Association of the Recombination-Deficient Phenotype of Bacillus subtilis recC Strains with the Presence of an SPO2 Prophage

The recombination-defective phenotype associated with the recC genetic locus in Bacillus subtilis is not due to a chromosomal mutation at this site but rather to the presence of an integrated SPO2 prophage.     

Coregulation mapping based on individual phenotypic variation in response to virus infection

Background

Biology is moving fast toward the virtuous circle of other disciplines: from data to quantitative modeling and back to data. Models are usually developed by mathematicians, physicists, and computer scientists to translate qualitative or semi-quantitative biological knowledge into a quantitative approach. To eliminate semantic confusion between biology and other disciplines, it is necessary to have a list of the most important and frequently used concepts coherently defined.

Results

We propose a novel paradigm for generating new concepts for an ontology, starting from model rather than developing a database. We apply that approach to generate concepts for cell and molecule interaction starting from an agent based model. This effort provides a solid infrastructure that is useful to overcome the semantic ambiguities that arise between biologists and mathematicians, physicists, and computer scientists, when they interact in a multidisciplinary field.

Conclusions

This effort represents the first attempt at linking molecule ontology with cell ontology, in IMGT-ONTOLOGY, the well established ontology in immunogenetics and immunoinformatics, and a paradigm for life science biology. With the increasing use of models in biology and medicine, the need to link different levels, from molecules to cells to tissues and organs, is increasingly important.     

A blood based 12-miRNA signature of Alzheimer disease patients

Background

Alzheimer disease (AD) is the most common form of dementia but the identification of reliable, early and non-invasive biomarkers remains a major challenge. We present a novel miRNA-based signature for detecting AD from blood samples.

Results

We apply next-generation sequencing to miRNAs from blood samples of 48 AD patients and 22 unaffected controls, yielding a total of 140 unique mature miRNAs with significantly changed expression levels. Of these, 82 have higher and 58 have lower abundance in AD patient samples. We selected a panel of 12 miRNAs for an RT-qPCR analysis on a larger cohort of 202 samples, comprising not only AD patients and healthy controls but also patients with other CNS illnesses. These included mild cognitive impairment, which is assumed to represent a transitional period before the development of AD, as well as multiple sclerosis, Parkinson disease, major depression, bipolar disorder and schizophrenia. miRNA target enrichment analysis of the selected 12 miRNAs indicates an involvement of miRNAs in nervous system development, neuron projection, neuron projection development and neuron projection morphogenesis. Using this 12-miRNA signature, we differentiate between AD and controls with an accuracy of 93%, a specificity of 95% and a sensitivity of 92%. The differentiation of AD from other neurological diseases is possible with accuracies between 74% and 78%. The differentiation of the other CNS disorders from controls yields even higher accuracies.

Conclusions

The data indicate that deregulated miRNAs in blood might be used as biomarkers in the diagnosis of AD or other neurological diseases.     

The influence of one-carbon metabolism on gene promoter methylation in a population-based breast cancer study

Abnormal methylation in gene promoters is a hallmark of the cancer genome; however, factors that may influence promoter methylation have not been well elucidated. As the one-carbon metabolism pathway provides the universal methyl donor for methylation reactions, perturbation of this pathway might influence DNA methylation and, ultimately, affect gene functions. Utilizing approximately 800 breast cancer tumor tissues from a large population-based study, we investigated the relationships between dietary and genetic factors involved in the one-carbon metabolism pathway and promoter methylation of a panel of 13 breast cancer-related genes. We found that CCND2, HIN1 and CHD1 were the most "dietary sensitive" genes, as methylation of their promoters was associated with intakes of at least two out of the eight dietary methyl factors examined. On the other hand, some micronutrients (i.e., B 2 and B 6) were more "epigenetically active" as their intake levels correlated with promoter methylation status in 3 out of the 13 breast cancer genes evaluated. Both positive (hypermethylation) and inverse (hypomethylation) associations with high micronutrient intake were observed. Unlike what we saw for dietary factors, we did not observe any clear patterns between one-carbon genetic polymorphisms and the promoter methylation status of the genes examined. Our results provide preliminary evidence that one-carbon metabolism may have the capacity to influence the breast cancer epigenome. Given that epigenetic alterations are thought to occur early in cancer development and are potentially reversible, dietary modifications may offer promising venues for cancer intervention and prevention.     

Ovariectomy and overeating palatable, energy-dense food increase subcutaneous adipose tissue more than intra-abdominal adipose tissue in rats

Background

Men are at an increased risk of dying from heart failure caused by inflammatory heart diseases such as atherosclerosis, myocarditis and dilated cardiomyopathy (DCM). We previously showed that macrophages in the spleen are phenotypically distinct in male compared to female mice at 12 h after infection. This innate immune profile mirrors and predicts the cardiac immune response during acute myocarditis.

Methods

In order to study sex differences in the innate immune response, five male and female BALB/c mice were infected intraperitoneally with coxsackievirus B3 (CVB3) or phosphate buffered saline and their spleens were harvested 12 h later for microarray analysis. Gene expression was determined using an Affymetrix Mouse Gene 1.0 ST Array. Significant gene changes were verified by quantitative real-time polymerase chain reaction or ELISA.

Results

During the innate immune response to CVB3 infection, infected males had higher splenic expression of genes which are important in regulating the influx of cholesterol into macrophages, such as phospholipase A₂ (PLA₂) and the macrophage scavenger receptor compared to the infected females. We also observed a higher expression in infected males compared to infected females of squalene synthase, an enzyme used to generate cholesterol within cells, and Cyp2e1, an enzyme important in metabolizing cholesterol and steroids. Infected males also had decreased levels of the translocator protein 18 kDa (TSPO), which binds PLA₂ and is the rate-limiting step for steroidogenesis, as well as decreased expression of the androgen receptor (AR), which indicates receptor activation. Gene differences were not due to increased viral replication, which was unaltered between sexes.

Conclusions

We found that, compared to females, male mice had a greater splenic expression of genes which are important for cholesterol metabolism and activation of the AR at 12 h after infection. Activation of the AR has been linked to increased cardiac hypertrophy, atherosclerosis, myocarditis/DCM and heart failure in male mice and humans.     

Activity of endonuclease S1 in denaturing solvents: dimethysulfoxide, dimethylformamide, formamide and formaldehyde.

The endonuclease S₁ from $\text{Aspergillus oryzae}$ is shown to be active in aqueous solutions of greater than 60 percent formamide, 50 percent dimethylsulfoxide, 30 percent dimethylformamide and in 2 percent formaldehyde. The melting profile of T7 DNA is determined by S₁ digestion in 50 percent formamide and is found to agree with the optical melting profile. The single-strand specificity of S₁ is retained in 50 percent formamide at 37°C, 3°C below the DNA melting temperature. S₁ is shown to be active at temperatures greater than 5°C above the DNA melting temperature in this solvent.