Comprehensive structural classification of ligand binding motifs in proteins

Comprehensive knowledge of protein-ligand interactions should provide a useful basis for annotating protein functions, studying protein evolution, engineering enzymatic activity, and designing drugs. To investigate the diversity and universality of ligand binding sites in protein structures, we conducted the all-against-all atomic-level structural comparison of over 180,000 ligand binding sites found in all the known structures in the Protein Data Bank by using a recently developed database search and alignment algorithm. By applying a hybrid top-down-bottom-up clustering analysis to the comparison results, we determined approximately 3000 well-defined structural motifs of ligand binding sites. Apart from a handful of exceptions, most structural motifs were found to be confined within single families or superfamilies, and to be associated with particular ligands. Furthermore, we analyzed the components of the similarity network and enumerated more than 4000 pairs of ligand binding sites that were shared across different protein folds.Comment: 13 pages, 8 figure

Robust aircraft conceptual design using automatic differentiation in Matlab

The need for robust optimisation in aircraft conceptual design, for which the design parameters are assumed stochastic, is introduced. We highlight two approaches, first-order method of moments and Sigma-Point reduced quadrature, to estimate the mean and variance of the design’s outputs. The method of moments requires the design model’s differentiation and here, since the model is implemented in Matlab, is performed using the AD tool MAD. Gradient-based constrained optimisation of the stochastic model is shown to be more efficient using AD-obtained gradients than finite-differencing. A post-optimality analysis, performed using ADenabled third-order method of moments and Monte-Carlo analysis, confirms the attractiveness of the Sigma-Point technique for uncertainty propagation

2019 ARIA Care pathways for allergen immunotherapy

Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence-based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including healthcare professionals. The decision to prescribe AIT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomarkers that can predict AIT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate pharmacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow-up of patients.Peer reviewe

ARIA-EAACI statement on asthma and COVID-19 (June 2, 2020)

Non peer reviewe

Сверхлегкие генераторные модули для КВЧ-терапии

Разработаны миниатюрные генераторные модули для КВЧ-терапии, лег-ко фиксируемые в любом месте тела пациента. Могут быть использованы не только в медицине

ARIA 2016 : Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.Peer reviewe

ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma a

Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology

Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.Peer reviewe

Adherence to treatment in allergic rhinitis using mobile technology. The MASK Study

Background: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. Objectives: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. Methods: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. Results: A total of 12143 users were registered. A total of 6949 users reported at least one VAS data recording. Among them, 1887 users reported >= 7 VAS data. About 1195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR >= 70% and PDC = 70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR Conclusion and clinical relevance: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.Peer reviewe

Nitric oxide responses in Arabidopsis hypocotyls are mediated by diverse phytohormone pathways

[EN] Plants are often exposed to high levels of nitric oxide (NO) that affects development and stress-triggered responses. However, the way in which plants sense NO is still largely unknown. Here we combine the analysis of early changes in the transcriptome of plants exposed to a short acute pulse of exogenous NO with the identification of transcription factors (TFs) involved in NO sensing. The NO-responsive transcriptome was enriched in hormone homeostasis and signaling-related genes. To assess events involved in NO sensing in hypocotyls, we used a functional sensing assay based on the NO-induced inhibition of hypocotyl elongation in etiolated seedlings. Hormone-related mutants and the TRANSPLANTA collection of transgenic lines conditionally expressing Arabidopsis TFs were screened for NO-triggered hypocotyl shortening. These approaches allowed the identification of hormone-related TFs, ethylene perception and signaling, strigolactone biosynthesis and signaling, and salicylate production and accumulation that are essential for or modulate hypocotyl NO sensing. Moreover, NO inhibits hypocotyl elongation through the positive and negative regulation of some abscisic acid (ABA) receptors and transcripts encoding brassinosteroid signaling components thereby also implicating these hormones in NO sensing.This work was supported by grants BIO2014-56067-P and BIO2017-82945-P from the Spanish Ministry of Economy, Industry and Competitiveness and FEDER funds. We thank the Genomics Unit of the Centro Nacional de Biotecnologia (CNB-CSIC, Madrid, Spain) for microarray processing. We gratefully acknowledged the kind donation of mutant seeds: Roberto Solano and Andrea Chini (CNB, Madrid, Spain) for the jaz and myc mutants; Paul Verslues (Institute of Plant and Microbial Biology, Academia Sinica, Taiwan) for the hai mutants; Javier Agusti, Pablo Tornero, and Pedro Rodriguez (IBMCP, Valencia, Spain) for the max, sid2eds5nahG, and pyr/pyl mutants, respectively; and Hiroaki Fujii (University of Turku, Finland) for the snrk2.3 and 2.9 mutants.Castillo López Del Toro, MC.; Coego Gonzalez, A.; Costa-Broseta, Á.; Leon Ramos, J. (2018). Nitric oxide responses in Arabidopsis hypocotyls are mediated by diverse phytohormone pathways. Journal of Experimental Botany. 69(21):5265-5278. https://doi.org/10.1093/jxb/ery286S52655278692