Piolhos hematófagos podem disseminar infecção pelo Trypanosoma cruzi em babuínos

Trypanosoma cruzi (Schyzotrypanum, Chagas, 1909), and Chagas disease are endemic in captive-reared baboons at the Southwest Foundation for Biomedical Research, San Antonio, Texas. We obtained PCR amplification products from DNA extracted from sucking lice collected from the hair and skin of T. cruzi-infected baboons, with specific nested sets of primers for the protozoan kinetoplast DNA, and nuclear DNA. These products were hybridized to their complementary internal sequences. Selected sequences were cloned and sequencing established the presence of T. cruzi nuclear DNA, and minicircle kDNA. Competitive PCR with a kDNA set of primers determined the quantity of approximately 23.9 ± 18.2 T. cruzi per louse. This finding suggests that the louse may be a vector incidentally contributing to the dissemination of T. cruzi infection in the baboon colony.As infecções pelo Trypanosoma cruzi e a doença de Chagas são endêmicas em babuínos (Papio hamadryas) reproduzidos em cativeiro na Southwest Foundation for Biomedical Research, em Santo Antonio, Texas. Nós obtivemos produtos de amplificação por PCR do DNA extraído de piolhos colhidos do cabelo e da pele de babuínos chagásicos, com primers aneladores específicos para DNAs nuclear e de cinetoplasto do protozoário. Esses produtos foram hibridizados com suas respectivas seqüências internas complementares. Seqüências selecionadas foram clonadas e o sequenciamento demonstrou a presença de DNA nuclear de T. cruzi, e de minicírculo de kDNA. A PCR competitiva com primers de kDNA determinou a quantidade de aproximadamente 23.9 ± 18.2 T. cruzi por piolho. Este achado sugere que o piolho pode ser um vetor contribuindo para a disseminação de T. cruzi na colônia de babuínos

Formalization of taxon-based constraints to detect inconsistencies in annotation and ontology development

<p>Abstract</p> <p>Background</p> <p>The Gene Ontology project supports categorization of gene products according to their location of action, the molecular functions that they carry out, and the processes that they are involved in. Although the ontologies are intentionally developed to be taxon neutral, and to cover all species, there are inherent taxon specificities in some branches. For example, the process 'lactation' is specific to mammals and the location 'mitochondrion' is specific to eukaryotes. The lack of an explicit formalization of these constraints can lead to errors and inconsistencies in automated and manual annotation.</p> <p>Results</p> <p>We have formalized the taxonomic constraints implicit in some GO classes, and specified these at various levels in the ontology. We have also developed an inference system that can be used to check for violations of these constraints in annotations. Using the constraints in conjunction with the inference system, we have detected and removed errors in annotations and improved the structure of the ontology.</p> <p>Conclusions</p> <p>Detection of inconsistencies in taxon-specificity enables gradual improvement of the ontologies, the annotations, and the formalized constraints. This is progressively improving the quality of our data. The full system is available for download, and new constraints or proposed changes to constraints can be submitted online at <url>https://sourceforge.net/tracker/?atid=605890&group_id=36855</url>.</p

Extension of Longevity and Reduction of Inflammation is Ovarian-Dependent, but Germ Cell-Independent in Post-Reproductive Female Mice

Cardiovascular disease, rare in premenopausal women, increases sharply at menopause and is typically accompanied by chronic inflammation. Previous work in our laboratory demonstrated that replacing senescent ovaries in post-reproductive mice with young, actively cycling ovaries restored many health benefits, including decreased cardiomyopathy and restoration of immune function. Our objective here was to determine if depletion of germ cells from young transplanted ovaries would alter the ovarian-dependent extension of life and health span. Sixty-day-old germ cell-depleted and germ cell-containing ovaries were transplanted to post-reproductive, 17-month-old mice. Mean life span for female CBA/J mice is approximately 644 days. Mice that received germ cell-containing ovaries lived 798 days (maximum = 815 days). Mice that received germ cell-depleted ovaries lived 880 days (maximum = 1046 days), 29% further past the time of surgery than mice that received germ cell-containing ovaries. The severity of inflammation was reduced in all mice that received young ovaries, whether germ cell-containing or germ cell-depleted. Aging-associated inflammatory cytokine changes were reversed in post-reproductive mice by 4 months of new-ovary exposure. In summary, germ cell depletion enhanced the longevity-extending effects of the young, transplanted ovaries and, as with germ cell-containing ovaries, decreased the severity of inflammation, but did so independent of germ cells. Based on these observations, we propose that gonadal somatic cells are programed to preserve the somatic health of the organism with the intent of facilitating future germline transmission. As reproductive potential decreases or is lost, the incentive to preserve the somatic health of the organism is lost as well

