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103 results on '"Macauley, M."'

5. Repression of phagocytosis by human CD33 is not conserved with mouse CD33

Author

Bhattacherjee, A., Rodrigues, E., Jung, J., Luzentales-Simpson, M., Enterina, J., Galleguillos, D., Laurent, S., D., C., Nakhaei-Nejad, M., Fuchsberger, F., Streith, L., Wang, Q., Kawasaki, N., Duan, S., Bains, A., Paulson, J., Rademacher, C., Giuliani, F., Sipione, S., and Macauley, M.

Subjects
0301 basic medicine, Genetically modified mouse, Microglia, Phagocytosis, Cell, Neuroimmunology, Medicine (miscellaneous), Biology, General Biochemistry, Genetics and Molecular Biology, Transmembrane protein, Article, Cell biology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, lcsh:Biology (General), Cell culture, medicine, General Agricultural and Biological Sciences, Receptor, lcsh:QH301-705.5, 030217 neurology & neurosurgery
Abstract

CD33 is an immunomodulatory receptor linked to Alzheimer’s disease (AD) susceptibility via regulation of phagocytosis in microglia. Divergent features between human CD33 (hCD33) and murine CD33 (mCD33) include a unique transmembrane lysine in mCD33 and cytoplasmic tyrosine in hCD33. The functional consequences of these differences in restraining phagocytosis remains poorly understood. Using a new αmCD33 monoclonal antibody, we show that mCD33 is expressed at high levels on neutrophils and low levels on microglia. Notably, cell surface expression of mCD33 is entirely dependent on Dap12 due to an interaction with the transmembrane lysine in mCD33. In RAW264.7 cultured macrophages, BV-2 cultured microglia, primary neonatal and adult microglia, uptake of cargo — including aggregated Aβ1–42 — is not altered upon genetic ablation of mCD33. Alternatively, deletion of hCD33 in monocytic cell lines increased cargo uptake. Moreover, transgenic mice expressing hCD33 in the microglial cell lineage showed repressed cargo uptake in primary microglia. Therefore, mCD33 and hCD33 have divergent roles in regulating phagocytosis, highlighting the importance of studying hCD33 in AD susceptibility., Abhishek Bhattacherjee et al. investigate the functional differences between human and mouse CD33, an immunomodulatory receptor linked to Alzheimer’s disease. They find that loss of mouse CD33 does not affect cargo uptake in macrophages in contrast to human CD33, which represses phagocytosis when expressed in cells or mice.

