Characteristics of a microbial assay for the detection of halogenated hydrocarbons using cells of an actinomycete-like organism as a biological component

Cells of an Actinomycete-like bacterium, strain GJ70, with the ability to degrade several haloalkanes were used as a biological component in a discontinuous microbial bioassay for the detection of 1,3-dichloropropene and 1,2-dibromoethane in water. The cells were entrapped in different matrices such as calcium alginate, carrageenan, chitosan, polyacrylamide-hydrazide and chitosan-carboxy-methyl cellulose; the specific dehalogenating activity of the immobilized cells to a stirred sample solution and by the use of an ion selective electrode (ISE) for the quantification of enzymatically released halogen ions, the concentration of halogenated hydrocarbons could be estimated by determining the change of electrode potential within a period of 5 min. The detection limits for 1,3-dichloropropene and 1,2-dibromoethane were below 100 μg/l and 25 μg/l, respectively; the relative standard deviation was < 10%. In addition, several chlorinated and brominated hgydrocarbons were converted by the bacterial cells at a reduced rate e.g. 1, 2-dibromopropane, 1-bromoethane, 1,5-dichloropentane, etc. Moreover, temperatures of between 20 and 40%C did not affect the enzymatic activity of the cells, and a pH of between at 5 and 9 had little influence. Several organic substances and non-metabolizable compounds did not affect the conversion, whereas some heavy metal ions acted as inhibitors.     

Book Reviews

Book reviewed in this article:
ETHNOLOGY: Les Citadins Katangais et Leur Jardin: Aspects Psycho-sociaux de la Vie en Milieu Africain Urbain. Robert Dethier. Foreword by René Clémens.
ETHNOLOGY: Une Famille de Citadins du Katanga. Robert Dethier. Foreword by René Clémens.     

Reputational geographies and urban social cohesion

This article adds to recent literature in migration studies on the importance of place and space by drawing on extended interviews with residents in the Alum Rock area of East Birmingham. Our central theme is the exploration of reputational geographies; the symbolic and material boundaries drawn around places as indicators of social status, sites of memories and repositories of affect that can have profound socio-economic as well as emotional consequences for city residents. We argue that research and policy addressing urban social diversity must display a greater sensitivity to the deeply felt affiliations to, and memories of, local settings expressed by our respondents. We conclude that contemporary debates about multiculturalism and urban social cohesion require greater attention to the particularities of place and local identity.     

Prediction Errors in Learning Drug Response from Gene Expression Data – Influence of Labeling,Sample Size,and Machine Learning Algorithm

Model-based prediction is dependent on many choices ranging from the sample collection and prediction endpoint to the choice of algorithm and its parameters. Here we studied the effects of such choices, exemplified by predicting sensitivity (as IC50) of cancer cell lines towards a variety of compounds. For this, we used three independent sample collections and applied several machine learning algorithms for predicting a variety of endpoints for drug response. We compared all possible models for combinations of sample collections, algorithm, drug, and labeling to an identically generated null model. The predictability of treatment effects varies among compounds, i.e. response could be predicted for some but not for all. The choice of sample collection plays a major role towards lowering the prediction error, as does sample size. However, we found that no algorithm was able to consistently outperform the other and there was no significant difference between regression and two- or three class predictors in this experimental setting. These results indicate that response-modeling projects should direct efforts mainly towards sample collection and data quality, rather than method adjustment.     

Rare Variants in PLXNA4 and Parkinson’s Disease

Approximately 20% of individuals with Parkinson’s disease (PD) report a positive family history. Yet, a large portion of causal and disease-modifying variants is still unknown. We used exome sequencing in two affected individuals from a family with late-onset familial PD followed by frequency assessment in 975 PD cases and 1014 ethnically-matched controls and linkage analysis to identify potentially causal variants. Based on the predicted penetrance and the frequencies, a variant in PLXNA4 proved to be the best candidate and PLXNA4 was screened for additional variants in 862 PD cases and 940 controls, revealing an excess of rare non-synonymous coding variants in PLXNA4 in individuals with PD. Although we cannot conclude that the variant in PLXNA4 is indeed the causative variant, these findings are interesting in the light of a surfacing role of axonal guidance mechanisms in neurodegenerative disorders but, at the same time, highlight the difficulties encountered in the study of rare variants identified by next-generation sequencing in diseases with autosomal dominant or complex patterns of inheritance.     

