DNA simulation benchmarks revealed with the accumulation of high-resolution structures.

DNA carries more than the list of biochemical instructions that drive the basic functions of living systems. The sequence of base pairs includes a multitude of structural and energetic signals that determine the degree to which the long, threadlike molecule moves and how it responds to proteins and other molecules involved in its processing and packaging. The arrangements of successive base pairs in high-resolution protein-DNA crystal structures provide useful benchmarks for atomic-level simulations of double-helical DNA as well as information potentially useful in interpreting the properties of specific DNA sequences.

Revisiting DNA Sequence-Dependent Deformability in High-Resolution Structures: Effects of Flanking Base Pairs on Dinucleotide Morphology and Global Chain Configuration.

DNA carries more than the list of biochemical ingredients that drive the basic functions of living systems. The sequence of base pairs includes a multitude of structural and energetic signals, which determine the degree to which the long, threadlike molecule moves and how it responds to proteins and other molecules that control its processing and govern its packaging. The chemical composition of base pairs directs the spatial disposition and fluctuations of successive residues.

DNA topology confers sequence specificity to nonspecific architectural proteins.

Topological constraints placed on short fragments of DNA change the disorder found in chain molecules randomly decorated by nonspecific, architectural proteins into tightly organized 3D structures. The bacterial heat-unstable (HU) protein builds up, counter to expectations, in greater quantities and at particular sites along simulated DNA minicircles and loops. Moreover, the placement of HU along loops with the "wild-type" spacing found in the Escherichia coli lactose (lac) and galactose (gal) operons precludes access to key recognition elements on DNA.

Antimicrobial susceptibility of Helicobacter pylori isolates from Lower Silesia, Poland.

Introduction: In recent years the failure of standard therapy for Helicobacter pylori infections has been observed, which results primarily from the increasing resistance of H. pylori strains to antibiotics. The aim of the study was to estimate the prevalence of antimicrobial resistance of H.

Effect of confinement on DNA, solvent and counterion dynamics in a model biological nanopore.

The application of recent advances in nanopore technology to high-throughput DNA sequencing requires a more detailed understanding of solvent, ion and DNA interactions occurring within these pores. Here we present a combination of atomistic and coarse-grained modeling studies of the dynamics of short single-stranded DNA (ssDNA) homopolymers within the alpha-hemolysin pore, for the two single-stranded homopolymers poly(dA)40 and poly(dC)40. Analysis of atomistic simulations along with the per-residue decomposition of protein-DNA interactions in these simulations gives new insight into the very complex issues that have yet to be fully addressed with detailed MD simulations.

Upregulated expression and activation of membrane‑associated proteases in esophageal squamous cell carcinoma.

To better understand the role of membrane-associated proteolytic systems in the development of esophageal cancer, we studied the expression of two serine proteases, fibroblast activation protein-α (FAP-α) and dipeptidyl peptidase IV (DPPIV) and three metalloproteinases, matrix metalloproteinase (MMP)-2, MMP-9 and MT1-MMP in 24 primary esophageal squamous cell carcinoma (ESCC) tissues and paired non-cancer tissues. Using reverse-transcription PCR, western blotting and zymography, we showed that both serine proteases and all three metalloproteinases were highly altered in ESCC. A positive correlation between the expression of FAP-α and DPPIV and the activity of both gelatinases was found.

Molecular simulations of aromatase reveal new insights into the mechanism of ligand binding.

CYP19A1, also known as aromatase or estrogen synthetase, is the rate-limiting enzyme in the biosynthesis of estrogens from their corresponding androgens. Several clinically used breast cancer therapies target aromatase. In this work, explicitly solvated all-atom molecular dynamics simulations of aromatase with a model of the lipid bilayer and the transmembrane helix are performed.

Structural insights into the role of architectural proteins in DNA looping deduced from computer simulations.

Bacterial gene expression is regulated by DNA elements that often lie far apart along the genomic sequence, but come close together during genetic processing. The intervening residues form loops, which are organized by the binding of various proteins. For example, the Escherichia coli Lac repressor protein binds DNA operators, separated by 92 or 401 bp, and suppresses the formation of gene products involved in the metabolism of lactose.

Interplay of protein and DNA structure revealed in simulations of the lac operon.

The E. coli Lac repressor is the classic textbook example of a protein that attaches to widely spaced sites along a genome and forces the intervening DNA into a loop. The short loops implicated in the regulation of the lac operon suggest the involvement of factors other than DNA and repressor in gene control.

BROMOC-D: Brownian Dynamics/Monte-Carlo Program Suite to Study Ion and DNA Permeation in Nanopores.