Published
2019

9. Program and abstracts for the 2011 Meeting of the Society for Glycobiology

Author

Hollingsworth, MT, Hart, GW, Paulson, JC, Stansell, E, Canis, K, Huang, IC, Panico, M, Morris, H, Haslam, S, Farzan, M, Dell, A, Desrosiers, R, von Itzstein, M, Matroscovich, M, Luther, KB, Hülsmeier, AJ, Schegg, B, Hennet, T, Nycholat, C, McBride, R, Ekiert, D, Xu, R, Peng, W, Razi, N, Gilbert, M, Wakarchuk, W, Wilson, IA, Gahlay, G, Geisler, C, Aumiller, JJ, Moremen, K, Steel, J, Labaer, J, Jarvis, DL, Drickamer, K, Taylor, M, Nizet, V, Rabinovich, G, Lewis, C, Cobb, B, Kawasaki, N, Rademacher, C, Chen, W, Vela, J, Maricic, I, Crocker, P, Kumar, V, Kronenberg, M, Paulson, J, Glenn, K, Mallinger, A, Wen, H, Srivastava, L, Tundup, S, Harn, D, Menon, AK, Yamaguchi, Y, Mkhikian, H, Grigorian, A, Li, C, Chen, HL, Newton, B, Zhou, RW, Beeton, C, Torossian, S, Tatarian, GG, Lee, SU, Lau, K, Walker, E, Siminovitch, KA, Chandy, KG, Yu, Z, Dennis, JW, Demetriou, M, Pandey, MS, Baggenstoss, BA, Washburn, JL, Weigel, PH, Chen, CI, Keusch, JJ, Klein, D, Hofsteenge, J, Gut, H, Szymanski, C, Feldman, M, Schaffer, C, Gao, Y, Strum, S, Liu, B, Schutzbach, JS, Druzhinina, TN, Utkina, NS, Torgov, VI, Szarek, WA, Wang, L, Brockhausen, I, Hitchen, P, Peyfoon, E, Meyer, B, Albers, SV, Chen, C, Newburg, DS, Jin, C, Dinglasan, RD, Beverley, SM, Guo, H, Novozhilova, N, Hickerson, S, Elnaiem, DE, Sacks, D, Turco, SJ, McKay, D, Castro, E, Takahashi, H, Straus, AH, Stalnaker, SH, Live, D, Boons, GJ, Wells, L, Stuart, R, Aoki, K, Boccuto, L, Zhang, Q, Wang, H, Bartel, F, Fan, X, Saul, R, Chaubey, A, Yang, X, Steet, R, Schwartz, C, Tiemeyer, M, Pierce, M, Kraushaar, DC, Condac, E, Nakato, H, Nishihara, S, Sasaki, N, Hirano, K, Nasirikenari, M, Collins, CC, Lau, JT, Devarapu, SK, Jeyaweerasinkam, S, Albiez, RS, Kiessling, L, Gu, J, Clark, GF, Gagneux, P, Ulm, C, Mahavadi, P, Müller, S, Rinné, S, Geyer, H, Gerardy-Schahn, R, Mühlenhoff, M, Günther, A, Geyer, R, Galuska, SP, Shibata, T, Sugihara, K, Nakayama, J, Fukuda, M, Fukuda, MN, Ishikawa, A, Terao, M, Kimura, A, Kato, A, Katayama, I, Taniguchi, N, Miyoshi, E, Aderem, A, Yoneyama, T, Angata, K, Bao, X, Chanda, S, Lowe, J, Sonon, R, Ishihara, M, Talabnin, K, Wang, Z, Black, I, Naran, R, Heiss, C, Azadi, P, Hurum, D, Rohrer, J, Balland, A, Valliere-Douglass, J, Kodama, P, Mujacic, M, Eakin, C, Brady, L, Wang, WC, Wallace, A, Treuheit, M, Reddy, P, Schuman, B, Fisher, S, Borisova, S, Coates, L, Langan, P, Evans, S, Yang, SJ, Zhang, H, Hizal, DB, Tian, Y, Sarkaria, V, Betenbaugh, M, Lütteke, T, Agravat, S, Cholleti, S, Morris, T, Saltz, J, Song, X, Cummings, R, Smith, D, Hofhine, T, Nishida, C, Mialy, R, Sophie, D, Sebastien, F, Patricia, C, Eric, S, Stephane, H, Mokros, D, Joosten, RP, Dominik, A, Vriend, G, Nguyen, LD, Martinez, J, Hinderlich, S, Reissig, HU, Reutter, W, Fan, H, Saenger, W, Moniot, S, Asada, H, Nakahara, T, Miura, Y, Stevenson, T, Yamazaki, T, De Castro, C, Burr, T, Lanzetta, R, Molinaro, A, Parrilli, M, Sule, S, Gerken, TA, Revpredo, L, Thome, J, Cardenas, G, Almeida, I, Leung, MY, Yan, S, Paschinger, K, Bleuler-Martinez, S, Jantsch, V, Wilson, I, Yoshimura, Y, Adlercreutz, D, Mannerstedt, K, Wakarchuk, WW, Dovichi, NJ, Hindsgaul, O, Palcic, MM, Chandrasekaran, A, Bharadwaj, R, Deng, K, Adams, P, Singh, A, Datta, A, Konasani, V, Imamura, A, Lowry, T, Scaman, C, Zhao, Y, Zhou, YD, Yang, K, Zhang, XL, Leymarie, N, Hartshorn, K, White, M, Cafarella, T, Seaton, B, Rynkiewicz, M, Zaia, J, Acosta-Blanco, I, Ortega-Francisco, S, Dionisio-Vicuña, M, Hernandez-Flores, M, Fuentes-Romero, L, Newburg, D, Soto-Ramirez, LE, Ruiz-Palacios, G, Viveros-Rogel, M, Tong, C, Li, W, Kong, L, Qu, M, Jin, Q, Lukyanov, P, Zhang, W, Chicalovets, I, Molchanova, V, Wu, AM, Liu, JH, Yang, WH, Nussbaum, C, Grewal, PK, Sperandio, M, Marth, JD, Yu, R, Usuki, S, Wu, HC, O'Brien, D, Piskarev, V, Ramadugu, SK, Kashyap, HK, Ghirlanda, G, Margulis, C, Brewer, C, Gomery, K, Müller-Loennies, S, Brooks, CL, Brade, L, Kosma, P, Di Padova, F, Brade, H, Evans, SV, Asakawa, K, Kawakami, K, Kushi, Y, Suzuki, Y, Nozaki, H, Itonori, S, Malik, S, Lebeer, S, Petrova, M, Balzarini, J, Vanderleyden, J, Naito-Matsui, Y, Takematsu, H, Murata, K, Kozutsumi, Y, Subedi, GP, Satoh, T, Hanashima, S, Ikeda, A, Nakada, H, Sato, R, Mizuno, M, Yuasa, N, Fujita-Yamaguchi, Y, Vlahakis, J, Nair, DG, Wang, Y, Allingham, J, Anastassiades, T, Strachan, H, Johnson, D, Orlando, R, Harenberg, J, Haji-Ghassemi, O, Mackenzie, R, Lacerda, T, Toledo, M, Straus, A, Takahashi, HK, Woodrum, B, Ruben, M, O'Keefe, B, Samli, KN, Yang, L, Woods, RJ, Jones, MB, Maxwell, J, Song, EH, Manganiello, M, Chow, YH, Convertine, AJ, Schnapp, LM, Stayton, PS, Ratner, DM, Yegorova, S, Rodriguez, MC, Minond, D, Jiménez-Barbero, J, Calle, L, Ardá, A, Gabius, HJ, André, S, Martinez-Mayorga, K, Yongye, AB, Cudic, M, Ali, MF, Chachadi, VB, Cheng, PW, Kiwamoto, T, Na, HJ, Brummet, M, Finn, MG, Hong, V, Polonskaya, Z, Bovin, NV, Hudson, S, Bochner, B, Gallogly, S, Krüger, A, Hanley, S, Gerlach, J, Hogan, M, Ward, C, Joshi, L, Griffin, M, Demarco, C, Deveny, R, Aggeler, R, Hart, C, Nyberg, T, Agnew, B, Akçay, G, Ramphal, J, Calabretta, P, Nguyen, AD, Kumar, K, Eggers, D, Terrill, R, d'Alarcao, M, Ito, Y, Vela, JL, Matsumura, F, Hoshino, H, Lee, H, Kobayashi, M, Borén, T, Jin, R, Seeberger, PH, Pitteloud, JP, Cudic, P, Von Muhlinen, N, Thurston, T, von Muhlinen, N, Wandel, M, Akutsu, M, Foeglein, AÁ, Komander, D, Randow, F, Maupin, K, Liden, D, Haab, B, Dam, TK, Brown, RK, Wiltzius, M, Jokinen, M, Andre, S, Kaltner, H, Bullen, J, Balsbaugh, J, Neumann, D, Hardie, G, Shabanowitz, J, Hunt, D, Hart, G, Mi, R, Ding, X, Van