Uncertainties in the Production of p Nuclides in SN Ia Determined by Monte Carlo Variations

© Springer Nature Switzerland AG 2019Several thousand tracers from a 2D model of a thermonuclear supernova were used in a Monte Carlo post-processing approach to determine p-nuclide abundance uncertainties originating from nuclear physics uncertainties in the reaction rates.Final Accepted Versio

Crosstalk between Medulloblastoma Cells and Endothelium Triggers a Strong Chemotactic Signal Recruiting T Lymphocytes to the Tumor Microenvironment

Cancer cells can live and grow if they succeed in creating a favorable niche that often includes elements from the immune system. While T lymphocytes play an important role in the host response to tumor growth, the mechanism of their trafficking to the tumor remains poorly understood. We show here that T lymphocytes consistently infiltrate the primary brain cancer, medulloblastoma. We demonstrate, both in vitro and in vivo, that these T lymphocytes are attracted to tumor deposits only after the tumor cells have interacted with tumor vascular endothelium. Macrophage Migration Inhibitory Factor (MIF)” is the key chemokine molecule secreted by tumor cells which induces the tumor vascular endothelial cells to secrete the potent T lymphocyte attractant “Regulated upon Activation, Normal T-cell Expressed, and Secreted (RANTES).” This in turn creates a chemotactic gradient for RANTES-receptor bearing T lymphocytes. Manipulation of this pathway could have important therapeutic implications

Impairment of circulating endothelial progenitors in Down syndrome

<p>Abstract</p> <p>Background</p> <p>Pathological angiogenesis represents a critical issue in the progression of many diseases. Down syndrome is postulated to be a systemic anti-angiogenesis disease model, possibly due to increased expression of anti-angiogenic regulators on chromosome 21. The aim of our study was to elucidate some features of circulating endothelial progenitor cells in the context of this syndrome.</p> <p>Methods</p> <p>Circulating endothelial progenitors of Down syndrome affected individuals were isolated, <it>in vitro </it>cultured and analyzed by confocal and transmission electron microscopy. ELISA was performed to measure SDF-1α plasma levels in Down syndrome and euploid individuals. Moreover, qRT-PCR was used to quantify expression levels of <it>CXCL12 </it>gene and of its receptor in progenitor cells. The functional impairment of Down progenitors was evaluated through their susceptibility to hydroperoxide-induced oxidative stress with BODIPY assay and the major vulnerability to the infection with human pathogens. The differential expression of crucial genes in Down progenitor cells was evaluated by microarray analysis.</p> <p>Results</p> <p>We detected a marked decrease of progenitors' number in young Down individuals compared to euploid, cell size increase and some major detrimental morphological changes. Moreover, Down syndrome patients also exhibited decreased SDF-1α plasma levels and their progenitors had a reduced expression of SDF-1α encoding gene and of its membrane receptor. We further demonstrated that their progenitor cells are more susceptible to hydroperoxide-induced oxidative stress and infection with Bartonella henselae. Further, we observed that most of the differentially expressed genes belong to angiogenesis, immune response and inflammation pathways, and that infected progenitors with trisomy 21 have a more pronounced perturbation of immune response genes than infected euploid cells.</p> <p>Conclusions</p> <p>Our data provide evidences for a reduced number and altered morphology of endothelial progenitor cells in Down syndrome, also showing the higher susceptibility to oxidative stress and to pathogen infection compared to euploid cells, thereby confirming the angiogenesis and immune response deficit observed in Down syndrome individuals.</p

A Meta-analysis of Attachment to Parents and Delinquency

To investigate the link between attachment to parents and delinquency, and the potential moderating effects of age and sex, 74 published and unpublished manuscripts (N = 55,537 participants) were subjected to a multilevel meta-analysis. A mean small to moderate effect size was found (r = 0.18). Poor attachment to parents was significantly linked to delinquency in boys and girls. Stronger effect sizes were found for attachment to mothers than attachment to fathers. In addition, stronger effect sizes were found if the child and the parent had the same sex compared to cross-sex pairs of children and parents. Age of the participants moderated the link between attachment and delinquency: larger effect sizes were found in younger than in older participants. It can be concluded that attachment is associated with juvenile delinquency. Attachment could therefore be a target for intervention to reduce or prevent future delinquent behavior in juveniles

Massive-Scale RNA-Seq Analysis of Non Ribosomal Transcriptome in Human Trisomy 21

Hybridization- and tag-based technologies have been successfully used in Down syndrome to identify genes involved in various aspects of the pathogenesis. However, these technologies suffer from several limits and drawbacks and, to date, information about rare, even though relevant, RNA species such as long and small non-coding RNAs, is completely missing. Indeed, none of published works has still described the whole transcriptional landscape of Down syndrome. Although the recent advances in high-throughput RNA sequencing have revealed the complexity of transcriptomes, most of them rely on polyA enrichment protocols, able to detect only a small fraction of total RNA content. On the opposite end, massive-scale RNA sequencing on rRNA-depleted samples allows the survey of the complete set of coding and non-coding RNA species, now emerging as novel contributors to pathogenic mechanisms. Hence, in this work we analysed for the first time the complete transcriptome of human trisomic endothelial progenitor cells to an unprecedented level of resolution and sensitivity by RNA-sequencing. Our analysis allowed us to detect differential expression of even low expressed genes crucial for the pathogenesis, to disclose novel regions of active transcription outside yet annotated loci, and to investigate a plethora of non-polyadenilated long as well as short non coding RNAs. Novel splice isoforms for a large subset of crucial genes, and novel extended untranslated regions for known genes—possibly novel miRNA targets or regulatory sites for gene transcription—were also identified in this study. Coupling the rRNA depletion of samples, followed by high-throughput RNA-sequencing, to the easy availability of these cells renders this approach very feasible for transcriptome studies, offering the possibility of investigating in-depth blood-related pathological features of Down syndrome, as well as other genetic disorders

