Explore the vast range of titles available.

In this paper, we determine by fluorescent in situ hybridization the variability in the chromosomal location of 45S rDNA clusters in 38 species belonging to 7 genera of the Triatominae subfamily, using a triatomine-specific 18S rDNA probe. Our results show a striking variability at the inter- and intraspecific level, never reported so far in holocentric chromosomes, revealing the extraordinary genomic dynamics that occurred during the evolution in this group of insects. Our results also demonstrate that the chromosomal position of rDNA clusters is an important marker to disclose chromosomal differentiation in species karyotypically homogenous in their chromosome number.

The subfamily Triatominae (Hemiptera, Reduviidae), vectors of Chagas disease, includes over 140 species. Karyotypic information is currently available for 80 of these species. This paper summarizes the chromosomal variability of the subfamily and how it may reveal aspects of genome evolution in this group. The Triatominae present a highly conserved chromosome number. All species, except 3, present 20 autosomes. The differences in chromosome number are mainly caused by variation in the number of sex chromosomes, due to the existence of 3 sex systems in males (XY, X 1 X 2 Y and X 1 X 2 X 3 Y). However, inter- and intraspecific differences in the position, quantity and meiotic behavior of constitutive heterochromatin, in the total genome size, and in the location of ribosomal 45S rRNA clusters, have revealed considerable cytogenetic variability within the subfamily. This cytogenetic diversity offers the opportunity to perform cytotaxonomic and phylogenetic studies, as well as structural, evolutionary, and functional analyses of the genome. The imminent availability of the complete genome of Rhodnius prolixus also opens new perspectives for understanding the evolution and genome expression of triatomines. The application of fluorescence in situ hybridization for the mapping of genes and sequences, as well as comparative analyses of genome homology by comparative genomic hybridization will be useful tools for understanding the genomic changes in relation to evolutionary processes such as speciation and adaptation to different environments.

Chromosomal translocations involving the MALT1 gene are hallmarks of mucosa-associated lymphoid tissue (MALT) lymphoma. To date, targeting these translocations to mouse B cells has failed to reproduce human disease. Here, we induced MALT1 expression in mouse Sca1 ⁺Lin ⁻ hematopoietic stem/progenitor cells, which showed NF-κB activation and early lymphoid priming, being selectively skewed toward B-cell differentiation. These cells accumulated in extranodal tissues and gave rise to clonal tumors recapitulating the principal clinical, biological, and molecular genetic features of MALT lymphoma. Deletion of p53 gene accelerated tumor onset and induced transformation of MALT lymphoma to activated B-cell diffuse large-cell lymphoma (ABC-DLBCL). Treatment of MALT1-induced lymphomas with a specific inhibitor of MALT1 proteolytic activity decreased cell viability, indicating that endogenous Malt1 signaling was required for tumor cell survival. Our study shows that human-like lymphomas can be modeled in mice by targeting MALT1 expression to hematopoietic stem/progenitor cells, demonstrating the oncogenic role of MALT1 in lymphomagenesis. Furthermore, this work establishes a molecular link between MALT lymphoma and ABC-DLBCL, and provides mouse models to test MALT1 inhibitors. Finally, our results suggest that hematopoietic stem/progenitor cells may be involved in the pathogenesis of human mature B-cell lymphomas.

In Spain, the contribution of BRCA mutations to the population incidence of early‐onset breast cancer was unknown. We carried out a mutational analysis of the BRCA1 and BRCA2 genes in 124 Spanish women diagnosed with breast cancer before the age 41 and who were not selected for a family history of this disease. The genetic study was performed by PCR‐SSCP analysis and DNA sequencing. We identified 6 pathogenic BRCA mutations in 7 unrelated probands (5.6%; 95% CI=2.3% to 11.3%): 1 BRCA1 (c.2080delA) and 5 BRCA2 (p.Y3006X, p.Q1994X, c.9204_9217del14, c.9254_9258del5 and c.295+2T>C). Three out of 6 mutations were novel (BRCA2 p.Y3006X, c.9204_9217del14, and c.295+2T>C), and two further mutations had not been previously found in Spain (BRCA1 c.2080delA and BRCA2 p.Q1994X). The one remaining (BRCA2 c.9254_9258del5) was detected in two probands of our sample. Additionally, we identified two new missense mutations: BRCA1 p.P1812A and BRCA2 p.G2044A. Our data support the notion that Spaniards represent a heterogeneous population with its own spectrum of BRCA mutations, some of which appear as founding mutations. We categorized patients into familial or non‐familial groups on the basis of her family history of breast/ovarian cancer; this analysis indicated that among Spanish women with early‐onset breast cancer, an even moderate family history is a good predictor of being a BRCA mutation carrier. © 2003 Wiley‐Liss, Inc.

