266 resultados para copy number variant


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A measurement campaign was conducted from 3 to 19 December 2012 at an urban site of Brisbane, Australia. Size distribution of ions and particle number concentrations were measured to investigate the influence of particle formation and biomass burning on atmospheric ion and particle concentrations. Overall ion and particle number concentrations during the measurement period were found to be (-1.2 x 103 cm-3 | +1.6 x 103 cm-3) and 4.4 x 103, respectively. The results of correlation analysis between concentrations of ions and nitrogen oxides indicated that positive and negative ions originated from similar sources, and that vehicle exhaust emissions had a more significant influence on intermediate/large ions, while cluster ions rapidly attached to larger particles once emitted into the atmosphere. Diurnal variations in ion concentration suggested the enrichment of intermediate and large ions on new particle formation event days, indicating that they were involved in the particle formation processes. Elevated total ions, particularly larger ions, and particle number concentrations were found during biomass burning episodes. This could be due to the attachment of cluster ions onto accumulation mode particles or production of charged particles from biomass burning, which were in turn transported to the measurement site. The results of this work enhance scientific understanding of the sources of atmospheric ions in an urban environment, as well as their interactions with particles during particle formation processes.

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In the development of technological systems the focus of system analysis is often on the sub-system that delivers insufficient performance – i.e. the reverse salient – which subsequently limits the performance of the system in its entirety. The reverse salient is therefore a useful concept in the study of technological systems and while the literature holds numerous accounts of its use, it is not known how often, in which streams of literature, and in what type of application the concept has been utilized by scholars since its introduction by Thomas Hughes in 1983. In this paper we employ bibliometric citation analysis between 1983 and 2008, inclusively, to study the impact of the reverse salient concept in the literature at large as well as study the dissemination of the concept into different fields of research. The study results show continuously growing number of concept citations in the literature over time as well as increasing concept diffusion into different research areas. The analysis of article contents additionally suggests the opportunity for scholars to engage in deeper conceptual application. Finally, the continuing increase in the number of citations highlights the importance of the reverse salient concept to scholars and practitioners.

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The NTRK1 gene (also known as TRKA) encodes a high-affinity receptor for NGF, a neurotrophin involved in nervous system development and myelination. NTRK1 has been implicated in neurological function via links between the T allele at rs6336 (NTRK1-T) and schizophrenia risk. A variant in the neurotrophin gene, BDNF, was previously associated with white matter integrity in young adults, highlighting the importantce of neurotrophins to white matter development. We hypothesized that NTRK1-T would relate to lower fractional anisotropy in healthy adults. We scanned 391 healthy adult human twins and their siblings (mean age: 23.6 ± 2.2 years; 31 NTRK1-T carriers, 360 non-carriers) using 105-gradient diffusion tensor imaging at 4 tesla. We evaluated in brain white matter how NTRK1-T and NTRK1 rs4661063 allele A (rs4661063-A, which is in moderate linkage disequilibrium with rs6336) related to voxelwise fractional anisotropy-acommondiffusion tensor imaging measure of white matter microstructure. We used mixed-model regression to control for family relatedness, age, and sex. The sample was split in half to test reproducibility of results. The false discovery rate method corrected for voxelwise multiple comparisons. NTRK1-T and rs4661063-A correlated with lower white matter fractional anisotropy, independent of age and sex (multiple-comparisons corrected: false discovery rate critical p=0.038 forNTRK1-Tand0.013 for rs4661063-A). In each half-sample, theNTRK1-T effectwasreplicated in the cingulum, corpus callosum, superior and inferior longitudinal fasciculi, inferior fronto-occipital fasciculus, superior corona radiata, and uncinate fasciculus. Our results suggest that NTRK1-T is important for developing white matter microstructure.

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Obesity is a crucial public health issue in developed countries, with implications for cardiovascular and brain health as we age. A number of commonly-carried genetic variants are associated with obesity. Here we aim to see whether variants in obesity-associated genes - NEGR1, FTO, MTCH2, MC4R, LRRN6C, MAP2K5, FAIM2, SEC16B, ETV5, BDNF- AS, ATXN2L, ATP2A1, KCTD15, and TNN13K - are associated with white matter microstructural properties, assessed by high angular resolution diffusion imaging (HARDI) in young healthy adults between 20 and 30. years of age from the Queensland Twin Imaging study (QTIM). We began with a multi-locus approach testing how a number of common genetic risk factors for obesity at the single nucleotide polymorphism (SNP) level may jointly influence white matter integrity throughout the brain and found a wide spread genetic effect. Risk allele rs2815752 in NEGR1 was most associated with lower white matter integrity across a substantial portion of the brain. Across the area of significance in the bilateral posterior corona radiata, each additional copy of the risk allele was associated with a 2.2% lower average FA. This is the first study to find an association between an obesity risk gene and differences in white matter integrity. As our subjects were young and healthy, our results suggest that NEGR1 has effects on brain structure independent of its effect on obesity.

