Structure-function analyses point to a polynucleotide-accommodating groove essential for APOBEC3A restriction activities.

Members of the human APOBEC3 family of editing enzymes can inhibit various mobile genetic elements. APOBEC3A (A3A) can block the retrotransposon LINE-1 and the parvovirus adeno-associated virus type 2 (AAV-2) but does not inhibit retroviruses. In contrast, APOBEC3G (A3G) can block retroviruses but has only limited effects on AAV-2 or LINE-1. What dictates this differential target specificity remains largely undefined. Here, we modeled the structure of A3A based on its homology with the C-terminal domain of A3G and further compared the sequence of human A3A to those of 11 nonhuman primate orthologues. We then used these data to perform a mutational analysis of A3A, examining its ability to restrict LINE-1, AAV-2, and foreign plasmid DNA and to edit a single-stranded DNA substrate. The results revealed an essential functional role for the predicted single-stranded DNA-docking groove located around the A3A catalytic site. Within this region, amino acid differences between A3A and A3G are predicted to affect the shape of the polynucleotide-binding groove. Correspondingly, transferring some of these A3A residues to A3G endows the latter protein with the ability to block LINE-1 and AAV-2. These results suggest that the target specificity of APOBEC3 family members is partly defined by structural features influencing their interaction with polynucleotide substrates.

Neige à Paris, St Cloud [Hauts-de-Seine], 16/11/19 [luges et enfants] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 56941

City of Center Point, June 30, 2002

City Audit Report

Saint-Cloud, 28/12/19, challenge de la Nézière [i. e. Georges de La Nézière], Guillemot [du Club athlétique de la Société générale] 2e : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57341

Saint-Cloud, [28/12/19], équipe de la [Société] générale [le C. A. S. G., Club athlétique de la Société générale] gagnante du challenge de la Nézière [i. e. Georges de La Nézière, les coureurs: Isola, Felter [Ferser], Corlet, Guillemot et Brossard] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57344

City of Center Point, Independent Auditor's Reports, Basic Financial Statements and Supplementary Information, Schedule of Findings, June 30, 2004

City Audit Report

Point Mutations in the Monocarboxylate Transporter SLC16A12 Lead to Juvenile and Age-Related Cataract

Purpose: Previously we reported on a premature termination mutation in SLC16A12 that leads to dominant juvenile cataract and renal glucosuria. To assess the mutation rate and genotype-phenotype correlations of SLC16A12 in juvenile or age-related forms of cataract, we performed a mutation screen in cataract patients. Methods: Clinical data of approximately 660 patients were collected, genomic DNA was isolated and analyzed. Exons 3 to 8 including flanking intron sequences of SLC16A12 were PCR amplified and DNA sequence was determined. Selected mutations were tested by cell culture assays, in silico analysis and RT-PCR. Results: We found sequence alterations at a rate of approximately 1/75 patients. None of them was found in 360 control alleles. Alterations affect splice site and regulatory region but most mutations caused an amino acid substitution. The majority of the coding region mutations maps to trans-membrane domains. One mutation located to the 5'UTR. It affects translational efficiency of SLC16A12. In addition, we identified a cataract-predisposing SNP in the non-coding region that causes allele-specific splicing of the 5'UTR region. Conclusions: Altered translational efficiency of the solute carrier SLC16A12 and its allele-specific splicing strongly support a model of challenged homeostasis to cause various forms of cataract. In addition, the pathogenic property of the here reported sequence alterations is supported by the lack of known sequence variations within the coding region of SLC16A12. Due to the relatively high mutation rate, we suggest to include SLC16A12 in diagnostic cataract screening. Generally, our data recommend the assessment of regulatory sequences for diagnostic purposes.

Virtualización y cloud computing en la PYME

El presente documento introduce a las pequeñas y medianas empresas en el mundo de la virtualización y el cloud computing. Partiendo de la presentación de ambas tecnologías, se recorren las diferentes fases por las que atraviesa un proyecto tecnológico consistente en la instalación de una plataforma virtualizada que alberga los sistemas informáticos básicos en una PYME.

City of Strawberry Point, June 30, 2003

City Audit Report

22/2/20, [stade de] Saint Cloud, équipe de France [de hockey sur gazon] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58134

22/2/20, [stade de] Saint Cloud, hockey [match de sélection], équipe du reste : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58133