1,338 research outputs found

    Analysis of soil texture using terrasar x-band sar

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    International audienceIn this paper, it is proposed to use TERRASAR-X data for analysis and estimation of soil surface texture. Our study is based on experimental campaigns carried out over a semi-arid area in North Africa. Simultaneously to TERRASAR-X radar acquisitions, ground measurements (texture, soil moisture and roughness) were made on different test fields. A strong correlation is observed between soil texture and a processed signal from two radar images, the first acquired just after a rain event and the second corresponding to dry soil conditions, acquired three weeks later. An empirical relationship is proposed for the retrieval from radar signals of clay content percent. Soil texture mapping is proposed over the study site, which includes bare soils and olive groves

    Intermittent preventive treatment of malaria provides substantial protection against malaria in children already protected by an insecticide-treated bednet in Burkina Faso: a randomised, double-blind, placebo-controlled trial.

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    BACKGROUND: Intermittent preventive treatment of malaria in children (IPTc) is a promising new approach to the control of malaria in areas of seasonal malaria transmission but it is not known if IPTc adds to the protection provided by an insecticide-treated net (ITN). METHODS AND FINDINGS: An individually randomised, double-blind, placebo-controlled trial of seasonal IPTc was conducted in Burkina Faso in children aged 3 to 59 months who were provided with a long-lasting insecticide-treated bednet (LLIN). Three rounds of treatment with sulphadoxine pyrimethamine plus amodiaquine or placebos were given at monthly intervals during the malaria transmission season. Passive surveillance for malaria episodes was established, a cross-sectional survey was conducted at the end of the malaria transmission season, and use of ITNs was monitored during the intervention period. Incidence rates of malaria were compared using a Cox regression model and generalized linear models were fitted to examine the effect of IPTc on the prevalence of malaria infection, anaemia, and on anthropometric indicators. 3,052 children were screened and 3,014 were enrolled in the trial; 1,505 in the control arm and 1,509 in the intervention arm. Similar proportions of children in the two treatment arms were reported to sleep under an LLIN during the intervention period (93%). The incidence of malaria, defined as fever or history of fever with parasitaemia ≥ 5,000/µl, was 2.88 (95% confidence interval [CI] 2.70-3.06) per child during the intervention period in the control arm versus 0.87 (95% CI 0.78-0.97) in the intervention arm, a protective efficacy (PE) of 70% (95% CI 66%-74%) (p<0.001). There was a 69% (95% CI 6%-90%) reduction in incidence of severe malaria (p = 0.04) and a 46% (95% CI 7%-69%) (p = 0.03) reduction in the incidence of all-cause hospital admissions. IPTc reduced the prevalence of malaria infection at the end of the malaria transmission season by 73% (95% CI 68%-77%) (p<0.001) and that of moderately severe anaemia by 56% (95% CI 36%-70%) (p<0.001). IPTc reduced the risks of wasting (risk ratio [RR] = 0.79; 95% CI 0.65-1.00) (p = 0.05) and of being underweight (RR = 0.84; 95% CI 0.72-0.99) (p = 0.03). Children who received IPTc were 2.8 (95% CI 2.3-3.5) (p<0.001) times more likely to vomit than children who received placebo but no drug-related serious adverse event was recorded. CONCLUSIONS: IPT of malaria provides substantial protection against malaria in children who sleep under an ITN. There is now strong evidence to support the integration of IPTc into malaria control strategies in areas of seasonal malaria transmission. TRIAL REGISTRATION: ClinicalTrials.govNCT00738946. Please see later in the article for the Editors' Summary

    Epigenetics as a mechanism driving polygenic clinical drug resistance

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    Aberrant methylation of CpG islands located at or near gene promoters is associated with inactivation of gene expression during tumour development. It is increasingly recognised that such epimutations may occur at a much higher frequency than gene mutation and therefore have a greater impact on selection of subpopulations of cells during tumour progression or acquisition of resistance to anticancer drugs. Although laboratory-based models of acquired resistance to anticancer agents tend to focus on specific genes or biochemical pathways, such 'one gene : one outcome' models may be an oversimplification of acquired resistance to treatment of cancer patients. Instead, clinical drug resistance may be due to changes in expression of a large number of genes that have a cumulative impact on chemosensitivity. Aberrant CpG island methylation of multiple genes occurring in a nonrandom manner during tumour development and during the acquisition of drug resistance provides a mechanism whereby expression of multiple genes could be affected simultaneously resulting in polygenic clinical drug resistance. If simultaneous epigenetic regulation of multiple genes is indeed a major driving force behind acquired resistance of patients' tumour to anticancer agents, this has important implications for biomarker studies of clinical outcome following chemotherapy and for clinical approaches designed to circumvent or modulate drug resistance

