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1,186 results on '"Dupré, J. '

3. The Jacobi Curvature Operator in Semi Riemannian Geometry and the Energy Momentum Stress Tensor of the Gravitational Field

Author

Dupré, Maurice J.

Subjects
General Relativity and Quantum Cosmology, Mathematical Physics, 83C05, 83C40, 83C99
Abstract

We give a justification for generalizing the notion of the energy momentum stress tensor in general relativity which results in the Jacobi curvature tensor being the embodiment of total energy momentum stress including gravity in general relativity., Comment: 110 pages. arXiv admin note: substantial text overlap with arXiv:0903.5225, arXiv:1403.2618, arXiv:0803.1684

Published
2020

4. Growth mechanism of polymer membranes obtained by H-bonding across immiscible liquid interfaces

Author

de Baubigny, J Dupré, Perrin, P., Pantoustier, N., Salez, Thomas, Reyssat, M., and Monteux, C.

Subjects
Condensed Matter - Soft Condensed Matter, Condensed Matter - Materials Science
Abstract

Complexation of polymers at liquid interfaces is an emerging technique to produce all-liquid printable and self-healing devices and membranes. It is crucial to control the assembly process but the mechanisms at play remain unclear. Using two different reflectometric methods, we investigate the spontaneous growth of H-bonded PPO-PMAA membranes at a flat liquid-liquid interface. We find that the membrane thickness h grows with time t as h~t^(1/2), which is reminiscent of a diffusion-limited process. However, counter-intuitively, we observe that this process is faster as the PPO molar mass increases. We are able to rationalize these results with a model which considers the diffusion of the PPO chains within the growing membrane. The architecture of the latter is described as a gel-like porous network, with a pore size much smaller than the radius of the diffusing PPO chains, thus inducing entropic barriers that hinder the diffusion process. From the comparison between the experimental data and the result of the model, we extract some key piece of information about the microscopic structure of the membrane. This study opens the route toward the rational design of self-assembled membranes and capsules with optimal properties.

Published
2020

8. Anti-cancer properties of cannflavin A and potential synergistic effects with gemcitabine, cisplatin, and cannabinoids in bladder cancer

Author

Andrea M. Tomko, Erin G. Whynot, and Denis J. Dupré

Subjects
Bladder cancer, Gemcitabine, Cisplatin, Cannabidiol, Δ9-Tetrahydrocannabinol, Cannabichromene, Pharmacy and materia medica, RS1-441, Plant culture, SB1-1110
Abstract

Abstract Introduction Several studies have shown anti-tumor effects of components present in cannabis in different models. Unfortunately, little is known about the potential anti-tumoral effects of most compounds present in cannabis in bladder cancer and how these compounds could potentially positively or negatively impact the actions of chemotherapeutic agents. Our study aims to evaluate the effects of a compound found in Cannabis sativa that has not been extensively studied to date, cannflavin A, in bladder cancer cell lines. We aimed to identify whether cannflavin A co-treatment with agents commonly used to treat bladder cancer, such as gemcitabine and cisplatin, is able to produce synergistic effects. We also evaluated whether co-treatment of cannflavin A with various cannabinoids could produce synergistic effects. Methods Two transitional cell carcinoma cell lines were used to assess the cytotoxic effects of the flavonoid cannflavin A up to 100 μM. We tested the potential synergistic cytotoxic effects of cannflavin A with gemcitabine (up to 100 nM), cisplatin (up to 100 μM), and cannabinoids (up to 10 μM). We also evaluated the activation of the apoptotic cascade using annexin V and whether cannflavin A has the ability to reduce invasion using a Matrigel assay. Results Cell viability of bladder cancer cell lines was affected in a concentration-dependent fashion in response to cannflavin A, and its combination with gemcitabine or cisplatin induced differential responses—from antagonistic to additive—and synergism was also observed in some instances, depending on the concentrations and drugs used. Cannflavin A also activated apoptosis via caspase 3 cleavage and was able to reduce invasion by 50%. Interestingly, cannflavin A displayed synergistic properties with other cannabinoids like Δ9-tetrahydrocannabinol, cannabidiol, cannabichromene, and cannabivarin in the bladder cancer cell lines. Discussion Our results indicate that compounds from Cannabis sativa other than cannabinoids, like the flavonoid cannflavin A, can be cytotoxic to human bladder transitional carcinoma cells and that this compound can exert synergistic effects when combined with other agents. In vivo studies will be needed to confirm the activity of cannflavin A as a potential agent for bladder cancer treatment.

