20 research outputs found

    The postcolonial framework and reinterpretation of Great expectations and Jane Eyre in Lloyd Jones' Mister Pip and Jean Rhys' Wide Sargasso Sea

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    In a postcolonial literary environment, intertextuality appears to be the key element, since a postcolonial reading is also a work whose references are a combination of intertwined societies and cultures. Jean Rhys and Lloyd Jones focused their writings on 'classics': Jean Rhys takes Charlotte Brontë's Jane Eyre as a reference for Wide Sargasso Sea, while Lloyd Jones' Mister Pip focuses on Charles Dickens' Great Expectations. My aim is to discuss similarities and differences in both settings, covering the theme of identity, while also analyzing the critique against postcolonial for plagiarism. I argue that the postcolonial rewriter does not lack imagination nor talent, but uses the 'classic' as a tool to approach the matter of imperialistic imposition on the colonies.En un entorn literari postcolonial, la intertextualitat sembla ser clau, ja que una lectura postcolonial també es pot analitzar com una lectura d'un conjunt de referències de cultures i societats entrellaçades. Jean Rhys i Lloyd Jones van centrar els seus escrits sobre dos "clàssics": Jean Rhys es basa en Jane Eyre de Charlotte Brontë com a referència per a Wide Sargasso Sea, mentre que Mister Pip de Lloyd Jones se centra en Great Expectations de Charles Dickens. El meu objectiu és discutir les similituds i diferències en els dos àmbits, centrant-me en el tema de la identitat, alhora fent un anàlisi de la crítica a la literatura postcolonial per plagi. Sostinc que els autors postcolonial no manquen imaginació ni talent, si no que utilitzen el "clàssic" com una eina per abordar l'assumpte de la imposició imperialista de les colònies

    Increasing efficiency and reducing bias in the sampling of seed-dispersal interactions based on mist-netted birds

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    Efficient and unbiased sampling of ecological interactions is essential to our understanding of the functions they mediate. Seed dispersal by frugivorous birds is a key mutualism for plant regeneration and community dynamics. Mist-netting is one of the most widely used methods to sample avian seed dispersal through the identification of seeds in droppings of captured birds kept inside cloth bags. However, birds may drop seeds on the ground before being extracted from the net, leading to a fraction of missing information due to ineffective sampling. Worryingly, this fraction could be unevenly distributed across bird and plant species, leading to sampling biases. Here, we assess the effectiveness of using a 1-m wide mesh below mist nets to sample seeds dropped by entangled birds. We used data from birds mist-netted during one-year-round. We sampled nearly 50% of interaction events and 75% of dispersed seeds on the mesh band below the mist nets (i.e. lost information without this optimization). The proportion of seeds sampled on the mesh bands was not evenly distributed among bird species but strongly related to bird size, ranging from 57–63% in warblers to 84–94% in thrushes. Moreover, the proportion of seeds sampled on the mesh was negatively related to seed size, although this relationship was weaker. We also evaluated accumulation curves of species and pairwise interactions with increasing sampling effort, both with and without using the mesh bands. The number of seed species sampled increased by 21% when using the mesh bands and the number of pairwise interactions by 36%. Our findings provide strong evidence on how inefficient and biased traditional mist-netting can be for sampling community-wide seed–dispersal interactions. We thus urge the use of mesh bands in future studies to increase sampling effectiveness and avoid biases, which will ultimately improve our understanding of the seed dispersal function

    Microtubule stabilization protects cognitive function and slows down the course of Alzheimer's like pathology in an amyloidogenic mouse model