A theoretical framework is presented to model ion and DNA translocation across a nanopore confinement under an applied electric field. A combined Grand Canonical Monte Carlo Brownian Dynamics (GCMC/BD) algorithm offers a general approach to study ion permeation through wide molecular pores with a direct account of ion-ion and ion-DNA correlations. This work extends previously developed theory by incorporating the recently developed coarse-grain polymer model of DNA by de Pablo and colleagues [Knotts, T.

[Exhaled nitric oxide in patients with esophagitis].

Introduction: Assessment of nitric oxide (NO) concentration in exhaled air is broadly used to monitor the airway inflammation in asthma. High level of NO are also observed in paranasal sinuses and gastrointestinal tract (GT). The intact esopahageal sphincters are responsible for maintain the NO within the GT.

Understanding apparent DNA flexibility enhancement by HU and HMGB architectural proteins.

Understanding and predicting the mechanical properties of protein/DNA complexes are challenging problems in biophysics. Certain architectural proteins bind DNA without sequence specificity and strongly distort the double helix. These proteins rapidly bind and unbind, seemingly enhancing the flexibility of DNA as measured by cyclization kinetics.

How stiff is DNA?

The natural stiffness of DNA, which contributes to the interactions of the many proteins involved in its biological processing and packaging, also plays an important role in modern nanotechnology. Here we report new Monte-Carlo simulations of deformable DNA molecules of potential utility in understanding the behavior of the long, double-helical polymer in the tight confines of a cell and in the design of novel nanomaterials and molecular devices. We directly determine the fluctuations in end-to-end extension associated with the conventional elastic-rod representation of DNA and with more realistic models that take account of the precise deformability of the constituent base-pair steps.

Immunohistochemical study of decorin expression in polyps and carcinomas of the colon.

Background: Recent studies showed that a small leucine-rich proteoglycan, decorin, may suppress tumor progression as a natural anticancer agent negatively controlling cellular growth. It was hypothesized that physiological expression of decorin may be associated with cellular senescence of the colorectal mucosa and that its down-regulation, promoting an increase in cellular proliferation, could participate in the progression of adenoma to adenocarcinoma. Therefore the expression of decorin in hyperplastic and neoplastic polyps of the colorectum was examined and compared with normal colonic mucosa and colon cancer tissues.

Effects of the nucleoid protein HU on the structure, flexibility, and ring-closure properties of DNA deduced from Monte Carlo simulations.

The histone-like HU (heat unstable) protein plays a key role in the organization and regulation of the Escherichia coli genome. The nonspecific nature of HU binding to DNA complicates analysis of the mechanism by which the protein contributes to the looping of DNA. Conventional models of the looping of HU-bound duplexes attribute the changes in biophysical properties of DNA brought about by the random binding of protein to changes in the effective parameters of an ideal helical wormlike chain.

Sequence-Dependent Effects in the Cyclization of Short DNA.

A new, computationally efficient Monte Carlo approach has been developed to estimate the ring-closure properties of short, realistically modeled DNA chains. The double helix is treated at the level of base-pair steps using an elastic potential that accounts for the sequence-dependent variability in the intrinsic structure and elastic moduli of the base-pair steps, including the known coupling of conformational variables. Rather than using traditional Metropolis-Monte Carlo techniques to generate representative configurations, a Gaussian sampling method is introduced to construct three-dimensional structures from linear combinations of the rigid-body parameters defining the relative orientation and displacement of successive base pairs.

[Comparative evaluation of postoperative complication in the reconstructive surgery of the esophagus].

The paper presents 78 patients with stenosis of the middle thoracic segment of the esophagus. The substitute, being pedunculated intestinal graft, was brought to the neck through the retrosternal space. Early post-operative complications occurred in 8.

[Endoscopic bouginage of benign esophageal and cardial strictures].

Endoscopic bouginage of benign esophageal and cardial strictures was compared with surgical treatment. Bouginage was performed by Celestin or Eder-Puestow bougies. Results obtained suggest usefulness of bouginage in many patients with benign stenosis of the upper gastrointestinal tract.

[Iatrogenic esophageal injuries].

Own experience regarding treatment of 25 iatrogenic oesophageal lesion are discussed. Diagnosis was established mainly by x-ray examination with the water soluble contrast and plain chest x-ray. One patient was treated conservatively.

[Benign esophageal tumors].

The authors present seven cases of benign oesophageal tumours treated in hospital in the years 1972-1990. Among the treated patients were six men and one woman, aged from 30 to 70 years. In four patients the tumour was situated in the middle part of the thoracic segment, and in three cases in the lower part of the supradiaphragmatic segment of the oesophagus.