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.     

Molecular cloning of a cDNA for human delta-aminolevulinate dehydratase

A cDNA encoding human delta-aminolevulinic acid dehydratase (ALA-D; EC 4.2.1.24), the second enzyme in the heme biosynthetic pathway, was isolated from a human liver cDNA expression library. Of the original 17 clones selected with anti-ALA-D antibody, only four expressed anti-ALA-D epitopes as assessed by rescreening with antibody preabsorbed with purified antigen. Subsequent screening of the antibody-positive clones with mixed oligodeoxynucleotide (oligo) probes, synthesized to correspond to human N-terminal and bovine active-site peptide sequences, identified three clones which hybridized only with the oligo probes for the bovine amino acid (aa) sequences. Restriction endonucleases analysis revealed that these three clones contained the same 800-bp cDNA insert. This insert was recloned into bacteriophage M13mp18 and mp19 and sequenced by primer extension. The aa sequence predicted from the partial nucleotide sequence was found to be essentially colinear with the sequences of four bovine ALA-D peptides, totaling 35 non-overlapping aa residues.     

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.