´Just Living Together´

This article tests the assumption that cohabitation makes a difference in the allocation of child care responsibilities within couples. It has often been presumed that cohabiting individuals are less likely to adhere to traditional gender ideology than married persons, because they tend to have a lower tolerance for poorly functioning relationships, assign more value to individual freedom and base their relationship on egalitarian individualism rather than on the joint utility maximization of married couples. So far, however, most studies have focused on the determinants and consequences of being in cohabitation and have overlooked its gender implications. Here we explore whether fathers in consensual unions are more prone than fathers in marital unions to share childcare responsibilities with their female partners. We use multilevel regression models for panel data to analyse ECHP in the period between 1996 and 2001. Our sample included around 13,000 couples living in heterosexual partnerships with small children (at least one child below age 13), and yielded around 45,000 observations over this period of time in ten Western European nations. We found weak evidence of the influence of cohabitation on gender equality as compared to married couples, while discovering that the diffusion of cohabitation at the societal level is associated with more equal allotment of child care among partners.cohabitation, ECHP, Europe, gender division of child care

Adrenomedullin as a potential biomarker involved in patients with hereditary hemorrhagic telangiectasia

Background: Adrenomedullin (AM) is a vasoactive peptide mostly secreted by endothelial cells with an important role in preserving endothelial integrity. The relationship between AM and hereditary hemorrhagic telangiectasia (HHT) is unknown. We aimed to compare the serum levels and tissue expression of AM between HHT patients and controls. Methods: Serum AM levels were measured by radioimmunoassay and compared between control and HHT groups. AM levels were also compared among HHT subgroups according to clinical characteristics. The single nucleotide polymorphism (SNP) rs4910118 was assessed by restriction analysis and sequencing. AM immunohistochemistry was performed on biopsies of cutaneous telangiectasia from eight HHT patients and on the healthy skin from five patients in the control group. Results: Forty-five HHT patients and 50 healthy controls were included, mean age (SD) was 50.7 (14.9) years and 46.4 (9.9) years (p = 0.102), respectively. HHT patients were mostly female (60% vs 38%, p = 0.032). Median [Q1-Q3] serum AM levels were 68.3 [58.1-80.6] pg/mL in the HHT group and 47.7 [43.2-53.8] pg/mL in controls (p<0.001), with an optimal AM cut-off according to Youden's J statistic of 55.32 pg/mL (J:0.729). Serum AM levels were similar in the HHT subgroups. No patient with HHT had the SNP rs4910118. AM immunoreactivity was found with high intensity in the abnormal blood vessels of HHT biopsies

Clinical pharmacogenomic testing of KRAS, BRAF and EGFR mutations by high resolution melting analysis and ultra-deep pyrosequencing

BACKGROUND: Epidermal growth factor receptor (EGFR) and its downstream factors KRAS and BRAF are mutated in several types of cancer, affecting the clinical response to EGFR inhibitors. Mutations in the EGFR kinase domain predict sensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in lung adenocarcinoma, while activating point mutations in KRAS and BRAF confer resistance to the anti-EGFR monoclonal antibody cetuximab in colorectal cancer. The development of new generation methods for systematic mutation screening of these genes will allow more appropriate therapeutic choices. METHODS: We describe a high resolution melting (HRM) assay for mutation detection in EGFR exons 19-21, KRAS codon 12/13 and BRAF V600 using formalin-fixed paraffin-embedded samples. Somatic variation of KRAS exon 2 was also analysed by massively parallel pyrosequencing of amplicons with the GS Junior 454 platform. RESULTS: We tested 120 routine diagnostic specimens from patients with colorectal or lung cancer. Mutations in KRAS, BRAF and EGFR were observed in 41.9%, 13.0% and 11.1% of the overall samples, respectively, being mutually exclusive. For KRAS, six types of substitutions were detected (17 G12D, 9 G13D, 7 G12C, 2 G12A, 2 G12V, 2 G12S), while V600E accounted for all the BRAF activating mutations. Regarding EGFR, two cases showed exon 19 deletions (delE746-A750 and delE746-T751insA) and another two substitutions in exon 21 (one showed L858R with the resistance mutation T590M in exon 20, and the other had P848L mutation). Consistent with earlier reports, our results show that KRAS and BRAF mutation frequencies in colorectal cancer were 44.3% and 13.0%, respectively, while EGFR mutations were detected in 11.1% of the lung cancer specimens. Ultra-deep amplicon pyrosequencing successfully validated the HRM results and allowed detection and quantitation of KRAS somatic mutations. CONCLUSIONS: HRM is a rapid and sensitive method for moderate-throughput cost-effective screening of oncogene mutations in clinical samples. Rather than Sanger sequence validation, next-generation sequencing technology results in more accurate quantitative results in somatic variation and can be achieved at a higher throughput scale.This work was supported by grants from Spanish Health Ministry (FIS) network RIRAAF (RD 07/0064).Ye

Three novel and the common Arg677Ter RP1 protein truncating mutations causing autosomal dominant retinitis pigmentosa in a Spanish population

