Alterations in common marmoset gut microbiome associated with duodenal strictures

Chronic gastrointestinal (GI) diseases are the most common diseases in captive common marmosets (Callithrix jacchus). Despite standardized housing, diet and husbandry, a recently described gastrointestinal syndrome characterized by duodenal ulcers and strictures was observed in a subset of marmosets sourced from the New England Primate Research Center. As changes in the gut microbiome have been associated with GI diseases, the gut microbiome of 52 healthy, non-stricture marmosets (153 samples) were compared to the gut microbiome of 21 captive marmosets diagnosed with a duodenal ulcer/stricture (57 samples). No significant changes were observed using alpha diversity metrics, and while the community structure was significantly different when comparing beta diversity between healthy and stricture cases, the results were inconclusive due to differences observed in the dispersion of both datasets. Differences in the abundance of individual taxa using ANCOM, as stricture-associated dysbiosis was characterized by Anaerobiospirillum loss and Clostridium perfringens increases. To identify microbial and serum biomarkers that could help classify stricture cases, we developed models using machine learning algorithms (random forest, classification and regression trees, support vector machines and k-nearest neighbors) to classify microbiome, serum chemistry or complete blood count (CBC) data. Random forest (RF) models were the most accurate models and correctly classified strictures using either 9 ASVs (amplicon sequence variants), 4 serum chemistry tests or 6 CBC tests. Based on the RF model and ANCOM results, C. perfringens was identified as a potential causative agent associated with the development of strictures. Clostridium perfringens was also isolated by microbiological culture in 4 of 9 duodenum samples from marmosets with histologically confirmed strictures. Due to the enrichment of C. perfringens in situ, we analyzed frozen duodenal tissues using both 16S microbiome profiling and RNAseq. Microbiome analysis of the duodenal tissues of 29 marmosets from the MIT colony confirmed an increased abundance of Clostridium in stricture cases. Comparison of the duodenal gene expression from stricture and non-stricture marmosets found enrichment of genes associated with intestinal absorption, and lipid metabolism, localization, and transport in stricture cases. Using machine learning, we identified increased abundance of C. perfringens, as a potential causative agent of GI disease and intestinal strictures in marmosets.National Institutes of Health/[T32 OD010978]/NIH/Estados UnidosNational Institutes of Health/[P30-ES002109]/NIH/Estados UnidosUniversidad de Costa Rica/[803-C1-163]/UCR/Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Enfermedades Tropicales (CIET

Isolation and genetic characterization of Toxoplasma gondii in Spanish sheep flocks

© The Author(s) 2020.[Background]: Toxoplasma gondii is a major cause of abortion in small ruminants and presents a zoonotic risk when undercooked meat containing cysts is consumed. The aim of the present study was to investigate the genetic diversity among the T. gondii strains circulating in ovine livestock in Spain.[Methods]: Selected samples collected from abortion outbreaks due to toxoplasmosis (n = 31) and from chronically infected adult sheep at slaughterhouses (n = 50) in different Spanish regions were bioassayed in mice, aiming at parasite isolation. In addition, all original clinical samples and the resulting isolates were genotyped by multi-nested PCR-RFLP analysis of 11 molecular markers and by PCR-DNA sequencing of portions of the SAG3, GRA6 and GRA7 genes.[Results]: As a result, 30 isolates were obtained from 9 Spanish regions: 10 isolates from abortion-derived samples and 20 isolates from adult myocardial tissues. Overall, 3 genotypes were found: ToxoDB#3 (type II PRU variant) in 90% (27/30) of isolates, ToxoDB#2 (clonal type III) in 6.7% (2/30), and ToxoDB#1 (clonal type II) in 3.3% (1/30). When T. gondii-positive tissue samples (n = 151) were directly subjected to RFLP genotyping, complete restriction profiles were obtained for 33% of samples, and up to 98% of the specimens belonged to the type II PRU variant. A foetal brain showed a clonal type II pattern, and four specimens showed unexpected type I alleles at the SAG3 marker, including two foetal brains that showed I + II alleles as co-infection events. Amplicons of SAG3, GRA6 and GRA7 obtained from isolates and clinical samples were subjected to sequencing, allowing us to confirm RFLP results and to detect different single-nucleotide polymorphisms.[Conclusions]: The present study informed the existence of a predominant type II PRU variant genotype (ToxoDB#3) infecting domestic sheep in Spain, in both abortion cases and chronic infections in adults, coexisting with other clonal (ToxoDB#1 and ToxoDB#2), much less frequent genotypes, as well as polymorphic strains as revealed by clinical sample genotyping. The use of multilocus sequence typing aided in accurately estimating T. gondii intragenotype diversity.This research was supported by projects funded by the Spanish Ministry of Science and Innovation (AGL2016-75935-C2-R) and the Community of Madrid (PLATESA2-CM-P2018/BAA-4370). MF and RC were funded by UCM-Santander/2017 pre-doctoral grants, and PLATESA2 post-doctoral grants, respectively. CG was funded by DGAPA, National Autonomous University of Mexico (UNAM). RC, EC and LO are part of the TOXOSOURCES consortium, supported by funding from the European Union’s Horizon 2020 Research and Innovation programme under grant agreement No. 773830: One Health European Joint Programme.Peer reviewe

