When Parasites Are Good for Health: Cestode Parasitism Increases Resistance to Arsenic in Brine Shrimps

Parasites and pollutants can both affect any living organism, and their interactions can be very important. To date, repeated studies have found that parasites and heavy metals or metalloids both have important negative effects on the health of animals, often in a synergistic manner. Here, we show for the first time that parasites can increase host resistance to metalloid arsenic, focusing on a clonal population of brine shrimp from the contaminated Odiel and Tinto estuary in SW Spain. We studied the effect of cestodes on the response of Artemia to arsenic (acute toxicity tests, 24h LC₅₀) and found that infection consistently reduced mortality across a range of arsenic concentrations. An increase from 25°C to 29°C, simulating the change in mean temperature expected under climate change, increased arsenic toxicity, but the benefits of infection persisted. Infected individuals showed higher levels of catalase and glutathione reductase activity, antioxidant enzymes with a very important role in the protection against oxidative stress. Levels of TBARS were unaffected by parasites, suggesting that infection is not associated with oxidative damage. Moreover, infected Artemia had a higher number of carotenoid-rich lipid droplets which may also protect the host through the “survival of the fattest” principle and the antioxidant potential of carotenoids. This study illustrates the need to consider the multi-stress context (contaminants and temperature increase) in which host-parasite interactions occur.     

Epistatic Gene-Based Interaction Analyses for Glaucoma in eMERGE and NEIGHBOR Consortium

Primary open angle glaucoma (POAG) is a complex disease and is one of the major leading causes of blindness worldwide. Genome-wide association studies have successfully identified several common variants associated with glaucoma; however, most of these variants only explain a small proportion of the genetic risk. Apart from the standard approach to identify main effects of variants across the genome, it is believed that gene-gene interactions can help elucidate part of the missing heritability by allowing for the test of interactions between genetic variants to mimic the complex nature of biology. To explain the etiology of glaucoma, we first performed a genome-wide association study (GWAS) on glaucoma case-control samples obtained from electronic medical records (EMR) to establish the utility of EMR data in detecting non-spurious and relevant associations; this analysis was aimed at confirming already known associations with glaucoma and validating the EMR derived glaucoma phenotype. Our findings from GWAS suggest consistent evidence of several known associations in POAG. We then performed an interaction analysis for variants found to be marginally associated with glaucoma (SNPs with main effect p-value <0.01) and observed interesting findings in the electronic MEdical Records and GEnomics Network (eMERGE) network dataset. Genes from the top epistatic interactions from eMERGE data (Likelihood Ratio Test i.e. LRT p-value <1e-05) were then tested for replication in the NEIGHBOR consortium dataset. To replicate our findings, we performed a gene-based SNP-SNP interaction analysis in NEIGHBOR and observed significant gene-gene interactions (p-value <0.001) among the top 17 gene-gene models identified in the discovery phase. Variants from gene-gene interaction analysis that we found to be associated with POAG explain 3.5% of additional genetic variance in eMERGE dataset above what is explained by the SNPs in genes that are replicated from previous GWAS studies (which was only 2.1% variance explained in eMERGE dataset); in the NEIGHBOR dataset, adding replicated SNPs from gene-gene interaction analysis explain 3.4% of total variance whereas GWAS SNPs alone explain only 2.8% of variance. Exploring gene-gene interactions may provide additional insights into many complex traits when explored in properly designed and powered association studies.     

Evaluation of metabolomics profiles of grain from maize hybrids derived from near-isogenic GM positive and negative segregant inbreds demonstrates that observed differences cannot be attributed unequivocally to the GM trait

Introduction

Past studies on plant metabolomes have highlighted the influence of growing environments and varietal differences in variation of levels of metabolites yet there remains continued interest in evaluating the effect of genetic modification (GM).

Objectives

Here we test the hypothesis that metabolomics differences in grain from maize hybrids derived from a series of GM (NK603, herbicide tolerance) inbreds and corresponding negative segregants can arise from residual genetic variation associated with backcrossing and that the effect of insertion of the GM trait is negligible.

Methods

Four NK603-positive and negative segregant inbred males were crossed with two different females (testers). The resultant hybrids, as well as conventional comparator hybrids, were then grown at three replicated field sites in Illinois, Minnesota, and Nebraska during the 2013 season. Metabolomics data acquisition using gas chromatography–time of flight-mass spectrometry (GC–TOF-MS) allowed the measurement of 367 unique metabolite features in harvested grain, of which 153 were identified with small molecule standards. Multivariate analyses of these data included multi-block principal component analysis and ANOVA-simultaneous component analysis. Univariate analyses of all 153 identified metabolites was conducted based on significance testing (α = 0.05), effect size evaluation (assessing magnitudes of differences), and variance component analysis.

Results

Results demonstrated that the largest effects on metabolomic variation were associated with different growing locations and the female tester. They further demonstrated that differences observed between GM and non-GM comparators, even in stringent tests utilizing near-isogenic positive and negative segregants, can simply reflect minor genomic differences associated with conventional back-crossing practices.

