A funerary perspective on Bell Beaker period in the Western Mediterranean. Reading the social context of individual burials at La Vital (Gandía, Valencia)

The discussion about social dynamics in recent Pre- history is supported by the study of funerary practices. The presence and significance of individual and collec- tive burials in Final Neolithic/Chalcolithic societies in the southeast of the Iberian Peninsula provides new evi- dence for the debate concerning the emergence of social inequalities in this region. Our contribution is based on the recent discovery and excavation of several individual pit burials in domestic contexts at the site of La Vital (Gandía, Valencia). The particularities of the identified burials (different ritual episodes) and their content (Bell Beaker pottery, metal objects, animal offerings) together with an accurate chronometric database allow us to con- sider several issues in relation to settlement dynamics, social networks and relationships for the period from the end of the 4th to the middle of the 3rd millennium cal BC in the central area of the Mediterranean coast of the Iberian Peninsula. La reflexión sobre la dinámica de las relaciones sociales en la Prehistoria reciente encuentra un apoyo clave en el análisis de las prácticas funerarias. La presencia y significación de los enterramientos individuales y colectivos en las sociedades del Neolítico final/ Calcolítico en el sureste de la Península Ibérica proporciona una nueva evidencia al debate sobre la aparición de las desigualdades sociales en la región. Nuestra contribución se basa en el reciente descubrimiento y excavación de varias tumbas individuales en fosa, localizadas en contextos domésticos, en el yacimiento de La Vital (Gandía, Valencia). Las peculiaridades del continente (detección de episodios rituales particulares en las distintas tumbas) y del contenido (vasos campaniformes, objetos metálicos, ofrendas animales), unido a una ajustada cronometría, permiten plantear diversas alternativas relativas a la dinámica poblacional, las redes de circulación de información y las formas de reproducción social entre finales del IV y el desarrollo del III milenio cal BC en el área central del Mediterráneo en la Península Ibérica

Attenuation of disease phenotype through alternative translation initiation in low-penetrance retinoblastoma

Hereditary predisposition to retinoblastoma (RB) is caused by germline mutations in the retinoblastoma 1 (RB1) gene and transmits as an autosomal dominant trait. In the majority of cases disease develops in greater than 90% of carriers. However, reduced penetrance with a large portion of disease-free carrier is seen in some families. Unambiguous identification of the predisposing mutation in these families is important for accurate risk prediction in relatives and their genetic counseling but also provides conceptual information regarding the relationship between the RB1 genotype and the disease phenotype. In this study we report a novel mutation detected in 10 individuals of an extended family, only three of whom are affected by RB disease. The mutation comprises a 23-basepair (bp) duplication in the first exon of RB1 (c.43_65dup) producing a frameshift in exon 1 and premature chain termination in exon 2. Mutations resulting in premature chain termination classically are associated with high penetrance disease, as message translation may not generate functional product and nonsense mediated RNA decay (NMD) frequently eliminates the mutant transcript. However, appreciable NMD does not follow from the mutation described here and transcript expression in tissue culture cells and translation in vitro reveals that alternative in-frame translation start sites involving Met113 and possibly Met233 are used to generate truncated RB1 products (pRB94 and pRB80), known and suspected to exhibit tumor suppressor activity. These results strongly suggest that modulation of disease penetrance in this family is achieved by internal translation initiation. Our observations provide the first example for rescue of a chain-terminating mutation in RB1 through alternative translation initiation

Severe and moderate hemophilia A: identification of 38 new genetic alterations

[EN] Hemophilia A is an X-linked recessive disorder caused by a lack or decrease of factor VIII activity. Its socio-economic impact is high given its high bleeding expression and treatment cost. Our aim was to establish the mutation of each patient to improve family management. A total of 116 unrelated families with severe and moderate hemophilia A were involved. Non-carriers of intron 22 and intron 1 rearrangements were included in F8 gene screening. Intron 1 and 22 inversion frequencies were 3% and 52.5% respectively. Putative mutations were identified in all the families; 38 were new, The cumulative inhibitor incidence was 22%. Approximately half the families carry non-recurrent mutations, which were unique in around one third. Harmful effects for mutations predicting null alleles are expected. Missense mutation consequences are not easily predictable, despite the help of some bio-informatics tools.this work was partly supported by FIS grant PI020612 (Spain) and by CSL Behring. We wish to thank all the staff of the 'Unidad de Coagulopatías Congénitas de la Comunidad Valenciana' for their technical and clinical assistance, and Helen Warburton for checking the English. Furthermore, the hematologists from the following hospitals for referring patients: Virgen de la Arrixaca (Murcia), San Pedro Alcántara (Cáceres), Torrecardenas and La Inmaculada (Almería), Marqués Valdecilla (Santander), and Pontificia Universidad Católica (Santiago de Chile).Casaña, P.; Cabrera, N.; Cid, AR.; Haya, S.; Beneyto, M.; Espinós-Armero, CÁ.; Cortina, V.... (2008). Severe and moderate hemophilia A: identification of 38 new genetic alterations. Haematologica. 93(7):1091-1094. https://doi.org/10.3324/haematol.123441091109493