Published
2022
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11. The structure of local gravity theories

Author

Dupre, Maurice J.

Subjects
General Relativity and Quantum Cosmology
Abstract

We discuss the structure of local gravity theories as resulting from the idea that locally gravity must be physically characterized by tidal acceleration, and show how this relates to both Newtonian gravity and Einstein's general relativity.

Published
2014

12. An observer principle for general relativity

Author

Dupre, Maurice J.

Subjects
General Relativity and Quantum Cosmology
Abstract

We give a mathematical uniqueness theorem which in particular shows that symmetric tensors in general relativity are uniquely determined by their monomial functions on the light cone. Thus, for an observer to observe a tensor at an event in general relativity is to contract with the velocity vector of the observer, repeatedly to the rank of the tensor. Thus two symmetric tensors observed to be equal by all observers at a specific event are necessarily equal at that event., Comment: arXiv admin note: substantial text overlap with arXiv:0903.5225

Published
2014

13. Demodulation of spatial carrier images : performance analysis of several algorithms using a single image

Author

Badulescu, Claudiu, Bornert, M., Dupré, J. C., Esquis, P., Grediac, Michel, Molimard, Jérôme, Picart, Pascal, Rotinat, René, and Valle, Valéry

Subjects
Physics - Optics
Abstract

Optical full-field techniques have a great importance in modern experimental mechanics. Even if they are reasonably spread among the university laboratories, their diffusion in industrial companies remains very narrow for several reasons, especially a lack of metrological performance assessment. A full-field measurement can be characterized by its resolution, bias, measuring range, and by a specific quantity, the spatial resolution. The present paper proposes an original procedure to estimate in one single step the resolution, bias and spatial resolution for a given operator (decoding algorithms such as image correlation, low-pass filters, derivation tools ...). This procedure is based on the construction of a particular multi-frequential field, and a Bode diagram representation of the results. This analysis is applied to various phase demodulating algorithms suited to estimate in-plane displacements

Published
2013
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16. Differential algebras with Banach-algebra coefficients I: From C*-algebras to the K-theory of the spectral curve

Author

Dupré, Maurice J., Glazebrook, James F., and Previato, Emma

Subjects
Mathematics - Operator Algebras, Mathematical Physics, Mathematics - K-Theory and Homology, Primary: 46L08, 19K33, 19K35. Secondary: 13N10, 14H40, 47C15
Abstract

We present an operator-coefficient version of Sato's infinite-dimensional Grassmann manifold, and tau-function. In this context, the Burchnall-Chaundy ring of commuting differential operators becomes a C*-algebra, to which we apply the Brown-Douglas-Fillmore theory, and topological invariants of the spectral ring become readily available. We construct KK classes of the spectral curve of the ring and, motivated by the fact that all isospectral Burchnall-Chaundy rings make up the Jacobian of the curve, we compare the (degree-1) K-homology of the curve with that of its Jacobian. We show how the Burchnall-Chaundy C*-algebra extension of the compact operators provides a family of operator-valued tau-functions.

Published
2011

17. Differential algebras with Banach-algebra coefficients II: The operator cross-ratio tau-function and the Schwarzian derivative

Author

Dupré, Maurice J., Glazebrook, James F., and Previato, Emma

Subjects
Mathematics - Operator Algebras, Mathematical Physics, Mathematics - Complex Variables, 46L08, 53B10, 53C30, 14H70
Abstract

Several features of an analytic (infinite-dimensional) Grassmannian of (commensurable) subspaces of a Hilbert space were developed in the context of integrable PDEs (KP hierarchy). We extended some of those features when polarized separable Hilbert spaces are generalized to a class of polarized Hilbert modules, in particular the Baker and tau-functions, which become operator-valued. Following from Part I we produce a pre-determinant structure for a class of tau-functions defined in the setting of the similarity class of projections of a certain Banach *-algebra. This structure is explicitly derived from the transition map of a corresponding principal bundle. The determinant of this map gives a generalized, operator-valued tau-function that takes values in a commutative C*-algebra. We extend to this setting the operator cross-ratio which had been used to produce the scalar-valued tau-function, as well as the associated notion of a Schwarzian derivative along curves inside the space of similarity classes. We link directly this cross-ratio with Fay's trisecant identity for the tau-function (equivalent to the KP hierarchy). By restriction to the image of the Krichever map, we use the Schwarzian to introduce the notion of operator-valued projective structure on a compact Riemann surface: this allows a deformation inside the Grassmannian (as it varies its complex structure). Lastly, we use our identification of the Jacobian of the Riemann surface in terms of extensions of the Burchnall-Chaundy C*-algebra (Part I) to describe the KP hierarchy.

