High toxicity and specificity of the saponin 3-GlcA-28-AraRhaxyl-medicagenate, from Medicago truncatula seeds, for Sitophilus oryzae

<p>Abstract</p> <p>Background</p> <p>Because of the increasingly concern of consumers and public policy about problems for environment and for public health due to chemical pesticides, the search for molecules more safe is currently of great importance. Particularly, plants are able to fight the pathogens as insects, bacteria or fungi; so that plants could represent a valuable source of new molecules.</p> <p>Results</p> <p>It was observed that <it>Medicago truncatul</it>a seed flour displayed a strong toxic activity towards the adults of the rice weevil <it>Sitophilus oryzae</it> (Coleoptera), a major pest of stored cereals. The molecule responsible for toxicity was purified, by solvent extraction and HPLC, and identified as a saponin, namely 3-GlcA-28-AraRhaxyl-medicagenate. Saponins are detergents, and the CMC of this molecule was found to be 0.65 mg per mL. Neither the worm <it>Caenorhabditis elegans</it> nor the bacteria <it>E. coli</it> were found to be sensitive to this saponin, but growth of the yeast <it>Saccharomyces cerevisiae</it> was inhibited at concentrations higher than 100 μg per mL. The purified molecule is toxic for the adults of the rice weevils at concentrations down to 100 μg per g of food, but this does not apply to the others insects tested, including the coleopteran <it>Tribolium castaneum</it> and the Sf9 insect cultured cells.</p> <p>Conclusions</p> <p>This specificity for the weevil led us to investigate this saponin potential for pest control and to propose the hypothesis that this saponin has a specific mode of action, rather than acting <it>via</it> its non-specific detergent properties.</p

Audio-Motor Integration for Robot Audition

International audienceIn the context of robotics, audio signal processing in the wild amounts to dealing with sounds recorded by a system that moves and whose actuators produce noise. This creates additional challenges in sound source localization, signal enhancement and recognition. But the speci-ficity of such platforms also brings interesting opportunities: can information about the robot actuators' states be meaningfully integrated in the audio processing pipeline to improve performance and efficiency? While robot audition grew to become an established field, methods that explicitly use motor-state information as a complementary modality to audio are scarcer. This chapter proposes a unified view of this endeavour, referred to as audio-motor integration. A literature review and two learning-based methods for audio-motor integration in robot audition are presented, with application to single-microphone sound source localization and ego-noise reduction on real data

