Dating the Anthropocene in deep-sea sediments: a gamma spectrometric approach

1 poster presented at the International meeting of Sedimentology 2017 in Toulouse, France, from October 10th to 13thUtilizando muestras de sedimentos superficiales obtenidas durante la campaña OVIDE/BOCATS 2016 y una innovadora técnica para establecer cronologías absolutas, se ha obtenido una primera estimación cuantitativa de los flujos de carbono hacia sedimentos profundos en la cuenca subpolar de Irminger. La geocronología basada en espectrometría gamma de alta resolución y bajo fondo con dos detectores simultáneos de germanio hiper-puro (HPGe) es una técnica suficientemente precisa y sensible como para datar sedimentos pelágicos profundos. El papel cuantitativo del Irminger como sumidero de carbono durante el Antropoceno se evaluó combinando una cronología basada en el radionúclido natural 210Pb junto a análisis sedimentológicos y de composición elemental. La tasa media de sedimentación para el canal central del Irminger es de 0.83±0.14 mm·yr-1. Los cálculos de flujos de carbono concluyen que durante el Antropoceno 32±14 g·Cinorg·m-2·año-1 y 4.5±3 g·Corg·m-2·año-1 sedimentan en la cuenca del Irminger, suponiendo un considerable sumidero de carbono en el área cuantificado en más de 22 Tg-C·año−1N

Linking chemical exposure to lipid homeostasis: A municipal waste water treatment plant influent is obesogenic for zebrafish larvae

Obesity, a risk factor for the development of type-2 diabetes, hypertension, cardiovascular disease, hepatic steatosis and some cancers, has been ranked in the top 10 health risk in the world by the World Health Organization. Despite the growing body of literature evidencing an association between the obesity epidemic and specific chemical exposure across a wide range of animal taxa, very few studies assessed the effects of chemical mixtures and environmental samples on lipid homeostasis. Additionally, the mode of action of several chemicals reported to alter lipid homeostasis is still poorly understood. Aiming to fill some of these gaps, we combined an in vivo assay with the model species zebrafish (Danio rerio) to screen lipid accumulation and evaluate expression changes of key genes involved in lipid homeostasis, alongside with an in vitro transactivation assay using human and zebrafish nuclear receptors, retinoid X receptor α and peroxisome proliferator-activated receptor γ. Zebrafish larvae were exposed from 4 th day post-fertilization until the end of the experiment (day 18), to six different treatments: experimental control, solvent control, tributyltin at 100 ng/L Sn and 200 ng/L Sn (positive control), and wastewater treatment plant influent at 1.25% and 2.5%. Exposure to tributyltin and to 2.5% influent led to a significant accumulation of lipids, with white adipose tissue deposits concentrating in the perivisceral area. The highest in vitro tested influent concentration (10%) was able to significantly transactivate the human heterodimer PPARγ/RXRα, thus suggesting the presence in the influent of HsPPARγ/RXRα agonists. Our results demonstrate, for the first time, the ability of complex environmental samples from a municipal waste water treatment plant influent to induce lipid accumulation in zebrafish larvae.This work was supported by the Norte2020 and FEDER (Coral—Sustainable Ocean Exploitation—Norte-01-0145-FEDER-000036), by the Spanish Agencia Estatal de Investigación (CTM2017-84763-C3-2-R), the Galician Council of Culture, Education and Universities (ED431C2017/36) and FEDER/ERDF, and by the project NOR-WATER (0725), financed by “Programa de Cooperação Interreg Portugal/Espanha, (POCTEP) 2014-2020. Ricardo Capela was supported by grant SFRH/BD/112483/2015S

Creatine Kinase Elevation in Autosomal Dominant Polycystic Kidney Disease Patients on Tolvaptan Treatment