Published
2011

18. General Relativity As an Aether Theory

Author

Dupre, Maurice J. and Tipler, Frank J.

Subjects
General Relativity and Quantum Cosmology, Mathematical Physics
Abstract

Most early twentieth century relativists --- Lorentz, Einstein, Eddington, for examples --- claimed that general relativity was merely a theory of the aether. We shall confirm this claim by deriving the Einstein equations using aether theory. We shall use a combination of Lorentz's and Kelvin's conception of the aether. Our derivation of the Einstein equations will not use the vanishing of the covariant divergence of the stress-energy tensor, but instead equate the Ricci tensor to the sum of the usual stress-energy tensor and a stress-energy tensor for the aether, a tensor based on Kelvin's aether theory. A crucial first step is generalizing the Cartan formalism of Newtonian gravity to allow spatial curvature, as conjectured by Gauss and Riemann.

Published
2010
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19. Covariant energy-momentum and an uncertainty principle for general relativity

Author

Cooperstock, F. I. and Dupre, M. J.

Subjects
General Relativity and Quantum Cosmology, High Energy Physics - Theory
Abstract

We introduce a naturally-defined totally invariant spacetime energy expression for general relativity incorporating the contribution from gravity. The extension links seamlessly to the action integral for the gravitational field. The demand that the general expression for arbitrary systems reduces to the Tolman integral in the case of stationary bounded distributions, leads to the matter-localized Ricci integral for energy-momentum in support of the energy localization hypothesis. The role of the observer is addressed and as an extension of the special relativistic case, the field of observers comoving with the matter is seen to compute the intrinsic global energy of a system. The new localized energy supports the Bonnor claim that the Szekeres collapsing dust solutions are energy-conserving. It is suggested that in the extreme of strong gravity, the Heisenberg Uncertainty Principle be generalized in terms of spacetime energy-momentum., Comment: 11 pages, new material added

Published
2009
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20. The Fully Covariant Energy Momentum Stress Tensor For Gravity and the Einstein Equation in General Relativity

Author

Dupré, Maurice J.

Subjects
General Relativity and Quantum Cosmology, 83C05, 83C40, 83C99
Abstract

We give a fully covariant energy momentum stress tensor for the gravitational field which is easily physically motivated, and which leads to a very general derivation of the Einstein equation for gravity. We do not need to assume any property of the surce matter fields' energy momentum stress tensor other than symmetry. We give a physical motivation for this choice using laser light pressure. As a consequence of our derivation, the energy momentum stress tensor for the total source matter and fields must be divergence free, when spacetime is 4 dimensional. Moreoverr, if the total source matter fields are assumed to be divergence free, then either spacetime is dimension 4 or the spacetime has constant scalar curvature., Comment: preprint

Published
2009

21. The Einstein equation and the energy density of the gravitational field

Author

Dupre, Maurice J.

Subjects
Mathematical Physics, Mathematics - Differential Geometry, 83C05, 83C40, 83C99
Abstract

We give a derivation of the Einstein equation for gravity which employs a definition of the local energy density of the gravitational field as a symmetric second rank tensor whose value for each observer gives the trace of the spatial part of the energy-stress tensor as seen by that observer. We give a physical motivation for this choice using light pressure.

Published
2008

24. The Cox Theorem: Unknowns And Plausible Value

Author

Dupre, Maurice J. and Tipler, Frank J.

Subjects
Mathematics - Probability
Abstract

We give a proof of Cox's Theorem on the product rule and sum rule for conditional plausibility without assuming continuity or differentiablity of plausibility. Instead, we extend the notion of plausibility to apply to unknowns giving them plausible values. Our proof is enormously simpler than others that have recently appeared in the literature, yet completely rigorous. For example, we do not need to investigate the 11 possibilities for conditional plausibilities as described on page 25 of Jaynes' recent book Probability Theory.