Reductions in serum IGF-1 during aging impair health span

In lower or simple species, such as worms and flies, disruption of the insulin-like growth factor (IGF)-1 and the insulin signaling pathways has been shown to increase lifespan. In rodents, however, growth hormone (GH) regulates IGF-1 levels in serum and tissues and can modulate lifespan via/or independent of IGF- 1. Rodent models, where the GH/IGF-1 axis was ablated congenitally, show increased lifespan. However, in contrast to rodents where serum IGF-1 levels are high throughout life, in humans, serum IGF-1 peaks during puberty and declines thereafter during aging. Thus, animal models with congenital disruption of the GH/ IGF-1 axis are unable to clearly distinguish between developmental and age-related effects of GH/IGF-1 on health. To overcome this caveat, we developed an inducible liver IGF-1- deficient (iLID) mouse that allows temporal control of serum IGF- 1. Deletion of liver Igf -1 gene at one year of age reduced serum IGF-1 by 70% and dramatically impaired health span of the iLID mice. Reductions in serum IGF-1 were coupled with increased GH levels and increased basal STAT5B phosphorylation in livers of iLID mice. These changes were associated with increased liver weight, increased liver inflammation, increased oxidative stress in liver and muscle, and increased incidence of hepatic tumors. Lastly, despite elevations in serum GH, low levels of serum IGF-1 from 1 year of age compromised skeletal integrity and accelerated bone loss. We conclude that an intact GH/IGF-1 axis is essential to maintain health span and that elevated GH, even late in life, associates with increased pathology

Gene3D: merging structure and function for a Thousand genomes

Over the last 2 years the Gene3D resource has been significantly improved, and is now more accurate and with a much richer interactive display via the Gene3D website (http://gene3d.biochem.ucl.ac.uk/). Gene3D provides accurate structural domain family assignments for over 1100 genomes and nearly 10 000 000 proteins. A hidden Markov model library, constructed from the manually curated CATH structural domain hierarchy, is used to search UniProt, RefSeq and Ensembl protein sequences. The resulting matches are refined into simple multi-domain architectures using a recently developed in-house algorithm, DomainFinder 3 (available at: ftp://ftp.biochem.ucl.ac.uk/pub/gene3d_data/DomainFinder3/). The domain assignments are integrated with multiple external protein function descriptions (e.g. Gene Ontology and KEGG), structural annotations (e.g. coiled coils, disordered regions and sequence polymorphisms) and family resources (e.g. Pfam and eggNog) and displayed on the Gene3D website. The website allows users to view descriptions for both single proteins and genes and large protein sets, such as superfamilies or genomes. Subsets can then be selected for detailed investigation or associated functions and interactions can be used to expand explorations to new proteins. Gene3D also provides a set of services, including an interactive genome coverage graph visualizer, DAS annotation resources, sequence search facilities and SOAP services

PANTHER version 7: improved phylogenetic trees, orthologs and collaboration with the Gene Ontology Consortium

