Influence of DNMT Genotype on Global and Site Specific DNA Methylation Patterns in Neonates and Pregnant Women

This study examines the relationship between common genetic variation within DNA methyltransferase genes and inter-individual variation in DNA methylation. Eleven polymorphisms spanning DNMT1 and DNMT3B were genotyped. Global and gene specific (IGF2, IGFBP3, ZNT5) DNA methylation was quantified by LUMA and bisulfite Pyrosequencing assays, respectively, in neonatal cord blood and in maternal peripheral blood. Associations between maternal genotype and maternal methylation (n ^≈ 333), neonatal genotype and neonatal methylation (n ^≈ 454), and maternal genotype and neonatal methylation (n ^≈ 137) were assessed. The findings of this study provide some support to the hypothesis that genetic variation in DNA methylating enzymes influence DNA methylation at global and gene-specific levels; however observations were not robust to correction for multiple testing. More comprehensive analysis of the influence of genetic variation on global and site specific DNA methylation is warranted.     

In vivo signaling through the neurokinin 1 receptor favors transgene expression by Langerhans cells and promotes the generation of Th1- and Tc1-biased immune responses

The proinflammatory capacities of the skin and the presence of high numbers of resident dendritic cells (DCs) constitute an ideal microenvironment for successful immunizations. Regardless of the ability of DCs to respond to local inflammatory signals in an immunostimulatory fashion, the immune functions of skin-resident DCs remain controversial, and epidermal Langerhans cells (LCs) have been referred to recently as anti-inflammatory/protolerogenic APCs. Substance P (SP), released by skin nerve fibers, is a potent proinflammatory neuropeptide that favors development of skin-associated cellular immunity. SP exerts its proinflammatory functions by binding with high affinity to the neurokinin 1 receptor (NK1R). In this study, we tested whether signaling skin cells via the NK1R promotes humoral and cellular immunity during skin genetic immunizations. We used the gene gun to deliver transgenic (tg) Ag to the skin of C57BL/6 mice and the selective NK1R agonist [Sar(9)Met (O(2)) (11)]-SP as a potential proinflammatory Th1-biasing adjuvant. Our strategy expressed tg Ag exclusively in the epidermis and induced a preferential migration of activated LCs to skin-draining lymph nodes. Local administration of the NK1R agonist during skin genetic immunizations increased significantly the expression of tg Ag by a mechanism involving the translocation of NF-kappaB into the nuclei of cutaneous DCs homing to skin-draining lymph nodes. Importantly, our immunization approach resulted in Th1 and T cytotoxic (CTL)-1 bias of effector T cells that supported cellular and Ab-mediated immune responses. We demonstrate that signaling skin cells via the NK1R provides the adjuvant effect which favors the immunostimulatory functions of LCs.     

Assessment of dietary intake: NuGO symposium report

Advances in genomics science and associated bioinformatics and technology mean that excellent tools are available for characterising human genotypes. At the same time, approaches for characterising individual phenotypes are developing rapidly. In contrast, there has been much less investment in novel methodology for measuring dietary exposures so that there is now a significant gap in the toolkit for those investigating how diet interacts with genotype to determine phenotype. This symposium reviewed the strengths and limitations of current tools used in assessment of dietary intake and the potential to improve these tools through, for example, the use of statistical techniques that combine information from different sources (such as modelling and calibration methods) to ameliorate measurement error and to provide validity checks. Speakers examined the use of approaches based on technologies such as mobile 'phones, digital cameras and Web-based systems which offer the potential for more acceptable (for study participants) and less laborious (for researchers and participants) routes to more robust data collection. In addition, the application of omics, especially metabolomics, tools to biofluids to identify new biomarkers of intake offers great potential to provide objective measures of food consumption with the advantage that data may be collected in forms that can be integrated readily with other high throughput (nutrigenomic) technologies.     

Benthic and hyporheic macroinvertebrate distribution within the heads and tails of riffles during baseflow conditions

The distribution of lotic fauna is widely acknowledged to be patchy reflecting the interaction between biotic and abiotic factors. In an in situ field study, the distribution of benthic and hyporheic invertebrates in the heads (downwelling) and tails (upwelling) of riffles were examined during stable baseflow conditions. Riffle heads were found to contain a greater proportion of interstitial fine sediment than riffle tails. Significant differences in the composition of benthic communities were associated with the amount of fine sediment. Riffle tail habitats supported a greater abundance and diversity of invertebrates sensitive to fine sediment such as EPT taxa. Shredder feeding taxa were more abundant in riffle heads suggesting greater availability of organic matter. In contrast, no significant differences in the hyporheic community were recorded between riffle heads and tails. We hypothesise that clogging of hyporheic interstices with fine sediments may have resulted in the homogenisation of the invertebrate community by limiting faunal movement into the hyporheic zone at both the riffle heads and tails. The results suggest that vertical hydrological exchange significantly influences the distribution of fine sediment and macroinvertebrate communities at the riffle scale.     

