An in vitro co-culture model of esophageal cells identifies ascorbic acid as a modulator of cell competition

<p>Abstract</p> <p>Background</p> <p>The evolutionary dynamics between interacting heterogeneous cell types are fundamental properties of neoplastic progression but can be difficult to measure and quantify. Cancers are heterogeneous mixtures of mutant clones but the direct effect of interactions between these clones is rarely documented. The implicit goal of most preventive interventions is to bias competition in favor of normal cells over neoplastic cells. However, this is rarely explicitly tested. Here we have developed a cell culture competition model to allow for direct observation of the effect of chemopreventive or therapeutic agents on two interacting cell types. We have examined competition between normal and Barrett's esophagus cell lines, in the hopes of identifying a system that could screen for potential chemopreventive agents.</p> <p>Methods</p> <p>One fluorescently-labeled normal squamous esophageal cell line (EPC2-hTERT) was grown in competition with one of four Barrett's esophagus cell lines (CP-A, CP-B, CP-C, CP-D) under varying conditions and the outcome of competition measured over 14 days by flow cytometry.</p> <p>Results</p> <p>We demonstrate that ascorbic acid (vitamin C) can help squamous cells outcompete Barrett's cells in this system. We are also able to show that ascorbic acid's boost to the relative fitness of squamous cells was increased in most cases by mimicking the pH conditions of gastrointestinal reflux in the lower esophagus.</p> <p>Conclusions</p> <p>This model is able to integrate differential fitness effects on various cell types, allowing us to simultaneously capture effects on interacting cell types without having to perform separate experiments. This model system may be used to screen for new classes of cancer prevention agents designed to modulate the competition between normal and neoplastic cells.</p

Paraphyly of Cinclodes fuscus (Aves: Passeriformes: Furnariidae): Implications for taxonomy and biogeography

The Andes are a hotspot of global avian diversity, but studies on the historical diversification of Andean birds remain relatively scarce. Evolutionary studies on avian lineages with Andean-Patagonian distributions have focused on reconstructing species-level phylogenies, whereas no detailed phylogeographic studies on widespread species have been conducted. Here, we describe phylogeographic patterns in the Bar-winged Cinclodes (Cinclodes fuscus), a widespread and common species of ovenbird (Furnariidae) that breeds from Tierra del Fuego to the northern Andes. Traditionally, C. fuscus has been considered a single species composed of nine subspecies, but its long and narrow range suggests the possibility of considerable genetic variation among populations. Sequences of two mitochondrial genes revealed three discrete and geographically coherent groups of C. fuscus, occupying the southern, central, and northern Andes. Surprisingly, phylogenetic analyses indicated that these groups were more closely related to other species of Cinclodes than to each other. Relationships of the southern and northern C. fuscus clades to other species of Cinclodes were straightforward; in combination with available information on plumage, behavioral, and vocal variation, this suggests that each should be recognized as a distinct biological species. The central Andean group was paraphyletic with respect to C. oustaleti, and relationships among these taxa and C. olrogi were poorly resolved. We suggest that the central Andean C. fuscus should also be considered a different species, pending new information to clarify species limits in this group. These new phylogenetic data, along with recently developed methods, allowed us to review the biogeography of the genus, confirming southern South America and the central Andes as important areas for the diversification of these birds.Fil: Sanín, Camilo. National Museum of Natural History; Estados Unidos. Universidad de los Andes; ColombiaFil: Cadena, Carlos Daniel. Universidad de los Andes; ColombiaFil: Maley, James M.. State University of Louisiana; Estados UnidosFil: Lijtmaer, Dario Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Tubaro, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Chesser, R. Terry. National Museum of Natural History; Estados Unido

Fibre Diffraction of Hair can Provide a Screening Test for Alzheimer\u27s Disease: a Human and Animal Model Study

Studies of molecular changes in hair as possible biomarkers for specific cancers revealed an additional molecular change in the diffraction patterns of some persons aged over 75. This change was found to correlate with the presence of Alzheimer\u27s disease. To confirm this correlation and its relation to the presence of a human APP mutation known to definitely cause AD, hairs were examined from AD patients, pregnant women known to have an increase in in plasma beta amyloid and transgenic mice carrying a mutated human APP gene

Fibre diffraction of hair can provide a screening test for Alzheimers disease: a human and animal model study

Background: Studies of molecular changes in hair as possible biomarkers for specific cancers revealed an additional molecular change in the diffraction patterns of some persons aged over 75. This change was found to correlate with the presence of Alzheimer's disease (AD). To confirm this correlation and its relation to the presence of a human APP mutation, known to definitely cause AD, hairs were examined from AD patients, pregnant women known to have an increase in plasma beta amyloid and transgenic mice carrying a mutated human APP gene. Material/Methods: Patients were clinically examined by an experienced physician who recorded the patient's history and completed physical and neurological examinations. Hair samples were held taut and centred in the beam. The diffraction patterns were collected on Fuji-Bas Imaging plates and analysed using standard programs. Results: A fan-shaped set of spot-like reflections was observed in the equatorial diffraction patterns from the hair of all AD patients and all third trimester pregnant women. Combined fibre diffraction of hair and histopathologic examination of brains from transgenic mice carrying a mutated human APP gene confirmed that these changes are related to the mutated human APP genes and the formation of beta amyloid plaques. Conclusions: Here we show results that fibre diffraction analysis would provide a non-invasive, accurate bio-marker for Alzheimer's disease. Our results are consistent with the hypothesis that this marker is related to the presence of mutated human APP genes and indicate that the structural change precedes the significant development of plaques

Why do citizens want to keep refugees out? Threats, fairness and hostile norms in the treatment of asylum seekers

A social identity framework was employed to understand why people support the exclusionary treatment of refugee claimants ('asylum seekers') in Australia. Over and above individual difference affects of social dominance orientation and individuals' instrumental threat perceptions, insecure intergroup relations between citizens and asylum seekers were proposed to motivate exclusionary attitudes and behaviour In addition, perceived procedural and distributive fairness were proposed to mediate the effects of social identity predictors on intergroup competitiveness, serving to legitimise citizens' exclusionary behaviours. Support for these propositions was obtained in a longitudinal study, of 'Australians' social attitudes and behaviour. Small and inconsistent individual-level effects were noted. In contrast, after controlling,for these variables, hostile Australian norms, perceived legitimacy of citizen status, and threatening socio-structural relations were strongly and consistently linked to intentions to support the harsh Treatment of asylum seekers, and exclusionary attitudes and action at Time 2. Moreover, perceived procedural and distributive justice significantly mediated these relationships. The roles of fairness and intergroup socio-structural perceptions in social attitudes and actions are discussed