    Use of quercetin in animal feed : effects on the P-gp expression and pharmacokinetics of orally administrated enrofloxacin in chicken

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    Modulation of P-glycoprotein (P-gp, encoded by Mdr1) by xenobiotics plays central role in pharmacokinetics of various drugs. Quercetin has a potential to modulate P-gp in rodents, however, its effects on P-gp modulation in chicken are still unclear. Herein, study reports role of quercetin in modulation of P-gp expression and subsequent effects on the pharmacokinetics of enrofloxacin in broilers. Results show that P-gp expression was increased in a dose-dependent manner following exposure to quercetin in Caco-2 cells and tissues of chicken. Absorption rate constant and apparent permeability coefficient of rhodamine 123 were decreased, reflecting efflux function of P-gp in chicken intestine increased by quercetin. Quercetin altered pharmacokinetic of enrofloxacin by decreasing area under curve, peak concentration, and time to reach peak concentration and by increasing clearance rate. Molecular docking shows quercetin can form favorable interactions with binding pocket of chicken xenobiotic receptor (CXR). Results provide convincing evidence that quercetin induced P-gp expression in tissues by possible interaction with CXR, and consequently reducing bioavailability of orally administered enrofloxacin through restricting its intestinal absorption and liver/kidney clearance in broilers. The results can be further extended to guide reasonable use of quercetin to avoid drug-feed interaction occurred with co-administered enrofloxacin or other similar antimicrobials.Peer reviewedFinal Published versio

    The stationary wavelet transform as an efficient reductor of powerline interference for atrial bipolar electrograms in cardiac electrophysiology

