Antimicrobial volatile glucosinolate autolysis products from Hornungia petraea (L.) Rchb. (Brassicaceae)

Plant samples of Hornungia petraea were analyzed for glucosinolate (GLS) autolysis metabolites for the first time. GC–MS analysis of the autolysate and the synthesis of a series (12 compounds) of possible glucosinolate breakdown products revealed/corroborated the presence of glucoaubrietin, glucolimnanthin, glucolepigramin and glucotropaeolin in this species as the most likely “mustard oil” precursors. GLS degradation products identified in the autolysate of H. petraea, benzyl isothiocyanate, 3- and 4-methoxybenzyl isothiocyanate, along with several other structurally related compounds were evaluated for antimicrobial activity in order to possibly pinpoint the role of the latter secondary metabolites in the plant tissues. The assays showed a very high antibacterial activity of the tested isothiocyanates against Sarcina lutea and an antifungal effect against Aspergillus fumigatus and Candida albicans with MIC values in the order of 1 μg/ml value.     

Sulforaphane Preconditioning Sensitizes Human Colon Cancer Cells towards the Bioreductive Anticancer Prodrug PR-104A

The chemoprotective properties of sulforaphane (SF), derived from cruciferous vegetables, are widely acknowledged to arise from its potent induction of xenobiotic-metabolizing and antioxidant enzymes. However, much less is known about the impact of SF on the efficacy of cancer therapy through the modulation of drug-metabolizing enzymes. To identify proteins modulated by a low concentration of SF, we treated HT29 colon cancer cells with 2.5 μM SF. Protein abundance changes were detected by stable isotope labeling of amino acids in cell culture. Among 18 proteins found to be significantly up-regulated, aldo-keto reductase 1C3 (AKR1C3), bioactivating the DNA cross-linking prodrug PR-104A, was further characterized. Preconditioning HT29 cells with SF reduced the EC₅₀ of PR-104A 3.6-fold. The increase in PR-104A cytotoxicity was linked to AKR1C3 abundance and activity, both induced by SF in a dose-dependent manner. This effect was reproducible in a second colon cancer cell line, SW620, but not in other colon cancer cell lines where AKR1C3 abundance and activity were absent or barely detectable and could not be induced by SF. Interestingly, SF had no significant influence on PR-104A cytotoxicity in non-cancerous, immortalized human colonic epithelial cell lines expressing either low or high levels of AKR1C3. In conclusion, the enhanced response of PR-104A after preconditioning with SF was apparent only in cancer cells provided that AKR1C3 is expressed, while its expression in non-cancerous cells did not elicit such a response. Therefore, a subset of cancers may be susceptible to combined food-derived component and prodrug treatments with no harm to normal tissues.     

A previously unobserved conformation for the human Pex5p receptor suggests roles for intrinsic flexibility and rigid domain motions in ligand binding

Background  

The C-terminal tetratricopeptide (TPR) repeat domain of Pex5p recognises proteins carrying a peroxisomal targeting signal type 1 (PTS1) tripeptide in their C-terminus. Previously, structural data have been obtained from the TPR domain of Pex5p in both the liganded and unliganded states, indicating a conformational change taking place upon cargo protein binding. Such a conformational change would be expected to play a major role both during PTS1 protein recognition as well as in cargo release into the peroxisomal lumen. However, little information is available on the factors that may regulate such structural changes.     

Taenia solium Cysticercosis in the Democratic Republic of Congo: How Does Pork Trade Affect the Transmission of the Parasite?

Background

Taenia solium, a zoonotic parasite that is endemic in most developing countries where pork is consumed, is recognised as the main cause of acquired epilepsy in these regions. T. solium has been reported in almost all of the neighboring countries of Democratic Republic of Congo (DRC) but data on the current prevalence of the disease in the country itself are lacking. This study, focusing on porcine cysticercosis (CC), makes part of a first initiative to assess whether cysticercosis is indeed actually present in DRC.

Methods

An epidemiological study on porcine CC was conducted (1) on urban markets of Kinshasa where pork is sold and (2) in villages in Bas-Congo province where pigs are traditionally reared. Tongue inspection and ELISA for the detection of circulating antigen of the larval stage of T. solium were used to assess the prevalence of active CC in both study sites.

Findings

The overall prevalence of pigs with active cysticercosis did not significantly differ between the market and the village study sites (38.8 [CI95%: 34–43] versus 41.2% [CI95%: 33–49], respectively). However, tongue cysticercosis was only found in the village study site together with a significantly higher intensity of infection (detected by ELISA).

Interpretation

Pigs reared at village level are sold for consumption on Kinshasa markets, but it seems that highly infected animals are excluded at a certain level in the pig trade chain. Indeed, preliminary informal surveys on common practices conducted in parallel revealed that pig farmers and/or buyers select the low infected animals and exclude those who are positive by tongue inspection at village level. This study provides the only recent evidence of CC presence in DRC and gives the first estimates to fill an important gap on the African taeniasis/cysticercosis distribution map.     

Plant volatiles providing additional evidences to the occurence of a wild-growing population of Calamintha vardarensis (Greuter et Burdet) Šilić outside of its natural habitat

The essential‐oil profile of a Calamintha species, wild‐growing in the urban settings of the city of Ni? (South Serbia) and botanically tentatively identified as C. vardarensis (endemic species native to FYR Macedonia and East Serbia), has been statistically (multivariate statistical analyses) compared with those of other Calamintha species, including two previously investigated C. vardarensis populations, as a means of corroboration of the surprising occurence of this Calamintha population outside of its natural distributional range. Agglomerative hierarchical clustering reveals a close link of C. vardarensis from Ni? (with neo‐menthol (40.0%), menthone (21.8%), and pulegone (27.2%) as its major oil contributors) and C. vardarensis from FYR Macedonia.     

Models of RNA virus evolution and their roles in vaccine design

Viruses are fast evolving pathogens that continuously adapt to the highly variable environments they live and reproduce in. Strategies devoted to inhibit virus replication and to control their spread among hosts need to cope with these extremely heterogeneous populations and with their potential to avoid medical interventions. Computational techniques such as phylogenetic methods have broadened our picture of viral evolution both in time and space, and mathematical modeling has contributed substantially to our progress in unraveling the dynamics of virus replication, fitness, and virulence. Integration of multiple computational and mathematical approaches with experimental data can help to predict the behavior of viral pathogens and to anticipate their escape dynamics. This piece of information plays a critical role in some aspects of vaccine development, such as viral strain selection for vaccinations or rational attenuation of viruses. Here we review several aspects of viral evolution that can be addressed quantitatively, and we discuss computational methods that have the potential to improve vaccine design.     

Distribution patterns of boreal marshland birds: modelling the relationships to land cover and climate

Aim The aims of this work were (1) to study how well land‐cover and climatic data are capable of explaining distribution patterns of ten bird species breeding and/or feeding primarily on marshes and other wetlands and (2) to compare the differences between red‐listed and common marshland species in explanatory variables, and to study the predictability of their distribution patterns. Location Finland, northern Europe. Methods The data of the bird atlas survey carried out in 1986–89 using a 10 × 10 km uniform grid system in Finland were used in the analyses. Land‐cover data based on CORINE (Coordination of Information on the Environment) classification and climatic variables were compiled using the same 10 × 10 km grid. Generalized additive models (GAM) with a stepwise selection procedure were used to select relevant explanatory variables and to examine the complexity of the response shapes of the different species to each variable. The original data set was randomly divided into model training (70%) and model evaluation (30%) sets. The final models of common and red‐listed bird species richness were validated by fitting them to the model evaluation set, and the correlation between observed and predicted species richness was calculated. We assessed the discrimination ability of the binary models (single species) with the area under the curve (AUC) of a receiver operating characteristic (ROC) plot and the Kappa coefficient. Results Cover of marshland, shoreline length and mean temperature in April–June were significantly (P < 0.01) related to the common marshland species richness. Cover and clumping of marshland and mean temperature and precipitation in April–June were selected in the model of red‐listed marshland species richness. The level of discrimination in our single species models varied in ROC from fair to excellent (AUC values 0.70–0.95). Cover of marshland was included in all GAM models built for the target species, but clumping of marshland, shoreline length and cover of mires also appeared as important predictors in single species models. Seven species had statistically significant relationships with climatic variables in the multivariate GAMs. Cover of marshland was highest in squares in which the red‐listed bittern Botaurus stellaris, marsh harrier Circus aeruginosus and great reed warbler Acrocephalus arundinaceus and the water rail Rallus aquaticus were observed. Main conclusions Cover of marshland was the only variable which was included in all the models, reinforcing the close connection between the studied species and marshlands. Broad‐scale clumping of marshlands was important for the red‐listed species, probably due to the much lower population sizes of red‐listed species than those of common species. Land‐cover data produced in CORINE seems to be well suited for modelling the distribution patterns of marshland birds. Although climatic variables also strongly affect the studied marshland birds, habitat availability plays a crucial role in their occurrence. The distribution patterns of marshland birds at the scale of 10 × 10 km reflect the interplay between habitat availability and direct climatic variables.     

True versus apparent malaria infection prevalence: the contribution of a Bayesian approach

Aims

To present a new approach for estimating the “true prevalence” of malaria and apply it to datasets from Peru, Vietnam, and Cambodia.

Methods

Bayesian models were developed for estimating both the malaria prevalence using different diagnostic tests (microscopy, PCR & ELISA), without the need of a gold standard, and the tests'' characteristics. Several sources of information, i.e. data, expert opinions and other sources of knowledge can be integrated into the model. This approach resulting in an optimal and harmonized estimate of malaria infection prevalence, with no conflict between the different sources of information, was tested on data from Peru, Vietnam and Cambodia.

Results

Malaria sero-prevalence was relatively low in all sites, with ELISA showing the highest estimates. The sensitivity of microscopy and ELISA were statistically lower in Vietnam than in the other sites. Similarly, the specificities of microscopy, ELISA and PCR were significantly lower in Vietnam than in the other sites. In Vietnam and Peru, microscopy was closer to the “true” estimate than the other 2 tests while as expected ELISA, with its lower specificity, usually overestimated the prevalence.

Conclusions

Bayesian methods are useful for analyzing prevalence results when no gold standard diagnostic test is available. Though some results are expected, e.g. PCR more sensitive than microscopy, a standardized and context-independent quantification of the diagnostic tests'' characteristics (sensitivity and specificity) and the underlying malaria prevalence may be useful for comparing different sites. Indeed, the use of a single diagnostic technique could strongly bias the prevalence estimation. This limitation can be circumvented by using a Bayesian framework taking into account the imperfect characteristics of the currently available diagnostic tests. As discussed in the paper, this approach may further support global malaria burden estimation initiatives.