Evidence for classification of c.1852_1853AA>GC in MLH1 as a neutral variant for Lynch syndrome

Background: Lynch syndrome (LS) is an autosomal dominant inherited cancer syndrome characterized by early onset cancers of the colorectum, endometrium and other tumours. A significant proportion of DNA variants in LS patients are unclassified. Reports on the pathogenicity of the c.1852_1853AA>GC (p.Lys618Ala) variant of the MLH1 gene are conflicting. In this study, we provide new evidence indicating that this variant has no significant implications for LS.Methods: The following approach was used to assess the clinical significance of the p.Lys618Ala variant: frequency in a control population, case-control comparison, co-occurrence of the p.Lys618Ala variant with a pathogenic mutation, co-segregation with the disease and microsatellite instability in tumours from carriers of the variant. We genotyped p.Lys618Ala in 1034 individuals (373 sporadic colorectal cancer [CRC] patients, 250 index subjects from families suspected of having LS [revised Bethesda guidelines] and 411 controls). Three well-characterized LS families that fulfilled the Amsterdam II Criteria and consisted of members with the p.Lys618Ala variant were included to assess co-occurrence and co-segregation. A subset of colorectal tumour DNA samples from 17 patients carrying the p.Lys618Ala variant was screened for microsatellite instability using five mononucleotide markers.Results: Twenty-seven individuals were heterozygous for the p.Lys618Ala variant; nine had sporadic CRC (2.41%), seven were suspected of having hereditary CRC (2.8%) and 11 were controls (2.68%). There were no significant associations in the case-control and case-case studies. The p.Lys618Ala variant was co-existent with pathogenic mutations in two unrelated LS families. In one family, the allele distribution of the pathogenic and unclassified variant was in trans, in the other family the pathogenic variant was detected in the MSH6 gene and only the deleterious variant co-segregated with the disease in both families. Only two positive cases of microsatellite instability (2/17, 11.8%) were detected in tumours from p.Lys618Ala carriers, indicating that this variant does not play a role in functional inactivation of MLH1 in CRC patients.Conclusions: The p.Lys618Ala variant should be considered a neutral variant for LS. These findings have implications for the clinical management of CRC probands and their relatives.

Distribution of events of positive selection and population differentiation in a metabolic pathway: the case of asparagine N-glycosylation

Background: Asparagine N-Glycosylation is one of the most important forms of protein post-translational modification in eukaryotes. This metabolic pathway can be subdivided into two parts: an upstream sub-pathway required for achieving proper folding for most of the proteins synthesized in the secretory pathway, and a downstream sub-pathway required to give variability to trans-membrane proteins, and involved in adaptation to the environment andinnate immunity. Here we analyze the nucleotide variability of the genes of this pathway in human populations, identifying which genes show greater population differentiation and which genes show signatures of recent positive selection. We also compare how these signals are distributed between the upstream and the downstream parts of the pathway, with the aim of exploring how forces of population differentiation and positive selection vary among genes involved in the same metabolic pathway but subject to different functional constraints. Results:Our results show that genes in the downstream part of the pathway are more likely to show a signature of population differentiation, while events of positive selection are equally distributed among the two parts of the pathway. Moreover, events of positive selection arefrequent on genes that are known to be at bifurcation points, and that are identified as beingin key position by a network-level analysis such as MGAT3 and GCS1.Conclusions: These findings indicate that the upstream part of the Asparagine N-Glycosylation pathway has lower diversity among populations, while the downstream part is freer to tolerate diversity among populations. Moreover, the distribution of signatures of population differentiation and positive selection can change between parts of a pathway, especially between parts that are exposed to different functional constraints. Our results support the hypothesis that genes involved in constitutive processes can be expected to show lower population differentiation, while genes involved in traits related to the environment should show higher variability. Taken together, this work broadens our knowledge on how events of population differentiation and of positive selection are distributed among different parts of a metabolic pathway.

