Differential DNA Methylation in Umbilical Cord Blood of Infants Exposed to Low Levels of Arsenic in Utero

Background: There is increasing epidemiologic evidence that arsenic exposure in utero, even at low levels found throughout much of the world, is associated with adverse reproductive outcomes and may contribute to long-term health effects. Animal models, in vitro studies, and human cancer data suggest that arsenic may induce epigenetic alterations, specifically by altering patterns of DNA methylation. Objectives: In this study we aimed to identify differences in DNA methylation in cord blood samples of infants with in utero, low-level arsenic exposure. Methods: DNA methylation of cord-blood derived DNA from 134 infants involved in a prospective birth cohort in New Hampshire was profiled using the Illumina Infinium Methylation450K array. In utero arsenic exposure was estimated using maternal urine samples collected at 24–28 weeks gestation. We used a novel cell mixture deconvolution methodology for examining the association between inferred white blood cell mixtures in infant cord blood and in utero arsenic exposure; we also examined the association between methylation at individual CpG loci and arsenic exposure levels. Results: We found an association between urinary inorganic arsenic concentration and the estimated proportion of CD8+ T lymphocytes (1.18; 95% CI: 0.12, 2.23). Among the top 100 CpG loci with the lowest p-values based on their association with urinary arsenic levels, there was a statistically significant enrichment of these loci in CpG islands (p = 0.009). Of those in CpG islands (n = 44), most (75%) exhibited higher methylation levels in the highest exposed group compared with the lowest exposed group. Also, several CpG loci exhibited a linear dose-dependent relationship between methylation and arsenic exposure. Conclusions: Our findings suggest that in utero exposure to low levels of arsenic may affect the epigenome. Long-term follow-up is planned to determine whether the observed changes are associated with health outcomes

An Amazonian rainforest and its fragments as a laboratory of global change

We synthesize findings from one of the world’s largest and longest-running experimental investigations, the Biological Dynamics of Forest Fragments Project (BDFFP). Spanning an area of ~1,000 km2 in central Amazonia, the BDFFP was initially designed to evaluate the effects of fragment area on rainforest biodiversity and ecological processes. However, over its 38-year history to date the project has far transcended its original mission, and now focuses more broadly on landscape dynamics, forest regeneration, regional- and global-change phenomena, and their potential interactions and implications for Amazonian forest conservation. The project has yielded a wealth of insights into the ecological and environmental changes in fragmented forests. For instance, many rainforest species are naturally rare and hence are either missing entirely from many fragments or so sparsely represented as to have little chance of long-term survival. Additionally, edge effects are a prominent driver of fragment dynamics, strongly affecting forest microclimate, tree mortality, carbon storage and a diversity of fauna. Even within our controlled study area, the landscape has been highly dynamic: for example, the matrix of vegetation surrounding fragments has changed markedly over time, succeeding from large cattle pastures or forest clearcuts to secondary regrowth forest. This, in turn, has influenced the dynamics of plant and animal communities and their trajectories of change over time. In general, fauna and flora have responded differently to fragmentation: the most locally extinction-prone animal species are those that have both large area requirements and low tolerance of the modified habitats surrounding fragments, whereas the most vulnerable plants are those that respond poorly to edge effects or chronic forest disturbances, and that rely on vulnerable animals for seed dispersal or pollination. Relative to intact forests, most fragments are hyperdynamic, with unstable or fluctuating populations of species in response to a variety of external vicissitudes. Rare weather events such as droughts, windstorms and floods have had strong impacts on fragments and left lasting legacies of change. Both forest fragments and the intact forests in our study area appear to be influenced by larger-scale environmental drivers operating at regional or global scales. These drivers are apparently increasing forest productivity and have led to concerted, widespread increases in forest dynamics and plant growth, shifts in tree-community composition, and increases in liana (woody vine) abundance. Such large-scale drivers are likely to interact synergistically with habitat fragmentation, exacerbating its effects for some species and ecological phenomena. Hence, the impacts of fragmentation on Amazonian biodiversity and ecosystem processes appear to be a consequence not only of local site features but also of broader changes occurring at landscape, regional and even global scales

Constraining the Nature of Dark Energy using the SKA

We investigate the potential of the Square Kilometer Array Telescope (SKA) to constrain the sound speed of dark energy. The Integrated Sachs Wolfe (ISW) effect results in a significant power spectrum signal when CMB temperature anisotropies are cross-correlated with galaxies detectable with the SKA in HI. We consider using this measurement, the autocorrelation of HI galaxies and the CMB temperature power spectrum to derive constraints on the sound speed. We study the contributions to the cross-correlation signal made by galaxies at different redshifts and use redshift tomography to improve the signal-to-noise. We use a chi-square analysis to estimate the significance of detecting a sound speed different from that expected in quintessence models, finding that there is potential to distinguish very low sound speeds from the quintessence value.Comment: 8 pages, 8 figures; updated references for publication MNRA

