Maternal nutritional status, C1 metabolism and offspring DNA methylation: a review of current evidence in human subjects.

: Evidence is growing for the long-term effects of environmental factors during early-life on later disease susceptibility. It is believed that epigenetic mechanisms (changes in gene function not mediated by DNA sequence alteration), particularly DNA methylation, play a role in these processes. This paper reviews the current state of knowledge of the involvement of C1 metabolism and methyl donors and cofactors in maternal diet-induced DNA methylation changes in utero as an epigenetic mechanism. Methyl groups for DNA methylation are mostly derived from the diet and supplied through C1 metabolism by way of choline, betaine, methionine or folate, with involvement of riboflavin and vitamins B6 and B12 as cofactors. Mouse models have shown that epigenetic features, for example DNA methylation, can be altered by periconceptional nutritional interventions such as folate supplementation, thereby changing offspring phenotype. Evidence of early nutrient-induced epigenetic change in human subjects is scant, but it is known that during pregnancy C1 metabolism has to cope with high fetal demands for folate and choline needed for neural tube closure and normal development. Retrospective studies investigating the effect of famine or season during pregnancy indicate that variation in early environmental exposure in utero leads to differences in DNA methylation of offspring. This may affect gene expression in the offspring. Further research is needed to examine the real impact of maternal nutrient availability on DNA methylation in the developing fetus

The Emergent Role of the Social Designer

This paper responds to the Academic Design Management Conference, Design Management Futures theme. It answers questions relating to the way in which we think about the future of Design Management, and the way in which Design Management may need to adapt to the changing nature of design and new management theories. This piece draws on the work of an interdisciplinary team of researchers from the fields of Engineering, Sociology and Graphic Design, and their experience in the areas of user-engagement, anti-oppressive education/pedagogy and inclusive design. This position paper is a reflective piece that examines the value of designers, engineers and sociologists working together. It puts forward the question ‘What can designers and engineers learn from the emancipatory paradigm of the Social Scientist?’ Reflections from a UK-based team of undergraduate designers and engineers provide insight to their experience of engaging with the user through an inclusive design project. They cast light upon their experience of cross-faculty studies, interdisciplinary collaborations and both the challenges and benefits to working with different user groups. This paper concludes by examining the practical implications for Design Management, providing insights for Design Management education, research and practice

Appreciating interconnectivity between habitats is key to Blue Carbon management

We welcome the recent synthesis by Howard et al. (2017), which drew attention to the role of marine systems and natural carbon sequestration in the oceans as a fundamental aspect of climate-change mitigation. The importance of long-term carbon storage in marine habitats (ie “blue carbon”) is rapidly gaining recognition and is increasingly a focus of national and international attempts to mitigate rising atmospheric emissions of carbon dioxide. However, effectively managing blue carbon requires an appreciation of the inherent connectivity between marine populations and habitats. More so than their terrestrial counterparts, marine ecosystems are “open”, with high rates of transfer of energy, matter, genetic material, and species across regional seascapes (Kinlan and Gaines 2003). We suggest that policy frameworks, and the science underpinning them, should focus not only on carbon sink habitats but also on carbon source habitats, which play critical roles in marine carbon cycling and natural carbon sequestration in the oceans

Anomaly-Free Supersymmetric SO(2N+2)/U(N+1) sigma-Model Based on the SO(2N+1) Lie Algebra of the Fermion Operators

The extended supersymmetric (SUSY) sigma-model has been proposed on the bases of SO(2N+1) Lie algebra spanned by fermion annihilation-creation operators and pair operators. The canonical transformation, extension of an SO(2N) Bogoliubov transformation to an SO(2N+1) group, is introduced. Embedding the SO(2N+1) group into an SO(2N+2) group and using SO(2N+2)/U(N+1) coset variables, we have investigated the SUSY sigma-model on the Kaehler manifold, the coset space SO(2N+2)/U(N+1). We have constructed the Killing potential, extension of the potential in the SO(2N)/U(N) coset space to that in the SO(2N+2)/U(N+1) coset space. It is equivalent to the generalized density matrix whose diagonal-block part is related to a reduced scalar potential with a Fayet-Ilipoulos term. The f-deformed reduced scalar potential is optimized with respect to vacuum expectation value of the sigma-model fields and a solution for one of the SO(2N+1) group parameters has been obtained. The solution, however, is only a small part of all solutions obtained from anomaly-free SUSY coset models. To construct the coset models consistently, we must embed a coset coordinate in an anomaly-free spinor representation (rep) of SO(2N+2) group and give corresponding Kaehler and Killing potentials for an anomaly-free SO(2N+2)/U(N+1) model based on each positive chiral spinor rep. Using such mathematical manipulation we construct successfully the anomaly-free SO(2N+2)/U(N+1) SUSY sigma-model and investigate new aspects which have never been seen in the SUSY sigma-model on the Kaehler coset space SO(2N)/U(N). We reach a f-deformed reduced scalar potential. It is minimized with respect to the vacuum expectation value of anomaly-free SUSY sigma-model fields. Thus we find an interesting f-deformed solution very different from the previous solution for an anomaly-free SO(2.5+2)/(SU(5+1)*U(1)) SUSY sigma-model.Comment: 24 pages, no fiure

