Browsing by Issue Date, starting with "2019-07-10"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
- Setting up a collaborative European human biological monitoring study on occupational exposure to hexavalent chromiumPublication . Santonen, Tiina; Alimonti, Alessandro; Bocca, Beatrice; Duca, Radu Corneliu; Galea, Karen S; Godderis, Lode; Göen, Thomas; Gomes, Bruno; Hanser, Ogier; Iavicoli, Ivo; Janasik, Beata; Jones, Kate; Kiilunen, Mirja; Koch, Holger M; Leese, Elizabeth; Leso, Veruscka; Louro, Henriqueta; Ndaw, Sophie; Porras, Simo P; Robert, Alain; Ruggieri, Flavia; Scheepers, Paul T J; Silva, Maria J; Viegas, Susana; Wasowicz, Wojciech; Castano, Argelia; Sepai, OvnairThe EU human biomonitoring initiative, HBM4EU, aims to co-ordinate and advance human biomonitoring (HBM) across Europe. Within its remit, the project is gathering new, policy relevant, EU-wide data on occupational exposure to relevant priority chemicals and developing new approaches for occupational biomonitoring. In this manuscript, the hexavalent chromium [Cr(VI)] study design is presented as the first example of this HBM4EU approach. This study involves eight European countries and plans to recruit 400 workers performing Cr(VI) surface treatment e.g. electroplating or stainless steel welding activities. The aim is to collect new data on current occupational exposure to Cr(VI) in Europe and to test new methods for Cr biomonitoring, specifically the analysis of Cr(VI) in exhaled breath condensate (EBC) and Cr in red blood cells (RBC) in addition to traditional urinary total Cr analyses. Furthermore, exposure data will be complemented with early biological effects data, including genetic and epigenetic effects. Personal air samples and wipe samples are collected in parallel to help informing the biomonitoring results. We present standard operational procedures (SOPs) to support the harmonized methodologies for the collection of occupational hygiene and HBM samples in different countries.
- Evaluation of the potential association of SOHLH2 polymorphisms with non-obstructive azoospermia susceptibility in a large European populationPublication . Sánchez, Maria I.S.; Martín, Miriam C.; Egea, Rocío R.; Puchalt, Nicolás G.; Marco, Saturnino L.; Magraner, Gema R.; Ribeiro, Samuel; Castilla Alcalá, José A.; Gonzalvo López, Maria C.; Gilabert, Ana C.; Vicente Prados, F. Javier; Ezequiel, Vicente M.; Poyatos, Miguel B.; Rodrigo, Olga L.; Peraza Godoy, María F.; Caetano, Iris; Marques, Patricia; Arnau, Lluis B.; Seixas, Susana; Gonçalves, João; Bartolomé, Sara L.; Lopes, Alexandra; Carmona López, F. David; Palomino Morales, Rogelio J.Non-obstructive azoospermia (NOA) or spermatogenic failure is a complex disease with an important genetic component that causes infertility in men. Known genetic factors associated with NOA include AZF microdeletions of the Y chromosome or karyotype abnormalities; however, most causes of NOA are idiopathic. During the last decade, a large list of associations between single-nucleotide polymorphisms (SNP) and NOA have been reported. However, most of the genetic studies have been performed only in Asian populations. We aimed to evaluate whether the previously described association in Han Chinese between NOA and two SNPs of the SOHLH2 gene (involved in the spermatogenesis process) may also confer risk for NOA in a population of European ancestry. We genotyped a total of 551 NOA patients (218 from Portugal and 333 from Spain) and 1,050 fertile controls (226 from Portugal and 824 from Spain) for the genetic variants rs1328626 and rs6563386 using TaqMan assays. To test for association, we compared the allele and genotype frequencies between cases and controls using an additive model. A haplotype analysis and a meta-analysis using the inverse variance method with our data and those of the original Asian study were also performed. No statistically significant differences were observed in any of the analyses described above. Therefore, considering the high statistical power of our study, it is not likely that the two analysed SOHLH2 genetic variants are related with an increase susceptibility to NOA in the European population.
- Network biology approaches in the identification of novel pharmacological targets – the case of cystic fibrosisPublication . Loureiro, Cláudia; Matos, Ana; Santos, João; Farinha, Carlos; Jordan, Peter; Matos, Paulo; Pinto, FranciscoIn cystic fibrosis, the most common disease-causing mutation is F508del, which causes not only intracellular retention and degradation of CFTR, but also defective channel gating and decreased membrane stability of the small amount that reaches the plasma membrane (PM). Thus, pharmacological correction of mutant CFTR requires targeting of multiple cellular defects in order to achieve clinical benefit. Although small-molecule compounds have been identified and commercialized that can correct its folding or gating, an efficient retention of F508del CFTR at the PM has not yet been explored pharmacologically despite being recognized as a crucial factor for improving functional rescue of chloride transport. In ongoing efforts to determine the CFTR interactome at the PM, we used three complementary approaches: targeting proteins binding to tyrosine-phosphorylated CFTR, protein complexes involved in cAMP-mediated CFTR stabilization at the PM, and proteins selectively interacting at the PM with rescued F508del-CFTR but not wt-CFTR. Using co-immunoprecipitation or peptide–pull down strategies, we identified around 400 candidate proteins through sequencing of complex protein mixtures using the nano-LC Triple TOF MS technique. Key candidate proteins were validated for their robust interaction with CFTR-containing protein complexes and for their ability to modulate the amount of CFTR expressed at the cell surface of bronchial epithelial cells. Here, we describe how we explored the abovementioned experimental datasets to build a protein interaction network with the aim of identifying novel pharmacological targets to rescue CFTR function in cystic fibrosis (CF) patients. We identified and validated novel candidate proteins that were essential components of the network but not detected in previous proteomic analyses.