Synergistic and Antagonistic Mutation Responses of Human MCL-5 Cells to Mixtures of Benzo[a]pyrene and 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]pyridine: Dose-Related Variation in the Joint Effects of Common Dietary Carcinogens.

BACKGROUND: Chemical carcinogens such as benzo[a]pyrene (BaP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) may contribute to the etiology of human diet-associated cancer. Individually, these compounds are genotoxic, but the consequences of exposure to mixtures of these chemicals have not been systematically examined. OBJECTIVES: We determined the mutagenic response to mixtures of BaP and PhIP at concentrations relevant to human exposure (micromolar to subnanomolar). METHODS: Human MCL-5 cells (metabolically competent) were exposed to BaP or PhIP individually or in mixtures. Mutagenicity was assessed at the thymidine kinase (TK) locus, CYP1A activity was determined by ethoxyresorufin-O-deethylase (EROD) activity and qRT-PCR, and cell cycle was measured by flow cytometry. RESULTS: Mixtures of BaP and PhIP produced dose responses different from those of the individual chemicals; we observed remarkably increased mutant frequency (MF) at lower concentrations of the mixtures (not mutagenic individually), and decreased MF at higher concentrations of the mixtures, than the calculated predicted additive MF of the individual chemicals. EROD activity and CYP1A1 mRNA levels were correlated with TK MF, supporting involvement of the CYP1A family in mutation. Moreover, a cell cycle G2/M phase block was observed at high-dose combinations, consistent with DNA damage sensing and repair. CONCLUSIONS: Mixtures of these genotoxic chemicals produced mutation responses that differed from those expected for the additive effects of the individual chemicals. The increase in MF for certain combinations of chemicals at low concentrations that were not genotoxic for the individual chemicals, as well as the nonmonotonic dose response, may be important for understanding the mutagenic potential of food and the etiology of diet-associated cancers. CITATION: David R, Ebbels T, Gooderham N. 2016. Synergistic and antagonistic mutation responses of human MCL-5 cells to mixtures of benzo[a]pyrene and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine: dose-related variation in the joint effects of common dietary carcinogens. Environ Health Perspect 124:88–96; http://dx.doi.org/10.1289/ehp.140955

Detecting depression in dyadic conversations with multimodal narratives and visualizations

Conversations contain a wide spectrum of multimodal information that gives us hints about the emotions and moods of the speaker. In this paper, we developed a system that supports humans to analyze conversations. Our main contribution is the identification of appropriate multimodal features and the integration of such features into verbatim conversation transcripts. We demonstrate the ability of our system to take in a wide range of multimodal information and automatically generated a prediction score for the depression state of the individual. Our experiments showed that this approach yielded better performance than the baseline model. Furthermore, the multimodal narrative approach makes it easy to integrate learnings from other disciplines, such as conversational analysis and psychology. Lastly, this interdisciplinary and automated approach is a step towards emulating how practitioners record the course of treatment as well as emulating how conversational analysts have been analyzing conversations by hand.Comment: 12 page

Predicting selective drug targets in cancer through metabolic networks

The authors develop a genome-scale model of cancer metabolism and use it to predict genes that are essential for cancer cell growth. An array of target combinations are then identified that could potentially provide novel selective treatments for specific cancers

Baseline clinical characteristics of predicted structural and pain progressors in the IMI-APPROACH knee OA cohort

[Abstract] Objectives: To describe the relations between baseline clinical characteristics of the Applied Public-Private Research enabling OsteoArthritis Clinical Headway (IMI-APPROACH) participants and their predicted probabilities for knee osteoarthritis (OA) structural (S) progression and/or pain (P) progression. Methods: Baseline clinical characteristics of the IMI-APPROACH participants were used for this study. Radiographs were evaluated according to Kellgren and Lawrence (K&L grade) and Knee Image Digital Analysis. Knee Injury and Osteoarthritis Outcome Score (KOOS) and Numeric Rating Scale (NRS) were used to evaluate pain. Predicted progression scores for each individual were determined using machine learning models. Pearson correlation coefficients were used to evaluate correlations between scores for predicted progression and baseline characteristics. T-tests and χ2 tests were used to evaluate differences between participants with high versus low progression scores. Results: Participants with high S progressions score were found to have statistically significantly less structural damage compared with participants with low S progression scores (minimum Joint Space Width, minJSW 3.56 mm vs 1.63 mm; p<0.001, K&L grade; p=0.028). Participants with high P progression scores had statistically significantly more pain compared with participants with low P progression scores (KOOS pain 51.71 vs 82.11; p<0.001, NRS pain 6.7 vs 2.4; p<0.001). Conclusions: The baseline minJSW of the IMI-APPROACH participants contradicts the idea that the (predicted) course of knee OA follows a pattern of inertia, where patients who have progressed previously are more likely to display further progression. In contrast, for pain progressors the pattern of inertia seems valid, since participants with high P score already have more pain at baseline compared with participants with a low P score