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cause of end-stage kidney disease. Currently, tolvaptan is the only treatment that has proven to delay disease progression. The most notable side effect of this therapy is drug-induced liver injury; however, recently, there have been two reports of creatine kinase (CK) elevation in ADPKD patients on tolvaptan treatment. We set out to monitor and determine the actual incidence of CK elevation and evaluate its potential association with other clinical factors. This is an observational retrospective multicenter study performed in rapidly progressive ADPKD patients on tolvaptan treatment from Barcelona, Spain. Laboratory tests, demographics, treatment dose, and reported symptoms were collected from October 2018 to March 2021. Ninety-five patients initiated tolvaptan treatment during follow-up. The medication had to be discontinued in 31 (32.6%) patients, primarily due to aquaretic effects (12.6%), elevated liver enzymes (8.4%), and symptomatic or persistently elevated CK levels (3.2%). Moreover, a total of 27 (28.4%) patients had elevated CK levels, with most of them being either transient (12.6%), mild and asymptomatic (4.2%), or resolved after dose reduction (3.2%) or temporary discontinuation (2.1%). We pre­sent the largest cohort that has monitored CK levels in a real-life setting, finding them elevated in 28.4% of patients. More research and monitoring will help us understand the clinical implications and the pathophysiological mechanism of CK elevation in this population

New Insights into the Lake Chad Basin Population Structure Revealed by High-Throughput Genotyping of Mitochondrial DNA Coding SNPs

BACKGROUND: Located in the Sudan belt, the Chad Basin forms a remarkable ecosystem, where several unique agricultural and pastoral techniques have been developed. Both from an archaeological and a genetic point of view, this region has been interpreted to be the center of a bidirectional corridor connecting West and East Africa, as well as a meeting point for populations coming from North Africa through the Saharan desert. METHODOLOGY/PRINCIPAL FINDINGS: Samples from twelve ethnic groups from the Chad Basin (n = 542) have been high-throughput genotyped for 230 coding region mitochondrial DNA (mtDNA) Single Nucleotide Polymorphisms (mtSNPs) using Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight (MALDI-TOF) mass spectrometry. This set of mtSNPs allowed for much better phylogenetic resolution than previous studies of this geographic region, enabling new insights into its population history. Notable haplogroup (hg) heterogeneity has been observed in the Chad Basin mirroring the different demographic histories of these ethnic groups. As estimated using a Bayesian framework, nomadic populations showed negative growth which was not always correlated to their estimated effective population sizes. Nomads also showed lower diversity values than sedentary groups. CONCLUSIONS/SIGNIFICANCE: Compared to sedentary population, nomads showed signals of stronger genetic drift occurring in their ancestral populations. These populations, however, retained more haplotype diversity in their hypervariable segments I (HVS-I), but not their mtSNPs, suggesting a more ancestral ethnogenesis. Whereas the nomadic population showed a higher Mediterranean influence signaled mainly by sub-lineages of M1, R0, U6, and U5, the other populations showed a more consistent sub-Saharan pattern. Although lifestyle may have an influence on diversity patterns and hg composition, analysis of molecular variance has not identified these differences. The present study indicates that analysis of mtSNPs at high resolution could be a fast and extensive approach for screening variation in population studies where labor-intensive techniques such as entire genome sequencing remain unfeasible

Evaluation of Mannan oligosaccharides (MOS) in balanced diets for tropical gar juveniles (Atractosteus tropicus)