Die, I, Chapman, AB, Cummings, RD, Ju, T, Aryal, R, Ashley, J, Feng, X, Hanover, JA, Wang, P, Keembiyehetty, C, Ghosh, S, Bond, M, Krause, M, Love, D, Radhakrishnan, P, Grandgenet, PM, Mohr, AM, Bunt, SK, Yu, F, Hollingsworth, MA, Ethen, C, Machacek, M, Prather, B, Wu, Z, Kotu, V, Zhao, P, Zhang, D, van der Wel, H, Johnson, JM, West, CM, Abdulkhalek, S, Amith, SR, Jayanth, P, Guo, M, Szewczuk, M, Ohtsubo, K, Chen, M, Olefsky, J, Marth, J, Zapater, J, Foley, D, Colley, K, Kawashima, N, Fujitani, N, Tsuji, D, Itoh, K, Shinohara, Y, Nakayama, K, Zhang, L, Ten Hagen, K, Koren, S, Yehezkel, G, Cohen, L, Kliger, A, Khalaila, I, Finkelstein, E, Parker, R, Kohler, J, Sacoman, J, Badish, L, Hollingsworth, R, Tian, E, Hoffman, M, Hou, X, Tashima, Y, Stanley, P, Kizuka, Y, Kitazume, S, Yoshida, M, Kunze, A, Nasir, W, Bally, M, Hook, F, Larson, G, Mahan, A, Alter, G, Zeidan, Q, Copeland, R, Pokrovskaya, I, Willett, R, Smith, R, Morelle, W, Kudlyk, T, Lupashin, V, Vasudevan, D, Takeuchi, H, Majerus, E, Haltiwanger, RS, Boufala, S, Lee, YA, Min, D, Kim, SH, Shin, MH, Gesteira, T, Pol-Fachin, L, Coulson-Thomas, VJ, Verli, H, Nader, H, Liu, X, Yang, P, Thoden, J, Holden, H, Tytgat, H, Sánchez-Rodríguez, A, Schoofs, G, Verhoeven, T, De Keersmaecker, S, Marchal, K, Ventura, V, Sarah, N, Joann, P, Ding, Y, Jarrell, K, Cook, MC, Gibeault, S, Filippenko, V, Ye, Q, Wang, J, Kunkel, JP, Arteaga-Cabello, FJ, Arciniega-Fuentes, MT, McCoy, J, Ruiz-Palacios, GM, Francoleon, D, Loo, RO, Loo, J, Ytterberg, AJ, Kim, U, Gunsalus, R, Costello, C, Soares, R, Assis, R, Ibraim, I, Noronha, F, De Godoy, AP, Bale, MS, Xu, Y, Brown, K, Blader, I, West, C, Chen, S, Ye, X, Xue, C, Li, G, Yu, G, Yin, L, Chai, W, Gutierrez-Magdaleno, G, Tan, C, Wu, D, Li, Q, Hu, H, Ye, M, Liu, D, Mink, W, Kaese, P, Fujiwara, M, Uchimura, K, Sakai, Y, Nakada, T, Mabashi-Asazuma, H, Toth, AM, Scott, DW, Chacko, BK, Patel, RP, Batista, F, Mercer, N, Ramakrishnan, B, Pasek, M, Boeggeman, E, Verdi, L, Qasba, PK, Tran, D, Lim, JM, Liu, M, Mo, KF, Kirby, P, Yu, X, Lin, C, Costello, CE, Akama, TO, Nakamura, T, Huang, Y, Shi, X, Han, L, Yu, SH, Zhang, Z, Knappe, S, Till, S, Nadia, I, Catarello, J, Quinn, C, Julia, N, Ray, J, Tran, T, Scheiflinger, F, Szabo, C, Dockal, M, Niimi, S, Hosono, T, Michikawa, M, Kannagi, R, Takashima, S, Amano, J, Nakamura, N, Kaneda, E, Nakayama, Y, Kurosaka, A, Takada, W, Matsushita, T, Hinou, H, Nishimura, S, Igarashi, K, Abe, H, Mothere, M, Leonhard-Melief, C, Johnson, H, Nagy, T, Nairn, A, Rosa, MD, Porterfield, M, Kulik, M, Dalton, S, Pierce, JM, Hansen, SF, McAndrew, R, Degiovanni, A, McInerney, P, Pereira, JH, Hadi, M, Scheller, HV, Barb, A, Prestegard, J, Zhang, S, Jiang, J, Tharmalingam, T, Pluta, K, McGettigan, P, Gough, R, Struwe, W, Fitzpatrick, E, Gallagher, ME, Rudd, PM, Karlsson, NG, Carrington, SD, Katoh, T, Panin, V, Gelfenbeyn, K, Freire-de-Lima, L, Handa, K, Hakomori, SI, Bielik, AM, McLeod, E, Landry, D, Mendoza, V, Guthrie, EP, Mao, Y, Wang, X, Moremen, KW, Meng, L, Ramiah, AP, Gao, Z, Johnson, R, Xiang, Y, Rosa, MDEL, Wu, SC, Gilbert, HJ, Karaveg, K, Chen, L, Wang, BC, Mast, S, Sun, B, Fulton, S, Kimzey, M, Pourkaveh, S, Minalla, A, Haxo, T, Wegstein, J, Murray, AK, Nichols, RL, Giannini, S, Grozovsky, R, Begonja, AJ, Hoffmeister, KM, Suzuki-Anekoji, M, Suzuki, A, Yu, SY, Khoo, KH, van Alphen, L, Fodor, C, Wenzel, C, Ashmus, R, Miller, W, Stahl, M, Stintzi, A, Lowary, T, Wiederschain, G, Saba, J, Zumwalt, A, Meitei, NS, Apte, A, Viner, R, Gandy, M, Debowski, A, Stubbs, K, Witzenman, H, Pandey, D, Repnikova, E, Nakamura, M, Islam, R, Kc, N, Caster, C, Chaubard, JL, Krishnamurthy, C, Hsieh-Wilson, L, Pranskevich, J, Rangarajan, J, Guttman, A, Szabo, Z, Karger, B, Chapman, J, Chavaroche, A, Bionda, N, Fields, G, Jacob, F, Tse, BW, Guertler, R, Nixdorf, S, Hacker, NF, Heinzelmann-Schwarz, V, Yang, F, Kohler, JJ, Losfeld, ME, Ng, B, Freeze, HH, He, P, Wondimu, A, Liu, Y, Zhang, Y, Su, Y, Ladisch, S, Grewal, P, Mann, C, Ditto, D, Lardone, R, Le, D, Varki, N, Kulinich, A, Kostjuk, O, Maslak, G, Pismenetskaya, I, Shevtsova, A, Takeishi, S, Okudo, K, Moriwaki, K, Terao, N, Kamada, Y, Kuroda, S, Li, Y, Peiris, D, Markiv, A, Dwek, M, Adamczyk, B, Thanabalasingham, G, Huffman, J, Kattla, J, Novokmet, M, Rudan, I, Gloyn, A, Hayward, C, Reynolds, R, Hansen, T, Klimes, I, Njolstad, P, Wilson, J, Hastie, N, Campbell, H, McCarthy, M, Rudd, P, Owen, K, Lauc, G, Wright, A, Goletz, S, Stahn, R, Danielczyk, A, Baumeister, H, Hillemann, A, Löffler, A, Stöckl, L, Jahn, D, Bahrke, S, Flechner, A, Schlangstedt, M, Karsten, U, Goletz, C, Mikolajczyk, S, Ulsemer, P, Gao, N, Cline, A, Flanagan-Steet, H, Sadler, KC, Lehrman, MA, Coulson-Thomas, YM, Gesteira, TF, Mader, AM, Waisberg, J, Pinhal, MA, Friedl, A, Toma, L, Nader, HB, Mbua, EN, Johnson, S, Wolfert, M, Dimitrievska, S, Huizing, M, Niklason, L, Perdivara, I, Petrovich, R, Tokar, EJ, Waalkes, M, Fraser, P, Tomer, K, Chu, J, Rosa, S, Mir, A, Lehrman, M, Sadler, K, Lauer, M, Hascall, V, Calabro, A, Cheng, G, Swaidani, S, Abaddi, A, Aronica, M, Yuzwa, S, Shan, X, Macauley, M, Clark, T, Skorobogatko, Y, Vosseller, K, Vocadlo, D, Banerjee, A, Baksi, K, Banerjee, D, Melcher, R, Kraus, I, Moeller, D, Demmig, S, Rogoll, D, Kudlich, T, Scheppach, W, Scheurlen, M, Hasilik, A, Steirer, L, Lee, J, Moe, G, Troy, FA, Wang, F, Xia, B, Wang, B, Yi, S, Yu, H, Suzuki, M, Kobayashi, T, Sato, Y, Zhou, H, Briscoe, A, Lee, R, Wolfert, MA, Matsumoto, Y, Hamamura, K, Yoshida, T, Akita, K, Okajima, T, Furukawa, K, Urano, T, Ruhaak, LR, Miyamoto, S, and Lebrilla, CB

