Rare coding SNP in DZIP1 gene associated with late-onset sporadic Parkinson's disease

We present the first application of the hypothesis-rich mathematical theory to genome-wide association data. The Hamza et al. late-onset sporadic Parkinson's disease genome-wide association study dataset was analyzed. We found a rare, coding, non-synonymous SNP variant in the gene DZIP1 that confers increased susceptibility to Parkinson's disease. The association of DZIP1 with Parkinson's disease is consistent with a Parkinson's disease stem-cell ageing theory.Comment: 14 page

Neither fair nor unchangeable but part of the natural order: orientations towards inequality in the face of criticism of the economic system

The magnitude of climate change threats to life on the planet is not matched by the level of current mitigation strategies. To contribute to our understanding of inaction in the face of climate change, the reported study draws upon the pro status quo motivations encapsulated within System Justification Theory. In an online questionnaire study, participants (N = 136) initially completed a measure of General System Justification. Participants in a “System-critical” condition were then exposed to information linking environmental problems to the current economic system; participants in a Control condition were exposed to information unrelated to either environmental problems or the economic system. A measure of Economic System Justification was subsequently administered. Regressions of Economic System Justification revealed interactions between General System Justification and Information Type: higher general system justifiers in the System-critical condition rated the economic system as less fair than did their counterparts in the Control condition. However, they also indicated inequality as more natural than did their counterparts in the Control condition. The groups did not differ in terms of beliefs about the economic system being open to change. The results are discussed in terms of how reassurance about the maintenance of the status quo may be bolstered by recourse to beliefs in a natural order

The Effect of Epstein-Barr Virus Latent Membrane Protein 2 Expression on the Kinetics of Early B Cell Infection

Infection of human B cells with wild-type Epstein-Barr virus (EBV) in vitro leads to activation and proliferation that result in efficient production of lymphoblastoid cell lines (LCLs). Latent Membrane Protein 2 (LMP2) is expressed early after infection and previous research has suggested a possible role in this process. Therefore, we generated recombinant EBV with knockouts of either or both protein isoforms, LMP2A and LMP2B (Δ2A, Δ2B, Δ2A/Δ2B) to study the effect of LMP2 in early B cell infection. Infection of B cells with Δ2A and Δ2A/Δ2B viruses led to a marked decrease in activation and proliferation relative to wild-type (wt) viruses, and resulted in higher percentages of apoptotic B cells. Δ2B virus infection showed activation levels comparable to wt, but fewer numbers of proliferating B cells. Early B cell infection with wt, Δ2A and Δ2B viruses did not result in changes in latent gene expression, with the exception of elevated LMP2B transcript in Δ2A virus infection. Infection with Δ2A and Δ2B viruses did not affect viral latency, determined by changes in LMP1/Zebra expression following BCR stimulation. However, BCR stimulation of Δ2A/Δ2B cells resulted in decreased LMP1 expression, which suggests loss of stability in viral latency. Long-term outgrowth assays revealed that LMP2A, but not LMP2B, is critical for efficient long-term growth of B cells in vitro. The lowest levels of activation, proliferation, and LCL formation were observed when both isoforms were deleted. These results suggest that LMP2A appears to be critical for efficient activation, proliferation and survival of EBV-infected B cells at early times after infection, which impacts the efficient long-term growth of B cells in culture. In contrast, LMP2B did not appear to play a significant role in these processes, and long-term growth of infected B cells was not affected by the absence of this protein. © 2013 Wasil et al

Diet, physical activity, and adiposity in children in poor and rich neighbourhoods: a cross-sectional comparison

BACKGROUND: Obesity in Canadian children increased three-fold in twenty years. Children living in low-income neighborhoods exercise less and are more overweight than those living in more affluent neighborhoods after accounting for family socio-economic status. Strategies to prevent obesity in children have focused on personal habits, ignoring neighborhood characteristics. It is essential to evaluate diet and physical activity patterns in relation to socio-economic conditions to understand the determinants of obesity. The objective of this pilot study was to compare diet, physical activity, and the built environment in two Hamilton area elementary schools serving socio-economically different communities. METHODS: We conducted a cross-sectional study (November 2005-March 2006) in two public elementary schools in Hamilton, Ontario, School A and School B, located in low and high socioeconomic areas respectively. We assessed dietary intake, physical activity, dietary restraint, and anthropometric measures in consenting children in grades 1 and higher. From their parents we assessed family characteristics and walkability of the built environment. RESULTS: 160 children (n = 48, School A and n = 112, School B), and 156 parents (n = 43, School A and n = 113, School B) participated in this study. The parents with children at School A were less educated and had lower incomes than those at School B. The School A neighborhood was perceived to be less walkable than the School B neighborhood. Children at School A consumed more baked foods, chips, sodas, gelatin desserts, and candies and less low fat dairy, and dark bread than those at School B. Children at School A watched more television and spent more time in front of the computer than children studying at School B, but reported spending less time sitting on weekdays and weekends. Children at both schools were overweight but there was no difference in their mean BMI z-scores (School A = 0.65 versus School B = 0.81, p-value = 0.38). CONCLUSION: The determinants of overweight in children may be more complex than imagined. In future intervention programs researchers may consider addressing environmental factors, and customizing lifestyle interventions so that they are closer to community needs

A nonlinear updating algorithm captures suboptimal inference in the presence of signal-dependent noise

