TRAIL/TRAIL Receptor System and Susceptibility to Multiple Sclerosis

The TNF-related apoptosis inducing ligand (TRAIL)/TRAIL receptor system participates in crucial steps in immune cell activation or differentiation. It is able to inhibit proliferation and activation of T cells and to induce apoptosis of neurons and oligodendrocytes, and seems to be implicated in autoimmune diseases. Thus, TRAIL and TRAIL receptor genes are potential candidates for involvement in susceptibility to multiple sclerosis (MS). To test whether single-nucleotide polymorphisms (SNPs) in the human genes encoding TRAIL, TRAILR-1, TRAILR-2, TRAILR-3 and TRAILR-4 are associated with MS susceptibility, we performed a candidate gene case-control study in the Spanish population. 59 SNPs in the TRAIL and TRAIL receptor genes were analysed in 628 MS patients and 660 controls, and validated in an additional cohort of 295 MS patients and 233 controls. Despite none of the SNPs withstood the highly conservative Bonferroni correction, three SNPs showing uncorrected p values<0.05 were successfully replicated: rs4894559 in TRAIL gene, p = 9.8×10−4, OR = 1.34; rs4872077, in TRAILR-1 gene, p = 0.005, OR = 1.72; and rs1001793 in TRAILR-2 gene, p = 0.012, OR = 0.84. The combination of the alleles G/T/A in these SNPs appears to be associated with a reduced risk of developing MS (p = 2.12×10−5, OR = 0.59). These results suggest that genes of the TRAIL/TRAIL receptor system exerts a genetic influence on MS

NMR spin-spin coupling constants and hyperconjugative interactions

The potential of NMR spin-spin coupling constants as probes to study fine details of electronic molecular structures is briefly discussed in this work through two different examples. A qualitative analysis of the polarization propagator expression for the Fermi contact term is applied for predicting factors affecting 1JCH, and comments are made about how to generalize those results to different types of one-bond spin-spin couplings. Moreover, the Natural J Coupling method is applied to get insight into electronic factors defining a. Karplus relationship of type 3J HH (180°) < 3JHH(0°) known in the literature for some amino acids. © 2009 Wiley Periodicals, Inc.Fil: Contreras, Ruben Horacio. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Suardíaz, R.. Universidad de La Habana; CubaFil: Pérez, C.. Universidad de La Habana; CubaFil: Crespo-Otero, R.. Universidad de La Habana; CubaFil: San Fabián, J.. Universidad Autónoma de Madrid; EspañaFil: De La García Vega, J.M.. Universidad Autónoma de Madrid; Españ

Computational NMR coupling constants:Shifting and scaling factors for evaluating 1JCH

Optimized shifting and/or scaling factors for calculating one-bond carbon–hydrogen spin–spin coupling constants have been determined for 35 combinations of representative functionals (PBE, B3LYP, B3P86, B97-2 and M06-L) and basis sets (TZVP, HIIIsu3, EPR-III, aug-cc-pVTZ-J, ccJ-pVDZ, ccJ-pVTZ, ccJ-pVQZ, pcJ-2 and pcJ-3) using 68 organic molecular systems with 88 1JCH couplings including different types of hybridized carbon atoms. Density functional theory assessment for the determination of 1JCH coupling constants is examined, comparing the computed and experimental values. The use of shifting constants for obtaining the calculated coupling improves substantially the results, and most models become qualitatively similar. Thus, for the whole set of couplings and for all approaches excluding those using the M06 functional, the root-mean-square deviations lie between 4.7 and 16.4 Hz and are reduced to 4–6.5 Hz when shifting constants are considered. Alternatively, when a specific rovibrational contribution of 5 Hz is subtracted from the experimental values, good results are obtained with PBE, B3P86 and B97-2 functionals in combination with HIII-su3, aug-cc-pVTZ-J and pcJ-2 basis sets.Fil: San Fabián, J.. Universidad Autónoma de Madrid. Facultad de Ciencias. Departamento de Química Física Aplicada; España;Fil: García de la Vega, J. M.. Universidad Autónoma de Madrid. Facultad de Ciencias. Departamento de Química Física Aplicada; España;Fil: Suardíaz, R.. Universitat Autónoma de Barcelona. Department de Química; España; Universitat Autónoma de Barcelona. Institut de Biotecnologia i de Biomedicina; España;Fil: Fernandez Oliva, M.. Universidad de la Habana. Facultad de Química. Departamento de Química Física; Cuba;Fil: Pérez, C.. Universidad de la Habana. Facultad de Química. Departamento de Química Física; Cuba;Fil: Crespo Otero, R.. Max Planck Institut für Kohlenforschung; Alemania;Fil: Contreras, Ruben Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires; Argentina; Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; Argentina

Structural Characterization of Arginine Fingers - Identification of an Arginine Finger for the Pyrophosphatase dUTPases - Part 2

The files are compressed as tarballs. Some files were split in smaller files. The whole original file can be obtained by using the cat command in unix.warehouse.tar.gz contain preliminary data and test calculations not explicitly mentioned in the publication. As we plan to include a link to this data in the final version of the article we prefer to keep restricted the access to this part of the data. See the related dataset linked to under REFERENCES, containing the classical MD trajectories and QM/MM reaction path geometries. 'Structural Characterization of Arginine Fingers - Identification of an Arginine Finger for the Pyrophosphatase dUTPases' https://doi.org/10.18742/RDM01-7