Published
2006

29. Antitumor Activity of Abnormal Cannabidiol and Its Analog O-1602 in Taxol-Resistant Preclinical Models of Breast Cancer

Author

Andrea Tomko, Lauren O’Leary, Hilary Trask, John C. Achenbach, Steven R. Hall, Kerry B. Goralski, Lee D. Ellis, and Denis J. Dupré

Subjects
cannabinoid, taxol, paclitaxel, breast cancer, apoptosis, cell migration, Therapeutics. Pharmacology, RM1-950
Abstract

Cannabinoids exhibit anti-inflammatory and antitumorigenic properties. Contrary to most cannabinoids present in the Cannabis plant, some, such as O-1602 and abnormal cannabidiol, have no or only little affinity to the CB1 or CB2 cannabinoid receptors and instead exert their effects through other receptors. Here, we investigated whether the synthetic regioisomers of cannabidiol, abnormal cannabidiol, and a closely related compound, O-1602, display antitumorigenic effects in cellular models of breast cancer and whether it could reduce tumorigenesis in vivo. Several studies have shown the effects of cannabinoids on chemotherapy-sensitive breast cancer cell lines, but less is known about the antitumorigenic effects of cannabinoids in chemotherapy-resistant cell lines. Paclitaxel-resistant MDA-MB-231 and MCF-7 breast cancer cell lines were used to study the effect of O-1602 and abnormal cannabidiol on viability, apoptosis, and migration. The effects of O-1602 and abnormal cannabidiol on cell viability were completely blocked by the combination of GPR55 and GPR18-specific siRNAs. Both O-1602 and abnormal cannabidiol decreased viability in paclitaxel-resistant breast cancer cells in a concentration-dependent manner through induction of apoptosis. The effect of these cannabinoids on tumor growth in vivo was studied in a zebrafish xenograft model. In this model, treatment with O-1602 and abnormal cannabidiol (2 µM) significantly reduced tumor growth. Our results suggest that atypical cannabinoids, like O-1602 and abnormal cannabidiol, exert antitumorigenic effects on paclitaxel-resistant breast cancer cells. Due to their lack of central sedation and psychoactive effects, these atypical cannabinoids could represent new leads for the development of additional anticancer treatments when resistance to conventional chemotherapy occurs during the treatment of breast and possibly other cancers.

Published
2019
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31. Glycemic Control and Urinary Tract Infections in Women with Type 1 Diabetes: Results from the DCCT/EDIC

