A GTT microsatellite repeat motif and differentiation between morphological forms of Littorina saxatilis: speciation in progress?

A size (and sequence) variable microsatellite has been identified in the gastropod Littorina saxatilis following sequencing of products obtained through randomly amplified polymorphic DNA amplification. Size frequency distributions for this GTT repeat motif have been produced from a total of 439 L. saxatilis. Although there is evidence for a high prevalence of null alleles, consistent, largely significant, differences are found between the average size of this repeat in high shore, thin shelled morphs (L. saxatilis H) compared to mid shore, thick shelled animals (L. saxatilis M), with the former having consistently larger allele sizes. These findings are evident on both a large scale (around the coast of Britain) and a microgeographic scale (replicated sampling of a single shore). Unusually large alleles (>400 bp) are also considerably more prevalent in L. saxatilis H, and sequencing of these, including DNA flanking the GTT repeat, indicates that they do not represent independent expansion events. The significant difference in GTT repeat size, and increased prevalence of such related alleles in the H form compared to the M morph suggests that either gene flow is greater within, than between, morphs or that selection is acting on this locus or a closely linked locus. We argue for the latter scenario and discuss why this indicates that these forms are diverging across their range in the British Isles

Correlation of morphological diversity with molecular marker diversity in the rough periwinkle Littorina saxatilis (Olivi)

Two morphological varieties of Littorina saxatilis, widespread around the United Kingdom, are a thin-shelled, high-shore morph (L. saxatilis H) and a thick-shelled, mid-shore animal (L. saxatilis M). Mitochondrial DNA (mtDNA) analysis by PCR-RFLP was used to test whether gene flow between these morphs is restricted. At Galloway, Scotland, replicated sampling (different years and different transects over a distance of 800 m) has been undertaken. One mtDNA haplotype is predominant in H and a different haplotype common in the M animals. Repeatability in space and time suggests a real H/M differentiation. A similar pattern of mtDNA haplotype variation is seen in a single sample of the Swedish E and S morphs of Littorina saxatilis. However, this pattern is not evident everywhere. Variation in the mtDNA and four nuclear DNA loci was examined within and between L. saxatilis H and M morphs from the south coast of England. Because shape variation in this region additionally separates into three shape groupings (regions identified from multivariate morphometric analysis where shape is more homogeneous within, than between groups), generic variability was examined within and between these groupings as well as between H and M. On the south coast, an apparent association of shape and mtDNA haplotype is identified, but AMOVA analysis shows no support for the association being with shape grouping or H and M morphs. Although the nature of this shape-genotype association is unknown, a mtDNA haplotype and an allele at the nuclear CAL-2 locus are confined mainly to one shape group. Analysis of association of mtDNA haplotype with H and M morphology suggests a strong correlation can be found in some areas (Galloway, Mumbles (south Wales), and between similar morphs in Sweden) yet no association is seen at others (Ravenscar, UK, Ballynahown, Ireland, and the south coast of England). Thus, unravelling the basis of the H and M forms will require more detailed studies, with replication, as at Galloway, and also with additional molecular markers

Lagoonal littorinids: Shell shape and speciation

Variables related to shell shape have been measured in littorinids from brackish lagoons and coastal sites. After removal of size related effects, the data were analyzed using multivariate techniques. On Canonical Variate 1 there was good separation of the shells of the lagoonal animals from those of animals from the coast and a tidal lagoon. The former, for example, had lighter, and therefore thinner, shells for any given shell size and a smaller jugosity of the aperture lip. The lagoonal shells from Golam Head and the coastal animals from Robin Hood's Bay could each be separated clearly from the other samples. Although there are clear morphometric differences in the shells, it is not possible without appropriate breeding experiments to raise the lagoonal animals from L. saxatilis var. lagunae (L. tenebrosa) to species status. The importance of conserving lagoonal habitats is considered in terms of the preservation of biodiversit

Epigenetic regulation of adult neural stem cells: implications for Alzheimer's disease.

Published onlineJournal ArticleResearch Support, Non-U.S. Gov'tReviewExperimental evidence has demonstrated that several aspects of adult neural stem cells (NSCs), including their quiescence, proliferation, fate specification and differentiation, are regulated by epigenetic mechanisms. These control the expression of specific sets of genes, often including those encoding for small non-coding RNAs, indicating a complex interplay between various epigenetic factors and cellular functions.Previous studies had indicated that in addition to the neuropathology in Alzheimer's disease (AD), plasticity-related changes are observed in brain areas with ongoing neurogenesis, like the hippocampus and subventricular zone. Given the role of stem cells e.g. in hippocampal functions like cognition, and given their potential for brain repair, we here review the epigenetic mechanisms relevant for NSCs and AD etiology. Understanding the molecular mechanisms involved in the epigenetic regulation of adult NSCs will advance our knowledge on the role of adult neurogenesis in degeneration and possibly regeneration in the AD brain.Internationale Stichting Alzheimer Onderzoek (ISAO)Netherlands Organization for Scientific Research (NWO)Maastricht University Medical Centre 

Genome-Wide DNA Methylation Patterns in Persistent Attention-Deficit/Hyperactivity Disorder and in Association With Impulsive and Callous Traits

