Applications of High Content Screening in Life Science Research

Over the last decade, imaging as a detection mode for cell based assays has opened a new world of opportunities to measure “phenotypic endpoints” in both current and developing biological models. These “high content” methods combine multiple measurements of cell physiology, whether it comes from sub-cellular compartments, multicellular structures, or model organisms. The resulting multifaceted data can be used to derive new insights into complex phenomena from cell differentiation to compound pharmacology and toxicity. Exploring the major application areas through review of the growing compendium of literature provides evidence that this technology is having a tangible impact on drug discovery and the life sciences

Ontology in Coq for a Guided Message Composition

International audienceNatural language generation is based on messages that represent meanings , and goals that are the usual starting points for communicate. How to help people to provide this conceptual input or, in other words, how to communicate thoughts to the computer? In order to express something, one needs to have something to express as an idea, a thought or a concept. The question is how to represent this. In 2009, Michael Zock, Paul Sabatier and Line Jakubiec-Jamet suggested the building of a resource composed of a linguistically motivated ontology, a dictionary and a graph generator. The ontology guides the user to choose among a set of concepts (or words) to build the message from; the dictionary provides knowledge of how to link the chosen elements to yield a message (compositional rules); the graph generator displays the output in visual form (message graph representing the user's input). While the goal of the ontology is to generate (or analyse) sentences and to guide message composition (what to say), the graph's function is to show at an intermediate level the result of the encoding process. The Illico system already proposes a way to help a user for generating (or analyzing) sentences and guiding their composition. Another system, the Drill Tutor, is an exercise generator whose goal is to help people to become fluent in a foreign language. It helps people (users have to make choices from the interface in order to build their messages) to produce a sentence expressing a message from an idea (or a concept) to its linguistic realization (or a correct sentence given in a foreign language). These two systems led us to consider the representation of the conceptual information into a symbolic language; this representation is encoded in a logic system in order to automatically check conceptual well-formedness of messages. This logic system is the Coq system used here only for its high level language. Coq is based on a typed λ-calculus. It is used for analysing conceptual input interpreted as types and also for specifying general definitions representing messages. These definitions are typed and they will be instanciated for type-checking the conceptual well-formedness of messages. 2 Line Jakubiec-Jame

Effect of a lipid-rich fraction from boiled coffee on serum cholesterol

Scandinavian-style boiled coffee, which raises serum cholesterol, was found to contain more lipid material than drip filter coffee, which does not. Ten volunteers consumed a lipid-enriched fraction from boiled coffee for six weeks: the supplement provided 77 g of water, 1?3 g of lipid, and 1?6 g of other solids per day. Serum cholesterol rose in every subject; the mean rise was 0?74 mmol/l after three weeks (range - 0?09 to 1?48 mmol/l) and 1 ?06 SD 0?37 mmol/l or 23% after six weeks (range 0?48 to 1?52 mmol/l). The increase was mainly due to low-density-lipoprotein cholesterol, which rose by 29%, but very-low-density lipoprotein cholesterol was also raised, as evidenced by a 55% rise in triglycerides. High-density-lipoprotein cholesterol was unchanged. After supplementation had ended, lipid levels returned to baseline. Boiled coffee thus contains a lipid that powerfully raises serum cholesterol

An international prospective general population-based study of respiratory work disability

