2,084 research outputs found
Measurement error in a multi-level analysis of air pollution and health: a simulation study.
BACKGROUND: Spatio-temporal models are increasingly being used to predict exposure to ambient outdoor air pollution at high spatial resolution for inclusion in epidemiological analyses of air pollution and health. Measurement error in these predictions can nevertheless have impacts on health effect estimation. Using statistical simulation we aim to investigate the effects of such error within a multi-level model analysis of long and short-term pollutant exposure and health. METHODS: Our study was based on a theoretical sample of 1000 geographical sites within Greater London. Simulations of "true" site-specific daily mean and 5-year mean NO2 and PM10 concentrations, incorporating both temporal variation and spatial covariance, were informed by an analysis of daily measurements over the period 2009-2013 from fixed location urban background monitors in the London area. In the context of a multi-level single-pollutant Poisson regression analysis of mortality, we investigated scenarios in which we specified: the Pearson correlation between modelled and "true" data and the ratio of their variances (model versus "true") and assumed these parameters were the same spatially and temporally. RESULTS: In general, health effect estimates associated with both long and short-term exposure were biased towards the null with the level of bias increasing to over 60% as the correlation coefficient decreased from 0.9 to 0.5 and the variance ratio increased from 0.5 to 2. However, for a combination of high correlation (0.9) and small variance ratio (0.5) non-trivial bias (>â25%) away from the null was observed. Standard errors of health effect estimates, though unaffected by changes in the correlation coefficient, appeared to be attenuated for variance ratios >â1 but inflated for variance ratios <â1. CONCLUSION: While our findings suggest that in most cases modelling errors result in attenuation of the effect estimate towards the null, in some situations a non-trivial bias away from the null may occur. The magnitude and direction of bias appears to depend on the relationship between modelled and "true" data in terms of their correlation and the ratio of their variances. These factors should be taken into account when assessing the validity of modelled air pollution predictions for use in complex epidemiological models
The OPAL bugs count survey: exploring the effects of urbanisation and habitat characteristics using citizen science
Citizen science projects can gather datasets with observation counts and spatiotemporal coverage far in excess of what can easily be achieved using only professional scientists. However, there exists a potential trade-off between the number of participants and the quality of data gathered. The Bugs Count citizen science project had thousands of participants because of its few barriers to taking part, allowing participation by anyone in England with access to any area of outdoor space. It was designed to scope for both the effects of variation in local habitat and urbanisation on broad taxonomic groups of invertebrates, and the responses of six target âSpecies Questâ species (Adalia bipunctata, Ocypus olens, Aglais urticae, Palomena prasina, Limax maximus, and Bombus hypnorum) to urbanisation. Participants were asked to search for invertebrates in three areas: âsoft ground surfacesâ, âhuman-made hard surfacesâ, and âplantsâ for 15 min per search. Participants recorded counts of taxa found and a range of environmental information about the survey area. Data samples were weighted according to identification experience and participant age and analysed using canonical correspondence analysis, and tests of observation homogeneity. Species Quest species showed species-specific relationships with urbanisation, but broad taxonomic groups did not show significant relationships with urbanisation. The latter were instead influenced by habitat type and microhabitat availability. The approach used demonstrates that citizen science projects with few barriers to entry can gather viable datasets for scoping broad trends, providing that the projects are carefully designed and analysed to ensure data quality
Multilevel Deconstruction of the In Vivo Behavior of Looped DNA-Protein Complexes
Protein-DNA complexes with loops play a fundamental role in a wide variety of
cellular processes, ranging from the regulation of DNA transcription to
telomere maintenance. As ubiquitous as they are, their precise in vivo
properties and their integration into the cellular function still remain
largely unexplored. Here, we present a multilevel approach that efficiently
connects in both directions molecular properties with cell physiology and use
it to characterize the molecular properties of the looped DNA-lac repressor
complex while functioning in vivo. The properties we uncover include the
presence of two representative conformations of the complex, the stabilization
