Truncating Variants in NAA15 Are Associated with Variable Levels of Intellectual Disability, Autism Spectrum Disorder, and Congenital Anomalies

Genetics of disease, diagnosis and treatmen

Study of the doubly charmed tetraquark T+cc

Quantum chromodynamics, the theory of the strong force, describes interactions of coloured quarks and gluons and the formation of hadronic matter. Conventional hadronic matter consists of baryons and mesons made of three quarks and quark-antiquark pairs, respectively. Particles with an alternative quark content are known as exotic states. Here a study is reported of an exotic narrow state in the D0D0π+ mass spectrum just below the D*+D0 mass threshold produced in proton-proton collisions collected with the LHCb detector at the Large Hadron Collider. The state is consistent with the ground isoscalar T+cc tetraquark with a quark content of ccu⎯⎯⎯d⎯⎯⎯ and spin-parity quantum numbers JP = 1+. Study of the DD mass spectra disfavours interpretation of the resonance as the isovector state. The decay structure via intermediate off-shell D*+ mesons is consistent with the observed D0π+ mass distribution. To analyse the mass of the resonance and its coupling to the D*D system, a dedicated model is developed under the assumption of an isoscalar axial-vector T+cc state decaying to the D*D channel. Using this model, resonance parameters including the pole position, scattering length, effective range and compositeness are determined to reveal important information about the nature of the T+cc state. In addition, an unexpected dependence of the production rate on track multiplicity is observed

Evolution of magnetic fields in supernova remnants

Supernova remnants (SNR) are now widely believed to be a source of cosmic rays (CRs) up to an energy of 10(15) eV. The magnetic fields required to accelerate CRs to sufficiently high energies need to be much higher than can result from compression of the circumstellar medium (CSM) by a factor 4, as is the case in strong shocks. Non-thermal synchrotron maps of these regions indicate that indeed the magnetic field is much stronger, and for young SNRs has a dominant radial component while for old SNRs it is mainly toroidal. How these magnetic fields get enhanced, or why the field orientation is mainly radial for young remnants, is not yet fully understood. We use an adaptive mesh refinement MHD code, AMRVAC, to simulate the evolution of supernova remnants and to see if we can reproduce a mainly radial magnetic field in early stages of evolution. We follow the evolution of the SNR with three different configurations of the initial magnetic field in the CSM: an initially mainly toroidal field, a turbulent magnetic field, and a field parallel to the symmetry axis. Although for the latter two topologies a significant radial field component arises at the contact discontinuity due to the Rayleigh-Taylor instability, no radial component can be seen out to the forward shock. Ideal MHD appears not sufficient to explain observations. Possibly a higher compression ratio and additional turbulence due to dominant presence of CRs can help us to better reproduce the observations in future studies

Genotype-Phenotype Comparison in POGZ-Related Neurodevelopmental Disorders by Using Clinical Scoring

POGZ-related disorders (also known as White-Sutton syndrome) encompass a wide range of neurocognitive abnormalities and other accompanying anomalies. Disease severity varies widely among POGZ patients and studies investigating genotype-phenotype association are scarce. Therefore, our aim was to collect data on previously unreported POGZ patients and perform a large-scale phenotype-genotype comparison from published data. Overall, 117 POGZ patients' genotype and phenotype data were included in the analysis, including 12 novel patients. A severity scoring system was developed for the comparison. Mild and severe phenotypes were compared with the types and location of the variants and the predicted presence or absence of nonsense-mediated RNA decay (NMD). Missense variants were more often associated with mild phenotypes (p = 0.0421) and truncating variants predicted to escape NMD presented with more severe phenotypes (p < 0.0001). Within this group, variants in the prolin-rich region of the POGZ protein were associated with the most severe phenotypes (p = 0.0004). Our study suggests that gain-of-function or dominant negative effect through escaping NMD and the location of the variants in the prolin-rich domain of the protein may play an important role in the severity of manifestations of POGZ-associated neurodevelopmental disorders

Intracellular innate resistance to bacterial pathogens

Mammalian innate immunity stimulates antigen-specific immune responses and acts to control infection prior to the onset of adaptive immunity. Some bacterial pathogens replicate within the host cell and are therefore sheltered from some protective aspects of innate immunity such as complement. Here we focus on mechanisms of innate intracellular resistance encountered by bacterial pathogens and how some bacteria can evade destruction by the innate immune system. Major strategies of intracellular antibacterial defence include pathogen compartmentalization and iron limitation. Compartmentalization of pathogens within the host endocytic pathway is critical for generating high local concentrations of antimicrobial molecules, such as reactive oxygen species, and regulating concentrations of divalent cations that are essential for microbial growth. Cytosolic sensing, autophagy, sequestration of essential nutrients and membrane attack by antimicrobial peptides are also discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71916/1/j.1462-5822.2006.00795.x.pd