General scheme for stable single and multiatom nanomagnets according to symmetry selection rules

Article / Letter to editorLeids Instituut Onderzoek Natuurkund

General scheme for stable single and multiatom nanomagnets according to symmetry selection rules

Article / Letter to editorLeids Instituut Onderzoek Natuurkund

Genome-wide co-expression analysis in multiple tissues

Expression quantitative trait loci (eQTLs) represent genetic control points of gene expression, and can be categorized as cis- and trans-acting, reflecting local and distant regulation of gene expression respectively. Although there is evidence of co-regulation within clusters of trans-eQTLs, the extent of co-expression patterns and their relationship with the genotypes at eQTLs are not fully understood. We have mapped thousands of cis- and trans-eQTLs in four tissues (fat, kidney, adrenal and left ventricle) in a large panel of rat recombinant inbred (RI) strains. Here we investigate the genome-wide correlation structure in expression levels of eQTL transcripts and underlying genotypes to elucidate the nature of co-regulation within cis- and trans-eQTL datasets. Across the four tissues, we consistently found statistically significant correlations of cis-regulated gene expression to be rare (<0.9% of all pairs tested). Most (>80%) of the observed significant correlations of cis-regulated gene expression are explained by correlation of the underlying genotypes. In comparison, co-expression of trans-regulated gene expression is more common, with significant correlation ranging from 2.9%-14.9% of all pairs of trans-eQTL transcripts. We observed a total of 81 trans-eQTL clusters (hot-spots), defined as consisting of > or =10 eQTLs linked to a common region, with very high levels of correlation between trans-regulated transcripts (77.2-90.2%). Moreover, functional analysis of large trans-eQTL clusters (> or =30 eQTLs) revealed significant functional enrichment among genes comprising 80% of the large clusters. The results of this genome-wide co-expression study show the effects of the eQTL genotypes on the observed patterns of correlation, and suggest that functional relatedness between genes underlying trans-eQTLs is reflected in the degree of co-expression observed in trans-eQTL clusters. Our results demonstrate the power of an integrative, systematic approach to the analysis of a large gene expression dataset to uncover underlying structure, and inform future eQTL studies

Simulation, Experiment, and Evolution: Understanding Nucleation in Protein S6 Folding

In this study, we explore nucleation and the transition state ensemble of the ribosomal protein S6 using a Monte Carlo Go model in conjunction with restraints from experiment. The results are analyzed in the context of extensive experimental and evolutionary data. The roles of individual residues in the folding nucleus are identified and the order of events in the S6 folding mechanism is explored in detail. Interpretation of our results agrees with, and extends the utility of, experiments that shift f-values by modulating denaturant concentration and presents strong evidence for the realism of the mechanistic details in our Monte Carlo Go model and the structural interpretation of experimental f-values. We also observe plasticity in the contacts of the hydrophobic core that support the specific nucleus. For S6, which binds to RNA and protein after folding, this plasticity may result from the conformational flexibility required to achieve biological function. These results present a theoretical and conceptual picture that is relevant in understanding the mechanism of nucleation in protein folding.Comment: PNAS in pres

Experimental study exploring the factors that promote rib fragility in the elderly

Rib fractures represent a common injury type due to blunt chest trauma, affecting hospital stay and mortality especially in elderly patients. Factors promoting rib fragility, however, are little investigated. The purpose of this in vitro study was to explore potential determinants of human rib fragility in the elderly. 89 ribs from 13 human donors (55\u201399 years) were loaded in antero-posterior compression until fracture using a material testing machine, while surface strains were captured using a digital image correlation system. The effects of age, sex, bone mineral density, rib level and side, four global morphological factors (e.g. rib length), and seven rib cross-sectional morphological factors (e.g. cortical thickness, determined by \u3bcCT), on fracture load were statistically examined using Pearson correlation coefficients, Mann\u2013Whitney U test as well as Kruskal\u2013Wallis test with Dunn-Bonferroni post hoc correction. Fracture load showed significant dependencies (p < 0.05) from bone mineral density, age, antero-posterior rib length, cortical thickness, bone volume/tissue volume ratio, trabecular number, trabecular separation, and both cross-sectional area moments of inertia and was significantly higher at rib levels 7 and 8 compared to level 4 (p = 0.001/0.013), whereas side had no significant effect (p = 0.989). Cortical thickness exhibited the highest correlation with fracture load (r = 0.722), followed by the high correlation of fracture load with the area moment of inertia around the longitudinal rib cross-sectional axis (r = 0.687). High correlations with maximum external rib surface strain were detected for bone volume/tissue volume ratio (r = 0.631) and trabecular number (r = 0.648), which both also showed high correlations with the minimum internal rib surface strain (r = 12 0.644/ 12 0.559). Together with rib level, the determinants cortical thickness, area moment of inertia around the longitudinal rib cross-sectional axis, as well as bone mineral density exhibited the largest effects on human rib fragility with regard to the fracture load. Sex, rib cage side, and global morphology, in contrast, did not affect rib fragility in this study. When checking elderly patients for rib fractures due to blunt chest trauma, patients with low bone mineral density and the mid-thoracic area should be carefully examined