Subjects
Embryogenesis, Cancer screening, Cancer research, medicine, Cell migration, Neural cell adhesion molecule, Biology, medicine.disease, Biochemistry, Metastasis
Abstract

Cell surface mucins configure the cell surface by presenting extended protein backbones that are heavily O-glycosylated. The glycopeptide structures establish physicochemical properties at the cell surface that enable and block the formation of biologically important molecular complexes. Some mucins, such as MUC1, associate with receptor tyrosine kinases and other cell surface receptors, and engage in signal transduction in order to communicate information regarding conditions at the cell surface to the nucleus. In that context, the MUC1 cytoplasmic tail (MUC1CT) receives phosphorylation signals from receptor tyrosine kinases and serine/threonine kinases, which enables its association with different signaling complexes that conduct these signals to the nucleus and perhaps other subcellular organelles. We have detected the MUC1CT at promoters of over 500 genes, in association with several different transcription factors, and have shown that promoter occupancy can vary under different growth factor conditions. However, the full biochemical nature of the nuclear forms of MUC1 and its function at these promoter regions remain undefined. I will present evidence that nuclear forms of the MUC1CT include extracellular and cytoplasmic tail domains. In addition, I will discuss evidence for a hypothesis that the MUC1CT possesses a novel catalytic function that enables remodeling of the transcription factor occupancy of promoters, and thereby engages in regulation of gene expression.

