Developing As and Cu Tissue Residue Thresholds to Attain the Good Ecological Status of Rivers in Mining Areas

[EN] The study was performed on residue-effects datasets from polluted and unpolluted sites in the Nalon River basin (northern Spain). The effects were measured in terms of alteration of field macroinvertebrate communities, and measured as ecological status scores, and number of families and abundance of Ephemeroptera, Plecoptera and Trichoptera (EPT). Non-linear regression models of the field-measured tissue residues in 10 taxa related to the ecological status of the macroinvertebrate communities were used to derive effective tissue residues (ERs). These were estimated for the good/moderate boundary defined by the ecological quality ratio (EQRs) score and for the 50% reduction of EQR and EPT metrics. As, Cu, Hg and Se ERs were calculated for several macroinvertebrate taxa with different feeding styles. The ER dataset allowed us to estimate As and Cu hazardous concentrations (HC), using species sensitivity distribution models, and were interpreted as community thresholds. Further studies for Hg and Se are needed to complete the database required for HC estimation. The reliability and differences of the several thresholds were tested in a risk assessment using a tissue-residue approach (TRA) conducted with field organisms from Cauxa Creek, a tributary from the same basin exposed to high levels of metals in the sediments due to gold mining activities. This risk assessment identified that As and Cu tissue residues satisfactorily explained the reduction in the ecological status of the macroinvertebrate assemblages. Our results indicate that TRA can help in setting future environmental quality standards for the protection of aquatic biota.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. Funding was provided by Spanish Ministry of Economy, Industry and Competitiveness, (Grant no. CGL 2013-44655-R), University of the Basque Country, (Grant no. PIF16/162

Proposal of integrative scores and biomonitor selection for metal bioaccumulation risk assessment in mine-impacted rivers

Development of sound criteria for metal and metalloid bioaccumulation risk assessment in river basins affected by mining activities is a necessary tool to protect the aquatic communities. The aim of this study is to propose integrative scores for tissue residues that are suitable for surveillance programs and readily interpreted in terms of risk assessment in mining impacted rivers. Tissue residues of 7 trace metals and 2 metalloids were measured in ten macroinvertebrate taxa from the Nal ' on River basin (Spain), affected by Hg, Cu and Au mining activities. Compared with reference sites, biomonitor taxa from Hg and Au mining districts showed the highest bioaccumulation. However, low or non-significant bioaccumulation was found in sites influenced by historical Cu mining. Multivariate analyses (ANOSIM) performed on individual taxa revealed significant differences in tissue residues between sites classified according to their ecological status. The bioaccumulation risk assessment was based on the average ratio of the actual metal tissue residues in each macroinvertebrate taxon to the corresponding Ecological Threshold tissue concentration (Tissue residue Ratio to Threshold, TRT). The suitability of the biomonitors was evaluated using linear regression models fitted to the relationships between TRT scores and site sediment pollution or ecological status scores. Biomonitor selection also considered differences in invertebrate functional traits, which can influence metal and metalloid bioavailability. Site bioaccumulation risk was assessed on an Integrated Tissue concentration score (INTISS), calculated over a selection of the most relevant chemicals (As, Cu and Hg) and 3 biomonitor taxa (Baetidae, Hydropsychidae, Microdrile oligochaetes) comprising a set of feeding styles. Based on INTISS, it was possible to predict community alteration scores, using linear regression models. A comparison of site bioaccumulation and ecological status assessments based on the departure from reference conditions showed that operational monitoring programs in basins impaired by mining can be optimized by combining both approaches.This investigation was sponsored by the Spanish Ministry of Econ-omy and Competitiveness (MINECO) through the CGL 2013-44655-R research project. Inigo Moreno-Ocio was granted a PhD fellowship from the University of the Basque Country (UPV/EHU) . We thank Steven V. Fend for the English revision and his useful comments on the pre-liminary version of this paper. We greatly appreciate the support pro-vided by Amanda Miranda and the staff of the Cantabrian Hydrographical Confederation, who assisted in the selection and sam-pling of the sites of the Nalon River and their encouragement and generous attitude along the study

Satisfaction, Assessment and Adaptation to a Virtual Environment of the University Mentoring Programme GuíaMe-AC-UMA for Gifted High School Students

The purpose of this study is to analyse the satisfaction levels of participants (mentees, mentors, and technical-research team) of a university mentoring programme. The GuíaMe-AC-UMA is aimed at gifted high school students. Due to the COVID-19 pandemic, the IX edition was carried out in an online format. The results were compared to those of the in-person edition (VII edition) to assess whether there were differences between the editions. For this purpose, three versions (one for each participant type) of a Likert-type questionnaire were distributed among the participants of the 22 workshops offered by the GuíaMe-AC-UMA Programme. A total of 224 responses were received: 21 from the mentors, 181 from the mentees and 22 from the technical-research team. The results indicate a high level of satisfaction with the development of the workshops by all participants. While the mentees preferred the in-person edition, the rest of the participants showed no difference in satisfaction levels between editions. A similar result was observed when correcting for the subject area of the workshop. The in-person edition was valued higher than the online version by all. The overall level of satisfaction shown by all participants and the support for continuation of the programme suggest that this type of educational offer is beneficial and satisfactory for all involved, in accordance with previous research on mentoring programmes. These results indicate that programmes focused on young pre-university students with high abilities are valued; these results encourage us to continue the programmeThis research received no external funding.Partial funding for open access charge: Universidad de Málag

