Nuclear magnetic resonance measurements reveal the origin of the Debye process in monohydroxy alcohols

Monohydroxy alcohols show a structural relaxation and at longer time scales a Debye-type dielectric peak. From spin-lattice relaxation experiments using different nuclear probes an intermediate, slower-than-structural dynamics is identified for n-butanol. Based on these findings and on diffusion measurements, a model of self-restructuring, transient chains is proposed. The model is demonstrated to explain consistently the so far puzzling observations made for this class of hydrogen-bonded glass forming liquids.Comment: 4 pages, 4 figure

Valuation of scleroderma and psoriatic arthritis health states by the general public

<p>Abstract</p> <p>Objective</p> <p>Psoriatic arthritis (PsA) and scleroderma (SSc) are chronic rheumatic disorders with detrimental effects on health-related quality of life. Our objective was to assess health values (utilities) from the general public for health states common to people with PsA and SSc for economic evaluations.</p> <p>Methods</p> <p>Adult subjects from the general population in a Midwestern city (N = 218) completed the SF-12 Health Survey and computer-assisted 0-100 rating scale (RS), time trade-off (TTO, range: 0.0-1.0) and standard gamble (SG, range: 0.0-1.0) utility assessments for several hypothetical PsA and SSc health states.</p> <p>Results</p> <p>Subjects included 135 (62%) females, 143 (66%) Caucasians, and 62 (28%) African-Americans. The mean (SD) scores for the SF-12 Physical Component Summary scale were 52.9 (8.3) and for the SF-12 Mental Component Summary scale were 49.0 (9.1), close to population norms. The mean RS, TTO, and SG scores for PsA health states varied with severity, ranging from 20.2 to 63.7 (14.4-20.3) for the RS 0.29 to 0.78 (0.24-0.31) for the TTO, and 0.48 to 0.82 (0.24-0.34) for the SG. The mean RS, TTO, and SG scores for SSc health states were 25.3-69.7 (15.2-16.3) for the RS, 0.36-0.80 (0.25-0.31) for the TTO, and 0.50-0.81 (0.26-0.32) for the SG, depending on disease severity.</p> <p>Conclusion</p> <p>Health utilities for PsA and SSc health states as assessed from the general public reflect the severity of the diseases. These descriptive findings could have implications regarding comparative effectiveness research for tests and treatments for PsA and SSc.</p

Wide-Scale Analysis of Human Functional Transcription Factor Binding Reveals a Strong Bias towards the Transcription Start Site

We introduce a novel method to screen the promoters of a set of genes with shared biological function, against a precompiled library of motifs, and find those motifs which are statistically over-represented in the gene set. The gene sets were obtained from the functional Gene Ontology (GO) classification; for each set and motif we optimized the sequence similarity score threshold, independently for every location window (measured with respect to the TSS), taking into account the location dependent nucleotide heterogeneity along the promoters of the target genes. We performed a high throughput analysis, searching the promoters (from 200bp downstream to 1000bp upstream the TSS), of more than 8000 human and 23,000 mouse genes, for 134 functional Gene Ontology classes and for 412 known DNA motifs. When combined with binding site and location conservation between human and mouse, the method identifies with high probability functional binding sites that regulate groups of biologically related genes. We found many location-sensitive functional binding events and showed that they clustered close to the TSS. Our method and findings were put to several experimental tests. By allowing a "flexible" threshold and combining our functional class and location specific search method with conservation between human and mouse, we are able to identify reliably functional TF binding sites. This is an essential step towards constructing regulatory networks and elucidating the design principles that govern transcriptional regulation of expression. The promoter region proximal to the TSS appears to be of central importance for regulation of transcription in human and mouse, just as it is in bacteria and yeast.Comment: 31 pages, including Supplementary Information and figure

A new bivalve fauna from the Permian-Triassic boundary section of southwestern China