Complex binding interactions between multicomponent mixtures and odorant receptors in the olfactory organ of the Caribbean spiny lobster Panulirus argus

Our study was designed to examine how components of complex mixtures can inhibit the binding of other components to receptor sites in the olfactory system of the spiny lobster Panulirus argus. Biochemical binding assays were used to study how two- to six-component mixtures inhibit binding of the radiolabeled odorants taurine, L-glutamate and adenosine-5'-monophosphate to a tissue fraction rich in dendritic membrane of olfactory receptor neurons. Our results indicate that binding inhibition by mixtures can be large and is dependent on the nature of the odorant ligand and on the concentration and composition of the mixture. The binding inhibition by mixtures of structurally related components was generally predicted using a competitive binding model and binding inhibition data for the individual components. This was not the case for binding inhibition by most mixtures of structurally unrelated odorants. The binding inhibition for these mixtures was generally smaller than that for one or more of their components, indicating that complex binding interactions between components can reduce their ability to inhibit binding. The magnitude of binding inhibition was influenced more by the mixture's precise composition than by the number of components in it, since mixtures with few components were sometimes more inhibitory than mixtures with more components. These findings raise the possibility that complex binding interactions between components of a mixture and their receptors may shape the output of olfactory receptor neurons to complex mixtures.      

Anti-cytokine therapy in the treatment of psoriasis

Psoriasis is a chronic, inflammatory skin disease with many associated co-morbidities including diabetes, hypertension, obesity, psoriatic arthritis, and cardiovascular disease. It has long been known that psoriasis is a T cell-mediate disease and recent findings further demonstrate the important roles of the Th17 and Th22 arms of the immune system in the pathogenesis of psoriasis. Our understanding of this disease has progressed greatly and agents that target the cytokines involved in disease activity are under development or currently being used to treat psoriasis. A comprehensive review of the literature for cytokine-targeted therapies, their safety concerns, and efficacy in psoriasis are discussed here.     

Beneath the surface: Application of transparent super absorbent polymer substrates to track faunal activity within the sediment layer

1. Tracking the movement of organisms is a fundamental goal of many ecological studies. Several techniques exist in the study of terrestrial and aquatic fauna; however, to date, the ability to monitor aquatic fauna within the sediment layer efficiently and in multiple dimensions is lacking. Given the importance of subsurface sediments in supporting ecosystem functioning, this inability to observe organism behaviour represents a fundamental gap in our knowledge and limits our capability to holistically characterise the response of freshwater systems to stressors.
2. Here we present an experimental study that employs novel transparent super absorbent polymer substrates (c. 8–12 mm in diameter) in combination with computer vision technology, which enables, for the first time, real-time observation and tracking of organisms within the sediment layer under lotic flow conditions. Use of these substrates allowed the successful extraction of organism trajectories, which enabled the velocity and body orientation of a freshwater amphipod (Gammarus fossarum) in the sediment layer to be calculated in response to a number of vertical hydrological exchange treatments (upwelling, downwelling, and no vertical exchange).
3. Results indicate that under vertical hydrological exchange, a higher proportion of fast velocities (both horizontal and vertical) were recorded for G. fossarum in the sediment layer compared to no vertical exchange (control) conditions. This increase was most marked for upwelling flow exchange. We also observed a change in the body orientation of individuals in the sediment layer from a vertical alignment under no vertical exchange to a more horizontal one under downwelling and more notably upwelling flow exchange. This shift in body position was exacerbated under stronger vertical exchange rates.
4. We identified that following the flow transition of downwelling to upwelling conditions, there was an immediate shift (0–2 min) in both the orientation angle and activity level of individuals. This increased rate of activity was maintained for the individuals' velocity but not for their changing orientation angle. These trends were not apparent within the flow transition of no vertical exchange to downwelling flow.
5. Our new methodological approach enables vital insights into the behaviour of organisms within the sediment layer. Use of super absorbent polymer substrates allows real-time multi-directional tracking of multiple organisms in parallel. We believe the method represents an innovative tool that can be employed to tackle a wide range of ecological questions and thereby improve our mechanistic understanding of ecological responses to biotic and abiotic processes/stressors.