Ancient genomics support deep divergence between Eastern and Western Mediterranean Indo-European languages.

The Indo-European languages are among the most widely spoken in the world, yet their early diversification remains contentious. It is widely accepted that the spread of this language family across Europe from the 5th millennium BP correlates with the expansion and diversification of steppe-related genetic ancestry from the onset of the Bronze Age. However, multiple steppe-derived populations co-existed in Europe during this period, and it remains unclear how these populations diverged and which provided the demographic channels for the ancestral forms of the Italic, Celtic, Greek, and Armenian languages.

Association between STAT4 gene polymorphism and susceptibility to pulmonary tuberculosis in the Moldavian population.

Signal transducer and activator of transcription 4 (STAT4) plays a crucial role in the host immune response against Mycobacterium tuberculosis. This study investigates the association between STAT4 gene polymorphisms and pulmonary tuberculosis (TB) risk in the Moldavian population. A total of 272 TB patients and 251 community-matched controls underwent screening for functional single-nucleotide polymorphisms (SNPs) rs897200 and rs7574865 in the STAT4 gene.

BestCRM: An Exhaustive Search for Optimal Cis-Regulatory Modules in Promoters Accelerated by the Multidimensional Hash Function.

The concept of cis-regulatory modules located in gene promoters represents today's vision of the organization of gene transcriptional regulation. Such modules are a combination of two or more single, short DNA motifs. The bioinformatic identification of such modules belongs to so-called NP-hard problems with extreme computational complexity, and therefore, simplifications, assumptions, and heuristics are usually deployed to tackle the problem.

Modeling and cleaning RNA-seq data significantly improve detection of differentially expressed genes.

Background: RNA-seq has become a standard technology to quantify mRNA. The measured values usually vary by several orders of magnitude, and while the detection of differences at high values is statistically well grounded, the significance of the differences for rare mRNAs can be weakened by the presence of biological and technical noise.

Results: We have developed a method for cleaning RNA-seq data, which improves the detection of differentially expressed genes and specifically genes with low to moderate transcription.

Candidate genes and sequence variants for susceptibility to mycobacterial infection identified by whole-exome sequencing.

Inborn errors of immunity are known to influence susceptibility to mycobacterial infections. The aim of this study was to characterize the genetic profile of nine patients with mycobacterial infections (eight with BCGitis and one with disseminated tuberculosis) from the Republic of Moldova using whole-exome sequencing. In total, 12 variants in eight genes known to be associated with Mendelian Susceptibility to Mycobacterial Disease (MSMD) were detected in six out of nine patients examined.

Hormonal Regulation and Crosstalk of Auxin/Cytokinin Signaling Pathways in Potatoes In Vitro and in Relation to Vegetation or Tuberization Stages.

Auxins and cytokinins create versatile regulatory network controlling virtually all aspects of plant growth and development. These hormonal systems act in close contact, synergistically or antagonistically, determining plant phenotype, resistance and productivity. However, the current knowledge about molecular interactions of these systems is still scarce.

Synergistic effect of genetic polymorphisms in and genes on the risk of pulmonary tuberculosis in a Moldavian population.

Polymorphisms in genes that control immune function and regulation may influence susceptibility to pulmonary tuberculosis (TB). In this study, 14 polymorphisms in 12 key genes involved in the immune response (, , , , , , , , , , , and ) were tested for their association with pulmonary TB in 271 patients with TB and 251 community-matched controls from the Republic of Moldova. In addition, gene-gene interactions involved in TB susceptibility were analyzed for a total of 43 genetic loci.

Evaluation of variation in genes of the arylhydrocarbon receptor pathway for an association with multiple sclerosis.

The aryl hydrocarbon receptor (AhR) contributes to immune regulation in autoimmune diseases such as multiple sclerosis (MS). Analysis of selected polymorphisms in AhR pathway genes in 805 MS patients and 1023 controls revealed a modest association of a CYP1B1 polymorphism with secondary progressive MS that became more pronounced in combination with other SNPs in the pathway, suggesting interactive effects. Additionally, first evidence for an interaction with smoking was found, but due to small sample sizes statistical significance was only nominal.

Genetic variation in TLR pathway and the risk of pulmonary tuberculosis in a Moldavian population.

Toll-like receptors (TLRs) play a critical role in initiating an immune response to infections. In this study, we examined whether single nucleotide polymorphisms (SNPs) in TLR pathway genes are associated with pulmonary tuberculosis (PTB) in a Moldavian population. Thirty-four SNPs in genes associated with the TLR pathway and two SNPs in ASAP1 gene identified by GWAS were selected for genotyping in 272 patients and 251 community-matched healthy controls.

Age-Specific Association of CCL5 Gene Polymorphism with Pulmonary Tuberculosis: A Case-Control Study.

Objectives: Chemokines play a key role in immune regulation and response, and have been implicated in the pathogenesis of tuberculosis (TB). In this study, we investigated whether functional polymorphisms of the chemokines CCL5, CCL2, and CXCL8 are associated with pulmonary TB in a Moldavian population.

Materials And Methods: A total of 250 patients with TB and 184 healthy controls were screened for CCL5 -403G/A (rs2107538), CCL5 In1.

Poor knowledge of vaccination recommendations and negative attitudes towards vaccinations are independently associated with poor vaccination uptake among adults - Findings of a population-based panel study in Lower Saxony, Germany.