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Deficits in lentiform nucleus volume and morphometry are implicated in a number of genetically influenced disorders, including Parkinson's disease, schizophrenia, and ADHD. Here we performed genome-wide searches to discover common genetic variants associated with differences in lentiform nucleus volume in human populations. We assessed structural MRI scans of the brain in two large genotyped samples: the Alzheimer's Disease Neuroimaging Initiative (ADNI; N = 706) and the Queensland Twin Imaging Study (QTIM; N = 639). Statistics of association from each cohort were combined meta-analytically using a fixed-effects model to boost power and to reduce the prevalence of false positive findings. We identified a number of associations in and around the flavin-containing monooxygenase (FMO) gene cluster. The most highly associated SNP, rs1795240, was located in the FMO3 gene; after meta-analysis, it showed genome-wide significant evidence of association with lentiform nucleus volume (PMA = 4. 79 × 10-8). This commonly-carried genetic variant accounted for 2. 68 % and 0. 84 % of the trait variability in the ADNI and QTIM samples, respectively, even though the QTIM sample was on average 50 years younger. Pathway enrichment analysis revealed significant contributions of this gene to the cytochrome P450 pathway, which is involved in metabolizing numerous therapeutic drugs for pain, seizures, mania, depression, anxiety, and psychosis. The genetic variants we identified provide replicated, genome-wide significant evidence for the FMO gene cluster's involvement in lentiform nucleus volume differences in human populations.

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Aberrant connectivity is implicated in many neurological and psychiatric disorders, including Alzheimer's disease and schizophrenia. However, other than a few disease-associated candidate genes, we know little about the degree to which genetics play a role in the brain networks; we know even less about specific genes that influence brain connections. Twin and family-based studies can generate estimates of overall genetic influences on a trait, but genome-wide association scans (GWASs) can screen the genome for specific variants influencing the brain or risk for disease. To identify the heritability of various brain connections, we scanned healthy young adult twins with high-field, highangular resolution diffusion MRI. We adapted GWASs to screen the brain's connectivity pattern, allowing us to discover genetic variants that affect the human brain's wiring. The association of connectivity with the SPON1 variant at rs2618516 on chromosome 11 (11p15.2) reached connectome-wide, genome-wide significance after stringent statistical corrections were enforced, and it was replicated in an independent subsample. rs2618516 was shown to affect brain structure in an elderly population with varying degrees of dementia. Older people who carried the connectivity variant had significantly milder clinical dementia scores and lower risk of Alzheimer's disease. As a posthoc analysis, we conducted GWASs on several organizational and topological network measures derived from the matrices to discover variants in and around genes associated with autism (MACROD2), development (NEDD4), and mental retardation (UBE2A) significantly associated with connectivity. Connectome-wide, genome-wide screening offers substantial promise to discover genes affecting brain connectivity and risk for brain diseases.

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Delta opioid receptors are implicated in a variety of psychiatric and neurological disorders. These receptors play a key role in the reinforcing properties of drugs of abuse, and polymorphisms in OPRD1 (the gene encoding delta opioid receptors) are associated with drug addiction. Delta opioid receptors are also involved in protecting neurons against hypoxic and ischemic stress. Here, we first examined a large sample of 738 elderly participants with neuroimaging and genetic data from the Alzheimer's Disease Neuroimaging Initiative. We hypothesized that common variants in OPRD1 would be associated with differences in brain structure, particularly in regions relevant to addictive and neurodegenerative disorders. One very common variant (rs678849) predicted differences in regional brain volumes. We replicated the association of this single-nucleotide polymorphism with regional tissue volumes in a large sample of young participants in the Queensland Twin Imaging study. Although the same allele was associated with reduced volumes in both cohorts, the brain regions affected differed between the two samples. In healthy elderly, exploratory analyses suggested that the genotype associated with reduced brain volumes in both cohorts may also predict cerebrospinal fluid levels of neurodegenerative biomarkers, but this requires confirmation. If opiate receptor genetic variants are related to individual differences in brain structure, genotyping of these variants may be helpful when designing clinical trials targeting delta opioid receptors to treat neurological disorders.

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Several common genetic variants influence cholesterol levels, which play a key role in overall health. Myelin synthesis and maintenance are highly sensitive to cholesterol concentrations, and abnormal cholesterol levels increase the risk for various brain diseases, including Alzheimer's disease. We report significant associations between higher serum cholesterol (CHOL) and high-density lipoprotein levels and higher fractional anisotropy in 403 young adults (23.8 ± 2.4years) scanned with diffusion imaging and anatomic magnetic resonance imaging at 4Tesla. By fitting a multi-locus genetic model within white matter areas associated with CHOL, we found that a set of 18 cholesterol-related, single-nucleotide polymorphisms implicated in Alzheimer's disease risk predicted fractional anisotropy. We focused on the single-nucleotide polymorphism with the largest individual effects, CETP (rs5882), and found that increased G-allele dosage was associated with higher fractional anisotropy and lower radial and mean diffusivities in voxel-wise analyses of the whole brain. A follow-up analysis detected white matter associations with rs5882 in the opposite direction in 78 older individuals (74.3 ± 7.3years). Cholesterol levels may influence white matter integrity, and cholesterol-related genes may exert age-dependent effects on the brain.

