The EurOPDX Data Portal: an open platform for patient-derived cancer xenograft data sharing and visualization.

Background: Patient-derived xenografts (PDX) mice models play an important role in preclinical trials and personalized medicine. Sharing data on the models is highly valuable for numerous reasons - ethical, economical, research cross validation etc. The EurOPDX Consortium was established 8 years ago to share such information and avoid duplicating efforts in developing new PDX mice models and unify approaches to support preclinical research.

Semalytics: a semantic analytics platform for the exploration of distributed and heterogeneous cancer data in translational research.

Each cancer is a complex system with unique molecular features determining its dynamics, such as its prognosis and response to therapies. Understanding the role of these biological traits is fundamental in order to personalize cancer clinical care according to the characteristics of each patient's disease. To achieve this, translational researchers propagate patients' samples through in vivo and in vitro cultures to test different therapies on the same tumor and to compare their outcomes with the molecular profile of the disease.

One tool to find them all: a case of data integration and querying in a distributed LIMS platform.

In the last years, Laboratory Information Management Systems (LIMS) have been growing from mere inventory systems into increasingly comprehensive software platforms, spanning functionalities as diverse as data search, annotation and analysis. Our institution started in 2011 a LIMS project named the Laboratory Assistant Suite with the purpose of assisting researchers throughout all of their laboratory activities, providing graphical tools to support decision-making tasks and building complex analyses on integrated data. The modular architecture of the system exploits multiple databases with different technologies.

Mitochondrial Cochaperone Mge1 Is Involved in Regulating Susceptibility to Fluconazole in and Species.

encodes a yeast chaperone involved in Fe-S cluster metabolism and protein import into the mitochondria. In this study, we identified as a multicopy suppressor of susceptibility to the antifungal fluconazole in the model yeast We demonstrate that this phenomenon is not exclusively dependent on the integrity of the mitochondrial DNA or on the presence of the drug efflux pump Pdr5. Instead, we show that the increased dosage of Mge1 plays a protective role by retaining increased amounts of ergosterol upon fluconazole treatment.

Selective analysis of cancer-cell intrinsic transcriptional traits defines novel clinically relevant subtypes of colorectal cancer.

Stromal content heavily impacts the transcriptional classification of colorectal cancer (CRC), with clinical and biological implications. Lineage-dependent stromal transcriptional components could therefore dominate over more subtle expression traits inherent to cancer cells. Since in patient-derived xenografts (PDXs) stromal cells of the human tumour are substituted by murine counterparts, here we deploy human-specific expression profiling of CRC PDXs to assess cancer-cell intrinsic transcriptional features.

Characterising atypical Candida albicans clinical isolates from six third-level hospitals in Bogotá, Colombia.

Background: Candida species are the most frequently found fungal pathogens causing nosocomial disease in a hospital setting. Such species must be correctly identified to ensure that appropriate control measures are taken and that suitable treatment is given for each species. Candida albicans is causing most fungal disease burden worldwide; the challenge lies in differentiating it from emerging atypical, minor and related species such as Candida dubliniensis and Candida africana.

Deletion of the DNA Ligase IV Gene in Candida glabrata Significantly Increases Gene-Targeting Efficiency.

Candida glabrata is reported as the second most prevalent human opportunistic fungal pathogen in the United States. Over the last decades, its incidence increased, whereas that of Candida albicans decreased slightly. One of the main reasons for this shift is attributed to the inherent tolerance of C.

New echinocandin susceptibility patterns for nosocomial Candida albicans in Bogotá, Colombia, in ten tertiary care centres: an observational study.

Background: Candida albicans remains as the first cause of nosocomial fungal infections in hospitals worldwide and its susceptibility pattern should be better described in our tertiary care hospitals.

Methods: This study aimed at identifying the caspofungin susceptibility pattern regarding nosocomial Candida albicans infection in ten tertiary care hospitals using the methodology proposed by CLSI M27-A3 and CLSI M27-S4, and its association with risk factors and clinical outcome. The approach involved descriptive research concerning the diagnosis of nosocomial infection during a 7-month period in 10 hospitals in Bogotá, Colombia.

Ascorbic acid inhibition of Candida albicans Hsp90-mediated morphogenesis occurs via the transcriptional regulator Upc2.

Morphogenetic transitions of the opportunistic fungal pathogen Candida albicans are influenced by temperature changes, with induction of filamentation upon a shift from 30 to 37°C. Hsp90 was identified as a major repressor of an elongated cell morphology at low temperatures, as treatment with specific inhibitors of Hsp90 results in elongated growth forms at 30°C. Elongated growth resulting from a compromised Hsp90 is considered neither hyphal nor pseudohyphal growth.

LAS: a software platform to support oncological data management.

The rapid technological evolution in the biomedical and molecular oncology fields is providing research laboratories with huge amounts of complex and heterogeneous data. Automated systems are needed to manage and analyze this knowledge, allowing the discovery of new information related to tumors and the improvement of medical treatments. This paper presents the Laboratory Assistant Suite (LAS), a software platform with a modular architecture designed to assist researchers throughout diverse laboratory activities.