Solucionando necesidades tecnológicas con zentyal 7.0 development

Se abordan temáticas puntuales como DHCP y DNS Server, Controlador de Dominio, Proxy no Transparente, Cortafuegos, File y Print Server, así como Virtual Private Network a través de Zentyal Development 7.0 que, gracias a su interfaz Figura y amigable, permite la puesta en marcha de estos servicios los cuales brindan seguridad tecnológica y potencializan el desarrollo de las sociedades.Specific topics such as DHCP and DNS Server, Domain Controller, Non-Transparent Proxy, Firewall, File and Print Server are addressed, as well as Virtual Private Network through Zentyal Development 7.0 that, thanks to its graphical and friendly interface, allows the implementation operation of these services which provide technological security and enhance the development of societies

Nephrin mutations cause childhood- and adult-onset focal segmental glomerulosclerosis

Mutations in the NPHS1 gene cause congenital nephrotic syndrome of the Finnish type presenting before the first 3 months of life. Recently, NPHS1 mutations have also been identified in childhood-onset steroid-resistant nephrotic syndrome and milder courses of disease, but their role in adults with focal segmental glomerulosclerosis remains unknown. Here we developed an in silico scoring matrix to evaluate the pathogenicity of amino-acid substitutions using the biophysical and biochemical difference between wild-type and mutant amino acid, the evolutionary conservation of the amino-acid residue in orthologs, and defined domains, with the addition of contextual information. Mutation analysis was performed in 97 patients from 89 unrelated families, of which 52 presented with steroid-resistant nephrotic syndrome after 18 years of age. Compound heterozygous or homozygous NPHS1 mutations were identified in five familial and seven sporadic cases, including one patient 27 years old at onset of the disease. Substitutions were classified as ‘severe’ or ‘mild’ using this in silico approach. Our results suggest an earlier onset of the disease in patients with two ‘severe’ mutations compared to patients with at least one ‘mild’ mutation. The finding of mutations in a patient with adult-onset focal segmental glomerulosclerosis indicates that NPHS1 analysis could be considered in patients with later onset of the disease

Response trajectories of gambling severity after cognitive behavioral therapy in young-adult pathological gamblers

Background and aims: the significant increase in the prevalence of gambling disorder (GD) among young adults in recent years has attracted interest in determining therapeutic efficiency in this sector of the population. The aim of this work was to estimate the response trajectories of gambling severity during the six-month follow-up after a cognitive behavioral therapy (CBT) program in young adult patients and to identify the main variables associated with each trajectory. Methods: the sample included n = 192 patients, aged 19-35 years old, seeking treatment for GD. Response trajectories were identified through latent class growth analysis. Results: three trajectories emerged: T1 (n = 118, 61.5%), composed of patients with severe GD at pre-treatment and good evolution to recovery; T2 (n = 62, 32.3%), with patients with moderate-high GD affectation at baseline and good evolution to recovery; and T3 (n = 12, 6.3%), with participants with severe baseline GD severity and poor evolution after CBT (Abbott, 2019). The highest risk of poor therapeutic outcomes was related to lower social index positions, high emotional distress, high scores in harm avoidance and low scores in self-directedness. Discussion and conclusions: differences in the response trajectories at short-term follow-up after CBT reveal heterogeneity in the samples including young and young-adult GD patients. Patients' phenotype at baseline should be considered when developing efficient, person-centered intervention programs, which should comprise strategies aimed at increasing emotional regulation capacities, self-esteem and self-efficacy, with the aim of avoiding relapses in the medium-long term after therapy

Gambling phenotypes in online sports betting

Background and objectives: The Internet provides easy access to multiple types of gambling and has led to changes in betting habits. A severe rise in problematic gambling has been predicted among all sectors of the population, and studies are required to assess the emerging phenotypes related to the new structures of gambling activities. This study aimed to explore the existence of latent classes associated with gambling habits among treatment-seeking gamblers due to Online Sports Betting (OSB). Method: Initial sample included n = 4,516 patients consecutively admitted for treatment in a hospital unit specialized in behavioral addictions. Two-step clustering analysis was used within the subsample of n = 323 patients who reported problems related with OSB, within a set of indicators including sociodemographics, psychopathological distress, personality, and severity of the gambling activity. Results: The prevalence of OSB as a main type of gambling problem in the study was 7.2% (95% confidence interval: 6.4 to 7.9%). Two latent clusters were identified, with differences in sociodemographics and clinical status. Cluster 1 (n = 247, 76.5%) grouped patients that were more affected due to the OSB behaviors, and it was characterized by non-married patients, lower socioeconomic position index, higher comorbidity with other substance related addictions, younger age, and early onset of the gambling activity, as well as higher debts due to the OSB, higher psychopathological distress, and a more dysfunctional personality profile. Cluster 2 (n = 76, 23.5%) grouped patients that were less affected by OSB, mostly married (or living with a stable partner), with higher social position levels, older age and older onset of the gambling activity, as well as a more functional psychopathological and personality profile. Conclusion: The increasing understanding of latent classes underlying OSB phenotypes is essential in guiding the development of reliable screening tools to identify individuals highly vulnerable to addictive behaviors among Internet gamblers, as well as in planning prevention and treatment initiatives focused on the precise profiles of these patients