CYP450 and Its Implications in the Clinical Use of Antipsychotic Drugs

Polypharmacy implies a high potential for drug-drug interactions. The capacity of the cytochrome P450 enzyme system involved in the metabolism of psychoactive drugs differs greatly, which leads to variable drug elimination rates and inter-subject differences in serum drug concentrations. Polymorphisms in genes coding for CYP450 enzymes contribute to this inter-subject variability. Therapeutic response and adverse effects vary among patients treated with the same dose of a certain drug. Polypharmacy, comorbidity and the use of certain substances (grapefruit juice, caffeine and tobacco) increase the chances of clinically relevant interactions in a psychotic patient. Choosing drugs with low interaction potential seems to be the best strategy to prevent clinically relevant interactions particularly in elderly, polymedicated, oncologic and HIV patients

Frozen ground and snow cover monitoring in Livingston and Deception islands, Antarctica: preliminary results of the 2015-2019 PERMASNOW project

Since 2006, our research team has been establishing in the islands of Livingston and Deception, (South Shetland archipelago, Antarctica) several monitoring stations of the active layer thickness within the international network Circumpolar Active Layer Monitoring (CALM), and the ground thermal regime for the Ground Terrestrial Network-Permafrost (GTN-P). Both networks were developed within the International Permafrost Association (IPA). In the GTN-P stations, in addition to the temperature of the air, soil, and terrain at different depths, the snow thickness is also monitored by snow poles. Since 2006, a delay in the disappearance of the snow layer has been observed, which could explain the variations we observed in the active layer thickness and permafrost temperatures. Therefore, in late 2015 our research group started the PERMASNOW project (2015-2019) to pay attention to the effect of snow cover on ground thermal This project had two different ways to study the snow cover. On the first hand, in early 2017 we deployed new instrumentation, including new time lapse cameras, snow poles with high number of sensors and a complete and complex set of instruments and sensors to configure a snow pack analyzer station providing 32 environmental and snow parameters. We used the data acquired along 2017 and 2018 years with the new instruments, together with the available from all our already existing sensors, to study in detail the snow cover. On the other hand, remote sensing data were used to try to map the snow cover, not only at our monitoring stations but the entire islands in order to map and study the snow cover distribution, as well as to start the way for future permafrost mapping in the entire islands. MODIS-derived surface temperatures and albedo products were used to detect the snow cover and to test the surface temperature. Since cloud presence limited the acquisition of valid observations of MODIS sensor, we also analyzed Terrasar X data to overcome this limitation. Remote sensing data validation required the acquirement of in situ ground-true data, consisting on data from our permanent instruments, as well as ad hoc measurements in the field (snow cover mapping, snow pits, albedo characterization, etc.). Although the project is finished, the data analysis is still ongoing. We present here the different research tasks we are developing as well as the most important results we already obtained about the snow cover. These results confirm how the snow cover duration has been changing in the last years, affecting the ground thermal behavior.info:eu-repo/semantics/publishedVersio

