Predicted binding site information improves model ranking in protein docking using experimental and computer-generated target structures

BACKGROUND: Protein-protein interactions (PPIs) mediate the vast majority of biological processes, therefore, significant efforts have been directed to investigate PPIs to fully comprehend cellular functions. Predicting complex structures is critical to reveal molecular mechanisms by which proteins operate. Despite recent advances in the development of new methods to model macromolecular assemblies, most current methodologies are designed to work with experimentally determined protein structures. However, because only computer-generated models are available for a large number of proteins in a given genome, computational tools should tolerate structural inaccuracies in order to perform the genome-wide modeling of PPIs. RESULTS: To address this problem, we developed eRank(PPI), an algorithm for the identification of near-native conformations generated by protein docking using experimental structures as well as protein models. The scoring function implemented in eRank(PPI) employs multiple features including interface probability estimates calculated by eFindSite(PPI) and a novel contact-based symmetry score. In comparative benchmarks using representative datasets of homo- and hetero-complexes, we show that eRank(PPI) consistently outperforms state-of-the-art algorithms improving the success rate by ~10 %. CONCLUSIONS: eRank(PPI) was designed to bridge the gap between the volume of sequence data, the evidence of binary interactions, and the atomic details of pharmacologically relevant protein complexes. Tolerating structure imperfections in computer-generated models opens up a possibility to conduct the exhaustive structure-based reconstruction of PPI networks across proteomes. The methods and datasets used in this study are available at www.brylinski.org/erankppi

The LHCb upgrade I

The LHCb upgrade represents a major change of the experiment. The detectors have been almost completely renewed to allow running at an instantaneous luminosity five times larger than that of the previous running periods. Readout of all detectors into an all-software trigger is central to the new design, facilitating the reconstruction of events at the maximum LHC interaction rate, and their selection in real time. The experiment's tracking system has been completely upgraded with a new pixel vertex detector, a silicon tracker upstream of the dipole magnet and three scintillating fibre tracking stations downstream of the magnet. The whole photon detection system of the RICH detectors has been renewed and the readout electronics of the calorimeter and muon systems have been fully overhauled. The first stage of the all-software trigger is implemented on a GPU farm. The output of the trigger provides a combination of totally reconstructed physics objects, such as tracks and vertices, ready for final analysis, and of entire events which need further offline reprocessing. This scheme required a complete revision of the computing model and rewriting of the experiment's software

Taekwondo and physical fitness components in middle-aged healthy volunteers : the Sekwondo study

For one year, healthy participants over the age of forty were given Taekwondo training. Several tests administered before and after this training period showed that the participants improved their balance in several respects and even demonstrated balance checks typically seen in younger people. Another noteworthy finding was that their coordination improved as well. These improvements could not be ascribed to an increase in muscle strength or flexibility, which suggests that these changes took place in the central nervous system. The study also found an improvement in several cognitive functions, which made multitasking easier. This, combined with the fact that the training was both safe and enjoyable, means Taekwondo can be recommended for people over the age of forty to help them maintain and improve their mental and physical condition

Taekwondo training improves balance in volunteers over 40

Balance deteriorates with age, and may eventually lead to falling accidents which may threaten independent living. As Taekwondo contains various highly dynamic movement patterns, Taekwondo practice may sustain or improve balance. Therefore, in 24 middle-aged healthy volunteers (40–71 year) we investigated effects of age-adapted Taekwondo training of 1 h a week during 1 year on various balance parameters, such as: motor orientation ability (primary outcome measure), postural and static balance test, single leg stance, one leg hop test, and a questionnaire. Motor orientation ability significantly increased in favor of the antero-posterior direction with a difference of 0.62° toward anterior compared to pre-training measurement, when participants corrected the tilted platform rather toward the posterior direction; female gender being an independent outcome predictor. On postural balance measurements sway path improved in all 19 participants, with a median of 9.3 mm/s (range 0.71–45.86), and sway area in 15 participants with 4.2 mm(2)/s (range 17.39–1.22). Static balance improved with an average of 5.34 s for the right leg, and with almost 4 s for the left. Median single leg stance duration increased in 17 participants with 5 s (range 1–16), and in 13 participants with 8 s (range 1–18). The average one leg hop test distance increased (not statistically significant) with 9.5 cm. The questionnaire reported a better “ability to maintain balance” in 16. In conclusion, our data suggest that age-adapted Taekwondo training improves various aspects of balance control in healthy people over the age of 40

Naive antibody gene-segment frequencies are heritable and unaltered by chronic lymphocyte ablation

A diverse antibody repertoire is essential for an effective adaptive immune response to novel molecular surfaces. Although past studies have observed common patterns of V-segment use, as well as variation in V-segment use between individuals, the relative contributions to variance from genetics, disease, age, and environment have remained unclear. Using high-throughput sequence analysis of monozygotic twins, we show that variation in naive VH and DH segment use is strongly determined by an individual's germ-line genetic background. The inherited segment-use profiles are resilient to differential environmental exposure, disease processes, and chronic lymphocyte depletion therapy. Signatures of the inherited profiles were observed in class switched germ-line use of each individual. However, despite heritable segment use, the rearranged complementarity-determining region-H3 repertoires remained highly specific to the individual. As it has been previously demonstrated that certain V-segments exhibit biased representation in autoimmunity, lymphoma, and viral infection, we anticipate our findings may provide a unique mechanism for stratifying individual risk profiles in specific diseases

Data from: Geographical parthenogenesis and population genetic structure in the alpine species Ranunculus kuepferi (Ranunculaceae)

Geographical parthenogenesis describes the enigmatic phenomenon that asexual organisms have larger distribution areas than their sexual relatives, especially in previously glaciated areas. Classical models suggest temporary advantages to asexuality in colonization scenarios because of uniparental reproduction and clonality. We analyzed population genetic structure and self-fertility of the plant species Ranunculus kuepferi on 59 populations from the whole distribution area (European Alps, Apennines and Corsica). Amplified fragment length polymorphisms (AFLPs) and five microsatellite loci revealed individual genotypes for all populations and mostly insignificant differences between diploid sexuals and tetraploid apomicts in all measures of genetic diversity. Low frequencies of private AFLP fragments/simple sequence repeat alleles, and character incompatibility analyses suggest that facultative recombination explains best the unexpectedly high genotypic diversity of apomicts. STRUCTURE analyses using AFLPs revealed a higher number of partitions and a stronger geographical subdivision for diploids than for tetraploids, which contradicts expectations of standard gene flow models, but indicates a reduction of genetic structure in asexuals. Apomictic populations exhibited high admixture near the sexual area, but appeared rather uniform in remote areas. Bagging experiments and analyses of pollen tube growth confirmed self-fertility for pollen-dependent apomicts, but self-sterility for diploid sexuals. Facultative apomixis combines advantages of both modes of reproduction: uniparental reproduction allows for rapid colonization of remote areas, whereas facultative sexuality and polyploidy maintains genetic diversity within apomictic populations. The density dependence of outcrossing limits range expansions of sexual populations