Effects of four monoterpenoids on growth and reproduction of the German cockroach (Blattodea: Blattellidae).

The effects of the monoterpenoids d-limonene, linalool, beta-myrcene, and alpha-terpineol on the growth and development of the German cockroach Blattella germanica (L.) were examined. We evaluated the chemicals' attractiveness in cockroach diet, quantified growth effects induced by monoterpenoids, examined embryotoxic properties of the compounds, and examined their effects on reproduction when administered by oral, topical, and vapor routes of entry. Untreated diet was significantly preferred compared with diet treated with high levels of d-limonene, linalool, and alpha-terpineol. The threshold for acceptance was between 1 and 10% (AI). All four monoterpenoids significantly influenced the days required by nymphs to reach the adult stage; in general, higher monoterpenoid concentrations in the diet were associated with a reduction in the days required by nymphs to mature. Application of high doses of d-limonene or linalool to oothecae of gravid female cockroaches significantly decreased the probability of young emerging from them but did not affect female mortality. Feeding on diet treated with monoterpenoids during nymphal development and through the early, premating period of the adult stage did not significantly influence numbers of broods produced per pair, numbers of offspring per brood, days required to produce a brood, total offspring produced by a pair, or female life span. Topical applications of linalool, beta-myrcene, or alpha-terpineol at near lethal rates to adult cockroaches before they mated had no significant influence on the reproductive parameters examined. A single exposure to sublethal levels of monoterpenoid vapors before mating had no significant influence on any reproductive parameters examined.     

A comparative analysis of the synergistic interaction between N1-phenylsulfanilamides and benzylpyrimidines using qsar techniques

Growth inhibition of E. coli cell culture has been determined for a series of 4-substituted-N1-phenylsulfonilamides tested in the presence and absence of synergistic concentrations of trimethoprim. Quantitative structure-activity relationships, established by regression analysis, exhibit an identical dependence of bacterial growth inhibition on sulfonamide pKa irrespective of the presence or absence of trimethoprim. Examination of a small series of benzylpyrimidines in the presence or absence of 4-dimethylamino-N1-phenylsulfanilamide gave similar results. Since the presence of a synergistic agent affords no change in structure-activity relationships, it is concluded that no direct interaction between sulfonamides and benzylpyrimidines occurs and that the synergism observed is solely the result of the kinetic consequences of sequential blockade of the folate biosynthetic pathway.     

Identifying rare and common disease associated variants in genomic data using Parkinson’s disease as a model

Background

Genome-wide association studies have been successful in identifying common genetic variants for human diseases. However, much of the heritable variation associated with diseases such as Parkinson’s disease remains unknown suggesting that many more risk loci are yet to be identified. Rare variants have become important in disease association studies for explaining missing heritability. Methods for detecting this type of association require prior knowledge on candidate genes and combining variants within the region. These methods may suffer from power loss in situations with many neutral variants or causal variants with opposite effects.

Results

We propose a method capable of scanning genetic variants to identify the region most likely harbouring disease gene with rare and/or common causal variants. Our method assigns a score at each individual variant based on our scoring system. It uses aggregate scores to identify the region with disease association. We evaluate performance by simulation based on 1000 Genomes sequencing data and compare with three commonly used methods. We use a Parkinson’s disease case–control dataset as a model to demonstrate the application of our method.Our method has better power than CMC and WSS and similar power to SKAT-O with well-controlled type I error under simulation based on 1000 Genomes sequencing data. In real data analysis, we confirm the association of α-synuclein gene (SNCA) with Parkinson’s disease (p = 0.005). We further identify association with hyaluronan synthase 2 (HAS2, p = 0.028) and kringle containing transmembrane protein 1 (KREMEN1, p = 0.006). KREMEN1 is associated with Wnt signalling pathway which has been shown to play an important role for neurodegeneration in Parkinson’s disease.

Conclusions

Our method is time efficient and less sensitive to inclusion of neutral variants and direction effect of causal variants. It can narrow down a genomic region or a chromosome to a disease associated region. Using Parkinson’s disease as a model, our method not only confirms association for a known gene but also identifies two genes previously found by other studies. In spite of many existing methods, we conclude that our method serves as an efficient alternative for exploring genomic data containing both rare and common variants.

Electronic supplementary material

The online version of this article (doi:10.1186/s12929-014-0088-9) contains supplementary material, which is available to authorized users.     

Distinct Lipid A Moieties Contribute to Pathogen-Induced Site-Specific Vascular Inflammation

Several successful pathogens have evolved mechanisms to evade host defense, resulting in the establishment of persistent and chronic infections. One such pathogen, Porphyromonas gingivalis, induces chronic low-grade inflammation associated with local inflammatory bone loss and systemic inflammation manifested as atherosclerosis. P. gingivalis expresses an atypical lipopolysaccharide (LPS) structure containing heterogeneous lipid A species, that exhibit Toll-like receptor-4 (TLR4) agonist or antagonist activity, or are non-activating at TLR4. In this study, we utilized a series of P. gingivalis lipid A mutants to demonstrate that antagonistic lipid A structures enable the pathogen to evade TLR4-mediated bactericidal activity in macrophages resulting in systemic inflammation. Production of antagonistic lipid A was associated with the induction of low levels of TLR4-dependent proinflammatory mediators, failed activation of the inflammasome and increased bacterial survival in macrophages. Oral infection of ApoE^−/− mice with the P. gingivalis strain expressing antagonistic lipid A resulted in vascular inflammation, macrophage accumulation and atherosclerosis progression. In contrast, a P. gingivalis strain producing exclusively agonistic lipid A augmented levels of proinflammatory mediators and activated the inflammasome in a caspase-11-dependent manner, resulting in host cell lysis and decreased bacterial survival. ApoE^−/− mice infected with this strain exhibited diminished vascular inflammation, macrophage accumulation, and atherosclerosis progression. Notably, the ability of P. gingivalis to induce local inflammatory bone loss was independent of lipid A expression, indicative of distinct mechanisms for induction of local versus systemic inflammation by this pathogen. Collectively, our results point to a pivotal role for activation of the non-canonical inflammasome in P. gingivalis infection and demonstrate that P. gingivalis evades immune detection at TLR4 facilitating chronic inflammation in the vasculature. These studies support the emerging concept that pathogen-mediated chronic inflammatory disorders result from specific pathogen-mediated evasion strategies resulting in low-grade chronic inflammation.     