Variation on a Theme: Vibrational Signaling in Caterpillars of the Rose Hook-Tip Moth, Oreto rosea

Abstract Vibrational communication in hook-tip moth caterpillars is thought to be widely used and highly variable across species, but this phenomenon has been experimentally examined in only two species to date. The purpose of this study is to characterize and describe the function of vibrational signaling in a species, Oreta rosea Walker 1855 (Lepidoptera: Drepanidae), that differs morphologically from previously studied species. Caterpillars of this species produce three distinct types of vibrational signals during territorial encounters with conspecifics — mandible drumming, mandible scraping and lateral tremulation. Signals were recorded using a laser-doppler vibrometer and characterized based on temporal and spectral components. Behavioural encounters between a leaf resident and a conspecific intruder were staged to test the hypothesis that signaling functions as a territorial display. Drumming and scraping signals both involve the use of the mandibles, being hit vertically on, or scraped laterally across, the leaf surface. Lateral tremulation involves quick, short, successive lateral movements of the anterior body region that vibrates the entire leaf. Encounters result in residents signaling, with the highest rates observed when intruders make contact with the resident. Residents signal significantly more than intruders and most conflicts are resolved within 10 minutes, with residents winning 91% of trials. The results support the hypothesis that vibrational signals function to advertise leaf occupancy. Signaling is compared between species, and evolutionary origins of vibrational communication in caterpillars are discussed

Collembola are Unlikely to Cause Human Dermatitis

There have been several unconfirmed case reports of dermatitis caused by Collembola (springtails). We recently investigated two nurses with dermatitis suspected to be caused by Drepanura Schött (Collembola: Entomobryidae). IgE antibodies to Collembola proteins were not detected in sera from the nurses and skin tests with the Collembola extract and crushed whole Collembola were negative in both the nurses and volunteers. This study suggests that the springtail Drepanura may not cause human dermatitis and that other organisms and organic matter that are also found in the moist environment inhabited by Collembola might instead be responsible

Ferritin is secreted via 2 distinct nonclassical vesicular pathways

Ferritin turnover plays a major role in tissue iron homeostasis, and ferritin malfunction is associated with impaired iron homeostasis and neurodegenerative diseases. In most eukaryotes, ferritin is considered an intracellular protein that stores iron in a nontoxic and bioavailable form. In insects, ferritin is a classically secreted protein and plays a major role in systemic iron distribution. Mammalian ferritin lacks the signal peptide for classical endoplasmic reticulum–Golgi secretion but is found in serum and is secreted via a nonclassical lysosomal secretion pathway. This study applied bioinformatics and biochemical tools, alongside a protein trafficking mouse models, to characterize the mechanisms of ferritin secretion. Ferritin trafficking via the classical secretion pathway was ruled out, and a 2:1 distribution of intracellular ferritin between membrane-bound compartments and the cytosol was observed, suggesting a role for ferritin in the vesicular compartments of the cell. Focusing on nonclassical secretion, we analyzed mouse models of impaired endolysosomal trafficking and found that ferritin secretion was decreased by a BLOC-1 mutation but increased by BLOC-2, BLOC-3, and Rab27A mutations of the cellular trafficking machinery, suggesting multiple export routes. A 13-amino-acid motif unique to ferritins that lack the secretion signal peptide was identified on the BC-loop of both subunits and plays a role in the regulation of ferritin secretion. Finally, we provide evidence that secretion of iron-rich ferritin was mediated via the multivesicular body–exosome pathway. These results enhance our understanding of the mechanism of ferritin secretion, which is an important piece in the puzzle of tissue iron homeostasis

Collembola are Unlikely to Cause Human Dermatitis

There have been several unconfirmed case reports of dermatitis caused by Collembola (springtails). We recently investigated two nurses with dermatitis suspected to be caused by Drepanura Schött (Collembola: Entomobryidae). IgE antibodies to Collembola proteins were not detected in sera from the nurses and skin tests with the Collembola extract and crushed whole Collembola were negative in both the nurses and volunteers. This study suggests that the springtail Drepanura may not cause human dermatitis and that other organisms and organic matter that are also found in the moist environment inhabited by Collembola might instead be responsible