A dispositional approach to psychological climate: relationships between interpersonal harmony motives and psychological climate for communication safety

This study examined the dispositional antecedents of a climate at the individual level, psychological climate for communication safety. The impact of two interpersonal harmony motives, harmony enhancement and disintegration avoidance, on psychological climate for communication safety, innovative performance and the moderated mediated processes associated with job autonomy were examined in a survey study in China. Results showed that harmony enhancement was positively related to innovative performance through psychological climate for communication safety. Moreover, job autonomy moderated the relationship between harmony motives and psychological climate for communication safety. Harmony enhancement was more strongly associated with psychological climate for communication safety when job autonomy was low. The relationship between disintegration avoidance and psychological climate for communication safety was positive when job autonomy was high, but negative when job autonomy was low. Conditional indirect effects consistent with these interaction effects were also found

Inhibition of histone methyltransferase EZH2 in Schistosoma mansoni in vitro by GSK343 reduces egg laying and decreases the expression of genes implicated in DNA replication and noncoding RNA metabolism

Background: The possibility of emergence of praziquantel-resistant Schistosoma parasites and the lack of other effective drugs demand the discovery of new schistosomicidal agents. In this context the study of compounds that target histone-modifying enzymes is extremely promising. Our aim was to investigate the effect of inhibition of EZH2, a histone methyltransferase that is involved in chromatin remodeling processes and gene expression control; we tested different developmental forms of Schistosoma mansoni using GKS343, a selective inhibitor of EZH2 in human cells. Methodology/Principal findings: Adult male and female worms and schistosomula were treated with different concentrations of GSK343 for up to two days in vitro. Western blotting showed a decrease in the H3K27me3 histone mark in all three developmental forms. Motility, mortality, pairing and egg laying were employed as schistosomicidal parameters for adult worms. Schistosomula viability was evaluated with propidium iodide staining and ATP quantification. Adult worms showed decreased motility when exposed to GSK343. Also, an approximate 40% reduction of egg laying by GSK343-treated females was observed when compared with controls (0.1% DMSO). Scanning electron microscopy showed the formation of bulges and bubbles throughout the dorsal region of GSK343-treated adult worms. In schistosomula the body was extremely contracted with the presence of numerous folds, and growth was markedly slowed. RNA-seq was applied to identify the metabolic pathways affected by GSK343 sublethal doses. GSK343-treated adult worms showed significantly altered expression of genes related to transmembrane transport, cellular homeostasis and egg development. In females, genes related to DNA replication and noncoding RNA metabolism processes were downregulated. Schistosomula showed altered expression of genes related to cell adhesion and membrane synthesis pathways. Conclusions/Significance: The results indicated that GSK343 presents in vitro activities against S. mansoni, and the characterization of EZH2 as a new potential molecular target establishes EZH2 inhibitors as part of a promising new group of compounds that could be used for the development of schistosomicidal agents

Presence of extracellular DNA in the Candida albicans biofilm matrix and its contribution to biofilms

DNA has been described as a structural component of the extracellular matrix (ECM) in bacterial biofilms. In Candida albicans, there is a scarce knowledge concerning the contribution of extracellular DNA (eDNA) to biofilm matrix and overall structure. This work examined the presence and quantified the amount of eDNA in C. albicans biofilm ECM and the effect of DNase treatment and the addition of exogenous DNA on C. albicans biofilm development as indicators of a role for eDNA in biofilm development. We were able to detect the accumulation of eDNA in biofilm ECM extracted from C. albicans biofilms formed under conditions of flow, although the quantity of eDNA detected differed according to growth conditions, in particular with regards to the medium used to grow the biofilms. Experiments with C. albicans biofilms formed statically using a microtiter plate model indicated that the addition of exogenous DNA (>160 ng/ml) increases biofilm biomass and, conversely, DNase treatment (>0.03 mg/ml) decreases biofilm biomass at later time points of biofilm development. We present evidence for the role of eDNA in C. albicans biofilm structure and formation, consistent with eDNA being a key element of the ECM in mature C. albicans biofilms and playing a predominant role in biofilm structural integrity and maintenance.National Institute of Dental & Craniofacial ResearchFundação para a Ciência e Tecnologia (FCT) - SFRH/BD/28222/2006National Institute of Allergy and Infectious Disease