Published
2016

12. Order Independence in Asynchronous Cellular Automata

Author

Macauley, M., Mccammond, J., and Henning Mortveit

Subjects
37B99, 68Q80, FOS: Mathematics, Dynamical Systems (math.DS), Mathematics - Dynamical Systems, Nonlinear Sciences::Cellular Automata and Lattice Gases
Abstract

A sequential dynamical system, or SDS, consists of an undirected graph Y, a vertex-indexed list of local functions F_Y, and a permutation pi of the vertex set (or more generally, a word w over the vertex set) that describes the order in which these local functions are to be applied. In this article we investigate the special case where Y is a circular graph with n vertices and all of the local functions are identical. The 256 possible local functions are known as Wolfram rules and the resulting sequential dynamical systems are called finite asynchronous elementary cellular automata, or ACAs, since they resemble classical elementary cellular automata, but with the important distinction that the vertex functions are applied sequentially rather than in parallel. An ACA is said to be pi-independent if the set of periodic states does not depend on the choice of pi, and our main result is that for all n>3 exactly 104 of the 256 Wolfram rules give rise to a pi-independent ACA. In 2005 Hansson, Mortveit and Reidys classified the 11 symmetric Wolfram rules with this property. In addition to reproving and extending this earlier result, our proofs of pi-independence also provide significant insight into the dynamics of these systems., 18 pages. New version distinguishes between functions that are pi-independent but not w-independent

Published
2007

13. Forest Carbon Index: The Geography of Forests in Climate Solutions

Author

Deveney, A., Nackoney, J., Purvis, N., Gusti, M., Kopp, R., Myers, E., Stevenson, A., Kindermann, G., Macauley, M., Obersteiner, M., Deveney, A., Nackoney, J., Purvis, N., Gusti, M., Kopp, R., Myers, E., Stevenson, A., Kindermann, G., Macauley, M., and Obersteiner, M.

Published
2009

24. Distribution of vaccine/antivirals and the ‘least spread line’ in a stratified population

Author

Goldstein, E., Apolloni, A., Lewis, B., Miller, J. C., Macauley, M., Eubank, S., Lipsitch, M., and Wallinga, J.

Abstract

We describe a prioritization scheme for an allocation of a sizeable quantity of vaccine or antivirals in a stratified population. The scheme builds on an optimal strategy for reducing the epidemic's initial growth rate in a stratified mass-action model. The strategy is tested on the EpiSims network describing interactions and influenza dynamics in the population of Utah, where the stratification we have chosen is by age (0–6, 7–13, 14–18, adults). No prior immunity information is available, thus everyone is assumed to be susceptible—this may be relevant, possibly with the exception of persons over 50, to the 2009 H1N1 influenza outbreak. We have found that the top priority in an allocation of a sizeable quantity of seasonal influenza vaccinations goes to young children (0–6), followed by teens (14–18), then children (7–13), with the adult share being quite low. These results, which rely on the structure of the EpiSims network, are compared with the current influenza vaccination coverage levels in the US population.

Published
2010
Full Text
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28. Iliacus hematoma syndrome

Author

Kounis, N. G., Macauley, M. B., and Ghorbal, M. S.

Subjects
Adult, Hematoma, Thigh, Heparin, Muscles, Nerve Compression Syndromes, Humans, Female, cardiovascular diseases, Warfarin, Pulmonary Embolism, Femoral Nerve, Research Article
Abstract

In a patient receiving warfarin and heparin in the treatment of pulmonary embolism, a hematoma developed in the iliacus muscle, compressing the overlying femoral nerve. Femoral nerve paralysis ensued, causing inability to walk, pain and loss of sensation in the sensory distribution of the nerve. Surgical intervention and removal of the hematoma relieved the nerve compression and the condition gradually improved.

Published
1975

29. The economics of the space station

Author

Macauley, M. K., Ledyard, John O., Macauley, M. K., and Ledyard, John O.

Abstract

Space exploration and development are naturally conducted on the cutting edge of science and technology. Such efforts inevitably involve decisions made in the presence of extensive uncertainty. For some projects, particularly those which involve the creation and maintenance of an infrastructure, the emphasis is switching from specific engineering goals (for example, a man on the moon by 1969) to more diffuse, continuing, multiple-dimensional goals. This is especially true of the space station, which is envisioned as both a vital link in the exploration of the planets and a major facility for the advancement of commercial efforts in space. The combination of uncertainty and diffuse, long-term goals fundamentally alters the viability and validity of traditional economic and engineering approaches to the management of large public research and development projects. It has become popular to call into question the recent management of continuing projects like the space shuttle or major new weapons systems. We must, however, recognize that cost overruns, gold plating and other forms of apparent mismanagement are usually not the result of individual venality and misbehavior but only the natural outcomes of the existing organizational rules of the game. Just as the performance of an engineering design is guided by the laws of physics, the performance of an organizational design is guided by the laws of behavior. This fact means that to improve performance we cannot simply add more or better manpower; rather, we must look for new organizational solutions. There are many ad hoc opinions about how to do this; what I propose is a more systematic, scientific approach. This paper examines some of the economic and management issues which must be addressed if the space station is to effectively and efficiently pursue the myriad goals that have been chosen for it. I characterize and evaluate in a somewhat stylized fashion three possible policies: an "engineering" approach, an "econo

Published
1987

30. Effects of leflunomide and cyclosporine on aortic allograft chronic rejection in the rat

Author

Macdonald, A. S., Sabr, K., Macauley, M. A., Vivian McAlister, Bitter-Suermann, H., and Lee, T.

Subjects
Graft Rejection, Rats, Inbred WF, Aorta, Thoracic, Isoxazoles, Muscle, Smooth, Vascular, Rats, Rats, Inbred Lew, Chronic Disease, Cyclosporine, Animals, Transplantation, Homologous, Drug Therapy, Combination, Tunica Intima, Immunosuppressive Agents, Leflunomide

41. Siglec-7 mediates immunomodulation by colorectal cancer-associated Fusobacterium nucleatum ssp. animalis

Author

Pilar Garcia-Vello, Nathalie Juge, Matthew S. Macauley, Kelli A. McCord, Cristina De Castro, Kristian M. Bowles, Dimitra Lamprinaki, Charlotte Hellmich, Alba Silipo, Paul R. Crocker, Roberta Marchetti, Lamprinaki, D., Garcia-Vello, P., Marchetti, R., Hellmich, C., Mccord, K. A., Bowles, K. M., Macauley, M. S., Silipo, A., De Castro, C., Crocker, P. R., and Juge, N.

