Genetic influences on brain asymmetry: A DTI study of 374 twins and siblings

Brain asymmetry, or the structural and functional specialization of each brain hemisphere, has fascinated neuroscientists for over a century. Even so, genetic and environmental factors that influence brain asymmetry are largely unknown. Diffusion tensor imaging (DTI) now allows asymmetry to be studied at a microscopic scale by examining differences in fiber characteristics across hemispheres rather than differences in structure shapes and volumes. Here we analyzed 4. Tesla DTI scans from 374 healthy adults, including 60 monozygotic twin pairs, 45 same-sex dizygotic pairs, and 164 mixed-sex DZ twins and their siblings; mean age: 24.4 years ± 1.9 SD). All DTI scans were nonlinearly aligned to a geometrically-symmetric, population-based image template. We computed voxel-wise maps of significant asymmetries (left/right differences) for common diffusion measures that reflect fiber integrity (fractional and geodesic anisotropy; FA, GA and mean diffusivity, MD). In quantitative genetic models computed from all same-sex twin pairs (N=210 subjects), genetic factors accounted for 33% of the variance in asymmetry for the inferior fronto-occipital fasciculus, 37% for the anterior thalamic radiation, and 20% for the forceps major and uncinate fasciculus (all L > R). Shared environmental factors accounted for around 15% of the variance in asymmetry for the cortico-spinal tract (R > L) and about 10% for the forceps minor (L > R). Sex differences in asymmetry (men > women) were significant, and were greatest in regions with prominent FA asymmetries. These maps identify heritable DTI-derived features, and may empower genome-wide searches for genetic polymorphisms that influence brain asymmetry.

Genetic influences on sulcal patterns of the brain

We present a shape-space approach for analyzing genetic influences on the shapes of the sulcal folding patterns on the cortex. Sulci are represented as continuously parameterized functions in a shape space, and shape differences between sulci are obtained via geodesics between them. The resulting statistical shape analysis framework is used not only to construct populations averages, but also used to compute meaningful correlations within and across groups of sulcal shapes. More importantly, we present a new algorithm that extends the traditional Euclidean estimate of the intra-class correlation to the geometric shape space, thereby allowing us to study heritability of sulcal shape traits for a population of 193 twin pairs. This new methodology reveals strong genetic influences on the sulcal geometry of the cortex.

Discovery and replication of gene influences on brain structure using LASSO regression

We implemented least absolute shrinkage and selection operator (LASSO) regression to evaluate gene effects in genome-wide association studies (GWAS) of brain images, using an MRI-derived temporal lobe volume measure from 729 subjects scanned as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Sparse groups of SNPs in individual genes were selected by LASSO, which identifies efficient sets of variants influencing the data. These SNPs were considered jointly when assessing their association with neuroimaging measures. We discovered 22 genes that passed genome-wide significance for influencing temporal lobe volume. This was a substantially greater number of significant genes compared to those found with standard, univariate GWAS. These top genes are all expressed in the brain and include genes previously related to brain function or neuropsychiatric disorders such as MACROD2, SORCS2, GRIN2B, MAGI2, NPAS3, CLSTN2, GABRG3, NRXN3, PRKAG2, GAS7, RBFOX1, ADARB2, CHD4, and CDH13. The top genes we identified with this method also displayed significant and widespread post hoc effects on voxelwise, tensor-based morphometry (TBM) maps of the temporal lobes. The most significantly associated gene was an autism susceptibility gene known as MACROD2.We were able to successfully replicate the effect of the MACROD2 gene in an independent cohort of 564 young, Australian healthy adult twins and siblings scanned with MRI (mean age: 23.8±2.2 SD years). Our approach powerfully complements univariate techniques in detecting influences of genes on the living brain.

Tensor-based analysis of genetic influences on brain integrity using DTI in 100 twins

Information from the full diffusion tensor (DT) was used to compute voxel-wise genetic contributions to brain fiber microstructure. First, we designed a new multivariate intraclass correlation formula in the log-Euclidean framework. We then analyzed used the full multivariate structure of the tensor in a multivariate version of a voxel-wise maximum-likelihood structural equation model (SEM) that computes the variance contributions in the DTs from genetic (A), common environmental (C) and unique environmental (E) factors. Our algorithm was tested on DT images from 25 identical and 25 fraternal twin pairs. After linear and fluid registration to a mean template, we computed the intraclass correlation and Falconer's heritability statistic for several scalar DT-derived measures and for the full multivariate tensors. Covariance matrices were found from the DTs, and inputted into SEM. Analyzing the full DT enhanced the detection of A and C effects. This approach should empower imaging genetics studies that use DTI.

