Differentiation-dependent localisation of tissue-type plasminogen activator in human bladder urothelium

Human bladder urothelium is able to secrete tissue-type plasminogen activator (tPA). The aim of our study was to analyse localisation of tPA antigen in comparison to differentiation state of cells in samples of histologically normal urothelium and non-invasive tumours of the human urinary bladder. Twenty-five samples of normal urothelium and 31 non-invasive papillary tumours from 36 patients were examined. The presence of tPA antigen was evaluated immunohistochemically. Differentiation of superficial cells was assessed by the presence of urothelial cell differentiation markers, uroplakins (UPs; immunohistochemistry) and cell's apical surface architecture (scanning electron microscopy). All tissue samples stained anti-tPA positive. In normal urothelium, the intensity of anti-tPA staining was the strongest in superficial cells, which were well-differentiated. In tumours, all cell layers stained anti-tPA positive. The intensity of anti-tPA positive reaction in the upper cell layer correlated with the percentage of anti-UP positive superficial cells. Superficial cells showed various differentiation states. The localisation of tPA antigen in human in vivo tissue is not confined to the well-differentiated superficial cells. Our results suggest a positive correlation between tPA secretion and cell differentiation.     

B-mode and color Doppler ultrasound of the forearm arteries in the preoperative screening prior to coronary artery bypass grafting

The objective of this paper was to establish the normal findings of B-mode and color Doppler ultrasound of the forearm arteries in candidates for coronary artery bypass grafting with radial artery graft. Examination of radial and ulnar arteries was performed in 127 patients. The vessel diameters and peak systolic velocities were measured and the presence of atherosclerotic changes, calcifications and anatomical variants was assessed. Radial artery proved to be dominant forearm artery with non-significant side-to-side asymmetry. The luminal changes were present in 30% of the patients. Ulnar arteries were more prone to these changes than radial arteries (28.4% vs. 24.4%). The anatomical variants found included ulnar artery hypoplasia in 3.9% of patients and high brachial artery bifurcation in 2.4% of patients. No cases of high-grade stenosis or occlusion were found. The results of the present study indicate that B-mode and color Doppler are valuable methods for preoperative screening as they enable morphological and functional evaluation of the forearm circulation.     

A Systematic Framework for Molecular Dynamics Simulations of Protein Post-Translational Modifications

By directly affecting structure, dynamics and interaction networks of their targets, post-translational modifications (PTMs) of proteins play a key role in different cellular processes ranging from enzymatic activation to regulation of signal transduction to cell-cycle control. Despite the great importance of understanding how PTMs affect proteins at the atomistic level, a systematic framework for treating post-translationally modified amino acids by molecular dynamics (MD) simulations, a premier high-resolution computational biology tool, has never been developed. Here, we report and validate force field parameters (GROMOS 45a3 and 54a7) required to run and analyze MD simulations of more than 250 different types of enzymatic and non-enzymatic PTMs. The newly developed GROMOS 54a7 parameters in particular exhibit near chemical accuracy in matching experimentally measured hydration free energies (RMSE = 4.2 kJ/mol over the validation set). Using this tool, we quantitatively show that the majority of PTMs greatly alter the hydrophobicity and other physico-chemical properties of target amino acids, with the extent of change in many cases being comparable to the complete range spanned by native amino acids.     

Regular dog-walking improves physical capacity in elderly patients after myocardial infarction

Various positive effects of pet ownership on cardiovascular health are well known. The aim of this prospective and controlled longitudinal study was to determine the effects of everyday dog-walking on physical capacity in elderly patients during the first year after myocardial infarction. Regularly dog-walking for at least 15 minutes three times a day is related to significantly higher work load on the bicycle exercise test (72.5 +/- 10.75 versus 67.6 +/- 11.6 W p < 0.05) in the "dog-walking" group (N = 29, mean age 72.5 years) at 12 months compared to the control group (N = 30, mean age 71.7 years). Our results suggest that dogs may help to maintain continuous physical activity in elderly cardiovascular patients promoting their physical capacity. Further researches are needed to confirm this association as well to identify other possible influences of dog ownership on the cardiovascular health and on the outcome in patients after myocardial infarction.     

Native-like mean structure in the unfolded ensemble of small proteins

The nature of the unfolded state plays a great role in our understanding of proteins. However, accurately studying the unfolded state with computer simulation is difficult, due to its complexity and the great deal of sampling required. Using a supercluster of over 10,000 processors we have performed close to 800 micros of molecular dynamics simulation in atomistic detail of the folded and unfolded states of three polypeptides from a range of structural classes: the all-alpha villin headpiece molecule, the beta hairpin tryptophan zipper, and a designed alpha-beta zinc finger mimic. A comparison between the folded and the unfolded ensembles reveals that, even though virtually none of the individual members of the unfolded ensemble exhibits native-like features, the mean unfolded structure (averaged over the entire unfolded ensemble) has a native-like geometry. This suggests several novel implications for protein folding and structure prediction as well as new interpretations for experiments which find structure in ensemble-averaged measurements.     

Clustering of protein domains for functional and evolutionary studies

Background  

The number of protein family members defined by DNA sequencing is usually much larger than those characterised experimentally. This paper describes a method to divide protein families into subtypes purely on sequence criteria. Comparison with experimental data allows an independent test of the quality of the clustering.     

H?herkuckuck (Clamator glandarius) — Brutvogel in Bulgarien

Summary Of the Great Spotted Cuckoo 15 records exist in Blugaria. Breeding has been supposed so far. In 1988, a fledgling Great Spotted Cuckoo was seen together with a family of Magpies in the southwestern part of the country. So breeding is confirmed.     

Of RNA-binding proteins and their targets: interaction determines expression

Combining the prediction of interactions between mRNAs and RNA-binding proteins with experimental expression profiles uncovers novel regulatory paradigms concerning proliferation and differentiation processes.See related research, http://genomebiology.com/2014/15/1/R13