Flower: extracting information from pyrosequencing data

Summary: The SFF file format produced by Roche's 454 sequencing technology is a compact, binary format that contains the flow values that are used for base and quality calling of the reads. Applications, e.g. in metagenomics, often depend on accurate sequence information, and access to flow values is important to estimate the probability of errors. Unfortunately, the programs supplied by Roche for accessing this information are not publicly available. Flower is a program that can extract the information contained in SFF files, and convert it to various textual output formats

Infrared spectroscopy of phytochrome and model pigments

Fourier-transform infrared difference spectra between the red-absorbing and far-red-absorbing forms of oat phytochrome have been measured in H2O and 2H2O. The difference spectra are compared with infrared spectra of model compounds, i.e. the (5Z,10Z,15Z)- and (5Z,10Z,15E)-isomers of 2,3,7,8,12,13,17,18-octaethyl-bilindion (Et8-bilindion), 2,3-dihydro-2,3,7,8,12,13,17,18-octaethyl-bilindion (H2Et8-bilindion), and protonated H2Et8-bilindion in various solvents. The spectra of the model compounds show that only for the protonated forms can clear differences between the two isomers be detected. Since considerable differences are present between the spectra of Et8-bilindion and H2Et8-bilindion, it is concluded that only the latter compound can serve as a model system of phytochrome. The 2H2O effect on the difference spectrum of phytochrome supports the view that the chromophore in red-absorbing phytochrome is protonated and suggests, in addition, that it is also protonated in far-red-absorbing phytochrome. The spectra show that protonated carboxyl groups are influenced. The small amplitudes in the difference spectra exclude major changes of protein secondary structure

Pebble and Rock Band: Heuristic Resolution of Repeats and Scaffolding in the Velvet Short-Read de Novo Assembler

BACKGROUND: Despite the short length of their reads, micro-read sequencing technologies have shown their usefulness for de novo sequencing. However, especially in eukaryotic genomes, complex repeat patterns are an obstacle to large assemblies. PRINCIPAL FINDINGS: We present a novel heuristic algorithm, Pebble, which uses paired-end read information to resolve repeats and scaffold contigs to produce large-scale assemblies. In simulations, we can achieve weighted median scaffold lengths (N50) of above 1 Mbp in Bacteria and above 100 kbp in more complex organisms. Using real datasets we obtained a 96 kbp N50 in Pseudomonas syringae and a unique 147 kbp scaffold of a ferret BAC clone. We also present an efficient algorithm called Rock Band for the resolution of repeats in the case of mixed length assemblies, where different sequencing platforms are combined to obtain a cost-effective assembly. CONCLUSIONS: These algorithms extend the utility of short read only assemblies into large complex genomes. They have been implemented and made available within the open-source Velvet short-read de novo assembler

The impact of ischemic stroke on connectivity gradients

The functional organization of the brain can be represented as a low-dimensional space that reflects its macroscale hierarchy. The dimensions of this space, described as connectivity gradients, capture the similarity of areas' connections along a continuous space. Studying how pathological perturbations with known effects on functional connectivity affect these connectivity gradients provides support for their biological relevance. Previous work has shown that localized lesions cause widespread functional connectivity alterations in structurally intact areas, affecting a network of interconnected regions. By using acute stroke as a model of the effects of focal lesions on the connectome, we apply the connectivity gradient framework to depict how functional reorganization occurs throughout the brain, unrestricted by traditional definitions of functional network boundaries. We define a three-dimensional connectivity space template based on functional connectivity data from healthy controls. By projecting lesion locations into this space, we demonstrate that ischemic strokes result in dimension-specific alterations in functional connectivity over the first week after symptom onset. Specifically, changes in functional connectivity were captured along connectivity Gradients 1 and 3. The degree of functional connectivity change was associated with the distance from the lesion along these connectivity gradients (a measure of functional similarity) regardless of the anatomical distance from the lesion. Together, these results provide support for the biological validity of connectivity gradients and suggest a novel framework to characterize connectivity alterations after stroke

Biomarkers of Myocardial Stress and Systemic Inflammation in Patients Who Engage in Heart Failure Self-Care Management