of one conformation by DNA architectural proteins, and precise values of the
underlying twisting elastic constants and bending free energies. Incorporation
of all this molecular information into gene-regulation models reveals an
unprecedented versatility of looped DNA-protein complexes at shaping the
properties of gene expression.Comment: Open Access article available at
http://www.plosone.org/article/fetchArticle.action?articleURI=info%3Adoi%2F10.1371%2Fjournal.pone.000035
Endocrine resistance in breast cancer: new roles for ErbB3 and ErbB4
Endocrine resistance is a major limitation to the successful treatment of estrogen receptor-positive (ER+) breast cancer, and the EGFR (epidermal growth factor receptor) and ErbB-2 receptor tyrosine kinases are involved in this process. A recent study now implicates the other two ErbB family members, ErbB-3 and -4. Exposure of ER+ breast cancer cells to the pure antiestrogen, fulvestrant, increased levels of ErbB-3 or ErbB-4 and sensitivity to the growth-stimulatory effects of heregulin Ýą, a potent ligand for these receptors. Thus, the initial growth-inhibitory effects of fulvestrant appear compromised by cellular plasticity that allows rapid compensatory growth stimulation via ErbB-3/4. Further evaluation of pan-ErbB receptor inhibitors in endocrine-resistant disease appears warranted
On the behaviour of lung tissue under tension and compression
Lung injuries are common among those who suffer an impact or trauma. The relative severity of injuries up to physical tearing of tissue have been documented in clinical studies. However, the specific details of energy required to cause visible damage to the lung parenchyma are lacking. Furthermore, the limitations of lung tissue under simple mechanical loading are also not well documented. This study aimed to collect mechanical test data from freshly excised lung, obtained from both Sprague-Dawley rats and New Zealand White rabbits. Compression and tension tests were conducted at three different strain rates: 0.25, 2.5 and 25âminâ1. This study aimed to characterise the quasi-static behaviour of the bulk tissue prior to extending to higher rates. A nonlinear viscoelastic analytical model was applied to the data to describe their behaviour. Results exhibited asymmetry in terms of differences between tension and compression. The rabbit tissue also appeared to exhibit stronger viscous behaviour than the rat tissue. As a narrow strain rate band is explored here, no conclusions are being drawn currently regarding the rate sensitivity of rat tissue. However, this study does highlight both the clear differences between the two tissue types and the important role that composition and microstructure can play in mechanical response
Mining multi-item drug adverse effect associations in spontaneous reporting systems
<p>Abstract</p> <p>Background</p> <p>Multi-item adverse drug event (ADE) associations are associations relating multiple drugs to possibly multiple adverse events. The current standard in pharmacovigilance is bivariate association analysis, where each single drug-adverse effect combination is studied separately. The importance and difficulty in the detection of multi-item ADE associations was noted in several prominent pharmacovigilance studies. In this paper we examine the application of a well established data mining method known as association rule mining, which we tailored to the above problem, and demonstrate its value. The method was applied to the FDAs spontaneous adverse event reporting system (AERS) with minimal restrictions and expectations on its output, an experiment that has not been previously done on the scale and generality proposed in this work.</p> <p>Results</p> <p>Based on a set of 162,744 reports of suspected ADEs reported to AERS and published in the year 2008, our method identified 1167 multi-item ADE associations. A taxonomy that characterizes the associations was developed based on a representative sample. A significant number (67% of the total) of potential multi-item ADE associations identified were characterized and clinically validated by a domain expert as previously recognized ADE associations. Several potentially novel ADEs were also identified. A smaller proportion (4%) of associations were characterized and validated as known drug-drug interactions.</p> <p>Conclusions</p> <p>Our findings demonstrate that multi-item ADEs are present and can be extracted from the FDAâs adverse effect reporting system using our methodology, suggesting that our method is a valid approach for the initial identification of multi-item ADEs. The study also revealed several limitations and challenges that can be attributed to both the method and quality of data.</p
Environmental-dependent proline accumulation in plants living on gypsum soils