Non-invasive diagnostic tests for Helicobacter pylori infection

BACKGROUND: Helicobacter pylori (H pylori) infection has been implicated in a number of malignancies and non-malignant conditions including peptic ulcers, non-ulcer dyspepsia, recurrent peptic ulcer bleeding, unexplained iron deficiency anaemia, idiopathic thrombocytopaenia purpura, and colorectal adenomas. The confirmatory diagnosis of H pylori is by endoscopic biopsy, followed by histopathological examination using haemotoxylin and eosin (H & E) stain or special stains such as Giemsa stain and Warthin-Starry stain. Special stains are more accurate than H & E stain. There is significant uncertainty about the diagnostic accuracy of non-invasive tests for diagnosis of H pylori. OBJECTIVES: To compare the diagnostic accuracy of urea breath test, serology, and stool antigen test, used alone or in combination, for diagnosis of H pylori infection in symptomatic and asymptomatic people, so that eradication therapy for H pylori can be started. SEARCH METHODS: We searched MEDLINE, Embase, the Science Citation Index and the National Institute for Health Research Health Technology Assessment Database on 4 March 2016. We screened references in the included studies to identify additional studies. We also conducted citation searches of relevant studies, most recently on 4 December 2016. We did not restrict studies by language or publication status, or whether data were collected prospectively or retrospectively. SELECTION CRITERIA: We included diagnostic accuracy studies that evaluated at least one of the index tests (urea breath test using isotopes such as13C or14C, serology and stool antigen test) against the reference standard (histopathological examination using H & E stain, special stains or immunohistochemical stain) in people suspected of having H pylori infection. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the references to identify relevant studies and independently extracted data. We assessed the methodological quality of studies using the QUADAS-2 tool. We performed meta-analysis by using the hierarchical summary receiver operating characteristic (HSROC) model to estimate and compare SROC curves. Where appropriate, we used bivariate or univariate logistic regression models to estimate summary sensitivities and specificities. MAIN RESULTS: We included 101 studies involving 11,003 participants, of which 5839 participants (53.1%) had H pylori infection. The prevalence of H pylori infection in the studies ranged from 15.2% to 94.7%, with a median prevalence of 53.7% (interquartile range 42.0% to 66.5%). Most of the studies (57%) included participants with dyspepsia and 53 studies excluded participants who recently had proton pump inhibitors or antibiotics.There was at least an unclear risk of bias or unclear applicability concern for each study.Of the 101 studies, 15 compared the accuracy of two index tests and two studies compared the accuracy of three index tests. Thirty-four studies (4242 participants) evaluated serology; 29 studies (2988 participants) evaluated stool antigen test; 34 studies (3139 participants) evaluated urea breath test-13C; 21 studies (1810 participants) evaluated urea breath test-14C; and two studies (127 participants) evaluated urea breath test but did not report the isotope used. The thresholds used to define test positivity and the staining techniques used for histopathological examination (reference standard) varied between studies. Due to sparse data for each threshold reported, it was not possible to identify the best threshold for each test.Using data from 99 studies in an indirect test comparison, there was statistical evidence of a difference in diagnostic accuracy between urea breath test-13C, urea breath test-14C, serology and stool antigen test (P = 0.024). The diagnostic odds ratios for urea breath test-13C, urea breath test-14C, serology, and stool antigen test were 153 (95% confidence interval (CI) 73.7 to 316), 105 (95% CI 74.0 to 150), 47.4 (95% CI 25.5 to 88.1) and 45.1 (95% CI 24.2 to 84.1). The sensitivity (95% CI) estimated at a fixed specificity of 0.90 (median from studies across the four tests), was 0.94 (95% CI 0.89 to 0.97) for urea breath test-13C, 0.92 (95% CI 0.89 to 0.94) for urea breath test-14C, 0.84 (95% CI 0.74 to 0.91) for serology, and 0.83 (95% CI 0.73 to 0.90) for stool antigen test. This implies that on average, given a specificity of 0.90 and prevalence of 53.7% (median specificity and prevalence in the studies), out of 1000 people tested for H pylori infection, there will be 46 false positives (people without H pylori infection who will be diagnosed as having H pylori infection). In this hypothetical cohort, urea breath test-13C, urea breath test-14C, serology, and stool antigen test will give 30 (95% CI 15 to 58), 42 (95% CI 30 to 58), 86 (95% CI 50 to 140), and 89 (95% CI 52 to 146) false negatives respectively (people with H pylori infection for whom the diagnosis of H pylori will be missed).Direct comparisons were based on few head-to-head studies. The ratios of diagnostic odds ratios (DORs) were 0.68 (95% CI 0.12 to 3.70; P = 0.56) for urea breath test-13C versus serology (seven studies), and 0.88 (95% CI 0.14 to 5.56; P = 0.84) for urea breath test-13C versus stool antigen test (seven studies). The 95% CIs of these estimates overlap with those of the ratios of DORs from the indirect comparison. Data were limited or unavailable for meta-analysis of other direct comparisons. AUTHORS' CONCLUSIONS: In people without a history of gastrectomy and those who have not recently had antibiotics or proton ,pump inhibitors, urea breath tests had high diagnostic accuracy while serology and stool antigen tests were less accurate for diagnosis of Helicobacter pylori infection.This is based on an indirect test comparison (with potential for bias due to confounding), as evidence from direct comparisons was limited or unavailable. The thresholds used for these tests were highly variable and we were unable to identify specific thresholds that might be useful in clinical practice.We need further comparative studies of high methodological quality to obtain more reliable evidence of relative accuracy between the tests. Such studies should be conducted prospectively in a representative spectrum of participants and clearly reported to ensure low risk of bias. Most importantly, studies should prespecify and clearly report thresholds used, and should avoid inappropriate exclusions

Embodiment and ontologies of inequality in medicine: Towards an integrative understanding of disease and health disparities

In this article, I draw on my fieldwork creating protein models of hepatitis B at a biotech laboratory to think through how to approach the body and disease from ontological and phenomenological perspectives. I subsequently draw on Mariella Pandolfi’s work on how bodies can be made to suffer history and Paul Farmer’s work on global tuberculosis disparities to explore ways of analysing embodied activity as a means of identifying and clinically addressing enactments of social inequality and disease. I also introduce Merleau-Ponty’s phenomenological concept of ‘flesh’ as a conceptual heuristic that allows us to understand the meaningful structuring of ontological worlds beyond our own. As I argue, bringing these perspectives together not only allows us to re-envision what an effective disease treatment should be in diverse medical contexts, but also how to better understand health disparities and the nature of disease itself

Exposome-wide analysis of human aging mechanisms, age-related diseases, and mortality in a UK population

