"GenotypeColour?": colour visualisation of SNPs and CNVs

Background  

The volume of data available on genetic variations has increased considerably with the recent development of high-density, single-nucleotide polymorphism (SNP) arrays. Several software programs have been developed to assist researchers in the analysis of this huge amount of data, but few can rely upon a whole genome variability visualisation system that could help data interpretation.     

Molecular dynamics simulations of a lithium/sodium carbonate mixture

The diffusion and ionic conductivity of Li _x Na_1?x CO₃ salt mixtures were studied by means of Molecular Dynamics (MD) simulations, using the Janssen and Tissen model (Janssen and Tissen, Mol Simul 5:83–98; 1990). These salts have received particular attention due to their central role in fuel cells technology, and reliable numerical methods that could perform as important interpretative tool of experimental data are thus required but still lacking. The chosen computational model nicely reproduces the main structural behaviour of the pure Li₂CO₃, Na₂CO₃ and K₂CO₃ carbonates, but also of their Li/K and Li/Na mixtures. However, it fails to accurately describe dynamic properties such as activation energies of diffusion and conduction processes, outlining the need to develop more accurate models for the simulation of molten salt carbonates.     

Designing and Implementing an Assay for the Detection of Rare and Divergent NRPS and PKS Clones in European,Antarctic and Cuban Soils

The ever increasing microbial resistome means there is an urgent need for new antibiotics. Metagenomics is an underexploited tool in the field of drug discovery. In this study we aimed to produce a new updated assay for the discovery of biosynthetic gene clusters encoding bioactive secondary metabolites. PCR assays targeting the polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS) were developed. A range of European soils were tested for their biosynthetic potential using clone libraries developed from metagenomic DNA. Results revealed a surprising number of NRPS and PKS clones with similarity to rare Actinomycetes. Many of the clones tested were phylogenetically divergent suggesting they were fragments from novel NRPS and PKS gene clusters. Soils did not appear to cluster by location but did represent NRPS and PKS clones of diverse taxonomic origin. Fosmid libraries were constructed from Cuban and Antarctic soil samples; 17 fosmids were positive for NRPS domains suggesting a hit rate of less than 1 in 10 genomes. NRPS hits had low similarities to both rare Actinobacteria and Proteobacteria; they also clustered with known antibiotic producers suggesting they may encode for pathways producing novel bioactive compounds. In conclusion we designed an assay capable of detecting divergent NRPS and PKS gene clusters from the rare biosphere; when tested on soil samples results suggest the majority of NRPS and PKS pathways and hence bioactive metabolites are yet to be discovered.     

Physique and Performance of Young Wheelchair Basketball Players in Relation with Classification

The relationships among physical characteristics, performance, and functional ability classification of younger wheelchair basketball players have been barely investigated to date. The purpose of this work was to assess anthropometry, body composition, and performance in sport-specific field tests in a national sample of Italian younger wheelchair basketball players as well as to evaluate the association of these variables with the players’ functional ability classification and game-related statistics. Several anthropometric measurements were obtained for 52 out of 91 eligible players nationwide. Performance was assessed in seven sport-specific field tests (5m sprint, 20m sprint with ball, suicide, maximal pass, pass for accuracy, spot shot and lay-ups) and game-related statistics (free-throw points scored per match, two- and three-point field-goals scored per match, and their sum). Association between variables, and predictivity was assessed by correlation and regression analysis, respectively. Players were grouped into four Classes of increasing functional ability (A-D). One-way ANOVA with Bonferroni’s correction for multiple comparisons was used to assess differences between Classes. Sitting height and functional ability Class especially correlated with performance outcomes, but wheelchair basketball experience and skinfolds did not. Game-related statistics and sport-specific field-test scores all showed significant correlation with each other. Upper arm circumference and/or maximal pass and lay-ups test scores were able to explain 42 to 59% of variance in game-related statistics (P<0.001). A clear difference in performance was only found for functional ability Class A and D. Conclusion: In younger wheelchair basketball players, sitting height positively contributes to performance. The maximal pass and lay-ups test should be carefully considered in younger wheelchair basketball training plans. Functional ability Class reflects to a limited extent the actual differences in performance.     

Unraveling the complex maternal history of Southern African Khoisan populations

The Khoisan populations of southern Africa are known to harbor some of the deepest‐rooting lineages of human mtDNA; however, their relationships are as yet poorly understood. Here, we report the results of analyses of complete mtDNA genome sequences from nearly 700 individuals representing 26 populations of southern Africa who speak diverse Khoisan and Bantu languages. Our data reveal a multilayered history of the indigenous populations of southern Africa, who are likely to be the result of admixture of different genetic substrates, such as resident forager populations and pre‐Bantu pastoralists from East Africa. We find high levels of genetic differentiation of the Khoisan populations, which can be explained by the effect of drift together with a partial uxorilocal/multilocal residence pattern. Furthermore, there is evidence of extensive contact, not only between geographically proximate groups, but also across wider areas. The results of this contact, which may have played a role in the diffusion of common cultural and linguistic features, are especially evident in the Khoisan populations of the central Kalahari. Am J Phys Anthropol 153:435–448, 2014. © 2013 Wiley Periodicals, Inc.     