Presence of problematic and disordered gambling in older age and validation of the South Oaks Gambling Scale

The use of instruments originally developed for measuring gambling activity in younger populations may not be appropriate in older age individuals. The aim of this study was to examine the presence of problematic and disordered gambling in seniors aged 50 or over, and study the reliability and validity properties of the SOGS (a screening measure to identify gambling related problems). Two independent samples were recruited: a clinical group of n = 47 patients seeking treatment at a Pathological Gambling Outpatient Unit, and a population-based group of n = 361 participants recruited from the same geographical area. Confirmatory factor analysis verified the bifactor structure for the SOGS with two correlated underlying dimensions [measuring the impact of gambling on the self primarily (Cronbach's alpha α = 0.87) or on both the self and others also (α = 0.82)], and a global dimension of gambling severity (also with excellent internal consistency, α = 0.90). The SOG obtained excellent accuracy/validity for identifying gambling severity based on the DSM-5 criteria (area under the ROC curve AUC = 0.97 for discriminating disordered gambling and AUC = 0.91 for discriminating problem gambling), and good convergent validity with external measures of gambling (Pearson's correlation R = 0.91 with the total number of DSM-5 criteria for gambling disorder, and R = 0.55 with the debts accumulated due to gambling) and psychopathology (R = 0.50, 0.43 and 0.44 with the SCL-90R depression, anxiety and GSI scales). The optimal cutoff point for identifying gambling disorder was 4 (sensitivity Se = 92.3% and specificity Sp = 98.6%) and 2 for identifying problem gambling (Se = 78.8% and Sp = 96.7%). This study provides empirical support for the reliability and validity of the SOGS for assessing problem gambling in elders, and identifies two specific factors that could help both research and clinical decision-making, based on the severity and consequences of the gambling activity

Long runs of homozygosity are associated with Alzheimer's disease

Altres ajuts: The Genome Research at Fundació ACE project (GR@ACE) is supported by Fundación bancaria "La Caixa," Grifols SA and Fundació ACE. L.M.R. is supported by Consejería de Salud de la Junta de Andalucía (Grant PI-0001/2017).Long runs of homozygosity (ROH) are contiguous stretches of homozygous genotypes, which are a footprint of inbreeding and recessive inheritance. The presence of recessive loci is suggested for Alzheimer's disease (AD); however, their search has been poorly assessed to date. To investigate homozygosity in AD, here we performed a fine-scale ROH analysis using 10 independent cohorts of European ancestry (11,919 AD cases and 9181 controls.) We detected an increase of homozygosity in AD cases compared to controls [ β (CI 95%) = 0.070 (0.037-0.104); P = 3.91 × 10 −5 ; β (CI95%) = 0.043 (0.009-0.076); P = 0.013]. ROHs increasing the risk of AD (OR > 1) were significantly overrepresented compared to ROHs increasing protection (p < 2.20 × 10 −16). A significant ROH association with AD risk was detected upstream the HS3ST1 locus (chr4:11,189,482‒11,305,456), (β (CI 95%) = 1.09 (0.48 ‒ 1.48), p value = 9.03 × 10 −4), previously related to AD. Next, to search for recessive candidate variants in ROHs, we constructed a homozygosity map of inbred AD cases extracted from an outbred population and explored ROH regions in whole-exome sequencing data (N = 1449). We detected a candidate marker, rs117458494, mapped in the SPON1 locus, which has been previously associated with amyloid metabolism. Here, we provide a research framework to look for recessive variants in AD using outbred populations. Our results showed that AD cases have enriched homozygosity, suggesting that recessive effects may explain a proportion of AD heritability

Epigenetic loss of RNA‑methyltransferase NSUN5 in glioma targets ribosomes to drive stress adaptive translational program

Tumors have aberrant proteomes that often do not match their corresponding transcriptome profiles. One possible cause of this discrepancy is the existence of aberrant RNA modification landscapes in the so-called epitranscriptome. Here, we report that human glioma cells undergo DNA methylation-associated epigenetic silencing of NSUN5, a candidate RNA methyltransferase for 5-methylcytosine. In this setting, NSUN5 exhibits tumor-suppressor characteristics in vivo glioma models. We also found that NSUN5 loss generates an unmethylated status at the C3782 position of 28S rRNA that drives an overall depletion of protein synthesis, and leads to the emergence of an adaptive translational program for survival under conditions of cellular stress. Interestingly, NSUN5 epigenetic inactivation also renders these gliomas sensitive to bioactivatable substrates of the stress-related enzyme NQO1. Most importantly, NSUN5 epigenetic inactivation is a hallmark of glioma patients with long-term survival for this otherwise devastating disease