A Database of Domain Definitions for Proteins with Complex Interdomain Geometry

Protein structural domains are necessary for understanding evolution and protein folding, and may vary widely from functional and sequence based domains. Although, various structural domain databases exist, defining domains for some proteins is non-trivial, and definitions of their domain boundaries are not available. Here, we present a novel database of manually defined structural domains for a representative set of proteins from the SCOP “multi-domain proteins” class. (http://prodata.swmed.edu/multidom/). We consider our domains as mobile evolutionary units, which may rearrange during protein evolution. Additionally, they may be visualized as structurally compact and possibly independently folding units. We also found that representing domains as evolutionary and folding units do not always lead to a unique domain definition. However, unlike existing databases, we retain and refine these “alternate” domain definitions after careful inspection of structural similarity, functional sites and automated domain definition methods. We provide domain definitions, including actual residue boundaries, for proteins that well known databases like SCOP and CATH do not attempt to split. Our alternate domain definitions are suitable for sequence and structure searches by automated methods. Additionally, the database can be used for training and testing domain delineation algorithms. Since our domains represent structurally compact evolutionary units, the database may be useful for studying domain properties and evolution

Theoretical study of the insulating oxides and nitrides: SiO2, GeO2, Al2O3, Si3N4, and Ge3N4

An extensive theoretical study is performed for wide bandgap crystalline oxides and nitrides, namely, SiO_{2}, GeO_{2}, Al_{2}O_{3}, Si_{3}N_{4}, and Ge_{3}N_{4}. Their important polymorphs are considered which are for SiO_{2}: $\alpha$-quartz, $\alpha$- and $\beta$-cristobalite and stishovite, for GeO_{2}: $\alpha$-quartz, and rutile, for Al_{2}O_{3}: $\alpha$-phase, for Si_{3}N_{4} and Ge_{3}N_{4}: $\alpha$- and $\beta$-phases. This work constitutes a comprehensive account of both electronic structure and the elastic properties of these important insulating oxides and nitrides obtained with high accuracy based on density functional theory within the local density approximation. Two different norm-conserving \textit{ab initio} pseudopotentials have been tested which agree in all respects with the only exception arising for the elastic properties of rutile GeO_{2}. The agreement with experimental values, when available, are seen to be highly satisfactory. The uniformity and the well convergence of this approach enables an unbiased assessment of important physical parameters within each material and among different insulating oxide and nitrides. The computed static electric susceptibilities are observed to display a strong correlation with their mass densities. There is a marked discrepancy between the considered oxides and nitrides with the latter having sudden increase of density of states away from the respective band edges. This is expected to give rise to excessive carrier scattering which can practically preclude bulk impact ionization process in Si_{3}N_{4} and Ge_{3}N_{4}.Comment: Published version, 10 pages, 8 figure

A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2

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Evolutionary relationships among barley and <i>Arabidopsis</i> core circadian clock and clock-associated genes

The circadian clock regulates a multitude of plant developmental and metabolic processes. In crop species, it contributes significantly to plant performance and productivity and to the adaptation and geographical range over which crops can be grown. To understand the clock in barley and how it relates to the components in the Arabidopsis thaliana clock, we have performed a systematic analysis of core circadian clock and clock-associated genes in barley, Arabidopsis and another eight species including tomato, potato, a range of monocotyledonous species and the moss, Physcomitrella patens. We have identified orthologues and paralogues of Arabidopsis genes which are conserved in all species, monocot/dicot differences, species-specific differences and variation in gene copy number (e.g. gene duplications among the various species). We propose that the common ancestor of barley and Arabidopsis had two-thirds of the key clock components identified in Arabidopsis prior to the separation of the monocot/dicot groups. After this separation, multiple independent gene duplication events took place in both monocot and dicot ancestors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00239-015-9665-0) contains supplementary material, which is available to authorized users