Involvement of the tyrosine phosphorylation on GSH transport in NIH3T3 fibroblasts

This study demonstrates the involvement of phosphotyrosine phosphatases on the activity and regulation of GSH ATP-dependent transport system that we have previously identified in NIH3T3 fibroblasts. This is shown by the fact that increases of the initial rate of GSH uptake were measured in NIH3T3 overexpressing a synthetic gene coding for a low-Mr-phosphotyrosine protein phosphatase (LMW-PTP), while decreases were obtained in NIH3T3 overexpressing the phosphatase inactive mutant (LMW-C12SPTP), with respect to NIH3T3neo. Moreover, these results have been confirmed by experiments performed in the same cells by vanadate, and H2O2 treatment on both GSH transport and mediated passive transport of glucose. A possible regulation of this transport system by platelet-derived growth factor receptor (PDGFr) with tyrosine kinase activity is also demonstrated. Moreover, these data show a relationship among GSH, PDGFr and phosphotyrosine phosphatase activity, and suggest a role of GSH transport systems on the cell proliferation process.     

Enhanced Tethered-Particle Motion Analysis Reveals Viscous Effects

Tethered-particle motion experiments do not require expensive or technically complex hardware, and increasing numbers of researchers are adopting this methodology to investigate the topological effects of agents that act on the tethering polymer or the characteristics of the polymer itself. These investigations depend on accurate measurement and interpretation of changes in the effective length of the tethering polymer (often DNA). However, the bead size, tether length, and buffer affect the confined diffusion of the bead in this experimental system. To evaluate the effects of these factors, improved measurements to calibrate the two-dimensional range of motion (excursion) versus DNA length were carried out. Microspheres of 160 or 240 nm in radius were tethered by DNA molecules ranging from 225 to 3477 basepairs in length in aqueous buffers containing 100 mM potassium glutamate and 8 mM MgCl₂ or 10 mM Tris-HCl and 200 mM KCl, with or without 0.5% Tween added to the buffer, and the motion was recorded. Different buffers altered the excursion of beads on identical DNA tethers. Buffer with only 10 mM NaCl and >5 mM magnesium greatly reduced excursion. Glycerol added to increase viscosity slowed confined diffusion of the tethered beads but did not change excursion. The confined-diffusion coefficients for all tethered beads were smaller than those expected for freely diffusing beads and decreased for shorter tethers. Tethered-particle motion is a sensitive framework for diffusion experiments in which small beads on long leashes most closely resemble freely diffusing, untethered beads.     

Glucose compensation, serum lipids and thyroid hormones (rT3 and rT3/T3 ratio in non-insulin-dependent (type 2) diabetics: 2

In 45 type 2 diabetics it was unable to be found a relation between the plasma lipids and the fasting blood glucose (G), HbA1c, reverse T3 (rT3), rT3/T3 ratio, and relative body weight (R.B.W.). The conclusion was reached that the alteration of the lipoprotein metabolism and the thyroid hormones in type 2 diabetics could be primitive and independent from the availability of the insulin.     

Selective roles for cholesterol and actin in compartmentalization of different proteins in the Golgi and plasma membrane of polarized cells

To determine the roles of cholesterol and the actin cytoskeleton in apical and basolateral protein organization and sorting, we have performed comprehensive confocal fluorescence recovery after photobleaching analyses of apical and basolateral and raft- and non-raft-associated proteins, both at the plasma membrane and in the Golgi apparatus of polarized MDCK cells. We show that at both the apical and basolateral plasma membrane domains, raft-associated proteins diffuse faster than non-raft-associated proteins and that, different from the latter, they become restricted upon depletion of cholesterol. Furthermore, only transmembrane apical proteins are restricted by the actin network. This indicates that cholesterol-dependent domains exist both at the apical and basolateral membranes of polarized cells and that the actin cytoskeleton has a predominant role in the organization of transmembrane proteins independent of their association with rafts at the apical membrane. In the Golgi apparatus apical proteins appear to be segregated from the basolateral ones in a compartment that is sensitive both to cholesterol depletion and actin rearrangements. Furthermore, consistent with the role of actin rearrangements in apical protein sorting, we found that apical proteins exhibit a differential sensitivity to actin depolymerization in the Golgi of polarized and nonpolarized cells.