Putative association of a mutant ROM1 allele with retinitis pigmentosa

13 páginas, 1 figura, 1 tabla.Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous form of retinal degeneration. Several genes and loci have been shown to be involved in the disease, although each of them only accounts for a few cases. Mutations in the gene encoding ROM1, a rod-specific protein, have been putatively associated with several forms of RP. Here we describe a double-mutant allele of this gene, P60T and T108M, present in two affected sibs and also in two healthy members of a Spanish RP family. The same double-mutant allele was previously considered to be responsible for autosomal dominant RP in one family. We now report data that question the potential pathogenicity of these two ROM1 mutations.This work was supported by Spanish CICYT (SAF93-0479-062-01; SAF96-0329) and the “Federación de Asociaciones de Afectados de Retinosis Pigmentaria del Estado Español” (FAARPE). A. Martínez-Mir and M. Bayés are recipients of fellowships from the “Generalitat de Catalunya” and L. Dain received an R. H. Thalmann fellowship from Universidad de Buenos Aires.Peer reviewe

Mutations in the pre-mRNA splicing-factor genes PRPF3, PRPF8, and PRPF31 in Spanish families with autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci.

PURPOSE. Mutations in the systemically expressed pre-mRNA splicing-factor genes PRPF3, PRPF8, and PRPF31 have recently been associated with autosomal dominant retinitis pigmentosa (adRP). This study was intended to identify mutations in PRPF3, PRPF8, and PRPF31 in 150 Spanish families affected by adRP, to measure the contribution of mutations in these genes to adRP in that population, and to correlate RP phenotype expression with mutations in pre-mRNA splicing-factor genes. METHODS. Denaturing gradient gel electrophoresis (DGGE) and direct genomic sequencing were used to evaluate the complete coding region and flanking intronic sequences of the PRPF31 gene, exon 42 of PRPF8, and exon 11 of PRPF3 for mutations in 150 unrelated index patients with adRP. Ophthalmic and electrophysiological examination of patients with RP and their relatives was performed according to preexisting protocols. RESULTS. Three nonsense mutations caused by insertion and deletion sequences and two missense mutations (Arg2310Gly) and within the stop codon of the PRPF8 gene (TGA3 TTG), were detected in five unrelated heterozygous patients. Three patients were heterozygous carriers of different nonsense mutations in exon 8 of the PRPF31, gene and one Thr494Met mutation was found in exon 11 of the PRPF3 gene. Cosegregation of the mutation in PRPF8 and PRPF3 with adRP was observed. However, two nonsense mutations in PRPF31 causing adRP detected in two families showed asymptomatic carriers. CONCLUSIONS. Nine mutations, six of which are novel, in the pre-mRNA splicing-factor genes PRPF3, PRPF8, and PRPF31, causing adRP have been identified in the Spanish population. Their contribution to adRP is approximately 5% after correction in relation to mutations found in other genes causing adRP. The patients carrying a mutation in the pre-mRNA splicing-factor PRPF8 gene showed a type 1 diffuse RP. The existence of asymptomatic carriers of the nonsense mutation in the PRPF31 gene suggests incomplete penetrance for these mutations in the families. 1 The genetics of RP is complex, and the disorder may be inherited through an autosomal dominant (adRP), autosomal recessive (arRP), X-linked (XLRP), 2,3 or digenic 4 trait. Mutations within six genes (RHO, peripherin/RDS, RP1, NRL, CRX, and FSCN2) that encode proteins specifically expressed in photoreceptor cells have been reported to cause adRP. From th

El aprendizaje basado en tareas como metodología activa en la enseñanza histórico-jurídica

El significado y la interpretación de los sistemas jurídicos y su contextualización histórica se hayan en un momento sociopolítico, cultural e institucional complejo, pues la historia nos revela la importancia de conocer las fuentes normativas y su aplicación e interpretación en cada momento y situación concreta, desde una óptica contemporánea y multifocal. De igual modo que la tecnología ha reorientado la mirada de la persona y las relaciones de ésta con su entorno, en las ciencias sociales y jurídicas también urge ofrecer herramientas de interpretación adecuadas a la sociedad plural y heterogénea actual, donde la implementación de metodologías activas juega un papel trascendental en el proceso de enseñanza-aprendizaje. En consecuencia, el objetivo de esta experiencia educativa se centra en implementar un proceso de enseñanza-aprendizaje proclive hacia metodologías que fomenten mayor participación del alumnado, en aras a aumentar y perfeccionar la adquisición de las competencias académicas y profesionales necesarias, incentivando la cooperación y colaboración a nivel grupal a través de un aprendizaje basado en tareas (ABT). Los resultados obtenidos permiten afirmar que el 71% de los y las estudiantes entrevistados afirma haber alcanzado las competencias transversales, técnicas y profesionales establecidas, ya que el ABT permite interiorizar los conocimientos de forma gradual, mejorando, de esta forma, su aprendizaje