Protein Analysis THrough Evolutionary Relationships (PANTHER) is a comprehensive software system for inferring the functions of genes based on their evolutionary relationships. Phylogenetic trees of gene families form the basis for PANTHER and these trees are annotated with ontology terms describing the evolution of gene function from ancestral to modern day genes. One of the main applications of PANTHER is in accurate prediction of the functions of uncharacterized genes, based on their evolutionary relationships to genes with functions known from experiment. The PANTHER website, freely available at http://www.pantherdb.org, also includes software tools for analyzing genomic data relative to known and inferred gene functions. Since 2007, there have been several new developments to PANTHER: (i) improved phylogenetic trees, explicitly representing speciation and gene duplication events, (ii) identification of gene orthologs, including least diverged orthologs (best one-to-one pairs), (iii) coverage of more genomes (48 genomes, up to 87% of genes in each genome; see http://www.pantherdb.org/panther/summaryStats.jsp), (iv) improved support for alternative database identifiers for genes, proteins and microarray probes and (v) adoption of the SBGN standard for display of biological pathways. In addition, PANTHER trees are being annotated with gene function as part of the Gene Ontology Reference Genome project, resulting in an increasing number of curated functional annotations

MACiE: exploring the diversity of biochemical reactions

MACiE (which stands for Mechanism, Annotation and Classification in Enzymes) is a database of enzyme reaction mechanisms, and can be accessed from http://www.ebi.ac.uk/thornton-srv/databases/MACiE/. This article presents the release of Version 3 of MACiE, which not only extends the dataset to 335 entries, covering 182 of the EC sub-subclasses with a crystal structure available (∼90%), but also incorporates greater chemical and structural detail. This version of MACiE represents a shift in emphasis for new entries, from non-homologous representatives covering EC reaction space to enzymes with mechanisms of interest to our users and collaborators with a view to exploring the chemical diversity of life. We present new tools for exploring the data in MACiE and comparing entries as well as new analyses of the data and new searches, many of which can now be accessed via dedicated Perl scripts

Genome Expression Pathway Analysis Tool – Analysis and visualization of microarray gene expression data under genomic, proteomic and metabolic context

<p>Abstract</p> <p>Background</p> <p>Regulation of gene expression is relevant to many areas of biology and medicine, in the study of treatments, diseases, and developmental stages. Microarrays can be used to measure the expression level of thousands of mRNAs at the same time, allowing insight into or comparison of different cellular conditions. The data derived out of microarray experiments is highly dimensional and often noisy, and interpretation of the results can get intricate. Although programs for the statistical analysis of microarray data exist, most of them lack an integration of analysis results and biological interpretation.</p> <p>Results</p> <p>We have developed GEPAT, Genome Expression Pathway Analysis Tool, offering an analysis of gene expression data under genomic, proteomic and metabolic context. We provide an integration of statistical methods for data import and data analysis together with a biological interpretation for subsets of probes or single probes on the chip. GEPAT imports various types of oligonucleotide and cDNA array data formats. Different normalization methods can be applied to the data, afterwards data annotation is performed. After import, GEPAT offers various statistical data analysis methods, as hierarchical, k-means and PCA clustering, a linear model based t-test or chromosomal profile comparison. The results of the analysis can be interpreted by enrichment of biological terms, pathway analysis or interaction networks. Different biological databases are included, to give various information for each probe on the chip. GEPAT offers no linear work flow, but allows the usage of any subset of probes and samples as a start for a new data analysis. GEPAT relies on established data analysis packages, offers a modular approach for an easy extension, and can be run on a computer grid to allow a large number of users. It is freely available under the LGPL open source license for academic and commercial users at <url>http://gepat.sourceforge.net</url>.</p> <p>Conclusion</p> <p>GEPAT is a modular, scalable and professional-grade software integrating analysis and interpretation of microarray gene expression data. An installation available for academic users can be found at <url>http://gepat.bioapps.biozentrum.uni-wuerzburg.de</url>.</p

Improving disease gene prioritization using the semantic similarity of Gene Ontology terms

Motivation: Many hereditary human diseases are polygenic, resulting from sequence alterations in multiple genes. Genomic linkage and association studies are commonly performed for identifying disease-related genes. Such studies often yield lists of up to several hundred candidate genes, which have to be prioritized and validated further. Recent studies discovered that genes involved in phenotypically similar diseases are often functionally related on the molecular level