Exploring gene-environment interactions in Parkinson’s disease

The objective of this study was to explore combined effects of four candidate susceptibility genes and two exposures on Parkinson’s disease (PD) risk; namely, α-synuclein (SNCA) promoter polymorphism REP1, microtubule-associated protein tau (MAPT) H1/H2 haplotypes, apolipoprotein E (APOE) ε2/ε3/ε4 polymorphism, ubiquitin carboxy-terminal esterase L1 (UCHL1) S18Y variant, cigarette smoking and caffeinated coffee consumption. 932 PD patients and 664 control subjects from the NeuroGenetics Research Consortium, with complete data on all six factors, were studied. Uniform protocols were used for diagnosis, recruitment, data collection and genotyping. A logistic regression model which included gene-exposure interactions was applied. Likelihood ratio tests (LRTs) were used for significance testing and Bayesian inference was used to estimate odds ratios (ORs). MAPT (P = 0.007), SNCA REP1 (P = 0.012), smoking (P = 0.001), and coffee (P = 0.011) were associated with PD risk. Two novel interactions were detected: APOE with coffee (P = 0.005), and REP1 with smoking (P = 0.021). While the individual main effects were modest, each yielding OR < 1.6, the effects were cumulative, with some combinations reaching OR = 12.6 (95% CI: 5.9–26.8). This study provides evidence for the long-held notion that PD risk is modulated by cumulative and interactive effects of genes and exposures. Furthermore, the study demonstrates that while interaction studies are useful for exploring risk relationships that might otherwise go undetected, results should be interpreted with caution because of the inherent loss of power due to multiple testing. The novel findings of this study that warrant replication are the evidence for interaction of coffee with APOE, and of smoking with REP1 on PD risk. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Exploring glia to better understand Alzheimer’s disease

The amyloid-β (Aβ) hypothesis has been the leading explanation for the pathogenesis of Alzheimer’s disease (AD). The most common traits of AD are cognitive impairments and memory loss, which are associated with the accumulation of Aβ. Aβ aggregates activate glial cells, which in turn remove Aβ. Because microglia act as immune cells in the brain, most glia-related studies of AD have focused primarily on this cell type. However, astrocytes, another type of glial cell, also participate in the brain immune system, synaptic formation, brain homeostasis, and various other brain functions. Accordingly, many studies on the underlying mechanisms of AD have investigated not only neurons but also glial cells. Although these studies suggest that microglia and astrocytes are effective targets for AD therapeutics, other recent studies have raised questions regarding whether microglial cells and/or astrocytes serve a neuroprotective or neurotoxic function in AD. To gain a better understanding of the mechanisms of AD and identify novel targets for AD treatment, in this review, we consider the role of both microglia and astrocytes in AD.     

You Are What You Tweet: Connecting the Geographic Variation in America’s Obesity Rate to Twitter Content

We conduct a detailed investigation of the relationship among the obesity rate of urban areas and expressions of happiness, diet and physical activity on social media. We do so by analyzing a massive, geo-tagged data set comprising over 200 million words generated over the course of 2012 and 2013 on the social network service Twitter. Among many results, we show that areas with lower obesity rates: (1) have happier tweets and frequently discuss (2) food, particularly fruits and vegetables, and (3) physical activities of any intensity. Additionally, we provide evidence that each of these results offer different and unique insight into the variation of the obesity rate in urban areas within the United States. Our work shows how the contents of social media may potentially be used to estimate real-time, population-scale measures of factors related to obesity.     

School’s Out: Seasonal Variation in the Movement Patterns of School Children

School children are core groups in the transmission of many common infectious diseases, and are likely to play a key role in the spatial dispersal of disease across multiple scales. However, there is currently little detailed information about the spatial movements of this epidemiologically important age group. To address this knowledge gap, we collaborated with eight secondary schools to conduct a survey of movement patterns of school pupils in primary and secondary schools in the United Kingdom. We found evidence of a significant change in behaviour between term time and holidays, with term time weekdays characterised by predominately local movements, and holidays seeing much broader variation in travel patterns. Studies that use mathematical models to examine epidemic transmission and control often use adult commuting data as a proxy for population movements. We show that while these data share some features with the movement patterns reported by school children, there are some crucial differences between the movements of children and adult commuters during both term-time and holidays.     