Complement C3 variant and the risk of age-related macular degeneration

Background: Age-related macular degeneration is the most common cause of blindness in Western populations. Susceptibility is influenced by age and by genetic and environmental factors. Complement activation is implicated in the pathogenesis.Methods: We tested for an association between age-related macular degeneration and 13 single-nucleotide polymorphisms (SNPs) spanning the complement genes C3 and C5 in case subjects and control subjects from the southeastern region of England. All subjects were examined by an ophthalmologist and had independent grading of fundus photographs to confirm their disease status. To test for replication of the most significant findings, we genotyped a set of Scottish cases and controls.Results: The common functional polymorphism rs2230199 (Arg80Gly) in the C3 gene, corresponding to the electrophoretic variants C3S (slow) and C3F (fast), was strongly associated with age-related macular degeneration in both the English group (603 cases and 350 controls, P=5.9 x 10(sup -5)) and the Scottish group (244 cases and 351 controls, P=5.0 x 10(sup -5)). The odds ratio for age-related macular degeneration in C3 S/F heterozygotes as compared with S/S homozygotes was 1.7 (95% confidence interval [CI], 1.3 to 2.1); for F/F homozygotes, the odds ratio was 2.6 (95% CI, 1.6 to 4.1). The estimated population attributable risk for C3F was 22%.Conclusions: Complement C3 is important in the pathogenesis of age-related macular degeneration. This finding further underscores the influence of the complement pathway in the pathogenesis of this disease

Evolution of Landau Levels into Edge States at an Atomically Sharp Edge in Graphene

The quantum-Hall-effect (QHE) occurs in topologically-ordered states of two-dimensional (2d) electron-systems in which an insulating bulk-state coexists with protected 1d conducting edge-states. Owing to a unique topologically imposed edge-bulk correspondence these edge-states are endowed with universal properties such as fractionally-charged quasiparticles and interference-patterns, which make them indispensable components for QH-based quantum-computation and other applications. The precise edge-bulk correspondence, conjectured theoretically in the limit of sharp edges, is difficult to realize in conventional semiconductor-based electron systems where soft boundaries lead to edge-state reconstruction. Using scanning-tunneling microscopy and spectroscopy to follow the spatial evolution of bulk Landau-levels towards a zigzag edge of graphene supported above a graphite substrate we demonstrate that in this system it is possible to realize atomically sharp edges with no edge-state reconstruction. Our results single out graphene as a system where the edge-state structure can be controlled and the universal properties directly probed.Comment: 16 pages, 4 figure

Seminar Users in the Arabic Twitter Sphere

We introduce the notion of "seminar users", who are social media users engaged in propaganda in support of a political entity. We develop a framework that can identify such users with 84.4% precision and 76.1% recall. While our dataset is from the Arab region, omitting language-specific features has only a minor impact on classification performance, and thus, our approach could work for detecting seminar users in other parts of the world and in other languages. We further explored a controversial political topic to observe the prevalence and potential potency of such users. In our case study, we found that 25% of the users engaged in the topic are in fact seminar users and their tweets make nearly a third of the on-topic tweets. Moreover, they are often successful in affecting mainstream discourse with coordinated hashtag campaigns.Comment: to appear in SocInfo 201

Interleukin 7 from Maternal Milk Crosses the Intestinal Barrier and Modulates T- Cell Development in Offspring

Background Breastfeeding protects against illnesses and death in hazardous environments, an effect partly mediated by improved immune function. One hypothesis suggests that factors within milk supplement the inadequate immune response of the offspring, but this has not been able to account for a series of observations showing that factors within maternally derived milk may supplement the development of the immune system through a direct effect on the primary lymphoid organs. In a previous human study we reported evidence suggesting a link between IL-7 in breast milk and the thymic output of infants. Here we report evidence in mice of direct action of maternally-derived IL-7 on T cell development in the offspring. Methods and Findings  We have used recombinant IL-7 labelled with a fluorescent dye to trace the movement in live mice of IL-7 from the stomach across the gut and into the lymphoid tissues. To validate the functional ability of maternally derived IL- 7 we cross fostered IL-7 knock-out mice onto normal wild type mothers. Subsets of thymocytes and populations of peripheral T cells were significantly higher than those found in knock-out mice receiving milk from IL-7 knock-out mothers. Conclusions/Significance Our study provides direct evidence that interleukin 7, a factor which is critical in the development of T lymphocytes, when maternally derived can transfer across the intestine of the offspring, increase T cell production in the thymus and support the survival of T cells in the peripheral secondary lymphoid tissue