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1. Simultaneous Kidney and Parathyroid Transplantation in the Management of Genetic Hypoparathyroidism in a Child

Author

Natalie Vallant, MD, PhD, Manish D. Sinha, MRCP, PhD, Moira Cheung, MRCPCH, PhD, Nick Ware, MBBS, MRCPCH, Helen Jones, MB, BChir, Jackie Buck, BM, BS, DCH, FRCPCH, Catherine Boffa, MD, Melita Irving, MRCPH, MD (Res), Paul V. Carroll, MD, MRCPI, FRCP, Johnathan Hubbard, MD, FRCS, EBQ, Refik Gökmen, MRCP, PhD, Lesley Rees, MBChB, MRCP (UK), MD, FRCP, FRCPCH, Petrut Gogalniceanu, PhD, FRCS, and Nicos Kessaris, MBBS, FRCS

Subjects
Surgery, RD1-811
Abstract

Background. Genetically determined hypoparathyroidism can lead to life-threatening episodes of hypocalcemia and, more rarely, to end-stage kidney disease at a young age. Parathyroid allotransplantation is the only curative treatment, and in patients already receiving immunosuppression for kidney transplantation, there may be little additional risk involved. We report the first such case in a child. Methods. An 11-y-old girl, known to have hypoparathyroidism secondary to an activating pathogenic variant in the calcium-sensing receptor, developed end-stage kidney disease and was started on intermittent hemodialysis. Since the age of 2.5 y, she had been receiving treatment with exogenous synthetic parathyroid hormone (PTH). In June 2019, at the age of 11.8 y, she received a living-donor kidney and simultaneous parathyroid gland transplant from her father. The kidney was implanted into the right iliac fossa, followed by implantation of the parathyroid gland into the exposed rectus muscle. Results. The kidney graft showed immediate function while the intrinsic serum PTH level remained low at 3 ng/L. Exogenous PTH infusion was reduced on day 6 posttransplantation to stimulate PTH production by the new gland, which resulted in improving intrinsic PTH concentrations of 28 ng/L by day 9. Twelve months after transplantation, PTH levels remain in normal range and the kidney graft function is stable with a serum creatinine of 110 μmol/L. Conclusions. Simultaneous living donation and transplantation of a kidney and a parathyroid gland into a child is safe and feasible and has the potential to cure primary hypoparathyroidism as well as kidney failure.

Published
2022
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2. Library preparation methodology can influence genomic and functional predictions in human microbiome research

Author

Jones, MB, Highlander, SK, Anderson, EL, Li, W, Dayrit, M, Klitgord, N, Fabani, MM, Seguritan, V, Green, J, Pride, DT, Yooseph, S, Biggs, W, Nelson, KE, and Craig Venter, J

Subjects
MD Multidisciplinary
Abstract

Observations from human microbiome studies are often conflicting or inconclusive. Many factors likely contribute to these issues including small cohort sizes, sample collection, and handling and processing differences. The field of microbiome research is moving from 16S rDNA gene sequencing to a more comprehensive genomic and functional representation through whole-genome sequencing (WGS) of complete communities. Here we performed quantitative and qualitative analyses comparingWGS metagenomic data from human stool specimens using the Illumina Nextera XT and Illumina TruSeq DNA PCR-free kits, and the KAPA Biosystems Hyper Prep PCR and PCR-free systems. Significant differences in taxonomy are observed among the four different next-generation sequencing library preparations using a DNA mock community and a cell control of known concentration. We also revealed biases in error profiles, duplication rates, and loss of reads representing organisms that have a high %G+C content that can significantly impact results. As with all methods, the use of benchmarking controls has revealed critical differences among methods that impact sequencing results and later would impact study interpretation. We recommend that the community adopt PCR-free-based approaches to reduce PCR bias that affects calculations of abundance and to improve assemblies for accurate taxonomic assignment. Furthermore, the inclusion of a known-input cell spike-in control provides accurate quantitation of organisms in clinical samples.