Background: Self-care is believed to improve heart failure (HF) outcomes, but the mechanisms by which such improvement occurs remain unclear. Methods: We completed a secondary analysis of cross-sectional data collected on adults with symptomatic HF to test our hypothesis that effective self-care is associated with less myocardial stress and systemic inflammation. Multivariate logistic regression modeling was used to determine if better HF self-care reduced the odds of having serum levels of amino-terminal pro-B-type natriuretic peptide and soluble tumor necrosis factor α receptor type 1 at or greater than the sample median. Heart failure self-care was measured using the Self-care of Heart Failure Index. Results: The sample (n = 168) was predominantly male (65.5%), and most (50.6%) had New York Heart Association III HF (mean left ventricular ejection fraction, 34.9% [SD, 14.0%]); mean age was 58.8 (SD, 11.5) years. Self-care management was an independent factor in the model (block χ2 = 14.74; P = .005) after controlling for pertinent confounders (model χ2 = 52.15; P \u3c .001). Each 1-point increase in self-care management score (range, 15-100) was associated with a 12.7% reduction in the odds of having levels of both biomarkers at or greater than the sample median (adjusted odds ratio, 0.873; 95% confidence interval, 0.77-0.99; P = .03). Conclusion: Better self-care management was associated with reduced odds of myocardial stress and systemic inflammation over and above pharmacological therapy and other common confounding factors. Teaching HF patients early symptom recognition and self-care of symptoms may decrease myocardial stress and systemic inflammation

Elevated myocardial and lymphocyte GRK2 expression and activity in human heart failure.

The G protein-coupled receptor kinase-2 (GRK2 or beta-ARK1) regulates beta-adrenergic receptors (beta-ARs) in the heart, and its cardiac expression is elevated in human heart failure (HF). We sought to determine whether myocardial levels and activity of GRK2 could be monitored using white blood cells, which have been used to study cardiac beta-ARs. Moreover, we were interested in determining whether GRK2 levels in myocardium and lymphocytes may be associated with beta-AR dysfunction and HF severity.In myocardial biopsies from explanted failing human hearts, GRK activity was inversely correlated with beta-AR-mediated cAMP production (R(2)=-0.215, P<0.05, n=24). Multiple regression analysis confirmed that GRK activity participates with beta-AR density to regulate catecholamine-sensitive cAMP responses. Importantly, there was a direct correlation between myocardial and lymphocytes GRK2 activity (R(2)=0.5686, P<0.05, n=10). Lymphocyte GRK activity was assessed in HF patients with various ejection fractions (EFs) (n=33), and kinase activity was significantly higher in patients with lower EFs and was higher with increasing NYHA class (P<0.001).Myocardial GRK2 expression and activity are mirrored by lymphocyte levels of this kinase, and its elevation in HF is associated with the loss of beta-AR responsiveness and appears to increase with disease severity. Therefore, lymphocytes may provide a surrogate for monitoring cardiac GRK2 in human HF

Disentangling cortical functional connectivity strength and topography reveals divergent roles of genes and environment

The human brain varies across individuals in its morphology, function, and cognitive capacities. Variability is particularly high in phylogenetically modern regions associated with higher order cognitive abilities, but its relationship to the layout and strength of functional networks is poorly understood. In this study we disentangled the variability of two key aspects of functional connectivity: strength and topography. We then compared the genetic and environmental influences on these two features. Genetic contribution is heterogeneously distributed across the cortex and differs for strength and topography. In heteromodal areas genes predominantly affect the topography of networks, while their connectivity strength is shaped primarily by random environmental influence such as learning. We identified peak areas of genetic control of topography overlapping with parts of the processing stream from primary areas to network hubs in the default mode network, suggesting the coordination of spatial configurations across those processing pathways. These findings provide a detailed map of the diverse contribution of heritability and individual experience to the strength and topography of functional brain architecture.Nanyang Technological UniversityPublished versionThis work was supported by the Medical University of Vienna, the Austrian Research Fund (FWF) [grants P 35189, P 34198, and I 3925-B27] in collaboration with the French National Research Agency (ANR), the Vienna Science and Technology Fund (WWTF) [LS20-065], the European Research Council Grant [866533-CORTIGRAD], the National Natural Science Foundation of China [Grant No. 81790652, No.81790650] and the NAM Advanced Biomedical Imaging Program [FY2016] between Nanyang Technological University, Singapore and Medical University of Vienna, Austria