Pseudohypoparathyroidism Type Ib Associated with Novel Duplications in the GNAS Locus

Context Pseudohypoparathyroidism type 1b (PHP-Ib) is characterized by renal resistance to PTH (and, sometimes, a mild resistance to TSH) and absence of any features of Albright's hereditary osteodystrophy. Patients with PHP-Ib suffer of defects in the methylation pattern of the complex GNAS locus. PHP-Ib can be either sporadic or inherited in an autosomal dominant pattern. Whereas familial PHP-Ib is well characterized at the molecular level, the genetic cause of sporadic PHP-Ib cases remains elusive, although some molecular mechanisms have been associated with this subtype. Objective The aim of the study was to investigate the molecular and imprinting defects in the GNAS locus in two unrelated patients with PHP-Ib. Design We have analyzed the GNAS locus by direct sequencing, Methylation-Specific Multiplex Ligation-dependent Probe Amplification, microsatellites, Quantitative Multiplex PCR of Short Fluorescent fragments and array-Comparative Genomic Hybridization studies in order to characterize two unrelated families with clinical features of PHP-Ib. Results We identified two duplications in the GNAS region in two patients with PHP-Ib: one of them, comprising similar to 320 kb, occurred 'de novo' in the patient, whereas the other one, of similar to 179 kb in length, was inherited from the maternal allele. In both cases, no other known genetic cause was observed. Conclusion In this article, we describe the to-our-knowledge biggest duplications reported so far in the GNAS region. Both are associated to PHP-Ib, one of them occurring 'de novo' and the other one being maternally inherited.

Modelling rail corrugation with specific track parameters focusing on ballasted track and slab track

The objective of this paper is to compare 3 types of track (high performance ballasted track, STEDEF and AFTRAV) from the corrugation growth point of view. This work has considered different vehicle speeds and track radii, and the results have taken into account the four wheels of a bogie. These tracks have been studied using Finite Elements with Nastran-Patran and RACING, a tool developed in Matlab by the authors which estimates the corrugation growth tendency. The tracks are studied using the Finite Strip Method and the Periodic Structure Theory. Lateral and vertical receptances for track and vehicle have been obtained, as well as the corrugation growth functions. In the paper the tracks are ranked according to corrugation development.

Global pressures, specific responses: effects of nutrient enrichment in streams from different biomes

13 p. + 2 p. (Erratum)

Surface Expression and Subunit Specific Control of Steady Protein Levels by the Kv7.2 Helix A-B Linker

12 p.

Design and synthesis of biofunctional magnetic/fluorescent glyco-nanoparticles and quantum dots and their application as specific molecular imaging probes

206 p.

On innate and specific aspects of human language

Mixel Aurnague, Kepa Korta and Jesus M. Larrazabal (eds.)

PIM-SM extension for Source-Specific Multicast through non multicast networks

Barneko ikerkuntza-txostena

Specific Interaction with Cardiolipin Triggers Functional Activation of Dynamin-Related Protein 1

Dynamin-Related Protein 1 (Drp1), a large GTPase of the dynamin superfamily, is required for mitochondrial fission in healthy and apoptotic cells. Drp1 activation is a complex process that involves translocation from the cytosol to the mitochondrial outer membrane (MOM) and assembly into rings/spirals at the MOM, leading to membrane constriction/division. Similar to dynamins, Drp1 contains GTPase (G), bundle signaling element (BSE) and stalk domains. However, instead of the lipid-interacting Pleckstrin Homology (PH) domain present in the dynamins, Drp1 contains the so-called B insert or variable domain that has been suggested to play an important role in Drp1 regulation. Different proteins have been implicated in Drp1 recruitment to the MOM, although how MOM-localized Drp1 acquires its fully functional status remains poorly understood. We found that Drp1 can interact with pure lipid bilayers enriched in the mitochondrion-specific phospholipid cardiolipin (CL). Building on our previous study, we now explore the specificity and functional consequences of this interaction. We show that a four lysine module located within the B insert of Drp1 interacts preferentially with CL over other anionic lipids. This interaction dramatically enhances Drp1 oligomerization and assembly-stimulated GTP hydrolysis. Our results add significantly to a growing body of evidence indicating that CL is an important regulator of many essential mitochondrial functions.

Optimal Taxation and Indeterminacy in the Uzawa-Lucas Model with Sector-specific Externalities

Documento de trabajo

Financial and Economic Report of a Specific Business Group

As a result of the natural evolution of the economy, ever-changing, unpredictable and cyclical, companies must adapt as far as possible to the changes that have taken place in order to continue with their normal operating activities. Likewise, they should also try to maintain a structure for long-term growth, trying at all times to generate the maximum value. The main objective of this project is to provide financial advisory services to a business group, trying to forward solutions and measures that according to the author can be effective. For this end, the situation of the group in question is analysed from early 2008 to the present day, examining its evolution, what steps have been taken together with their corresponding results and the economic-financial situation of the company at the end of last year. Contact with the company was kept throughout the process of analysis and assessment trying to take advantage of the feedback generated so that the appropriate measures can be adopted if the management considers it to be adequate.

Cellular and molecular responses of zebrafish to legacy and emerging pollutants: the specific cases of PAHs and metal oxide nanoparticles

270 p.