Fabrication of calcium phosphate microcapsules using emulsion droplets stabilized with branched copolymers as templates

We report on a versatile and time-efficient method to fabricate calcium phosphate (CaP) microcapsules by utilizing oil-in-water emulsion droplets stabilized with synthetic branched copolymer (BCP) as templates. The BCP was designed to provide a suitable architecture and functionality to produce stable emulsion droplets, and to permit the mineralization of CaP at the surface of the oil droplet when incubated in a solution containing calcium and phosphate ions. The CaP shells of the microcapsules were established to be calcium deficient hydroxyapatite with incorporated chlorine and carbonate species. These capsule walls were made fluorescent by decoration with a fluorescein-bisphosphonate conjugate

Molecular mechanism of influenza A NS1-mediated TRIM25 recognition and inhibition

RIG-I is a viral RNA sensor that induces the production of type I interferon (IFN) in response to infection with a variety of viruses. Modification of RIG-I with K63-linked poly-ubiquitin chains, synthesised by TRIM25, is crucial for activation of the RIG-I/MAVS signalling pathway. TRIM25 activity is targeted by influenza A virus non-structural protein 1 (NS1) to suppress IFN production and prevent an efficient host immune response. Here we present structures of the human TRIM25 coiled-coil-PRYSPRY module and of complexes between the TRIM25 coiled-coil domain and NS1. These structures show that binding of NS1 interferes with the correct positioning of the PRYSPRY domain of TRIM25 required for substrate ubiquitination and provide a mechanistic explanation for how NS1 suppresses RIG-I ubiquitination and hence downstream signalling. In contrast, the formation of unanchored K63-linked poly-ubiquitin chains is unchanged by NS1 binding, indicating that RING dimerisation of TRIM25 is not affected by NS1

Essential Hypertension Is Associated With Changes in Gut Microbial Metabolic Pathways A Multisite Analysis of Ambulatory Blood Pressure

Recent evidence supports a role for the gut microbiota in hypertension, but whether ambulatory blood pressure is associated with gut microbiota and their metabolites remains unclear. We characterized the function of the gut microbiota, their metabolites and receptors in untreated human hypertensive participants in Australian metropolitan and regional areas. Ambulatory blood pressure, fecal microbiome predicted from 16S rRNA gene sequencing, plasma and fecal metabolites called short-chain fatty acid, and expression of their receptors were analyzed in 70 untreated and otherwise healthy participants from metropolitan and regional communities. Most normotensives were female (66%) compared with hypertensives (35%, P<0.01), but there was no difference in age between the groups (59.2±7.7 versus 60.3±6.6 years old). Based on machine learning multivariate covariance analyses of de-noised amplicon sequence variant prevalence data, we determined that there were no significant differences in predicted gut microbiome α- and β-diversity metrics between normotensives versus essential or masked hypertensives. However, select taxa were specific to these groups, notably Acidaminococcus spp., Eubacterium fissicatena, and Muribaculaceae were higher, while Ruminococcus and Eubacterium eligens were lower in hypertensives. Importantly, normotensive and essential hypertensive cohorts could be differentiated based on gut microbiome gene pathways and metabolites. Specifically, hypertensive participants exhibited higher plasma acetate and butyrate, but their immune cells expressed reduced levels of short-chain fatty acid-activated GPR43 (G-protein coupled receptor 43). In conclusion, gut microbial diversity did not change in essential hypertension, but we observed a significant shift in microbial gene pathways. Hypertensive subjects had lower levels of GPR43, putatively blunting their response to blood pressure-lowering metabolites

