University of Calgary

About: University of Calgary is a education organization based out in Calgary, Alberta, Canada. It is known for research contribution in the topics: Population & Health care. The organization has 44284 authors who have published 104970 publications receiving 3669161 citations. The organization is also known as: U of C & UCalgary.

Tumor necrosis factor-alpha dependent cytotoxicity of human skin mast cells is enhanced by anti-IgE antibodies.

Abstract: Mast cells dispersed from human skin and purified by density-gradient centrifugation were cytotoxic toward the mouse fibrosarcoma cell line WEHI-164. Skin mast cells were not cytotoxic toward the NK cell-sensitive cell line K562. Killing of WEHI-164 occurred over a prolonged (greater than 18 h) period of incubation with mast cells and was effectively inhibited by polyclonal antibodies and mAb against TNF-alpha suggesting that this cytokine plays an important role in mast cell-mediated cytotoxicity. Whereas lysates of rat peritoneal mast cells exhibited cytotoxicity toward WEHI-164, this was not found with lysates of unstimulated skin mast cells suggesting that TNF-alpha is not stored preformed in the latter. Killing of WEHI-164 cells by skin mast cells was enhanced by anti-IgE and there was a significant correlation between histamine release and cytotoxicity after activation with this stimulus. We conclude that human skin mast cells are a potential source of TNF-alpha and suggest that these cells, particularly after activation, might contribute to the synthesis of this multifunctional cytokine in inflammatory sites.

Estrogen receptor α-mediated transcription induces cell cycle-dependent DNA double-strand breaks.

Abstract: Prolonged exposure to estrogen increases breast cancer risk. Estrogen is known to induce chromosomal aberrations, yet the mechanisms by which estrogen promotes genomic instability are not fully understood. Here, we show that exposure of MCF-7 cells to 17β-estradiol (E2) induces DNA double-strand breaks (DSBs), as determined by the formation of γH2AX foci. Foci formation was dependent upon estrogen receptor-α (ERα) and the catalytic activity of the type II topoisomerase, topoisomerase IIβ (topoIIβ). Moreover, we show by chromatin immunoprecipitation that topoIIβ-dependent E2-induced γH2AX localizes to the promoter of the estrogen-inducible gene, trefoil factor 1. E2-induced foci were associated with cyclin A expression and inhibited by pre-incubation with the DNA polymerase inhibitor aphidicolin suggesting that E2-induced DSBs are mediated by progression through S phase. Furthermore, E2-induced γH2AX foci colocalized with Rad51, suggesting that E2-induced DSBs are repaired by homologous recombination. We propose that DNA DSBs formed by the strand-cleaving activity of the topoIIβ-DNA cleavage complex at estrogen-inducible genes can present a barrier to DNA replication, leading to persistent DNA DSBs in ERα-positive breast cancer cells.

Estimating Power Generation of Invisible Solar Sites Using Publicly Available Data

Abstract: Large-scale integration of invisible solar photovoltaic generation into power systems could significantly affect the system net load and pose new challenges in the operation of power systems. Invisible solar photovoltaic refers mainly to small-scale roof-top solar sites that are not monitored, and thus are invisible to utilities and system operators. Invisible solar generation affects the shape of system net electrical load and could make net load forecasting more challenging. In this paper, a methodology is proposed to estimate the power generation of invisible solar photovoltaic sites. The proposed method only uses the measured power generation data of publicly available sites. It uses real time data of a small subset of sites to estimate the aggregated power generation from known sites within a region. The proposed model is validated using actual invisible solar generation data of the California power system.

Estimation of elastic constants for HTI media using Gauss-Newton and full-Newton multiparameter full-waveform inversion

Abstract: In seismic full-waveform inversion (FWI), subsurface parameters are estimated by iteratively minimizing the difference between the modeled and the observed data. We have considered the problem of estimating the elastic constants of a fractured medium using multiparameter FWI and modeling naturally fractured reservoirs as equivalent anisotropic media. Multiparameter FWI, although promising, remains exposed to a range of challenges, one being the parameter crosstalk problem resulting from the overlap of Frechet derivative wavefields. Parameter crosstalk is strongly influenced by the form of the scattering pattern for each parameter. We have derived 3D radiation patterns associated with scattering from a range of elastic constants in general anisotropic media. Then, we developed scattering patterns specific to a horizontal transverse isotropic (HTI) medium to draw conclusions about parameter crosstalk in FWI. Bare gradients exhibit crosstalk, as well as artifacts caused by doubly scattered energy in ...

Secretome Analysis of Vibrio cholerae Type VI Secretion System Reveals a New Effector-Immunity Pair

Abstract: The type VI secretion system (T6SS) is a dynamic macromolecular organelle that many Gram-negative bacteria use to inhibit or kill other prokaryotic or eukaryotic cells. The toxic effectors of T6SS are delivered to the prey cells in a contact-dependent manner. In Vibrio cholerae, the etiologic agent of cholera, T6SS is active during intestinal infection. Here, we describe the use of comparative proteomics coupled with bioinformatics to identify a new T6SS effector-immunity pair. This analysis was able to identify all previously identified secreted substrates of T6SS except PAAR (proline, alanine, alanine, arginine) motif-containing proteins. Additionally, this approach led to the identification of a new secreted protein encoded by VCA0285 (TseH) that carries a predicted hydrolase domain. We confirmed that TseH is toxic when expressed in the periplasm of Escherichia coli and V. cholerae cells. The toxicity observed in V. cholerae was suppressed by coexpression of the protein encoded by VCA0286 (TsiH), indicating that this protein is the cognate immunity protein of TseH. Furthermore, exogenous addition of purified recombinant TseH to permeabilized E. coli cells caused cell lysis. Bioinformatics analysis of the TseH protein sequence suggest that it is a member of a new family of cell wall-degrading enzymes that include proteins belonging to the YD repeat and Rhs superfamilies and that orthologs of TseH are likely expressed by species belonging to phyla as diverse as Bacteroidetes and Proteobacteria . IMPORTANCE The Gram-negative bacterium Vibrio cholerae causes cholera, a severe and often lethal diarrheal disease. The 2010-2012 epidemic in Haiti and new explosive epidemics in Africa show that cholera remains a significant global public health problem. The type VI secretion system (T6SS) is a dynamic organelle expressed by many Gram-negative bacteria, which use it to inject toxic effector proteins into eukaryotic and bacterial prey cells. In this study, we applied a comparative proteomics approach to the V. cholerae T6SS secretome to identify new substrates of this secretion apparatus. We show that the product of the gene VCA0285 is likely a new peptidoglycan hydrolase that is secreted by T6SS and that its cognate immunity protein is encoded by the gene that is immediately downstream (VCA0286). Bioinformatics analysis shows that VCA0285 carries four conserved motifs that likely define a large family of hydrolases with antibacterial activity. The identification of new antibacterial T6SS effectors provides useful information for the development of novel antibiotics and therapeutic agents.