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    Cognitive decline in Alzheimer's disease (AD) is highly related to synaptic dysfunction and neuronal loss. In AD, the hyperphosphorylation of tau compromises axonal transport and leads to the generation of dystrophic neurites, contributing to synaptic impairment. In addition to phospho-tau, AD brains accumulate amyloid-beta. This study evaluated the effect of the brain-penetrant microtubule-stabilizing agent, Epothilone D (EpoD) in the progression of the disease in a double transgenic mouse model of amyloidosis. Young APP/PS1 mice were weekly treated with intraperitoneal injections of EpoD (2 mg/kg) or vehicle solution for 3 months. Memory performance was tested using object-recognition tasks, Y-maze and Morris water maze. EpoD-treated mice improved their performance of cognitive tests, while hippocampal phospho-tau and Aβ levels, especially soluble oligomers, decreased significantly. β/γ-secretase activities were not affected by EpoD in vitro. A significant amelioration of synaptic/neuritic pathology was found. Remarkably, EpoD exerted a neuroprotective effect on SOM-interneurons, a highly AD-vulnerable GABAergic subpopulation. In conclusion, EpoD improved microtubule dynamics and axonal transport in an AD-like context, reducing tau and Abeta accumulation, and promoting neuronal and cognitive protection. These results underline the crosstalk between cytoskeleton pathology and proteinopathy. Therefore, microtubule-stabilizing drugs could be candidates for slowing AD progression at both tau and Aβ pathologies.Supported by PI18/01557 (to AG) and PI18/01556 (to JV) grants from ISCiii of Spain, co-financed by FEDER funds from European Union, CIBERNED collaborative grant (to AG and JV), and by PPIT.UMA.B1.2017/26 grant (to RSV). Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

    c-Src functionality controls self-renewal and glucose metabolism in MCF7 breast cancer stem cells

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    Deregulation of Src kinases is associated with cancer. We previously showed that SrcDN conditional expression in MCF7 cells reduces tumorigenesis and causes tumor regression in mice. However, it remained unclear whether SrcDN affected breast cancer stem cell functionality or it reduced tumor mass. Here, we address this question by isolating an enriched population of Breast Cancer Stem Cells (BCSCs) from MCF7 cells with inducible expression of SrcDN. Induction of SrcDN inhibited self-renewal, and stem-cell marker expression (Nanog, Oct3-4, ALDH1, CD44). Quantitative proteomic analyses of mammospheres from MCF7-Tet-On-SrcDN cells (data are available via ProteomeXchange with identifier PXD017789, project DOI: 10.6019/PXD017789) and subsequent GSEA showed that SrcDN expression inhibited glycolysis. Indeed, induction of SrcDN inhibited expression and activity of hexokinase, pyruvate kinase and lactate dehydrogenase, resulting in diminished glucose consumption and lactate production, which restricted Warburg effect. Thus, c-Src functionality is important for breast cancer stem cell maintenance and renewal, and stem cell transcription factor expression, effects linked to glucose metabolism reduction.This work has been supported by grand SAF2016–75991-R (MINECO, AEI/FEDER, UE) to Jorge Martín-Pérez and ISCIII [grand PI 16/00789] to Miguel Ángel Fernández-Moreno. Víctor Mayoral-Varo was supported by the grand SAF2016–75991-R (MINECO, AEI/FEDER, UE). We acknowledge support for publication fee by the CSIC Open Access Publication Support Initiative through its Unit for Information Resources for Research (URICI)

    Transgenic Mouse Models of Alzheimer’s Disease: An Integrative Analysis

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    Alzheimer’s disease (AD) constitutes the most prominent form of dementia among elderly individuals worldwide. Disease modeling using murine transgenic mice was first initiated thanks to the discovery of heritable mutations in amyloid precursor protein (APP) and presenilins (PS) genes. However, due to the repeated failure of translational applications from animal models to human patients, along with the recent advances in genetic susceptibility and our current understanding on disease biology, these models have evolved over time in an attempt to better reproduce the complexity of this devastating disease and improve their applicability. In this review, we provide a comprehensive overview about the major pathological elements of human AD (plaques, tauopathy, synaptic damage, neuronal death, neuroinflammation and glial dysfunction), discussing the knowledge that available mouse models have provided about the mechanisms underlying human disease. Moreover, we highlight the pros and cons of current models, and the revolution offered by the concomitant use of transgenic mice and omics technologies that may lead to a more rapid improvement of the present modeling batterThis research was funded by INSTITUTO DE SALUD CARLOS III (ISCiii) of Spain, cofinanced by FEDER funds from European Union, through grants PI21/00915 (to AG) and PI21/00914 (to JV); by JUNTA DE ANDALUCIA CONSEJERÍA DE ECONOMÍA Y CONOCIMIENTO through grants UMA18-FEDERJA-211 (to AG), UMA20-FEDERJA-104 (to IMG), P18-RT-2233 (to AG) and US-1262734 (to JV) co-financed by Programa Operativo FEDER 2014–2020 and CONSEJERIA DE SALUD grant PI-0276-2018 (to JAGL); by SPANISH MINISTER OF SCIENCE AND INNOVATION grant PID2019-108911RA-100 (to DBV), BEATRIZ GALINDO PROGRAM BAGAL18/00052 (to DBV), Alzheimer Association AARG-22-928219 (to DBV), grant PID2019-107090RA-100 (to IMG) and RAMON Y CAJAL PROGRAM RYC-2017-21879 (to IMG); and by MALAGA UNIVERSITY grant B1-2019_07 (to ESM), grant B1-2020_04 (to JAGL), grant B1-2019_06 (to IMG) and NASARD grant 27565 2018 (to IMG). M.M.-O. held a predoctoral contract from Malaga University, J.J.F.-V. held a postdoctoral contract from Malaga University, and E.S.-M. a postdoctoral contract (DOC_00251) from Junta de Andalucia. Partial funding for open access charge: Universidad de Málaga