Reliability of two behavioral tools to assess pain in preterm neonates

CONTEXT: One of the main difficulties in adequately treating the pain of neonatal patients is the scarcity of validated pain evaluation methods for this population. OBJECTIVE: To analyze the reliability of two behavioral pain scales in neonates. TYPE OF STUDY: Cross-sectional. SETTING: University hospital neonatal intensive care unit. PARTICIPANTS: 22 preterm neonates were studied, with gestational age of 34 ± 2 weeks, birth weight of 1804 ± 584 g, 68% female, 30 ± 12 hours of life, and 30% intubated. PROCEDURES: Two neonatologists (A and B) observed the patients at the bedside and on video films for 10 minutes. The Neonatal Facial Coding System and the Clinical Scoring System were scored at 1, 5, and 10 minutes. The final score was the median of the three values for each observer and scale. A and B were blinded to each other. Video assessments were made three months after bedside evaluations. MAIN MEASUREMENTS: End scores were compared between the observers using the intraclass correlation coefficient and bias analysis (paired t test and signal test). RESULTS: For the Neonatal Facial Coding System, at the bedside and on video, A and B showed a significant correlation of scores (intraclass correlation score: 0.62), without bias between them (t test and signal test: p > 0.05). For the Clinical Scoring System bedside assessment, A and B showed correlation of scores (intraclass correlation score: 0.55), but bias was also detected between them: A scored on average two points higher than B (paired t test and signal test: p 0,05). Para a Escala de Conforto Clínico à beira do leito, os escores obtidos por A e B mostraram uma correlação significante (0,55), foi detectado: o escore obtido por A foi, em média, dois pontos superior ao de B (teste t e do sinal: p < 0,05). Para a mesma escala aplicada em vídeo, os escores obtidos por A e B não mostraram correlação (0,25) e detectou-se viés (teste t e do sinal: p < 0,05). CONCLUSÃO: Os resultados reforçam a confiabilidade do Sistema de Codificação da Atividade Facial Neonatal aplicado à beira do leito para a avaliação da dor no recém-nascido pré-termo.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Neonatal DivisionUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Department of EpidemiologyUNIFESP, EPM, Neonatal DivisionUNIFESP, EPM, Department of EpidemiologySciEL

Upper atmospheres and ionospheres of planets and satellites

The upper atmospheres of the planets and their satellites are more directly exposed to sunlight and solar wind particles than the surface or the deeper atmospheric layers. At the altitudes where the associated energy is deposited, the atmospheres may become ionized and are referred to as ionospheres. The details of the photon and particle interactions with the upper atmosphere depend strongly on whether the object has anintrinsic magnetic field that may channel the precipitating particles into the atmosphere or drive the atmospheric gas out to space. Important implications of these interactions include atmospheric loss over diverse timescales, photochemistry and the formation of aerosols, which affect the evolution, composition and remote sensing of the planets (satellites). The upper atmosphere connects the planet (satellite) bulk composition to the near-planet (-satellite) environment. Understanding the relevant physics and chemistry provides insight to the past and future conditions of these objects, which is critical for understanding their evolution. This chapter introduces the basic concepts of upper atmospheres and ionospheres in our solar system, and discusses aspects of their neutral and ion composition, wind dynamics and energy budget. This knowledge is key to putting in context the observations of upper atmospheres and haze on exoplanets, and to devise a theory that explains exoplanet demographics.Comment: Invited Revie

Individual rules for trail pattern formation in Argentine ants (Linepithema humile)

We studied the formation of trail patterns by Argentine ants exploring an empty arena. Using a novel imaging and analysis technique we estimated pheromone concentrations at all spatial positions in the experimental arena and at different times. Then we derived the response function of individual ants to pheromone concentrations by looking at correlations between concentrations and changes in speed or direction of the ants. Ants were found to turn in response to local pheromone concentrations, while their speed was largely unaffected by these concentrations. Ants did not integrate pheromone concentrations over time, with the concentration of pheromone in a 1 cm radius in front of the ant determining the turning angle. The response to pheromone was found to follow a Weber's Law, such that the difference between quantities of pheromone on the two sides of the ant divided by their sum determines the magnitude of the turning angle. This proportional response is in apparent contradiction with the well-established non-linear choice function used in the literature to model the results of binary bridge experiments in ant colonies (Deneubourg et al. 1990). However, agent based simulations implementing the Weber's Law response function led to the formation of trails and reproduced results reported in the literature. We show analytically that a sigmoidal response, analogous to that in the classical Deneubourg model for collective decision making, can be derived from the individual Weber-type response to pheromone concentrations that we have established in our experiments when directional noise around the preferred direction of movement of the ants is assumed.Comment: final version, 9 figures, submitted to Plos Computational Biology (accepted

Successful up-scaled population interventions to reduce risk factors for non-communicable disease in adults: Results from the International Community Interventions for Health (CIH) project in China, India and Mexico