[EN] Biosynthesis of prolineÂżor other compatible solutesÂżis a conserved response of all organisms to different abiotic stress conditions leading to cellular dehydration. However, the biological relevance of this reaction for plant stress tolerance mechanisms remains largely unknown, since there are very few available data on proline levels in stress-tolerant plants under natural conditions. The aim of this work was to establish the relationship between proline levels and different environmental stress factors in plants living on gypsum soils. During the 2-year study (2009Âż2010), soil parameters and climatic data were monitored, and proline contents were determined, in six successive samplings, in ten taxa present in selected
experimental plots, three in a gypsum area and one in a semiarid zone, both located in the province of Valencia, in south-east Spain. Mean proline values varied significantly between species; however, seasonal variations within species
were in many cases even wider, with the most extreme differences registered in Helianthemum syriacum (almost 30 lmol g-1 of DW in summer 2009, as compared to ca. 0.5 in spring, in one of the plots of the gypsum zone). Higher proline contents in plants were generally observed under lower soil humidity conditions, especially in the
2009 summer sampling preceded by a severe drought period. Our results clearly show a positive correlation between the degree of environmental stress and the proline level in most of the taxa included in this study, supporting a functional role of proline in stress tolerance mechanisms of plants adapted to gypsum. However, the main trigger of proline biosynthesis in this type of habitat, as in arid or semiarid zones, is water deficit, while the component of Âżsalt stressÂż due to the presence of gypsum in the soil only plays a secondary role.This work has been supported by the Spanish Ministry of Science and Innovation (Project CGL2008-00438/BOS), with contribution from the European Regional Development Fund.Boscaiu, M.; Bautista Carrascosa, I.; LidĂłn Cerezuela, AL.; Llinares Palacios, JV.; Lull, C.; Donat-Torres, M.; Mayoral GarcĂa-Berlanga, O.... (2013). Environmental-dependent proline accumulation in plants living on gypsum soils. Acta Physiologiae Plantarum. 35:2193-2204. https://doi.org/10.1007/s11738-013-1256-3S2193220435Alvarado JJ, Ruiz JM, LĂłpez-Cantarero I, Molero J, Romero L (2000) Nitrogen metabolism in five plant species characteristic of gypsiferous soils. J Plant Physiol 156:612â616Ashraf M, Foolad MR (2007) Roles of glycine betaine and proline in improving plant abiotic stress resistance. Environ Exp Bot 59:206â216Bates LS, Waldren RP, Teare ID (1973) Rapid determination of free proline for water stress studies. Plant Soil 39:205â207Briens M, Larher F (1982) Osmoregulation in halophytic higher plants: a comparative study of soluble carbohydrates, polyols, betaines and free proline. Plant, Cell Environ 5:287â292Burriel F, Hernando V (1947) Nuevo mĂŠtodo para determinar el fĂłsforo asimilable en los suelos. Anales de EdafologĂa y FisiologĂa Vegetal 9:611â622Caballero I, Olano JM, Loidi J, Escudero A (2003) Seed bank structure along a semi-arid gypsum gradient in Central Spain. J Arid Environ 55:287â299Escudero A, Carnes LF, PĂŠrez GarcĂa F (1997) Seed germination of gypsophytes and gypsovags in semi-arid central Spain. J Arid Environ 36:487â497Escudero A, Somolinos RC, Olano JM, Rubio A (1999) Factors controlling the establishment of Helianthemum squamatum, an endemic gypsophite of semi-arid Spain. J Ecol 87:290â302FAO (1990) Management of gypsiferous soils. FAO Soils Bull 62Ferriol M, PĂŠrez I, Merle H, Boira H (2006) Ecological germination requirements of the aggregate species Teucrium pumilum (Labiatae) endemic to Spain. Plant Soil 284:205â216Flowers TJ, Colmer TD (2008) Salinity tolerance in halophytes. New Phytol 179:945â963Flowers TJ, Troke PF, Yeo AR (1977) The mechanism of salt tolerance in halophytes. Ann Rev Plant Physiol 28:89â121Gil R, Lull C, Boscaiu M, Bautista I, LidĂłn A, Vicente O (2011) Soluble carbohydrates as osmolytes in several halophytes from a Mediterranean salt marsh. Not Bot Horti Agrobo 39(2):9â17Grigore MN, Boscaiu M, Vicente O (2011) Assessment of the relevance of osmolyte biosynthesis for salt tolerance of halophytes under natural conditions. Eur J Plant Sci Biotech 5:12â19Hare PD, Cress WA, Van Standen J (1998) Dissecting the roles of osmolyte accumulation during stress. Plant Cell Environ 21:535â553Keeney DR, Nelson DW (1982) Nitrogen inorganic forms. In: Page AL et al (eds) Methods of soil analysis, part 2: chemical and microbiological properties. Soil Science Society of America, Madison, pp 643â698Knudsen D, Peterson GA, Pratt PF (1982) Lithium, Sodium and Potassium. In: Page AL et al (eds) Methods of soil analysis, part 2: chemical and microbiological properties. Soil Science Society of America, Madison, pp 225â246Kuo S (1996) Phosphorus. In: Spark DL (ed) Methods of soil analysis: chemical methods, part 3. Soil Science Society of America, Madison, pp 869â919Martens H, Maes T (1989) Multivariate calibration. Wiley, New York, pp 97â108MartĂnez-Duro E, Ferrandis P, Escudero A, Luzuriaga AL, Herranz