Published
2015

6. The relationship between hair metabolites, air pollution exposure and gestational diabetes mellitus: A longitudinal study from pre-conception to third trimester

Author

Chen, X, Zhao, X, Jones, MB, Harper, A, de Seymour, JV, Yang, Y, Xia, Y, Zhang, T, Qi, H, Gulliver, J, Cannon, RD, Saffery, R, Zhang, H, Han, T-L, Baker, PN, Chen, X, Zhao, X, Jones, MB, Harper, A, de Seymour, JV, Yang, Y, Xia, Y, Zhang, T, Qi, H, Gulliver, J, Cannon, RD, Saffery, R, Zhang, H, Han, T-L, and Baker, PN

Abstract

BACKGROUND: Gestational diabetes mellitus (GDM) is a metabolic condition defined as glucose intolerance with first presentation during pregnancy. Many studies suggest that environmental exposures, including air pollution, contribute to the pathogenesis of GDM. Although hair metabolite profiles have been shown to reflect pollution exposure, few studies have examined the link between environmental exposures, the maternal hair metabolome and GDM. The aim of this study was to investigate the longitudinal relationship (from pre-conception through to the third trimester) between air pollution exposure, the hair metabolome and GDM in a Chinese cohort. METHODS: A total of 1020 women enrolled in the Complex Lipids in Mothers and Babies (CLIMB) birth cohort were included in our study. Metabolites from maternal hair segments collected pre-conception, and in the first, second, and third trimesters were analysed using gas chromatography-mass spectrometry (GC-MS). Maternal exposure to air pollution was estimated by two methods, namely proximal and land use regression (LUR) models, using air quality data from the air quality monitoring station nearest to the participant's home. Logistic regression and mixed models were applied to investigate associations between the air pollution exposure data and the GDM associated metabolites. RESULTS: Of the 276 hair metabolites identified, the concentrations of fourteen were significantly different between GDM cases and non-GDM controls, including some amino acids and their derivatives, fatty acids, organic acids, and exogenous compounds. Three of the metabolites found in significantly lower concentrations in the hair of women with GDM (2-hydroxybutyric acid, citramalic acid, and myristic acid) were also negatively associated with daily average concentrations of PM2.5, PM10, SO2, NO2, CO and the exposure estimates of PM2.5 and NO2, and positively associated with O3. CONCLUSIONS: This study demonstrated that the maternal hair metabolome reflect

Published
2022

7. Obstructive Sleep Apnea in MPS

Author

Abhijit Ricky Pal MBBChir, MA, MD, FRCS(ORL-HNS), Nailah Brown BSc, MPhil, Simon A. Jones MB ChB, MRCPCH, Brian W. Bigger PhD, and Iain A. Bruce MB ChB, MD, FRCS(ORL-HNS)

Subjects
Medicine (General), R5-920
Abstract

The mucopolysaccharidoses (MPSs) are a group of inherited, metabolic disorders characterized by progressive multisystem accumulation of partially degraded glycosaminoglycans. This manifests with multilevel airway obstruction, presenting with obstructive sleep apnea (OSA). We systematically reviewed the literature to determine the severity and prevalence of OSA in MPS based on polysomnography analysis. Fifteen studies with 294 participants met the inclusion criteria for review. The pretreatment prevalence of OSA in MPS was 81% with a mean apnea–hypopnea index (AHI) of 10.4. Patients with MPS I are most significantly affected, with 75% suffering with moderate to severe OSA (mean AHI, 16.6). Enzyme replacement therapy (ERT) results in an almost significant reduction in OSA in MPS I ( P = .06), while adenotonsillar surgery significantly improves AHI ( P = .002). Obstructive sleep apnea least affects MPS III. There is a lack of long-term post-ERT and hematopoietic stem cell transplant data relating to OSA outcomes in this population, with further prospective studies required to determine the ongoing response to treatment.

