A genetic ensemble approach for gene-gene interaction identification

Background  

It has now become clear that gene-gene interactions and gene-environment interactions are ubiquitous and fundamental mechanisms for the development of complex diseases. Though a considerable effort has been put into developing statistical models and algorithmic strategies for identifying such interactions, the accurate identification of those genetic interactions has been proven to be very challenging.     

Dissociating pleasantness and intensity with quinine sulfate/sucrose mixtures in taste

Independent experimental manipulation of subjective intensity and hedonic tone is required if one wants to study their separate effects on brain activity and behavior. This is problematic because hedonic tone and subjective intensity are related, leading to a pleasantness change each time the stimulus intensity is altered. In the present study, a solution to this problem was explored by combining a pleasant-tasting substance (sucrose) and a bad-tasting substance (quinine sulfate) into a number of different isointense mixtures. Here we show that subjective intensity as well as pleasantness can be accurately predicted, particularly in midrange, only if one corrects for mixture suppression.     

A partial BRCA1 sequence homology mapping to 4q28.

Using a BRCA1 cDNA probe in Southern analysis, we detected a sequence of 348 bp on 4q28 that is homologous to the 3' end of BRCA1. A 28-kb sequence contig has been assembled spanning the homologous region, which we designated BRCA1-h. An open reading frame was identified encoding a sequence of 82 amino acids; 22 of the last 23 amino acids are identical to the last 23 residues of BRCA1. BLAST-searches, RT-PCR and RACE-experiments have been unable to provide evidence that BRCA1-h is part of an expressed gene.     

Gene-gene interaction filtering with ensemble of filters

BACKGROUND: Complex diseases are commonly caused by multiple genes and their interactions with each other. Genome-wide association (GWA) studies provide us the opportunity to capture those disease associated genes and gene-gene interactions through panels of SNP markers. However, a proper filtering procedure is critical to reduce the search space prior to the computationally intensive gene-gene interaction identification step. In this study, we show that two commonly used SNP-SNP interaction filtering algorithms, ReliefF and tuned ReliefF (TuRF), are sensitive to the order of the samples in the dataset, giving rise to unstable and suboptimal results. However, we observe that the 'unstable' results from multiple runs of these algorithms can provide valuable information about the dataset. We therefore hypothesize that aggregating results from multiple runs of the algorithm may improve the filtering performance. RESULTS: We propose a simple and effective ensemble approach in which the results from multiple runs of an unstable filter are aggregated based on the general theory of ensemble learning. The ensemble versions of the ReliefF and TuRF algorithms, referred to as ReliefF-E and TuRF-E, are robust to sample order dependency and enable a more informative investigation of data characteristics. Using simulated and real datasets, we demonstrate that both the ensemble of ReliefF and the ensemble of TuRF can generate a much more stable SNP ranking than the original algorithms. Furthermore, the ensemble of TuRF achieved the highest success rate in comparison to many state-of-the-art algorithms as well as traditional χ2-test and odds ratio methods in terms of retaining gene-gene interactions.     

云南省米虾属一新种(十足目：匙指虾科)

报道了米虾属一新种-昆明米虾Caridina kunmingensis Wang et Liang,sp.nov.。昆明米虾与石林米虾Caridina shilinica Liang et Cai2000有相似之处,但前者额角较短,前两对步足腕节和螯短而粗,雄性第1腹肢内肢、雄附肢形态和结构均与后者不同。     

Structure and function of the third intracellular loop of the 5-hydroxytryptamine2A receptor: the third intracellular loop is alpha-helical and binds purified arrestins

Understanding the precise structure and function of the intracellular domains of G protein-coupled receptors is essential for understanding how receptors are regulated, and how they transduce their signals from the extracellular milieu to intracellular sites. To understand better the structure and function of the intracellular domain of the 5-hydroxytryptamine2A (5-HT2A) receptor, a model G(alpha)q-coupled receptor, we overexpressed and purified to homogeneity the entire third intracellular loop (i3) of the 5-HT2A receptor, a region previously implicated in G-protein coupling. Circular dichroism spectroscopy of the purified i3 protein was consistent with alpha-helical and beta-loop, -turn, and -sheet structure. Using random peptide phage libraries, we identified several arrestin-like sequences as i3-interacting peptides. We subsequently found that all three known arrestins (beta-arrestin, arrestin-3, and visual arrestin) bound specifically to fusion proteins encoding the i3 loop of the 5-HT(2A) receptor. Competition binding studies with synthetic and recombinant peptides showed that the middle portion of the i3 loop, and not the extreme N and C termini, was likely to be involved in i3-arrestin interactions. Dual-label immunofluorescence confocal microscopic studies of rat cortex indicated that many cortical pyramidal neurons coexpressed arrestins (beta-arrestin or arrestin-3) and 5-HT2A receptors, particularly in intracellular vesicles. Our results demonstrate (a) that the i3 loop of the 5-HT2A receptor represents a structurally ordered domain composed of alpha-helical and beta-loop, -turn, and -sheet regions, (b) that this loop interacts with arrestins in vitro, and is hence active, and (c) that arrestins are colocalized with 5-HT2A receptors in vivo.     