Subjects
Lipopolysaccharide, Carcinogenesis, medicine.medical_treatment, Immunology, Antigens, Differentiation, Myelomonocytic, colorectal cancer, Colorectal Neoplasm, outer membrane vesicle, Dendritic Cell, Microbiology, Cell Line, Immunomodulation, chemistry.chemical_compound, Immune system, stomatognathic system, Lectins, medicine, Immunology and Allergy, Macrophage, Humans, innate immunity, Carcinogenesi, Original Research, Innate immune system, biology, Fusobacterium nucleatum, Chemistry, Macrophages, lipopolysaccharide, SIGLEC, Siglec-7, Dendritic Cells, RC581-607, Fusobacterium, respiratory system, biology.organism_classification, stomatognathic diseases, Cytokine, Immunologic diseases. Allergy, Bacterial outer membrane, Colorectal Neoplasms, Lectin, Human
Abstract

Fusobacterium nucleatum is involved in the development of colorectal cancer (CRC) through innate immune cell modulation. However, the receptors of the interaction between F. nucleatum ssp. and immune cells remain largely undetermined. Here, we showed that F. nucleatum ssp. animalis interacts with Siglecs (sialic acid–binding immunoglobulin-like lectins) expressed on innate immune cells with highest binding to Siglec-7. Binding to Siglec-7 was also observed using F. nucleatum-derived outer membrane vesicles (OMVs) and lipopolysaccharide (LPS). F. nucleatum and its derived OMVs or LPS induced a pro-inflammatory profile in human monocyte-derived dendritic cells (moDCs) and a tumour associated profile in human monocyte-derived macrophages (moMϕs). Siglec-7 silencing in moDCs or CRISPR-cas9 Siglec-7-depletion of U-937 macrophage cells altered F. nucleatum induced cytokine but not marker expression. The molecular interaction between Siglec-7 and the LPS O-antigen purified from F. nucleatum ssp. animalis was further characterised by saturation transfer difference (STD) NMR spectroscopy, revealing novel ligands for Siglec-7. Together, these data support a new role for Siglec-7 in mediating immune modulation by F. nucleatum strains and their OMVs through recognition of LPS on the bacterial cell surface. This opens a new dimension in our understanding of how F. nucleatum promotes CRC progression through the generation of a pro-inflammatory environment and provides a molecular lead for the development of novel cancer therapeutic approaches targeting F. nucleatum-Siglec-7 interaction.

Published
2021

44. The economics of the space station

Author

Ledyard, John O. and Macauley, M. K.

Abstract

Space exploration and development are naturally conducted on the cutting edge of science and technology. Such efforts inevitably involve decisions made in the presence of extensive uncertainty. For some projects, particularly those which involve the creation and maintenance of an infrastructure, the emphasis is switching from specific engineering goals (for example, a man on the moon by 1969) to more diffuse, continuing, multiple-dimensional goals. This is especially true of the space station, which is envisioned as both a vital link in the exploration of the planets and a major facility for the advancement of commercial efforts in space. The combination of uncertainty and diffuse, long-term goals fundamentally alters the viability and validity of traditional economic and engineering approaches to the management of large public research and development projects. It has become popular to call into question the recent management of continuing projects like the space shuttle or major new weapons systems. We must, however, recognize that cost overruns, gold plating and other forms of apparent mismanagement are usually not the result of individual venality and misbehavior but only the natural outcomes of the existing organizational rules of the game. Just as the performance of an engineering design is guided by the laws of physics, the performance of an organizational design is guided by the laws of behavior. This fact means that to improve performance we cannot simply add more or better manpower; rather, we must look for new organizational solutions. There are many ad hoc opinions about how to do this; what I propose is a more systematic, scientific approach. This paper examines some of the economic and management issues which must be addressed if the space station is to effectively and efficiently pursue the myriad goals that have been chosen for it. I characterize and evaluate in a somewhat stylized fashion three possible policies: an "engineering" approach, an "economics" approach, and a systematic custom design approach. I will use the space station as an example to highlight some of the major economic issues facing large-scale multipurpose research and development efforts, the analytical capabilities we now have to address these issues, and the (non-engineering) research that needs to be done to advance the successful long-term development of space.

Published
1987

45. Sweden surpasses the UNAIDS 95-95-95 target: estimating HIV-1 incidence, 2003 to 2022.

Author

Lundgren E, Locke M, Romero-Severson E, Dimitrijevic M, Axelsson M, Andersson E, Carlander C, Brännström J, Norrgren H, Mansson F, Elvstam O, Gisslén M, Fohlin L, Sönnerborg A, Albert J, and Leitner T

Subjects
Humans, Sweden epidemiology, Incidence, Male, Female, Adult, SARS-CoV-2, Middle Aged, Homosexuality, Male statistics & numerical data, Pandemics, Registries, Anti-HIV Agents therapeutic use, Young Adult, HIV Infections epidemiology, HIV Infections drug therapy, HIV Infections diagnosis, HIV-1 drug effects, COVID-19 epidemiology
Abstract

