Biomedical subjects

Miguel A Andrade-Navarro

Publications and source records attributed to Miguel A Andrade-Navarro.

8 recordsLinked to original sources

PubMed2026

Integrative multi-omics analysis reveals lipid/metabolite dysregulation and temporal decoupling in disease progression.

Our study presents and applies a metabolomics-driven multi-omics integration strategy to elucidate dynamic pathway interactions during disease progression. We analyzed longitudinal metabolomics datasets from a Duchenne muscular dystrophy (DMD) mouse model (6-30 weeks) and an acute Bothrops asper envenomation model (1-24 h) to contrast chronic versus acute inflammation. In the DMD model, we predicted phased cross-talk between sphingolipid metabolism and neurotrophin signaling: an early proteomic surge followed by lipid-mediated amplification and a late convergence at the protein level. Arginine and proline metabolism exhibited early metabolite accumulation preceding delayed inferred protein changes, consistent with impaired nitric oxide synthesis and argininemia-like effect. We also predicted late-stage activation of the AGE-RAGE pathway in DMD, likely triggered by ceramide buildup, and an autophagy-related lipid metabolic shift at mid-stage. In the envenomation model, tryptophan-kynurenine and nicotinamide pathways for NAD⁺ biosynthesis were rapidly perturbed at the metabolite level (1-3 h) but induced corresponding predicted enzymes only by 24 h. Thyroid hormone signaling showed an early coupling of substrate availability (tyrosine surge at 1 h) with predicted stress-response proteins and a second, delayed wave of inferred transcriptional regulators at 24 h. Acute envenomation also triggered immediate glycine/serine utilization possibly for antioxidant defense and glycerophospholipid breakdown (via phospholipase A₂), whereas chronic DMD showed sustained glycine/serine engagement and inferred, unresolved phospholipid perturbation without protein-level compensation, which may result from chronic oxidative stress. Overall, our integrative analysis revealed time-specific, multi-layer molecular perturbations distinguishing acute toxin injury from chronic muscle degeneration. Key metabolic control points (ceramide accumulation, arginine flux diversion, autophagy-lipid cross-talk, NAD⁺ salvage timing) were identified, highlighting potential targets for stage-specific therapeutic or nutritional interventions.

Animals↗

PubMed2006

Evolving research trends in bioinformatics.

The cross-disciplinary nature of bioinformatics entails co-evolution with other biomedical disciplines, whereby some bioinformatics applications become popular in certain disciplines and, in turn, these disciplines influence the focus of future bioinformatics development efforts. We observe here that the growth of computational approaches within various biomedical disciplines is not merely a reflection of a general extended usage of computers and the Internet, but due to the production of useful bioinformatics databases and methods for the rest of the biomedical scientific community. We have used the abstracts stored both in the MEDLINE database of biomedical literature and in NIH-funded project grants, to quantify two effects. First, we examine the biomedical literature as a whole and find that the use of computational methods has become increasingly prevalent across biomedical disciplines over the past three decades, while use of databases and the Internet have been rapidly increasing over the past decade. Second, we study the recent trends in the use of bioinformatics topics. We observe that molecular sequence databases are a widely adopted contribution in biomedicine from the field of bioinformatics, and that microarray analysis is one of the major new topics engaged by the bioinformatics community. Via this analysis, we were able to identify areas of rapid growth in the use of informatics to aid in curriculum planning, development of computational infrastructure and strategies for workforce education and funding.

Computational Biology↗

PubMed2006

Microtubule-associated AIR9 recognizes the cortical division site at preprophase and cell-plate insertion.

In plants, the preprophase band (PPB) of microtubules marks the cortical site where the cross-wall will fuse with the parental wall during cytokinesis . This band disappears before metaphase, and it is not known how the division plane is "memorized". One idea is that the PPB leaves behind molecules involved in the maturation of the cell plate . Here, we report on the proteomic isolation of a novel 187 kDa microtubule-associated protein, AIR9, conserved in land plants and trypanosomatid parasites. AIR9 decorates cortical microtubules and the PPB but is downregulated during mitosis. AIR9 reappears at the former PPB site precisely when the cortex is contacted by the outwardly growing cytokinetic apparatus. AIR9 then moves inward on the new cross-wall and thus forms a torus. Truncation studies show that formation of the torus requires a repeated domain separate from AIR9's microtubule binding site. Cell plates induced to insert outside the predicted division site do not elicit an AIR9 torus, suggesting that AIR9 recognizes a component of the former PPB. Such misplaced walls remain immature, based on their prolonged staining for the cell-plate polymer callose. We propose that AIR9 may be part of the mechanism ensuring the maturation of those cell plates successfully contacting the "programmed" cortical division site.

Amino Acid Sequence↗

PubMed2006

Expression of protein elongation factor eEF1A2 predicts favorable outcome in breast cancer.

Breast cancer is the most common malignancy among North American women. The identification of factors that predict outcome is key to individualized disease management and to our understanding of breast oncogenesis. We have analyzed mRNA expression of protein elongation factor eEF1A2 in two independent breast tumor populations of size n = 345 and n = 88, respectively. We find that eEF1A2 mRNA is expressed at a low level in normal breast epithelium but is detectably expressed in approximately 50-60% of primary human breast tumors. We have derived an eEF1A2-specific antibody and measured eEF1A2 protein expression in a sample of 438 primary breast tumors annotated with 20-year survival data. We find that high levels of eEF1A2 protein are detected in 60% of primary breast tumors independent of HER-2 protein expression, tumor size, lymph node status, and estrogen receptor (ER) expression. Importantly, we find that high eEF1A2 is a significant predictor of outcome. Women whose tumor has high eEF1A2 protein expression have an increased probability of 20-year survival compared to those women whose tumor does not express substantial eEF1A2. In addition, eEF1A2 protein expression predicts increased survival probability in those breast cancer patients whose tumor is HER-2 negative or who have lymph node involvement.