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    [EN] Objective :The most relevant source of signal contamination in the cardiac electrophysiology (EP) laboratory is the ubiquitous powerline interference (PLI). To reduce this perturbation, algorithms including common fixed-bandwidth and adaptive-notch filters have been proposed. Although such methods have proven to add artificial fractionation to intra-atrial electrograms (EGMs), they are still frequently used. However, such morphological alteration can conceal the accurate interpretation of EGMs, specially to evaluate the mechanisms supporting atrial fibrillation (AF), which is the most common cardiac arrhythmia. Given the clinical relevance of AF, a novel algorithm aimed at reducing PLI on highly contaminated bipolar EGMs and, simultaneously, preserving their morphology is proposed. Approach: The method is based on the wavelet shrinkage and has been validated through customized indices on a set of synthesized EGMs to accurately quantify the achieved level of PLI reduction and signal morphology alteration. Visual validation of the algorithm¿s performance has also been included for some real EGM excerpts. Main results: The method has outperformed common filtering-based and wavelet-based strategies in the analyzed scenario. Moreover, it possesses advantages such as insensitivity to amplitude and frequency variations in the PLI, and the capability of joint removal of several interferences. Significance: The use of this algorithm in routine cardiac EP studies may enable improved and truthful evaluation of AF mechanisms.Research supported by grants DPI2017-83952-C3 MINECO/AEI/FEDER, UE and SBPLY/17/180501/000411 from Junta de Comunidades de Castilla-La Mancha.Martinez-Iniesta, M.; Ródenas, J.; Rieta, JJ.; Alcaraz, R. (2019). The stationary wavelet transform as an efficient reductor of powerline interference for atrial bipolar electrograms in cardiac electrophysiology. Physiological Measurement. 40(7):1-17. https://doi.org/10.1088/1361-6579/ab2cb8S117407Addison, P. S. (2017). The Illustrated Wavelet Transform Handbook. doi:10.1201/9781315372556Allen, D. P. (2009). A frequency domain Hampel filter for blind rejection of sinusoidal interference from electromyograms. Journal of Neuroscience Methods, 177(2), 303-310. doi:10.1016/j.jneumeth.2008.10.019Atienza, F., Almendral, J., Jalife, J., Zlochiver, S., Ploutz-Snyder, R., Torrecilla, E. G., … Berenfeld, O. (2009). Real-time dominant frequency mapping and ablation of dominant frequency sites in atrial fibrillation with left-to-right frequency gradients predicts long-term maintenance of sinus rhythm. Heart Rhythm, 6(1), 33-40. doi:10.1016/j.hrthm.2008.10.024Atienza, F., Almendral, J., Moreno, J., Vaidyanathan, R., Talkachou, A., Kalifa, J., … Berenfeld, O. (2006). Activation of Inward Rectifier Potassium Channels Accelerates Atrial Fibrillation in Humans. Circulation, 114(23), 2434-2442. doi:10.1161/circulationaha.106.633735Bahoura, M., & Ezzaidi, H. (2011). FPGA-Implementation of Discrete Wavelet Transform with Application to Signal Denoising. Circuits, Systems, and Signal Processing, 31(3), 987-1015. doi:10.1007/s00034-011-9355-0Baumert, M., Sanders, P., & Ganesan, A. (2016). Quantitative-Electrogram-Based Methods for Guiding Catheter Ablation in Atrial Fibrillation. Proceedings of the IEEE, 104(2), 416-431. doi:10.1109/jproc.2015.2505318Castillo, E., Morales, D. P., García, A., Martínez-Martí, F., Parrilla, L., & Palma, A. J. (2013). Noise Suppression in ECG Signals through Efficient One-Step Wavelet Processing Techniques. Journal of Applied Mathematics, 2013, 1-13. doi:10.1155/2013/763903Chen, S.-W., & Chen, Y.-H. (2015). Hardware Design and Implementation of a Wavelet De-Noising Procedure for Medical Signal Preprocessing. Sensors, 15(10), 26396-26414. doi:10.3390/s151026396El B’charri, O., Latif, R., Elmansouri, K., Abenaou, A., & Jenkal, W. (2017). ECG signal performance de-noising assessment based on threshold tuning of dual-tree wavelet transform. BioMedical Engineering OnLine, 16(1). doi:10.1186/s12938-017-0315-1Everett, T. H., Lai-Chow Kok, Vaughn, R. H., Moorman, R., & Haines, D. E. (2001). Frequency domain algorithm for quantifying atrial fibrillation organization to increase defibrillation efficacy. IEEE Transactions on Biomedical Engineering, 48(9), 969-978. doi:10.1109/10.942586Ganesan, A. N., Kuklik, P., Lau, D. H., Brooks, A. G., Baumert, M., Lim, W. W., … Sanders, P. (2013). Bipolar Electrogram Shannon Entropy at Sites of Rotational Activation. Circulation: Arrhythmia and Electrophysiology, 6(1), 48-57. doi:10.1161/circep.112.976654Goldberger, A. L., Amaral, L. A. N., Glass, L., Hausdorff, J. M., Ivanov, P. C., Mark, R. G., … Stanley, H. E. (2000). PhysioBank, PhysioToolkit, and PhysioNet. Circulation, 101(23). doi:10.1161/01.cir.101.23.e215GOLDBERGER, J. J. (2017). Substrate Ablation for Treatment of Atrial Fibrillation: Back to Basics. Journal of Cardiovascular Electrophysiology, 28(2), 156-158. doi:10.1111/jce.13149Gutiérrez-Gnecchi, J. A., Morfin-Magaña, R., Lorias-Espinoza, D., Tellez-Anguiano, A. del C., Reyes-Archundia, E., Méndez-Patiño, A., & Castañeda-Miranda, R. (2017). DSP-based arrhythmia classification using wavelet transform and probabilistic neural network. Biomedical Signal Processing and Control, 32, 44-56. doi:10.1016/j.bspc.2016.10.005Hamilton, P. S. (1996). A comparison of adaptive and nonadaptive filters for reduction of power line interference in the ECG. IEEE Transactions on Biomedical Engineering, 43(1), 105-109. doi:10.1109/10.477707Heijman, J., Algalarrondo, V., Voigt, N., Melka, J., Wehrens, X. H. T., Dobrev, D., & Nattel, S. (2015). The value of basic research insights into atrial fibrillation mechanisms as a guide to therapeutic innovation: a critical analysis. Cardiovascular Research, 109(4), 467-479. doi:10.1093/cvr/cvv275Honarbakhsh, S., Schilling, R. J., Orini, M., Providencia, R., Keating, E., Finlay, M., … Hunter, R. J. (2019). Structural remodeling and conduction velocity dynamics in the human left atrium: Relationship with reentrant mechanisms sustaining atrial fibrillation. Heart Rhythm, 16(1), 18-25. doi:10.1016/j.hrthm.2018.07.019Jadidi, A. S., Lehrmann, H., Weber, R., Park, C.