Studying complex interventions : reflections from the FEMHealth project on evaluating fee exemption policies in West Africa and Morocco

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High anthropogenic carbon content in the eastern Mediterranean

This work presents data of dichlorodifluoromethane (CFC-12), dissolved inorganic carbon and total alkalinity from a cruise to the Mediterranean Sea during October–November 2001, with the main focus on the CFC-12 data and on the eastern basin. Using the transit time distribution method, the anthropogenic carbon concentrations in the basin were estimated. Results were cross-checked with a back-calculation technique. The entire water column of the Mediterranean Sea contains anthropogenic CO2, with minimum concentrations of 20.5 μmol kg−1 (error range: 16.9–27.1 μmol kg−1) in the most eastern part of the basin at intermediate depths, where the waters' mean age is >130 yr. Column inventories of up to 154 mol m−2 (132–179 mol m−2) are found and a total inventory of 1.7 Pg (1.3–2.1 Pg) of anthropogenic carbon in the Mediterranean Sea was estimated. There is a net flux of 38 Tg yr−1 (30–47 Tg yr−1) of dissolved inorganic carbon through the Strait of Gibraltar into the Atlantic Ocean and an opposite net flux of 3.5 Tg yr−1 (−1.8–9.2 Tg yr−1) of anthropogenic carbon into the Mediterranean Sea

Aragonite saturation state in a continental shelf (Gulf of Cádiz, SW IberianPeninsula): Evidences of acidification in the coastal area

The spatiotemporal variability of aragonite saturation state (ΩAr) has been studied in the eastern shelf of the Gulf of Cádiz (GoC) (SW Iberian Peninsula). The study was carried out during the years 2014 and 2016 aboard twelve oceanographic cruises, along three or five transects, located between Cape Trafalgar and the Guadiana River. The GoC exhibited oversaturated of calcium carbonate with ΩAr mean values of 2.68 ± 0.30 in surface and 2.05 ± 0.15 in deep waters. pH, total alkalinity (TA), calcium concentration (Ca2+) and ΩAr showed a high variability within the surface mixed layer (SML, z 100 m), TA and Ca2+ concentration presented a conservative behaviour related to the distribution of the different water masses located in the GoC. The vertical variation of ΩAr also depends on the degree of mineralization of these water masses, obtaining the maximum values in the Subtropical North Atlantic Central Water (100–200 m), minimum values in the Subpolar North Atlantic Central Water (about 400 m), and intermediate values associated to the presence of the Mediterranean Water (>500 m). Results showed a significative acidification of the coastal areas, for those depths lower than 100 m from 2006 to 2016, with a mean decrease of pH and ΩAr of −0.0089 and −0.0552 yr−1, respectively. © 2021 The AuthorsThis work was funded by the Spanish CICYT (Spanish Program for Science and Technology) under the contract RTI2018-100865-B-C21 . Dolores Jiménez-López was financed by the University of Cádiz with a FPI fellowship (FPI-UCA) and Ana Sierra was financed by the Spanish Ministry of Education with a FPU fellowship (FPU2014-04048)

A Genome-Wide Screen for Genetic Variants That Modify the Recruitment of REST to Its Target Genes

Increasing numbers of human diseases are being linked to genetic variants, but our understanding of the mechanistic links leading from DNA sequence to disease phenotype is limited. The majority of disease-causing nucleotide variants fall within the non-protein-coding portion of the genome, making it likely that they act by altering gene regulatory sequences. We hypothesised that SNPs within the binding sites of the transcriptional repressor REST alter the degree of repression of target genes. Given that changes in the effective concentration of REST contribute to several pathologies—various cancers, Huntington's disease, cardiac hypertrophy, vascular smooth muscle proliferation—these SNPs should alter disease-susceptibility in carriers. We devised a strategy to identify SNPs that affect the recruitment of REST to target genes through the alteration of its DNA recognition element, the RE1. A multi-step screen combining genetic, genomic, and experimental filters yielded 56 polymorphic RE1 sequences with robust and statistically significant differences of affinity between alleles. These SNPs have a considerable effect on the the functional recruitment of REST to DNA in a range of in vitro, reporter gene, and in vivo analyses. Furthermore, we observe allele-specific biases in deeply sequenced chromatin immunoprecipitation data, consistent with predicted differenes in RE1 affinity. Amongst the targets of polymorphic RE1 elements are important disease genes including NPPA, PTPRT, and CDH4. Thus, considerable genetic variation exists in the DNA motifs that connect gene regulatory networks. Recently available ChIP–seq data allow the annotation of human genetic polymorphisms with regulatory information to generate prior hypotheses about their disease-causing mechanism

Application of Magnetic Nanoparticles to Gene Delivery

Nanoparticle technology is being incorporated into many areas of molecular science and biomedicine. Because nanoparticles are small enough to enter almost all areas of the body, including the circulatory system and cells, they have been and continue to be exploited for basic biomedical research as well as clinical diagnostic and therapeutic applications. For example, nanoparticles hold great promise for enabling gene therapy to reach its full potential by facilitating targeted delivery of DNA into tissues and cells. Substantial progress has been made in binding DNA to nanoparticles and controlling the behavior of these complexes. In this article, we review research on binding DNAs to nanoparticles as well as our latest study on non-viral gene delivery using polyethylenimine-coated magnetic nanoparticles

Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits