87 research outputs found

    The PANTHER database of protein families, subfamilies, functions and pathways

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    PANTHER is a large collection of protein families that have been subdivided into functionally related subfamilies, using human expertise. These subfamilies model the divergence of specific functions within protein families, allowing more accurate association with function (ontology terms and pathways), as well as inference of amino acids important for functional specificity. Hidden Markov models (HMMs) are built for each family and subfamily for classifying additional protein sequences. The latest version, 5.0, contains 6683 protein families, divided into 31 705 subfamilies, covering ∼90% of mammalian protein-coding genes. PANTHER 5.0 includes a number of significant improvements over previous versions, most notably (i) representation of pathways (primarily signaling pathways) and association with subfamilies and individual protein sequences; (ii) an improved methodology for defining the PANTHER families and subfamilies, and for building the HMMs; (iii) resources for scoring sequences against PANTHER HMMs both over the web and locally; and (iv) a number of new web resources to facilitate analysis of large gene lists, including data generated from high-throughput expression experiments. Efforts are underway to add PANTHER to the InterPro suite of databases, and to make PANTHER consistent with the PIRSF database. PANTHER is now publicly available without restriction at http://panther.appliedbiosystems.com

    Derivation of therapeutic lung spheroid cells from minimally invasive transbronchial pulmonary biopsies

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    BACKGROUND: Resident stem and progenitor cells have been identified in the lung over the last decade, but isolation and culture of these cells remains a challenge. Thus, although these lung stem and progenitor cells provide an ideal source for stem-cell based therapy, mesenchymal stem cells (MSCs) remain the most popular cell therapy product for the treatment of lung diseases. Surgical lung biopsies can be the tissue source but such procedures carry a high risk of mortality. METHODS: In this study we demonstrate that therapeutic lung cells, termed "lung spheroid cells" (LSCs) can be generated from minimally invasive transbronchial lung biopsies using a three-dimensional culture technique. The cells were then characterized by flow cytometry and immunohistochemistry. Angiogenic potential was tested by in-vitro HUVEC tube formation assay. In-vivo bio- distribution of LSCs was examined in athymic nude mice after intravenous delivery. RESULTS: From one lung biopsy, we are able to derive >50 million LSC cells at Passage 2. These cells were characterized by flow cytometry and immunohistochemistry and were shown to represent a mixture of lung stem cells and supporting cells. When introduced systemically into nude mice, LSCs were retained primarily in the lungs for up to 21 days. CONCLUSION: Here, for the first time, we demonstrated that direct culture and expansion of human lung progenitor cells from pulmonary tissues, acquired through a minimally invasive biopsy, is possible and straightforward with a three-dimensional culture technique. These cells could be utilized in long-term expansion of lung progenitor cells and as part of the development of cell-based therapies for the treatment of lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF)

    On Online Collaboration and Construction of Shared Knowledge: Assessing Mediation Capability in Computer Supported Argument Visualization Tools

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    Collaborative Computer-Supported Argument Visualization (CCSAV) has often been proposed as an alternative over more conventional, mainstream platforms for online discussion (e.g., online forums and wikis). CCSAV tools require users to contribute to the creation of a joint artifact (argument map) instead of contributing to a conversation. In this paper we assess empirically the effects of this fundamental design choice and show that the absence of conversational affordances and socially salient information in representation-centric tools is detrimental to the users' collaboration experience. We report empirical findings from a study in which subjects using different collaborative platforms (a forum, an argumentation platform, and a socially augmented argumentation tool) were asked to discuss and predict the price of a commodity. By comparing users' experience across several metrics we found evidence that the collaborative performance decreases gradually when we remove conversational interaction and other types of socially salient information. We interpret these findings through theories developed in conversational analysis (common ground theory) and communities of practice and discuss design implications. In particular, we propose balancing the trade-off between knowledge reification and participation in representation-centric tools with the provision of social feedback and functionalities supporting meaning negotiation

    Comprehensive survey of energetic electron events in Mercury\u27s magnetosphere with data from the MESSENGER Gamma-Ray and Neutron Spectrometer

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    Data from the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) Gamma-Ray and Neutron Spectrometer have been used to detect and characterize energetic electron (EE) events in Mercury\u27s magnetosphere. This instrument detects EE events indirectly via bremsstrahlung photons that are emitted when instrument and spacecraft materials stop electrons having energies of tens to hundreds of keV. From Neutron Spectrometer data taken between 18 March 2011 and 31 December 2013 we have identified 2711 EE events. EE event amplitudes versus energy are distributed as a power law and have a dynamic range of a factor of 400. The duration of the EE events ranges from tens of seconds to nearly 20 min. EE events may be classified as bursty (large variation with time over an event) or smooth (small variation). Almost all EE events are detected inside Mercury\u27s magnetosphere on closed field lines. The precise occurrence times of EE events are stochastic, but the events are located in well-defined regions with clear boundaries that persist in time and form what we call “quasi-permanent structures.” Bursty events occur closer to dawn and at higher latitudes than smooth events, which are seen near noon-to-dusk local times at lower latitudes. A subset of EE events shows strong periodicities that range from hundreds of seconds to tens of milliseconds. The few-minute periodicities are consistent with the Dungey cycle timescale for the magnetosphere and the occurrence of substorm events in Mercury\u27s magnetotail region. Shorter periods may be related to phenomena such as north-south bounce processes for the energetic electrons

    Adult Lung Spheroid Cells Contain Progenitor Cells and Mediate Regeneration in Rodents With Bleomycin-Induced Pulmonary Fibrosis: Lung Spheroid Cells for Lung Regeneration

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    Lung diseases are devastating conditions and ranked as one of the top five causes of mortality worldwide according to the World Health Organization. Stem cell therapy is a promising strategy for lung regeneration. Previous animal and clinical studies have focused on the use of mesenchymal stem cells (from other parts of the body) for lung regenerative therapies. We report a rapid and robust method to generate therapeutic resident lung progenitors from adult lung tissues. Outgrowth cells from healthy lung tissue explants are self-aggregated into three-dimensional lung spheroids in a suspension culture. Without antigenic sorting, the lung spheroids recapitulate the stem cell niche and contain a natural mixture of lung stem cells and supporting cells. In vitro, lung spheroid cells can be expanded to a large quantity and can form alveoli-like structures and acquire mature lung epithelial phenotypes. In severe combined immunodeficiency mice with bleomycin-induced pulmonary fibrosis, intravenous injection of human lung spheroid cells inhibited apoptosis, fibrosis, and infiltration but promoted angiogenesis. In a syngeneic rat model of pulmonary fibrosis, lung spheroid cells outperformed adipose-derived mesenchymal stem cells in reducing fibrotic thickening and infiltration. Previously, lung spheroid cells (the spheroid model) had only been used to study lung cancer cells. Our data suggest that lung spheroids and lung spheroid cells from healthy lung tissues are excellent sources of regenerative lung cells for therapeutic lung regeneration

    Genetic and behavioral determinants of hippocampal volume recovery during abstinence from alcohol

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    Alcohol-dependent individuals (ALC) have smaller hippocampi and poorer neurocognition than healthy controls. Results from studies on the association between alcohol consumption and hippocampal volume have been mixed, suggesting that comorbid or premorbid factors (i.e., those present prior to the initiation of alcohol dependence) determine hippocampal volume in ALC. We aimed to characterize the effects of select comorbid (i.e., cigarette smoking) and premorbid factors (brain-derived neurotrophic factor [BDNF] genotype [Val66Met rs6265]) on hippocampal volume in an ALC cohort followed longitudinally into extended abstinence. One hundred twenty-one adult ALC in treatment (76 smokers, 45 non-smokers) and 35 non-smoking light-drinking controls underwent quantitative magnetic resonance imaging, BDNF genotyping, and neurocognitive assessments. Representative subgroups were studied at 1 week, 1 month, and at an average of 7 months of abstinence. ALC had smaller hippocampi than healthy controls at all time points. Hippocampal volume at 1 month of abstinence correlated with lower visuospatial function. Smoking status did not influence hippocampal volume or hippocampal volume recovery during abstinence. However, only BDNF Val homozygotes tended to have hippocampal volume increases over 7 months of abstinence, and Val homozygotes had significantly larger hippocampi than Met carriers at 7 months of abstinence. These findings suggest that BDNF genotype, but not smoking status or measures of drinking severity, regulate functionally relevant hippocampal volume recovery in abstinent ALC. Future studies aimed at exploring genetic determinants of brain morphometry in ALC may need to evaluate individuals during extended abstinence after the acute environmental effects of chronic alcohol consumption have waned
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