Published
2015
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8. Supragingival Plaque Microbiome Ecology and Functional Potential in the Context of Health and Disease

Author

Relman, DA, Espinoza, JL, Harkins, DM, Torralba, M, Gomez, A, Highlander, SK, Jones, MB, Leong, P, Saffery, R, Bockmann, M, Kuelbs, C, Inman, JM, Hughes, T, Craig, JM, Nelson, KE, Dupont, CL, Relman, DA, Espinoza, JL, Harkins, DM, Torralba, M, Gomez, A, Highlander, SK, Jones, MB, Leong, P, Saffery, R, Bockmann, M, Kuelbs, C, Inman, JM, Hughes, T, Craig, JM, Nelson, KE, and Dupont, CL

Abstract

To address the question of how microbial diversity and function in the oral cavities of children relates to caries diagnosis, we surveyed the supragingival plaque biofilm microbiome in 44 juvenile twin pairs. Using shotgun sequencing, we constructed a genome encyclopedia describing the core supragingival plaque microbiome. Caries phenotypes contained statistically significant enrichments in specific genome abundances and distinct community composition profiles, including strain-level changes. Metabolic pathways that are statistically associated with caries include several sugar-associated phosphotransferase systems, antimicrobial resistance, and metal transport. Numerous closely related previously uncharacterized microbes had substantial variation in central metabolism, including the loss of biosynthetic pathways resulting in auxotrophy, changing the ecological role. We also describe the first complete Gracilibacteria genomes from the human microbiome. Caries is a microbial community metabolic disorder that cannot be described by a single etiology, and our results provide the information needed for next-generation diagnostic tools and therapeutics for caries.IMPORTANCE Oral health has substantial economic importance, with over $100 billion spent on dental care in the United States annually. The microbiome plays a critical role in oral health, yet remains poorly classified. To address the question of how microbial diversity and function in the oral cavities of children relate to caries diagnosis, we surveyed the supragingival plaque biofilm microbiome in 44 juvenile twin pairs. Using shotgun sequencing, we constructed a genome encyclopedia describing the core supragingival plaque microbiome. This unveiled several new previously uncharacterized but ubiquitous microbial lineages in the oral microbiome. Caries is a microbial community metabolic disorder that cannot be described by a single etiology, and our results provide the information needed for next-generation diag

Published
2018

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

10. The Reality-Sampling Deficit and ADHD: Indication for an Active Technique

Author

Barry Jones Mb BSc ChB MRCPsych

Subjects
Psychiatry and Mental health, Clinical Psychology, Analytic frame, mental disorders, Perspective (graphical), In patient, External reality, Medical prescription, Psychology, Developmental psychology
Abstract

Attention-deficit hyperactivity disorder (ADHD) is a common condition and one that the current evidence base highlights as not being best served by the prescription of medication alone (Jensen et al., 2007). The demand facing clinicians is twofold. For the psychiatrist, there is a need to be open to and accommodating of an analytic perspective of ADHD, as one extending understanding of the condition beyond the neurological. For the analyst, I suggest there is a requirement to be open to altering the analytic frame. It is this latter demand that I shall aim to help answer in this article, by highlighting the existence of a reality-sampling deficit in patients with ADHD. Using clinical examples, I shall examine how the concept of a reality-sampling deficit may aid our understanding of the ADHD child's internal experience and their relationship to external reality. In turn, this will lead us toward some adaptations of analytic technique, with an emphasis more upon process than content and links to mentalizat...