Author

Nathan, D.M., Zinman, B., Crofford, O., Genuth, S., Brown-Friday, J., Crandall, J., Engel, H., Engel, S., Martinez, H., Phillips, M., Reid, M., Shamoon, H., Sheindlin, J., Gubitosi-Klug, R., Mayer, L., Pendegast, S., Zegarra, H., Miller, D., Singerman, L., Smith-Brewer, S., Novak, M., Quin, J., Genuth, Saul, Palmert, M., Brown, E., McConnell, J., Pugsley, P., Crawford, P., Dahms, W., Brillon, D., Lackaye, M.E., Kiss, S., Chan, R., Orlin, A., Rubin, M., Reppucci, V., Lee, T., Heinemann, M., Chang, S., Levy, B., Jovanovic, L., Richardson, M., Bosco, B., Dwoskin, A., Hanna, R., Barron, S., Campbell, R., Bhan, A., Kruger, D., Jones, J.K., Edwards, P.A., Carey, J.D., Angus, E., Thomas, A., Galprin, A., McLellan, M., Whitehouse, F., Bergenstal, R., Johnson, M., Gunyou, K., Thomas, L., Laechelt, J., Hollander, P., Spencer, M., Kendall, D., Cuddihy, R., Callahan, P., List, S., Gott, J., Rude, N., Olson, B., Franz, M., Castle, G., Birk, R., Nelson, J., Freking, D., Gill, L., Mestrezat, W., Etzwiler, D., Morgan, K., Aiello, L.P., Golden, E., Arrigg, P., Asuquo, V., Beaser, R., Bestourous, L., Cavallerano, J., Cavicchi, R., Ganda, O., Hamdy, O., Kirby, R., Murtha, T., Schlossman, D., Shah, S., Sharuk, G., Silva, P., Silver, P., Stockman, M., Sun, J., Weimann, E., Wolpert, H., Aiello, L.M., Jacobson, A., Rand, L., Rosenzwieg, J., Larkin, M.E., Christofi, M., Folino, K., Godine, J., Lou, P., Stevens, C., Anderson, E., Bode, H., Brink, S., Cornish, C., Cros, D., Delahanty, L., deManbey, A., Haggan, C., Lynch, J., McKitrick, C., Norman, D., Moore, D., Ong, M., Taylor, C., Zimbler, D., Crowell, S., Fritz, S., Hansen, K., Gauthier-Kelly, C., Service, F.J., Ziegler, G., Colligan, R., Schmidt, L., French, B., Woodwick, R., Rizza, R., Schwenk, W.F., Haymond, M., Pach, J., Mortenson, J., Zimmerman, B., Lucas, A., Luttrell, L., Lopes-Virella, M., Caulder, S., Pittman, C., Patel, N., Lee, K., Nutaitis, M., Fernandes, J., Hermayer, K., Kwon, S., Blevins, A., Parker, J., Colwell, J., Lee, D., Soule, J., Lindsey, P., Bracey, M., Farr, A., Elsing, S., Thompson, T., Selby, J., Lyons, T., Yacoub-Wasef, S., Szpiech, M., Wood, D., Mayfield, R., Molitch, M., Adelman, D., Colson, S., Jampol, L., Lyon, A., Gill, M., Strugula, Z., Kaminski, L., Mirza, R., Simjanoski, E., Ryan, D., Johnson, C., Wallia, A., Ajroud-Driss, S., Astelford, P., Leloudes, N., Degillio, A., Schaefer, B., Mudaliar, S., Lorenzi, G., Goldbaum, M., Jones, K., Prince, M., Swenson, M., Grant, I., Reed, R., Lyon, R., Kolterman, O., Giotta, M., Clark, T., Friedenberg, G., Sivitz, W.I., Vittetoe, B., Kramer, J., Bayless, M., Zeitler, R., Schrott, H., Olson, N., Snetselaar, L., Hoffman, R., MacIndoe, J., Weingeist, T., Fountain, C., Mendley, S., Johnsonbaugh, S., Patronas, M., Carney, M., Salemi, P., Liss, R., Hebdon, M., Counts, D., Donner, T., Gordon, J., Hemady, R., Kowarski, A., Ostrowski, D., Steidl, S., Jones, B., Herman, W.H., Martin, C.L., Pop-Busui, R., Greene, D.A., Stevens, M.J., Burkhart, N., Sandford, T., Floyd, J., Bantle, J., Wimmergren, N., Terry, J., Koozekanani, D., Montezuma, S., Rogness, B., Mech, M., Strand, T., Olson, J., McKenzie, L., Kwong, C., Goetz, F., Warhol, R., Hainsworth, D., Goldstein, D., Hitt, S., Giangiacomo, J., Schade, D.S., Canady, J.L., Burge, M.R., Das, A., Avery, R.B., Ketai, L.H., Chapin, J.E., Schluter, M.L., Rich, J., Johannes, C., Hornbeck, D., Schutta, M., Bourne, P.A., Brucker, A., Braunstein, S., Schwartz, S., Maschak-Carey, B.J., Baker, L., Orchard, T., Cimino, L., Songer, T., Doft, B., Olson, S., Becker, D., Rubinstein, D., Bergren, R.L., Fruit, J., Hyre, R., Palmer, C., Silvers, N., Lobes, L., Rath, P. Paczan, Conrad, P.W., Yalamanchi, S., J.Wesche, Bratkowksi, M., Arslanian, S., Rinkoff, J., Warnicki, J., Curtin, D., Steinberg, D., Vagstad, G., Harris, R., Steranchak, L., Arch, J., Kelly, K., Ostrosaka, P., Guiliani, M., Good, M., Williams, T., Olsen, K., Campbell, A., Shipe, C., Conwit, R., Finegold, D., Zaucha, M., Drash, A., Morrison, A., Malone, J.I., Bernal, M.L., Pavan, P.R., Grove, N., Tanaka, E.A., McMillan, D., Vaccaro-Kish, J., Babbione, L., Solc, H., DeClue, T.J., Dagogo-Jack, S., Wigley, C., Ricks, H., Kitabchi, A., Chaum, E., Murphy, M.B., Moser, S., Meyer, D., Iannacone, A., Yoser, S., Bryer-Ash, M., Schussler, S., Lambeth, H., Raskin, P., Strowig, S., Basco, M., Cercone, S., Barnie, A., Devenyi, R., Mandelcorn, M., Brent, M., Rogers, S., Gordon, A., Bakshi, N., Perkins, B., Tuason, L., Perdikaris, F., Ehrlich, R., Daneman, D., Perlman, K., Ferguson, S., Palmer, J., Fahlstrom, R., de Boer, I.H., Kinyoun, J., Van Ottingham, L., Catton, S., Ginsberg, J., McDonald, C., Harth, J., Driscoll, M., Sheidow, T., Mahon, J., Canny, C., Nicolle, D., Colby, P., Dupre, J., Hramiak, I., Rodger, N.W., Jenner, M., Smith, T., Brown, W., May, M., Hagan, J. Lipps, Agarwal, A., Adkins, T., Lorenz, R., Feman, S., Survant, L., White, N.H., Levandoski, L., Grand, G., Thomas, M., Joseph, D., Blinder, K., Shah, G., Burgess, D., Boniuk, I., Santiago, J., Tamborlane, W., Gatcomb, P., Stoessel, K., Ramos, P., Fong, K., Ossorio, P., Ahern, J., Beck, C., Gaston, P., Trail, R., Lachin, J., Cleary, P., Backlund, J., Bebu, I., Braffett, B., Diminick, L., Gao, X., Hsu, W., Klumpp, K., Larsen, M., McGee, P., Sun, W., Villavicencio, S., Anderson, K., Dews, L., Younes, Naji, Rutledge, B., Chan, K., Rosenberg, D., Petty, B., Determan, A., Kenny, D., Williams, C., Cowie, C., Siebert, C., Steffes, M., Arends, V., Bucksa, J., Nowicki, M., Chavers, B., O’Leary, D., Polak, J., Harrington, A., Funk, L., Crow, R., Gloeb, B., Thomas, S., O’Donnell, C., Soliman, E.Z., Zhang, Z.M., Li, Y., Campbell, C., Keasler, L., Hensley, S., Hu, J., Barr, M., Taylor, T., Prineas, R., Feldman, E.L., Albers, J.W., Low, P., Sommer, C., Nickander, K., Speigelberg, T., Pfiefer, M., Schumer, M., Moran, M., Farquhar, J., Ryan, C., Sandstrom, D., Geckle, M., Cupelli, E., Thoma, F., Burzuk, B., Woodfill, T., Danis, R., Blodi, B., Lawrence, D., Wabers, H., Gangaputra, S., Neill, S., Burger, M., Dingledine, J., Gama, V., Sussman, R., Davis, M., Hubbard, L., Budoff, M., Darabian, S., Rezaeian, P., Wong, N., Fox, M., Oudiz, R., Kim, L., Detrano, R., Cruickshanks, K., Dalton, D., Bainbridge, K., Lima, J., Bluemke, D., Turkbey, E., van der Geest, R.J., Liu, C., Malayeri, A., Jain, A., Miao, C., Chahal, H., Jarboe, R., Monnier, V., Sell, D., Strauch, C., Hazen, S., Pratt, A., Tang, W., Brunzell, J., Purnell, J., Natarajan, R., Miao, F., Zhang, L., Chen, Z., Paterson, A., Boright, A., Bull, S., Sun, L., Scherer, S., Lyons, T.J., Jenkins, A., Klein, R., Virella, G., Jaffa, A., Carter, R., Stoner, J., Garvey, W.T., Lackland, D., Brabham, M., McGee, D., Zheng, D., Mayfield, R.K., Maynard, J., Wessells, H., Sarma, A., Dunn, R., Holt, S., Hotaling, J., Kim, C., Clemens, Q., Brown, J., McVary, K., Lenherr, Sara M., Clemens, J. Quentin, Braffett, Barbara H., Cleary, Patricia A., Dunn, Rodney L., Hotaling, James M., Jacobson, Alan M., Kim, Catherine, Herman, William, Brown, Jeanette S., Wessells, Hunter, and Sarma, Aruna V.