The BOS™ as a species-specific method to deliver baits to wild boar in a Mediterranean area

The impact of wild boar Sus scrofa and feral pigs on ecosystems and human activities is of interest worldwide. Bait-delivered pharmaceuticals such as contraceptives or disease vaccines are increasingly advocated to assist the management of such impacts. We evaluated the Boar-Operated-System (BOS?) to deliver baits to wild boar in a Mediterranean area with a large community of potential nontarget species. In a pre-trial phase (BOS? open), both wild boar and 12 nontarget species (wildlife and livestock) visited the BOS? and eight species consumed the baits. In the trial phase, when the BOS? were closed, only wild boar consumed baits. From pre-trial to trial, the rate of visits by nontarget species to the BOS? decreased significantly, but that of wild boar did not change. We observed that crested porcupines Hystrix cristata prevented the wild boar from using BOS?. We confirmed the effectiveness of BOS? to deliver baits selectively to wild boar in a Mediterranean area.     

Disposition of Atrazine Metabolites Following Uptake and Degradation of Atrazine in Switchgrass

Extensive use of the agricultural herbicide atrazine has led to contamination of numerous ground and surface water bodies. Research has shown that it can have a variety of negative impacts on numerous non-target organisms in the environment. Phytoremediation is one strategy that has been studied to remove atrazine contamination. This paper investigates the hypothesis that switchgrass (Panicum virgatum) can exude metabolites of atrazine after uptake and degradation, which has been suggested by prior research. Pots planted with switchgrass were treated with a 4 ppm solution of atrazine spiked with [¹⁴C]atrazine. After 4 days, switchgrass plants were transplanted to new pots with fresh sand. Four days later, the pots were sacrificed, and sand and plant samples were extracted. Plant and sand samples were analyzed for the presence of atrazine and its major metabolites. The percentage of radiotracer remaining as the parent atrazine was observed to decrease over the course of the study while the percentages of the metabolites were observed to increase. The presence of the metabolite cyanuric acid in a switchgrass phytoremediation system is reported for the first time.     

Impact of temperature on Na2Sr(PO4)F:Eu3+ phosphor

In this article, we report the synthesis of Na₂Sr_1‐x(PO₄)F:Eu_x phosphor via a combustion method. The influence of different annealing temperatures on the photoluminescence properties was investigated. The phosphor was excited at both 254 and 393 nm. Na₂Sr_1‐x(PO₄)F:Eu_x³⁺ phosphors emit strong orange and red color at 593 and 612 nm, respectively, under both excitation wavelengths. Na₂Sr_1‐x(PO₄)F:Eu_x³⁺ phosphors annealed at 1050°C showed stronger emission intensity compared with 600, 900 and 1200°C. Moreover, Na₂Sr_1‐x(PO₄)F:Eu_x³⁺ phosphor was found to be more intense when compared with commercial Y₂O₃:Eu³⁺ phosphor. Copyright © 2013 John Wiley & Sons, Ltd.     

Long-lasting systemic bait markers for Eurasian badgers

This study was carried out to assess whether Rhodamine B, ethyl-iophenoxic acid (EtIPA), and propyl-iophenoxic acid (PrIPA) can be used as long-lasting systemic bait markers for free-living badgers (Meles meles). Between June and November 2003, these chemicals were incorporated into bait distributed around badger setts. Serum, hair, and whiskers from individually marked badgers were collected in the following 4 to 24 wk. Rhodamine B was detectable as fluorescent bands up to 24 wk after ingestion of the bait. Individual badgers were found positive for EtIPA and PrIPA up to 20 wk and 18 wk after exposure, respectively. This study indicates that Rhodamine B, PrIPA, and EtIPA could be used as long-lasting markers for badgers.     

Porphyromonas gingivalis lipopolysaccharide lipid A heterogeneity: differential activities of tetra- and penta-acylated lipid A structures on E-selectin expression and TLR4 recognition

Porphyromonas gingivalis is a gram-negative bacterium strongly associated with periodontitis, a chronic inflammatory disease of the tissue surrounding the tooth root surface. Lipopolysaccharide (LPS) obtained from P. gingivalis is unusual in that it has been shown to display an unusual amount of lipid A heterogeneity containing both tetra- and penta-acylated lipid A structures. In this report, it is shown that penta-acylated lipid A structures facilitate E-selectin expression whereas tetra-acylated lipid A structures do not. Furthermore, it is shown that tetra-acylated lipid A structures are potent antagonists for E-selectin expression. Both tetra- and penta-acylated lipid A structures interact with TLR4 although experiments utilizing human, mouse and human/mouse chimeric TLR4 proteins demonstrated that they interact differentially with the TLR4 signalling complexes. The presence of two different structural types of lipid A in P. gingivalis LPS, with opposing effects on the E-selectin response suggests that this organism is able to modulate innate host responses by alterations in the relative amount of these lipid A structures.