Sports Participation and Juvenile Delinquency: A Meta-Analytic Review

Participation in sports activities is very popular among adolescents, and is frequently encouraged among youth. Many psychosocial health benefits in youth are attributed to sports participation, but to what extent this positive influence holds for juvenile delinquency is still not clear on both the theoretical and empirical level. There is much controversy on whether sports participation should be perceived as a protective or a risk factor for the development of juvenile delinquency. A multilevel meta-analysis of 51 published and unpublished studies, with 48 independent samples containing 431 effect sizes and N = 132,366 adolescents, was conducted to examine the relationship between sports participation and juvenile delinquency and possible moderating factors of this association. The results showed that there is no overall significant association between sports participation and juvenile delinquency, indicating that adolescent athletes are neither more nor less delinquent than non-athletes. Some study, sample and sports characteristics significantly moderated the relationship between sports participation and juvenile delinquency. However, this moderating influence was modest. Implications for theory and practice concerning the use of sports to prevent juvenile delinquency are discussed. Keywords Sports participation Juvenile delinquency Multilevel meta-analysis Revie

Independent Quality Assessment of Essential Climate Variables: Lessons learnt from the Copernicus Climate Change Service

If climate services are to lead to effective use of climate information in decision-making to enable the transition to a climate-smart, climate-ready world, then the question of trust in the products and services is of paramount importance. The Copernicus Climate Change Service (C3S) has been actively grappling with how to build such trust: provision of demonstrably independent assessments of the quality of products, which was deemed an important element in such trust-building processes. C3S provides access to essential climate variables (ECVs) from multiple sources to a broad set of users ranging from scientists to private companies and decision-makers. Here we outline the approach undertaken to coherently assess the quality of a suite of observation- and reanalysis-based ECV products covering the atmosphere, ocean, land, and cryosphere. The assessment is based on four pillars: basic data checks, maturity of the datasets, fitness for purpose (scientific use cases and climate studies), and guidance to users. It is undertaken independently by scientific experts and presented alongside the datasets in a fully traceable, replicable, and transparent manner. The methodology deployed is detailed, and example assessments are given. These independent scientific quality assessments are intended to guide users to ensure they use tools and datasets that are fit for purpose to answer their specific needs rather than simply use the first product they alight on. This is the first such effort to develop and apply an assessment framework consistently to all ECVs. Lessons learned and future perspectives are outlined to potentially improve future assessment activities and thus climate services.ISSN:0003-0007ISSN:1520-047

Aging is associated with an increased susceptibility for ischaemic necrosis due to microvascular perfusion failure but not a reduction in ischaemic tolerance

In the present study in a murine model of chronic ischaemia, we analysed: (i) whether aging was associated with an increased susceptibility to ischaemic necrosis, and (ii) whether this was based on microvascular dysfunction or reduced ischaemic tolerance. An ischaemic pedicled skin flap was created in the ear of homozygous hairless mice. The animals were assigned to three age groups, including adolescent (2+/-1 months), adult (10+/-2 months) and senescent (19+/-3 months). Microvascular perfusion of the ischaemic flap was assessed over 5 days by intravital microscopy, evaluating FCD (functional capillary density), capillary dilation response and the area of tissue necrosis. Expression of the stress-protein HO (haem oxygenase)-1 was determined by immunohistochemistry and Western blotting. Induction of chronic ischaemia stimulated a significant expression of HO-1 without a significant difference between the three age groups. This was associated with capillary dilation, which, however, was more pronounced in adolescent (10.5+/-2.8 microm compared with 3.95+/-0.79 microm at baseline) and adult (12.1+/-3.1 microm compared with 3.36+/-0.45 microm at baseline) animals compared with senescent animals (8.5+/-1.7 microm compared with 3.28+/-0.69 microm at baseline; P value not significant). In senescent animals, flap creation further resulted in complete cessation of capillary flow in the distal area of the flap (FCD, 0+/-0 cm/cm(2)), whereas adult (11.9+/-13.5 cm/cm(2)) and, in particular, adolescent animals (58.4+/-33.6 cm/cm(2); P<0.05) were capable of maintaining residual capillary perfusion. The age-associated microcirculatory dysfunction resulted in a significantly increased flap necrosis of 49+/-8% (P<0.05) and 42+/-8% (P<0.05) in senescent and adult animals respectively, compared with 31+/-6% in adolescent mice. Of interest, functional inhibition of HO-1 by SnPP-IX (tin protoporphyrin-IX) in adolescent mice abrogated capillary dilation, decreased functional capillary density and aggravated tissue necrosis comparably with that observed in senescent mice. Thus aging is associated with an increased susceptibility to tissue necrosis, which is due to a loss of vascular reactivity to endogenous HO-1 expression, rather than a reduction in ischaemic tolerance

Predictors of Intervention Success in a Sports-Based Program for Adolescents at Risk of Juvenile Delinquency

To prevent juvenile delinquency, there is growing interest in the use of sports-based interventions. To date, there is little empirical research that provides insights into for whom, how, and when sports-based crime prevention programs are most effective. Therefore, the current study assessed which youth, coach, and context factors were predictive of change in risk factors and protective factors for delinquency in a sports-based crime prevention program for at-risk adolescents. Participants (N = 155) and their teachers filled in questionnaires about risk and protective factors for delinquency at the start of the intervention and 13 months later. In addition, the coaches and participants filled in questionnaires about the predictors of intervention success. The youths showed significant improvements over the course of the intervention. Various youth, coach, and context factors (e.g., the type of education of youth and the sociomoral climate at the sports club) were associated to change in the outcome variables