113 research outputs found
Relationship between Strain Effect and Martensitic Transformation in Multifilamentary Nb3Sn Wires
Hot Extrusion of Ceramics
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65963/1/j.1151-2916.1992.tb07206.x.pd
The practice of child and adolescent psychiatry: a survey of early-career psychiatrists in Japan
<p>Abstract</p> <p>Background</p> <p>Child and adolescent psychiatry (CAP), a subspecialty of psychiatry in Japan, is facing a serious workforce shortage. To resolve this situation, the Japanese government has organized a task force and has been working to increase psychiatrists' clinical skills to improve care for children and adolescents with mental health problems. Using an online questionnaire system, the authors have conducted a survey to investigate the perceptions, experiences, and interests of early-career psychiatrists in CAP.</p> <p>Methods</p> <p>The subjects of this study were 182 psychiatrists in Japan whose individual clinical experiences did not exceed 15 years. The authors of this study created an online questionnaire system and e-mailed the URL and login password to all subjects. Respondents anonymously answered the questions. Most questions required an answer indicating a level of agreement scored on a nine-point scale. Responding to the questionnaire was considered to constitute consent, and all respondents' privacy was carefully protected.</p> <p>Results</p> <p>The mean age and clinical psychiatric experience of the subjects were found to be 33.1 ± 4.5 years and 5.43 ± 3.5 years, respectively. On a nine-point scale (with nine being the highest), experience and interest in CAP measured 3.05 ± 1.9 and 5.34 ± 2.5, respectively; further, these two factors showed significant correlation (r = 0.437, p < 0.0001). The mean score for the early-career psychiatrists' confidence in their ability to diagnose and appropriately treat was notably low, at 3.13 ± 1.9.</p> <p>Conclusion</p> <p>Our results demonstrated that early-career psychiatrists self-evaluated their CAP clinical experience as insufficient, and these clinicians' CAP experiences and interests correlated significantly. Therefore, in order to improve child and adolescent medical care, we need to expose young psychiatrists to sufficient CAP cases and explore the factors that could attract them to this field.</p
Modulation of dendritic spine development and plasticity by BDNF and vesicular trafficking: fundamental roles in neurodevelopmental disorders associated with mental retardation and autism
The process of axonal and dendritic development establishes the synaptic circuitry of the central nervous system (CNS) and is the result of interactions between intrinsic molecular factors and the external environment. One growth factor that has a compelling function in neuronal development is the neurotrophin brain-derived neurotrophic factor (BDNF). BDNF participates in axonal and dendritic differentiation during embryonic stages of neuronal development, as well as in the formation and maturation of dendritic spines during postnatal development. Recent studies have also implicated vesicular trafficking of BDNF via secretory vesicles, and both secretory and endosomal trafficking of vesicles containing synaptic proteins, such as neurotransmitter and neurotrophin receptors, in the regulation of axonal and dendritic differentiation, and in dendritic spine morphogenesis. Several genes that are either mutated or deregulated in neurodevelopmental disorders associated with mental retardation have now been identified, and several mouse models of these disorders have been generated and characterized. Interestingly, abnormalities in dendritic and synaptic structure are consistently observed in human neurodevelopmental disorders associated with mental retardation, and in mouse models of these disorders as well. Abnormalities in dendritic and synaptic differentiation are thought to underlie altered synaptic function and network connectivity, thus contributing to the clinical outcome. Here, we review the roles of BDNF and vesicular trafficking in axonal and dendritic differentiation in the context of dendritic and axonal morphological impairments commonly observed in neurodevelopmental disorders associated with mental retardation
DIA1R Is an X-Linked Gene Related to Deleted In Autism-1
Background: Autism spectrum disorders (ASDs) are frequently occurring disorders diagnosed by deficits in three core functional areas: social skills, communication, and behaviours and/or interests. Mental retardation frequently accompanies the most severe forms of ASDs, while overall ASDs are more commonly diagnosed in males. Most ASDs have a genetic origin and one gene recently implicated in the etiology of autism is the Deleted-In-Autism-1 (DIA1) gene. Methodology/Principal Findings: Using a bioinformatics-based approach, we have identified a human gene closely related to DIA1, we term DIA1R (DIA1-Related). While DIA1 is autosomal (chromosome 3, position 3q24), DIA1R localizes to the X chromosome at position Xp11.3 and is known to escape X-inactivation. The gene products are of similar size, with DIA1 encoding 430, and DIA1R 433, residues. At the amino acid level, DIA1 and DIA1R are 62 % similar overall (28 % identical), and both encode signal peptides for targeting to the secretory pathway. Both genes are ubiquitously expressed, including in fetal and adult brain tissue. Conclusions/Significance: Examination of published literature revealed point mutations in DIA1R are associated with X-linked mental retardation (XLMR) and DIA1R deletion is associated with syndromes with ASD-like traits and/or XLMR. Together, these results support a model where the DIA1 and DIA1R gene products regulate molecular traffic through the cellular secretory pathway or affect the function of secreted factors, and functional deficits cause disorders with ASD-lik
Phospholipase D Family Member 4, a Transmembrane Glycoprotein with No Phospholipase D Activity, Expression in Spleen and Early Postnatal Microglia
