Positive selection on a bacterial oncoprotein associated with gastric cancer

<p>Background</p> <p><it>Helicobacter pylori </it>is a vertically inherited gut commensal that is carcinogenic if it possesses the <it>cag</it> pathogenicity island (<it>cag </it>PaI); infection with <it>H.pylori </it>is the major risk factor for gastric cancer, the second leading cause of death from cancer worldwide (WHO). The <it>cag </it>PaI locus encodes the <it>cagA </it>gene, whose protein product is injected into stomach epithelial cells via a Type IV secretion system, also encoded by the <it>cag </it>PaI. Once there, the cagA protein binds to various cellular proteins, resulting in dysregulation of cell division and carcinogenesis. For this reason, cagA may be described as an oncoprotein. A clear understanding of the mechanism of action of cagA and its benefit to the bacteria is lacking.</p> <p>Results</p> <p>Here, we reveal that the <it>cagA </it>gene displays strong signatures of positive selection in bacteria isolated from amerindian populations, using the Ka/Ks ratio. Weaker signatures are also detected in the gene from bacteria isolated from asian populations, using the Ka/Ks ratio and the more sensitive branches-sites model of the PAML package. When the <it>cagA </it>gene isolated from amerindian populations was examined in more detail it was found that the region under positive selection contains the EPIYA domains, which are known to modulate the carcinogenicity of the gene. This means that the carcinogenicity modulating region of the gene is undergoing adaptation. The results are discussed in relation to the high incidences of stomach cancer in some latin american and asian populations.</p> <p>Conclusion</p> <p>Positive selection on cagA indicates antagonistic coevolution between host and bacteria, which appears paradoxical given that cagA is detrimental to the human host upon which the bacteria depends. This suggests several non-exclusive possibilities; that gastric cancer has not been a major selective pressure on human populations, that cagA has an undetermined benefit to the human host, or that horizontal transmission of <it>H.pylori </it>between hosts has been more important in the evolution of <it>H.pylori </it>than previously recognized, reducing the selective pressure to lower the pathogenicity of the bacteria. The different patterns of adaptation of the gene in different human populations indicates that there are population specific differences in the human gut environment - due either to differences in host genetics or diet and other lifestyle features.</p

Spatial characteristics and temporal evolution of chemical and biological freshwater status as baseline assessment on the tropical island San Cristóbal (Galapagos, Ecuador)

The fragility of geographically isolated islands stresses the necessity of evaluating the current situation, identifying temporal trends and suggesting appropriate conservation measures. To support this, we assessed the freshwater quality of three stream basins on San Cristóbal (Galapagos) for two consecutive years. Abiotic conditions generally complied with existing guidelines, except for the pH in the Cerro Gato basin (0.12 mg P L−1). Macroinvertebrate communities were characterized by low family richness (3–11) and were dominated by Atyidae or Chironomidae, thereby causing low diversity (0.33–1.65). Spatial analysis via principal component analysis (PCA) illustrated that abiotic differences between stream basins were mostly related to turbidity, pH, dissolved oxygen (DO), and conductivity. Biotic differences were less clear due to masking by anthropogenic disturbances and dispersal limitations, yet indicated a negative effect of reduced pH and DO on Atyidae presence. In 2017, significantly narrower ranges were found for turbidity, temperature, pH, and diversity (p < 0.01), suggesting a decrease in habitat variability and a need for conservation measures, including mitigating measures related to dam construction for water extraction. As such, further follow-up is highly recommended for the sustainable development and environmental protection of this unique archipelago

Carbon dynamics and CO2 and CH4 exchange in the mangrove dominated Guayas river delta, Ecuador

Although estuaries are considered important pathways in the global carbon cycle, carbon dynamics in tropical estuaries is relatively understudied. Here, the tidal, seasonal and spatial variability of particulate organic carbon (POC), dissolved inorganic carbon (DIC), carbon dioxide (CO2) and methane (CH4), among other biogeochemical variables related to carbon cycling, were studied in the Guayas river delta (Ecuador) to document the sources, processing and fluxes of these carbon forms. All variables were studied during a semi-diurnal (13 hour) tidal cycle and along river transects at low and high tides, all carried out during one dry and rainy season. POC and total suspended matter (TSM) strongly covaried and peaked at high tidal flow velocities during a tidal cycle and at high river discharge during the rainy season, suggesting that resuspension of bottom sediments and/or surface erosion in the river catchment were a dominant source of particulate matter in the water column. The δ13C of POC, (from ~-22‰ to ~-27‰) showed an increasing contribution of marine phytoplankton to the POC pool as moving downstream along the delta during the dry season. Upstream DIC concentrations (~1200 μmol L-1) were high in the Guayas river delta as compared to other tropical estuarine systems, and the δ13C of DIC revealed a shift from a more phytoplankton dominated source in the dry season and downstream (~-4‰) to a relatively more terrestrial source in the rainy season and upstream (~-12.5‰). Both DIC and its δ13C showed slight but consistent deviations from conservative mixing that hint at inputs of 13C depleted DIC from mineralization along the delta. High values of the partial pressure of CO2 (pCO2) observed upstream and in the rainy season (~5250 μatm), associated with O2 undersaturation (~60%) and low δ13CDIC, suggest a strongly heterotrophic system, and resulted in high CO2 efflux to the atmosphere. CH4 concentrations were also higher during the rainy than dry season (93.5±62.5 vs. 61.3±39.5 nmol L-1), but unlike pCO2, showed tidal variations similar to TSM and POC, thus alluding to potential CH4 release from sediments during resuspension events at high tidal flow velocities. This explorative survey revealed complex drivers and biogeochemical processes acting upon various spatio-temporal scales which are necessary to consider for a complete understanding of the carbon biogeochemistry in estuarine systems. Similar surveys on estuarine carbon in data scarce regions are encouraged to constrain uncertainties in coastal zone carbon budgets

