ISOGAL: A deep survey of the obscured inner Milky Way with ISO at 7 and 15 micron and with DENIS in the near-infrared

The ISOGAL project is an infrared survey of specific regions sampling the Galactic Plane selected to provide information on Galactic structure,stellar populations,stellar mass-loss and the recent star formation history of the inner disk and Bulge of the Galaxy. ISOGAL combines 7 and 15 micron ISOCAM observations - with a resolution of 6'' at worst - with DENIS IJKs data to determine the nature of the sources and theinterstellar extinction. We have observed about 16 square degrees with a sensitivity approaching 10-20mJy, detecting ~10^5 sources,mostly AGB stars,red giants and young stars. The main features of the ISOGAL survey and the observations are summarized in this paper,together with a brief discussion of data processing and quality. The primary ISOGAL products are described briefly (a full description is given in Schuller et al. 2003, astro-ph/0304309): viz. the images and theISOGAL-DENIS five-wavelength point source catalogue. The main scientific results already derived or in progress are summarized. These include astrometrically calibrated 7 and 15um images,determining structures of resolved sources; identification and properties of interstellar dark clouds; quantification of the infrared extinction law and source dereddening; analysis of red giant and (especially) AGB stellar populations in the central Bulge,determining luminosity,presence of circumstellar dust and mass--loss rate,and source classification,supplemented in some cases by ISO/CVF spectroscopy; detection of young stellar objects of diverse types,especially in the inner Bulge with information about the present and recent star formation rate; identification of foreground sources with mid-IR excess. These results are the subject of about 25 refereed papers published or in preparation.Comment: A&A in press. 19 pages,10 Ps figures; problems with figures fixe

Functional brain defects in a mouse model of a chromosomal t(1;11) translocation that disrupts DISC1 and confers increased risk of psychiatric illness

A balanced t(1;11) translocation that directly disrupts DISC1 is linked to schizophrenia and affective disorders. We previously showed that a mutant mouse, named Der1, recapitulates the effect of the translocation upon DISC1 expression. Here, RNAseq analysis of Der1 mouse brain tissue found enrichment for dysregulation of the same genes and molecular pathways as in neuron cultures generated previously from human t(1;11) translocation carriers via the induced pluripotent stem cell route. DISC1 disruption therefore apparently accounts for a substantial proportion of the effects of the t(1;11) translocation. RNAseq and pathway analysis of the mutant mouse predicts multiple Der1-induced alterations converging upon synapse function and plasticity. Synaptosome proteomics confirmed that the Der1 mutation impacts synapse composition, and electrophysiology found reduced AMPA:NMDA ratio in hippocampal neurons, indicating changed excitatory signalling. Moreover, hippocampal parvalbumin-positive interneuron density is increased, suggesting that the Der1 mutation affects inhibitory control of neuronal circuits. These phenotypes predict that neurotransmission is impacted at many levels by DISC1 disruption in human t(1;11) translocation carriers. Notably, genes implicated in schizophrenia, depression and bipolar disorder by large-scale genetic studies are enriched among the Der1-dysregulated genes, just as we previously observed for the t(1;11) translocation carrier-derived neurons. Furthermore, RNAseq analysis predicts that the Der1 mutation primarily targets a subset of cell types, pyramidal neurons and interneurons, previously shown to be vulnerable to the effects of common schizophrenia-associated genetic variants. In conclusion, DISC1 disruption by the t(1;11) translocation may contribute to the psychiatric disorders of translocation carriers through commonly affected pathways and processes in neurotransmission

The Genetic Association Between ADHD Symptoms and Reading Difficulties: The Role of Inattentiveness and IQ

Previous studies have documented the primarily genetic aetiology for the stronger phenotypic covariance between reading disability and ADHD inattention symptoms, compared to hyperactivity-impulsivity symptoms. In this study, we examined to what extent this covariation could be attributed to “generalist genes” shared with general cognitive ability or to “specialist” genes which may specifically underlie processes linking inattention symptoms and reading difficulties. We used multivariate structural equation modeling on IQ, parent and teacher ADHD ratings and parent ratings on reading difficulties from a general population sample of 1312 twins aged 7.9–10.9 years. The covariance between reading difficulties and ADHD inattention symptoms was largely driven by genetic (45%) and child-specific environment (21%) factors not shared with IQ and hyperactivity-impulsivity; only 11% of the covariance was due to genetic effects common with IQ. Aetiological influences shared among all phenotypes explained 47% of the variance in reading difficulties. The current study, using a general population sample, extends previous findings by showing, first, that the shared genetic variability between reading difficulties and ADHD inattention symptoms is largely independent from genes contributing to general cognitive ability and, second, that child-specific environment factors, independent from IQ, also contribute to the covariation between reading difficulties and inattention symptoms

Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions

While germline copy-number variants (CNVs) contribute to schizophrenia (SCZ) risk, the contribution of somatic CNVs (sCNVs)—present in some but not all cells—remains unknown. We identified sCNVs using blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls, filtering sCNVs at loci recurrently mutated in clonal blood disorders. Likely early-developmental sCNVs were more common in cases (0.91%) than controls (0.51%, p = 2.68e−4), with recurrent somatic deletions of exons 1–5 of the NRXN1 gene in five SCZ cases. Hi-C maps revealed ectopic, allele-specific loops forming between a potential cryptic promoter and non-coding cis-regulatory elements upon 5′ deletions in NRXN1. We also observed recurrent intragenic deletions of ABCB11, encoding a transporter implicated in anti-psychotic response, in five treatment-resistant SCZ cases and showed that ABCB11 is specifically enriched in neurons forming mesocortical and mesolimbic dopaminergic projections. Our results indicate potential roles of sCNVs in SCZ risk

Comparison of Prescribed Physical Therapy to a Home Exercise Program for Pediatric Sports-Related Concussion Patients

The purpose of this retrospective chart review was to compare sports-related concussion (SRC) recovery time in protracted recovery (≥28 days) patients who were prescribed physical therapy (PPT) with those who were only provided a home exercise program (HEP). We hypothesized PPT would be associated with shorter recovery times relative to HEP. Associations were evaluated with multivariable zero-truncated negative binomial regressions. Among the 48 (30.2%) PPT and 111 (69.8%) HEP patients, the majority were female (57.9%), the mean age was 15.3 ± 1.4 (PPT) and 14.2 ± 2.8 (HEP), and time to clinic was a median 6.0 (IQR = 3.0–27.0; PPT) and 7.0 (IQR = 3.0–23.0; HEP) days. After adjusting for demographic (age, sex) and clinical measures (concussion history, convergence, VOMS, PCSS score, and days to clinic), PPT unexpectedly was associated with 1.21 (95% CI: 1.05, 1.41) additional recovery days compared with HEP. One reason for this could be related to patients adhering to the number of a priori prescribed PT sessions which may or may not have aligned with the patient’s symptom resolution. Future research should explore this hypothesis while aiming to evaluate the effect of PPT versus HEP using a randomized design. If confirmed, these findings are encouraging for patients who could not otherwise access or afford specialty rehabilitation