-I., & Arentz, T. (2013). Optimizing Signal Acquisition and Recording in an Electrophysiology Laboratory. Cardiac Electrophysiology Clinics, 5(2), 137-142. doi:10.1016/j.ccep.2013.01.005JARMAN, J. W. E., WONG, T., KOJODJOJO, P., SPOHR, H., DAVIES, J. E. R., ROUGHTON, M., … PETERS, N. S. (2014). Organizational Index Mapping to Identify Focal Sources During Persistent Atrial Fibrillation. Journal of Cardiovascular Electrophysiology, 25(4), 355-363. doi:10.1111/jce.12352KOTTKAMP, H., BERG, J., BENDER, R., RIEGER, A., & SCHREIBER, D. (2015). Box Isolation of Fibrotic Areas (BIFA): A Patient-Tailored Substrate Modification Approach for Ablation of Atrial Fibrillation. Journal of Cardiovascular Electrophysiology, 27(1), 22-30. doi:10.1111/jce.12870Krijthe, B. P., Kunst, A., Benjamin, E. J., Lip, G. Y. H., Franco, O. H., Hofman, A., … Heeringa, J. (2013). Projections on the number of individuals with atrial fibrillation in the European Union, from 2000 to 2060. European Heart Journal, 34(35), 2746-2751. doi:10.1093/eurheartj/eht280Lau, D. H., Schotten, U., Mahajan, R., Antic, N. A., Hatem, S. N., Pathak, R. K., … Sanders, P. (2015). Novel mechanisms in the pathogenesis of atrial fibrillation: practical applications. European Heart Journal, 37(20), 1573-1581. doi:10.1093/eurheartj/ehv375Lenis, G., Pilia, N., Loewe, A., Schulze, W. H. W., & Dössel, O. (2017). Comparison of Baseline Wander Removal Techniques considering the Preservation of ST Changes in the Ischemic ECG: A Simulation Study. Computational and Mathematical Methods in Medicine, 2017, 1-13. doi:10.1155/2017/9295029Levkov, C., Mihov, G., Ivanov, R., Daskalov, I., Christov, I., & Dotsinsky, I. (2005). Removal of power-line interference from the ECG: a review of the subtraction procedure. BioMedical Engineering OnLine, 4(1). doi:10.1186/1475-925x-4-50Lian, J., Garner, G., Muessig, D., & Lang, V. (2010). A simple method to quantify the morphological similarity between signals. Signal Processing, 90(2), 684-688. doi:10.1016/j.sigpro.2009.07.010Liu, H., Li, Y., Zhou, Y., Jing, X., & Truong, T.-K. (2018). Joint power line interference suppression and ECG signal recovery in transform domains. Biomedical Signal Processing and Control, 44, 58-66. doi:10.1016/j.bspc.2018.04.001Mamun, M., Al-Kadi, M., & Marufuzzaman, M. (2013). Effectiveness of Wavelet Denoising on Electroencephalogram Signals. Journal of Applied Research and Technology, 11(1), 156-160. doi:10.1016/s1665-6423(13)71524-4Martens, S. M. M., Mischi, M., Oei, S. G., & Bergmans, J. W. M. (2006). An Improved Adaptive Power Line Interference Canceller for Electrocardiography. IEEE Transactions on Biomedical Engineering, 53(11), 2220-2231. doi:10.1109/tbme.2006.883631Mart�nez, M., R�denas, J., Alcaraz, R., & Rieta, J. J. (2017). Application of the Stationary Wavelet Transform to Reduce Power-line Interference in Atrial Electrograms. 2017 Computing in Cardiology Conference (CinC). doi:10.22489/cinc.2017.112-049Martínez-Iniesta, M., Ródenas, J., Alcaraz, R., & Rieta, J. J. (2017). Waveform Integrity in Atrial Fibrillation: The Forgotten Issue of Cardiac Electrophysiology. Annals of Biomedical Engineering, 45(8), 1890-1907. doi:10.1007/s10439-017-1832-6Metting van Rijn, A. C., Peper, A., & Grimbergen, C. A. (1990). High-quality recording of bioelectric events. Medical & Biological Engineering & Computing, 28(5), 389-397. doi:10.1007/bf02441961Nademanee, K., McKenzie, J., Kosar, E., Schwab, M., Sunsaneewitayakul, B., Vasavakul, T., … Ngarmukos, T. (2004). A new approach for catheter ablation of atrial fibrillation: mapping of the electrophysiologic substrate. Journal of the American College of Cardiology, 43(11), 2044-2053. doi:10.1016/j.jacc.2003.12.054Naseri, H., & Homaeinezhad, M. R. (2012). Computerized quality assessment of phonocardiogram signal measurement-acquisition parameters. Journal of Medical Engineering & Technology, 36(6), 308-318. doi:10.3109/03091902.2012.684832NG, J., BORODYANSKIY, A. I., CHANG, E. T., VILLUENDAS, R., DIBS, S., KADISH, A. H., & GOLDBERGER, J. J. (2010). Measuring the Complexity of Atrial Fibrillation Electrograms. Journal of Cardiovascular Electrophysiology, 21(6), 649-655. doi:10.1111/j.1540-8167.2009.01695.xNg, J., Sehgal, V., Ng, J. K., Gordon, D., & Goldberger, J. J. (2014). Iterative Method to Detect Atrial Activations and Measure Cycle Length From Electrograms During Atrial Fibrillation. IEEE Transactions on Biomedical Engineering, 61(2), 273-278. doi:10.1109/tbme.2013.2290003Oesterlein, T. G., Lenis, G., Rudolph, D.-T., Luik, A., Verma, B., Schmitt, C., & Dössel, O. (2015). Removing ventricular far-field signals in intracardiac electrograms during stable atrial tachycardia using the periodic component analysis. Journal of Electrocardiology, 48(2), 171-180. doi:10.1016/j.jelectrocard.2014.12.004Platonov, P. G., Corino, V. D. A., Seifert, M., Holmqvist, F., & Sornmo, L. (2014). Atrial fibrillatory rate in the clinical context: natural course and prediction of intervention outcome. Europace, 16(suppl 4), iv110-iv119. doi:10.1093/europace/euu249Poornachandra, S., & Kumaravel, N. (2008). A novel method for the elimination of power line frequency in ECG signal using hyper shrinkage function. Digital Signal Processing, 18(2), 116-126. doi:10.1016/j.dsp.2007.03.011Quintanilla, J. G., Pérez-Villacastín, J., Pérez-Castellano, N., Pandit, S. V., Berenfeld, O., Jalife, J., & Filgueiras-Rama, D. (2016). Mechanistic Approaches to Detect, Target, and Ablate the Drivers of Atrial Fibrillation. Circulation: Arrhythmia and Electrophysiology, 9(1). doi:10.1161/circep.115.002481Ravelli, F., Masè, M., Cristoforetti, A., Marini, M., & Disertori, M. (2014). The logical operator map identifies novel candidate markers for critical sites in patients with atrial fibrillation. Progress in Biophysics and Molecular Biology, 115(2-3), 186-197. doi:10.1016/j.pbiomolbio.2014.07.006Schanze, T. (2017). Removing noise in biomedical signal recordings by singular value decomposition. Current Directions in Biomedical Engineering, 3(2), 253-256. doi:10.1515/cdbme-2017-0052Schotten, U., Dobrev, D., Platonov, P. G., Kottkamp, H., & Hindricks, G. (2016). Current controversies in determining the main mechanisms of atrial fibrillation. Journal of Internal Medicine, 279(5), 428-438. doi:10.1111/joim.12492Singh, B. N., & Tiwari, A. K. (2006). Optimal selection of wavelet basis function applied to ECG signal denoising. Digital Signal Processing, 16(3), 275-287. doi:10.1016/j.dsp.2005.12.003Van Wagoner, D. R., Piccini, J. P., Albert, C. M., Anderson, M. E., Benjamin, E. J., Brundel, B., … Wehrens, X. H. T. (2015). Progress toward the prevention and treatment of atrial fibrillation: A summary of the Heart Rhythm Society Research Forum on the Treatment and Prevention of Atrial Fibrillation, Washington, DC, December 9–10, 2013. Heart Rhythm, 12(1), e5-e29. doi:10.1016/j.hrthm.2014.11.011Venkatachalam, K. L., Herbrandson, J. E., & Asirvatham, S. J. (2011). Signals and Signal Processing for the Electrophysiologist. Circulation: Arrhythmia and Electrophysiology, 4(6), 965-973. doi:10.1161/circep.111.96430

