Monte Carlo Simulation of Hydration of the Guanine-Uracil Pairs with Guanine in Two Tautomeric Forms: Contribution of Water Bridging to Relative Stability of Mispairs

Abstract

Results are presented from Monte Carlo simulation of hydration of guanine-uracil mispairs by 25 and 50 water molecules. The hydration shells of three mispairs formed between “normal” dioxo form of uracil (U) and three forms of guanine (“normal” amino-oxo tautomer G and two rotamers of the “rare” amino-hydroxy tautomer G*) depend on the tautomeric forms of the guanine molecule. The simulation shows the important role of hydration effects on the relative stability of the mispairs.     

Nucleosome DNA Bendability Matrix (C. elegans)

Abstract

An original signal extraction procedure is applied to database of 146 base nucleosome core DNA sequences from C. elegans (S. M. Johnson et al. Genome Research 16, 1505–1516, 2006). The positional preferences of various dinucleotides within the 10.4 base nucleosome DNA repeat are calculated, resulting in derivation of the nucleosome DNA bendability matrix of 16x10 elements. A simplified one-line presentation of the matrix (“consensus” repeat) is…A(TTTCCGGAAA)T…. All 6 chromosomes of C. elegans conform to the bendability pattern. The strongest affinity to their respective positions is displayed by dinucleotides AT and CG, separated within the repeat by 5 bases. The derived pattern makes a basis for sequence-directed mapping of nucleosome positions in the genome of C. elegans. As the first complete matrix of bendability available the pattern may serve for iterative calculations of the species-specific matrices of bendability applicable to other genomic sequences.     

Protein Sequence Modules

Abstract

Conserved protein sequence segments are commonly believed to correspond to functional sites in the protein sequence. A novel approach is proposed to profile the changing degree of conservation along the protein sequence, by evaluating the occurrence frequencies of all short oligopeptides of the given sequence in a large proteome database. Thus, a protein sequence conservation profile can be plotted for every protein. The profile indicates where along the sequences the potential functional (conserved) sites are located. The corresponding oligopeptides belonging to the sites are very frequent across many prokaryotic species. Analysis of a representative set of such profiles reveals a common feature of all examined proteins: they consist of sequence modules represented by the peaks of conservation. Typical size of the modules (peak-to-peak distance) is 25–30 amino acid residues.     

Sequence-directed Mapping of Nucleosome Positions

Abstract

A nucleosome DNA sequence probe is designed that combines recently derived RR/YY counter-phase and AA/TT in-phase periodical patterns. A simple nucleosome mapping procedure is introduced for prediction of the nucleosome positions in the sequence of interest, to serve as a guide for experimental studies of the chromatin structure.     

Oncolytic Vesicular Stomatitis Virus in an Immunocompetent Model of MUC1-Positive or MUC1-Null Pancreatic Ductal Adenocarcinoma

Vesicular stomatitis virus (VSV) is a promising oncolytic agent against various malignancies. Here, for the first time, we tested VSV in vitro and in vivo in a clinically relevant, immunocompetent mouse model of pancreatic ductal adenocarcinoma (PDA). Our system allows the study of virotherapy against PDA in the context of overexpression (80% of PDA patients) or no expression of human mucin 1 (MUC1), a major marker for poor prognosis in patients. In vitro, we tested three VSV recombinants, wild-type VSV, VSV-green fluorescent protein (VSV-GFP), and a safe oncolytic VSV-ΔM51-GFP, against five mouse PDA cell lines that either expressed human MUC1 or were MUC1 null. All viruses demonstrated significant oncolytic abilities independent of MUC1 expression, although VSV-ΔM51-GFP was somewhat less effective in two PDA cell lines. In vivo administration of VSV-ΔM51-GFP resulted in significant reduction of tumor growth for tested mouse PDA xenografts (+MUC1 or MUC1 null), and antitumor efficacy was further improved when the virus was combined with the chemotherapeutic drug gemcitabine. The antitumor effect was transient in all tested groups. The developed system can be used to study therapies involving various oncolytic viruses and chemotherapeutics, with the goal of inducing tumor-specific immunity while preventing premature virus clearance.     

Antimicrobial potential of deep surface sediment associated bacteria from the Sea of Japan

The aim of this study was to survey microorganisms from the deep surface sediment samples collected from the Sea of Japan and to screen them for antimicrobial and antagonistic effects. Phylogenetic analysis revealed most isolates sharing 98–100 % sequence similarity to recognized species, including those recovered previously from marine or saline environments. Alteromonas, Halomonas, Marinobacter, Pseudoalteromonas, Salinicola, within the class Gammaproteobacteria, Sulfitobacter (Alphaproteobacteria), Bacillus, Paenibacillus and Paenisporosarcina (Firmicutes), Nocardiopsis and Streptomyces (Actinobacteria) occurred abundantly in all sediment samples. Antimicrobial screening revealed twenty three strains (13 %) capable to inhibit growth of one to eight test cultures and deep sediment isolates. Based on phylogenetic analysis mostly active strains belonged to the genera Bacillus, Brevibacillus, Nocardiopsis, Paenibacillus and Streptomyces. Antimicrobial substances (1–3) were isolated from strain Paenibacillus sp. Sl 79w showing a high inhibitory activity. On the basis of combined spectral analyses (IR, UV, ¹H and ¹³C NMR) the compounds 1, 2 and 3 with [M + H]⁺ at 409.1 and 409.2 m/z, and with [M + Na]⁺ at 822.5 m/z were found to have a carbon skeleton of isocoumarin and peptide antibiotics, respectively. Our findings demonstrated that the deep surface sediments of the Sea of Japan represent an untapped source of diverse microorganisms capable of antimicrobial metabolite production.     

How fast is fast? Eco‐evolutionary dynamics and rates of change in populations and phenotypes

It is increasingly recognized that evolution may occur in ecological time. It is not clear, however, how fast evolution – or phenotypic change more generally – may be in comparison with the associated ecology, or whether systems with fast ecological dynamics generally have relatively fast rates of phenotypic change. We developed a new dataset on standardized rates of change in population size and phenotypic traits for a wide range of species and taxonomic groups. We show that rates of change in phenotypes are generally no more than 2/3, and on average about 1/4, the concurrent rates of change in population size. There was no relationship between rates of population change and rates of phenotypic change across systems. We also found that the variance of both phenotypic and ecological rates increased with the mean across studies following a power law with an exponent of two, while temporal variation in phenotypic rates was lower than in ecological rates. Our results are consistent with the view that ecology and evolution may occur at similar time scales, but clarify that only rarely do populations change as fast in traits as they do in abundance.