Published
2011

13. Mapping autism risk loci using genetic linkage and chromosomal rearrangements

Author

Szatmari, P, Paterson, AD, Zwaigenbaum, L, Roberts, W, Brian, J, Liu, XQ, Vincent, JB, Skaug, JL, Thompson, AP, Senman, L, Feuk, L, Qian, C, Bryson, SE, Jones, MB, Marshall, CR, Scherer, SW, Vieland, VJ, Bartlett, C, Mangin, LV, Goedken, R, Segre, A, Pericak-Vance, MA, Cuccaro, ML, Gilbert, JR, Wright, HH, Abramson, RK, Betancur, C, Bourgeron, T, Gillberg, C, Leboyer, M, Buxbaum, JD, Davis, KL, Hollander, E, Silverman, JM, Hallmayer, J, Lotspeich, L, Sutcliffe, JS, Haines, JL, Folstein, SE, Piven, J, Wassink, TH, Sheffield, V, Geschwind, DH, Bucan, M, Brown, WT, Cantor, RM, Constantino, JN, Gilliam, TC, Herbert, M, LaJonchere, C, Ledbetter, DH, Lese-Martin, C, Miller, J, Nelson, S, Samango-Sprouse, CA, Spence, S, State, M, Tanzi, RE, Coon, H, Dawson, G, Devlin, B, Estes, A, Flodman, P, Klei, L, McMahon, WM, Minshew, N, Munson, J, Korvatska, E, Rodier, PM, Schellenberg, GD, Smith, M, Spence, MA, Stodgell, C, Tepper, PG, Wijsman, EM, Yu, CE, Rogé, B, Mantoulan, C, Wittemeyer, K, Poustka, A, Felder, B, Klauck, SM, Schuster, C, Poustka, F, Bölte, S, Feineis-Matthews, S, Herbrecht, E, Schmötzer, G, Tsiantis, J, Papanikolaou, K, Maestrini, E, and Bacchelli, E

Subjects
mental disorders
Abstract

Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,168 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs. © 2007 Nature Publishing Group.

Published
2007

15. Seasonal changes in tissue elasticity and water transport efficiency in three co-occurring Mediterranean shrubs under natural long-term CO2 enrichment

Author

Tognetti R, Raschi A, and Jones MB

Subjects
fungi, food and beverages
Abstract

Seasonal changes in hydraulic properties and tissue elasticity were evaluated in Erica arborea L., Myrtus communis L. and Juniperus communis L., three Mediterranean shrubs that differ in adaptations to drought. These parameters were analysed over 12 months under field conditions, by comparing plants grown in the proximity of a natural CO2 spring (about 700 mumol mol(-1) atmospheric CO2 concentration, [CO2]) with plants in ambient conditions. Plants at the CO2-spring site have been growing for generations at elevated [CO2]. At both sites, stem hydraulic and structural properties followed the prevailing climatic constraints. However, these shrub species co-occurring in the same environment differed in their capacity to tolerate water deficits, in xylem efficiency, and in strategies for regulating water movement between plant compartments. Either an increase or a decrease in tissue elasticity was effective in promoting resistance to drought stress, depending on the species. Long-term elevated [CO2] influenced all the studied parameters. Species-dependent differences existed in hydraulic architecture between the CO2-spring plants and control plants of E. arborea and M. communis, while J. communis plants rarely showed differences between sites. Less distinct differences between sites were observed for wood structure. The three species showed somewhat lower tissue elasticity under elevated [CO2], in particular during stress periods. The effects of elevated [CO2] on stem hydraulic pathway and structure and shoot elastic properties persist in the long term, but differ in absolute values and sign among the studied species and with the seasonal course, and thus might alter competitive relations between these shrubs.

Published
2002

21. Influence of climate variables on Cyperus papyrus stomatal conductance in Lubigi wetland, Kampala, Uganda.

Author

Opio, A, Jones, MB, Kansiime, F, and Otiti, T

Subjects
*VAPOUR pressure measurement, *TEMPERATURE measurements, *WETLANDS, *CELL adhesion, *PLANT transpiration
Abstract

Cyperus papyrusforms highly productive wetlands in tropical Africa, but the environmental control of transpirational water loss in wetlands is poorly understood. The influence of climate variables on papyrus stomatal conductance in dry and wet seasons of the year was investigated in a wetland in Kampala, Uganda, in June–December, 2012.In situmeasurements were made of local climate conditions in a papyrus canopy and of bracteole stomatal conductance. Stomatal conductance was highest early in the day and declined as the day progressed, but stomata were more consistently open in the wet season than in the dry season. The daily cycle of stomatal conductance was influenced by temperature, incident radiation and vapour pressure deficit. Stomata were more sensitive to vapour pressure deficit changes during the wet season than in the dry season, closing sharply as vapour pressure deficit increased. This would seem to be a useful strategy for regulating transpiration, as it reduces water loss when the vapour pressure deficit gradient between the leaf intercellular spaces and the atmosphere is greatest. [ABSTRACT FROM AUTHOR]