Mutations underlying FH in Spain are largely unknown because only a few and limited surveys have been carried out on Spanish FH patients up to now. To gain information on this issue, we have analysed a group of 113 unrelated Spanish FH patients from an eastern area of Spain (Valencian Community). We have screened the LDLR gene by Southern blot and PCR‐SSCP analysis to detect large rearrangements and small mutations, respectively. In addition, we have screened the Apo B gene for mutations known to cause FDB by PCR‐SSCP analysis. We have identified a total of 47 different mutations in the LDLR gene (5 large rearrangements, and 42 small mutations, which were characterized by DNA sequencing), 19 of which have not been described in other populations (Valencia‐1 to ‐4, 112insA, P160R, 790DelATGA, 920insTCAG, G642E, and the ten novel mutations E246A, 884delT, I289T, S305F, Q328X, Y354C, I603del, 2312‐3C>A, V779M, and N804K). Three of these mutations (15%) were present in more than 1 proband, being mutation 112insA the most prevalent (frequency ∼ 8%) in our sample. The Apo B gene R3500Q mutation was found in only one patient and no underlying defect was found in about 27% of patients. Our data support the notion that Spaniards represent a heterogeneous population with its own spectrum of LDLR gene mutations and that, in our population, FDB has a lower frequency or a milder expression than in central Europe countries. © Wiley‐Liss, Inc.

We screened index cases from 410 Spanish breast/ovarian cancer families and 214 patients (19 of them males) with breast cancer for germ‐line mutations in the BRCA1 and BRCA2 genes, using SSCP, PTT, CSGE, DGGE, and direct sequencing. We identified 60 mutations in BRCA1 and 53 in BRCA2. Of the 53 distinct mutations observed, 11 are novel and 12 have been reported only in Spanish families (41.5%). The prevalence of mutations in this set of families was 26.3%, but the percentage was higher in the families with breast and ovarian cancer (52.1%). The lowest proportion of mutations was found in the site‐specific female breast cancer families (15.4%). Of the families with male breast cancer cases, 59.1% presented mutations in the BRCA2 gene. We found a higher frequency of ovarian cancer associated with mutations localized in the 5′ end of the BRCA1 gene, but there was no association between the prevalence of this type of cancer and mutations situated in the ovarian cancer cluster region (OCCR) region of exon 11 of the BRCA2 gene. The mutations 187underscore;188delAG, 330A>G, 5236G>A, 5242C>A, and 589underscore;590del (numbered after GenBank U14680) account for 46.6% of BRCA1 detected mutations whereas 3036underscore;3039del, 6857underscore;6858del, 9254underscore;9258del, and 9538underscore;9539del (numbered after GenBank U43746) account for 56.6% of the BRCA2 mutations. The BRCA1 330A>G has a Galician origin (northwest Spain), and BRCA2 6857underscore;6858del and 9254underscore;9258del probably originated in Catalonia (northeast Spain). Knowledge of the spectrum of mutations and their geographical distribution in Spain will allow a more effective detection strategy in countries with large Spanish populations. Hum Mutat 22:301–312, 2003. © 2003 Wiley‐Liss, Inc.

Background There is increasing attention paid to the arrival of migrants from outwith the EU region to the European countries. Healthcare that is universally and equably accessible needs to be provided for these migrants throughout the range of national contexts and in response to complex and evolving individual needs. It is important to look at the evidence available on provision and access to healthcare for migrants to identify barriers to accessing healthcare and better plan necessary changes. Methods This review scoped 77 papers from nine European countries (Austria, Cyprus, France, Germany, Greece, Italy, Malta, Spain, and Sweden) in English and in country-specific languages in order to provide an overview of migrants’ access to healthcare. The review aims at identifying what is known about access to healthcare as well as healthcare use of migrants and refugees in the EU member states. The evidence included documents from 2011 onwards. Results The literature reviewed confirms that despite the aspiration to ensure equality of access to healthcare, there is evidence of persistent inequalities between migrants and non-migrants in access to healthcare services. The evidence shows unmet healthcare needs, especially when it comes to mental and dental health as well as the existence of legal barriers in accessing healthcare. Language and communication barriers, overuse of emergency services and underuse of primary healthcare services as well as discrimination are described. Conclusions The European situation concerning migrants’ and refugees’ health status and access to healthcare is heterogeneous and it is difficult to compare and draw any firm conclusions due to the scant evidence. Different diseases are prioritised by different countries, although these priorities do not always correspond to the expressed needs or priorities of the migrants. Mental healthcare, preventive care (immunization) and long-term care in the presence of a growing migrant older population are identified as priorities that deserve greater attention. There is a need to improve the existing data on migrants’ health status, needs and access to healthcare to be able to tailor care to the needs of migrants. To conduct research that highlights migrants’ own views on their health and barriers to access to healthcare is key.