JM (2010) Secondary old-field succession in an ecosystem with restrictive soils: does time from abandonment matter? Appl Veg Sci 13:234â248Meyer SE (1986) The ecology of gypsophile endemism in the eastern Mojave desert. Ecology 67:1303â1313Meyer SE, GarcĂa-Moya E (1989) Plant community patterns and soil moisture regime in gypsum grasslands of north central Mexico. J Arid Environ 16:147â155Meyer SE, GarcĂa-Moya E, Lagunes-Espinoza LC (1992) Topographic and soil surface effects on gypsophile plant community patterns in central Mexico. J Veg Sci 3:429â438Moruno F, Soriano P, Vicente O, Boscaiu M, Estrelles E (2011) Opportunistic germination behaviour of Gypsophila (Caryophyllaceae) in two priority habitats from semi-arid Mediterranean steppes. Not Bot Horti Agrobo 39(1):18â23Mota JF, SĂĄnchez GĂłmez P, Merlo Calvente ME, CatalĂĄn RodrĂguez P, Laguna Lumbreras E, de la Cruz Rot M, Navarro Reyes FB, Marchal Gallardo F, BartolomĂŠ Esteban C, MartĂnez Labarga JM, Sainz Ollero H, Valle Tendero F, Serra Laliga L, MartĂnez HernĂĄndez F, Garrido Becerra JA, PĂŠrez GarcĂa FJ (2009) AproximaciĂłn a la checklist de los gipsĂłfitos ibĂŠricos. Anales de BiologĂa 31:71â80MurakeĂśzy ĂP, Nagy Z, DuhazĂŠ C, Bouchereau A, Tuba Z (2003) Seasonal changes in the levels of compatible osmolytes in three halophytic species of inland saline vegetation in Hungary. J Plant Physiol 160:395â401Nelson DW, Sommers LE (1982) Total carbon, organic carbon, and organic matter. In: Page AL et al (eds) Methods of soil analysis, part 2: chemical and microbiological properties. Soil Science Society of America, Madison, pp 539â577Palacio S, Escudero A, Montserrat-MartĂ G, Maestro M, Milla R, Albert M (2007) Plants living on gypsum: beyond the specialist model. Ann Bot 99:333â343Parsons RF (1977) Gypsophily in plantsâa review. Am Midl Nat 96:1â20Pueyo Y, Alados CL, Maestro M, Komac B (2007) Gypsophile vegetation patterns under a range of soil properties induced by topographical position. Plant Ecol 189:301â311Rivas-MartĂnez S, Rivas-SĂĄenz S (2009) Worldwide Bioclimatic Classification System. Phytosociological Research Center, Complutense University of Madrid, Spain. http://www.globalbioclimatics.org/ . Accessed 15 Nov 2012RomĂŁo RL, Escudero A (2005) Gypsum physical soil crusts and the existence of gypsophytes in semi-arid central Spain. Plant Ecol 181:127â137Rubio A, Escudero A (2000) Small-scale spatial soil-plant relationship in semi-arid gypsum environment. Plant Soil 220:139â150RuĂz JM, LĂłpez-Cantarero I, Rivero RM, Romero L (2003) Sulphur phytoaccumulation in plant species characteristic of gypsiferous soils. Int J Phytorem 5:203â210Szabados L, SavourĂŠ A (2010) Proline: a multifunctional amino acid. Trends Plant Sci 15:89â97Szabados L, KovĂĄcs H, Zilberstein A, Bouchereau A (2011) Plants in extreme environments: importance of protective compounds in stress tolerance. Adv Bot Res 57:105â150Tecator Application Note (1984) AN 5226: Determination of ammonium in 2Â M KCl soil extracts by FIAstar 5000. AN 5201: Determination of the sum of nitrate and nitrite in water by FIAstar 5000. (Adapted for 2Â M KCl soil extracts)Tipirdamaz R, Gagneul D, DuhazĂŠ C, AĂŻnouche A, Monnier C, Ăzkum D, Larher F (2006) Clustering of halophytes from an inland salt marsh in Turkey according to their ability to accumulate sodium and nitrogenous osmolytes. Environ Exp Bot 57:139â153Verheye WH, Boyadgiev TG (1997) Evaluating the land use potential of gypsiferous soils from field pedogenic characteristics. Soil Use Manage 13:97â103Vicente O, Boscaiu M, Naranjo MA, Estrelles E, BellĂŠs JM, Soriano P (2004) Responses to salt stress in the halophyte Plantago crassifolia (Plantaginaceae). J Arid Environ 58:463â481Yancey PH (2005) Organic osmolytes as compatible, metabolic and counteracting cytoprotectants in high osmolarity and other stresses. J Exp Biol 208:2819â283
The hr1 and Fusion Peptide Regions of the Subgroup B Avian Sarcoma and Leukosis Virus Envelope Glycoprotein Influence Low pH-Dependent Membrane Fusion
The avian sarcoma and leukosis virus (ASLV) envelope glycoprotein (Env) is activated to trigger fusion by a two-step mechanism involving receptor-priming and low pH fusion activation. In order to identify regions of ASLV Env that can regulate this process, a genetic selection method was used to identify subgroup B (ASLV-B) virus-infected cells resistant to low pH-triggered fusion when incubated with cells expressing the cognate TVB receptor. The subgroup B viral Env (envB) genes were then isolated from these cells and characterized by DNA sequencing. This led to identification of two frequent EnvB alterations which allowed TVB receptor-binding but altered the pH-threshold of membrane fusion activation: a 13 amino acid deletion in the host range 1 (hr1) region of the surface (SU) EnvB subunit, and the A32V amino acid change within the fusion peptide of the transmembrane (TM) EnvB subunit. These data indicate that these two regions of EnvB can influence the pH threshold of fusion activation
- âŚ