Serum metabolomics profile of type 2 diabetes mellitus in a Brazilian rural population

Introduction

The development of common forms of diabetes comes from the interaction between environmental and genetic factors, and the consequences of poor glycemic control in these patients could result in several complications. Metabolomic studies for type 2 diabetes mellitus in serum/plasma have reported changes in numerous metabolites, which might be considered possible targets for future mechanistic research. However, the specific role of a particular metabolite as cause or consequence of diabetes derangements is difficult to establish.

Objectives

As type 2 diabetes is a disease that changes the metabolic profile in several levels, this work aimed to compare the metabolomic profiles of type 2 diabetes mellitus and non-diabetic participants. In addition, we exploited our family-based study design to bring a better understanding of the causal relationship of identified metabolites and diabetes.

Methods

In the current study, population based metabolomics was applied in 939 subjects from the Baependi Heart Study. Participants were separated into two groups: diabetic (77 individuals) and non-diabetic (862 individuals), and the metabolic profile was performed by GC/MS technique.

Results

We have identified differentially concentrated metabolites in serum of diabetic and non-diabetic individuals. We identified 72 metabolites up-regulated in type 2 diabetes mellitus compared to non-diabetics. It was possible to recapitulate the main pathways that the literature shows as changed in diabetes. Also, based on metabolomic profile, we separated pre-diabetic individuals (with glucose concentration between 100–125 mg/dL) from non-diabetics and diabetics. Finally, using heritability analysis, we were able to suggest metabolites in which altered levels may precede diabetic development.

Conclusion

Our data can be used to derive a better understanding of the causal relationship of the observed associations and help to prioritize diabetes-associated metabolites for further work.

     

Structural basis for the antagonistic roles of RNP-8 and GLD-3 in GLD-2 poly(A)-polymerase activity

Cytoplasmic polyadenylation drives the translational activation of specific mRNAs in early metazoan development and is performed by distinct complexes that share the same catalytic poly(A)-polymerase subunit, GLD-2. The activity and specificity of GLD-2 depend on its binding partners. In Caenorhabditis elegans, GLD-2 promotes spermatogenesis when bound to GLD-3 and oogenesis when bound to RNP-8. GLD-3 and RNP-8 antagonize each other and compete for GLD-2 binding. Following up on our previous mechanistic studies of GLD-2–GLD-3, we report here the 2.5 Å resolution structure and biochemical characterization of a GLD-2–RNP-8 core complex. In the structure, RNP-8 embraces the poly(A)-polymerase, docking onto several conserved hydrophobic hotspots present on the GLD-2 surface. RNP-8 stabilizes GLD-2 and indirectly stimulates polyadenylation. RNP-8 has a different amino-acid sequence and structure as compared to GLD-3. Yet, it binds the same surfaces of GLD-2 by forming alternative interactions, rationalizing the remarkable versatility of GLD-2 complexes.     

Heterologous gene expression in continuous cultures of budding yeast

Summary In a previous paper we have studied the expression of -galactosidase from Escherichia coli, driven from the inducible GAL1-10/CYC1 hybrid promoter, in batch cultures of budding Saccharomyces cerevisiae and have described operating conditions for maximal productivity. In this paper we show that the plasmid instability in continuous cultures can be overcome by utilizing appropriate selection markers and a high copy number vector. The maximal level of expression is influenced by the dilution rate. Moreover, enzyme accumulation appears to depend also upon the degree of oxygenation. A possible explanation of these modulations is discussed, taking into account the interactions of the UAS-GAL and TATA-CYC1 elements. Offprint requests to: D. Porro     

Loss of the zona pellucida-binding protein 2 (Zpbp2) gene in mice impacts airway hypersensitivity and lung lipid metabolism in a sex-dependent fashion

Mammalian Genome - The human chromosomal region 17q12–q21 is one of the best replicated genome-wide association study loci for childhood asthma. The associated SNPs span a large genomic...     

Mutations in Cytosine-5 tRNA Methyltransferases Impact Mobile Element Expression and Genome Stability at Specific DNA Repeats

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The value of microparticles in detecting acute rejection episodes after liver transplantation

Context: Non-invasive markers for diagnosis of acute rejection (AR) following liver transplantation have not been developed, yet.

Objective: We analyzed the correlation of plasma microparticle levels (MP) with AR.

Materials and Methods: MP (CD4, CD8, CD25, CD31, MHC) of 11?AR patients and 11 controls were analyzed within the first week after transplantation.

Results: CD4, CD8 and CD31 positive MP were higher in the AR, whereas overall MP count, CD25 and MHCI positive MP proportions did not differ between both groups.

Discussion and Conclusion: MP dynamics within the first period of transplantation could help to clarify on-going mechanisms of immunomodulation.     

Genomic Regions in Local Endangered Sheep Encode Potentially Favorable Genes

The economic evaluation of farm animal genetic resources plays a key role in developing conservation programs. However, to date, the link between diversity as assessed by neutral genetic markers and the functional diversity is not yet understood. Two genome-wide comparisons, using over 44,000 Single Nucleotide Polymorphisms, identified the markers with the highest difference in allele frequency between the Alpago endangered breed and two clusters, composed of four specialized dairy sheep, and four meat breeds respectively. The genes in proximity of these markers were mapped to known pathways of the Gene Ontology to determine which ones were most represented. Our results indicated that the differences of the Alpago breed from the more productive sheep rely upon genes involved in cellular defense and repair mechanisms. A higher number of different markers and genes were detected in the comparison with the specialized dairy sheep. These genes play a role in complex biological processes: metabolic, homeostatic, neurological system, and macromolecular organization; such processes may possibly explain the evolution of gene function as a result of selection to improve milk yield.     

Ants Response to Human-Induced Disturbance in a Rain Tropical Forest

A high rate of human-induced disturbance of tropical ecosystems results in enormous loss of biodiversity due to local extinctions. Yet, mechanisms at the population level that lead to the extinction are still poorly understood. Here we tested the hypothesis that human-induced disturbance results in smaller amount of nesting sites for wood-dwelling arthropods that leads to smaller population size and diminished reproduction, and therefore, may promote local extinctions. We completed censuses in less-disturbed and human-disturbed secondary rain forest plots in Puerto Rico. We measured population size and brood production in wood-nesting ants and examined whether these parameters differ between less-disturbed and more-disturbed habitats. In addition, we measured volume of wood parts of all inhabited and potential nesting sites to assess nest site availability. We found that more human-disturbed forests furnish smaller nest sites, resulting in diminished population size and lowered brood production. Our study shows that human-induced disturbance decreases volume of available nesting sites that leads to decreased population size and lowered reproduction. Thus, in addition to the well-documented loss of species richness in human-disturbed tropical habitats, we demonstrated the direct effect of the disturbance that may promote vulnerability of local populations.