Submicroscopic deletion in patients with Williams-Beuren syndrome influences expression levels of the nonhemizygous flanking genes.

Genomic imbalance is a common cause of phenotypic abnormalities. We measured the relative expression level of genes that map within the microdeletion that causes Williams-Beuren syndrome and within its flanking regions. We found, unexpectedly, that not only hemizygous genes but also normal-copy neighboring genes show decreased relative levels of expression. Our results suggest that not only the aneuploid genes but also the flanking genes that map several megabases away from a genomic rearrangement should be considered possible contributors to the phenotypic variation in genomic disorders.

[Exposition internationale de géographie au Congrès national des sociétés françaises de géographie, Toulouse, 1884, 11 phot. des objets exposés, don Prévost]

Donateur : Prevost, E. (18..-18..?)

Two high throughput technologies to detect segmental aneuploidies identify new Williams-Beuren syndrome patients with atypical deletions.

OBJECTIVE: To develop and compare two new technologies for diagnosing a contiguous gene syndrome, the Williams-Beuren syndrome (WBS). METHODS: The first proposed method, named paralogous sequence quantification (PSQ), is based on the use of paralogous sequences located on different chromosomes and quantification of specific mismatches present at these loci using pyrosequencing technology. The second exploits quantitative real time polymerase chain reaction (QPCR) to assess the relative quantity of an analysed locus. RESULTS: A correct and unambiguous diagnosis was obtained for 100% of the analysed samples with either technique (n = 165 and n = 155, respectively). These methods allowed the identification of two patients with atypical deletions in a cohort of 182 WBS patients. Both patients presented with mild facial anomalies, mild mental retardation with impaired visuospatial cognition, supravalvar aortic stenosis, and normal growth indices. These observations are consistent with the involvement of GTF2IRD1 or GTF2I in some of the WBS facial features. CONCLUSIONS: Both PSQ and QPCR are robust, easy to interpret, and simple to set up. They represent a competitive alternative for the diagnosis of segmental aneuploidies in clinical laboratories. They have advantages over fluorescence in situ hybridisation or microsatellites/SNP genotyping for detecting short segmental aneuploidies as the former is costly and labour intensive while the latter depends on the informativeness of the polymorphisms.

Los límites de la obligatoriedad escolar en Buenos Aires, 1884-1915

En este artículo pretendemos enriquecer el marco explicativo que inquiere en las razones del hiato entre el trazado ideal y la constitución efectiva del sistema público de instrucción en Argentina en el periodo que va desde la sanción de la Ley 1.420 hasta la entrada en la década de 1910. Nos interesará dejar asentado que tal distancia no dependió únicamente de las limitaciones materiales con las que se enfrentaron las autoridades escolares, o de las decisiones de los padres con respecto de la asistencia de sus hijos a la escuela, sino que la misma estuvo enraizada en un elemento más profundo, del orden de las representaciones, que desde muy temprano funcionó como un impedimento para la realización de la vocación educativa pretendidamente ecuménica de las élites argentinas. De hecho, las posturas educativas universalistas convivieron con ostras que rechazaban la posibilidad e incluso la conveniencia de que todos los niños se educaran en escuelas comunes, aparente contradicción que atravesó los discursos y las prácticas de casi todos los miembros de las élites, incluyendo los de los adalides de la "educación popular". A través del análisis y de la puesta en relación de la ley de Educación común (Ley n.1.420/1884) y la Ley de Reglamentación del Trabajo de Mujeres y Niños (Ley n.5.291/1907), exploraremos cómo se fueran estableciendo los criterios que desde temprano determinaron que "niños" podrían convertirse en alumnos, y cuáles no.

Las Topografías médicas burgalesas : 1884-1917. Un intento de contribución a la historia natural, social y sanitaria de la província de Burgos en los siglos XIX y XX

Aquest és un dels treballs de López Gómez que s'insereix en la línia d'estudi de les topografies mèdiques com a material molt útil per al¿estudi de la història de la medicina a nivell local. En aquest cas estudia les topografies mèdiques de la província de Burgos a partir de documents conservats a l¿Arxiu de la Reial Acadèmia de Medicina de Barcelona. També inclou un petit estudi sobre la biografia i obra del doctor Ildefonso Díez Santaolalla (1851-1929).

Relation des évènemens mémorables arrivés dans l'exploitation de houille de Beaujonc, près de Liege, le 28 février 1812 , suivie du Précis de ce qui s'est passé le 14 janvier précédent dans celle de Horlot,..., d'une Notice sur les mines de houille du département de l'Ourte, et du Plan des exploitations Beaujonc et Mamonster...

Comprend : Détail de la cérémonie qui a eu lieu le dimanche 22 mars 1812, à l'Hôtel de ville de Liege....

Using transcription modules to identify expression clusters perturbed in Williams-Beuren syndrome.

The genetic dissection of the phenotypes associated with Williams-Beuren Syndrome (WBS) is advancing thanks to the study of individuals carrying typical or atypical structural rearrangements, as well as in vitro and animal studies. However, little is known about the global dysregulations caused by the WBS deletion. We profiled the transcriptomes of skin fibroblasts from WBS patients and compared them to matched controls. We identified 868 differentially expressed genes that were significantly enriched in extracellular matrix genes, major histocompatibility complex (MHC) genes, as well as genes in which the products localize to the postsynaptic membrane. We then used public expression datasets from human fibroblasts to establish transcription modules, sets of genes coexpressed in this cell type. We identified those sets in which the average gene expression was altered in WBS samples. Dysregulated modules are often interconnected and share multiple common genes, suggesting that intricate regulatory networks connected by a few central genes are disturbed in WBS. This modular approach increases the power to identify pathways dysregulated in WBS patients, thus providing a testable set of additional candidates for genes and their interactions that modulate the WBS phenotypes.

Regulation of interleukin 1α secretion by inflammasomes.

The crucial role of the proinflammatory cytokine interleukin 1β (IL-1β) in driving inflammatory disorders, such as Muckle-Wells syndrome and gout, has been extensively characterised. Owing to its high potency to induce inflammation the activation and secretion of IL-1β is tightly regulated. The sensing of various host 'dangers', including infections and metabolic deregulation, results in the formation of large protein complexes, termed inflammasomes. Formation of the inflammasomes leads to the cleavage and activation of caspase-1, which in turn proteolytically processes its substrates, including pro-IL-1β. Biologically active IL-1β is subsequently secreted by the cell. In contrast to IL-1β, little is known about mechanisms underlying the activation and secretion of its close homologue IL-1α. Moreover, the physiological role of IL-1α is still not well defined. Several studies hypothesise that IL-1α serves as a danger signal, which is passively released from dying cells. However, recent studies suggest a more complex function of this cytokine. Indeed, NLRP3 inflammasome agonists such as uric acid crystal or nigericin induce IL-1α cleavage and secretion, leading to the cosecretion of both IL-1β and IL-1α. Depending on the type of NLRP3 agonist, release of IL-1α is NLRP3-inflammasome/caspase-1 dependent or independent, but in both cases IL-1α processing depends on calpain protease activity. Taken together, these results suggest that the promotion and progression of inflammatory diseases is not solely due to IL-1β but also to its close relative IL-1α. This should be considered when IL-1 blockade is applied as a therapeutic strategy for diseases such as cryopyrin-associated periodic syndromes or gout.