Glutamine Metabolism Regulates Proliferation and Lineage Allocation in Skeletal Stem Cells

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Dietary medicinal plant extracts improve growth, immune activity and survival of tilapia Oreochromis mossambicus

The effects of supplementing diets with acetone extract (1% w/w) from four medicinal plants (Bermuda grass Cynodon dactylon, H₁, beal Aegle marmelos, H₂, winter cherry Withania somnifera, H₃ and ginger Zingiber officinale, H₄) on growth, the non‐specific immune response and ability to resist pathogen infection in tilapia Oreochromis mossambicus were assessed. In addition, the antimicrobial properties of the extract were assessed against Vibrio alginolyticus, Vibrioparahaemolyticus, Vibrio mimicus, Vibrio campbelli, Vibrio vulnificus, Vibrio harveyi and Photobacterium damselae. Oreochromis mossambicus were fed 5% of their body mass per day for 45 days, and those fed the experimental diets showed a greater increase in mass (111–139%) over the 45 days compared to those that received the control diet (98%). The specific growth rate of O. mossambicus fed the four diets was also significantly greater (1·66–1·93%) than control (1·52%) diet‐fed fish. The blood plasma chemistry analysis revealed that protein, albumin, globulin, cholesterol, glucose and triglyceride levels of experimental fish were significantly higher than that of control fish. Packed cell volume of the blood samples of experimental diet‐fed fish was also significantly higher (34·16–37·95%) than control fish (33·0%). Leucocrit value, phagocytic index and lysozyme activity were enhanced in fish fed the plant extract‐supplemented diets. The acetone extract of the plants inhibited growth of Vibrio spp. and P. damselae with extracts from W. somnifera showing maximum growth inhibition. A challenge test with V. vulnificus showed 100% mortality in O. mossambicus fed the control diet by day 15, whereas the fish fed the experimental diets registered only 63–80% mortality at the end of challenge experiment (30 days). The cumulative mortality index for the control group was 12 000, which was equated to 1·0% mortality, and accordingly, the lowest mortality of 0·35% was registered in H₄‐diet‐fed group.     

MET and PI3K/mTOR as a Potential Combinatorial Therapeutic Target in Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is an aggressive disease with a poor prognosis. Studies have shown that both MET and its key downstream intracellular signaling partners, PI3K and mTOR, are overexpressed in MPM. Here we determined the combinatorial therapeutic efficacy of a new generation small molecule inhibitor of MET, ARQ 197, and dual PI3K/mTOR inhibitors NVP-BEZ235 and GDC-0980 in mesothelioma cell and mouse xenograft models. Cell viability results show that mesothelioma cell lines were sensitive to ARQ 197, NVP-BEZ235 and GDC-0980 inhibitors. The combined use of ARQ 197 with either NVP-BEZ235 or GDC-0980, was synergistic (CI<1). Significant delay in wound healing was observed with ARQ 197 (p<0.001) with no added advantage of combining it with either NVP-BEZ235 or GDC-0980. ARQ 197 alone mainly induced apoptosis (20±2.36%) that was preceded by suppression of MAPK activity, while all the three suppressed cell cycle progression. Both GDC-0980 and NVP-BEZ235 strongly inhibited activities of PI3K and mTOR as evidenced from the phosphorylation status of AKT and S6 kinase. The above observation was further substantiated by the finding that a majority of the MPM archival samples tested revealed highly active AKT. While the single use of ARQ 197 and GDC-0980 inhibited significantly the growth of MPM xenografts (p<0.05, p<0.001 respectively) in mice, the combination of the above two drugs was highly synergistic (p<0.001). Our results suggest that the combined use of ARQ 197/NVP-BEZ235 and ARQ 197/GDC-0980 is far more effective than the use of the drugs singly in suppressing MPM tumor growth and motility and therefore merit further translational studies.