Active Galactic Nuclei under the scrutiny of CTA

Active Galactic Nuclei (hereafter AGN) produce powerful outflows which offer excellent conditions for efficient particle acceleration in internal and external shocks, turbulence, and magnetic reconnection events. The jets as well as particle accelerating regions close to the supermassive black holes (hereafter SMBH) at the intersection of plasma inflows and outflows, can produce readily detectable very high energy gamma-ray emission. As of now, more than 45 AGN including 41 blazars and 4 radiogalaxies have been detected by the present ground-based gamma-ray telescopes, which represents more than one third of the cosmic sources detected so far in the VHE gamma-ray regime. The future Cherenkov Telescope Array (CTA) should boost the sample of AGN detected in the VHE range by about one order of magnitude, shedding new light on AGN population studies, and AGN classification and unification schemes. CTA will be a unique tool to scrutinize the extreme high-energy tail of accelerated particles in SMBH environments, to revisit the central engines and their associated relativistic jets, and to study the particle acceleration and emission mechanisms, particularly exploring the missing link between accretion physics, SMBH magnetospheres and jet formation. Monitoring of distant AGN will be an extremely rewarding observing program which will inform us about the inner workings and evolution of AGN. Furthermore these AGN are bright beacons of gamma-rays which will allow us to constrain the extragalactic infrared and optical backgrounds as well as the intergalactic magnetic field, and will enable tests of quantum gravity and other "exotic" phenomena.Comment: 28 pages, 23 figure

Dark matter powered stars: Constraints from the extragalactic background light

The existence of predominantly cold non-baryonic dark matter is unambiguously demonstrated by several observations (e.g., structure formation, big bang nucleosynthesis, gravitational lensing, and rotational curves of spiral galaxies). A candidate well motivated by particle physics is a weakly interacting massive particle (WIMP). Self-annihilating WIMPs would affect the stellar evolution especially in the early universe. Stars powered by self-annihilating WIMP dark matter should possess different properties compared with standard stars. While a direct detection of such dark matter powered stars seems very challenging, their cumulative emission might leave an imprint in the diffuse metagalactic radiation fields, in particular in the mid-infrared part of the electromagnetic spectrum. In this work the possible contributions of dark matter powered stars (dark stars; DSs) to the extragalactic background light (EBL) are calculated. It is shown that existing data and limits of the EBL intensity can already be used to rule out some DS parameter sets.Comment: Accepted for publication in ApJ; 7 pages, 5 figure

Genetic Variants Associated With Glycine Metabolism and Their Role in Insulin Sensitivity and Type 2 Diabetes

Circulating metabolites associated with insulin sensitivity may represent useful biomarkers, but their causal role in insulin sensitivity and diabetes is less certain. We previously identified novel metabolites correlated with insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp. The top-ranking metabolites were in the glutathione and glycine biosynthesis pathways. We aimed to identify common genetic variants associated with metabolites in these pathways and test their role in insulin sensitivity and type 2 diabetes. With 1,004 nondiabetic individuals from the RISC study, we performed a genome-wide association study (GWAS) of 14 insulin sensitivity-related metabolites and one metabolite ratio. We replicated our results in the Botnia study (n = 342). We assessed the association of these variants with diabetes-related traits in GWAS meta-analyses (GENESIS [including RISC, EUGENE2, and Stanford], MAGIC, and DIAGRAM). We identified four associations with three metabolites-glycine (rs715 at CPS1), serine (rs478093 at PHGDH), and betaine (rs499368 at SLC6A12; rs17823642 at BHMT)-and one association signal with glycine-to-serine ratio (rs1107366 at ALDH1L1). There was no robust evidence for association between these variants and insulin resistance or diabetes. Genetic variants associated with genes in the glycine biosynthesis pathways do not provide consistent evidence for a role of glycine in diabetes-related traits

The impact of sequencing depth on the inferred taxonomic composition and AMR gene content of metagenomic samples

Shotgun metagenomics is increasingly used to characterise microbial communities, particularly for the investigation of antimicrobial resistance (AMR) in different animal and environmental contexts. There are many different approaches for inferring the taxonomic composition and AMR gene content of complex community samples from shotgun metagenomic data, but there has been little work establishing the optimum sequencing depth, data processing and analysis methods for these samples. In this study we used shotgun metagenomics and sequencing of cultured isolates from the same samples to address these issues. We sampled three potential environmental AMR gene reservoirs (pig caeca, river sediment, effluent) and sequenced samples with shotgun metagenomics at high depth (~ 200 million reads per sample). Alongside this, we cultured single-colony isolates of Enterobacteriaceae from the same samples and used hybrid sequencing (short- and long-reads) to create high- quality assemblies for comparison to the metagenomic data. To automate data processing, we developed an open- source software pipeline, ‘ResPipe’