How religiosity influences consumption: The impact of consumer religiosity on perceptions of psychological and social risk

For some people, religion is an important influence in decision-making. This thesis investigates the relationship between the religiosity of consumers and their perceived risk in adopting new products. Two studies gathered data from religious consumers living in Saudi Arabia, Australia, Canada, New Zealand, the UK and the USA. The results confirm the significant impact of religion on perceived risk, and suggest why this may lead to delays in adoption. Theoretically, these studies provide a better explanation of how religion influences consumption decisions, and offer brand managers options to improve the adoption of new products in religious markets.

The influences of Bislama on lexical choices in children's written English: A case study in Vanuatu

In Vanuatu, there have been concerns that Bislama (the national language of Vanuatu and a creole with an adapted English vocabulary) hinders English language learning. Consequently, previous language policy restricted the use of Bislama in schools. The findings from this study offer significant insights and implications that may assist teachers with using Bislama in their classrooms in a way that furthers English language and literacy development. This research is timely because the Vanuatu Government have recently implemented a new language policy that allows the vernacular island languages and Bislama to be used as a linguistic resource in schools.

Exploring the influences of country-level factors on mature-aged women’s drink driving attitudes

The current study examined drink driving attitudes among mature-aged women in Sweden and Australia, two countries with a Blood Alcohol Concentration (BAC) limit of 0.02% and 0.05%, respectively. The study aimed to identify attitudes that might influence drink driving tendency among this group of women and further show how these attitudes vary across countries. Using an ethnographic approach, 15 mature-aged women (Sweden: mean age = 52.5years, SD = 4.8; Australia: mean age 52.2 years, SD = 3.4) were interviewed in each country. General patterns and themes from the data were developed using thematic analysis methods. The findings indicate that while women in both countries viewed drink driving negatively, the understanding of what the concept entailed differed between the two samples. The Swedish women appeared to cognitively separate alcohol consumption and driving, and consequently, drink driving was often spoken of as driving after any alcohol consumption. The Australian women’s understanding of drink driving was more closely related to the legal BAC limit. However, for some Australian women, a “Grey Zone” existed, which denoted driving with a BAC of just above the enforceable limit. While illegal, these instances were subjectively seen as similar to driving with a BAC of just under the legal limit and therefore not morally reprehensible. The practice of cognitively separating drinking from driving appeared to have implications for the tendency to drink and drive among the interviewed women. These findings are discussed in relation to current policy and legislation in Australia and the need for further research into mature-aged women’s drink driving is outlined.

WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk

We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ~2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr>Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of -0.11 standard deviations [SD] per C allele, P = 6.2×10-9). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly>Arg), also had genome-wide significant association with forearm BMD (-0.14 SD per C allele, P = 2.3×10-12, and -0.16 SD per G allele, P = 1.2×10-15, respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide significant increased risk of forearm fracture (OR = 1.33, P = 7.3×10-9), with genome-wide suggestive signals from the two missense variants in WNT16 (rs2908004: OR = 1.22, P = 4.9×10-6 and rs2707466: OR = 1.22, P = 7.2×10-6). We next generated a homozygous mouse with targeted disruption of Wnt16. Female Wnt16-/- mice had 27% (P<0.001) thinner cortical bones at the femur midshaft, and bone strength measures were reduced between 43%-61% (6.5×10-13<P<5.9×10-4) at both femur and tibia, compared with their wild-type littermates. Natural variation in humans and targeted disruption in mice demonstrate that WNT16 is an important determinant of CBT, BMD, bone strength, and risk of fracture. © 2012 Zheng et al.

