Sox21a is requiered for posterior lateral line patterning by regulating Fgf signalling

Resumen del póster presentado al IX Meeting of the Spanish Society for Developmental Biology celebrado en Granada del 12 al 14 de noviembre de 2012.Peer Reviewe

Metabolomic study of lipids in serum for biomarker discovery in Alzheimer's disease using direct infusion mass spectrometry

In this study, we demonstrated the potential of direct infusion mass spectrometry for the lipidomic characterization of Alzheimer's disease. Serum samples were extracted for lipids recovery, and directly analyzed using an electrospray source. Metabolomic fingerprints were subjected to multivariate analysis in order to discriminate between groups of patients and healthy controls, and then some key-compounds were identified as possible markers of Alzheimer's disease. Major differences were found in lipids, although some low molecular weight metabolites also showed significant changes. Thus, important metabolic pathways involved in neurodegeneration could be studied on the basis of these perturbations, such as membrane breakdown (phospholipids and diacylglycerols), oxidative stress (prostaglandins, imidazole and histidine), alterations in neurotransmission systems (oleamide and putrescine) and hyperammonaemia (guanidine and arginine). Moreover, it is noteworthy that some of these potential biomarkers have not been previously described for Alzheimer's disease.This work was supported by the projects CTM2012-38720-C03-01 from the Ministerio de Ciencia e Innovacion and P008-FQM-3554 and P009-FQM-4659 from the Consejeria de Innovacion, Ciencia y Empresa (Junta de Andalucia). Raul Gonzalez Dominguez thanks the Ministerio de Educacion for a predoctoral scholarship. The authors also thank to Dr. Alberto Blanco and Carlos Salgado from Hospital Juan Ramon Jimenez for providing serum samples

The Subjective Well-Being Challenge in the Accounting Profession: The Role of Job Resources

The main activity of the accountant is the preparation and audit of the financial information of a company. The subjective well-being of the accountant is important to ensure a balanced professional judgment and to offer a positive image of the profession in the face of the incorporation and retention of talent. However, accountants are subjected to intense pressures that affect their well-being in the performance of their tasks. In this paper, the job demands–resources theoretical framework is adopted to analyze the relationships between job demands, job resources, and the subjective well-being of a large sample of 739 accounting experts at the European level. Applying a structural equations model, the results confirm, on the one hand, the direct effects provided in the theoretical framework and, on the other, a new mediating role of job demands–subjective well-being relationship resources

Toenail zinc as a biomarker: Relationship with sources of environmental exposure and with genetic variability in MCC-Spain study

Background: Toenails are commonly used as biomarkers of exposure to zinc (Zn), but there is scarce information about their relationship with sources of exposure to Zn. Objectives: To investigate the main determinants of toenail Zn, including selected sources of environmental exposure to Zn and individual genetic variability in Zn metabolism. Methods: We determined toenail Zn by inductively coupled plasma mass spectrometry in 3,448 general population controls from the MultiCase-Control study MCC-Spain. We assessed dietary and supplement Zn intake using food frequency questionnaires, residential proximity to Zn-emitting industries and residential topsoil Zn levels through interpolation methods. We constructed a polygenic score of genetic variability based on 81 single nucleotide polymorphisms in genes involved in Zn metabolism. Geometric mean ratios of toenail Zn across categories of each determinant were estimated from multivariate linear regression models on log-transformed toenail Zn. Results: Geometric mean toenail Zn was 104.1 μg/g in men and 100.3 μg/g in women. Geometric mean toenail Zn levels were 7 % lower (95 % confidence interval 1–13 %) in men older than 69 years and those in the upper tertile of fibre intake, and 9 % higher (3–16 %) in smoking men. Women residing within 3 km from Zn-emitting industries had 4 % higher geometric mean toenail Zn levels (0–9 %). Dietary Zn intake and polygenic score were unrelated to toenail Zn. Overall, the available determinants only explained 9.3 % of toenail Zn variability in men and 4.8 % in women. Discussion: Sociodemographic factors, lifestyle, diet, and environmental exposure explained little of the individual variability of toenail Zn in the study population. The available genetic variants related to Zn metabolism were not associated with toenail Zn

Iodine deficiency disturbs the metabolic profile and elemental composition of human breast milk