A Reappraisal of Iberian Copper Age Goldwork: Craftmanship, Symbolism and Art in a Non-funerary Gold Sheet from Valencina de la Concepción

Taking as a point of departure the in-depth analysis and description of an exceptional discovery, consisting of a large hammered gold sheet decorated with embossed motifs from the well-known Chalcolithic settlement of Valencina de la Concepción (Seville, Spain), this article presents a general appraisal of the social and ideological role of gold in Copper Age Iberia. The information available for this find, including both its context and its inherent characteristics, opens up new perspectives for research into the technology, use, sociology and symbolism of gold during this time period. We describe and analyse this unique item in detail, including the characterization of the raw material used and the manufacturing process (via SEM-BSE and LA-ICP-MS), as well as an extensive reconstruction of the graphic motifs that are represented, by using digital imaging processing techniques (RTI). We compare this find with the data currently available for the (approximately) 100 Chalcolithic golden artefacts (or fragments of artefacts) found in Iberia to date. Finally, we present an appraisal of the social and ideological framework in which gold was used in Copper Age Iberia, discussing its relevance in aspects such as the dynamics of social complexity, worldviews or artistic creations

Differential Role of Human Choline Kinase α and β Enzymes in Lipid Metabolism: Implications in Cancer Onset and Treatment

11 pages, 6 figures, 1 table.Background The Kennedy pathway generates phosphocoline and phosphoethanolamine through its two branches. Choline Kinase (ChoK) is the first enzyme of the Kennedy branch of synthesis of 1phosphocholine, the major component of the plasma membrane. ChoK family of proteins is composed by ChoKα and ChoKβ isoforms, the first one with two different variants of splicing. Recently ChoKα has been implicated in the carcinogenic process, since it is over-expressed in a variety of human cancers. However, no evidence for a role of ChoKβ in carcinogenesis has been reported. Methodology/Principal Findings Here we compare the in vitro and in vivo properties of ChoKα1 and ChoKβ in lipid metabolism, and their potential role in carcinogenesis. Both ChoKα1 and ChoKβ showed choline and ethanolamine kinase activities when assayed in cell extracts, though with different affinity for their substrates. However, they behave differentially when overexpressed in whole cells. Whereas ChoKβ display an ethanolamine kinase role, ChoKα1 present a dual choline/ethanolamine kinase role, suggesting the involvement of each ChoK isoform in distinct biochemical pathways under in vivo conditions. In addition, while overexpression of ChoKα1 is oncogenic when overexpressed in HEK293T or MDCK cells, ChoKβ overexpression is not sufficient to induce in vitro cell transformation nor in vivo tumor growth. Furthermore, a significant upregulation of ChoKα1 mRNA levels in a panel of breast and lung cancer cell lines was found, but no changes in ChoKβ mRNA levels were observed. Finally, MN58b, a previously described potent inhibitor of ChoK with in vivo antitumoral activity, shows more than 20-fold higher efficiency towards ChoKα1 than ChoKβ. Conclusion/Significance This study represents the first evidence of the distinct metabolic role of ChoKα and ChoKβ isoforms, suggesting different physiological roles and implications in human carcinogenesis. These findings constitute a step forward in the design of an antitumoral strategy based on ChoK inhibition.This work has been supported by grants to JCL from Comunidad de Madrid (GR-SAL-0821-2004), Ministerio de Ciencia e Innovación (SAF2008-03750, RD06/0020/0016), Fundación Mutua Madrileña, and by a grant to ARM from Fundación Mutua Madrileña.Peer reviewe

