The zipper mechanism in phagocytosis: energetic requirements and variability in phagocytic cup shape

Phagocytosis is the fundamental cellular process by which eukaryotic cells bind and engulf particles by their cell membrane. Particle engulfment involves particle recognition by cell-surface receptors, signaling and remodeling of the actin cytoskeleton to guide the membrane around the particle in a zipper-like fashion. Despite the signaling complexity, phagocytosis also depends strongly on biophysical parameters, such as particle shape, and the need for actin-driven force generation remains poorly understood. Here, we propose a novel, three-dimensional and stochastic biophysical model of phagocytosis, and study the engulfment of particles of various sizes and shapes, including spiral and rod-shaped particles reminiscent of bacteria. Highly curved shapes are not taken up, in line with recent experimental results. Furthermore, we surprisingly find that even without actin-driven force generation, engulfment proceeds in a large regime of parameter values, albeit more slowly and with highly variable phagocytic cups. We experimentally confirm these predictions using fibroblasts, transfected with immunoreceptor FcyRIIa for engulfment of immunoglobulin G-opsonized particles. Specifically, we compare the wild-type receptor with a mutant receptor, unable to signal to the actin cytoskeleton. Based on the reconstruction of phagocytic cups from imaging data, we indeed show that cells are able to engulf small particles even without support from biological actin-driven processes. This suggests that biochemical pathways render the evolutionary ancient process of phagocytic highly robust, allowing cells to engulf even very large particles. The particle-shape dependence of phagocytosis makes a systematic investigation of host-pathogen interactions and an efficient design of a vehicle for drug delivery possible.Comment: Accepted for publication in BMC Systems Biology. 17 pages, 6 Figures, + supplementary informatio

Platte River Evapotranspiration: A Historical Perspective in Central Nebraska

A computational model was developed to estimate evapotranspiration (ET) in the Platte River ecosystem of central Nebraska. Data used in the model were mostly derived from the literature, although leaftemperature data were collected to estimate species transpirationcoefficients. Preliminary estimates for ET are 35.5 in per yr during the April-tooctober growing season. Riparian forest accounted for 30% of the total ET, followed in order of importance by open-water evaporation, forested islands, herbaceous riparian-transpiration, sandbar evaporation, and then hcrbaceous island-vegetation, which accounted for only 10% of the total ET. The Platte River has changed markedly during the last 40 years, with reduced flows and narrowed channel-width. Much riparian forest has grown up in that time and vegetated islands occupy a greater percentage of the remaining channel than previously. A comparison of ET rates between the 1930s and 1970s was attempted, using the computational model developed. Total ET rates in the 1930s were about the same as today (37.3 in per yr) but proportion by habitat differed greatly, with open-water evaporation probably accounting for about one-half the total ET then. The total loss due to evapotranspiration between Kingsley Dam and Duncan, Nebraska, from Platte River ecosystems (except for wet-meadow and cropland) was estimated to be 379,000 acre-feet per year

Blackwood's and the Cockney School of Prose

This article looks at the changing attitude of the Blackwood's leading writers John Wilson and John Gibson Lockhart to the so-called Cockney Prose writers, Coleridge, Hazlitt, Hunt, Lamb, and Ollier. It shows how a tendency to lump all the Cockneys together in October 1817 slowly developed into a more discriminating attitude in the course of the revamped magazine's first year. It also shows how the principles behind that discrimination lay in Lockhart's reading of Schlegel's lectures, and in the models of scholarship and genial reading that were contained therein

The prohibitin-repressive interaction with E2F1 is rapidly inhibited by androgen signalling in prostate cancer cells

Prohibitin (PHB) is a tumour suppressor molecule with pleiotropic activities across several cellular compartments including mitochondria, cell membrane and the nucleus. PHB and the steroid-activated androgen receptor (AR) have an interplay where AR downregulates PHB, and PHB represses AR. Additionally, their cellular locations and chromatin interactions are in dynamic opposition. We investigated the mechanisms of cell cycle inhibition by PHB and how this is modulated by AR in prostate cancer. Using a prostate cancer cell line overexpressing PHB, we analysed the gene expression changes associated with PHB-mediated cell cycle arrest. Over 1000 gene expression changes were found to be significant and gene ontology analysis confirmed PHB-mediated repression of genes essential for DNA replication and synthesis, for example, MCMs and TK1, via an E2F1 regulated pathway-agreeing with its G1/S cell cycle arrest activity. PHB is known to inhibit E2F1-mediated transcription, and the PHB:E2F1 interaction was seen in LNCaP nuclear extracts, which was then reduced by androgen treatment. Upon two-dimensional western blot analysis, the PHB protein itself showed androgen-mediated charge differentiation (only in AR-positive cells), indicating a potential dephosphorylation event. Kinexus phosphoprotein array analysis indicated that Src kinase was the main interacting intracellular signalling hub in androgen-treated LNCaP cells, and that Src inhibition could reduce this AR-mediated charge differentiation. PHB charge change may be associated with rapid dissociation from chromatin and E2F1, allowing the cell cycle to proceed. The AR and androgens may deactivate the repressive functions of PHB upon E2F1 leading to cell cycle progression, and indicates a role for AR in DNA replication licensing

Digital soil mapping for soil class prediction in a dry forest of Minas Gerais, Brazil.