Background: Non-communicable disease (NCD) is increasing rapidly in low and middle-income countries (LMIC), and is associated with tobacco use, unhealthy diet and physical inactivity. There is little evidence for up-scaled interventions at the population level to reduce risk in LMIC. Methods: The Community Interventions for Health (CIH) program was a population-scale community intervention study with comparator population group undertaken in communities in China, India, and Mexico, each with populations between 150,000-250,000. Culturally appropriate interventions were delivered over 18-24 months. Two independent cross-sectional surveys of a stratified sample of adults aged 18-64 years were conducted at baseline and follow-up. Results: A total of 6,194 adults completed surveys at baseline, and 6,022 at follow-up. The proportion meeting physical activity recommendations decreased significantly in the control group (C) (44.1 to 30.2%), but not in the intervention group (I) (38.0 to 36.1%), p<0.001. Those eating ≥5 portions of fruit and vegetables daily decreased significantly in C (19.2 to 17.2%), but did not change in I (20.0 to 19.6%,), p=0.013. The proportion adding salt to food was unchanged in C (24.9 to 25.3%) and decreased in I (25.9 to 19.6%), p<0.001. Prevalence of obesity increased in C (8.3 to 11.2%), with no change in I (8.6 to 9.7%,) p=0.092. Concerning tobacco, for men the difference-in-difference analysis showed that the reduction in use was significantly greater in I compared to C (p=0.014) Conclusions: Up-scaling known health promoting interventions designed to reduce the incidence of NCD in whole communities in LMIC is feasible, and has measurable beneficial outcomes on risk factors for NCD, namely tobacco use, diet, and physical inactivity

Geological archive of the onset of plate tectonics

© 2018 The Author(s) Published by the Royal Society. All rights reserved. Plate tectonics, involving a globally linked system of lateral motion of rigid surface plates, is a characteristic feature of our planet, but estimates of how long it has been the modus operandi of lithospheric formation and interactions range from the Hadean to the Neoproterozoic. In this paper, we review sedimentary, igneous and metamorphic proxies along with palaeomagnetic data to infer both the development of rigid lithospheric plates and their independent relative motion, and conclude that significant changes in Earth behaviour occurred in the mid- to late Archaean, between 3.2 Ga and 2.5 Ga. These data include: sedimentary rock associations inferred to have accumulated in passive continental margin settings, marking the onset of seafloor spreading; the oldest foreland basin deposits associated with lithospheric convergence; a change from thin, new continental crust of mafic composition to thicker crust of intermediate composition, increased crustal reworking and the emplacement of potassic and peraluminous granites, indicating stabilization of the lithosphere; replacement of dome and keel structures in granite-greenstone terranes, which relate to vertical tectonics, by linear thrust imbricated belts; the commencement of temporally paired systems of intermediate and high dT/dP gradients, with the former interpreted to represent subduction to collisional settings and the latter representing possible hinterland back-arc settings or ocean plateau environments. Palaeomagnetic data from the Kaapvaal and Pilbara cratons for the interval 2780-2710Ma and from the Superior, Kaapvaal and Kola-Karelia cratons for 2700-2440Ma suggest significant relative movements. We consider these changes in the behaviour and character of the lithosphere to be consistent with a gestational transition from a non-plate tectonic mode, arguably with localized subduction, to the onset of sustained plate tectonics

Costs of the 'Hartslag Limburg' community heart health intervention

BACKGROUND: Little is known about the costs of community programmes to prevent cardiovascular diseases. The present study calculated the economic costs of all interventions within a Dutch community programme called Hartslag Limburg, in such a way as to facilitate generalisation to other countries. It also calculated the difference between the economic costs and the costs incurred by the coordinating institution. METHODS: Hartslag Limburg was a large-scale community programme that consisted of many interventions to prevent cardiovascular diseases. The target population consisted of all inhabitants of the region (n = 180.000). Special attention was paid to reach persons with a low socio-economic status. Costs were calculated using the guidelines for economic evaluation in health care. An overview of the material and staffing input involved was drawn up for every single intervention, and volume components were attached to each intervention component. These data were gathered during to the implementation of the intervention. Finally, the input was valued, using Dutch price levels for 2004. RESULTS: The economic costs of the interventions that were implemented within the five-year community programme (n = 180,000) were calculated to be about €900,000. €555,000 was spent on interventions to change people's exercise patterns, €250,000 on improving nutrition, €50,000 on smoking cessation, and €45,000 on lifestyle in general. The coordinating agency contributed about 10% to the costs of the interventions. Other institutions that were part of the programme's network and external subsidy providers contributed the other 90% of the costs. CONCLUSION: The current study calculated the costs of a community programme in a detailed and systematic way, allowing the costs to be easily adapted to other countries and regions. The study further showed that the difference between economic costs and the costs incurred by the coordinating agency can be very large. Cost sharing was facilitated by the unique approach used in the Hartslag Limburg programme