Elevated DNA methylation across a 48-kb region spanning the HOXA gene cluster is associated with Alzheimer's disease neuropathology

Introduction Alzheimer's disease is a neurodegenerative disorder that is hypothesized to involve epigenetic dysregulation of gene expression in the brain. Methods We performed an epigenome-wide association study to identify differential DNA methylation associated with neuropathology in prefrontal cortex and superior temporal gyrus samples from 147 individuals, replicating our findings in two independent data sets (N = 117 and 740). Results We identify elevated DNA methylation associated with neuropathology across a 48-kb region spanning 208 CpG sites within the HOXA gene cluster. A meta-analysis of the top-ranked probe within the HOXA3 gene (cg22962123) highlighted significant hypermethylation across all three cohorts (P = 3.11 × 10−18). Discussion We present robust evidence for elevated DNA methylation associated with Alzheimer's disease neuropathology spanning the HOXA gene cluster on chromosome 7. These data add to the growing evidence highlighting a role for epigenetic variation in Alzheimer's disease, implicating the HOX gene family as a target for future investigation

Reciprocity as a foundation of financial economics

This paper argues that the subsistence of the fundamental theorem of contemporary financial mathematics is the ethical concept ‘reciprocity’. The argument is based on identifying an equivalence between the contemporary, and ostensibly ‘value neutral’, Fundamental Theory of Asset Pricing with theories of mathematical probability that emerged in the seventeenth century in the context of the ethical assessment of commercial contracts in a framework of Aristotelian ethics. This observation, the main claim of the paper, is justified on the basis of results from the Ultimatum Game and is analysed within a framework of Pragmatic philosophy. The analysis leads to the explanatory hypothesis that markets are centres of communicative action with reciprocity as a rule of discourse. The purpose of the paper is to reorientate financial economics to emphasise the objectives of cooperation and social cohesion and to this end, we offer specific policy advice

Why the increase in under five mortality in Uganda from 1995 to 2000? A retrospective analysis

<p>Abstract</p> <p>Background</p> <p>From 1995-2000 the under five mortality rate in Uganda increased from 147.3 to 151.5 deaths per 1000 live births and reasons for the increase were not clear. This study was undertaken to understand factors influencing the increase in under five mortality rate during 1995-2000 in Uganda with a view of suggesting remedial actions.</p> <p>Methods</p> <p>We performed a comparative retrospective analysis of data derived from the 1995 and the 2000 Uganda demographic and health surveys. We correlated the change of under five mortality rate in Uganda desegregated by region (central, eastern, north and western) with change in major known determinants of under five mortality such social economic circumstances, maternal factors, access to health services, and level of nutrition.</p> <p>Results</p> <p>The increase in under five mortality rate only happened in western Uganda with the other 3 regions of Uganda (eastern, northern and central) showing a decrease. The changes in U5MR could not be explained by changes in poverty, maternal conditions, level of nutrition, or in access to health and other social services and in the prevalence of HIV among women attending for ante-natal care. All these factors did not reach statistical significance (P > 0.05) using Pearson's correlation coefficient.</p> <p>Conclusion</p> <p>In order to explain these findings, there is need to find something that happened in western Uganda (but not other parts of the country) during the period 1995-2000 and has the potential to change the under five mortality by a big margin. We hypothesize that the increase in under five mortality could be explained by the severe malaria epidemic that occurred in western Uganda (but not other regions) in 1997/98.</p

A histone acetylome-wide association study of Alzheimer’s disease identifies disease-associated H3K27ac differences in the entorhinal cortex

We quantified genome-wide patterns of lysine H3K27 acetylation (H3K27ac) in entorhinal cortex samples from Alzheimer’s disease (AD) cases and matched controls using chromatin immunoprecipitation and highly parallel sequencing. We observed widespread acetylomic variation associated with AD neuropathology, identifying 4,162 differential peaks (false discovery rate < 0.05) between AD cases and controls. Differentially acetylated peaks were enriched in disease-related biological pathways and included regions annotated to genes involved in the progression of amyloid-β and tau pathology (for example, APP, PSEN1, PSEN2, and MAPT), as well as regions containing variants associated with sporadic late-onset AD. Partitioned heritability analysis highlighted a highly significant enrichment of AD risk variants in entorhinal cortex H3K27ac peak regions. AD-associated variable H3K27ac was associated with transcriptional variation at proximal genes including CR1, GPR22, KMO, PIM3, PSEN1, and RGCC. In addition to identifying molecular pathways associated with AD neuropathology, we present a framework for genome-wide studies of histone modifications in complex disease

The head morphology of Pyrrhosoma nymphula larvae (Odonata: Zygoptera) focusing on functional aspects of the mouthparts

BACKGROUND: The understanding of concerted movements and its underlying biomechanics is often complex and elusive. Functional principles and hypothetical functions of these complex movements can provide a solid basis for biomechanical experiments and modelling. Here a description of the cephalic anatomy of Pyrrhosoma nymphula (Zygoptera, Coenagrionidae) focusing on functional aspects of the mouthparts using micro computed tomography (μCT) is presented. RESULTS: We compared six different instars of the damselfly P. nymphula as well as one instar of the dragonfly Aeshna cyanea and Epiophlebia superstes each. In total 42 head muscles were described with only minor differences of the attachment points between the examined species and the absence of antennal muscle M. scapopedicellaris medialis (0an7) in Epiophlebia as a probable apomorphy of this group. Furthermore, the ontogenetic differences between the six larval instars are minor; the only considerable finding is the change of M. submentopraementalis (0la8), which is dichotomous in the early instars (I1,I2 and I3) with a second point of origin at the postero-lateral base of the submentum. This dichotomy is not present in any of the older instars studied (I6, middle-late and pen-ultimate). CONCLUSION: However, the main focus of the study herein, is to use these detailed morphological descriptions as basis for hypothetic functional models of the odonatan mouthparts. We present blueprint like description of the mouthparts and their musculature, highlighting the caused direction of motion for every single muscle. This data will help to elucidate the complex concerted movements of the mouthparts and will contribute to the understanding of its biomechanics not in Odonata only