Computational analysis of the interaction between transcription factors and the predicted secreted proteome of the yeast Kluyveromyces lactis

<p>Abstract</p> <p>Background</p> <p>Protein secretion is a cell translocation process of major biological and technological significance. The secretion and downstream processing of proteins by recombinant cells is of great commercial interest. The yeast <it>Kluyveromyces lactis </it>is considered a promising host for heterologous protein production. Because yeasts naturally do not secrete as many proteins as filamentous fungi, they can produce secreted recombinant proteins with few contaminants in the medium. An ideal system to address the secretion of a desired protein could be exploited among the native proteins in certain physiological conditions. By applying algorithms to the completed <it>K. lactis </it>genome sequence, such a system could be selected. To this end, we predicted protein subcellular locations and correlated the resulting extracellular secretome with the transcription factors that modulate the cellular response to a particular environmental stimulus.</p> <p>Results</p> <p>To explore the potential <it>Kluyveromyces lactis </it>extracellular secretome, four computational prediction algorithms were applied to 5076 predicted <it>K. lactis </it>proteins from the genome database. SignalP v3 identified 418 proteins with N-terminal signal peptides. From these 418 proteins, the Phobius algorithm predicted that 176 proteins have no transmembrane domains, and the big-PI Predictor identified 150 proteins as having no glycosylphosphatidylinositol (GPI) modification sites. WoLF PSORT predicted that the <it>K. lactis </it>secretome consists of 109 putative proteins, excluding subcellular targeting. The transcription regulators of the putative extracellular proteins were investigated by searching for DNA binding sites in their putative promoters. The conditions to favor expression were obtained by searching Gene Ontology terms and using graph theory.</p> <p>Conclusion</p> <p>A public database of <it>K. lactis </it>secreted proteins and their transcription factors are presented. It consists of 109 ORFs and 23 transcription factors. A graph created from this database shows 134 nodes and 884 edges, suggesting a vast number of relationships to be validated experimentally. Most of the transcription factors are related to responses to stress such as drug, acid and heat resistance, as well as nitrogen limitation, and may be useful for inducing maximal expression of potential extracellular proteins.</p

Development of a Brazilian maize core collection

The aim of this study was to evaluate methods for developing a Brazilian maize core collection. For an initial survey of the active collection, passport information, as well as characterization and evaluation of accessions, were taken into consideration, these then being divided according to geographic region and kernel-type. Multiple sampling methods were evaluated. The strategy of constant sampling generated extensive alterations in extract accession frequency. The multivariate strategy with dispersion graphs and principal components associated with the Tocher method was considered efficient for identifying the most divergent genotypes. The multivariate strategy generated greater alterations in the variance of traits. The average number of traits revealed few modifications with the various sampling strategies used. Therefore, the active collection could be considered as possessing a satisfactory amount of information for most of its accessions. Moreover, the multivariate strategy generated modifications in the variance of the traits, independent of sampling intensity

Effect of Acute Posttransplant Renal Failure on the Survival of Perfused Cadaver Kidneys

Between 7973 and 7977 we encountered 22 cases of acute renal failure after transplantation in 70 patients who received perfused cadaver kidneys. Nearly two-thirds of 76 nonfunctioning grafts were lost due to subsequent superimposed rejection, often undetected and, hence, untreated. Thirty-one percent of the 76 recovered function. The recovery rate, we believe, can be improved by earlier diagnosis and treatment of rejection and by avoiding invasive diagnostic procedures in the early postoperative period. If the oliguric period extends beyond two weeks, a closed percutaneous renal biopsy is justified. The diagnosis of rejection and/or other abnormality as well as subsequent treatment are very important in these patients

Retrospective analysis of risk factors and gaps in prevention strategies for mother-to-child HIV transmission in Rio de Janeiro, Brazil

Background Despite great progress made in methods to prevent mother-to-child transmission of HIV (MTCT), delivery and uptake of these measures remains a challenge in many countries. Although the Brazilian Ministry of Health aimed to eliminate MTCT by 2015, infection still occured in 15–24% of infants born to HIV-infected mothers. We sought to identify remaining factors that constrain MTCT elimination. Methods We conducted a retrospective, matched case-control study by reviewing hospital charts of infants born to HIV-infected mothers between 1997 and 2014 at three MTCT reference hospitals in the Rio de Janeiro metropolitan area. Cases were defined as HIV-exposed children with two positive HIV tests before 18 months of age; controls were defined as HIV-exposed children with two negative HIV tests before 18 months of age. We performed bivariate and MTCT cascade analyses to identify risk factors for MTCT and gaps in prevention services. Results We included 435 infants and their mothers (145 cases, 290 controls). Bivariate analyses of MTCT preventative care (PMTCT) indicated that cases were less likely to complete all individual measures in the antenatal, delivery, and postnatal period (p < 0.05). Assessing completion of the PMTCT cascade, the sequential steps of PMTCT interventions, we found inadequate retention in care among both cases and controls, and cases were significantly less likely than controls to continue receiving care throughout the cascade (p < 0.05). Motives for incompletion of PMTCT measures included infrastructural issues, such as HIV test results not being returned, but were most often due to lack of care-seeking. Over the course of the study period, PMTCT completion improved, although it remained below the 95% target for antenatal care, HIV testing, and antenatal ART set by the WHO. Adding concern, evaluation of co-infections indicated that case infants were also more likely to have congenital syphilis (OR: 4.29; 95% CI: 1.66 to 11.11). Conclusions While PMTCT coverage has improved over the years, completion of services remains insufficient. Along with interventions to promote care-seeking behaviour, increased infrastructural support for PMTCT services is needed to meet the HIV MTCT elimination goal in Brazil as well as address rising national rates of congenital syphilis