Effects of an exercise program on brain health outcomes for children with overweight or obesity

Importance Pediatric overweight and obesity are highly prevalent across the world, with implications for poorer cognitive and brain health. Exercise might potentially attenuate these adverse consequences. Objectives To investigate the effects of an exercise program on brain health indicators, including intelligence, executive function, academic performance, and brain outcomes, among children with overweight or obesity and to explore potential mediators and moderators of the main effects of exercise. Design, Setting, and Participants All preexercise and postexercise data for this 20-week randomized clinical trial of 109 children aged 8 to 11 years with overweight or obesity were collected from November 21, 2014, to June 30, 2016, with neuroimaging data processing and analyses conducted between June 1, 2017, and December 20, 2021. All 109 children were included in the intention-to-treat analyses; 90 children (82.6%) completed the postexercise evaluation and attended 70% or more of the recommended exercise sessions and were included in per-protocol analyses. Interventions All participants received lifestyle recommendations. The control group continued their usual routines, whereas the exercise group attended a minimum of 3 supervised 90-minute sessions per week in an out-of-school setting. Main Outcomes and Measures Intelligence, executive function (cognitive flexibility, inhibition, and working memory), and academic performance were assessed with standardized tests, and hippocampal volume was measured with magnetic resonance imaging. Results The 109 participants included 45 girls (41.3%); participants had a mean (SD) body mass index of 26.8 (3.6) and a mean (SD) age of 10.0 (1.1) years at baseline. In per-protocol analyses, the exercise intervention improved crystallized intelligence, with the exercise group improving from before exercise to after exercise (mean z score, 0.62 [95% CI, 0.44-0.80]) compared with the control group (mean z score, –0.10 [95% CI, –0.28 to 0.09]; difference between groups, 0.72 SDs [95% CI, 0.46-0.97]; P < .001). Total intelligence also improved significantly more in the exercise group (mean z score, 0.69 [95% CI, 0.48-0.89]) than in the control group (mean z score, 0.07 [95% CI, –0.14 to 0.28]; difference between groups, 0.62 SDs [95% CI, 0.31-0.91]; P < .001). Exercise also positively affected a composite score of cognitive flexibility (mean z score: exercise group, 0.25 [95% CI, 0.05-0.44]; control group, –0.17 [95% CI, –0.39 to 0.04]; difference between groups, 0.42 SDs [95% CI, 0.13-0.71]; P = .005). These main effects were consistent in intention-to-treat analyses and after multiple-testing correction. There was a positive, small-magnitude effect of exercise on total academic performance (mean z score: exercise group, 0.31 [95% CI, 0.18-0.44]; control group, 0.10 [95% CI, –0.04 to 0.24]; difference between groups, 0.21 SDs [95% CI, 0.01-0.40]; P = .03), which was partially mediated by cognitive flexibility. Inhibition, working memory, hippocampal volume, and other brain magnetic resonance imaging outcomes studied were not affected by the exercise program. The intervention increased cardiorespiratory fitness performance as indicated by longer treadmill time to exhaustion (mean z score: exercise group, 0.54 [95% CI, 0.27-0.82]; control group, 0.13 [95% CI, –0.16 to 0.41]; difference between groups, 0.42 SDs [95% CI, 0.01-0.82]; P = .04), and these changes in fitness mediated some of the effects (small percentage of mediation [approximately 10%-20%]). The effects of exercise were overall consistent across the moderators tested, except for larger improvements in intelligence among boys compared with girls. Conclusions and Relevance In this randomized clinical trial, exercise positively affected intelligence and cognitive flexibility during development among children with overweight or obesity. However, the structural and functional brain changes responsible for these improvements were not identified

COVID-19 : Age, Interleukin-6, C-reactive protein, and lymphocytes as key clues from a multicentre retrospective study