Human breast milk (HBM) has a beneficial impact on health programming, growth and neurodevelopment of newborns. Increase in iodine intake is recommended for pregnant women in order to produce enough thyroid hormones to meet foetal requirements. In this work, a combined analytical multiplatform based on gas chromatography coupled to mass spectrometry and ultra-high performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry has been applied in the first metabolomic study of HBM of iodinedeficient women. In addition, the elemental composition of HBM has been determined by inductively coupled plasma triple quadrupole mass spectrometry. Remarkably, 31 metabolites with important biological roles (e.g.glycerophospholipids for neurodevelopment) were seen to be altered in the HBM of iodine-deficient women. The main metabolic pathways altered include lipid metabolism, amino acid cycle, the tricarboxylic acid cycle and glycolysis. Additionally, the concentration of selenium, zinc and copper were seen to be significantly lower in HBM of iodine-deficient women.PG2018-096608-B-C21 (Spanish Ministry of Science and innovation (MCIN). Generaci´on del Conocimiento. MCIN/ AEI /10.13039/501100011033/ FEDER “Una manera de hacer Europa”), UHU-1256905 and UHU-202009 from the FEDER Andalusian operative program (Regional Ministry of Economy, Knowledge, Business and University, Andalusia, Spain). Authors are grateful to FEDER (European Community) for financial support, Grants UNHU13-1E-1611 and UNHU15-CE-3140. Funding for open access charge: Universidad de Huelva / CBU

Gene-environment interaction analysis of redox-related metals and genetic variants with plasma metabolic patterns in a general population from Spain: The Hortega Study

Background: Limited studies have evaluated the joint influence of redox-related metals and genetic variation on metabolic pathways. We analyzed the association of 11 metals with metabolic patterns, and the interacting role of candidate genetic variants, in 1145 participants from the Hortega Study, a population-based sample from Spain. Methods: Urine antimony (Sb), arsenic, barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), molybdenum (Mo) and vanadium (V), and plasma copper (Cu), selenium (Se) and zinc (Zn) were measured by ICP-MS and AAS, respectively. We summarized 54 plasma metabolites, measured with targeted NMR, by estimating metabolic principal components (mPC). Redox-related SNPs (N = 291) were measured by oligo-ligation assay. Results: In our study, the association with metabolic principal component (mPC) 1 (reflecting non-essential and essential amino acids, including branched chain, and bacterial co-metabolism versus fatty acids and VLDL subclasses) was positive for Se and Zn, but inverse for Cu, arsenobetaine-corrected arsenic (As) and Sb. The association with mPC2 (reflecting essential amino acids, including aromatic, and bacterial co-metabolism) was inverse for Se, Zn and Cd. The association with mPC3 (reflecting LDL subclasses) was positive for Cu, Se and Zn, but inverse for Co. The association for mPC4 (reflecting HDL subclasses) was positive for Sb, but inverse for plasma Zn. These associations were mainly driven by Cu and Sb for mPC1; Se, Zn and Cd for mPC2; Co, Se and Zn for mPC3; and Zn for mPC4. The most SNP-metal interacting genes were NOX1, GSR, GCLC, AGT and REN. Co and Zn showed the highest number of interactions with genetic variants associated to enriched endocrine, cardiovascular and neurological pathways. Conclusions: Exposures to Co, Cu, Se, Zn, As, Cd and Sb were associated with several metabolic patterns involved in chronic disease. Carriers of redox-related variants may have differential susceptibility to metabolic alterations associated to excessive exposure to metals.This work was supported by the Strategic Action for Research in Health sciences [CP12/03080, PI15/00071, PI10/0082, PI13/01848, PI14/00874, PI16/01402, PI21/00506 and PI11/00726], CIBER Fisiopatología Obesidad y Nutrición (CIBEROBN) (CIBER-02-08-2009, CB06/03 and CB12/03/30,016), the State Agency for Research (PID2019-108973RB- C21 and C22), the Valencia Government (GRUPOS 03/101; PROM- ETEO/2009/029 and ACOMP/2013/039, IDIFEDER/ 2021/072 and GRISOLIAP/2021/119), the Castilla-Leon Government (GRS/279/A/08) and European Network of Excellence Ingenious Hypercare (EPSS- 037093) from the European Commission. The Strategic Action for Research in Health sciences, CIBERDEM and CIBEROBN are initiatives from Carlos III Health Institute Madrid and cofunded with European Funds for Regional Development (FEDER). The State Agency for Research and Carlos III Health Institute belong to the Spanish Ministry of Science and Innovation. ADR received the support of a fellowship from “la Caixa” Foundation (ID 100010434) (fellowship code “LCF/BQ/DR19/11740016”). MGP received the support of a fellowship from “la Caixa” Foundation (ID 100010434, fellowship code LCFLCF/BQ/DI18/11660001). The funding bodies had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript

Metal dyshomeostasis based biomarkers for lung cancer diagnosis using human biofluids