Published
2015
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32. A cost–benefit framework for assessing advanced manufacturing technology development: A case study

Author

Jones, MB, Webb, PF, Summers, MD, Baguley, P, and Valerdi, R

Abstract

Development of new advanced manufacturing technology for the aerospace industry is critical to enhance the manufacture and assembly of aerospace products. This article presents, verifies and validates a cost–benefit forecasting framework for the initial stages of advanced manufacturing technology development. The framework improves the decision-making process of which potential advanced manufacturing technologies to select and develop from concept to full-scale demonstration. Cost is the first element and is capable of forecasting the advanced manufacturing technology development effort in person-hours and cost of hardware using two parametric cost models. Benefit is the second element and forecasts the advanced manufacturing technology tangible and intangible performance. The proposed framework plots these quantified cost–benefit parameters to present development value advice for a diverse range of advanced manufacturing technologies. A detailed case study evaluating a total of 23 novel aerospace advanced manufacturing technologies verifies the capability and high accuracy of the framework within a large aerospace manufacturing organisation. Further validation is provided by quantifying the responses from 10 advanced manufacturing technology development experts, after utilising the methodology within an industrial setting. The case study demonstrates that quantifying the cost-benefit parameters provides the ability to select advanced manufacturing technologies that generate the best value to a business.

Published
2015
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35. Analgesia and Continuous Propofol Infusion

Author

Jones Mb

Subjects
Text mining, Oncology, business.industry, Anesthesia, Pediatrics, Perinatology and Child Health, medicine, Hematology, business, Propofol, medicine.drug
Published
1996

37. Hepatitis due to nitrofurantoin

Author

Mollison, Lindsay C, primary, Angus, Peter, additional, Richards, Michael, additional, ChB, Robert McL Jones MB, additional, and Ireton, John, additional

Published
1992
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38. A questionnaire to measure health practitioners' attitudes to partnership in medicine taking: LATCon II.

Author

Knapp P, Raynor DK, Thistlethwaite JE, and Jones MB

Abstract

Objectives To revise and improve an existing scale to measure health practitioners' attitudes to partnership in medicine taking and to ascertain the views of medical students, nursing students and pre-registration pharmacists on concordance. Background The traditional model of the practitioner-patient interaction incorporates a practitioner-centred approach, focusing on the disease rather than the patient. The philosophy of 'concordance' (or 'partnership in medicine-taking') puts the patient at the centre of the interaction, with the patient interacting reciprocally with the practitioner. The Leeds Attitude to Concordance (LATCon) scale was developed in 2001 to assess practitioners' and patients' attitudes to concordance. However, thinking on concordance has developed since then and the present study aimed to revise the scale to ensure that it reflected current thinking and also to increase its reliability and validity. Design A pool of potential items was developed and sent to three subject experts for opinion. An attitudinal Likert scale of 31 items was developed. Its completion was followed by statistical item reduction to 20 items. The shorter scale was completed by the same participants 4-6 weeks later. Setting and participants The study was set in a university in the UK. Participants were 183 medical students, nursing students, and pre-registration pharmacists. Results and discussion The study derived a 20 item scale, including five negatively-worded items, with good levels of internal and test-retest reliability. Factor analysis suggested five main factors. A statistically significant difference in attitudes was found between student nurses and medical students, and student nurses and pre-registration pharmacists, with student nurses being more in agreement with the concordant approach. Overall, participants were in agreement with the concordant approach to medicine taking. The UK National Health Service advocates partnership in medical care and is encouraging both practitioners and patients to work to introduce this. There is increased awareness of the patients' perspective by practitioners, but its impact on their practice remains unclear. Education and skills teaching must continue for the benefits of a concordant approach to be seen. The LATCon scale could play a useful role in education and training, and in research assessing the movement towards the new approach. [ABSTRACT FROM AUTHOR]

Published
2009
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44. Serious Violent Offenders: Sentencing, Psychiatry and Law Reform

Author

Dpm., Bs., FRCPsych, Robert Finlay-Jones Mb, and Franzcp

Subjects
Law reform, Law, Sociology, Criminology, Pathology and Forensic Medicine
Abstract

Proceedings of a Conference held 29–31 October 1991. edited by Sally-Anne Gerull and William Lucas. Australian Institute of Criminology Conference Proceedings No. 19. Canberra, ACT, 1993; 269 pp.: recommended retail price $30; ISSN 1034-5086; ISBN 0 642 19258 8.