    In vitro efficacy of some plant aqueous extracts against two species of Lasiodiplodia associated to mango decline in Burkina Faso

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    Mango decline is a serious disease in production areas in Burkina Faso. The aim of this study was to contribute to the management of the disease through the use of plant aqueous extracts. Antifungal activities of Azadirachta indica, Calotropis procera, Gmelina arborea, Jatropha curcas, Eucalyptus camaldulensis and the synthetic fungicide (Mancozeb) were tested against Lasiodiplodia theobromae and Lasiodiplodia pseudotheobromae associated to mango decline in Burkina Faso. Three different concentrations of leaf extracts which 25%, 50%, 75% and 500 ppm of Mancozeb were tested for their antifungal activity in vitro. The results showed that leaf extracts have an inhibitor effect on the growth of the two Lasiodiplodia species. The aqueous extract of G. arborea was the most effective with average inhibition rates of L. theobromae of 42.62%, 73.84% and 74.23% respectively with the concentrations of 25 g/l, 50 g/l and 75 g/l. The aqueous extract of A. indica against L. pseudotheobromae showed maximum percentage inhibition with 50 g/l of 63.10% and with 75 g/l of 72.02%. Mancozeb completely inhibits the mycelial growth of both species of fungi. Ours findings showed that aqueous extracts from plants could be tried for the eco-friendly management of mango decline pathogens.Keywords: Antifungal, plants extract, Lasiodiplodia spp., mango decline, Burkina Faso