Reusable Components of Semantic Specifications

Semantic specifications of programming languages typically have poor modularity. This hinders reuse of parts of the semantics of one language when specifying a different language – even when the two languages have many constructs in common – and evolution of a language may require major reformulation of its semantics. Such drawbacks have discouraged language developers from using formal semantics to document their designs. In the PLanCompS project, we have developed a component-based approach to semantics. Here, we explain its modularity aspects, and present an illustrative case study: a component-based semantics for Caml Light. We have tested the correctness of the semantics by running programs on an interpreter generated from the semantics, comparing the output with that produced on the standard implementation of the language. Our approach provides good modularity, facilitates reuse, and should support co-evolution of languages and their formal semantics. It could be particularly useful in connection with domain-specific languages and language-driven software development

Off-Target Effects of Psychoactive Drugs Revealed by Genome-Wide Assays in Yeast

To better understand off-target effects of widely prescribed psychoactive drugs, we performed a comprehensive series of chemogenomic screens using the budding yeast Saccharomyces cerevisiae as a model system. Because the known human targets of these drugs do not exist in yeast, we could employ the yeast gene deletion collections and parallel fitness profiling to explore potential off-target effects in a genome-wide manner. Among 214 tested, documented psychoactive drugs, we identified 81 compounds that inhibited wild-type yeast growth and were thus selected for genome-wide fitness profiling. Many of these drugs had a propensity to affect multiple cellular functions. The sensitivity profiles of half of the analyzed drugs were enriched for core cellular processes such as secretion, protein folding, RNA processing, and chromatin structure. Interestingly, fluoxetine (Prozac) interfered with establishment of cell polarity, cyproheptadine (Periactin) targeted essential genes with chromatin-remodeling roles, while paroxetine (Paxil) interfered with essential RNA metabolism genes, suggesting potential secondary drug targets. We also found that the more recently developed atypical antipsychotic clozapine (Clozaril) had no fewer off-target effects in yeast than the typical antipsychotics haloperidol (Haldol) and pimozide (Orap). Our results suggest that model organism pharmacogenetic studies provide a rational foundation for understanding the off-target effects of clinically important psychoactive agents and suggest a rational means both for devising compound derivatives with fewer side effects and for tailoring drug treatment to individual patient genotypes

Genomic Phenotyping by Barcode Sequencing Broadly Distinguishes between Alkylating Agents, Oxidizing Agents, and Non-Genotoxic Agents, and Reveals a Role for Aromatic Amino Acids in Cellular Recovery after Quinone Exposure

Toxicity screening of compounds provides a means to identify compounds harmful for human health and the environment. Here, we further develop the technique of genomic phenotyping to improve throughput while maintaining specificity. We exposed cells to eight different compounds that rely on different modes of action: four genotoxic alkylating (methyl methanesulfonate (MMS), N-Methyl-N-nitrosourea (MNU), N,N′-bis(2-chloroethyl)-N-nitroso-urea (BCNU), N-ethylnitrosourea (ENU)), two oxidizing (2-methylnaphthalene-1,4-dione (menadione, MEN), benzene-1,4-diol (hydroquinone, HYQ)), and two non-genotoxic (methyl carbamate (MC) and dimethyl sulfoxide (DMSO)) compounds. A library of S. cerevisiae 4,852 deletion strains, each identifiable by a unique genetic ‘barcode’, were grown in competition; at different time points the ratio between the strains was assessed by quantitative high throughput ‘barcode’ sequencing. The method was validated by comparison to previous genomic phenotyping studies and 90% of the strains identified as MMS-sensitive here were also identified as MMS-sensitive in a much lower throughput solid agar screen. The data provide profiles of proteins and pathways needed for recovery after both genotoxic and non-genotoxic compounds. In addition, a novel role for aromatic amino acids in the recovery after treatment with oxidizing agents was suggested. The role of aromatic acids was further validated; the quinone subgroup of oxidizing agents were extremely toxic in cells where tryptophan biosynthesis was compromised.Unilever (Firm)National Cancer Institute (U.S.) (R01-CA055042 (now R01-ES022872))Massachusetts Institute of Technology. Center for Environmental Health Sciences (Grant NIEHS P30-ES002109