BACKGROUND: Retinitis pigmentosa (RP), a clinically and genetically heterogeneous group of retinal degeneration disorders affecting the photoreceptor cells, is one of the leading causes of genetic blindness. Mutations in the photoreceptor-specific gene RP1 account for 3–10% of cases of autosomal dominant RP (adRP). Most of these mutations are clustered in a 500 bp region of exon 4 of RP1. METHODS: Denaturing gradient gel electrophoresis (DGGE) analysis and direct genomic sequencing were used to evaluate the 5' coding region of exon 4 of the RP1 gene for mutations in 150 unrelated index adRP patients. Ophthalmic and electrophysiological examination of RP patients and relatives according to pre-existing protocols were carried out. RESULTS: Three novel disease-causing mutations in RP1 were detected: Q686X, K705fsX712 and K722fsX737, predicting truncated proteins. One novel missense mutation, Thr752Met, was detected in one family but the mutation does not co-segregate in the family, thereby excluding this amino acid variation in the protein as a cause of the disease. We found the Arg677Ter mutation, previously reported in other populations, in two independent families, confirming that this mutation is also present in a Spanish population. CONCLUSION: Most of the mutations reported in the RP1 gene associated with adRP are expected to encode mutant truncated proteins that are approximately one third or half of the size of wild type protein. Patients with mutations in RP1 showed mild RP with variability in phenotype severity. We also observed several cases of non-penetrant mutations

Anàlisi de l'expressió de mutacions de splicing en cis i trans en gens associats a retinosi pigmentària autosòmica dominant

Consultable des del TDXTítol obtingut de la portada digitalitzadaLa retinosi pigmentària (RP) és una malaltia degenerativa de la retina amb caràcter hereditari. Aquesta malaltia pot presentar diferents tipus d'herència: autosòmica dominant, autosòmica recessiva, lligada al cromosoma X i algunes formes digèniques i mitocondrials. La retinosi pigmentària autosòmica dominant (RPAD) està causada majoritàriament per mutacions en gens amb expressió específica a la retina i que codifiquen proteïnes involucrades principalment en la funció, estructura i desenvolupament de la retina. Tot i així, en els darrers anys, s'ha vist que mutacions en certs gens amb expressió ubiqua només provoquen patologia a la retina. Alguns d'aquests gens codifiquen proteïnes implicades en el processament del mRNA o «splicing». Tres d'aquests factors són les proteïnes PRPF3, PRPF8 i PRPF31. Mutacions en «trans» en aquests factors de «splicing» sembla ser que provoquen RPAD. D'altra banda, també s'ha vist que mutacions en «cis» en els senyals de «splicing» del gen de la rodopsina (RHO), associat a RP, també provoquen RPAD. En aquest treball es realitza un cribatge mutacional en els gens que codifiquen els factors PRPF3, PRPF8 i PRPF31 en pacients afectats per la RPAD. Es realitza la correlació fenotip-genotip en els pacients portadors de mutacions en aquests gens. Mitjançant microarrays de DNA s'estudia el perfil d'expressió gènica en alguns pacients portadors de mutacions en algun d'aquests gens per tal d'esbrinar el mecanisme patogènic que pot estar provocant la malaltia. Pel que fa a les mutacions en senyals de «splicing» del gen RHO, s'estudien els efectes d'aquestes mutacions sobre el processament del mRNA de RHO.Retinitis pigmentosa (RP) is an inherited and degenerative disease of the retina. This disease presents different types of inheritance: autosomal dominant, autosomal recessive, X-linked and some digenic and mitochondrial forms. In most cases, autosomal dominant retinitis pigmentosa (ADRP) is caused by mutations in genes specifically expressed in the retina that codify proteins mainly involved in function, structure and development of the retina. However, in the last years it seems that mutations in certain genes with ubiquituous expression only cause pathology in the retina. Some of these genes codify proteins involved in the pre-mRNA splicing. Three of these factors are PRPF3, PRPF8 and PRPF31. It seems that trans-mutations in these splicing factors can cause RPAD. On the other hand, cis-mutations in splicing sites in the rhodopsin gene, associated to RP, also cause RPAD. In this work, a mutational screening in genes coding for PRPF3, PRPF8 and PRPF31 factors has been performed in patients affected of ADRP. Phenotype-genotype correlation has been done in patients carrying mutations in these genes. Through DNA microarrays, gene expression profile has been studied in some patients carrying mutation in some of these genes to ascertain the pathogenic mechanism that can cause the disease. Regarding mutations in splicing sites of the RHO gene, effects of these mutations in the splicing process are discussed

Variability of diatom community composition and structure in mountain streams

Financiado para publicación en acceso aberto: Universidade de Vigo/CISUGSmall rivers support high levels of biodiversity, being especially sensitive to the effects of global change. Temporal records of community composition in minimally impaired streams can be used to explore trends in biodiversity in response to climate change and natural temporal variation. We approached the comparison of two time periods (2003–2008 and 2016–2020) to study whether the composition of diatom assemblages changed over time in twenty-three streams of the mountain range of Picos de Europa (Northern Spain). The stream’s water chemistry indicated significant decreases in N_NO3− and P_PO43− content over time. In these minimally disturbed streams, the specific diatom community was dominated by Achnanthidium pyrenaicum, Achnanthidium minutissimum and Cocconeis euglypta. PERMANOVA analyses did not identify significant changes in diatom assemblage composition between periods or river types. Diatom indices (e.g. IPS, NORTIdiat) indicated high or good ecological status and relatively high alpha diversity values were found in these mountain rivers during the studied years. Although diversity and evenness showed a significant decrease over time, the temporal stability of the river-type diatom reference community between the two periods should be considered as an indicator of biodiversity persistence of high importance when monitoring the ecological status following the reference condition approach