    Effets des Amendements Organiques sur la Gale Bactérienne et la Pourriture Apicale de la Tomate à Bobo-Dioulasso au Burkina Faso

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    L’étude a porté sur les effets des amendements organiques sur la gale bactérienne et la pourriture apicale de la tomate en milieu réel à l’Ouest du Burkina Faso. Un essai a été mis en place dans un dispositif en bloc de Fisher complètement randomisé. Il a comporté huit (08) traitements constitués des fertilisants organiques et minéraux tous répétés quatre (04) fois. L’incidence de la maladie et sa sévérité ont été évaluées ainsi que l’effet des traitements sur la qualité des fruits. La progression est relativement faible avec les déchets ménagers compostés associés aux engrais minéraux. La maladie est plus sévère avec les différents fertilisants pris individuellement. Dans l’ensemble, la maladie est évolutive avec tous les traitements. &nbsp; The study focused on the effects of organic amendments on bacterial scab and apical rot of tomato in a real environment in western Burkina Faso. Indeed, a trial was set up in a completely randomized Fisher block design. It included eight (08) treatments consisting of organic and mineral fertilizers all repeated four (04) times. The incidence of the disease and its severity were evaluated as well as the effect of the treatments on the quality of the fruits. The disease is progressive with all treatments. However, the progression is relatively low with composted household waste associated with mineral fertilizers. The disease is more severe with the different fertilizers taken individually

    Longitudinal study of DNA methylation during the first 5 years of life.