Sensory evaluation of character impact components in an apple model mixture

Food aromas generally are complex mixtures of volatiles. In the present study, we investigated the joint effects of hexyl acetate, trans-2-hexenal and 1-hexanol on the multi-attribute perception of an apple aroma. The first two substances were identified earlier as positive contributors to the apple aroma (high character impact), whereas the third component was identified as an irrelevant or negative contributor (low character impact). Aroma quality was quantified using a set of eight graphic rating scales. All three components had significant effects on the aroma profiles. These effects consist mainly of an effect of each component on the attribute that described its individual character and an effect of all three components on ratings on the main character attribute 'apple'. As expected, the high impact components increased 'apple' ratings, whereas the low character impact component decreased 'apple' ratings. Furthermore, intensity ratings on the attribute that corresponded with the odour of the low impact component were suppressed by the presence of high impact components. These results indicate that the contributions of odorants to the mixture's aroma are not linear combinations of separate odour intensities, because sensory interactions were observed. In addition, humans detect components in complex mixtures more accurately than studies on identification performance have suggested. We conclude that for an adequate assessment of the effects of multiple mixture components on changes in aroma perception, it is sufficient to employ multiple response scales measuring intensities of attributes that are distinctive with respect to the expected qualitative changes. Results of this approach should be subjected to multivariate methods of statistical analysis.     

Identification of Drosophila Yin and PEPT2 as Evolutionarily Conserved Phagosome-associated Muramyl Dipeptide Transporters

NOD2 (nucleotide-binding oligomerization domain containing 2) is an important cytosolic pattern recognition receptor that activates NF-κB and other immune effector pathways such as autophagy and antigen presentation. Despite its intracellular localization, NOD2 participates in sensing of extracellular microbes such as Staphylococcus aureus. NOD2 ligands similar to the minimal synthetic ligand muramyl dipeptide (MDP) are generated by internalization and processing of bacteria in hydrolytic phagolysosomes. However, how these derived ligands exit this organelle and access the cytosol to activate NOD2 is poorly understood. Here, we address how phagosome-derived NOD2 ligands access the cytosol in human phagocytes. Drawing on data from Drosophila phagosomes, we identify an evolutionarily conserved role of SLC15A transporters, Drosophila Yin and PEPT2, as MDP transporters in fly and human phagocytes, respectively. We show that PEPT2 is highly expressed by human myeloid cells. Ectopic expression of both Yin and PEPT2 increases the sensitivity of NOD2-dependent NF-κB activation. Additionally, we show that PEPT2 associates with phagosome membranes. Together, these data identify Drosophila Yin and PEPT2 as evolutionarily conserved phagosome-associated transporters that are likely to be of particular importance in delivery of bacteria-derived ligands generated in phagosomes to cytosolic sensors recruited to the vicinity of these organelles.     

Effects of inflammatory cytokine IL-27 on the activation of fibroblast-like synoviocytes in rheumatoid arthritis

Introduction  

Interleukin (IL)-27 is a novel member of the IL-6/IL-12 family cytokines that are produced early by antigen-presenting cells in T helper (Th)1-mediated inflammation. Elevated expression of IL-27 has been detected in the synovial membranes and fluid of rheumatoid arthritis (RA).     

Reducing the impact of irrigated crops on freshwater availability: the case of Brazilian yellow melons

Purpose

This study quantifies freshwater consumption throughout the life cycle of Brazilian exported yellow melons and assesses the resulting impact on freshwater availability. Results are used to identify improvement options. Moreover, the study explores the further impact of variations in irrigation volume, yield, and production location.

Methods

The product system boundary encompasses production of seeds, seedlings, and melon plants; melon packing; disposal of solid farm waste; and farm input and melon transportation to European ports. The primary data in the study were collected from farmers in order to quantify freshwater consumption related to packing and to production of seeds, seedlings, and melons. Open-field melon irrigation was also estimated, considering the region's climate and soil characteristics. Estimated and current water consumptions were compared in order to identify impact reduction opportunities. Sensitivity analysis was used to evaluate variations in the impact because of changes in melon field irrigation, yield, and farm location.

Results and discussion

This study shows that the average impact on freshwater availability of 1 kg of exported Brazilian yellow melons is 135 l H₂O-e, with a range from 17 to 224 l H₂O-e depending on the growing season's production period. Irrigation during plant production accounts for 98 % of this impact. Current melon field water consumption in the Low Jaguaribe and Açu region is at least 39 % higher than necessary, which affects the quality of fruits and yield. The impact of melon production in other world regions on freshwater availability may range from 0.3 l H₂O-e/kg in Costa Rica to 466 l H₂O-e/kg in the USA.

Conclusions

The impact of temporary crops, such as melons, on water availability should be presented in ranges, instead of as an average, since regional consumptive water and water stress variations occur in different growing season periods. Current and estimated water consumption for irrigation may also be compared in order to identify opportunities to achieve optimization and reduce water availability impact.