Neuronal precision and the limits for acoustic signal recognition in a small neuronal network

Recognition of acoustic signals may be impeded by two factors: extrinsic noise, which degrades sounds before they arrive at the receiver’s ears, and intrinsic neuronal noise, which reveals itself in the trial-to-trial variability of the responses to identical sounds. Here we analyzed how these two noise sources affect the recognition of acoustic signals from potential mates in grasshoppers. By progressively corrupting the envelope of a female song, we determined the critical degradation level at which males failed to recognize a courtship call in behavioral experiments. Using the same stimuli, we recorded intracellularly from auditory neurons at three different processing levels, and quantified the corresponding changes in spike train patterns by a spike train metric, which assigns a distance between spike trains. Unexpectedly, for most neurons, intrinsic variability accounted for the main part of the metric distance between spike trains, even at the strongest degradation levels. At consecutive levels of processing, intrinsic variability increased, while the sensitivity to external noise decreased. We followed two approaches to determine critical degradation levels from spike train dissimilarities, and compared the results with the limits of signal recognition measured in behaving animals

MicroRNA-375 plays a dual role in prostate carcinogenesis

Background: Prostate cancer (PCa), a highly incident and heterogeneous malignancy, mostly affects men from developed countries. Increased knowledge of the biological mechanisms underlying PCa onset and progression are critical for improved clinical management. MicroRNAs (miRNAs) deregulation is common in human cancers, and understanding how it impacts in PCa is of major importance. MiRNAs are mostly downregulated in cancer, although some are overexpressed, playing a critical role in tumor initiation and progression. We aimed to identify miRNAs overexpressed in PCa and subsequently determine its impact in tumorigenesis. Results: MicroRNA expression profiling in primary PCa and morphological normal prostate (MNPT) tissues identified 17 miRNAs significantly overexpressed in PCa. Expression of three miRNAs, not previously associated with PCa, was subsequently assessed in large independent sets of primary tumors, in which miR-182 and miR-375 were validated, but not miR-32. Significantly higher expression levels of miR-375 were depicted in patients with higher Gleason score and more advanced pathological stage, aswellaswithregionallymph nodesmetastases. Forced expression of miR-375 in PC-3 cells, which display the lowest miR-375 levels among PCa cell lines, increased apoptosis and reduced invasion ability and cell viability. Intriguingly, in 22Rv1 cells, which displayed the highest miR-375 expression, knockdown experiments also attenuated the malignant phenotype. Gene ontology analysis implicated miR-375 in several key pathways deregulated in PCa, including cell cycle and cell differentiation. Moreover, CCND2 was identified as putative miR-375 target in PCa, confirmed by luciferase assay. Conclusions: A dual role for miR-375 in prostate cancer progression is suggested, highlighting the importance of cellular context on microRNA targeting.Research Center of Portuguese Oncology Institute - Porto (CI-IPOP 4–2012) and by the Federal funds through Programa Operacional Temático Factores de Competitividade (COMPETE) with co-participation from the European Community Fund (FEDER) and by the National funds through Fundação para a Ciência e Tecnología (FCT) under the projects EXPL/BIM-ONC/0556/2012. FQV and JRC were or are supported by FCT-Fundação para a Ciência e a Tecnologia grants (SFRH/BD/70564/2010 and SFRH/BD/71293/2010, respectively)

The climatic impacts of land surface change and carbon management, and the implications for climate-change mitigation policy

http://www.sciencedirect.com/science/journal/14693062Strategies to mitigate anthropogenic climate change recognize that carbon sequestration in the terrestrial biosphere can reduce the build-up of carbon dioxide in the Earth’s atmosphere. However, climate mitigation policies do not generally incorporate the effects of these changes in the land surface on the surface albedo, the fluxes of sensible and latent heat to the atmosphere, and the distribution of energy within the climate system. Changes in these components of the surface energy budget can affect the local, regional, and global climate. Given the goal of mitigating climate change, it is important to consider all of the effects of changes in terrestrial vegetation and to work toward a better understanding of the full climate system. Acknowledging the importance of land surface change as a component of climate change makes it more challenging to create a system of credits and debits wherein emission or sequestration of carbon in the biosphere is equated with emission of carbon from fossil fuels. Recognition of the complexity of human-caused changes in climate does not, however, weaken the importance of actions that would seek to minimize our disturbance of the Earth’s environmental system and that would reduce societal and ecological vulnerability to environmental change and variability

Synergistic ecoclimate teleconnections from forest loss in different regions structure global ecological responses