    A model based on the quantification of complement C4c, CYFRA 21-1 and CRP exhibits high specificity for the early diagnosis of lung cancer

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    Lung cancer screening detects early-stage cancers, but also a large number of benign nodules. Molecular markers can help in the lung cancer screening process by refining inclusion criteria or guiding the management of indeterminate pulmonary nodules. In this study, we developed a diagnostic model based on the quantification in plasma of complement-derived fragment C4c, cytokeratin fragment 21-1 (CYFRA 21-1) and C-reactive protein (CRP). The model was first validated in two independent cohorts, and showed a good diagnostic performance across a range of lung tumor types, emphasizing its high specificity and positive predictive value. We next tested its utility in two clinically relevant contexts: assessment of lung cancer risk and nodule malignancy. The scores derived from the model were associated with a significantly higher risk of having lung cancer in asymptomatic individuals enrolled in a computed tomography (CT)-screening program (OR = 1.89; 95% CI = 1.20–2.97). Our model also served to discriminate between benign and malignant pulmonary nodules (AUC: 0.86; 95% CI = 0.80–0.92) with very good specificity (92%). Moreover, the model performed better in combination with clinical factors, and may be used to reclassify patients with intermediate-risk indeterminate pulmonary nodules into patients who require a more aggressive work-up. In conclusion, we propose a new diagnostic biomarker panel that may dictate which incidental or screening-detected pulmonary nodules require a more active work-up

    Animal and Cellular Models of Alzheimer’s Disease: Progress, Promise, and Future Approaches

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    Alzheimer’s disease (AD) is an incurable neurodegenerative disease affecting over 45 million people worldwide. Transgenic mouse models have made remarkable contributions toward clarifying the pathophysiological mechanisms behind the clinical manifestations of AD. However, the limited ability of these in vivo models to accurately replicate the biology of the human disease have precluded the translation of promising preclinical therapies to the clinic. In this review, we highlight several major pathogenic mechanisms of AD that were discovered using transgenic mouse models. Moreover, we discuss the shortcomings of current animal models and the need to develop reliable models for the sporadic form of the disease, which accounts for the majority of AD cases, as well as human cellular models to improve success in translating results into human treatments.Peer reviewe

    A model of energy deposition of energetic electrons and EUV emission in the Jovian and Saturnian atmospheres and implications

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    A model of the interaction between incident electron precipitation and H2 atmospheres is described. The local degraded primary and secondary electron energy distributions are calculated by using the continuous slowing down approximation. The altitude distribution of the ionization rate and various H and EUV H2 emissions are calculated for four different incident electron spectra. A total EUV H2 emission efficiency of 10.6 kR/incident erg/sq cm per sec is obtained for a pure H2 atmosphere. Comparison with the Voyager Jupiter observations indicates that an incident energy flux of about 8 ergs/sq cm per sec was present at the time of the encounter if the emission is located in an H2-dominated region. The local thermospheric heating rate was about 4 ergs/sq cm per sec for Jupiter and of the order of 0.1 erg/sq cm per sec for Saturn. A globally averaged atomic hydrogen production rate of about 1 x 10 to the 10th atoms/sq cm per sec is induced by the Jovian auroral electron precipitation, largely exceeding the solar EUV dissociation rate
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