Background: Although it has been recognized that environmental exposures may be the major determinants of human aging and mortality, progress in understanding the impact of the exposome (i.e., the totality of all the non-genetic, external exposures that contribute to health and disease for an individual across the lifecourse) on mortality and age-related morbidity is lacking. In this thesis, I aimed to quantify the effect of the exposome on mortality, aging biomarkers, and chronic diseases. Methods: I conducted a multi-step, exposome-wide analysis in the UK Biobank (n = 492,569). An exposome-wide association study (XWAS) of all-cause mortality was conducted using independent discovery and replication sets including participants recruited in England (median 12.5 follow-up years), with multiple further analyses conducted to evaluated replicated exposures for reverse causation due to prevalent disease and confounding due to exposome correlation. Remaining exposures were tested in relationship to 25 blood biomarkers related to aging mechanisms, 3 cardiometabolic risk factors (obesity, hypertension, dyslipidemia), and incidence of 25 age-related diseases. Finally, I fitted multivariable Cox models for mortality and each of the 25 disease outcomes, which included age and sex, all independent exposures associated with each outcome, polygenic risk scores (PRS), and clinical risk factors. C-index and R-squared for these models were validated in an independent set of participants from Scotland/Wales (median 13.7 follow-up years). Findings: I found 55 exposures that were associated with mortality after multiple analysis stages, including factors related to smoking, physical activity, early childhood, social networks, mental health, diet and supplements, air pollution, material deprivation, sociodemographics, and sleep. Each of the 55 exposures was associated with an average of 21/25 aging biomarkers, 11/25 diseases, and 3/3 cardiometabolic risk factors. I found that while age and sex explain 43-47% of the variance in mortality, adding these 55 exposures to the model increased the mortality R-squared estimate to 61-66%. Further adding PRS for 16 noncommunicable diseases only increased the ability to explain mortality by 0.03-0.6%. Finally, adding clinical risk factors to the model further increased explanation of mortality to 67-70%. Proportions of variance explained by age and sex, the exposome, PRS, and clinical factors for the 25 age-related diseases studied are also reported. Interpretation: These results provide the first comprehensive map of the environmental architecture of mortality, aging mechanisms, and age-related diseases. I identified many environmental exposures that are strongly associated with mortality in the UK Biobank, which seem to influence mortality through modulation of diverse biological mechanisms, cardiometabolic risk factors, and disease multimorbidity. I further demonstrated that aside from age and sex, the exposome explains the greatest amount of variation in mortality risk even after accounting for polygenic disease risk. Further analysis may be needed to establish causality of identified exposures and to detect residual reverse causation bias in exposures not detected via the methods used in this thesis.</p

Embodiment and ontologies of inequality in medicine: Towards an integrative understanding of disease and health disparities

In this article, I draw on my fieldwork creating protein models of hepatitis B at a biotech laboratory to think through how to approach the body and disease from ontological and phenomenological perspectives. I subsequently draw on Mariella Pandolfi’s work on how bodies can be made to suffer history and Paul Farmer’s work on global tuberculosis disparities to explore ways of analysing embodied activity as a means of identifying and clinically addressing enactments of social inequality and disease. I also introduce Merleau-Ponty’s phenomenological concept of ‘flesh’ as a conceptual heuristic that allows us to understand the meaningful structuring of ontological worlds beyond our own. As I argue, bringing these perspectives together not only allows us to re-envision what an effective disease treatment should be in diverse medical contexts, but also how to better understand health disparities and the nature of disease itself

Epigenetic pathways in human disease: The impact of DNA methylation on stress-related pathogenesis and current challenges in biomarker development

HPA axis genes implicated in glucocorticoid regulation play an important role in regulating the physiological impact of social and environmental stress, and have become a focal point for investigating the role of glucocorticoid regulation in the etiology of disease. We conducted a systematic review to critically assess the full range of clinical associations that have been reported in relation to DNA methylation of CRH, CRH-R1/2, CRH-BP, AVP, POMC, ACTH, ACTH-R, NR3C1, FKBP5, and HSD11β1/2 genes in adults. A total of 32 studies were identified. There is prospective evidence for an association between HSD11β2 methylation and hypertension, and functional evidence of an association between NR3C1 methylation and both small cell lung cancer (SCLC) and breast cancer. Strong associations have been reported between FKBP5 and NR3C1 methylation and PTSD, and biologically-plausible associations have been reported between FKBP5 methylation and Alzheimer's Disease. Mixed associations between NR3C1 methylation and mental health outcomes have been reported according to different social and environmental exposures, and according to varying gene regions investigated. We conclude by highlighting key challenges and future research directions that will need to be addressed in order to develop both clinically meaningful prognostic biomarkers and an evidence base that can inform public policy practice

Epigenetic pathways in human disease: The impact of DNA methylation on stress-related pathogenesis and current challenges in biomarker development

HPA axis genes implicated in glucocorticoid regulation play an important role in regulating the physiological impact of social and environmental stress, and have become a focal point for investigating the role of glucocorticoid regulation in the etiology of disease. We conducted a systematic review to critically assess the full range of clinical associations that have been reported in relation to DNA methylation of CRH, CRH-R1/2, CRH-BP, AVP, POMC, ACTH, ACTH-R, NR3C1, FKBP5, and HSD11β1/2 genes in adults. A total of 32 studies were identified. There is prospective evidence for an association between HSD11β2 methylation and hypertension, and functional evidence of an association between NR3C1 methylation and both small cell lung cancer (SCLC) and breast cancer. Strong associations have been reported between FKBP5 and NR3C1 methylation and PTSD, and biologically-plausible associations have been reported between FKBP5 methylation and Alzheimer's Disease. Mixed associations between NR3C1 methylation and mental health outcomes have been reported according to different social and environmental exposures, and according to varying gene regions investigated. We conclude by highlighting key challenges and future research directions that will need to be addressed in order to develop both clinically meaningful prognostic biomarkers and an evidence base that can inform public policy practice