CD209 in inflammatory bowel disease: a case-control study in the Spanish population

<p>Abstract</p> <p>Background</p> <p>The etiology of Ulcerative Colitis (UC) and Crohn's Disease (CD), considered together as Inflammatory Bowel Diseases (IBD), involves environmental and genetic factors. Although some genes are already known, the genetics underlying these diseases is complex and new candidates are continuously emerging. The <it>CD209 </it>gene is located in a region linked previously to IBD and a <it>CD209 </it>functional polymorphism (rs4804803) has been associated to other inflammatory conditions. Our aim was to study the potential involvement of this <it>CD209 </it>variant in IBD susceptibility.</p> <p>Methods</p> <p>We performed a case-control study with 515 CD patients, 497 UC patients and 731 healthy controls, all of them white Spaniards. Samples were typed for the <it>CD209 </it>single nucleotide polymorphism (SNP) rs4804803 by TaqMan technology. Frequency comparisons were performed using χ²tests.</p> <p>Results</p> <p>No association between <it>CD209 </it>and UC or CD was observed initially. However, stratification of UC patients by <it>HLA-DR3 </it>status, a strong protective allele, showed that carriage of the <it>CD209</it>_G allele could increase susceptibility in the subgroup of <it>HLA-DR3</it>-positive individuals (p = 0.03 OR = 1.77 95% CI 1.04–3.02, <it>vs. </it>controls).</p> <p>Conclusion</p> <p>A functional variant in the <it>CD209 </it>gene, rs4804803, does not seem to be influencing Crohn's disease susceptibility. However, it could be involved in the etiology or pathology of Ulcerative Colitis in <it>HLA-DR3</it>-positive individuals but further studies are necessary.</p

Sparse, continuous policy representations for uniform online bin packing via regression of interpolants

Online bin packing is a classic optimisation problem, widely tackled by heuristic methods. In addition to human-designed heuristic packing policies (e.g. first- or best- fit), there has been interest over the last decade in the automatic generation of policies. One of the main limitations of some previously-used policy representations is the trade-off between locality and granularity in the associated search space. In this article, we adopt an interpolation-based representation which has the jointly-desirable properties of being sparse and continuous (i.e. exhibits good genotype-to-phenotype locality). In contrast to previous approaches, the policy space is searchable via real-valued optimization methods. Packing policies using five different interpolation methods are comprehensively compared against a range of existing methods from the literature, and it is determined that the proposed method scales to larger instances than those in the literature

New insights into the classification and nomenclature of cortical GABAergic interneurons.

A systematic classification and accepted nomenclature of neuron types is much needed but is currently lacking. This article describes a possible taxonomical solution for classifying GABAergic interneurons of the cerebral cortex based on a novel, web-based interactive system that allows experts to classify neurons with pre-determined criteria. Using Bayesian analysis and clustering algorithms on the resulting data, we investigated the suitability of several anatomical terms and neuron names for cortical GABAergic interneurons. Moreover, we show that supervised classification models could automatically categorize interneurons in agreement with experts' assignments. These results demonstrate a practical and objective approach to the naming, characterization and classification of neurons based on community consensus

Scalar-field Pressure in Induced Gravity with Higgs Potential and Dark Matter

A model of induced gravity with a Higgs potential is investigated in detail in view of the pressure components related to the scalar-field excitations. The physical consequences emerging as an artifact due to the presence of these pressure terms are analysed in terms of the constraints parting from energy density, solar-relativistic effects and galactic dynamics along with the dark matter halos.Comment: 26 pages, 3 figures, Minor revision, Published in JHE

A functional PTPN22 polymorphism associated with several autoimmune diseases is not associated with IgA deficiency in the Spanish population

BACKGROUND: The 1858C/T SNP of the PTPN22 gene has been associated with many autoimmune diseases, suggesting the existence of an inflammatory process common to all of them. We studied the association of that polymorphism with immunoglobulin A deficiency (IgAD) following a double approach: a case-control and a TDT study. METHODS: A total of 259 IgAD patients and 455 unrelated matched controls, and 128 families were used for each approach. Comparisons were performed using Chi-Square tests or Fisher's exact test when necessary. RESULTS: No association between the PTPN22 1858C/T SNP and IgA deficiency was found in any case (allelic frequencies 8% vs. 6% in patients and controls, respectively, OR= 1.14 (0.72–1.79), p= 0.56; TDT p = 0.08). CONCLUSION: The result obtained seems to reinforce the consideration of IgA deficiency as a primary immunodeficiency rather than an autoimmune disease

