks

Distinct transcriptional regulatory modules underlie STAT3's cell type-independent and cell type-specific functions

Transcription factors (TFs) regulate gene expression by binding to short DNA sequence motifs, yet their binding specificities alone cannot explain how certain TFs drive a diversity of biological processes. In order to investigate the factors that control the functions of the pleiotropic TF STAT3, we studied its genome-wide binding patterns in four different cell types: embryonic stem cells, CD4+ T cells, macrophages and AtT-20 cells. We describe for the first time two distinct modes of STAT3 binding. First, a small cell type-independent mode represented by a set of 35 evolutionarily conserved STAT3-binding sites that collectively regulate STAT3's own functions and cell growth. We show that STAT3 is recruited to sites with E2F1 already pre-bound before STAT3 activation. Second, a series of different transcriptional regulatory modules (TRMs) assemble around STAT3 to drive distinct transcriptional programs in the four cell types. These modules recognize cell type-specific binding sites and are associated with factors particular to each cell type. Our study illustrates the versatility of STAT3 to regulate both universal- and cell type-specific functions by means of distinct TRMs, a mechanism that might be common to other pleiotropic TFs. © The Author(s) 2013. Published by Oxford University Press.Link_to_subscribed_fulltex

Draft Genome of the Filarial Nematode Parasite \u3ci\u3eBrugia malayi\u3c/i\u3e

Parasitic nematodes that cause elephantiasis and river blindness threaten hundreds of millions of people in the developing world. We have sequenced the ∼90 megabase (Mb) genome of the human filarial parasite Brugia malayi and predict ∼11,500 protein coding genes in 71 Mb of robustly assembled sequence. Comparative analysis with the free-living, model nematode Caenorhabditis elegans revealed that, despite these genes having maintained little conservation of local synteny during ∼350 million years of evolution, they largely remain in linkage on chromosomal units. More than 100 conserved operons were identified. Analysis of the predicted proteome provides evidence for adaptations of B. malayi to niches in its human and vector hosts and insights into the molecular basis of a mutualistic relationship with its Wolbachia endosymbiont. These findings offer a foundation for rational drug design