116 research outputs found

    The Effects of Overexpression of Histamine Releasing Factor (HRF) in a Transgenic Mouse Model

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    Asthma is a disease that affects all ages, races and ethnic groups. Its incidence is increasing both in Westernized countries and underdeveloped countries. It involves inflammation, genetics and environment and therefore, proteins that exacerbate the asthmatic, allergic phenotype are important. Our laboratory purified and cloned a histamine releasing factor (HRF) that was a complete stimulus for histamine and IL-4 secretion from a subpopulation of allergic donors' basophils. Throughout the course of studying HRF, it was uncovered that HRF enhances or primes histamine release and IL-13 production from all anti-IgE antibody stimulated basophils. In order to further delineate the biology of HRF, we generated a mouse model.We constructed an inducible transgenic mouse model with HRF targeted to lung epithelial cells, via the Clara cells. In antigen naïve mice, overproduction of HRF yielded increases in BAL macrophages and statistical increases in mRNA levels for MCP-1 in the HRF transgenic mice compared to littermate controls. In addition to demonstrating intracellular HRF in the lung epithelial cells, we have also been able to document HRF's presence extracellularly in the BAL fluid of these transgenic mice. Furthermore, in the OVA challenged model, we show that HRF exacerbates the allergic, asthmatic responses. We found statistically significant increases in serum and BAL IgE, IL-4 protein and eosinophils in transgenic mice compared to controls.This mouse model demonstrates that HRF expression enhances allergic, asthmatic inflammation and can now be used as a tool to further dissect the biology of HRF

    New tumour entities in the 4th edition of the World Health Organization Classification of Head and Neck tumours: odontogenic and maxillofacial bone tumours.

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    The latest (4th) edition of the World Health Organization Classification of Head and Neck tumours has recently been published with a number of significant changes across all tumour sites. In particular, there has been a major attempt to simplify classifications and to use defining criteria which can be used globally in all situations, avoiding wherever possible the use of complex molecular techniques which may not be affordable or widely available. This review summarises the changes in Chapter 8: Odontogenic and maxillofacial bone lesions. The most significant change is the re-introduction of the classification of the odontogenic cysts, restoring this books status as the only text which classifies and defines the full range of lesions of the odontogenic tissues. The consensus group considered carefully the terminology of lesions and were concerned to ensure that the names used properly reflected the best evidence regarding the true nature of specific entities. For this reason, this new edition restores the odontogenic keratocyst and calcifying odontogenic cyst to the classification of odontogenic cysts and rejects the previous terminology (keratocystic odontogenic tumour and calcifying cystic odontogenic tumour) which were intended to suggest that they are true neoplasms. New entities which have been introduced include the sclerosing odontogenic carcinoma and primordial odontogenic tumour. In addition, some previously poorly defined lesions have been removed, including the ameloblastic fibrodentinoma, ameloblastic fibro-odontoma, which are probably developing odontomas, and the odontoameloblastoma, which is not regarded as an entity. Finally, the terminology "cemento" has been restored to cemento-ossifying fibroma and cemento-osseous dysplasias, to properly reflect that they are of odontogenic origin and are found in the tooth-bearing areas of the jaws

    Tolerance to copper and to salinity in Daphnia longispina: implications within a climate change scenario

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    Considering IPPC climate change scenarios, it is pertinent to predict situations where coastal ecosystems already impacted with chemical contamination became exposed to an additional stressor under a future scenario of seawater intrusion. Accordingly, the present study aimed at evaluating if a negative association between tolerance to a metal and to saltwater exists among genotypes of a freshwater organism. For this, five clonal lineages of the cladoceran Daphnia longispina O.F. Müller, exhibiting a differential tolerance to lethal levels of copper, were selected. Each clonal lineage was exposed to lethal and sublethal concentrations of sodium chloride (assumed as a protective surrogate to evaluate the toxicity of increased salinity to freshwater organisms). Mortality, time to release the first brood and total number of neonates per female were monitored and the somatic growth rate and intrinsic rate of natural increase were computed for each clonal lineage. Data here obtained were compared with their lethal responses to copper and significant negative correlations were found. These results suggest that genetically eroded populations of D. longispina, due to copper or salinity, may be particularly susceptible to a later exposure to the other contaminant supporting the multiple stressors differential tolerance.This work has been developed under the scope of the Portuguese Science Foundation (FCT, Portugal) through FSE and POPH funds (Programa Ciencia 2007), and FEDER through COMPETE-programa Operacional Factores de Competitividade (research project FCOMP-01-0124-FEDER-014016; PTDC/AAC-CLI/ 111706/2009). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.publishe

    Genome-wide analysis of allelic imbalance in prostate cancer using the Affymetrix 50K SNP mapping array