A new marine bivalve fauna from the continuous Upper Permian Longtan Formation to Lower Triassic Yelang Formation of the Zhongzai section in southwestern China is documented. Four bivalve assemblages spanning the Permian&ndash;Triassic boundary are recognized and regionally correlated in South China. The bivalve assemblages changed from elements dominated by Palaeozoic types to those dominated by Mesozoic types. Three new species, Claraia zhongzaiensis sp. nov., Claraia sp. nov. 1 and Claraia sp. nov. 2, are described

Ortho2ExpressMatrix—a web server that interprets cross-species gene expression data by gene family information

<p>Abstract</p> <p>Background</p> <p>The study of gene families is pivotal for the understanding of gene evolution across different organisms and such phylogenetic background is often used to infer biochemical functions of genes. Modern high-throughput experiments offer the possibility to analyze the entire transcriptome of an organism; however, it is often difficult to deduct functional information from that data.</p> <p>Results</p> <p>To improve functional interpretation of gene expression we introduce Ortho2ExpressMatrix, a novel tool that integrates complex gene family information, computed from sequence similarity, with comparative gene expression profiles of two pre-selected biological objects: gene families are displayed with two-dimensional matrices. Parameters of the tool are object type (two organisms, two individuals, two tissues, etc.), type of computational gene family inference, experimental meta-data, microarray platform, gene annotation level and genome build. Family information in Ortho2ExpressMatrix bases on computationally different protein family approaches such as EnsemblCompara, InParanoid, SYSTERS and Ensembl Family. Currently, respective all-against-all associations are available for five species: human, mouse, worm, fruit fly and yeast. Additionally, microRNA expression can be examined with respect to miRBase or TargetScan families. The visualization, which is typical for Ortho2ExpressMatrix, is performed as matrix view that displays functional traits of genes (differential expression) as well as sequence similarity of protein family members (BLAST e-values) in colour codes. Such translations are intended to facilitate the user's perception of the research object.</p> <p>Conclusions</p> <p>Ortho2ExpressMatrix integrates gene family information with genome-wide expression data in order to enhance functional interpretation of high-throughput analyses on diseases, environmental factors, or genetic modification or compound treatment experiments. The tool explores differential gene expression in the light of orthology, paralogy and structure of gene families up to the point of ambiguity analyses. Results can be used for filtering and prioritization in functional genomic, biomedical and systems biology applications. The web server is freely accessible at <url>http://bioinf-data.charite.de/o2em/cgi-bin/o2em.pl</url>.</p

Genetics of Systemic Sclerosis: An Update

Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, immune cell activation, and fibrosis of the skin and internal organs. Over the past few years, a role for genetics in the susceptibility for SSc has been established. This review aims to provide an update on the progress made in the past year or so within the field of SSc genetics research. This year has been of particular interest due to the publication of a large genome-wide association study, further investigations into gene–gene interactions, and the tendency to validate genetic results in functional models

A torque-based method demonstrates increased rigidity in Parkinson’s disease during low-frequency stimulation

Low-frequency oscillations in the basal ganglia are prominent in patients with Parkinson’s disease off medication. Correlative and more recent interventional studies potentially implicate these rhythms in the pathophysiology of Parkinson’s disease. However, effect sizes have generally been small and limited to bradykinesia. In this study, we investigate whether these effects extend to rigidity and are maintained in the on-medication state. We studied 24 sides in 12 patients on levodopa during bilateral stimulation of the STN at 5, 10, 20, 50, 130 Hz and in the off-stimulation state. Passive rigidity at the wrist was assessed clinically and with a torque-based mechanical device. Low-frequency stimulation at ≤20 Hz increased rigidity by 24 % overall (p = 0.035), whereas high-frequency stimulation (130 Hz) reduced rigidity by 18 % (p = 0.033). The effects of low-frequency stimulation (5, 10 and 20 Hz) were well correlated with each other for both flexion and extension (r = 0.725 ± SEM 0.016 and 0.568 ± 0.009, respectively). Clinical assessments were unable to show an effect of low-frequency stimulation but did show a significant effect at 130 Hz (p = 0.002). This study provides evidence consistent with a mechanistic link between oscillatory activity at low frequency and Parkinsonian rigidity and, in addition, validates a new method for rigidity quantification at the wrist