ABSTRACT: Forest loss in hotspots around the world impacts not only local climate where loss occurs, but also influences climate and vegetation in remote parts of the globe through ecoclimate teleconnections. The magnitude and mechanism of remote impacts likely depends on the location and distribution of forest loss hotspots, but the nature of these dependencies has not been investigated. We use global climate model simulations to estimate the distribution of ecologically-relevant climate changes resulting from forest loss in two hotspot regions: western North America (wNA), which is experiencing accelerated dieoff, and the Amazon basin, which is subject to high rates of deforestation. The remote climatic and ecological net effects of simultaneous forest loss in both regions differed from the combined effects of loss from the two regions simulated separately, as evident in three impacted areas. Eastern South American Gross Primary Productivity (GPP) increased due to changes in seasonal rainfall associated with Amazon forest loss and changes in temperature related to wNA forest loss. Eurasia’s GPP declined with wNA forest loss due to cooling temperatures increasing soil ice volume. Southeastern North American productivity increased with simultaneous forest loss, but declined with only wNA forest loss due to changes in VPD. Our results illustrate the need for a new generation of local-to-global scale analyses to identify potential ecoclimate teleconnections, their underlying mechanisms, and most importantly, their synergistic interactions, to predict the responses to increasing forest loss under future land use change and climate change

Habitat fragmentation and the future structure of tree assemblages in a fragmented Atlantic forest landscape

The biodiversity value of human-modified landscapes has become a central question in the tropical forest conservation biology, yet the degree to which plant populations and communities are restructured in response to environmental change remains unclear. Here, we address tree species density in a fragmented Atlantic forest landscape to test the hypothesis that tree assemblages inhabiting edge-dominated forest habitats approach typical conditions of early successional systems. Seedlings and adults from 141 tree species were sampled across 39 0.1-ha plots: 19 in small fragments (55 % of all tree species exhibiting higher densities in small fragments than in mature forest, particularly pioneers (>60 % of all species). Seedlings and adults of these proliferating species differed from species exhibiting population declines in terms of wood density and seed size, respectively. Additionally, pioneers were more abundant than shade-tolerant species, as were hardwood species in the case of seedlings. Tree species showing highest population increases consisted largely of long-lived, light-demanding canopy species bearing soft or hardwood and small-to-medium-sized seeds. Tree assemblage structure also differed in terms of forest habitats with small forest fragments supporting few rare species, whereas the most rapidly proliferating species were much more widespread and abundant in fragments. However, 60 % of all adult pioneer species recorded in small fragments were not recorded as seedlings in this habitat type, although both seedling and adult assemblages were dominated by pioneer species. Edge-dominated tree assemblages are likely to experience long-term shifts toward greater dominance of long-lived, pioneer canopy species

Genomic features and computational identification of human microRNAs under long-range developmental regulation

<p>Abstract</p> <p>Background</p> <p>Recent functional studies have demonstrated that many microRNAs (miRNAs) are expressed by RNA polymerase II in a specific spatiotemporal manner during the development of organisms and play a key role in cell-lineage decisions and morphogenesis. They are therefore functionally related to a number of key protein coding developmental genes, that form genomic regulatory blocks (GRBs) with arrays of highly conserved non-coding elements (HCNEs) functioning as long-range enhancers that collaboratively regulate the expression of their target genes. Given this functional similarity as well as recent zebrafish transgenesis assays showing that the miR-9 family is indeed regulated by HCNEs with enhancer activity, we hypothesized that this type of miRNA regulation is prevalent. In this paper, we therefore systematically investigate the regulatory landscape around conserved self-transcribed miRNAs (ST miRNAs), with their own known or computationally inferred promoters, by analyzing the hallmarks of GRB target genes. These include not only the density of HCNEs in their vicinity but also the presence of large CpG islands (CGIs) and distinct patterns of histone modification marks associated with developmental genes.</p> <p>Results</p> <p>Our results show that a subset of the conserved ST miRNAs we studied shares properties similar to those of protein-coding GRB target genes: they are located in regions of significantly higher HCNE/enhancer binding density and are more likely to be associated with CGIs. Furthermore, their putative promoters have both activating as well as silencing histone modification marks during development and differentiation. Based on these results we used both an elevated HCNE density in the genomic vicinity as well as the presence of a bivalent promoter to identify 29 putative GRB target miRNAs/miRNA clusters, over two-thirds of which are known to play a role during development and differentiation. Furthermore these predictions include miRNAs of the miR-9 family, which are the only experimentally verified GRB target miRNAs.</p> <p>Conclusions</p> <p>A subset of the conserved miRNA loci we investigated exhibits typical characteristics of GRB target genes, which may partially explain their complex expression profiles during development.</p