Four Distances between Pairs of Amino Acids Provide a Precise Description of their Interaction

The three-dimensional structures of proteins are stabilized by the interactions between amino acid residues. Here we report a method where four distances are calculated between any two side chains to provide an exact spatial definition of their bonds. The data were binned into a four-dimensional grid and compared to a random model, from which the preference for specific four-distances was calculated. A clear relation between the quality of the experimental data and the tightness of the distance distribution was observed, with crystal structure data providing far tighter distance distributions than NMR data. Since the four-distance data have higher information content than classical bond descriptions, we were able to identify many unique inter-residue features not found previously in proteins. For example, we found that the side chains of Arg, Glu, Val and Leu are not symmetrical in respect to the interactions of their head groups. The described method may be developed into a function, which computationally models accurately protein structures

All-sky search for continuous gravitational waves from isolated neutron stars in the early O3 LIGO data

We report on an all-sky search for continuous gravitational waves in the frequency band 20-2000 Hz and with a frequency time derivative in the range of [-1.0,+0.1]×10-8 Hz/s. Such a signal could be produced by a nearby, spinning and slightly nonaxisymmetric isolated neutron star in our Galaxy. This search uses the LIGO data from the first six months of Advanced LIGO's and Advanced Virgo's third observational run, O3. No periodic gravitational wave signals are observed, and 95% confidence-level (C.L.) frequentist upper limits are placed on their strengths. The lowest upper limits on worst-case (linearly polarized) strain amplitude h0 are ∼1.7×10-25 near 200 Hz. For a circularly polarized source (most favorable orientation), the lowest upper limits are ∼6.3×10-26. These strict frequentist upper limits refer to all sky locations and the entire range of frequency derivative values. For a population-averaged ensemble of sky locations and stellar orientations, the lowest 95% C.L. upper limits on the strain amplitude are ∼1.4×10-25. These upper limits improve upon our previously published all-sky results, with the greatest improvement (factor of ∼2) seen at higher frequencies, in part because quantum squeezing has dramatically improved the detector noise level relative to the second observational run, O2. These limits are the most constraining to date over most of the parameter space searched

Transport of Folded Proteins by the Tat System

The twin-arginine protein translocation (Tat) system has been characterized in bacteria, archaea and the chloroplast thylakoidal membrane. This system is distinct from other protein transport systems with respect to two key features. Firstly, it accepts cargo proteins with an N-terminal signal peptide that carries the canonical twin-arginine motif, which is essential for transport. Second, the Tat system only accepts and translocates fully folded cargo proteins across the respective membrane. Here, we review the core essential features of folded protein transport via the bacterial Tat system, using the three-component TatABC system of Escherichia coli and the two-component TatAC systems of Bacillus subtilis as the main examples. In particular, we address features of twin-arginine signal peptides, the essential Tat components and how they assemble into different complexes, mechanistic features and energetics of Tat-dependent protein translocation, cytoplasmic chaperoning of Tat cargo proteins, and the remarkable proofreading capabilities of the Tat system. In doing so, we present the current state of our understanding of Tat-dependent protein translocation across biological membranes, which may serve as a lead for future investigations

Comparative outcome one year after formal cardiac rehabilitation: the effects of a randomized intervention to improve exercise adherence

BACKGROUND: Methods to ensure sustained benefits of cardiac rehabilitation need to be explored. The aim was to assess the effect of a home-based intervention (INT) on exercise adherence and risk factors after cardiac rehabilitation. DESIGN: Prospective randomized study. METHODS: We evaluated patients who were followed for 1 year after either inpatient (ICR) or outpatient cardiac rehabilitation (OCR) by assessment of exercise capacity, physical activity, risk factors and quality of life, both at the completion of rehabilitation, and after 1 year. Patients were randomized to either be instructed how to use a diary of physical activities complemented by quarterly group meetings (INT) or to receive standard treatment (usual care). RESULTS: Two hundred and sixty-one patients gave consent to be reevaluated after 1 year. Of these patients 33 were lost to follow-up (two deaths); thus 228 patients had complete 1-year follow-up data (195 male and 33 female, 91% with coronary artery disease). At 1-year follow-up significantly more patients of the INT group than of the control group adhered to regular physical activity (73 vs. 40%, P>0.0001). Moreover, INT patients showed a better evolution of body mass index and lipid values. In a stepwise multiple regression analysis the following variables showed a significant impact on regular physical activity at follow-up: study INT [odds ratio (OR): 4.19, P>0.0001], previous cardiac surgery (OR: 2.50, P=0.008), BMI at baseline (OR: 0.89, P=0.018) and quality of life at baseline (OR: 1.58, P=0.041). CONCLUSION: Sustained benefits of cardiac rehabilitation can be documented 1 year after both inpatient and outpatient programmes. Self-monitoring of physical activity greatly increased long-term adherence to regular exercise, which in turn was associated with greater improvements of risk factors and quality of life