Spatial Patterns of Prisoner’s Dilemma Game in Metapopulations

Because to defect is the evolutionary stable strategy in the prisoner’s dilemma game (PDG), understanding the mechanism generating and maintaining cooperation in PDG, i.e. the paradox of cooperation, has intrinsic significance for understanding social altruism behaviors. Spatial structure serves as the key to this dilemma. Here, we build the model of spatial PDG under a metapopulation framework: the sub-populations of cooperators and defectors obey the rules in spatial PDG as well as the colonization–extinction process of metapopulations. Using the mean-field approximation and the pair approximation, we obtain the differential equations for the dynamics of occupancy and spatial correlation. Cellular automaton is also built to simulate the spatiotemporal dynamics of the spatial PDG in metapopulations. Join-count statistics are used to measure the spatial correlation as well as the spatial association of the metapopulation. Simulation results show that the distribution is self-organized and that it converges to a static boundary due to the boycotting of cooperators to defectors. Metapopulations can survive even when the colonization rate is lower than the extinction rate due to the compensation of cooperation rewards for extinction debt. With a change of parameters in the model, a metapopulation can consist of pure cooperators, pure defectors, or cooperator–defector coexistence. The necessary condition of cooperation evolution is the local colonization of a metapopulation. The spatial correlation between the cooperators tends to be weaker with the increase in the temptation to defect and the habitat connectivity; yet the spatial correlation between defectors becomes stronger. The relationship between spatial structure and the colonization rate is complicated, especially for cooperators. The metapopulation may undergo a temporary period of prosperity just before the extinction, even while the colonization rate is declining. An erratum to this article can be found at     

Gulf War Syndrome: A Reaction to Psychiatry’s Invasion of the Military?

Following the 1991 Gulf War, a number of soldiers who fought there began to complain of various symptoms and disorders, the collection of which came to be known as Gulf War syndrome (GWS). A debate has raged about the nature and cause of this illness, with many suggesting that it is a psychiatric condition. GWS continues to be a contested illness, yet there is no disputing that many Gulf veterans are ill. This article considers the way in which GWS sufferers understand their illness to be physical in nature and the way in which they negotiate and resist psychological theories of their illness. Based on 14 months of ethnographic fieldwork in the United Kingdom, data for this article were collected mainly by in-depth, semistructured interviews with GWS sufferers, their family members, doctors, and scientists, as well as healthy Gulf veterans. A total of 93 informants were interviewed, including 67 UK Gulf veterans, most of whom were ill. The paper argues that despite the increasing presence of psychiatry in military discourse, GWS reveals the way that people are able to transform, negotiate and even negate its power and assumptions.     

Mango introduction in Florida and the ’haden’ cultivar’s significance to the modern industry

Mango (Mangifera indica L.) introductions to Florida began in 1861 with the importation of ’No. 11’, a polyembryonic, seed-propagated (nucellar) cultivarfrom Cuba. In the 1880s a collection of Cuban mangos was established near Bradenton. One resulting popular cultivar was ’Turpentine’, now widely used as a rootstock. The U. S. Department of Agriculture introduced ’Mulgoba’, an improved cultivarfrom India, in 1889. Other mangos were later brought from India, Vietnam, the Philippines, Thailand, Israel, Australia and Kenya. Related Mangifera species were collected in East Malaysian Borneo in 1990. Inasmuch as the breeding system of Mangifera favors outcrossing, the proximity of numerous genotypes of disparate geographic origin in Florida has made that state a secondary center of diversity for the mango and enabled it to make a unique contribution to the fruit industry.     