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    Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous cancer in male subjects in Western countries. The widespread use of prostate-specific antigen (PSA) has increased the detection of this cancer form in earlier stages. Moreover, it has increased the need for new diagnostic procedures to be developed for patient stratification based on risk of progression. We analysed laser-microdissected prostate tumour tissue from 43 patients with histologically verified PCa, using the new high-resolution Affymetrix Mapping 50K single-nucleotide polymorphism array. The results showed six major loss of heterozygosity regions at chromosomes 6q14–16, 8p23–11, 10q23, 13q13–21 and 16q21–24 and a novel region at chromosome 21q22.2, all of which reveal concomitant copy number loss. Tumour development was further characterised by numerous novel genomic regions almost exclusively showing copy number loss. However, tumour progression towards a metastatic stage, as well as poor differentiation, was identified by specific patterns of copy number gains of genomic regions located at chromosomes 8q, 1q, 3q and 7q. Androgen ablation therapy was further characterised by copy gain at chromosomes 2p and 10q. In conclusion, patterns of allelic imbalance were discovered in PCa, consisting allelic loss as an early event in tumour development, and distinct patterns of allelic amplification related to tumour progression and poor differentiation

    Applications of Genetic Programming to Finance and Economics: Past, Present, Future

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    While the origins of Genetic Programming (GP) stretch back over fifty years, the field of GP was invigorated by John Koza’s popularisation of the methodology in the 1990s. A particular feature of the GP literature since then has been a strong interest in the application of GP to real-world problem domains. One application domain which has attracted significant attention is that of finance and economics, with several hundred papers from this subfield being listed in the Genetic Programming Bibliography. In this article we outline why finance and economics has been a popular application area for GP and briefly indicate the wide span of this work. However, despite this research effort there is relatively scant evidence of the usage of GP by the mainstream finance community in academia or industry. We speculate why this may be the case, describe what is needed to make this research more relevant from a finance perspective, and suggest some future directions for the application of GP in finance and economics

    Mysid crustaceans as standard models for the screening and testing of endocrine-disrupting chemicals

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    Author Posting. © Springer, 2007. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Ecotoxicology 16 (2007): 205-219, doi:10.1007/s10646-006-0122-0.Investigative efforts into the potential endocrine-disrupting effects of chemicals have mainly concentrated on vertebrates, with significantly less attention paid to understanding potential endocrine disruption in the invertebrates. Given that invertebrates account for at least 95% of all known animal species and are critical to ecosystem structure and function, it remains essential to close this gap in knowledge and research. The lack of progress regarding endocrine disruption in invertebrates is still largely due to: (1) our ignorance of mode-of-action, physiological control, and hormone structure and function in invertebrates; (2) lack of a standardized invertebrate assay; (3) the irrelevance to most invertebrates of the proposed activity-based biological indicators for endocrine disruptor exposure (androgen, estrogen and thyroid); (4) limited field studies. Past and ongoing research efforts using the standard invertebrate toxicity test model, the mysid shrimp, have aimed at addressing some of these issues. The present review serves as an update to a previous publication on the use of mysid shrimp for the evaluation of endocrine disruptors (Verslycke et al., 2004a). It summarizes recent investigative efforts that have significantly advanced our understanding of invertebrate-specific endocrine toxicity, population modeling, field studies, and transgeneration standard test development using the mysid model.Supported by a Fellowship of the Belgian American Educational Foundation

    The benefit of directly comparing autism and schizophrenia for revealing mechanisms of social cognitive impairment

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    Autism and schizophrenia share a history of diagnostic conflation that was not definitively resolved until the publication of the DSM-III in 1980. Though now recognized as heterogeneous disorders with distinct developmental trajectories and dissociative features, much of the early nosological confusion stemmed from apparent overlap in certain areas of social dysfunction. In more recent years, separate but substantial literatures have accumulated for autism and schizophrenia demonstrating that abnormalities in social cognition directly contribute to the characteristic social deficits of both disorders. The current paper argues that direct comparison of social cognitive impairment can highlight shared and divergent mechanisms underlying pathways to social dysfunction, a process that can provide significant clinical benefit by informing the development of tailored treatment efforts. Thus, while the history of diagnostic conflation between autism and schizophrenia may have originated in similarities in social dysfunction, the goal of direct comparisons is not to conflate them once again but rather to reveal distinctions that illuminate disorder-specific mechanisms and pathways that contribute to social cognitive impairment

    The supernatural characters and powers of sacred trees in the Holy Land

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    This article surveys the beliefs concerning the supernatural characteristics and powers of sacred trees in Israel; it is based on a field study as well as a survey of the literature and includes 118 interviews with Muslims and Druze. Both the Muslims and Druze in this study attribute supernatural dimensions to sacred trees which are directly related to ancient, deep-rooted pagan traditions. The Muslims attribute similar divine powers to sacred trees as they do to the graves of their saints; the graves and the trees are both considered to be the abode of the soul of a saint which is the source of their miraculous powers. Any violation of a sacred tree would be strictly punished while leaving the opportunity for atonement and forgiveness. The Druze, who believe in the transmigration of souls, have similar traditions concerning sacred trees but with a different religious background. In polytheistic religions the sacred grove/forest is a centre of the community's official worship; any violation of the trees is regarded as a threat to the well being of the community. Punishments may thus be collective. In the monotheistic world (including Christianity, Islam and Druze) the pagan worship of trees was converted into the worship/adoration of saints/prophets; it is not a part of the official religion but rather a personal act and the punishments are exerted only on the violating individual
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