Objectives: The aims of this study were to (a) assess knowledge of official vaccination recommendations and attitudes towards vaccinations among adults and (b) examine their association with vaccination uptake among adults.

Methods: This study was part of the HaBIDS study (Hygiene and Behaviour Infectious Diseases Survey), which is an online panel established in March 2014 in Lower Saxony, Germany with males and females aged between 15 and 69 years (n = 2379). Every few months, participants completed questionnaires on different aspects of infectious diseases.

FlowerMorphology: fully automatic flower morphometry software.

The software FlowerMorphology is designed for automatic morphometry of actinomorphic flowers. The novel complex parameters of flowers calculated by FlowerMorphology allowed us to quantitatively characterize a polyploid series of tobacco. Morphological differences of plants representing closely related lineages or mutants are mostly quantitative.

Composing a Tumor Specific Bacterial Promoter.

Systemically applied Salmonella enterica spp. have been shown to invade and colonize neoplastic tissues where it retards the growth of many tumors. This offers the possibility to use the bacteria as a vehicle for the tumor specific delivery of therapeutic molecules.

Polymorphisms of glutathione S-transferase and methylenetetrahydrofolate reductase genes in Moldavian patients with ulcerative colitis: Genotype-phenotype correlation.

Background: Glutathione S-transferases (GSTM1, GSTT1, and GSTP1) and methylenetetrahydrofolate reductase (MTHFR) are important enzymes for protection against oxidative stress. In addition, MTHFR has an essential role in DNA synthesis, repair, and methylation. Their polymorphisms have been implicated in the pathogenesis of ulcerative colitis (UC).

Development of a unique epigenetic signature during in vivo Th17 differentiation.

Activated naive CD4(+) T cells are highly plastic cells that can differentiate into various T helper (Th) cell fates characterized by the expression of effector cytokines like IFN-γ (Th1), IL-4 (Th2) or IL-17A (Th17). Although previous studies have demonstrated that epigenetic mechanisms including DNA demethylation can stabilize effector cytokine expression, a comprehensive analysis of the changes in the DNA methylation pattern during differentiation of naive T cells into Th cell subsets is lacking. Hence, we here performed a genome-wide methylome analysis of ex vivo isolated naive CD4(+) T cells, Th1 and Th17 cells.

Analysis of polymorphisms in RIG-I-like receptor genes in German multiple sclerosis patients.

Variation in genes encoding retinoid acid-inducible gene I (RIG-I)-like receptors (RLRs) has been implicated in the pathogenesis of autoimmune disorders. We investigated if polymorphisms in the IFIH1, RIG-I, LGP2 and VISA genes influence the risk for multiple sclerosis (MS) in a German case-control cohort comprising 716 patients and 706 controls. Evaluation of 18 single nucleotide polymorphisms (SNPs) in the four genes did not reveal significant single-SNP associations with MS risk, but two VISA polymorphisms were modestly associated with age of onset.

MatrixCatch--a novel tool for the recognition of composite regulatory elements in promoters.

Background: Accurate recognition of regulatory elements in promoters is an essential prerequisite for understanding the mechanisms of gene regulation at the level of transcription. Composite regulatory elements represent a particular type of such transcriptional regulatory elements consisting of pairs of individual DNA motifs. In contrast to the present approach, most available recognition techniques are based purely on statistical evaluation of the occurrence of single motifs.

An integrative computational approach to effectively guide experimental identification of regulatory elements in promoters.

Background: Transcriptional activity of genes depends on many factors like DNA motifs, conformational characteristics of DNA, melting etc. and there are computational approaches for their identification. However, in real applications, the number of predicted, for example, DNA motifs may be considerably large.

Identification of tumor-specific Salmonella Typhimurium promoters and their regulatory logic.

Conventional cancer therapies are often limited in effectiveness and exhibit strong side effects. Therefore, alternative therapeutic strategies are demanded. The employment of tumor-colonizing bacteria that exert anticancer effects is such a novel approach that attracts increasing attention.

Human-chimpanzee promoter comparisons: property-conserved evolution?

Identification of different functional elements and their properties is a fundamental need in biomedical research and phylogenetic comparisons of a growing number of sequenced genomes form a solid basis for this task. Most available phylogenetic approaches are focused on searching for individual sequence alterations, responsible for the observed phenotype, or statistically evaluate observed mutations to infer general trends. However, being applied to close genomes such methods suffer from poor statistics of rare mutations and give only (at its best) coarse results concerning the potential functional importance of the nucleotide differences.

FeatureScan: revealing property-dependent similarity of nucleotide sequences.

FeatureScan is a software package aiming to reveal novel types of DNA sequence similarity by comparing physico-chemical properties. Thirty-eight different parameters of DNA double strands such as charge, melting enthalpy, conformational parameters and the like are provided. As input FeatureScan requires two sequences, a pattern sequence and a target sequence, search conditions are set by selecting a specific DNA parameter and a threshold value.

Signal-theoretical DNA similarity measure revealing unexpected similarities of E. coli promoters.

We present an implementation of the signal theory based approach for detection of novel types of DNA similarity which are based on physical properties of DNA. Systematic study of the sensitivity of the new similarity measure revealed qualitative differences to letter-based similarity. A variety of physical parameters of DNA double strands, which in a straightforward way reflect different kinds of information hidden behind the primary structure of DNA, showed a wide range of recognition power of the signal similarity measure.