Screening of male breast cancer and of breast-ovarian cancer families for BRCA2 mutations using large bifluorescent amplicons

41 breast cancer or breast-ovarian cancer families, including 12 families with at least one affected first-degree male relative, were screened for mutations in the BRCA2 gene. Mutations had not been found in the BRCA1 gene of these families. Chemical cleavage of Mismatch was used to identify nucleotide changes within large PCR products (average size 1.2 kb) that carried strand-specific fluorescent end-labels. 15 amplicons were sufficient to scan 18 exons, including the large exon 11. The remaining 9 small exons were examined by Denaturing Gradient Gel Electrophoresis. The high sensitivity of this approach was documented by the detection, in these 41 patients, of all 9 exonic single nucleotide polymorphisms reported with heterozygosity >0.1. Truncating BRCA2 mutations were found in 7 of the 41 families. 3 of them were in the group of 12 families comprising cases of male breast cancer. Since the methods used here have no bias for particular types of mutations, these data confirm the high proportion of frameshifts among mutations in BRCA2. However, relevant single nucleotide substitutions were also found: one resulting in a stop codon and another one, present in a male patient, was the previously reported change Asp2723His, that affects a highly conserved region of the BRCA2 protein. This study indicates a BRCA2 contribution of 10% (95% CI 2.5–17.5) to our original cohort of 59 breast-ovarian cancer families, whereas the contribution of BRCA1 had been estimated at 46% (95% CI 33–59). © 2001 Cancer Research Campaign http://www.bjcancer.co

Hidromedusas profundas del Mediterráneo: Un estudio que incluye la descripción de dos nuevas especies recolectadas en cañones submarinos del Mediterráneo Occidental

Two new species of hydromedusae (Foersteria antoniae and Cunina simplex) are described from plankton collected in sediment traps placed in the Lacaze-Duthiers Submarine Canyon and along Banyuls-sur-Mer coast (northwestern Mediterranean). The Mediterranean hydromedusan deep-water fauna contains 41 species which represent 45.5 % of the world-wide deep-sea hydromedusae fauna (90) and 20% of the total number of Mediterranean hydromedusae (204). The Mediterranean deep-water hydromedusan fauna is characterised by a large percentage of holoplanktonic species (61%), mainly Trachymedusae. Nevertheless, contrary to the general opinion, the percentage of meroplanktonic species is equally high. The most original features of this fauna lies however in the importance of the number of endemic species (22%) and in the fact that the majority of them are meroplanktonic Leptomedusae with a supposed bathybenthic stage. Some of the endemic species could still represent relics of the primitive Tethys fauna having survived to the Messinian crisis. The origin of the Mediterranean deep-water hydromedusan fauna is discussed and a general hypothesis is proposed.Se describen dos especies nuevas a partir de ejemplares recolectados mediante trampas de sedimento del cañón submarino de Lacaze-Duthiers situado en frente de la costa de Banyuls-sur-Mer (Mediterráneo noroccidental). La fauna profunda de hydromedusas en el Mediterráneo contiene 41 especies que representan 45.5 % de la fauna mundial del grupo y el 20% de la fauna de hydromedusas del Mediterráneo. La fauna Mediterránea de hydromedusas profundas se caracteriza por un gran porcentaje de especies holoplanctónicas (61%), fundamentalmente Trachymedusas, sin embargo, contrario a la opinión generalizada, el porcentaje de especies meroplanctónicas es igualmente importante (39%). La característica más interesante de esta fauna es el número de especies endémicas (22%) y el hecho de que la mayoría de estas especies son meroplanctónicas (Leptomedusas) con una supuesta fase bentónica. Algunas de estas especies endémicas, podrían ser especies relictas (endémica insular) de la fauna primitiva del Tetis que sobrevivieron a la crisis Mesiniana. Se discute el origen de la fauna de hydromedusas profundas en el Mediterráneo y se presenta una nueva hipótesis

Morphometric discrimination of two sympatric sibling species in the Palaearctic region, Culicoides obsoletus Meigen and C-scoticus Downes & Kettle (Diptera: Ceratopogonidae), vectors of bluetongue and Schmallenberg viruses

Background Some Palaearctic biting midge species (subgenus Avaritia) have been implicated as vectors of bluetongue virus in northern Europe. Separation of two species (C. obsoletus and C. scoticus) is considered difficult morphologically and, often, these female specimens are grouped in entomological studies. However, species-specific identification is desirable to understand their life history characteristics, assess their roles in disease transmission or measure their abundance during arboviral outbreaks. This study aims to investigate whether morphometric identification techniques can be applied to female C. obsoletus and C. scoticus individuals trapped at different geographical regions and time periods during the vector season. Methods C. obsoletus and C. scoticus were collected using light-suction traps from the UK, France and Spain, with two geographical locations sampled per country. A total of 759 C. obsoletus/C. scoticus individuals were identified using a molecular assay based on the cytochrome c oxidase subunit I gene. Fifteen morphometric measurements were taken from the head, wings and abdomen of slide-mounted specimens, and ratios calculated between these measurements. Multivariate analyses explored whether a combination of morphometric variables could lead to accurate species identification. Finally, Culicoides spp. collected in France at the start, middle and end of the adult vector season were compared, to determine whether seasonal variation exists in any of the morphometric measurements. Results The principal component analyses revealed that abdominal characteristics: length and width of the smaller and larger spermathecae, and the length of the chitinous plates and width between them, are the most reliable morphometric characteristics to differentiate between the species. Seasonal variation in the size of each species was observed for head and wing measurements, but not abdominal measurements. Geographical variation in the size of Culicoides spp. was also observed and is likely to be related to temperature at the trapping sites, with smaller individuals trapped at more southern latitudes. Conclusions Our results suggest that female C. obsoletus and C. scoticus individuals can be separated under a stereomicroscope using abdominal measurements. Although we show the length and width of the spermathecae can be used to differentiate between the species, this can be time-consuming, so we recommend undertaking this using standardized subsampling of catches. (Résumé d'auteur