Background: The SARS-CoV-2 infection has widely spread to become the greatest public health challenge to date, the COVID-19 pandemic. Different fatality rates among countries are probably due to non-standardized records being carried out by local health authorities. The Spanish case-fatality rate is 11.22%, far higher than those reported in Asia or by other European countries. A multicentre retrospective study of demographic, clinical, laboratory and immunological features of 584 Spanish COVID-19 hospitalized patients and their outcomes was performed. The use of renin-angiotensin system blockers was also analysed as a risk factor. Results: In this study, 27.4% of cases presented a mild course, 42.1% a moderate one and for 30.5% of cases, the course was severe. Ages ranged from 18 to 98 (average 63). Almost 60 % (59.8%) of patients were male. Interleukin 6 was higher as severity increased. On the other hand, CD8 lymphocyte count was significantly lower as severity grew and subpopulations CD4, CD8, CD19, and NK showed concordant lowering trends. Severity-related natural killer percent descents were evidenced just within aged cases. A significant severity-related decrease of CD4 lymphocytes was found in males. The use of angiotensin-converting enzyme inhibitors was associated with a better prognosis. The angiotensin II receptor blocker use was associated with a more severe course. Conclusions: Age and age-related comorbidities, such as dyslipidaemia, hypertension or diabetes, determined more frequent severe forms of the disease in this study than in previous literature cohorts. Our cases are older than those so far reported and the clinical course of the disease is found to be impaired by age. Immunosenescence might be therefore a suitable explanation for the hampering of immune system effectors. The adaptive immunity would become exhausted and a strong but ineffective and almost deleterious innate response would account for COVID-19 severity. Angiotensin-converting enzyme inhibitors used by hypertensive patients have a protective effect in regards to COVID-19 severity in our series. Conversely, patients on angiotensin II receptor blockers showed a severer disease

First Atmospheric Results from InSight APSS

NASA’s Mars InSight Spacecraft landed on Nov 26, 2018 (Ls=295°) in Elysium Planitia (~4.5°N, 136°E). InSight’s main scientific purpose is to investigate the interior structure and heat flux from Mars, but it is also equipped with instrumentation that can serve as a very capable meteorological station. To remove unwanted environmental noise from the seis- mic signals, InSight carries a very precise pressure sensor (PS) and the first magnetometer (IFG) to the surface of Mars. Additionally, to aid in removing the atmospheric pressure-induced seismic noise, and to identify periods when wind-induced seismic noise may reduce sensitivity, InSight also carries a pair of Wind and Air temperature sensors (TWINS). These three sensors comprise the Auxiliary Payload Sensor Suite (APSS) [1]. Complementing this are a radiometer in the HP3 suite to measure surface radiance, the seismic measurements of SEIS which can record interesting atmospheric phenomena, and the InSight cameras to image clouds and dust devils and estimate atmospheric opacity from dust or clouds. The Lander also carried accelerometers that can be used to reconstruct the at- mospheric structure during descent. We will discuss results drawn from atmospheric measurements on board InSight from the first months of operation, high- lighting the new perspectives permitted by the novel high-frequency, and continuous nature of the InSight data acquisition. Details on pre-landing scientific perspectives for atmospheric science with InSight are found in [2]

Highlights from the Pierre Auger Observatory

The Pierre Auger Observatory is the world's largest cosmic ray observatory. Our current exposure reaches nearly 40,000 km$^2$ str and provides us with an unprecedented quality data set. The performance and stability of the detectors and their enhancements are described. Data analyses have led to a number of major breakthroughs. Among these we discuss the energy spectrum and the searches for large-scale anisotropies. We present analyses of our X$_{max}$ data and show how it can be interpreted in terms of mass composition. We also describe some new analyses that extract mass sensitive parameters from the 100% duty cycle SD data. A coherent interpretation of all these recent results opens new directions. The consequences regarding the cosmic ray composition and the properties of UHECR sources are briefly discussed.Comment: 9 pages, 12 figures, talk given at the 33rd International Cosmic Ray Conference, Rio de Janeiro 201