BackgroundSweden reached the UNAIDS 90-90-90 target in 2015. It is important to reassess the HIV epidemiological situation due to ever-changing migration patterns, the roll-out of PrEP and the impact of the COVID-19 pandemic.AimWe aimed to assess the progress towards the UNAIDS 95-95-95 targets in Sweden by estimating the proportion of undiagnosed people with HIV (PWHIV) and HIV incidence trends.MethodsWe used routine laboratory data to inform a biomarker model of time since infection. When available, we used previous negative test dates, arrival dates for PWHIV from abroad and transmission modes to inform our incidence model. We also used data collected from the Swedish InfCareHIV register on antiretroviral therapy (ART).ResultsThe yearly incidence of HIV in Sweden decreased after 2014. In part, this was because the fraction of undiagnosed PWHIV had decreased almost twofold since 2006. After 2015, three of four PWHIV in Sweden were diagnosed within 1.9 and 3.2 years after infection among men who have sex with men and in heterosexual groups, respectively. While 80% of new PWHIV in Sweden acquired HIV before immigration, they make up 50% of the current PWHIV in Sweden. By 2022, 96% of all PWHIV in Sweden had been diagnosed, and 99% of them were on ART, with 98% virally suppressed.ConclusionsBy 2022, about half of all PWHIV in Sweden acquired HIV abroad. Using our new biomarker model, we assess that Sweden has reached the UNAIDS goal at 96-99-98.

Published
2024
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46. Chemoenzymatic Synthesis of Sulfated N -Glycans Recognized by Siglecs and Other Glycan-Binding Proteins.

Author

Huang K, Bashian EE, Zong G, Nycholat CM, McBride R, Gomozkova M, Wang S, Huang C, Chapla DG, Schmidt EN, Macauley M, Moremen KW, Paulson JC, and Wang LX

Abstract

Sulfated N -glycans are present in many glycoproteins, which are implicated in playing important roles in biological recognition processes. Here, we report the systematic chemoenzymatic synthesis of a library of sulfated and sialylated biantennary N -glycans and assess their binding to Siglecs and glycan-specific antibodies that recognize them as glycan ligands. The combined use of three human sulfotransferases, GlcNAc-6- O -sulfotransferase (CHST2), Gal-3- O -sulfotransferase (Gal3ST1), and keratan sulfate Gal-6- O -sulfotransferase (CHST1), resulted in asymmetric and symmetric branch-selective sulfation of the GlcNAc and/or Gal moieties of N -glycans. The extension of the sugar chain using α-2,3- and α-2,6-sialyltransferases afforded the sulfated and sialylated N -glycans. These synthetic glycans with different patterns of sulfation and sialylation were evaluated for binding to selected Siglecs and sulfoglycan-specific antibodies using glycan microarrays. The results confirm previously documented glycan-recognizing properties and further reveal novel specificities for these glycan-binding proteins, demonstrating the utility of the library for assessing the specificity of glycan-binding proteins recognizing sulfated and sialylated glycans., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Published
2024
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47. Sialic acid blockade inhibits the metastatic spread of prostate cancer to bone.

Author

Hodgson K, Orozco-Moreno M, Goode EA, Fisher M, Garnham R, Beatson R, Turner H, Livermore K, Zhou Y, Wilson L, Visser EA, Pijnenborg JF, Eerden N, Moons SJ, Rossing E, Hysenaj G, Krishna R, Peng Z, Nangkana KP, Schmidt EN, Duxfield A, Dennis EP, Heer R, Lawson MA, Macauley M, Elliott DJ, Büll C, Scott E, Boltje TJ, Drake RR, Wang N, and Munkley J

Subjects
Male, Humans, Animals, Mice, Cell Line, Tumor, Disease Models, Animal, Antigens, CD metabolism, Polysaccharides pharmacology, Glycosylation, beta-D-Galactoside alpha 2-6-Sialyltransferase, Prostatic Neoplasms pathology, Prostatic Neoplasms metabolism, Prostatic Neoplasms drug therapy, Sialyltransferases metabolism, Sialyltransferases genetics, Bone Neoplasms secondary, Bone Neoplasms metabolism, Bone Neoplasms drug therapy, N-Acetylneuraminic Acid metabolism
Abstract

Background: Bone metastasis is a common consequence of advanced prostate cancer. Bisphosphonates can be used to manage symptoms, but there are currently no curative treatments available. Altered tumour cell glycosylation is a hallmark of cancer and is an important driver of a malignant phenotype. In prostate cancer, the sialyltransferase ST6GAL1 is upregulated, and studies show ST6GAL1-mediated aberrant sialylation of N-glycans promotes prostate tumour growth and disease progression., Methods: Here, we monitor ST6GAL1 in tumour and serum samples from men with aggressive prostate cancer and using in vitro and in vivo models we investigate the role of ST6GAL1 in prostate cancer bone metastasis., Findings: ST6GAL1 is upregulated in patients with prostate cancer with tumours that have spread to the bone and can promote prostate cancer bone metastasis in vivo. The mechanisms involved are multi-faceted and involve modification of the pre-metastatic niche towards bone resorption to promote the vicious cycle, promoting the development of M2 like macrophages, and the regulation of immunosuppressive sialoglycans. Furthermore, using syngeneic mouse models, we show that inhibiting sialylation can block the spread of prostate tumours to bone., Interpretation: Our study identifies an important role for ST6GAL1 and α2-6 sialylated N-glycans in prostate cancer bone metastasis, provides proof-of-concept data to show that inhibiting sialylation can suppress the spread of prostate tumours to bone, and highlights sialic acid blockade as an exciting new strategy to develop new therapies for patients with advanced prostate cancer., Funding: Prostate Cancer Research and the Mark Foundation For Cancer Research, the Medical Research Council and Prostate Cancer UK., Competing Interests: Declaration of interests JM and ES are shareholders of GlycoScoreDx Ltd and have filed patent applications related to this work (GB patent numbers GB2,594,103, GB2,595,425 and US patent application 17/780,508). J.F.A.P., N.E., E.R. are shareholders of and employed by GlycoTherapeutics B.V.; C.B. and T.J.B. are shareholders of and scientific advisors of GlycoTherapeutics B.V.; S.J.M is a shareholder of and employed by Synvenio B.V.; J.F.A.P.; and T.J.B. are shareholders of Synvenio B.V.; Radboud University and Radboudumc have filed patent applications related to P-SiaFNEtoc (including patent number 11,639,364). MM has filed patents related to Siglec inhibitors (US patent applications 63/421,007 and 63/497,540). All other authors declare that there are no potential competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Published
2024
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48. ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (ST3Gal1) synthesis of Siglec ligands mediates anti-tumour immunity in prostate cancer.