Technical note: Open-paleo-data implementation pilot – the PAGES 2k special issue

Data stewardship is an essential element of the publication process. Knowing how to enact data polices that are described only in general terms can be difficult, however. Examples are needed to model the implementation of open-data polices in actual studies. Here we explain the procedure used to attain a high and consistent level of data stewardship across a special issue of the journal Climate of the Past. We discuss the challenges related to (1) determining which data are essential for public archival, (2) using data generated by others, and (3) understanding data citations. We anticipate that open-data sharing in paleo sciences will accelerate as the advantages become more evident and as practices that reduce data loss become the accepted convention

Natronoflexus pectinivorans gen. nov. sp. nov., an obligately anaerobic and alkaliphilic fermentative member of Bacteroidetes from soda lakes

Anaerobic enrichment with pectin at pH 10 and moderate salinity inoculated with sediments from soda lakes of the Kulunda Steppe (Altai, Russia) resulted in the isolation of a novel member of the Bacteroidetes, strain AP1T. The cells are long, flexible, Gram-negative rods forming pink carotenoids. The isolate is an obligate anaerobe, fermenting various carbohydrates to acetate and succinate. It can hydrolyze and utilize pectin, xylan, starch, laminarin and pullulan as growth substrates. Growth is possible in a pH range from 8 to 10.5, with an optimum at pH 9.5, and at a salinity range from 0.1 to 2 M Na+. Phylogenetic analysis based on 16S rRNA sequences placed the isolate into the phylum Bacteroidetes as a separate lineage within the family Marinilabilaceae. On the basis of distinct phenotype and phylogeny, the soda lake isolate AP1T is proposed to be assigned in a new genus and species Natronoflexus pectinivorans (=DSM24179T = UNIQEM U807T)

GSK3β inhibition and canonical Wnt signaling in mice hearts after myocardial ischemic damage

Altres ajuts: This work was supported by the Ministerio de Ciencia e Innovación (to LB); the Instituto de Salud Carlos III (to LB and to MBP); the Generalitat of Catalunya-Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement de la Generalitat (to LB); the Fundacion Investigación Cardiovascular to LB, and the Spanish Society of Cardiology (SEC2015 to MBP).Aims Myocardial infarction induces myocardial injury and tissue damage. During myocardial infarction strong cellular response is initiated to salvage the damaged tissues. This response is associated with the induction of different signaling pathways. Of these, the canonical Wnt signaling is increasingly important for its prosurvival cellular role, making it a good candidate for the search of new molecular targets to develop therapies to prevent heart failure in infarcted patients. Methods Herein we report that GSK3β regulates the canonical Wnt signaling in C57Bl6 mice hearts. GSK3β is a canonical Wnt pathway inhibitor. Using GSK3β inhibitors and inducing myocardial injury (MI) in Lrp5 mice model we show that GSK3β phosphorylation levels regulate downstream canonical Wnt pathway genes in the ischemic heart. In the setting of MI, myocardial damage assessment usually correlates with functional and clinical outcomes. Therefore, we measured myocardial injury size in Wt and Lrp5 mice in the presence and absence of two different GSK3 inhibitors prior to MI. Myocardial injury was independent of GSK3 inhibitor treatments and GSK3β expression levels. Results These studies support a central role for GSK3β in the activation of the canonical Wnt pathway in the Wt heart. Although LRP5 is protective against myocardial injury, GSK3β expression levels do not regulate heart damage

Enquête auprès du public de la bibliothèque municipale de Bordeaux (2002)

Résultats de l\u27enquête de la Bibliothèque municipale de Bordeaux menée auprès du public en 2002. Questionnaire, résultats détaillés et analyse

Tumour invasiveness, the local and systemic environment and the basis of staging systems in colorectal cancer

background: The present study aimed to examine the relationship between tumour invasiveness (T stage), the local and systemic environment and cancer-specific survival (CSS) of patients with primary operable colorectal cancer. methods: The tumour microenvironment was examined using measures of the inflammatory infiltrate (Klintrup-Makinen (KM) grade and Immunoscore), tumour stroma percentage (TSP) and tumour budding. The systemic inflammatory environment was examined using modified Glasgow Prognostic Score (mGPS) and neutrophil:lymphocyte ratio (NLR). A 5-year CSS was examined. results: A total of 331 patients were included. Increasing T stage was associated with colonic primary, N stage, poor differentiation, margin involvement and venous invasion (P<0.05). T stage was significantly associated with KM grade (P=0.001), Immunoscore (P=0.016), TSP (P=0.006), tumour budding (P<0.001), and elevated mGPS and NLR (both P<0.05). In patients with T3 cancer, N stage stratified survival from 88 to 64%, whereas Immunoscore and budding stratified survival from 100 to 70% and from 91 to 56%, respectively. The Glasgow Microenvironment Score, a score based on KM grade and TSP, stratified survival from 93 to 58%. conclusions: Although associated with increasing T stage, local and systemic tumour environment characteristics, and in particular Immunoscore, budding, TSP and mGPS, are stage-independent determinants of survival and may be utilised in the staging of patients with primary operable colorectal cancer

ShortRead: a bioconductor package for input, quality assessment and exploration of high-throughput sequence data

Summary: ShortRead is a package for input, quality assessment, manipulation and output of high-throughput sequencing data. ShortRead is provided in the R and Bioconductor environments, allowing ready access to additional facilities for advanced statistical analysis, data transformation, visualization and integration with diverse genomic resources