Antecedentes: Los prebióticos son polisacáridos no digestibles por el huésped, pero, por otro lado, son los encargados de estimular la actividad de microorganismos benéficos en el sistema digestivo, lo que puede maximizar la ganancia en peso, la conversión alimenticia y la activación de la respuesta inmune. Los oligosacáridos de manano (MOS) han sido evaluados en varias especies de peces de importancia comercial. Objetivos: Determinar el efecto de diferentes niveles de MOS integrados en dietas balanceadas para juveniles de Atractosteus tropicus sobre el crecimiento, parámetros productivos, supervivencia, índices somáticos y actividad de enzimas digestivas. Métodos: Se evaluaron por triplicado seis dietas experimentales con inclusión de MOS (0.0, 0.2, 0.4, 0.6 y 0.8%) y una dieta control de trucha (DC) durante 62 días. Se distribuyeron 180 juveniles (5.11 ± 0.08 g) en un sistema de recirculación con 18 tanques de 70 L con flujo de 10 L min-1. Resultados: La supervivencia en todos los tratamientos fue superior al 96%. La dieta 0.2% de MOS presentó los valores más altos en peso ganado (WG), tasa específica de crecimiento (SGR) y tasa de eficiencia proteínica (PER), y el menor valor en tasa de conversión alimenticia (FCR). El índice hepatosomático (HSI) fue mayor para el tratamiento 0.4%, mientras que el índice viscerosomático fue mayor para los tratamientos 0.4% y 0.6%. Todas las actividades enzimáticas determinadas mostraron diferencias entre tratamientos (proteasa ácida, proteasa alcalina, tripsina, quimotripsina, leucina aminopeptidasa, carboxipeptidasas, lipasas, α-amilasa, fosfatasas ácidas y fosfatasas alcalinas). Conclusiones: La suplementación de 0.2% de MOS en dietas para juveniles de A. tropicus genera beneficios en el crecimiento y el rendimiento productivo. La inclusión de MOS en dietas para juveniles de A. tropicus modifica los índices somáticos y la actividad de enzimas digestivas en juveniles.Background: Prebiotics are polysaccharides that cannot be digested by the host; however, they generate benefits by stimulating the activity of beneficial microorganisms in the digestive system, which can maximize weight gain, feed conversion, and stimulate the immune response. Mannan oligosaccharides (MOS) have been evaluated in several fish species of commercial importance. Goals: Determine inclusion effects of different MOS levels in balanced diets for juveniles of Atractosteus tropicus on the growth, productive parameters, survival, somatic indexes, and activity of digestive enzymes. Methods: Six experimental diets including MOS (0.0, 0.2, 0.4, 0.6, and 0.8%) and a trout control diet (DC) were designed, manufactured, and evaluated in triplicate during 62 days. A hundred and eighty juveniles (5.11 ± 0.08 g) were distributed in a recirculation system with 18 tanks of 70 L with a flow of 10 L min-1. Results: The 0.2% MOS diet produced the highest values in weight gained (WG), specific growth rate (SGR), and protein efficiency rate (PER) and the lowest value in feed conversion rate (FCR). Survival in all treatments was greater than 96%. The hepatosomatic index was higher for the 0.4% treatment, while the viscerosomatic index was higher for the 0.4% and 0.6% treatments. All the enzymatic activities (acid protease, alkaline protease, trypsin, chymotrypsin, leucine aminopeptidase, carboxypeptidases, lipases, α-amylase, acid phosphatases, and alkaline phosphatases) showed significant differences by the inclusion of MOS in the diet. Conclusions: Supplementation of 0.2% MOS in diets for juveniles of A. tropicus, generates benefits in growth and productive performance. The inclusion of MOS in diets for juveniles of A. tropicus modifies somatic indices and the activity of digestive enzymes of juveniles.info:eu-repo/semantics/publishedVersio

Exome sequencing of early-onset patients supports genetic heterogeneity in colorectal cancer

Colorectal cancer (CRC) is a complex disease that can be caused by a spectrum of genetic variants ranging from low to high penetrance changes, that interact with the environment to determine which individuals will develop the disease. In this study, we sequenced 20 early-onset CRC patients to discover novel genetic variants that could be linked to the prompt disease development. Eight genes, CHAD, CHD1L, ERCC6, IGTB7, PTPN13, SPATA20, TDG and TGS1, were selected and re-sequenced in a further 304 early onset CRC patients to search for rare, high-impact variants. Although we found a recurring truncating variant in the TDG gene shared by two independent patients, the results obtained did not help consolidate any of the candidates as promising CRC predisposing genes. However, we found that potential risk alleles in our extended list of candidate variants have a tendency to appear at higher numbers in younger cases. This supports the idea that CRC onset may be oligogenic in nature and may show molecular heterogeneity. Further, larger and robust studies are thus needed to unravel the genetics behind early-onset CRC development, coupled with novel functional analyses and omic approaches that may offer complementary insight