Author

Garnham R, Geh D, Nelson R, Ramon-Gil E, Wilson L, Schmidt EN, Walker L, Adamson B, Buskin A, Hepburn AC, Hodgson K, Kendall H, Frame FM, Maitland N, Coffey K, Strand DW, Robson CN, Elliott DJ, Heer R, Macauley M, Munkley J, Gaughan L, Leslie J, and Scott E

Subjects
Male, Humans, Benzamides pharmacology, Nitriles, Ligands, beta-Galactoside alpha-2,3-Sialyltransferase, Prostatic Neoplasms drug therapy, Phenylthiohydantoin
Abstract

Immune checkpoint blockade has yet to produce robust anti-cancer responses for prostate cancer. Sialyltransferases have been shown across several solid tumours, including breast, melanoma, colorectal and prostate to promote immune suppression by synthesising sialoglycans, which act as ligands for Siglec receptors. We report that ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (ST3Gal1) levels negatively correlate with androgen signalling in prostate tumours. We demonstrate that ST3Gal1 plays an important role in modulating tumour immune evasion through the synthesises of sialoglycans with the capacity to engage the Siglec-7 and Siglec-9 immunoreceptors preventing immune clearance of cancer cells. Here, we provide evidence of the expression of Siglec-7/9 ligands and their respective immunoreceptors in prostate tumours. These interactions can be modulated by enzalutamide and may maintain immune suppression in enzalutamide treated tumours. We conclude that the activity of ST3Gal1 is critical to prostate cancer anti-tumour immunity and provide rationale for the use of glyco-immune checkpoint targeting therapies in advanced prostate cancer., (© 2024. The Author(s).)

Published
2024
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49. Boolean Models of the Transport, Synthesis, and Metabolism of Tryptophan in Escherichia coli.

Author

Deal I, Macauley M, and Davies R

Subjects
Mathematical Concepts, Models, Biological, Homeostasis, Tryptophan, Escherichia coli genetics
Abstract

The tryptophan (trp) operon in Escherichia coli codes for the proteins responsible for the synthesis of the amino acid tryptophan from chorismic acid, and has been one of the most well-studied gene networks since its discovery in the 1960s. The tryptophanase (tna) operon codes for proteins needed to transport and metabolize it. Both of these have been modeled individually with delay differential equations under the assumption of mass-action kinetics. Recent work has provided strong evidence for bistable behavior of the tna operon. The authors of Orozco-Gómez et al. (Sci Rep 9(1):5451, 2019) identified a medium range of tryptophan in which the system has two stable steady-states, and they reproduced these experimentally. In this paper, we will show how a Boolean model can capture this bistability. We will also develop and analyze a Boolean model of the trp operon. Finally, we will combine these two to create a single Boolean model of the transport, synthesis, and metabolism of tryptophan. In this amalgamated model, the bistability disappears, presumably reflecting the ability of the trp operon to produce tryptophan and drive the system toward homeostasis. All of these models have longer attractors that we call "artifacts of synchrony", which disappear in the asynchronous automata. This curiously matches the behavior of a recent Boolean model of the arabinose operon in E. coli, and we discuss some open-ended questions that arise along these lines., (© 2023. The Author(s), under exclusive licence to Society for Mathematical Biology.)

Published
2023
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50. Reproducibility of the computational fluid dynamic analysis of a cerebral aneurysm monitored over a decade.

Author

Paritala PK, Anbananthan H, Hautaniemi J, Smith M, George A, Allenby M, Mendieta JB, Wang J, Maclachlan L, Liang E, Prior M, Yarlagadda PKDV, Winter C, and Li Z

Subjects
Humans, Hydrodynamics, Reproducibility of Results, Hemodynamics, Magnetic Resonance Angiography, Stress, Mechanical, Intracranial Aneurysm diagnostic imaging, Intracranial Aneurysm complications
Abstract

Computational fluid dynamics (CFD) simulations are increasingly utilised to evaluate intracranial aneurysm (IA) haemodynamics to aid in the prediction of morphological changes and rupture risk. However, these models vary and differences in published results warrant the investigation of IA-CFD reproducibility. This study aims to explore sources of intra-team variability and determine its impact on the aneurysm morphology and CFD parameters. A team of four operators were given six sets of magnetic resonance angiography data spanning a decade from one patient with a middle cerebral aneurysm. All operators were given the same protocol and software for model reconstruction and numerical analysis. The morphology and haemodynamics of the operator models were then compared. The segmentation, smoothing factor, inlet and outflow branch lengths were found to cause intra-team variability. There was 80% reproducibility in the time-averaged wall shear stress distribution among operators with the major difference attributed to the level of smoothing. Based on these findings, it was concluded that the clinical applicability of CFD simulations may be feasible if a standardised segmentation protocol is developed. Moreover, when analysing the aneurysm shape change over a decade, it was noted that the co-existence of positive and negative values of the wall shear stress divergence (WSSD) contributed to the growth of a daughter sac., (© 2023. The Author(s).)

Published
2023
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