Background: Previous cross-sectional studies have shown that job change due to breathing problems at the workplace (respiratory work disability) is common among adults of working age. That research indicated that occupational exposure to gases, dust and fumes was associated with job change due to breathing problems, although causal inferences have been tempered by the cross-sectional nature of previously available data. There is a need for general population-based prospective studies to assess the incidence of respiratory work disability and to delineate better the roles of potential predictors of respiratory work disability.Methods: A prospective general population cohort study was performed in 25 centres in 11 European countries and one centre in the USA. A longitudinal analysis was undertaken of the European Community Respiratory Health Survey including all participants employed at any point since the baseline survey, 6659 subjects randomly sampled and 779 subjects comprising all subjects reporting physician-diagnosed asthma. The main outcome measure was new-onset respiratory work disability, defined as a reported job change during follow-up attributed to breathing problems. Exposure to dusts (biological or mineral), gases or fumes during follow-up was recorded using a job-exposure matrix. Cox proportional hazard regression modelling was used to analyse such exposure as a predictor of time until job change due to breathing problems.Results: The incidence rate of respiratory work disability was 1.2/1000 person-years of observation in the random sample (95% CI 1.0 to 1.5) and 5.7/1000 person-years in the asthma cohort (95% CI 4.1 to 7.8). In the random population sample, as well as in the asthma cohort, high occupational exposure to biological dust, mineral dust or gases or fumes predicted increased risk of respiratory work disability. In the random sample, sex was not associated with increased risk of work disability while, in the asthma cohort, female sex was associated with an increased disability risk (hazard ratio 2.8, 95% CI 1.3 to 5.9).Conclusions: Respiratory work disability is common overall. It is associated with workplace exposures that could be controlled through preventive measures

Heart rate variability in association with frequent use of household sprays and scented products in SAPALDIA

Background: Household cleaning products are associated with adverse respiratory health outcomes, but the cardiovascular health effects are largely unknown.Objective: We determined if long-term use of household sprays and scented products at home was associated with reduced heart rate variability (HRV), a marker of autonomic cardiac dysfunction.Methods: We recorded 24-hr electrocardiograms in a cross-sectional survey of 581 Swiss adults, 1, 1-3, or 4-7 days/week, unexposed (reference)] of using cleaning sprays, air freshening sprays, and scented products.Results: Decreases in 24-hr SDNN and TP were observed with frequent use of all product types, but the strongest reductions were associated with air freshening sprays. Compared with unexposed participants, we found that using air freshening sprays 4-7 days/week was associated with 11% [95% confidence interval (CI): -20%, -2%] and 29% (95% CI: -46%, -8%) decreases in 24-hr SDNN and TP, respectively. Inverse associations of 24-SDNN and TP with increased use of cleaning sprays, air freshening sprays, and scented products were observed mainly in participants with obstructive lung disease (p > 0.05 for interactions).Conclusions: In predominantly older adult women, long-term frequent use of household spray and scented products was associated with reduced HRV, which suggests an increased risk of cardiovascular health hazards. People with preexisting pulmonary conditions may be more susceptibl

Ліберали України та вибори до і думи

Cytokine concentrations in biological fluids are widely used markers for activation of immunological processes. Confirming the reproducibility of measurements is important, especially in longitudinal or multicenter studies where time between analyses or different analyzing laboratories increases the intra-assay variability. In this study, the reproducibility of the cytokine analysis conducted with different assay platforms was studied by comparing the results of two cytokines [interleukin (IL)-6 in serum and nasal lavage fluid (NAL) and IL-8 in NAL] analyzed with Meso Scale Discovery (MSD) ultra-sensitive single and multiplex assay kits (n = 76). In addition, the difference in cytokine levels between two biological sample matrices was studied by comparing the results of altogether 9 cytokines [IL-6, IL-2, IL-8, IL12p70, IL-1β, granulocyte–macrophage colony-stimulating factor (GM-CSF), interferon (IFN)γ, IL-10 and tumor necrosis factor (TNF)α] measured from serum and NAL of the same study subjects (n = 460). The results show that the cytokine concentrations analyzed with single and multiplex assays are concordant but not equal. Comparison of the different matrices revealed that cytokine concentrations in serum do not correspond with concentrations detected in nasal lavage fluid. It can be concluded that comparability of the results from single and multiplex analysis of cytokines is high, but the concentrations should not be compared directly with each other. The differences between concentrations analyzed from serum and nasal lavage fluid indicate that the levels are specific for each matrix and represent distinct immunological conditions. (aut.ref.