How to Understand a Woman’s Obligations to the Fetus in Unwanted Pregnancies

Some have challenged Thomson’s case of the famous unconscious violinist (UV) by arguing that in cases of consensual sex a woman is partially morally responsible for the existence of a needy fetus; since she is partially responsible she ought to assist the fetus, and so abortion is morally wrong. Call this the Responsibility Objection (RO) to UV. In this paper, I briefly criticize one of the most widely discussed objections to RO and then suggest a new way to challenge RO. In so doing, I investigate the plausibility of the moral principle that appears to be driving RO: If a woman is partially morally responsible for the existence of a needy fetus, she has a moral obligation to assist the fetus. I argue that this principle is false. I suggest modified versions of this principle but argue that, even on the most plausible version, RO does not persuade.     

Upset in response to a Sibling’s partner’s infidelities

Using data collected from people with at least one brother and one sister, and consistent with an evolutionary perspective, we find that older men and women (a) are more upset by a brother’s partner’s sexual infidelity than by her emotional infidelity and (b) are more upset by a sister’s partner’s emotional infidelity than by his sexual infidelity. There were no effects of participant sex or sex of in-law on upset over a sibling’s partner’s infidelities, but there was an effect of participant sex on reports of upset over one’s own partner’s infidelities. The results suggest that the key variable among older participants is the sex of the sibling or, correspondingly, the sex of the sibling’s partner, as predicted from an evolutionary analysis of reproductive costs, and not the sex of the participant, as predicted from a socialization perspective. Discussion offers directions for future work on jealousy.     

Reactions to Media Violence: It’s in the Brain of the Beholder

Media portraying violence is part of daily exposures. The extent to which violent media exposure impacts brain and behavior has been debated. Yet there is not enough experimental data to inform this debate. We hypothesize that reaction to violent media is critically dependent on personality/trait differences between viewers, where those with the propensity for physical assault will respond to the media differently than controls. The source of the variability, we further hypothesize, is reflected in autonomic response and brain functioning that differentiate those with aggression tendencies from others. To test this hypothesis we pre-selected a group of aggressive individuals and non-aggressive controls from the normal healthy population; we documented brain, blood-pressure, and behavioral responses during resting baseline and while the groups were watching media violence and emotional media that did not portray violence. Positron Emission Tomography was used with [¹⁸F]fluoro-deoxyglucose (FDG) to image brain metabolic activity, a marker of brain function, during rest and during film viewing while blood-pressure and mood ratings were intermittently collected. Results pointed to robust resting baseline differences between groups. Aggressive individuals had lower relative glucose metabolism in the medial orbitofrontal cortex correlating with poor self-control and greater glucose metabolism in other regions of the default-mode network (DMN) where precuneus correlated with negative emotionality. These brain results were similar while watching the violent media, during which aggressive viewers reported being more Inspired and Determined and less Upset and Nervous, and also showed a progressive decline in systolic blood-pressure compared to controls. Furthermore, the blood-pressure and brain activation in orbitofrontal cortex and precuneus were differentially coupled between the groups. These results demonstrate that individual differences in trait aggression strongly couple with brain, behavioral, and autonomic reactivity to media violence which should factor into debates about the impact of media violence on the public.     

Autophagic Pathways to Clear the Tau Aggregates in Alzheimer’s Disease

Cellular and Molecular Neurobiology - Tau is a microtubule-associated protein with an intrinsically unstructured conformation. Tau is subjected to several pathological post-translational...     

European Union’s Public Fishing Access Agreements in Developing Countries

The imperative to increase seafood supply while dealing with its overfished local stocks has pushed the European Union (EU) and its Member States to fish in the Exclusive Economic Zones of other countries through various types of fishing agreements for decades. Although European public fishing agreements are commented on regularly and considered to be transparent, this is the first global and historical study on the fee regime that governs them. We find that the EU has subsidized these agreements at an average of 75% of their cost (financial contribution agreed upon in the agreements), while private European business interests paid the equivalent of 1.5% of the value of the fish that was eventually landed. This raises questions of fisheries benefit-sharing and resource-use equity that the EU has the potential to address during the nearly completed reform of its Common Fisheries Policy.     