This is the final version. Available on open access from Frontiers Media via the DOI in this recordData Availability Statement: The datasets for this article are not publicly available because of limitations in ethical approvals. A request procedure is in place, based on submission of a short proposal. Requests to access the datasets should be directed to BF, [email protected] or JB, [email protected]/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that often persists into adulthood. ADHD and related personality traits, such as impulsivity and callousness, are caused by genetic and environmental factors and their interplay. Epigenetic modifications of DNA, including methylation, are thought to mediate between such factors and behavior and may behave as biomarkers for disorders. Here, we set out to study DNA methylation in persistent ADHD and related traits. We performed epigenome-wide association studies (EWASs) on peripheral whole blood from participants in the NeuroIMAGE study (age range 12–23 years). We compared participants with persistent ADHD (n = 35) with healthy controls (n = 19) and with participants with remittent ADHD (n = 19). Additionally, we performed EWASs of impulsive and callous traits derived from the Conners Parent Rating Scale and the Callous-Unemotional Inventory, respectively, across all participants. For every EWAS, the linear regression model analyzed included covariates for age, sex, smoking scores, and surrogate variables reflecting blood cell type composition and genetic background. We observed no epigenome-wide significant differences in single CpG site methylation between participants with persistent ADHD and healthy controls or participants with remittent ADHD. However, epigenome-wide analysis of differentially methylated regions provided significant findings showing that hypermethylated regions in the APOB and LPAR5 genes were associated with ADHD persistence compared to ADHD remittance (p = 1.68 * 10−24 and p = 9.06 * 10−7, respectively); both genes are involved in cholesterol signaling. Both findings appeared to be linked to genetic variation in cis. We found neither significant epigenome-wide single CpG sites nor regions associated with impulsive and callous traits; the top-hits from these analyses were annotated to genes involved in neurotransmitter release and the regulation of the biological clock. No link to genetic variation was observed for these findings, which thus might reflect environmental influences. In conclusion, in this pilot study with a small sample size, we observed several DNA-methylation–disorder/trait associations of potential significance for ADHD and the related behavioral traits. Although we do not wish to draw conclusions before replication in larger, independent samples, cholesterol signaling and metabolism may be of relevance for the onset and/or persistence of ADHD.Donders Centre for Medical Neuroscience of RadboudumcDutch National Science AgendaEuropean Union Horizon 2020Netherlands Organization for Scientific Research (NWO

Dopamine transporter (DAT1) and dopamine receptor D4 (DRD4) genotypes differentially impact on electrophysiological correlates of error processing

Peer reviewedPublisher PD

HIV Testing and Care in Canadian Aboriginal Youth: A community based mixed methods study

<p>Abstract</p> <p>Background</p> <p>HIV infection is a serious concern in the Canadian Aboriginal population, particularly among youth; however, there is limited attention to this issue in research literature. The purpose of this national study was to explore HIV testing and care decisions of Canadian Aboriginal youth.</p> <p>Methods</p> <p>A community-based mixed-method design incorporating the Aboriginal research principles of Ownership, Control, Access and Possession (OCAP) was used. Data were collected through surveys (n = 413) and qualitative interviews (n = 28). Eleven community-based organizations including urban Aboriginal AIDS service organizations and health and friendship centres in seven provinces and one territory assisted with the recruitment of youth (15 to 30 years).</p> <p>Results</p> <p>Average age of survey participants was 21.5 years (median = 21.0 years) and qualitative interview participants was 24.4 years (median = 24.0). Fifty-one percent of the survey respondents (210 of 413 youth) and 25 of 28 interview participants had been tested for HIV. The most common reason to seek testing was having sex without a condom (43.6%) or pregnancy (35.4%) while common reasons for not testing were the perception of being low HIV risk (45.3%) or not having had sex with an infected person (34.5%). Among interviewees, a contributing reason for not testing was feeling invulnerable. Most surveyed youth tested in the community in which they lived (86.5%) and 34.1% visited a physician for the test. The majority of surveyed youth (60.0%) had tested once or twice in the previous 2 years, however, about one-quarter had tested more than twice. Among the 26 surveyed youth who reported that they were HIV-positive, 6 (23.1%) had AIDS at the time of diagnosis. Delays in care-seeking after diagnosis varied from a few months to seven years from time of test.</p> <p>Conclusion</p> <p>It is encouraging that many youth who had tested for HIV did so based on a realistic self-assessment of HIV risk behaviours; however, for others, a feeling of invulnerability was a barrier to testing. For those who tested positive, there was often a delay in accessing health services.</p

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

Variability in Isotope Discrimination Factors in Coral Reef Fishes: Implications for Diet and Food Web Reconstruction

Interpretation of stable isotope ratios of carbon and nitrogen (δ13C and δ15N) is generally based on the assumption that with each trophic level there is a constant enrichment in the heavier isotope, leading to diet-tissue discrimination factors of 3.4‰ for 15N (ΔN) and ∼0.5‰ for 13C (ΔC). Diet-tissue discrimination factors determined from paired tissue and gut samples taken from 152 individuals from 26 fish species at Ningaloo Reef, Western Australia demonstrate a large amount of variability around constant values. While caution is necessary in using gut contents to represent diet due to the potential for high temporal variability, there were significant effects of trophic position and season that may also lead to variability in ΔN under natural conditions. Nitrogen enrichment increased significantly at higher trophic levels (higher tissue δ15N), with significantly higher ΔN in carnivorous species. Changes in diet led to significant changes in ΔN, but not tissue δ15N, between seasons for several species: Acanthurus triostegus, Chromis viridis, Parupeneus signatus and Pomacentrus moluccensis. These results confirm that the use of meta-analysis averages for ΔN is likely to be inappropriate for accurately determining diets and trophic relationships using tissue stable isotope ratios. Where feasible, discrimination factors should be directly quantified for each species and trophic link in question, acknowledging the potential for significant variation away from meta-analysis averages and, perhaps, controlled laboratory diets and conditions