The heat-induced molecular disaggregase Hsp104 of Candida albicans plays a role in biofilm formation and pathogenicity in a worm infection model.

The consequences of deprivation of the molecular chaperone Hsp104 in the fungal pathogen Candida albicans were investigated. Mutants lacking HSP104 became hypersusceptible to lethally high temperatures, similarly to the corresponding mutants of Saccharomyces cerevisiae, whereas normal susceptibility was restored upon reintroduction of the gene. By use of a strain whose only copy of HSP104 is an ectopic gene under the control of a tetracycline-regulated promoter, expression of Hsp104 prior to the administration of heat shock could be demonstrated to be sufficient to confer protection from the subsequent temperature increase.

Potent synergistic effect of doxycycline with fluconazole against Candida albicans is mediated by interference with iron homeostasis.

Doxycycline was found to act synergistically with the antifungal fluconazole against Candida albicans. Combination with doxycycline converts fluconazole from fungistatic to fungicidal, prevents the onset of drug resistance, and is also effective against a clinical isolate characterized by elevated resistance to fluconazole. Investigation of the interactions between the two drugs by way of checkerboard assays indicated that doxycycline had an influence on the MIC for fluconazole, as defined by CLSI standards, only at high concentrations (200 μg/ml).

Candida albicans Pde1p and Gpa2p comprise a regulatory module mediating agonist-induced cAMP signalling and environmental adaptation.

Deletion of PDE2, but not of PDE1 has been shown to reduce invasion and virulence. However simultaneous deletion of PDE2 and PDE1 abolishes these processes completely, suggesting that although Pde1 has a secondary role it also contributes to virulence in Candida albicans. In the present study the roles of the two phosphodiesterases, as well as that of Gpa2, in agonist-induced cAMP signalling, growth, morphogenesis and response to some stresses have been investigated.

Minimum number of genes for microarray feature selection.

A fundamental problem in microarray analysis is to identify relevant genes from large amounts of expression data. Feature selection aims at identifying a subset of features for building robust learning models. However, finding the optimal number of features is a challenging problem, as it is a trade off between information loss when pruning excessively and noise increase when pruning is too weak.

The painter's feature selection for gene expression data.

Feature selection is a fundamental task in microarray data analysis. It aims at identifying the genes which are mostly associated with a tissue category, disease state or clinical outcome. An effective feature selection reduces computation costs and increases classification accuracy.

KlADH3, a gene encoding a mitochondrial alcohol dehydrogenase, affects respiratory metabolism and cytochrome content in Kluyveromyces lactis.

A Kluyveromyces lactis strain, harbouring KlADH3 as the unique alcohol dehydrogenase (ADH) gene, was used in a genetic screen on allyl alcohol to isolate mutants deregulated in the expression of this gene. Here we report the characterization of some mutants that lacked or had highly reduced amounts of KlAdh3p activity; in addition, these mutants showed alterations in glucose metabolism, reduced respiration and reduced cytochrome content. Our results confirm that the KlAdh3p activity contributes to the reoxidation of cytosolic NAD(P)H feeding the respiratory chain through KlNdi1p, the mitochondrial internal transdehydrogenase.

Overexpression of the COX2 translational activator, Pet111p, prevents translation of COX1 mRNA and cytochrome c oxidase assembly in mitochondria of Saccharomyces cerevisiae.

Dramatically elevated levels of the COX2 mitochondrial mRNA-specific translational activator protein Pet111p interfere with respiratory growth and cytochrome c oxidase accumulation. The respiratory phenotype appears to be caused primarily by inhibition of the COX1 mitochondrial mRNA translation, a finding confirmed by lack of cox1Delta::ARG8(m) reporter mRNA translation. Interference with Cox1p synthesis depends to a limited extent upon increased translation of the COX2 mRNA, but is largely independent of it.

Evidence that synthesis of the Saccharomyces cerevisiae mitochondrially encoded ribosomal protein Var1p may be membrane localized.

The 5'-untranslated leaders of mitochondrial mRNAs appear to localize translation within the organelle. VAR1 is the only yeast mitochondrial gene encoding a major soluble protein. A chimeric mRNA bearing the VAR1 untranslated regions and the coding sequence for pre-Cox2p appears to be translated at the inner membrane surface.

Suppression of a nuclear frameshift mutation by a mitochondrial tRNA in the yeast Kluyveromyces lactis.

A fragment of mitochondrial DNA containing the Kluyveromyces lactis gene for valine-tRNA (tRNAVAL) was isolated as a multicopy suppressor of a respiratory-deficient mutant of this yeast. The mutant produced a truncated Cox14p because of a +1 frameshift mutation in COX14, a nuclear gene encoding a protein imported into mitochondria which is necessary for respiration (Fiori et al. 2000 Yeast 16: 307-314).