Y-chromosome diversity in native mexicans reveals continental transition of genetic structure in the Americas

The genetic characterization of Native Mexicans is important to understand multiethnic based features influencing the medical genetics of present Mexican populations, as well as to the reconstruct the peopling of the Americas. We describe the Y-chromosome genetic diversity of 197 Native Mexicans from 11 populations and 1,044 individuals from 44 Native American populations after combining with publicly available data. We found extensive heterogeneity among Native Mexican populations and ample segregation of Q-M242* (46%) and Q-M3 (54%) haplogroups within Mexico. The northernmost sampled populations falling outside Mesoamerica (Pima and Tarahumara) showed a clear differentiation with respect to the other populations, which is in agreement with previous results from mtDNA lineages. However, our results point toward a complex genetic makeup of Native Mexicans whose maternal and paternal lineages reveal different narratives of their population history, with sex-biased continental contributions and different admixture proportions. At a continental scale, we found that Arctic populations and the northernmost groups from North America cluster together, but we did not find a clear differentiation within Mesoamerica and the rest of the continent, which coupled with the fact that the majority of individuals from Central and South American samples are restricted to the Q-M3 branch, supports the notion that most Native Americans from Mesoamerica southwards are descendants from a single wave of migration. This observation is compatible with the idea that present day Mexico might have constituted an area of transition in the diversification of paternal lineages during the colonization of the Americas.

A genomic analysis identifies a novel component in the genetic structure of sub-Saharan African populations

Studies of large sets of SNP data have proven to be a powerful tool in the analysis of the genetic structure of human populations. In this work, we analyze genotyping data for 2,841 SNPs in 12 Sub-Saharan African populations, including a previously unsampled region of south-eastern Africa (Mozambique). We show that robust results in a world-wide perspective can be obtained when analyzing only 1,000 SNPs. Our main results both confirm the results of previous studies, and show new and interesting features in Sub-Saharan African genetic complexity. There is a strong differentiation of Nilo-Saharans, much beyond what would be expected by geography. Hunter-gatherer populations (Khoisan and Pygmies) show a clear distinctiveness with very intrinsic Pygmy (and not only Khoisan) genetic features. Populations of the West Africa present an unexpected similarity among them, possibly the result of a population expansion. Finally, we find a strong differentiation of the south-eastern Bantu population from Mozambique, which suggests an assimilation of a pre-Bantu substrate by Bantu speakers in the region.

Linguistic and maternal genetic diversity are not correlated in native mexicans

Mesoamerica, defined as the broad linguistic and cultural area from middle southern Mexico to Costa Rica, might have played a pivotal role during the colonization of theAmerican continent. It has been suggested that the Mesoamerican isthmus could have played an important role in severely restricting prehistorically gene flow between North and SouthAmerica. Although the Native American component has been already described in admixedMexican populations, few studies have been carried out in native Mexican populations. In thisstudy we present mitochondrial DNA (mtDNA) sequence data for the first hypervariable region (HVR-I) in 477 unrelated individuals belonging to eleven different native populations from Mexico. Almost all the Native Mexican mtDNAs could be classified into the four pan-Amerindian haplogroups (A2, B2, C1 and D1); only three of them could be allocated to the rare Native American lineage D4h3. Their haplogroup phylogenies are clearly star-like, as expected from relatively young populations that have experienced diverse episodes of genetic drift (e.g. extensive isolation, genetic drift and founder effects) and posterior population expansions. In agreement with this observation is the fact that Native Mexican populations show a high degree of heterogeneity in their patterns of haplogroup frequencies. HaplogroupX2a was absent in our samples, supporting previous observations where this clade was only detected in the American northernmost areas. The search for identical sequences in the American continent shows that, although Native Mexican populations seem to show a closer relationship to North American populations, they cannot be related to a single geographical region within the continent. Finally, we did not find significant population structure on the maternal lineages when considering the four main and distinct linguistic groups represented in our Mexican samples (Oto-Manguean, Uto-Aztecan, Tarascan, and Mayan), suggesting that genetic divergence predates linguistic diversification in Mexico.