Interaction of mumps virus V protein variants with STAT1-STAT2 heterodimer: experimental and theoretical studies

<p>Abstract</p> <p>Background</p> <p>Mumps virus V protein has the ability to inhibit the interferon-mediated antiviral response by inducing degradation of STAT proteins. Two virus variants purified from Urabe AM9 mumps virus vaccine differ in their replication and transcription efficiency in cells primed with interferon. Virus susceptibility to IFN was associated with insertion of a non-coded glycine at position 156 in the V protein (VGly) of one virus variant, whereas resistance to IFN was associated with preservation of wild-type phenotype in the V protein (VWT) of the other variant.</p> <p>Results</p> <p>VWT and VGly variants of mumps virus were cloned and sequenced from Urabe AM9 vaccine strain. VGly differs from VWT protein because it possesses an amino acid change Gln₁₀₃Pro (Pro¹⁰³) and the Gly¹⁵⁶insertion. The effect of V protein variants on components of the interferon-stimulated gene factor 3 (ISGF3), STAT1 and STAT2 proteins were experimentally tested in cervical carcinoma cell lines. Expression of VWT protein decreased STAT1 phosphorylation, whereas VGly had no inhibitory effect on either STAT1 or STAT2 phosphorylation. For theoretical analysis of the interaction between V proteins and STAT proteins, 3D structural models of VWT and VGly were predicted by comparing with simian virus 5 (SV5) V protein structure in complex with STAT1-STAT2 heterodimer. <it>In silico </it>analysis showed that VWT-STAT1-STAT2 complex occurs through the V protein Trp-motif (W¹⁷⁴, W¹⁷⁸, W¹⁸⁹) and Glu⁹⁵residue close to the Arg⁴⁰⁹and Lys⁴¹⁵of the nuclear localization signal (NLS) of STAT2, leaving exposed STAT1 Lys residues (K⁸⁵, K⁸⁷, K²⁹⁶, K⁴¹³, K⁵²⁵, K⁶⁷⁹, K⁶⁸⁵), which are susceptible to proteasome degradation. In contrast, the interaction between VGly and STAT1-STAT2 heterodimer occurs in a region far from the NLS of STAT2 without blocking of Lys residues in both STAT1 and STAT2.</p> <p>Conclusions</p> <p>Our results suggest that VWT protein of Urabe AM9 strain of mumps virus may be more efficient than VGly to inactivate both the IFN signaling pathway and antiviral response due to differences in their finest molecular interaction with STAT proteins.</p

Properties of Graphene: A Theoretical Perspective

In this review, we provide an in-depth description of the physics of monolayer and bilayer graphene from a theorist's perspective. We discuss the physical properties of graphene in an external magnetic field, reflecting the chiral nature of the quasiparticles near the Dirac point with a Landau level at zero energy. We address the unique integer quantum Hall effects, the role of electron correlations, and the recent observation of the fractional quantum Hall effect in the monolayer graphene. The quantum Hall effect in bilayer graphene is fundamentally different from that of a monolayer, reflecting the unique band structure of this system. The theory of transport in the absence of an external magnetic field is discussed in detail, along with the role of disorder studied in various theoretical models. We highlight the differences and similarities between monolayer and bilayer graphene, and focus on thermodynamic properties such as the compressibility, the plasmon spectra, the weak localization correction, quantum Hall effect, and optical properties. Confinement of electrons in graphene is nontrivial due to Klein tunneling. We review various theoretical and experimental studies of quantum confined structures made from graphene. The band structure of graphene nanoribbons and the role of the sublattice symmetry, edge geometry and the size of the nanoribbon on the electronic and magnetic properties are very active areas of research, and a detailed review of these topics is presented. Also, the effects of substrate interactions, adsorbed atoms, lattice defects and doping on the band structure of finite-sized graphene systems are discussed. We also include a brief description of graphane -- gapped material obtained from graphene by attaching hydrogen atoms to each carbon atom in the lattice.Comment: 189 pages. submitted in Advances in Physic

Ca2+ Cycling in Heart Cells from Ground Squirrels: Adaptive Strategies for Intracellular Ca2+ Homeostasis