Temporal and environmental influences on the vocal behaviour of a nocturnal bird

Temporal and environmental variation in vocal activity can provide information on avian behaviour and call function not available to short-term experimental studies. Intersexual differences in this variation can provide insight into selection effects. Yet factors influencing vocal behaviour have not been assessed in many birds, even those monitored by acoustic methods. This applies to the New Zealand kiwi (Apterygidae), for which call censuses are used extensively in conservation monitoring, yet which have poorly understood acoustic ecology. We investigated little spotted kiwi Apteryx owenii vocal behaviour over 3 yr, measuring influences on vocal activity in both sexes from time of night, season, weather conditions and lunar cycle. We tested hypotheses that call rate variation reflects call function, foraging efficiency, historic predation risk and variability in sound transmission, and that there are inter-sexual differences in call function. Significant seasonal variation showed that vocalisations were important in kiwi reproduction, and inter-sexual synchronisation of call rates indicated that contact, pair-bonding or resource defence were key functions. All weather variables significantly affected call rates, with elevated calling during increased humidity and ground moisture indicating a relation between vocal activity and foraging conditions. A significant decrease in calling activity on cloudy nights, combined with no moonlight effect, suggests an impact of light pollution in this species. These influences on vocal activity provide insight into kiwi call function, have direct consequences for conservation monitoring of kiwi, and have wider implications in understanding vocal behaviour in a range of nocturnal birds

Social influences on risky driving behaviours among young drivers in Oman

Young drivers represent approximately 20% of the Omani population, yet account for over one third of crash injuries and fatalities on Oman's roads. Internationally, research has demonstrated that social influences play an important role within young driver safety, however, there is little research examining this within Arab gulf countries. This study sought to explore young driver behaviour using Akers' social learning theory. A self-report survey was conducted by 1319 (72.9% male and 27.1% female) young drivers aged 17-25 years. A hierarchical regression model was used to investigate the contribution of social learning variables (norms and behaviour of significant others, personal attitudes towards risky behaviour, imitation of significant others, beliefs about the rewards and punishments offered by risky behaviour), socio-demographic characteristics (age and gender), driving experience (initial training, time driving and previous driving without supervision) and sensitivity to rewards and punishments upon the self-reported risky driving behaviours of young drivers. It was found that 39.6% of the young drivers reported that they have been involved in at least one crash since the issuance of their driving licence and they were considered ‘at fault’ in 60.7% of these crashes. The hierarchical multiple regression models revealed that socio-demographic characteristics and driving experience alone explained 14.2% of the variance in risky driving behaviour. By introducing social learning factors into the model a further 37.0% of variance was explained. Finally, 7.9% of the variance in risky behaviour could be explained by including individual sensitivity to rewards and punishments. These findings and the implications are discussed.

Socio-cultural influences on vehicle defects in the Omani heavy vehicle industry

With recent economic growth in Oman there is increased use of heavy vehicles, presenting an increase in heavy vehicle crashes, associated fatalities and injuries. Vehicle defects cause a significant number of heavy vehicle crashes in Oman and increase the likelihood of fatalities. The aim of this study is to explore factors contributing to driving with vehicle defects in the Omani heavy vehicle industry. A series of qualitative participants observations were conducted in Oman with 49 drivers. These observations also involved discussion and interviews with drivers. The observations occurred at two road-side locations where heavy vehicle drivers gather for eating, resting, vehicle check-up, etc. Data collection was conducted over a three week period. The data was analysed using thematic analysis. A broad number of factors were identified as contributing to the driving of vehicles with defects. Participants indicated that tyres and vehicle mechanical faults were a common issue in the heavy vehicle industry. Participants regularly reported that their companies use cheap, poor quality standards parts and conducted minimal maintenance. Drivers also indicated that they felt powerless to resist company pressure to drive vehicles with known faults. In addition, drivers reported that traffic police were generally in effective and lacked skill to appropriately conduct roadside inspection on trucks. Further, participants stated that it was possible for companies to avoid being fined during annual or roadside vehicle inspections if members of the company knew the traffic police officer conducting the inspection. Moreover, fines issued by police are generally directed to the individual driver rather than being applied to the company, thus providing no incentive for companies to address vehicle faults. The implications of the findings are discussed.

'How much love are you going to give this brand?' Lifestyle journalists on commercial influences in their work

The news increasingly provides help, advice, guidance, and information about the management of self and everyday life, in addition to its traditional role in political communication. Yet such forms of journalism are still regularly denigrated in scholarly discussions, as they often deviate from normative ideals. This is particularly true in lifestyle journalism, where few studies have examined the impact of commercial influences. Through in-depth interviews with 89 Australian and German lifestyle journalists, this paper explores the ways in which journalists experience how the lifestyle industries try to shape their daily work, and how these journalists deal with these influences. We find that lifestyle journalists are in a constant struggle over the control of editorial content, and their responses to increasing commercial pressures vary between resistance and resignation. This has implications for our understanding of journalism as a whole in that it broadens it beyond traditional conceptualizations associated with political journalism.