Origin and genetic differentiation of Three Mexican Native Groups (Purépechas, Triquis and Mayas): contribution of CODIS-STRs to the history of human populations of Mesoamerica

BACKGROUND: CODIS-STRs in Native Mexican groups have rarely been analysed for human identification and anthropological purposes. AIM:To analyse the genetic relationships and population structure among three Native Mexican groups from Mesoamerica.SUBJECTS AND METHODS: 531 unrelated Native individuals from Mexico were PCR-typed for 15 and 9 autosomal STRs (Identifiler™ and Profiler™ kits, respectively), including five population samples: Purépechas (Mountain, Valley and Lake), Triquis and Yucatec Mayas. Previously published STR data were included in the analyses. RESULTS:Allele frequencies and statistical parameters of forensic importance were estimated by population. The majority of Native groups were not differentiated pairwise, excepting Triquis and Purépechas, which was attributable to their relative geographic and cultural isolation. Although Mayas, Triquis and Purépechas-Mountain presented the highest number of private alleles, suggesting recurrent gene flow, the elevated differentiation of Triquis indicates a different origin of this gene flow. Interestingly, Huastecos and Mayas were not differentiated, which is in agreement with the archaeological hypothesis that Huastecos represent an ancestral Maya group. Interpopulation variability was greater in Natives than in Mestizos, both significant.CONCLUSION: Although results suggest that European admixture has increased the similarity between Native Mexican groups, the differentiation and inconsistent clustering by language or geography stresses the importance of serial founder effect and/or genetic drift in showing their present genetic relationships.

Proposta didàctica: els temes en context

En aquesta proposta didàctica s'ofereixen algunes estratègies de treball per abordar el tema de l'aprenentatge de terminologia especialitzada a l'últim cicle de l'educació primària. La idea de què es parteix per fer una proposta d'aquesta mena és que la terminologia té un paper fonamental en el procés de coneixement i definició del món que ens envolta; per això es proposen unes activitats sobre el reconeixement dels conceptes i les seves relacions com un mitjà per construir el coneixement. L'article s'estructura en uns continguts teòrics adreçats al professorat i en unes activitats per als estudiants, preparades amb l'objectiu de treballar la terminologia en context.

Aggiornamento biogràfic de Joan Pere Fontanella (1575-1649)

Com tants altres personatges de la nostra història, el pare de FrancescFontanella i Garraver –el jurisconsult olotí Joan Pere Fontanella–ha estat objecte durant dècades d’un encadenament de notíciesbiogràfiques on s’han reiterat dades no sempre filtrades científicament.Això ha abocat diverses generacions a acumular imprecisions sobre ell,fins i tot a distorsionar-ne la significació ideològica i política, sovinten clau d’un patriotisme ardorós. Volem contribuir, sense cap ànimd’esmena, a esclarir i difondre algunes informacions sobre les sevesvida i obra i el seu pensament jurídic i polític. I considerem adientfer-ho en un marc que ratione loci convida a ventilar els forts lligamsque l’advocat mantingué amb la ciutat de Girona i ratione materiaeobliga a subratllar el seu vessant protector dels parents i pròxims i,més a l’engròs, la seva vocació per analitzar amb el dret a la mà elcomplexíssim món de les relacions familiars.

A reassessment of family reunification in Europe. The case of Senegalese couples

Contemporary policy makers in most European destination countriesexpress a great concern about reunification of migrants’ families. Newrestrictions multiply in almost all countries, on the grounds thatmigrants would take advantage of a too lax system and that it wouldfoster an influx of non-desirable migrants. So far, quantitative evidenceis scarce on migrants’ practices in matter of family reunification.Taking advantage of a unique longitudinal dataset that includesSenegalese individuals surveyed both at origin (in Senegal) and inEurope (France, Italy and Spain), we perform event-history analyses toshow three things. First, couple separation is very often a long lastingsituation. Second, when separated because of international migration,wives and husbands do not only reunify in Europe but quite commonlyin Senegal. And third, those who reunify in Europe are those who arethe most adapted or adaptable to the European culture and economy.