Nuclear astrophysics with radioactive ions at FAIR

R. Reifarth et al: ; 12 págs.; 9 figs.; Open Access funded by Creative Commons Atribution Licence 3.0 ; Nuclear Physics in Astrophysics VI (NPA6)The nucleosynthesis of elements beyond iron is dominated by neutron captures in the s and r processes. However, 32 stable, proton-rich isotopes cannot be formed during those processes, because they are shielded from the s-process ow and r-process -decay chains. These nuclei are attributed to the p and rp process. For all those processes, current research in nuclear astrophysics addresses the need for more precise reaction data involving radioactive isotopes. Depending on the particular reaction, direct or inverse kinematics, forward or time-reversed direction are investigated to determine or at least to constrain the desired reaction cross sections. The Facility for Antiproton and Ion Research (FAIR) will oer unique, unprecedented opportunities to investigate many of the important reactions. The high yield of radioactive isotopes, even far away from the valley of stability, allows the investigation of isotopes involved in processes as exotic as the r or rp processes.This project was supported by the HGF Young Investigators Project VH-NG-327, EMMI, H4F, HGS-HIRe, JINA, NAVI, DFG and ATHENA.Peer Reviewe

Experimental Characterisation of the Fire Behaviour of Thermal Insulation Materials for a Performance-Based Design Methodology

A novel performance-based methodology for the quantitative fire safe design of building assemblies including insulation materials has recently been proposed. This approach is based on the definition of suitable thermal barriers in order to control the fire hazards imposed by the insulation. Under this framework, the concept of “critical temperature” has been used to define an initiating failure criterion for the insulation, so as to ensure there will be no significant contribution to the fire nor generation of hazardous gas effluents. This paper proposes a methodology to evaluate this “critical temperature” using as examples some of the most common insulation materials used for buildings in the EU market, i.e. rigid polyisocyanurate foam, rigid phenolic foam, rigid expanded polystyrene foam and low density flexible stone wool. A characterisation of these materials, based on a series of ad-hoc Cone Calorimeter and thermo-gravimetric experiments, serves to establish the rationale behind the quantification of the critical temperature. The temperature of the main peak of pyrolysis, obtained from differential thermo-gravimetric analysis under a nitrogen atmosphere at low heating rates, is proposed as the “critical temperature” for materials that do not significantly shrink and melt, i.e. charring insulation materials. For materials with shrinking and melting behaviour it is suggested that the melting point could be used as “critical temperature”. Conservative values of “critical temperature” proposed are 300°C for polyisocyanurate, 425°C for phenolic foam and 240°C for expanded polystyrene. The concept of a “critical temperature” for the low density stone wool is examined in the same manner and found to be non-applicable due to the inability to promote a flammable mixture. Additionally, thermal inertia values required for the performance-based methodology are obtained for PIR and PF using a novel approach, providing thermal inertia values within the range 4.5 to 6.5\ua0×\ua010\ua0W\ua0s\ua0K\ua0m

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

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

Guidance to 2018 good practice : ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma

AimsMobile Airways Sentinel NetworK (MASK) belongs to the Fondation Partenariale MACVIA-LR of Montpellier, France and aims to provide an active and healthy life to rhinitis sufferers and to those with asthma multimorbidity across the life cycle, whatever their gender or socio-economic status, in order to reduce health and social inequities incurred by the disease and to improve the digital transformation of health and care. The ultimate goal is to change the management strategy in chronic diseases.MethodsMASK implements ICT technologies for individualized and predictive medicine to develop novel care pathways by a multi-disciplinary group centred around the patients.StakeholdersInclude patients, health care professionals (pharmacists and physicians), authorities, patient's associations, private and public sectors.ResultsMASK is deployed in 23 countries and 17 languages. 26,000 users have registered.EU grants (2018)MASK is participating in EU projects (POLLAR: impact of air POLLution in Asthma and Rhinitis, EIT Health, DigitalHealthEurope, Euriphi and Vigour).Lessons learnt(i) Adherence to treatment is the major problem of allergic disease, (ii) Self-management strategies should be considerably expanded (behavioural), (iii) Change management is essential in allergic diseases, (iv) Education strategies should be reconsidered using a patient-centred approach and (v) Lessons learnt for allergic diseases can be expanded to chronic diseases.Peer reviewe

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

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