Conclusion

The effect of GM on metabolomics variation was determined to be negligible and supports that there is no scientific rationale for prioritizing GM as a source of variation.

     

Reactivation of mutant p53: Constraints on mechanism highlighted by principal component analysis of the DNA binding domain

Most p53 mutations associated with cancer are located in its DNA binding domain (DBD). Many structures (X‐ray and NMR) of this domain are available in the protein data bank (PDB) and a vast conformational heterogeneity characterizes the various free and complexed states. The major difference between the apo and the holo‐complexed states appears to lie in the L1 loop. In particular, the conformations of this loop appear to depend intimately on the sequence of DNA to which it binds. This conclusion builds upon recent observations that implicate the tetramerization and the C‐terminal domains (respectively TD and Cter) in DNA binding specificity. Detailed PCA analysis of the most recent collection of DBD structures from the PDB have been carried out. In contrast to recommendations that small molecules/drugs stabilize the flexible L1 loop to rescue mutant p53, our study highlights a need to retain the flexibility of the p53 DNA binding surface (DBS). It is the adaptability of this region that enables p53 to engage in the diverse interactions responsible for its functionality. Proteins 2016; 84:1443–1461. © 2016 Wiley Periodicals, Inc.     

Biogenic production of DMSP and its degradation to DMS—their roles in the global sulfur cycle

Dimethyl sulfide(DMS) is the most abundant form of volatile sulfur in Earth's oceans, and is mainly produced by the enzymatic clevage of dimethylsulfoniopropionate(DMSP). DMS and DMSP play important roles in driving the global sulfur cycle and may affect climate. DMSP is proposed to serve as an osmolyte, a grazing deterrent, a signaling molecule, an antioxidant, a cryoprotectant and/or as a sink for excess sulfur. It was long believed that only marine eukaryotes such as phytoplankton produce DMSP. However, we recently discovered that marine heterotrophic bacteria can also produce DMSP, making them a potentially important source of DMSP. At present, one prokaryotic and two eukaryotic DMSP synthesis enzymes have been identified.Marine heterotrophic bacteria are likely the major degraders of DMSP, using two known pathways: demethylation and cleavage.Many phytoplankton and some fungi can also cleave DMSP. So far seven different prokaryotic and one eukaryotic DMSP lyases have been identified. This review describes the global distribution pattern of DMSP and DMS, the known genes for biosynthesis and cleavage of DMSP, and the physiological and ecological functions of these important organosulfur molecules, which will improve understanding of the mechanisms of DMSP and DMS production and their roles in the environment.     

Metabolite Profiling of Anti‐Addictive Alkaloids from Four Mexican Tabernaemontana Species and the Entheogenic African Shrub Tabernanthe iboga (Apocynaceae)

Ibogaine and other ibogan type alkaloids present anti‐addictive effects against several drugs of abuse and occur in different species of the Apocynaceae family. In this work, we used gas chromatography‐mass spectrometry (GC/MS) and principal component analysis (PCA) in order to compare the alkaloid profiles of the root and stem barks of four Mexican Tabernaemontana species with the root bark of the entheogenic African shrub Tabernanthe iboga. PCA demonstrated that separation between species could be attributed to quantitative differences of the major alkaloids, coronaridine, ibogamine, voacangine, and ibogaine. While T. iboga mainly presented high concentrations of ibogaine, Tabernaemontana samples either showed a predominance of voacangine and ibogaine, or coronaridine and ibogamine, respectively. The results illustrate the phytochemical proximity between both genera and confirm previous suggestions that Mexican Tabernaemontana species are viable sources of anti‐addictive compounds.     

Enhanced Stability and Thickness‐Independent Oxygen Evolution Electrocatalysis of Heterostructured Anodes with Buried Epitaxial Bilayers

Achieving high oxygen evolution reaction (OER) activity while maintaining performance stability is a key challenge for designing perovskite structure oxide OER catalysts, which are often unstable in alkaline environments transforming into an amorphous phase. While the chemical and structural transformation occurring during electrolysis at the electrolyte–catalyst interface is now regarded as a crucial factor influencing OER activity, here, using La_0.7Sr_0.3CoO_3?δ (LSCO) as an active OER catalyst, the critical influence of buried layers on the oxidation current stability in nanoscopically thin, chemically and structurally evolving, catalyst layers is revealed. The use of epitaxial thin films is demonstrated to engineer both depletion layer widths and chemical stability of the catalyst support structure resulting in heterostructured anodes that maintain facile transport kinetics across the electrolyte–anode interface for atomically thin (2–3 unit cells) LSCO catalyst layers and greatly enhanced oxidation current stability as the perovskite structure OER catalysts chemically and structurally transform. This work opens up an approach to design robust and active heterostructured anodes with dynamically evolving ultrathin OER electrocatalyst layers for future green fuel technologies such as conformal coatings of high‐density 3D anode topologies for water splitting.