Quantitative assessment of airborne exposures generated during common cleaning tasks: a pilot study

Background: A growing body of epidemiologic evidence suggests an association between exposure to cleaning products with asthma and other respiratory disorders. Thus far, these studies have conducted only limited quantitative exposure assessments. Exposures from cleaning products are difficult to measure because they are complex mixtures of chemicals with a range of physicochemical properties, thus requiring multiple measurement techniques. We conducted a pilot exposure assessment study to identify methods for assessing short term, task-based airborne exposures and to quantitatively evaluate airborne exposures associated with cleaning tasks simulated under controlled work environment conditions. Methods: Sink, mirror, and toilet bowl cleaning tasks were simulated in a large ventilated bathroom and a small unventilated bathroom using a general purpose, a glass, and a bathroom cleaner. All tasks were performed for 10 minutes. Airborne total volatile organic compounds (TVOC) generated during the tasks were measured using a direct reading instrument (DRI) with a photo ionization detector. Volatile organic ingredients of the cleaning mixtures were assessed utilizing an integrated sampling and analytic method, EPA TO-17. Ammonia air concentrations were also measured with an electrochemical sensor embedded in the DRI. Results: Average TVOC concentrations calculated for 10 minute tasks ranged 0.02 - 6.49 ppm and the highest peak concentrations observed ranged 0.14-11 ppm. TVOC time concentration profiles indicated that exposures above background level remained present for about 20 minutes after cessation of the tasks. Among several targeted VOC compounds from cleaning mixtures, only 2-BE was detectable with the EPA method. The ten minute average 2- BE concentrations ranged 0.30 -21 ppm between tasks. The DRI underestimated 2-BE exposures compared to the results from the integrated method. The highest concentration of ammonia of 2.8 ppm occurred during mirror cleaning. Conclusions: Our results indicate that airborne exposures from short-term cleaning tasks can remain in the air even after tasks' cessation, suggesting potential exposures to anyone entering the room shortly after cleaning. Additionally, 2-BE concentrations from cleaning could approach occupational exposure limits and warrant further investigation. Measurement methods applied in this study can be useful for workplace assessment of airborne exposures during cleaning, if the limitations identified here are addressed

Dietary and circulating long-chain omega-3 polyunsaturated fatty acids and mortality risk after myocardial infarction:A long-term follow-up of the alpha omega cohort

BACKGROUND: Habitual intake of long-chain omega-3 fatty acids, especially eicosapentaenoic and docosahexaenoic acid (EPA+DHA) from fish, has been associated with a lower risk of fatal coronary heart disease (CHD) in population-based studies. Whether that is also the case for patients with CHD is not yet clear. We studied the associations of dietary and circulating EPA+DHA and alpha-linolenic acid, a plant-derived omega-3 fatty acids, with long-term mortality risk after myocardial infarction. METHODS AND RESULTS: We analyzed data from 4067 Dutch patients with prior myocardial infarction aged 60 to 80 years (79% men, 86% on statins) enrolled in the Alpha Omega Cohort from 2002 to 2006 (baseline) and followed through 2018. Baseline intake of fish and omega-3 fatty acids were assessed through a validated 203-item food frequency questionnaire and circulating omega-3 fatty acids were assessed in plasma cholesteryl esters. Hazard ratios (HRs) with 95% CIs were obtained from Cox regression analyses. During a median follow-up period of 12 years, 1877 deaths occurred, of which 515 were from CHD and 834 from cardiovascular diseases. Dietary intake of EPA+DHA was significantly inversely associated with only CHD mortality (HR, 0.69 [0.52– 0.90] for >200 versus ≤50 mg/d; HR, 0.92 [0.86– 0.98] per 100 mg/d). Similar results were obtained for fish consumption (HRCHD, 0.74 [0.53–1.03] for >40 versus ≤5 g/d; Ptrend: 0.031). Circulating EPA+DHA was inversely associated with CHD mortality (HR, 0.71 [0.53– 0.94] for >2.52% versus ≤1.29%; 0.85 [0.77– 0.95] per 1-SD) and also with cardiovascular diseases and all-cause mortality. Dietary and circulating alpha-linolenic acid were not significantly associated with mortality end points. CONCLUSIONS: In a cohort of Dutch patients with prior myocardial infarction, higher dietary and circulating EPA+DHA and fish intake were consistently associated with a lower CHD mortality risk. REGISTRATION: URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT03192410