Published
1993

46. Maternal antecedents for cerebral palsy in extremely preterm babies: a case-control study

Author

*, MD FRCPI FRACP FRCPCH Peter H Gray, ‡, Jones, MB BS Peter, and O'Callaghan, MB BS FRACP Michael J

Abstract

The study aimed to identify significant antenatal risk factors for cerebral palsy (CP) among extremely preterm infants with a matched case-control design. Infants born between 1989 and 1996 at 24 to 27 weeks' gestation who survived to hospital discharge were evaluated: 30 with a proven diagnosis of CP at 2 years corrected for prematurity and 120 control children matched for gestational age without CP. Information on maternal obstetric risk factors and medication was obtained. Matched analyses were performed and odds ratios (OR) and 95% confidence intervals (CI) were calculated. An antenatal diagnosis of intrauterine growth restriction was associated with an increased risk of CP (OR 6.6; 95% CI 1.8 to 25.2), while maternal administration of corticosteroids was associated with a reduced risk of CP (OR 0.4; 95% CI 0.1 to 0.98). A high rate of placental histopathology was achieved but no relation between clinical or histological chorioamnionitis or funisitis and CP was demonstrated. Maternal preeclampsia was not associated with a statistically significant reduction in the risk of CP. It is concluded that a reduced risk of CP in extremely preterm infants is associated with the antenatal use of corticosteroids.

Published
2001

47. The Influence of Salinity on Growth, Water Relations and Photosynthesis in Diplachne fusca (L.) P. Beauv. Ex Roemer & Schultes

Author

Myers, BA, Neales, TF, and Jones, MB

Abstract

The responses to increasing salintiy (in the range 0-420 mol m-3 NaCl) of an Australian accession of the halophytic grass, Diplachne fusca, have been studied in two experiments; in terms of growth, water relations, ion uptake and leaf photosynthesis. Twenty-one to 41 days after salinisation, plant dry weight, leaf area and relative growth rate were decreased at salinities at and above 300 mol m-3. Although salinity in the range 0-200 mol m-3 did not significantly affect growth rate, the highest value was at 200 mol m-3. Towards the end of the sampling period, a recovery of leaf growth rates was greater in plants at salinity levels of 90-200 mol m-3. The salt tolerance of this accession is similar to that reported for other populations of this species. As salinity in the root environment was increased, the osmotic potential of the leaf sap (Ψs) and the difference between leaf water potential and Ψs increased progressively with each harvest. There was no evidence that a lack of a capacity to adjust osmotically was related to the observed inhibition of growth at high salinity levels. It was confirmed that D. fusca possessed a C4 mode of leaf photosynthesis: the maximum assimilation rate (A) observed was high (>50 μmol m-2 s-1), the operating intercellular CO2 concentration (Ci) was approximately 140 μmol mol-1, the initial slope of the A v. CI curve ('carboxylation efficiency') was steep (1.24 μmol m-2 s-1) and the optimum leaf temperature for photosynthesis was approximately 45°C. At high salinities leaf conductance (g) was reduced by 78%. Using an analysis of A v. I and A v. CI relationships, the components of the 'photosynthetic capacity' of the mesophyll reduced by high salinity were Amax, carboxylation efficiency and photorespiration rate. There was no consistent relationship, at three salinity levels, between growth rates and Amax and carboxylation efficiency. It appears unlikely, therefore, that the primary inhibitory effects of salinity on growth are attributable to effects on leaf photosynthetic processes.

Published
1990
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