Published
2016
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34. Systemic Inflammation and Normocytic Anemia in DOCK11 Deficiency

Author

Block J, Rashkova C, Castanon I, Zoghi S, Platon J, Ardy RC, Fujiwara M, Chaves B, Schoppmeyer R, van der Made CI, Jimenez Heredia R, Harms FL, Alavi S, Alsina L, Sanchez Moreno P, Ávila Polo R, Cabrera-Pérez R, Kostel Bal S, Pfajfer L, Ransmayr B, Mautner AK, Kondo R, Tinnacher A, Caldera M, Schuster M, Domínguez Conde C, Platzer R, Salzer E, Boyer T, Brunner HG, Nooitgedagt-Frons JE, Iglesias E, Deyà-Martinez A, Camacho-Lovillo M, Menche J, Bock C, Huppa JB, Pickl WF, Distel M, Yoder JA, Traver D, Engelhardt KR, Linden T, Kager L, Hannich JT, Hoischen A, Hambleton S, Illsinger S, Da Costa L, Kutsche K, Chavoshzadeh Z, van Buul JD, Antón J, Calzada-Hernández J, Neth O, Viaud J, Nishikimi A, Dupré L, Boztug K

Published
2023
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36. Superoxide Dismutase 1 Regulation of CXCR4-Mediated Signaling in Prostate Cancer Cells is Dependent on Cellular Oxidative State

Author

Brent Young, Chad Purcell, Yi-Qun Kuang, Nicholle Charette, and Denis J. Dupré

Subjects
Superoxide dismutase 1, CXCR4, Prostate cancer, Signaling, G protein-coupled receptor, Cell migration, Physiology, QP1-981, Biochemistry, QD415-436
Abstract

Background/Aims: CXCL12, acting via one of its G protein-coupled receptors, CXCR4, is a chemoattractant for a broad range of cell types, including several types of cancer cells. Elevated expression of CXCR4, and its ligand CXCL12, play important roles in promoting cancer metastasis. Cancer cells have the potential for rapid and unlimited growth in an area that may have restricted blood supply, as oxidative stress is a common feature of solid tumors. Recent studies have reported that enhanced expression of cytosolic superoxide dismutase (SOD1), a critical enzyme responsible for regulation of superoxide radicals, may increase the aggressive and invasive potential of malignant cells in some cancers. Methods: We used a variety of biochemical approaches and a prostate cancer cell line to study the effects of SOD1 on CXCR4 signaling. Results: Here, we report a direct interaction between SOD1 and CXCR4. We showed that SOD1 interacts directly with the first intracellular loop (ICL1) of CXCR4 and that the CXCL12/CXCR4-mediated regulation of AKT activation, apoptosis and cell migration in prostate cancer (PCa) cells is differentially modulated under normal versus hypoxic conditions when SOD1 is present. Conclusions: This study highlights a potential new regulatory mechanism by which a sensor of the oxidative environment could directly regulate signal transduction of a receptor involved in cancer cell survival and migration.

Published
2015
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37. Curvature of Universal Bundles of Banach Algebras

Author

Dupré, Maurice J., Glazebrook, James F., Previato, Emma, Dym, Harry, Ball, Joseph A., Kaashoek, Marinus A., Langer, Heinz, Tretter, Christiane, Adamyan, Vadim, Böttcher, Albrecht, Brown, B. Malcolm, Curto, Raul, Gesztesy, Fritz, Kurasov, Pavel, Lerer, Leonid E., Paulsen, Vern, Putinar, Mihai, Rodman, Leiba, Spitkovsky, Ilya M., Coburn, Lewis A., Foias, Ciprian, Helton, J. William, Kailath, Thomas, Lancaster, Peter, Lax, Peter D., Sarason, Donald, Silbermann, Bernd, Widom, Harold, and Bolotnikov, Vladimir

Published
2010
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45. β-catenin interacts with the TAZ1 and TAZ2 domains of CBP/p300 to activate gene transcription

Author

Alexandra D. Brown, Connor Cranstone, Denis J. Dupré, and David N. Langelaan

Subjects
Structural Biology, General Medicine, Molecular Biology, Biochemistry
Abstract