Heart tissues from hibernating mammals, such as ground squirrels, are able to endure hypothermia, hypoxia and other extreme insulting factors that are fatal for human and nonhibernating mammals. This study was designed to understand adaptive mechanisms involved in intracellular Ca2+ homeostasis in cardiomyocytes from the mammalian hibernator, ground squirrel, compared to rat. Electrophysiological and confocal imaging experiments showed that the voltage-dependence of L-type Ca2+ current (ICa) was shifted to higher potentials in ventricular myocytes from ground squirrels vs. rats. The elevated threshold of ICa did not compromise the Ca2+-induced Ca2+ release, because a higher depolarization rate and a longer duration of action potential compensated the voltage shift of ICa. Both the caffeine-sensitive and caffeine-resistant components of cytosolic Ca2+ removal were more rapid in ground squirrels. Ca2+ sparks in ground squirrels exhibited larger amplitude/size and much lower frequency than in rats. Due to the high ICa threshold, low SR Ca2+ leak and rapid cytosolic Ca2+ clearance, heart cells from ground squirrels exhibited better capability in maintaining intracellular Ca2+ homeostasis than those from rats and other nonhibernating mammals. These findings not only reveal adaptive mechanisms of hibernation, but also provide novel strategies against Ca2+ overload-related heart diseases

Validation of the use of Actigraph GT3X accelerometers to estimate energy expenditure in full time manual wheel chair users with Spinal Cord Injury

Study design: Cross-sectional validation study. Objectives: The goals of this study were to validate the use of accelerometers by means of multiple linear models (MLMs) to estimate the O2 consumption (VO2) in paraplegic persons and to determine the best placement for accelerometers on the human body. Setting: Non-hospitalized paraplegics’ community. Methods: Twenty participants (age=40.03 years, weight=75.8 kg and height=1.76 m) completed sedentary, propulsion and housework activities for 10 min each. A portable gas analyzer was used to record VO2. Additionally, four accelerometers (placed on the non-dominant chest, non-dominant waist and both wrists) were used to collect second-by-second acceleration signals. Minute-by-minute VO2 (ml kg−1 min−1) collected from minutes 4 to 7 was used as the dependent variable. Thirty-six features extracted from the acceleration signals were used as independent variables. These variables were, for each axis including the resultant vector, the percentiles 10th, 25th, 50th, 75th and 90th; the autocorrelation with lag of 1 s and three variables extracted from wavelet analysis. The independent variables that were determined to be statistically significant using the forward stepwise method were subsequently analyzed using MLMs. Results: The model obtained for the non-dominant wrist was the most accurate (VO2=4.0558−0.0318Y25+0.0107Y90+0.0051YND2−0.0061ZND2+0.0357VR50) with an r-value of 0.86 and a root mean square error of 2.23 ml kg−1 min−1. Conclusions: The use of MLMs is appropriate to estimate VO2 by accelerometer data in paraplegic persons. The model obtained to the non-dominant wrist accelerometer (best placement) data improves the previous models for this population.LM Garcia-Raffi and EA Sanchez-Perez gratefully acknowledge the support of the Ministerio de Economia y Competitividad under project #MTM2012-36740-c02-02. 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Genetic and Chemical Evaluation of Trypanosoma brucei Oleate Desaturase as a Candidate Drug Target

Background: Trypanosomes can synthesize polyunsaturated fatty acids. Previously, we have shown that they possess stearoyl-CoA desaturase (SCD) and oleate desaturase (OD) to convert stearate (C18) into oleate (C18:1) and linoleate (C18:2), respectively. Here we examine if OD is essential to these parasites. Methodology: Cultured procyclic (insect-stage) form (PCF) and bloodstream-form (BSF) Trypanosoma brucei cells were treated with 12- and 13-thiastearic acid (12-TS and 13-TS), inhibitors of OD, and the expression of the enzyme was knocked down by RNA interference. The phenotype of these cells was studied. Principal Findings: Growth of PCF T. brucei was totally inhibited by 100 mM of 12-TS and 13-TS, with EC50 values of 4062 and 3062 mM, respectively. The BSF was more sensitive, with EC50 values of 763 and 261 mM, respectively. This growth phenotype was due to the inhibitory effect of thiastearates on OD and, to a lesser extent, on SCD. The enzyme inhibition caused a drop in total unsaturated fatty-acid level of the cells, with a slight increase in oleate but a drastic decrease in linoleate level, most probably affecting membrane fluidity. After knocking down OD expression in PCF, the linoleate content was notably reduced, whereas that of oleate drastically increased, maintaining the total unsaturated fatty-acid level unchanged. Interestingly, the growth phenotype of the RNAi-induced cells was similar to that found for thiastearate-treated trypanosomes, with the former cells growing twofold slower than the latter ones, indicating that the linoleate content itsel