Union activism in an inclusive model of industrial relations : evidence from an Spanish case

In this article we analyze the reasons, within the context of Spanish industrial relations, for trade union members’ active participation in their regional union. The case of Spain is particularly interesting as the unions’ main activity, collective bargaining, is a public good. The text, based on research involving a representative survey of members of a regional branch of the “Workers” Commissions” (Comisiones Obreras) trade union, provides empirical evidence that the union presence in the workplace has a significant influence on members’ propensity for activism. By contrast, the alternative hypothesis based on instrumental reasons appears of little relevance in the Spanish industrial relations context.

Political mobilisation and models of trade unionism : Southern Europe in comparative perspective

The relationship between union membership and political mobilization has been studied under many perspectives, but quantitative cross-national analyses have been hampered by the absence of international comparable survey data until the first round of the European Social Survey (ESS-2002) was made available. Using different national samples from this survey in four moments of time (2002, 2004 and 2006), our paper provides evidence of cross-country divergence in the empirical association between political mobilisation and trade union membership. Cross-national differences in union members’ political mobilization, we argue, can be explained by the existence of models of unionism that in turn differ with respect to two decisive factors: the institutionalisation of trade union activity and the opportunities left-wing parties have available for gaining access to executive power.

The Predicate-Argument Structure

Aquest article conté una proposta per a la representació de les estructures predicatives (és a dir, dels predicats amb els seus arguments) en els formalismes basats en estructures de trets tipificades. L’article comença amb una discussió dels objectius i del nivell de descripció de la representació que es proprosa; i després se centra en una exemplificació minuciosa de les estructures predicatives de totes les categories majors (verbs, adjectius, preposicions i noms), així com d’algunes relacions de modificació.

Usos i abusos de la imatge en l’univers cinematogràfic de la Shoah

El present treball proposa un recorregut a través de les imatges del genocidi dels jueus a Europa rodades durant la Segona gerra mundial, i més especialment, durantl’alliberament dels camps nazis. Estudia conjuntament aquestes imatges, els seus usos i les seves migracions com a elements fonamentals en el procés de construcció del’imaginari de la Shoah. En segon lloc, analitza de quina manera els arxius visuals del genocidi constitueixen un referent en la representació contemporània de la de la víctima i les relacions que s’estableixen entre aquesta figura i la retòrica testimonial en la configuració d’una memòria i d’un relat sobre l’esdeveniment

Voice Transformations for Extreme Vocal Effects

Extreme Vocal Effects (EVE) in music are so recent that few studies have been carried out about how they are physiologically produced and whether they are harmful or not for the human voice.Voice Transformations in real-time are possible nowadays thanks to new technologies and voice processing algorithms. This Master's Thesis pretends to define and classify these new singing techniques and to create a mapping between the physiological aspect of each EVE to its relative spectrumvariations.Voice Transformation Models based on these mappings are proposed and discussed for each one of these EVEs. We also discuss different transformation methods and strategies in order to obtain better results.A subjective evaluation of the results of the transformations is also presented and discussed along with further work, improvements, and working lines on this field.

Extracción de características para la clasificación de estados cognitivos a partir de imágenes FMRI

L’estudi de les funcions cerebrals humanes s’ha incrementat enormement durant els últims anys donada l’aparició de les imatges funcionals de ressonància magnètica (FMRI). Mentre que la tècnica s’ha emprat principalment en la localització de diferents funcions cerebrals, el problema de classificació d’estats cognitius ha estat poc explorat. L’estudi d’aquest problemaés important perquè pot servir com a eina per a detectar i seguir processoscognitius (seqüències d’estats cognitius) amb la finalitat de diagnosticarproblemes en el moment d’executar una tasca complexa.En aquest treball s’investiguen diferents aproximacions per a detectar l’estat cognitiu d’una persona prenent com a base la seva imatge de ressonància magnètica. En particular, s’han investigat varis mecanismes de sel·lecció de característiques així com mètodes d’aprenentatge automàtic pelproblema de la discriminació d’estats cognitius procedents d’estimuls auditius.Es presenten els resultats d’un estudi sobre estímuls musicals.