A genetic variant of MDM4 influences regulation by multiple microRNAs in prostate cancer

The oncogene MDM4, also known as MDMX or HDMX, contributes to cancer susceptibility and progression through its capacity to negatively regulate a range of genes with tumour-suppressive functions. As part of a recent genome-wide association study it was determined that the A-allele of the rs4245739 SNP (A>C), located in the 3'-UTR of MDM4, is associated with an increased risk of prostate cancer. Computational predictions revealed that the rs4245739 SNP is located within a predicted binding site for three microRNAs (miRNAs): miR-191-5p, miR-887 and miR-3669. Herein, we show using reporter gene assays and endogenous MDM4 expression analyses that miR-191-5p and miR-887 have a specific affinity for the rs4245739 SNP C-allele in prostate cancer. These miRNAs do not affect MDM4 mRNA levels, rather they inhibit its translation in C-allele-containing PC3 cells but not in LNCaP cells homozygous for the A-allele. By analysing gene expression datasets from patient cohorts, we found that MDM4 is associated with metastasis and prostate cancer progression and that targeting this gene with miR-191-5p or miR-887 decreases in PC3 cell viability. This study is the first, to our knowledge, to demonstrate regulation of the MDM4 rs4245739 SNP C-allele by two miRNAs in prostate cancer, and thereby to identify a mechanism by which the MDM4 rs4245739 SNP A-allele may be associated with an increased risk for prostate cancer.

Do stakeholders or social obligations drive corporate social and environmental responsibility reporting? Managerial views from a developing country

Purpose – The purpose of this study is to explore senior managers’ perception and motivations of corporate social and environmental responsibility (CSER) reporting in the context of a developing country, Bangladesh. Design/methodology/approach – In-depth semi-structured interviews were conducted with 25 senior managers of companies listed on the Dhaka Stock Exchange. Publicly available annual reports of these companies were also analysed. Findings – The results indicate that senior managers perceive CSER reporting as a social obligation. The study finds that the managers focus mostly on child labour, human resources/rights, responsible products/services, health education, sports and community engagement activities as part of the social obligations. Interviewees identify a lack of a regulatory framework along with socio-cultural and religious factors as contributing to the low level of disclosures. These findings suggest that CSER reporting is not merely stakeholder-driven, but rather country-specific social and environmental issues play an important role in relation to CSER reporting practices. Research limitations/implications – This paper contributes to engagement-based studies by focussing on CSER reporting practices in developing countries and are useful for academics, practitioners and policymakers in understanding the reasons behind CSER reporting in developing countries. Originality/value – This paper addresses a literature “gap” in the empirical study of CSER reporting in a developing country, such as Bangladesh. This study fills a gap in the existing literature to understand managers’ motivations for CSER reporting in a developing country context. Managerial perceptions on CSER issues are largely unexplored in developing countries.

Grazing management influences the dynamics of populations of Stylosanthes hippocampoides (Oxley fine stem stylo)

This paper describes a study to identify those factors which control the persistence of the Subtropical legume Stylosanthes hippocampoides, formerly S. guianensis cv. Oxley (fine stem stylo). The dynamics of S. hippocampoides populations was recorded in permanent quadrats at 2 stocking rates in a grazing study conducted between 1987 and 1992 in south-eastern Queensland. Density of mature plants fluctuated between 10 and 60 plants/m(2) during the 5 years with the major contributing factors being variations in seedling recruitment and survival, which, in turn, reflected the size of the soil seed bank and seasonal rainfall. Plant density was consistently higher at the lower stocking rate of 1 beast/1.5 ha compared with 1 beast/1 ha; however, the effect of stocking rate was minor compared with fluctuation due to seasonal variation in rainfall. The maximum life span of the original plants exceeded 5 years, while the survival of seedling cohorts was strongly impacted by seasonal rainfall. Total exclosure from grazing during summer increased the size of the soil seed bank although a precise time period during summer was not identified, while grazing at the lower stocking pressure produced the same outcome. It was concluded that the large seasonal variation that occurs in S. hippocampoides density is driven by large seasonal variation in seedling recruitment, which, in turn, is influenced by the size of the soil seed bank.