Hodgkin’s disease in the spleen

Spleens with proven though small Hodgkin lesions were examined expecially in relation to the lymphoid tissue normally engaged in the immune response. These Hodgkin foci were always very close to small arteries and surrounded by a lymphocyte corona. Most of the red and white pulp seemed normal, but in some instances abnormal looking large and also multinucleated cells were found scattered through the p.a.l.s. and especially through some follicles. It is considered possible that these isolated cellular abnormalities in the white pulp, when associated with pre-existent Hodgkin foci, represent early Hodgkin lesions. The implications for the dissemination of the disease are discussed. Spread of malignant cells to the spleen is only acceptable within the concept of a homing principle. It is also possible that the lesions arise "de novo". The nature of the observed abnormal cells is not clear. An explanation for the origin of these Sternberg-Reed-like cells from B-lymphocytes would be in accordance with recent data, but another possibility still is that they originate from antigen trapping cells.     

Complex Network Theory Applied to the Growth of Kuala Lumpur’s Public Urban Rail Transit Network

Recently, the number of studies involving complex network applications in transportation has increased steadily as scholars from various fields analyze traffic networks. Nonetheless, research on rail network growth is relatively rare. This research examines the evolution of the Public Urban Rail Transit Networks of Kuala Lumpur (PURTNoKL) based on complex network theory and covers both the topological structure of the rail system and future trends in network growth. In addition, network performance when facing different attack strategies is also assessed. Three topological network characteristics are considered: connections, clustering and centrality. In PURTNoKL, we found that the total number of nodes and edges exhibit a linear relationship and that the average degree stays within the interval [2.0488, 2.6774] with heavy-tailed distributions. The evolutionary process shows that the cumulative probability distribution (CPD) of degree and the average shortest path length show good fit with exponential distribution and normal distribution, respectively. Moreover, PURTNoKL exhibits clear cluster characteristics; most of the nodes have a 2-core value, and the CPDs of the centrality’s closeness and betweenness follow a normal distribution function and an exponential distribution, respectively. Finally, we discuss four different types of network growth styles and the line extension process, which reveal that the rail network’s growth is likely based on the nodes with the biggest lengths of the shortest path and that network protection should emphasize those nodes with the largest degrees and the highest betweenness values. This research may enhance the networkability of the rail system and better shape the future growth of public rail networks.     

Exploring Children’s Perspectives on the Welfare Needs of Pet Animals

Children are increasingly viewed as important recipients of educational interventions to improve animal welfare, yet research examining their perspectives is lacking, particularly within the UK. Helping children to care appropriately for animals depends, not least, on an ability to understand the needs of different species and correctly identify cues given by the animal that indicate its welfare state. This study began to explore: (a) children’s perceptions of welfare needs, focusing on four common pet animals; (b) influences on the development of knowledge; (c) beliefs about whether or not (all) animals are sentient, and (d) their confidence in identifying when their own pets are in need. Fourteen focus groups were carried out with 53 children aged 7 to 13 years. Findings highlighted an affirmative response that animals have feelings (dogs especially), albeit with doubts about this applying universally. There was wide variation in children’s knowledge of welfare needs, even among owners of the animal in question. Conversely, some children lacked confidence in spite of the extensive knowledge they had developed through direct experience. An important finding was a perceived difficulty in identifying the needs of particular species or specific types of need in their own pets. Fitting well with a recent emphasis on “positive welfare,” children felt that many animals need demonstrative love and attention, especially cats and dogs. While there is clearly scope for educating children about common needs and cues that indicate animals’ welfare state, other areas pose a greater challenge. Emotional connection seems important in the development of extensive knowledge and concern for welfare. Accordingly, animals that do not possess the kind of behavioral repertoire that is easy to interpret or allows for a perceived sense of reciprocity are possibly at risk of negative welfare experiences.