Determining gene expression on a single pair of microarrays

<p>Abstract</p> <p>Background</p> <p>In microarray experiments the numbers of replicates are often limited due to factors such as cost, availability of sample or poor hybridization. There are currently few choices for the analysis of a pair of microarrays where N = 1 in each condition. In this paper, we demonstrate the effectiveness of a new algorithm called PINC (PINC is Not Cyber-T) that can analyze Affymetrix microarray experiments.</p> <p>Results</p> <p>PINC treats each pair of probes within a probeset as an independent measure of gene expression using the Bayesian framework of the Cyber-T algorithm and then assigns a corrected p-value for each gene comparison.</p> <p>The p-values generated by PINC accurately control False Discovery rate on Affymetrix control data sets, but are small enough that family-wise error rates (such as the Holm's step down method) can be used as a conservative alternative to false discovery rate with little loss of sensitivity on control data sets.</p> <p>Conclusion</p> <p>PINC outperforms previously published methods for determining differentially expressed genes when comparing Affymetrix microarrays with N = 1 in each condition. When applied to biological samples, PINC can be used to assess the degree of variability observed among biological replicates in addition to analyzing isolated pairs of microarrays.</p

The Structure of Tumor Endothelial Marker 8 (TEM8) Extracellular Domain and Implications for Its Receptor Function for Recognizing Anthrax Toxin

Anthrax toxin, which is released from the Gram-positive bacterium Bacillus anthracis, is composed of three proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). PA binds a receptor on the surface of the target cell and further assembles into a homo-heptameric pore through which EF and LF translocate into the cytosol. Two distinct cellular receptors for anthrax toxin, TEM8/ANTXR1 and CMG2/ANTXR2, have been identified, and it is known that their extracellular domains bind PA with low and high affinities, respectively. Here, we report the crystal structure of the TEM8 extracellular vWA domain at 1.7 Å resolution. The overall structure has a typical integrin fold and is similar to that of the previously published CMG2 structure. In addition, using structure-based mutagenesis, we demonstrate that the putative interface region of TEM8 with PA (consisting of residues 56, 57, and 154–160) is responsible for the PA-binding affinity differences between the two receptors. In particular, Leu56 was shown to be a key factor for the lower affinity of TEM8 towards PA compared with CMG2. Because of its high affinity for PA and low expression in normal tissues, an isolated extracellular vWA domain of the L56A TEM8 variant may serve as a potent antitoxin and a potential therapeutic treatment for anthrax infection. Moreover, as TEM8 is often over-expressed in tumor cells, our TEM8 crystal structure may provide new insights into how to design PA mutants that preferentially target tumor cells

Effects of rose hip intake on risk markers of type 2 diabetes and cardiovascular disease: a randomized, double-blind, cross-over investigation in obese persons

BACKGROUND/OBJECTIVES:In studies performed in mice, rose hip powder has been shown to both prevent and reverse high-fat diet-induced obesity and glucose intolerance as well as reduce plasma levels of cholesterol. The aim of this study was to investigate whether daily intake of rose hip powder over 6 weeks exerts beneficial metabolic effects in obese individuals.SUBJECTS/METHODS:A total of 31 obese individuals with normal or impaired glucose tolerance were enrolled in a randomized, double-blind, cross-over study in which metabolic effects of daily intake of a rose hip powder drink over 6 weeks was compared with a control drink. Body weight, glucose tolerance, blood pressure, blood lipids and markers of inflammation were assessed in the subjects.RESULTS:In comparison with the control drink, 6 weeks of daily consumption of the rose hip drink resulted in a significant reduction of systolic blood pressure (-3.4%; P=0.021), total plasma cholesterol (-4.9%; P=0.0018), low-density lipoprotein (LDL) cholesterol (-6.0%; P=0.012) and LDL/HDL ratio (-6.5%; P=0.041). The Reynolds risk assessment score for cardiovascular disease was decreased in the rose hip group compared with the control group (-17%; P=0.007). Body weight, diastolic blood pressure, glucose tolerance, and plasma levels of high-density lipoprotein (HDL) cholesterol, triglycerides, incretins and markers of inflammation did not differ between the two groups.CONCLUSIONS:Daily consumption of 40 g of rose hip powder for 6 weeks can significantly reduce cardiovascular risk in obese people through lowering of systolic blood pressure and plasma cholesterol levels.European Journal of Clinical Nutrition advance online publication, 14 December 2011; doi:10.1038/ejcn.2011.203