BACKGROUND: Phospholipase D (PLD) catalyzes conversion of phosphatidylcholine into choline and phosphatidic acid, leading to a variety of intracellular signal transduction events. Two classical PLDs, PLD1 and PLD2, contain phosphatidylinositide-binding PX and PH domains and two conserved His-x-Lys-(x)(4)-Asp (HKD) motifs, which are critical for PLD activity. PLD4 officially belongs to the PLD family, because it possesses two HKD motifs. However, it lacks PX and PH domains and has a putative transmembrane domain instead. Nevertheless, little is known regarding expression, structure, and function of PLD4. METHODOLOGY/PRINCIPAL FINDINGS: PLD4 was analyzed in terms of expression, structure, and function. Expression was analyzed in developing mouse brains and non-neuronal tissues using microarray, in situ hybridization, immunohistochemistry, and immunocytochemistry. Structure was evaluated using bioinformatics analysis of protein domains, biochemical analyses of transmembrane property, and enzymatic deglycosylation. PLD activity was examined by choline release and transphosphatidylation assays. Results demonstrated low to modest, but characteristic, PLD4 mRNA expression in a subset of cells preferentially localized around white matter regions, including the corpus callosum and cerebellar white matter, during the first postnatal week. These PLD4 mRNA-expressing cells were identified as Iba1-positive microglia. In non-neuronal tissues, PLD4 mRNA expression was widespread, but predominantly distributed in the spleen. Intense PLD4 expression was detected around the marginal zone of the splenic red pulp, and splenic PLD4 protein recovered from subcellular membrane fractions was highly N-glycosylated. PLD4 was heterologously expressed in cell lines and localized in the endoplasmic reticulum and Golgi apparatus. Moreover, heterologously expressed PLD4 proteins did not exhibit PLD enzymatic activity. CONCLUSIONS/SIGNIFICANCE: Results showed that PLD4 is a non-PLD, HKD motif-carrying, transmembrane glycoprotein localized in the endoplasmic reticulum and Golgi apparatus. The spatiotemporally restricted expression patterns suggested that PLD4 might play a role in common function(s) among microglia during early postnatal brain development and splenic marginal zone cells
Genome-Wide Analyses of Exonic Copy Number Variants in a Family-Based Study Point to Novel Autism Susceptibility Genes
The genetics underlying the autism spectrum disorders (ASDs) is complex and remains poorly understood. Previous work has demonstrated an important role for structural variation in a subset of cases, but has lacked the resolution necessary to move beyond detection of large regions of potential interest to identification of individual genes. To pinpoint genes likely to contribute to ASD etiology, we performed high density genotyping in 912 multiplex families from the Autism Genetics Resource Exchange (AGRE) collection and contrasted results to those obtained for 1,488 healthy controls. Through prioritization of exonic deletions (eDels), exonic duplications (eDups), and whole gene duplication events (gDups), we identified more than 150 loci harboring rare variants in multiple unrelated probands, but no controls. Importantly, 27 of these were confirmed on examination of an independent replication cohort comprised of 859 cases and an additional 1,051 controls. Rare variants at known loci, including exonic deletions at NRXN1 and whole gene duplications encompassing UBE3A and several other genes in the 15q11–q13 region, were observed in the course of these analyses. Strong support was likewise observed for previously unreported genes such as BZRAP1, an adaptor molecule known to regulate synaptic transmission, with eDels or eDups observed in twelve unrelated cases but no controls (p = 2.3×10−5). Less is known about MDGA2, likewise observed to be case-specific (p = 1.3×10−4). But, it is notable that the encoded protein shows an unexpectedly high similarity to Contactin 4 (BLAST E-value = 3×10−39), which has also been linked to disease. That hundreds of distinct rare variants were each seen only once further highlights complexity in the ASDs and points to the continued need for larger cohorts
Relationships between Gene Expression and Brain Wiring in the Adult Rodent Brain
We studied the global relationship between gene expression and neuroanatomical connectivity in the adult rodent brain. We utilized a large data set of the rat brain “connectome” from the Brain Architecture Management System (942 brain regions and over 5000 connections) and used statistical approaches to relate the data to the gene expression signatures of 17,530 genes in 142 anatomical regions from the Allen Brain Atlas. Our analysis shows that adult gene expression signatures have a statistically significant relationship to connectivity. In particular, brain regions that have similar expression profiles tend to have similar connectivity profiles, and this effect is not entirely attributable to spatial correlations. In addition, brain regions which are connected have more similar expression patterns. Using a simple optimization approach, we identified a set of genes most correlated with neuroanatomical connectivity, and find that this set is enriched for genes involved in neuronal development and axon guidance. A number of the genes have been implicated in neurodevelopmental disorders such as autistic spectrum disorder. Our results have the potential to shed light on the role of gene expression patterns in influencing neuronal activity and connectivity, with potential applications to our understanding of brain disorders. Supplementary data are available at http://www.chibi.ubc.ca/ABAMS
Locus of emotion influences psychophysiological reactions to music
It is now widely accepted that the perception of emotional expression in music can be vastly different from the feelings evoked by it. However, less understood is how the locus of emotion affects the experience of music, that is how the act of perceiving the emotion in music compares with the act of assessing the emotion induced in the listener by the music. In the current study, we compared these two emotion loci based on the psychophysiological response of 40 participants listening to 32 musical excerpts taken from movie soundtracks. Facial electromyography, skin conductance, respiration and heart rate were continuously measured while participants were required to assess either the emotion expressed by, or the emotion they felt in response to the music. Using linear mixed effects models, we found a higher mean response in psychophysiological measures for the “perceived” than the “felt” task. This result suggested that the focus on one’s self distracts from the music, leading to weaker bodily reactions during the “felt” task. In contrast, paying attention to the expression of the music and consequently to changes in timbre, loudness and harmonic progression enhances bodily reactions. This study has methodological implications for emotion induction research using psychophysiology and the conceptualization of emotion loci. Firstly, different tasks can elicit different psychophysiological responses to the same stimulus and secondly, both tasks elicit bodily responses to music. The latter finding questions the possibility of a listener taking on a purely cognitive mode when evaluating emotion expression
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