A critical base pair in k-turns that confers folding characteristics and correlates with biological function

Kink turns (k-turns) are widespread elements in RNA that mediate tertiary contacts by kinking the helical axis. We have found that the ability of k-turns to undergo ion-induced folding is conferred by a single base pair that follows the conserved A·G pairs, that is, the 3b·3n position. A Watson–Crick pair leads to an inability to fold in metal ions alone, while 3n=G or 3b=C (but not both) permits folding. Crystallographic study reveals two hydrated metal ions coordinated to O6 of G3n and G2n of Kt-7. Removal of either atom impairs Mg(2+)-induced folding in solution. While SAM-I riboswitches have 3b·3n sequences that would predispose them to ion-induced folding, U4 snRNA are strongly biased to an inability to such folding. Thus riboswitch sequences allow folding to occur independently of protein binding, while U4 should remain unfolded until bound by protein. The empirical rules deduced for k-turn folding have strong predictive value

Noncompaction of the Ventricular Myocardium Is Associated with a De Novo Mutation in the β-Myosin Heavy Chain Gene

Noncompaction of the ventricular myocardium (NVM) is the morphological hallmark of a rare familial or sporadic unclassified heart disease of heterogeneous origin. NVM results presumably from a congenital developmental error and has been traced back to single point mutations in various genes. The objective of this study was to determine the underlying genetic defect in a large German family suffering from NVM. Twenty four family members were clinically assessed using advanced imaging techniques. For molecular characterization, a genome-wide linkage analysis was undertaken and the disease locus was mapped to chromosome 14ptel-14q12. Subsequently, two genes of the disease interval, MYH6 and MYH7 (encoding the α- and β-myosin heavy chain, respectively) were sequenced, leading to the identification of a previously unknown de novo missense mutation, c.842G>C, in the gene MYH7. The mutation affects a highly conserved amino acid in the myosin subfragment-1 (R281T). In silico simulations suggest that the mutation R281T prevents the formation of a salt bridge between residues R281 and D325, thereby destabilizing the myosin head. The mutation was exclusively present in morphologically affected family members. A few members of the family displayed NVM in combination with other heart defects, such as dislocation of the tricuspid valve (Ebstein's anomaly, EA) and atrial septal defect (ASD). A high degree of clinical variability was observed, ranging from the absence of symptoms in childhood to cardiac death in the third decade of life. The data presented in this report provide first evidence that a mutation in a sarcomeric protein can cause noncompaction of the ventricular myocardium

Instabilities in the wake of an inclined prolate spheroid

We investigate the instabilities, bifurcations and transition in the wake behind a 45-degree inclined 6:1 prolate spheroid, through a series of direct numerical simulations (DNS) over a wide range of Reynolds numbers (Re) from 10 to 3000. We provide a detailed picture of how the originally symmetric and steady laminar wake at low Re gradually looses its symmetry and turns unsteady as Re is gradually increased. Several fascinating flow features have first been revealed and subsequently analysed, e.g. an asymmetric time-averaged flow field, a surprisingly strong side force etc. As the wake partially becomes turbulent, we investigate a dominating coherent wake structure, namely a helical vortex tube, inside of which a helical symmetry alteration scenario was recovered in the intermediate wake, together with self-similarity in the far wake.Comment: Book chapter in "Computational Modeling of Bifurcations and Instabilities in Fluid Dynamics (A. Gelfgat ed.)", Springe

Nothing Lasts Forever: Environmental Discourses on the Collapse of Past Societies

The study of the collapse of past societies raises many questions for the theory and practice of archaeology. Interest in collapse extends as well into the natural sciences and environmental and sustainability policy. Despite a range of approaches to collapse, the predominant paradigm is environmental collapse, which I argue obscures recognition of the dynamic role of social processes that lie at the heart of human communities. These environmental discourses, together with confusion over terminology and the concepts of collapse, have created widespread aporia about collapse and resulted in the creation of mixed messages about complex historical and social processes

Climate prediction: an evidence-based perspective

This paper considers climate prediction from the perspective of the experimental, physical sciences, and discusses three ways in which the two differ. First, the construction of long-term climate series requires benchmark measurements, i.e., measurements calibrated in situ against international standards. An instrument capable of accurate, benchmark measurements of thermal, spectral radiances from space is available but has yet to be used. Second, objective criteria are needed to evaluate measurements for the purpose of improving climate predictions. Techniques based on Bayesian inference are now available. Third is the question of how to use suitable data to improve a climate prediction, when they are available. A method based on the Bayesian Evidence Function is, in principle, available, but has yet to be exploited. None of these three aspects are considered in current operational climate forecasting. All three are potentially capable of improving forecasts, and all are subjects of current research programs, with the likelihood of their eventual adoption