Neurexin-1 and Frontal Lobe White Matter: An Overlapping Intermediate Phenotype for Schizophrenia and Autism Spectrum Disorders

Background: Structural variation in the neurexin-1 (NRXN1) gene increases risk for both autism spectrum disorders (ASD) and schizophrenia. However, the manner in which NRXN1 gene variation may be related to brain morphology to confer risk for ASD or schizophrenia is unknown. Method/Principal Findings: 53 healthy individuals between 18–59 years of age were genotyped at 11 single nucleotide polymorphisms of the NRXN1 gene. All subjects received structural MRI scans, which were processed to determine cortical gray and white matter lobar volumes, and volumes of striatal and thalamic structures. Each subject’s sensorimotor function was also assessed. The general linear model was used to calculate the influence of genetic variation on neural and cognitive phenotypes. Finally, in silico analysis was conducted to assess potential functional relevance of any polymorphisms associated with brain measures. A polymorphism located in the 39 untranslated region of NRXN1 significantly influenced white matter volumes in whole brain and frontal lobes after correcting for total brain volume, age and multiple comparisons. Follow-up in silico analysis revealed that this SNP is a putative microRNA binding site that may be of functional significance in regulating NRXN1 expression. This variant also influenced sensorimotor performance, a neurocognitive function impaired in both ASD and schizophrenia. Conclusions: Our findings demonstrate that the NRXN1 gene, a vulnerability gene for SCZ and ASD, influences brai

Using the canary genome to decipher the evolution of hormone-sensitive gene regulation in seasonal singing birds

Background While the song of all songbirds is controlled by the same neural circuit, the hormone dependence of singing behavior varies greatly between species. For this reason, songbirds are ideal organisms to study ultimate and proximate mechanisms of hormone-dependent behavior and neuronal plasticity. Results We present the high quality assembly and annotation of a female 1.2-Gbp canary genome. Whole genome alignments between the canary and 13 genomes throughout the bird taxa show a much-conserved synteny, whereas at the single-base resolution there are considerable species differences. These differences impact small sequence motifs like transcription factor binding sites such as estrogen response elements and androgen response elements. To relate these species-specific response elements to the hormone-sensitivity of the canary singing behavior, we identify seasonal testosterone-sensitive transcriptomes of major song-related brain regions, HVC and RA, and find the seasonal gene networks related to neuronal differentiation only in the HVC. Testosterone-sensitive up-regulated gene networks of HVC of singing males concerned neuronal differentiation. Among the testosterone-regulated genes of canary HVC, 20% lack estrogen response elements and 4 to 8% lack androgen response elements in orthologous promoters in the zebra finch. Conclusions The canary genome sequence and complementary expression analysis reveal intra-regional evolutionary changes in a multi-regional neural circuit controlling seasonal singing behavior and identify gene evolution related to the hormone-sensitivity of this seasonal singing behavior. Such genes that are testosterone- and estrogen-sensitive specifically in the canary and that are involved in rewiring of neurons might be crucial for seasonal re-differentiation of HVC underlying seasonal song patterning

Theory, a lost character? As presented in general practice education research papers

OBJECTIVES: The use of theory in research is reflected in its presence in research writing. Theory is often an ineffective presence in medical education research papers. To progress the effective use of theory in medical education, we need to understand how theory is presented in research papers. This study aims to elicit how theory is being written into general practice (GP) vocational education research papers in order to elucidate how theory might be more effectively used. This has relevance for the field of GP and for medical education more broadly. METHODS: This is a scoping review of the presentation of theory in GP vocational education research published between 2013 and 2017. An interpretive approach is taken. We frame research papers as a form of narrative and draw on the theories of Aristotle's poetics and Campbell's monomyth. We seek parallels between the roles of theory in a research story and theories of characterisation. RESULTS: A total of 23 papers were selected. Theories of 'reflective learning', 'communities of practice' and 'adult learning' were most used. Six tasks were assigned to theory: to align with a position; to identify a research problem; to serve as a vehicle for an idea; to provide a methodological tool; to interpret findings, and to represent an object of examination. The prominence of theory in the papers ranged from cameo to major roles. Depending on the way theory was used and the audience, theory had different impacts. There were parallels between the tasks assigned to theory and the roles of four of Campbell's archetypal characters. Campbell's typology offers guidance on how theory can be used in research paper 'stories'. CONCLUSIONS: Theory can be meaningfully present in the story of a research paper if it is assigned a role in a deliberate way and this is articulated. Attention to the character development of theory and its positioning in the research story is important