Protocol for the development and validation procedure of the managing the link and strengthening transition from child to adult mental health care (MILESTONE) suite of measures

Background: Mental health disorders in the child and adolescent population are a pressing public health concern. Despite the high prevalence of psychopathology in this vulnerable population, the transition from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS) has many obstacles such as deficiencies in planning, organisational readiness and policy gaps. All these factors contribute to an inadequate and suboptimal transition process. A suite of measures is required that would allow young people to be assessed in a structured and standardised way to determine the on-going need for care and to improve communication across clinicians at CAMHS and AMHS. This will have the potential to reduce the overall health economic burden and could also improve the quality of life for patients travelling across the transition boundary. The MILESTONE (Managing the Link and Strengthening Transition from Child to Adult Mental Health Care) project aims to address the significant socioeconomic and societal challenge related to the transition process. This protocol paper describes the development of two MILESTONE transition-related measures: The Transition Readiness and Appropriateness Measure (TRAM), designed to be a decision-making aide for clinicians, and the Transition Related Outcome Measure (TROM), for examining the outcome of transition. Methods: The TRAM and TROM have been developed and were validated following the US FDA Guidance for Patient-reported Outcome Measures which follows an incremental stepwise framework. The study gathers information from service users, parents, families and mental health care professionals who have experience working with young people undergoing the transition process from eight European countries. Discussion: There is an urgent need for comprehensive measures that can assess transition across the CAMHS/AMHS boundary. This study protocol describes the process of development of two new transition measures: the TRAM and TROM. The TRAM has the potential to nurture better transitions as the findings can be summarised and provided to clinicians as a clinician-decision making support tool for identifying cases who need to transition and the TROM can be used to examine the outcomes of the transition process. Trial registration: MILESTONE study registration: ISRCTN83240263 Registered 23-July-2015 - ClinicalTrials.gov NCT03013595 Registered 6 January 2017

Bi-allelic GAD1 variants cause a neonatal onset syndromic developmental and epileptic encephalopathy.

Developmental and epileptic encephalopathies are a heterogeneous group of early-onset epilepsy syndromes dramatically impairing neurodevelopment. Modern genomic technologies have revealed a number of monogenic origins and opened the door to therapeutic hopes. Here we describe a new syndromic developmental and epileptic encephalopathy caused by bi-allelic loss-of-function variants in GAD1, as presented by 11 patients from six independent consanguineous families. Seizure onset occurred in the first 2 months of life in all patients. All 10 patients, from whom early disease history was available, presented with seizure onset in the first month of life, mainly consisting of epileptic spasms or myoclonic seizures. Early EEG showed suppression-burst or pattern of burst attenuation or hypsarrhythmia if only recorded in the post-neonatal period. Eight patients had joint contractures and/or pes equinovarus. Seven patients presented a cleft palate and two also had an omphalocele, reproducing the phenotype of the knockout Gad1-/- mouse model. Four patients died before 4 years of age. GAD1 encodes the glutamate decarboxylase enzyme GAD67, a critical actor of the γ-aminobutyric acid (GABA) metabolism as it catalyses the decarboxylation of glutamic acid to form GABA. Our findings evoke a novel syndrome related to GAD67 deficiency, characterized by the unique association of developmental and epileptic encephalopathies, cleft palate, joint contractures and/or omphalocele

Law of Genome Evolution Direction : Coding Information Quantity Grows

The problem of the directionality of genome evolution is studied. Based on the analysis of C-value paradox and the evolution of genome size we propose that the function-coding information quantity of a genome always grows in the course of evolution through sequence duplication, expansion of code, and gene transfer from outside. The function-coding information quantity of a genome consists of two parts, p-coding information quantity which encodes functional protein and n-coding information quantity which encodes other functional elements except amino acid sequence. The evidences on the evolutionary law about the function-coding information quantity are listed. The needs of function is the motive force for the expansion of coding information quantity and the information quantity expansion is the way to make functional innovation and extension for a species. So, the increase of coding information quantity of a genome is a measure of the acquired new function and it determines the directionality of genome evolution.Comment: 16 page

Herschel observations of PNe in the MESS key program

In this paper we give a progress report on the Herschel imaging and spectroscopic observations of planetary nebulae that are carried out as part of the MESS guaranteed time key program. We present and discuss imaging and temperature maps of NGC 6720, NGC 650, and NGC 6853, as well as PACS and SPIRE spectroscopy of NGC 7027.Comment: 4 pages, 5 figures, proceedings IAU Symposium 283 Planetary Nebulae: An Eye to the Futur