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Developing nano/micro-structures which can effectively upgrade the intriguing properties of electrode materials for energy storage devices is always a key research topic. Ultrathin nanosheets were proved to be one of the potential nanostructures due to their high specific surface area, good active contact areas and porous channels. Herein, we report a unique hierarchical micro-spherical morphology of well-stacked and completely miscible molybdenum disulfide (MoS2) nanosheets and graphene sheets, were successfully synthesized via a simple and industrial scale spray-drying technique to take the advantages of both MoS2 and graphene in terms of their high practical capacity values and high electronic conductivity, respectively. Computational studies were performed to understand the interfacial behaviour of MoS2 and graphene, which proves high stability of the composite with high interfacial binding energy (−2.02 eV) among them. Further, the lithium and sodium storage properties have been tested and reveal excellent cyclic stability over 250 and 500 cycles, respectively, with the highest initial capacity values of 1300 mAh g−1 and 640 mAh g−1 at 0.1 A g−1.

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Human expert analyses are commonly used in bioacoustic studies and can potentially limit the reproducibility of these results. In this paper, a machine learning method is presented to statistically classify avian vocalizations. Automated approaches were applied to isolate bird songs from long field recordings, assess song similarities, and classify songs into distinct variants. Because no positive controls were available to assess the true classification of variants, multiple replicates of automatic classification of song variants were analyzed to investigate clustering uncertainty. The automatic classifications were more similar to the expert classifications than expected by chance. Application of these methods demonstrated the presence of discrete song variants in an island population of the New Zealand hihi (Notiomystis cincta). The geographic patterns of song variation were then revealed by integrating over classification replicates. Because this automated approach considers variation in song variant classification, it reduces potential human bias and facilitates the reproducibility of the results.

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This research investigated the use of DNA fingerprinting to characterise the bacteria Streptococcus pneumoniae or pneumococcus, and hence gain insight into the development of new vaccines or antibiotics. Different bacterial DNA fingerprinting methods were studied, and a novel method was developed and validated, which characterises different cell coatings that pneumococci produce. This method was used to study the epidemiology of pneumococci in Queensland before and after the introduction of the current pneumococcal vaccine. This study demonstrated that pneumococcal disease is highly prevalent in children under four years, that the bacteria can `switch' its cell coating to evade the vaccine, and that some DNA fingerprinting methods are more discriminatory than others. This has an impact on understanding which strains are more prone to cause invasive disease. Evidence of the excellent research findings have been published in high impact internationally refereed journals.

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Objective We examined whether exposure to a greater number of fruits, vegetables, and noncore foods (ie, nutrient poor and high in saturated fats, added sugars, or added salt) at age 14 months was related to children’s preference for and intake of these foods as well as maternal-reported food fussiness and measured child weight status at age 3.7 years. Methods This study reports secondary analyses of longitudinal data from mothers and children (n=340) participating in the NOURISH randomized controlled trial. Exposure was quantified as the number of food items (n=55) tried by a child from specified lists at age 14 months. At age 3.7 years, food preferences, intake patterns, and fussiness (also at age 14 months) were assessed using maternal-completed, established questionnaires. Child weight and length/height were measured by study staff at both age points. Multivariable linear regression models were tested to predict food preferences, intake patterns, fussy eating, and body mass index z score at age 3.7 years adjusting for a range of maternal and child covariates. Results Having tried a greater number of vegetables, fruits, and noncore foods at age 14 months predicted corresponding preferences and higher intakes at age 3.7 years but did not predict child body mass index z score. Adjusting for fussiness at age 14 months, having tried more vegetables at age 14 months was associated with lower fussiness at age 3.7 years. Conclusions These prospective analyses support the hypothesis that early taste and texture experiences influence subsequent food preferences and acceptance. These findings indicate introduction to a variety of fruits and vegetables and limited noncore food exposure from an early age are important strategies to improve later diet quality.

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This research investigated differences and associations in performance in number processing and executive function for children attending primary school in a large Australian metropolitan city. In a cross-sectional study, performance of 25 children in the first full-time year of school, (Prep; mean age = 5.5 years) and 21 children in Year 3 (mean age = 8.5 years) completed three number processing tasks and three executive function tasks. Year 3 children consistently outperformed the Prep year children on measures of accuracy and reaction time, on the tasks of number comparison, calculation, shifting, and inhibition but not on number line estimation. The components of executive function (shifting, inhibition, and working memory) showed different patterns of correlation to performance on number processing tasks across the early years of school. Findings could be used to enhance teachers’ understanding about the role of the cognitive processes employed by children in numeracy learning, and so inform teachers’ classroom practices.

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Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 × 10 -11; odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.