Investment on soil survey has become scarce over the past decades. Digital Soil Mapping (DSM) techniques emerged as an economic alternative to produce soil maps. We applied a classification tree algorithm to predict soil suborders in a tropical dry forest area with 102 km2 in the north of Minas Gerais state, Brazil. We tested environmental covariates with different spatial resolutions as predictors, and used 361 observations to train the model and 64 independent observations to validate the map. Prediction models included three decision trees and one logistic regression model. The results showed that freely available environmental covariates with coarser spatial resolution can produce as good or better suborder predictions than more expensive covariates with finer resolution

Autoantibody detection for diagnosis in direct immunofluorescence negative mucous membrane pemphigoid: ocular and other sites compared

Objective: To assess whether a panel of serum pemphigoid autoantibody tests could be used to confirm an immunopathological diagnosis of mucous membrane pemphigoid (MMP) in direct immunofluorescent negative (DIF-) MMP patients. / Design: Prospective cross-sectional study. / Subjects and controls: 76 patients with MMP involving ocular and non-ocular sites with 45 matched controls. / Tests: Enzyme linked immunosorbent assays (ELISA) for BP180 and BP230 (MBL International®), IgA and IgG indirect immunofluorescence on human salt-split skin (IIF SSS) and the keratinocyte footprint assay for anti-laminin 332 antibodies. / Main outcome measures: Sensitivity and specificity of autoantibody detection; significant differences for individual tests and test combinations for MMP involving different sites. / Results: All DIF- Cases (24/76, 31.8%) had either ocular only disease or ocular involvement in multi-site disease. Serum pemphigoid autoantibodies were detected in 29/76 (38.2%) of all MMP patients compared to 3/45 (6.7%) of controls. Autoantibody reactivity detected by any one or more of the tests was present in 6/24 (25%) DIF- cases compared to 22/49 (44.9%) in DIF positive (DIF+). Compared to controls ocular only MMP serum reactivity was not significantly different for any test or test combination whereas DIF- multisite ocular MMP differed for one ELISA and 3/7 test combinations. By contrast, for DIF+ non ocular MMP all the individual tests, apart from IgA IIF, and all test combinations were significantly different compared to controls. For the whole MMP cohort the sensitivity of all tests was low having a maximum of 21.05% for BP180 reactivity, increasing to 38.16% for an optimal test combination. Disease activity was strongly associated with positive serology findings. / Conclusions: Pemphigoid serum autoantibody tests did not provide alternative immunopathological evidence of MMP in ocular only MMP patients but had limited value in DIF- multisite ocular MMP. The requirement for immunopathological confirmation of MMP by autoantibody detection is inappropriate for DIF- ocular only MMP resulting in missed diagnoses, delayed therapy and poor outcomes. Alternative diagnostic criteria for MMP with ocular involvement are required, to exclude the other causes of scarring conjunctivitis, until more sensitive and specific immunopathology tests become available

Cardiovascular risk in patients without known cardiovascular disease

Understanding the risks of atherosclerotic cardiovascular disease (CVD) allows for better patient education and management. Multiple risk models have been validated in large patient populations and provide insights into the risks associated with CVD. When assessing such risks, we suggest using a model that predicts myocardial infarction, cardiovascular death, and/or cerebrovascular events. In this review, we analyze several risk models and stratify the risks associated with CVD. We suggest that appropriate profiling of patients at-risk of CVD will lead to better physician recognition and treatment of modifiable risk factors, appropriate application of ATP III treatment for hyperlipidemia, and achieving optimal blood pressure control.Understanding the risks of atherosclerotic cardiovascular disease (CVD) allows for better patient education and management. Multiple risk models have been validated in large patient populations and provide insights into the risks associated with CVD. When assessing such risks, we suggest using a model that predicts myocardial infarction, cardiovascular death, and/or cerebrovascular events. In this review, we analyze several risk models and stratify the risks associated with CVD. We suggest that appropriate profiling of patients at-risk of CVD will lead to better physician recognition and treatment of modifiable risk factors, appropriate application of ATP III treatment for hyperlipidemia, and achieving optimal blood pressure control

Treinamento em mapeamento digital de solos: carbono no Rio de Janeiro, Brasil.

No período de 24 a 28 de setembro de 2012 foi realizado na Embrapa Solos, Rio de Janeiro, RJ, o Curso de Capacitación en Cartografía Digital de Suelos, que contou com a presença de 17 pedólogos de 17 países da América Latina e Caribe. O objetivo do curso foi capacitar os pedólogos em mapeamento digital de solos utilizando os softwares livres SAGA, R e RStudio. No curso realizou-se, como estudo de caso, o mapeamento do carbono orgânico do solo na camada 0-10 cm no município de Campos dos Goytacazes, RJ, Brasil. Apresentamos as etapas de treinamento realizadas durante o curso, incluindo a preparação de dados de solos e covariáveis ambientais, análise exploratória de dados, modelagem espacial, produção de mapas e validação dos resultados obtidos. A combinação dos softwares livres SAGA, R e RStudio mostrou-se bastante flexível para a realização do curso e mapeamento digital de carbono orgânico do solo, sendo recomendada para outros cursos e projetos de mapeamento digital de solos. A estrutura do curso mostrou-se adequada também para implementação através de ensino à distância (resultados apresentados em outro trabalho nestes anais). Para êxito de cursos e projetos similares, salientamos a importância da experiência prévia dos participantes com conceitos e técnicas de pedologia, estatística, geoprocessamento e linguagem de programação, bem como da existência de um banco de dados de solos organizado e disponível