The transcriptional co-regulator β-catenin is a critical effector of the canonical Wnt-signalling pathway, which plays a crucial role in regulating cell fate and maintaining tissue homeostasis. Deregulation of the Wnt/β-catenin pathway is characteristic in the development of major types of cancer, where accumulation of β-catenin promotes cancer cell proliferation and renewal. β-catenin gene expression is facilitated through recruitment of co-activators such as histone acetyltransferases CBP/p300; however, the mechanism of their interaction is not fully understood. Here we investigate the interaction between the C-terminal transactivation domain of β-catenin and CBP/p300. Using a combination of pulldown assays, isothermal titration calorimetry, and nuclear resonance spectroscopy we determine the disordered C-terminal region of β-catenin binds promiscuously to the TAZ1 and TAZ2 domains of CBP/p300. We then map the interaction site of the C-terminal β-catenin transactivation domain onto TAZ1 and TAZ2 using chemical-shift perturbation studies. Luciferase-based gene reporter assays indicate Asp750-Leu781 is critical to β-catenin gene activation, and mutagenesis revealed that acidic and hydrophobic residues within this region are necessary to maintain TAZ1 binding. These results provide a mechanistic understanding of Wnt/β-catenin gene regulation that underlies cell development and provide a framework to develop methods to block β-catenin dependent signalling in the future.

Published
2022
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46. Structural basis of CBP/p300 recruitment by the microphthalmia-associated transcription factor

Author

Alexandra D. Brown, Kathleen L. Vergunst, Makenzie Branch, Connor M. Blair, Denis J. Dupré, George S. Baillie, and David N. Langelaan

Abstract

The microphthalmia-associated transcription factor (MITF) is a master regulator of the melanocyte cell lineage. Aberrant MITF activity can lead to multiple malignancies including skin cancer, where it modulates the proliferation and invasiveness of melanoma. MITF-dependent gene expression requires recruitment of transcriptional co-activators such as CBP/p300, but details of this process are not fully defined. Here, we investigate the structural and functional interaction between the MITF N-terminal transactivation domain (MITFTAD) and CBP/p300. A combination of pulldown assays and nuclear magnetic resonance spectroscopy determined that MITF binds both TAZ1 and TAZ2 domains of CBP/p300 with high affinity. The solution-state structure of the MITFTAD:TAZ2 complex reveals that MITF interacts with a hydrophobic surface of TAZ2, while remaining relatively dynamic. Peptide array and mutagenesis experiments determined that an acidic motif is integral to the MITFTAD:TAZ2 interaction and is necessary for transcriptional activity of MITF. Peptides that bind to the same surface of TAZ2 as MITFTAD, such as the adenoviral protein E1A, are capable of displacing MITF from TAZ2 and inhibiting transactivation. These results provide mechanistic insight into co-activator recruitment by MITF that are fundamental to our understanding of MITF targeted gene regulation and melanoma biology.

Published
2022
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49. Anterograde Trafficking of CXCR4 and CCR2 Receptors in a Prostate Cancer Cell Line

Author

Kelsie Gillies, Jaime Wertman, Nicholle Charette, and Denis J. Dupré

Subjects
G protein coupled receptor (GPCR), Prostate cancer metastasis, Rab GTPase, CXCR4 chemokine receptor, CCR2 chemokine receptor, Focal adhesion kinase, Physiology, QP1-981, Biochemistry, QD415-436
Abstract

Background: Most prostate cancer-related deaths result from metastasis. CXCR4 and CCR2 are known to govern cellular processes resulting in cell migration, proliferation and survival. These receptors are expressed at low levels on normal prostate cells and are highly expressed on malignant and metastatic prostate cancer cells. Signaling of these receptors is relatively well understood, but processes governing their expression at the cell membrane are not. PC3 prostate cancer cells were used to demonstrate the importance of various Rab GTPases on cell surface expression and signaling of CXCR4 and CCR2, along with the CXCR4/CCR2 heterodimer. Methods: PC3 prostate cancer cells were transfected with select Rab GTPase wild-type and dominant negative constructs. Effects of each Rab GTPase on endogenous cell surface expression of the individual receptors, along with the overexpressed CXCR4/CCR2 heterodimer, were determined by biotin-streptavidin cell surface assays. These results were corroborated by assessing signal transduction, measured by focal adhesion kinase (FAK) activation. Conclusion: Rab GTPases required for cell surface expression and signal transduction of CXCR4 or CCR2 differ from those required for the CXCR4/CCR2 heterodimer. Determining trafficking regulators of two key receptors involved in the metastatic transition may identify new targets to restrict expression of chemokine receptors employed during metastasis.

Published
2013
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