Predicting motions of vessels in extreme sea states represents one of the most challenging problems in naval hydrodynamics. It involves computing complex nonlinear wave-body interactions, hence taxing heavily computational resources. Here, we put forward a new simulation paradigm by training recurrent type neural networks (RNNs) that take as input the stochastic wave elevation at a certain sea state and output the main vessel motions, e.g. pitch, heave and roll. We first compare the performance of standard RNNs versus GRU and LSTM neural networks (NNs) and show that LSTM NNs lead to the best performance. We then examine the testing error of two representative vessels, a catamaran in sea state 1 and a battleship in sea state 8. We demonstrate that good accuracy is achieved for both cases in predicting the vessel motions for unseen wave elevations. We train the NNs with expensive CFD simulations offline, but upon training, the prediction of the vessel dynamics online can be obtained at a fraction of a second. This work is motivated by the universal approximation theorem for functionals (Chen & Chen, 1993. IEEE Trans. Neural Netw. 4, 910–918 (doi:10.1109/72.286886)), and it is the first implementation of such theory to realistic engineering problems.

“Ave Maria, gratia plena”, “Ecce ancilla Domini”, “Pulchra ut luna”, “Electa ut sol” i altres molts textos estan a l’abast de la mirada de tothom en els retaules gòtics i renaixentistes dedicats a la Mare de Déu o amb escenes de la seua vida. La qüestió és que no sempre són de fàcil lectura per múltiples circumstàncies ni responen a allò que hom podria esperar. En el present article, doncs, s’analitzaran les inscripcions de tall marià que ens ofereix la pintura valenciana dels segles XIV al XVI, atenent a la seua procedència i a l’estret vincle que les uneix a la imatge, a més d’oferir una transcripció i edició crítica d’aquestes inscripcions. “Ave Maria, gratia plena”, “Ecce ancilla Domini”, “Pulchra ut luna”, “Electa ut sol” and many other texts are within everyone’s reach in Gothic and Renaissance altarpieces dedicated to the Virgin Mary or with scenes from her life. The point is that they are not always easy to read due to multiple circumstances nor do they respond to what one might expect. In this article, therefore, the Marian inscriptions offered by Valencian painting from the 14th to the 16th centuries will be analyzed, taking into account their provenance and the close link that unites them to the image, in addition to offering a transcription and critical edition of these inscriptions. “Ave Maria, gratia plena”, “Ecce ancilla Domini”, “Pulchra ut luna”, “Electa ut sol” i altres molts textos estan a l’abast de la mirada de tothom en els retaules gòtics i renaixentistes dedicats a la Mare de Déu o amb escenes de la seua vida. La qüestió és que no sempre són de fàcil lectura per múltiples circumstàncies ni responen a allò que hom podria esperar. En el present article, doncs, s’analitzaran les inscripcions de tall marià que ens ofereix la pintura valenciana dels segles XIV al XVI, atenent a la seua procedència i a l’estret vincle que les uneix a la imatge, a més d’oferir una transcripció i edició crítica d’aquestes inscripcions. “Ave Maria, gratia plena”, “Ecce ancilla Domini”, “Pulchra ut luna”, “Electa ut sol” i altres molts textos estan a l’abast de la mirada de tothom en els retaules gòtics i renaixentistes dedicats a la Mare de Déu o amb escenes de la seua vida. La qüestió és que no sempre són de fàcil lectura per múltiples circumstàncies ni responen a allò que hom podria esperar. En el present article, doncs, s’analitzaran les inscripcions de tall marià que ens ofereix la pintura valenciana dels segles XIV al XVI, atenent a la seua procedència i a l’estret vincle que les uneix a la imatge, a més d’oferir una transcripció i edició crítica d’aquestes inscripcions. “Ave Maria, gratia plena”, “Ecce ancilla Domini”, “Pulchra ut luna”, “Electa ut sol” i altres molts textos estan a l’abast de la mirada de tothom en els retaules gòtics i renaixentistes dedicats a la Mare de Déu o amb escenes de la seua vida. La qüestió és que no sempre són de fàcil lectura per múltiples circumstàncies ni responen a allò que hom podria esperar. En el present article, doncs, s’analitzaran les inscripcions de tall marià que ens ofereix la pintura valenciana dels segles XIV al XVI, atenent a la seua procedència i a l’estret vincle que les uneix a la imatge, a més d’oferir una transcripció i edició crítica d’aquestes inscripcions. “Ave Maria, gratia plena”, “Ecce ancilla Domini”, “Pulchra ut luna”, “Electa ut sol” i altres molts textos estan a l’abast de la mirada de tothom en els retaules gòtics i renaixentistes dedicats a la Mare de Déu o amb escenes de la seua vida. La qüestió és que no sempre són de fàcil lectura per múltiples circumstàncies ni responen a allò que hom podria esperar. En el present article, doncs, s’analitzaran les inscripcions de tall marià que ens ofereix la pintura valenciana dels segles XIV al XVI, atenent a la seua procedència i a l’estret vincle que les uneix a la imatge, a més d’oferir una transcripció i edició crítica d’aquestes inscripcions.