Amino Acid Sequence↗

PubMed2006

Computational disease gene identification: a concert of methods prioritizes type 2 diabetes and obesity candidate genes.

Genome-wide experimental methods to identify disease genes, such as linkage analysis and association studies, generate increasingly large candidate gene sets for which comprehensive empirical analysis is impractical. Computational methods employ data from a variety of sources to identify the most likely candidate disease genes from these gene sets. Here, we review seven independent computational disease gene prioritization methods, and then apply them in concert to the analysis of 9556 positional candidate genes for type 2 diabetes (T2D) and the related trait obesity. We generate and analyse a list of nine primary candidate genes for T2D genes and five for obesity. Two genes, LPL and BCKDHA, are common to these two sets. We also present a set of secondary candidates for T2D (94 genes) and for obesity (116 genes) with 58 genes in common to both diseases.

Computational Biology↗

PubMed2006

An abnormal mitochondrial-hypoxia inducible factor-1alpha-Kv channel pathway disrupts oxygen sensing and triggers pulmonary arterial hypertension in fawn hooded rats: similarities to human pulmonary arterial hypertension.

BACKGROUND: The cause of pulmonary arterial hypertension (PAH) was investigated in humans and fawn hooded rats (FHR), a spontaneously pulmonary hypertensive strain. METHODS AND RESULTS: Serial Doppler echocardiograms and cardiac catheterizations were performed in FHR and FHR/BN1, a consomic control that is genetically identical except for introgression of chromosome 1. PAH began after 20 weeks of age, causing death by &60 weeks. FHR/BN1 did not develop PAH. FHR pulmonary arterial smooth muscle cells (PASMCs) had a rarified reticulum of hyperpolarized mitochondria with reduced expression of electron transport chain components and superoxide dismutase-2. These mitochondrial abnormalities preceded PAH and persisted in culture. Depressed mitochondrial reactive oxygen species (ROS) production caused normoxic activation of hypoxia inducible factor (HIF-1alpha), which then inhibited expression of oxygen-sensitive, voltage-gated K+ channels (eg, Kv1.5). Disruption of this mitochondrial-HIF-Kv pathway impaired oxygen sensing (reducing hypoxic pulmonary vasoconstriction, causing polycythemia), analogous to the pathophysiology of chronically hypoxic Sprague-Dawley rats. Restoring ROS (exogenous H2O2) or blocking HIF-1alpha activation (dominant-negative HIF-1alpha) restored Kv1.5 expression/function. Dichloroacetate, a mitochondrial pyruvate dehydrogenase kinase inhibitor, corrected the mitochondrial-HIF-Kv pathway in FHR-PAH and human PAH PASMCs. Oral dichloroacetate regressed FHR-PAH and polycythemia, increasing survival. Chromosome 1 genes that were dysregulated in FHRs and relevant to the mitochondria-HIF-Kv pathway included HIF-3alpha (an HIF-1alpha repressor), mitochondrial cytochrome c oxidase, and superoxide dismutase-2. Like FHRs, human PAH-PASMCs had dysmorphic, hyperpolarized mitochondria; normoxic HIF-1alpha activation; and reduced expression/activity of HIF-3alpha, cytochrome c oxidase, and superoxide dismutase-2. CONCLUSIONS: FHRs have a chromosome 1 abnormality that disrupts a mitochondria-ROS-HIF-Kv pathway, leading to PAH. Similar abnormalities occur in idiopathic human PAH. This study reveals an intersection between oxygen-sensing mechanisms and PAH. The mitochondria-ROS-HIF-Kv pathway offers new targets for PAH therapy.

Animals↗

PubMed2006

Amplification of the Gene Ontology annotation of Affymetrix probe sets.

BACKGROUND: The annotations of Affymetrix DNA microarray probe sets with Gene Ontology terms are carefully selected for correctness. This results in very accurate but incomplete annotations which is not always desirable for microarray experiment evaluation. RESULTS: Here we present a protocol to amplify the set of Gene Ontology annotations associated to Affymetrix DNA microarray probe sets using information from related databases. CONCLUSION: Predicted novel annotations and the evidence producing them can be accessed at Probe2GO: http://www.ogic.ca/p2g. Scripts are available on demand.

Algorithms↗

PubMed2006

Taxonomic colouring of phylogenetic trees of protein sequences.

BACKGROUND: Phylogenetic analyses of protein families are used to define the evolutionary relationships between homologous proteins. The interpretation of protein-sequence phylogenetic trees requires the examination of the taxonomic properties of the species associated to those sequences. However, there is no online tool to facilitate this interpretation, for example, by automatically attaching taxonomic information to the nodes of a tree, or by interactively colouring the branches of a tree according to any combination of taxonomic divisions. This is especially problematic if the tree contains on the order of hundreds of sequences, which, given the accelerated increase in the size of the protein sequence databases, is a situation that is becoming common. RESULTS: We have developed PhyloView, a web based tool for colouring phylogenetic trees upon arbitrary taxonomic properties of the species represented in a protein sequence phylogenetic tree. Provided that the tree contains SwissProt, SpTrembl, or GenBank protein identifiers, the tool retrieves the taxonomic information from the corresponding database. A colour picker displays a summary of the findings and allows the user to associate colours to the leaves of the tree according to any number of taxonomic partitions. Then, the colours are propagated to the branches of the tree. CONCLUSION: PhyloView can be used at http://www.ogic.ca/projects/phyloview/. A tutorial, the software with documentation, and GPL licensed source code, can be accessed at the same web address.

Algorithms↗