Bayesian models have advanced the idea that humans combine prior beliefs and sensory observations to optimize behavior. How the brain implements Bayes-optimal inference, however, remains poorly understood. Simple behavioral tasks suggest that the brain can flexibly represent probability distributions. An alternative view is that the brain relies on simple algorithms that can implement Bayes-optimal behavior only when the computational demands are low. To distinguish between these alternatives, we devised a task in which Bayes-optimal performance could not be matched by simple algorithms. We asked subjects to estimate and reproduce a time interval by combining prior information with one or two sequential measurements. In the domain of time, measurement noise increases with duration. This property takes the integration of multiple measurements beyond the reach of simple algorithms. We found that subjects were able to update their estimates using the second measurement but their performance was suboptimal, suggesting that they were unable to update full probability distributions. Instead, subjects’ behavior was consistent with an algorithm that predicts upcoming sensory signals, and applies a nonlinear function to errors in prediction to update estimates. These results indicate that the inference strategies employed by humans may deviate from Bayes-optimal integration when the computational demands are high

Management control systems in innovation companies: A literature based framework

Past research has traditionally argued that management control systems (MCSs) may present a hindrance to the creativity of innovation companies. This theoretical paper surveys the literature to focus an investigation on the MCSs of innovation companies. Within the object of control paradigm the paper develops and presents a theoretical model of the impact of eleven external, organisational and innovation related contingency factors on the MCSs in companies that engage in innovation activities. We also suggest measures for further empirical research. By formulating hypotheses on 43 potential interactions the model predicts contradictory influences on two direct control categories, results and action control, but stresses the importance of two indirect categories, personnel and cultural control. More specifically, the high levels of technological complexity and innovation capability in this type of company are expected to be negatively associated with the application of results and action control, whereas personnel and cultural seem to be more appropriate. Furthermore, important sources of finance, venture capital and public funding, are both hypothesised to be positively associated with the application of results, action and personnel control; whereas only public funding is predicted to be positively related to the application of cultural control. The principal contribution of this paper lies in synthesising the literature to provide a model of the impact of a unique set of eleven contingency factors for innovation companies on a broad scope of controls. In addition, the contingency model, if empirically validated, would add value by inferring the particular forms of management control which would be beneficial in innovative company settings. © 2014 Springer-Verlag Berlin Heidelberg

Household and community socioeconomic and environmental determinants of child nutritional status in Cameroon

BACKGROUND: Undernutrition is a leading cause of child mortality in developing countries, especially in sub-Saharan Africa. We examine the household and community level socioeconomic and environmental factors associated with child nutritional status in Cameroon, and changes in the effects of these factors during the 1990s economic crisis. We further consider age-specific effects of household economic status on child nutrition. METHODS: Child nutritional status was measured by weight-for-age (WAZ) and height-for-age (HAZ) z-scores. Data were from Demographic and Health Surveys conducted in 1991 and 1998. We used analysis of variance to assess the bivariate association between the explanatory factors and nutritional status. Multivariate, multilevel analyses were undertaken to estimate the net effects of both household and community factors. RESULTS: Average WAZ and HAZ declined respectively from -0.70 standard deviations (SD), i.e. 0.70 SD below the reference median, to -0.83 SD (p = 0.006) and from -1.03 SD to -1.14 SD (p = 0.026) between 1991 and 1998. These declines occurred mostly among boys, children over 12 months of age, and those of low socioeconomic status. Maternal education and maternal health seeking behavior were associated with better child nutrition. Household economic status had an overall positive effect that increased during the crisis, but it had little effect in children under 6 months of age. Improved household (water, sanitation and cooking fuel) and community environment had positive effects. Children living in the driest regions of the country were consistently worst off, and those in the largest cities were best off. CONCLUSION: Both household and community factors have significant impact on child health in Cameroon. Understanding these relationships can facilitate design of age- and community-specific intervention programs

A Functional Architecture of Optic Flow in the Inferior Parietal Lobule of the Behaving Monkey

The representation of navigational optic flow across the inferior parietal lobule was assessed using optical imaging of intrinsic signals in behaving monkeys. The exposed cortex, corresponding to the dorsal-most portion of areas 7a and dorsal prelunate (DP), was imaged in two hemispheres of two rhesus monkeys. The monkeys actively attended to changes in motion stimuli while fixating. Radial expansion and contraction, and rotation clockwise and counter-clockwise optic flow stimuli were presented concentric to the fixation point at two angles of gaze to assess the interrelationship between the eye position and optic flow signal. The cortical response depended upon the type of flow and was modulated by eye position. The optic flow selectivity was embedded in a patchy architecture within the gain field architecture. All four optic flow stimuli tested were represented in areas 7a and DP. The location of the patches varied across days. However the spatial periodicity of the patches remained constant across days at ∼950 and 1100 µm for the two animals examined. These optical recordings agree with previous electrophysiological studies of area 7a, and provide new evidence for flow selectivity in DP and a fine scale description of its cortical topography. That the functional architectures for optic flow can change over time was unexpected. These and earlier results also from inferior parietal lobule support the inclusion of both static and dynamic functional architectures that define association cortical areas and ultimately support complex cognitive function

Periodontitis is associated with significant hepatic fibrosis in patients with non-alcoholic fatty liver disease

This work was funded by the Diabetes Research and Wellness Fund. WA is in receipt of an MRC New Investigator Award