Identification of the Immunological Changes Appearing in the CSF During the Early Immunosenescence Process Occurring in Multiple Sclerosis

Patients with multiple sclerosis (MS) suffer with age an early immunosenescence process, which influence the treatment response and increase the risk of infections. We explored whether lipid-specific oligoclonal IgM bands (LS-OCMB) associated with highly inflammatory MS modify the immunological profile induced by age in MS. This cross-sectional study included 263 MS patients who were classified according to the presence (M+, n=72) and absence (M-, n=191) of LS-OCMB. CSF cellular subsets and molecules implicated in immunosenescence were explored. In M- patients, aging induced remarkable decreases in absolute CSF counts of CD4+ and CD8+ T lymphocytes, including Th1 and Th17 cells, and of B cells, including those secreting TNF-alpha. It also increased serum anti-CMV IgG antibody titers (indicative of immunosenescence) and CSF CHI3L1 levels (related to astrocyte activation). In contrast, M+ patients showed an age-associated increase of TIM-3 (a biomarker of T cell exhaustion) and increased values of CHI3L1, independently of age. Finally, in both groups, age induced an increase in CSF levels of PD-L1 (an inductor of T cell tolerance) and activin A (part of the senescence-associated secretome and related to inflammaging). These changes were independent of the disease duration. Finally, this resulted in augmented disability. In summary, all MS patients experience with age a modest induction of T-cell tolerance and an activation of the innate immunity, resulting in increased disability. Additionally, M- patients show clear decreases in CSF lymphocyte numbers, which could increase the risk of infections. Thus, age and immunological status are important for tailoring effective therapies in MS.This work was supported by grants FIS-PI15/00513, FIS-PI18/00572 and RD16/0015/0001 from the Instituto de Salud Carlos III. Ministerio de Ciencia e Innovación, Spain and FEDER: "Una manera de hacer Europa"

Exome sequencing study in patients with multiple sclerosis reveals variants associated with disease course

BACKGROUND: It remains unclear whether disease course in multiple sclerosis (MS) is influenced by genetic polymorphisms. Here, we aimed to identify genetic variants associated with benign and aggressive disease courses in MS patients. METHODS: MS patients were classified into benign and aggressive phenotypes according to clinical criteria. We performed exome sequencing in a discovery cohort, which included 20 MS patients, 10 with benign and 10 with aggressive disease course, and genotyping in 2 independent validation cohorts. The first validation cohort encompassed 194 MS patients, 107 with benign and 87 with aggressive phenotypes. The second validation cohort comprised 257 patients, of whom 224 patients had benign phenotypes and 33 aggressive disease courses. Brain immunohistochemistries were performed using disease course associated genes antibodies. RESULTS: By means of single-nucleotide polymorphism (SNP) detection and comparison of allele frequencies between patients with benign and aggressive phenotypes, a total of 16 SNPs were selected for validation from the exome sequencing data in the discovery cohort. Meta-analysis of genotyping results in two validation cohorts revealed two polymorphisms, rs28469012 and rs10894768, significantly associated with disease course. SNP rs28469012 is located in CPXM2 (carboxypeptidase X, M14 family, member 2) and was associated with aggressive disease course (uncorrected p value < 0.05). SNP rs10894768, which is positioned in IGSF9B (immunoglobulin superfamily member 9B) was associated with benign phenotype (uncorrected p value < 0.05). In addition, a trend for association with benign phenotype was observed for a third SNP, rs10423927, in NLRP9 (NLR family pyrin domain containing 9). Brain immunohistochemistries in chronic active lesions from MS patients revealed expression of IGSF9B in astrocytes and macrophages/microglial cells, and expression of CPXM2 and NLRP9 restricted to brain macrophages/microglia. CONCLUSIONS: Genetic variants located in CPXM2, IGSF9B, and NLRP9 have the potential to modulate disease course in MS patients and may be used as disease activity biomarkers to identify patients with divergent disease courses. Altogether, the reported results from this study support the influence of genetic factors in MS disease course and may help to better understand the complex molecular mechanisms underlying disease pathogenesis

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes