623 research outputs found

    Matter effects in the D0-D0bar system

    Full text link
    We discuss the impact of matter effects in the D0-D0bar system. We show that such effects could, in principle, be measured, but that they cannot be used to probe the mass difference x_D or the lifetime difference y_D. This occurs because the mixing effects and the matter effects decouple at short times. We also comment briefly on the B systems.Comment: 6 pages, RevTe

    Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex

    Get PDF
    The PAF complex (PAFC) coordinates transcription elongation and mRNA processing and its CDC73/parafibromin subunit functions as a tumour suppressor. The NF2/Merlin tumour suppressor functions both at the cell cortex and nucleus and is a key mediator of contact inhibition but the molecular mechanisms remain unclear. In this study we have used affinity proteomics to identify novel Merlin interacting proteins and show that Merlin forms a complex with multiple proteins involved in RNA processing including the PAFC and the CHD1 chromatin remodeller. Tumour-derived inactivating mutations in both Merlin and the CDC73 PAFC subunit mutually disrupt their interaction and growth suppression by Merlin requires CDC73. Merlin interacts with the PAFC in a cell density-dependent manner and we identify a role for FAT cadherins in regulating the Merlin-PAFC interaction. Our results suggest that in addition to its function within the Hippo pathway, Merlin is part of a tumour suppressor network regulated by cell-cell adhesion which coordinates post-initiation steps of the transcription cycle of genes mediating contact inhibition

    The Power of Environmental Observatories for Advancing Multidisciplinary Research, Outreach, and Decision Support: The Case of the Minnesota River Basin

    Get PDF
    An edited version of this paper was published by AGU. Copyright 2019 American Geophysical Union.Observatory‐scale data collection efforts allow unprecedented opportunities for integrative, multidisciplinary investigations in large, complex watersheds, which can affect management decisions and policy. Through the National Science Foundation‐funded REACH (REsilience under Accelerated CHange) project, in collaboration with the Intensively Managed Landscapes‐Critical Zone Observatory, we have collected a series of multidisciplinary data sets throughout the Minnesota River Basin in south‐central Minnesota, USA, a 43,400‐km2 tributary to the Upper Mississippi River. Postglacial incision within the Minnesota River valley created an erosional landscape highly responsive to hydrologic change, allowing for transdisciplinary research into the complex cascade of environmental changes that occur due to hydrology and land use alterations from intensive agricultural management and climate change. Data sets collected include water chemistry and biogeochemical data, geochemical fingerprinting of major sediment sources, high‐resolution monitoring of river bluff erosion, and repeat channel cross‐sectional and bathymetry data following major floods. The data collection efforts led to development of a series of integrative reduced complexity models that provide deeper insight into how water, sediment, and nutrients route and transform through a large channel network and respond to change. These models represent the culmination of efforts to integrate interdisciplinary data sets and science to gain new insights into watershed‐scale processes in order to advance management and decision making. The purpose of this paper is to present a synthesis of the data sets and models, disseminate them to the community for further research, and identify mechanisms used to expand the temporal and spatial extent of short‐term observatory‐scale data collection efforts

    The Power of Environmental Observatories for Advancing Multidisciplinary Research, Outreach, and Decision Support: The Case of the Minnesota River Basin

    Get PDF
    Observatory‐scale data collection efforts allow unprecedented opportunities for integrative, multidisciplinary investigations in large, complex watersheds, which can affect management decisions and policy. Through the National Science Foundation‐funded REACH (REsilience under Accelerated CHange) project, in collaboration with the Intensively Managed Landscapes‐Critical Zone Observatory, we have collected a series of multidisciplinary data sets throughout the Minnesota River Basin in south‐central Minnesota, USA, a 43,400‐km2 tributary to the Upper Mississippi River. Postglacial incision within the Minnesota River valley created an erosional landscape highly responsive to hydrologic change, allowing for transdisciplinary research into the complex cascade of environmental changes that occur due to hydrology and land use alterations from intensive agricultural management and climate change. Data sets collected include water chemistry and biogeochemical data, geochemical fingerprinting of major sediment sources, high‐resolution monitoring of river bluff erosion, and repeat channel cross‐sectional and bathymetry data following major floods. The data collection efforts led to development of a series of integrative reduced complexity models that provide deeper insight into how water, sediment, and nutrients route and transform through a large channel network and respond to change. These models represent the culmination of efforts to integrate interdisciplinary data sets and science to gain new insights into watershed‐scale processes in order to advance management and decision making. The purpose of this paper is to present a synthesis of the data sets and models, disseminate them to the community for further research, and identify mechanisms used to expand the temporal and spatial extent of short‐term observatory‐scale data collection efforts

    Widespread West Nile virus activity, eastern United States, 2000.

    Get PDF
    In 1999, the U.S. West Nile (WN) virus epidemic was preceded by widespread reports of avian deaths. In 2000, ArboNET, a cooperative WN virus surveillance system, was implemented to monitor the sentinel epizootic that precedes human infection. This report summarizes 2000 surveillance data, documents widespread virus activity in 2000, and demonstrates the utility of monitoring virus activity in animals to identify human risk for infection

    Capturing a Flavivirus Pre-Fusion Intermediate

    Get PDF
    During cell entry of flaviviruses, low endosomal pH triggers the rearrangement of the viral surface glycoproteins to a fusion-active state that allows the release of the infectious RNA into the cytoplasm. In this work, West Nile virus was complexed with Fab fragments of the neutralizing mAb E16 and was subsequently exposed to low pH, trapping the virions in a pre-fusion intermediate state. The structure of the complex was studied by cryo-electron microscopy and provides the first structural glimpse of a flavivirus fusion intermediate near physiological conditions. A radial expansion of the outer protein layer of the virion was observed compared to the structure at pH 8. The resulting ∼60 Å-wide shell of low density between lipid bilayer and outer protein layer is likely traversed by the stem region of the E glycoprotein. By using antibody fragments, we have captured a structural intermediate of a virus that likely occurs during cell entry. The trapping of structural transition states by antibody fragments will be applicable for other processes in the flavivirus life cycle and delineating other cellular events that involve conformational rearrangements

    Identification of Continuous Human B-Cell Epitopes in the Envelope Glycoprotein of Dengue Virus Type 3 (DENV-3)

    Get PDF
    BACKGROUND:Dengue virus infection is a growing global public health concern in tropical and subtropical regions of the world. Dengue vaccine development has been hampered by concerns that cross-reactive immunological memory elicited by a candidate vaccine could increase the risk of development of more severe clinical forms. One possible strategy to reduce risks associated with a dengue vaccine is the development of a vaccine composed of selected critical epitopes of each of the serotypes. METHODOLOGY/PRINCIPAL FINDINGS:Synthetic peptides were used to identify B-cell epitopes in the envelope (E) glycoprotein of dengue virus type 3 (DENV-3). Eleven linear, immunodominant epitopes distributed in five regions at amino acid (aa) positions: 51-65, 71-90, 131-170, 196-210 and 246-260 were identified by employing an enzyme- linked immunosorbent assay (ELISA), using a pool of human sera from dengue type 3 infected individuals. Peptides 11 (aa51-65), 27 and 28 (aa131-150) also reacted with dengue 1 (DENV-1) and dengue 2 (DENV-2) patient sera as analyzed through the ROC curves generated for each peptide by ELISA and might have serotype specific diagnostic potential. Mice immunized against each one of the five immunogenic regions showed epitopes 51-65, 131-170, 196-210 and 246-260 elicited the highest antibody response and epitopes131-170, 196-210 and 246-260, elicited IFN-gamma production and T CD4+ cell response, as evaluated by ELISA and ELISPOT assays respectively. CONCLUSIONS/SIGNIFICANCE:Our study identified several useful immunodominant IgG-specific epitopes on the envelope of DENV-3. They are important tools for understanding the mechanisms involved in antibody dependent enhancement and immunity. If proven protective and safe, in conjunction with others well-documented epitopes, they might be included into a candidate epitope-based vaccine
    • …
    corecore