Lung cancer (LC) is one of the most common causes of cancer-related deaths in the world and it is well known that trace elements play important roles in the carcinogenic process activating and inhibiting enzymatic reactions and metalloproteins, in which they usually participate as cofactors. A cross-sectional study was conducted on 48 lung cancer patients and 39 controls (56 men and 31 women), aged 44-76 years between March 2011 and June 2012. Eleven elements have been included in the study: V, Cr, Mn, Fe, Co, Cu, Zn, Se, Mo, Cd, and Pb, some of them considered toxic (V, Cd, Cr and Pb), while others are essential (Co, Mo, Se, Fe and Zn), and they have been analyzed by ICP-QQQ-MS in serum, urine and for the first time in bronchoalveolar lavage fluid (BALF). In order to understand the involvement of metals in this process, an analytical metallomic approach based on non-denaturing precipitation of proteins (NDPP) has been optimized for the fractionation of high molecular mass (HMM) and low molecular mass (LMM) metal species, in order to distinguish between metal species that affect the biological activity and toxicological potential of the elements. In this work, the NDPP followed by the analysis of metals by ICP-QQQ-MS has been applied for the first time to serum, urine and BALF samples from lung cancer patients and controls in order to get metal-size molecule profiles (MSMP), which can be used as metal-based biomarkers of altered metabolic processes such as oxidative stress and homeostasis. In this sense, we have demonstrated that several metals are good biomarkers when they are related to labile complexes, complexed with low molecular mass ligands, or in the form of metalloproteins (i.e. V and Cr in HMM and Cu in LMM), which has been described for the first time. On the other hand, metal dyshomeostasis biomarkers are proposed using metal ratios and correlations. Finally, the ratios between elements were shown to be important biomarkers for lung cancer in serum (V/Mn, V/Pb, V/Zn, Cr/Pb), urine (Cr/Cd, Mn/Cd, V/Cd, Co/Cd, Cd/Pb) and BALF (V/Cu), which reflects the dyshomeostasis of metals in lung cancer. In this sense, several metals are correlated to others suggesting also the existence of an interconnected homeostasis in lung cancer.The authors thank the Spanish Ministry of Economy and Competitiveness (CTM2015-67902-C2-1-P) and Regional Ministry of Economy, Innovation, Science and Employment (Andalusian Government. P12-FQM-0442). B. Callejon-Leblic thanks the Ministerio de Educacion for a predoctoral scholarship FPU13/03615. Finally, the authors are grateful to FEDER (European Community) (UNHU13-1E-1611 and UNHU15-CE-3140)

Single and joint effects of cadmium and selenium on bioaccumulation, oxidative stress and metabolomic responses in the clam Scrobicularia plana

Selenium (Se) is a vital trace element for many living organisms inclusive of aquatic species. Although the antagonistic action of this element against other pollutants has been previously described for mammals and birds, limited information on the join effects in bivalves is available. To this end, bivalves of the species Scrobicularia plana were exposed to Se and Cd individually and jointly. Digestive glands were analysed to determine dose-dependent effects, the potential influence of Se on Cd bioaccumulationas well as the possible recover of the oxidative stress and metabolic alterations induced by Cd. Selenium co-exposure decreased the accumulation of Cd at low concentrations. Cd exposure significantly altered the metabolome of clams such as aminoacyltRNA biosynthesis, glycerophospholipid and amino acid metabolism, while Se co-exposure ameliorated several altered metabolites such asLysoPC (14:0), LysoPE (20:4), LysoPE (22:6), PE (14:0/18:0), PE (20:3/18:4) andpropionyl-Lcarnitine. Additionally, Se seems to be able to regulate the redox status of the digestive gland of clams preventing the induction of oxidativedamage in this organ. This study shows the potential Se antagonism against Cd toxicity in S. plana and the importance to study join effects of pollutants to understand the mechanism underlined the effects.This study has been carried out within the research projects (CTM2012-38720-C03-03 and CTM2016-75908-R) founded by the Spanish Ministry of Economy and Competitiveness, who also provided a pre-doc grant for Chiara Trombini (BES-2013-063426), and the project PGC-2018- 096608-B-C21 from the Spanish Ministry of Science and innovation (MCIN). (Generaci´on del Conocimiento. MCIN/AEI/ 10.13039/501100011033/FEDER “Una manera de hacer Europa”). Authors are grateful to FEDER (European Community) for financial support, Grant UNHU13-1E-1611. Rodríguez-Moro, G. thanks to Plan Andaluz de Investigaci´on, Desarrollo e Innovaci´on (PAIDI 2020) and European Union for a post-doctoral grant (DOC_01115). Funding for open access charge: Universidad de Huelva / CBUA