104 research outputs found

    Analysis of chicken intestinal natural killer cells, a major IEL subset during embryonic and early life

    Get PDF
    Restrictions on antimicrobials demand alternative strategies to improve broiler health, such as supplying feed additives which stimulate innate immune cells like natural killer (NK) cells. The main objective of this study was to characterize intestinal NK cells in broiler chickens during embryonic and early life and compare these to NK cells in spleen, blood and bone marrow. Also T-cell subsets were determined. The majority of intestinal NK cells expressed IL-2Rα rather than 20E5 and 5C7, and showed low level of activation. Within intestinal NK cells the activation marker CD107 was mostly expressed on IL-2Rα+ cells while in spleen and blood 20E5+ NK cells primarily expressed CD107. High percentages of intestinal CD8αα+, CD8αβ+ and from 2 weeks onward also gamma delta T cells were found. Taken together, we observed several intestinal NK subsets in broiler chickens. Differences in NK subsets were mostly observed between organs, rather than differences over time. Targeting these intestinal NK subsets may be a strategy to improve immune-mediated resistance in broiler chickens.SUPPLEMENTARY MATERIAL : Table S1. Characterization of immune cells generated in broiler chickens in the present study compared to data known in layer chickens.The Dutch Research Council (NWO) and by Cargill Animal Nutrition and Health.http://www.elsevier.com/locate/desalhj2022Veterinary Tropical Disease

    Early motor outcomes in infants with critical congenital heart disease are related to neonatal brain development and brain injury

    Get PDF
    Aim To assess the relationship between neonatal brain development and injury with early motor outcomes in infants with critical congenital heart disease (CCHD). Method Neonatal brain magnetic resonance imaging was performed after open-heart surgery with cardiopulmonary bypass. Cortical grey matter (CGM), unmyelinated white matter, and cerebellar volumes, as well as white matter motor tract fractional anisotropy and mean diffusivity were assessed. White matter injury (WMI) and arterial ischaemic stroke (AIS) with corticospinal tract (CST) involvement were scored. Associations with motor outcomes at 3, 9, and 18 months were corrected for repeated cardiac surgery. Results Fifty-one infants (31 males, 20 females) were included prospectively. Median age at neonatal surgery and postoperative brain magnetic resonance imaging was 7 days (interquartile range [IQR] 5-11d) and 15 days (IQR 12-21d) respectively. Smaller CGM and cerebellar volumes were associated with lower fine motor scores at 9 months (CGM regression coefficient=0.51, 95% confidence interval [CI]=0.15-0.86; cerebellum regression coefficient=3.08, 95% CI=1.07-5.09) and 18 months (cerebellum regression coefficient=2.08, 95% CI=0.47-5.12). The fractional anisotropy and mean diffusivity of white matter motor tracts were not related with motor scores. WMI was related to lower gross motor scores at 9 months (mean difference -0.8SD, 95% CI=-1.5 to -0.2). AIS with CST involvement increased the risk of gross motor problems and muscle tone abnormalities. Cerebral palsy (n=3) was preceded by severe ischaemic brain injury. Interpretation Neonatal brain development and injury are associated with fewer favourable early motor outcomes in infants with CCHD

    Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

    Get PDF
    Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

    Humans to Mars: by MARS- plus EUROPA-INPPS Flagship Mission

    Get PDF
    The first non-human INPPS (International Nuclear Power and Propulsion System) flagship flight with orbits Earth-Mars-Earth-Jupiter/Europa (after 2025) is the most maximal space qualification test of INPPS flagship to carry out the second INPPS flagship flight to Mars with humans (in the 2030th). This high power space transportation tug is realistic because of A) the successful finalization of the European-Russian DEMOCRITOS and MEGAHIT projects with their three concepts of space, ground and nuclear demonstrators for INPPS realization (reached in 2017), B) the successful ground based test of the Russian nuclear reactor with 1MWel plus important heat dissipation solution via droplet radiators (confirmed in 2018), C) the space qualification of the Russian reactor by 2025 and D) the perfect celestial constellation for a Earth-Mars/Phobos-Earth-Jupiter/Europa trajectory between 2026 and 2035. Therefore the talk sketches the preparation status of INPPS flagship with its subsystems. Critical performance will be studied by parallel realizations of the ground and nuclear demonstrators of DEMOCRITOS (until 2025). The space qualification of INPPS with all subsystems including the nuclear reactor in the middle of the 2020th plus the INPPS tests for about one to two years - first in high Earth orbit robotic assembly phase of INPPS and later extended in nearby Earth space environment flight - means a complete concepts driven approval for all applied INPPS space subsystem technologies. It is also important to consider wider aspects for the overall mission implementation phase. Component like the nuclear reactor as the power source for the propulsion system will have to agree with the 1992 UN principles relevant to the use of nuclear power sources (NPS) in outer space. Therefore this talk will look into the legal and policy issues of nuclear space systems related to the international realization of mission design, requirements of associated safety regulations (including AI applications in the subsystems) and new aspects for INPPS flagship commercialization and new media communication on board

    Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

    Get PDF
    Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues
    corecore