Translational genetic modelling of 3D craniofacial dysmorphology: elaborating the facial phenotype of neurodevelopmental disorders through the prism of schizophrenia

Purpose of Review: In the context of human developmental conditions, we review the conceptualisation of schizophrenia as a neurodevelopmental disorder, the status of craniofacial dysmorphology as a clinically accessible index of brain dysmorphogenesis, the ability of genetically modified mouse models of craniofacial dysmorphology to inform on the underlying dysmorphogenic process and how geometric morphometric techniques in mutant mice can extend quantitative analysis. Recent Findings: Mutant mice with disruption of neuregulin-1, a gene associated meta-analytically with risk for schizophrenia, constitute proof-of-concept studies of murine facial dysmorphology in a manner analogous to clinical studies in schizophrenia. Geometric morphometric techniques informed on the topography of facial dysmorphology and identified asymmetry therein. Summary: Targeted disruption in mice of genes involved in individual components of developmental processes and analysis of resultant facial dysmorphology using geometric morphometrics can inform on mechanisms of dysmorphogenesis at levels of incisiveness not possible in human subjects

The charge and energy spectra of heavy cosmic ray nuclei

A charged particle detector array flown in a high altitude balloon detected and measured some 30,000 cosmic ray nuclei with Z greater than or equal to 12. The charge spectrum at the top of the atmosphere for nuclei with E greater than 650 MeV/n and the energy spectrum for 650 less than or equal to E less than 1800 MeV/n are reported and compared with previously published results. The charge spectrum at the source of cosmic rays is deduced from these data and compared with a recent compilation of galactic abundances

Impact of bidirectional relationships between streptococcus anginosus group and host tissue matrix components on cellular activity: Role in establishment of infection

This paper investigates pathogenic mechanisms of the Streptococcus anginosus group (SAG) of bacteria which influence the biological activity of periodontal ligament (PDL) cells, endothelial cells and also how matrix proteins produced by these host cells influence bacterial virulence factors. Isolates of SAG species, designated S. anginosus, S. constellatus and S. intermedius, were derived from healthy commensal and clinical pathogenic infection sites. SAG culture supernatants contained multiple protein components which differed between isolates. All SAG supernatants increased cellular proliferation and decreased decorin synthesis and collagen assembly by PDL cells and reduced endothelial cell migration. SAG isolates responded differently to extracellular matrix (ECM) components synthesised by PDL cells, but there was an overall notable increase in hydrolytic enzyme activity and in the production of the cytotoxin intermedilysin by S. intermedius. Collectively, the results indicate that both commensal and pathogenic SAG isolates were capable of impairing the ability of PDL cells and endothelial cells to make functional vascularised tissue. Reduced decorin synthesis is likely to have a major impact on cell signalling, angiogenesis and matrix assembly. Furthermore, ECM components produced by PDL cells were differentially capable of moderately increasing SAG enzymic activity, leading to subtle ECM modifications. The impact this bidirectional effect has on the tissue remodelling process is discussed

Energy spectra of elements with 18 or = Z or = 28 between 10 and 300 GeV/amu

The HEAO-3 Heavy Nuclei Experiment is composed of ionization chambers above and below a plastic Cerenkov counter. The energy dependence of the abundances of elements with atomic number, Z, between 18 and 28 at very high energies where they are rare and thus need the large area x time are measured. The measurements of the Danish-French HEAO-3 experiment (Englemann,, et al., 1983) are extended to higher energies, using the relativistic rise of ionization signal as a measure of energy. Source abundances for Ar and Ca were determined

Shaping Robust System through Evolution

Biological functions are generated as a result of developmental dynamics that form phenotypes governed by genotypes. The dynamical system for development is shaped through genetic evolution following natural selection based on the fitness of the phenotype. Here we study how this dynamical system is robust to noise during development and to genetic change by mutation. We adopt a simplified transcription regulation network model to govern gene expression, which gives a fitness function. Through simulations of the network that undergoes mutation and selection, we show that a certain level of noise in gene expression is required for the network to acquire both types of robustness. The results reveal how the noise that cells encounter during development shapes any network's robustness, not only to noise but also to mutations. We also establish a relationship between developmental and mutational robustness through phenotypic variances caused by genetic variation and epigenetic noise. A universal relationship between the two variances is derived, akin to the fluctuation-dissipation relationship known in physics

Interactions of heavy nuclei, Kr, Xe and Ho, in light targets

Over the past few years, the HEAO-3 measurements of the abundances of ultra-heavy cosmic ray nuclei (Z 26) at earth have been analyzed. In order to interpret these abundances in terms of a source composition, allowance must be made for the propagation of the nuclei in the interstellar medium. Vital to any calculation of the propagation is a knowlege of the total and partial interaction cross sections for these heavy nuclei on hydrogen. Until recently, data on such reactions have been scarce. However, now that relativistic heavy ion beams are available at the LBL Bevalac, some of the cross sections of interest can be measured at energies close to those of the cosmic ray nuclei being observed. During a recent calibration at the Bevalac of an array similar to the HEAO-C3 UH-nuclei detector, targets of raphite (C), polyethylene (CH2), and aluminum were exposed to five heavy ion beams ranging in charge (Z) from 36 to 92. Total and partial charge changing cross sections for the various beam nuclei on hydrogen can be determined from the measured cross sections on C and CH2, and will be applied to the propagation problem. The cross sections on Al can be used to correct the abundances of UH cosmic rays observed in the HEAO C-3 detector for interactions in the detector itself