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    Background: Early life epigenetic programming influences adult health outcomes. Moreover, DNA methylation levels have been found to change more rapidly during the first years of life. Our aim was the identification and characterization of the CpG sites that are modified with time during the first years of life. We hypothesize that these DNA methylation changes would lead to the detection of genes that might be epigenetically modulated by environmental factors during early childhood and which, if disturbed, might contribute to susceptibility to diseases later in life. Methods: The study of the DNA methylation pattern of 485577 CpG sites was performed on 30 blood samples from 15 subjects, collected both at birth and at 5 years old, using Illumina® Infinium 450 k array. To identify differentially methylated CpG (dmCpG) sites, the methylation status of each probe was examined using linear models and the Empirical Bayes Moderated t test implemented in the limma package of R/Bioconductor. Surogate variable analysis was used to account for batch effects. Results: DNA methylation levels significantly changed from birth to 5 years of age in 6641 CpG sites. Of these, 36.79 % were hypermethylated and were associated with genes related mainly to developmental ontology terms, while 63.21 % were hypomethylated probes and associated with genes related to immune function. Conclusions: Our results suggest that DNA methylation alterations with age during the first years of life might play a significant role in development and the regulation of leukocyte-specific functions. This supports the idea that blood leukocytes experience genome remodeling related to their interaction with environmental factors, underlining the importance of environmental exposures during the first years of life and suggesting that new strategies should be take into consideration for disease prevention

    The Invariance Hypothesis Implies Domain-Specific Regions in Visual Cortex

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    Is visual cortex made up of general-purpose information processing machinery, or does it consist of a collection of specialized modules? If prior knowledge, acquired from learning a set of objects is only transferable to new objects that share properties with the old, then the recognition system’s optimal organization must be one containing specialized modules for different object classes. Our analysis starts from a premise we call the invariance hypothesis: that the computational goal of the ventral stream is to compute an invariant-to-transformations and discriminative signature for recognition. The key condition enabling approximate transfer of invariance without sacrificing discriminability turns out to be that the learned and novel objects transform similarly. This implies that the optimal recognition system must contain subsystems trained only with data from similarly-transforming objects and suggests a novel interpretation of domain-specific regions like the fusiform face area (FFA). Furthermore, we can define an index of transformation-compatibility, computable from videos, that can be combined with information about the statistics of natural vision to yield predictions for which object categories ought to have domain-specific regions in agreement with the available data. The result is a unifying account linking the large literature on view-based recognition with the wealth of experimental evidence concerning domain-specific regions.National Science Foundation (U.S.). Science and Technology Center (Award CCF-1231216)National Science Foundation (U.S.) (Grant NSF-0640097)National Science Foundation (U.S.) (Grant NSF-0827427)United States. Air Force Office of Scientific Research (Grant FA8650-05-C-7262)Eugene McDermott Foundatio

    Epigenetic polypharmacology: from combination therapy to multitargeted drugs

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    The modern drug discovery process has largely focused its attention in the so-called magic bullets, single chemical entities that exhibit high selectivity and potency for a particular target. This approach was based on the assumption that the deregulation of a protein was causally linked to a disease state, and the pharmacological intervention through inhibition of the deregulated target was able to restore normal cell function. However, the use of cocktails or multicomponent drugs to address several targets simultaneously is also popular to treat multifactorial diseases such as cancer and neurological disorders. We review the state of the art with such combinations that have an epigenetic target as one of their mechanisms of action. Epigenetic drug discovery is a rapidly advancing field, and drugs targeting epigenetic enzymes are in the clinic for the treatment of hematological cancers. Approved and experimental epigenetic drugs are undergoing clinical trials in combination with other therapeutic agents via fused or linked pharmacophores in order to benefit from synergistic effects of polypharmacology. In addition, ligands are being discovered which, as single chemical entities, are able to modulate multiple epigenetic targets simultaneously (multitarget epigenetic drugs). These multiple ligands should in principle have a lower risk of drug-drug interactions and drug resistance compared to cocktails or multicomponent drugs. This new generation may rival the so-called magic bullets in the treatment of diseases that arise as a consequence of the deregulation of multiple signaling pathways provided the challenge of optimization of the activities shown by the pharmacophores with the different targets is addressed
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