PathogenMip Assay: A Multiplex Pathogen Detection Assay

The Molecular Inversion Probe (MIP) assay has been previously applied to a large-scale human SNP detection. Here we describe the PathogenMip Assay, a complete protocol for probe production and applied approaches to pathogen detection. We have demonstrated the utility of this assay with an initial set of 24 probes targeting the most clinically relevant HPV genotypes associated with cervical cancer progression. Probe construction was based on a novel, cost-effective, ligase-based protocol. The assay was validated by performing pyrosequencing and Microarray chip detection in parallel experiments. HPV plasmids were used to validate sensitivity and selectivity of the assay. In addition, 20 genomic DNA extracts from primary tumors were genotyped with the PathogenMip Assay results and were in 100% agreement with conventional sequencing using an L1-based HPV genotyping protocol. The PathogenMip Assay is a widely accessible protocol for producing and using highly discriminating probes, with experimentally validated results in pathogen genotyping, which could potentially be applied to the detection and characterization of any microbe

Maternal bonding styles in smokers and non-smokers: a comparative study

BACKGROUND: Parental bonding has been implicated in smoking behavior, and the quality of maternal bonding (MB) has been associated with poor mental health and substance use. However, little is known about the association of MB and the smoking of the offspring. METHODS: In our study, 129 smokers and 610 non-smoker medical students completed the parental bonding instrument, which measures MB along two dimensions: care and overprotection. Four categories can be created by high and low scores on care and overprotection: optimal parenting (OP; high care/low overprotection); affectionless control (ALC; low care/high overprotection); affectionate constraint (AC; high care/high overprotection), and neglectful parenting (NP; low care/low overprotection). Nicotine dependence was assessed by the Fagerstrom Nicotine Dependence Test, exhaled CO level, and daily cigarette consumption (CPD). RESULTS: Higher CPD was significantly associated with lower overprotection (p = 0.016) and higher care (p = 0.023) scores. The odds for being a smoker were significantly higher in the neglectful maternal bonding style compared to the other rearing styles (p = 0.022). Besides, smokers showed significantly higher care and lower overprotection scores with the Mann-Whitney U-test than non-smokers, although these associations did not remain significant in multiple regression models. CONCLUSION: Our results indicate that focusing on early life relationship between patient and mother can be important in psychotherapeutic interventions for smoking. Registration trials retrospectively registered

Environmental regulation of carbon isotope composition and crassulacean acid metabolism in three plant communities along a water availability gradient

Expression of crassulacean acid metabolism (CAM) is characterized by extreme variability within and between taxa and its sensitivity to environmental variation. In this study, we determined seasonal fluctuations in CAM photosynthesis with measurements of nocturnal tissue acidification and carbon isotopic composition (δ13C) of bulk tissue and extracted sugars in three plant communities along a precipitation gradient (500, 700, and 1,000 mm year−1) on the Yucatan Peninsula. We also related the degree of CAM to light habitat and relative abundance of species in the three sites. For all species, the greatest tissue acid accumulation occurred during the rainy season. In the 500 mm site, tissue acidification was greater for the species growing at 30% of daily total photon flux density (PFD) than species growing at 80% PFD. Whereas in the two wetter sites, the species growing at 80% total PFD had greater tissue acidification. All species had values of bulk tissue δ13C less negative than −20‰, indicating strong CAM activity. The bulk tissue δ13C values in plants from the 500 mm site were 2‰ less negative than in plants from the wetter sites, and the only species growing in the three communities, Acanthocereus tetragonus (Cactaceae), showed a significant negative relationship between both bulk tissue and sugar δ13C values and annual rainfall, consistent with greater CO2 assimilation through the CAM pathway with decreasing water availability. Overall, variation in the use of CAM photosynthesis was related to water and light availability and CAM appeared to be more ecologically important in the tropical dry forests than in the coastal dune