المؤلفون: Schober, FA, Tang, JX, Sergeant, K, Moedas, MF, Zierz, CM, Moore, D, Smith, C, Lewis, D, Guha, N, Hopton, S, Falkous, G, Lam, A, Pyle, A, Poulton, J, Gorman, GS, Taylor, RW, Freyer, C, Wredenberg, A

المصدر: Human molecular genetics. 31(12):2049-2062

مصطلحات موضوعية: Medicin och hälsovetenskap

الوصول الحر: http://kipublications.ki.se/Default.aspx?queryparsed=id:149482986Test

المؤلفون: Congreve, JVJ, Shi, Y, Tutt, NC, Taylor, RW, Bumby, C, Dennis, AR, Druiff, H, Weerakonda Arachchilage, D, Durrell, JH, Cardwell, DA

مصطلحات موضوعية: 40 Engineering, 4016 Materials Engineering

الوصف: Abstract The fabrication of large (RE)–Ba–Cu–O single grains [(RE)BCO], where RE = Y, Gd, Eu or Sm, with the complex geometries required for many practical applications is currently limited by the time intensive, complex nature of the grain growth process. In addition, the shapes achievable using established melt processing techniques, such as top seeded melt growth, are constrained significantly by the limited number of post-processing techniques readily available. Machining of these materials is also difficult given their ceramic-like mechanical properties, which makes them both brittle and hard. A potential alternative to the slow and inflexible melt growth processes is to join many small, single grains to form one large composite grain, connected by electrically and mechanically high-performance joints. A reliable joining technique would also greatly reduce the need for post-growth machining processes. In this work we extend our previous investigation of the use of single grain YBCO-Ag as an intermediate joining material to achieve effective and reliable superconducting joints between EuBCO-Ag bulk, single grain superconductors. The technique reported in the earlier studies requires limited specialist equipment and does not require tight process parameter control, since there is no need to re-grow the joining material at the intergrain interface. This technique is of particular interest given that the difference between the peritectic temperatures of the bulk superconductor and the intermediate joining material is large. We report the properties of seven joints engineered at different joining temperatures. The trapped field properties of the resulting joined samples were measured and the microstructure at the position of the joint examined. We demonstrate that this simple and the rapid joining technique makes it possible to manufacture composite grains in an industrially important (RE)BCO bulk superconductor with comparable superconducting properties to ...

وصف الملف: text/xml; application/pdf

العلاقة: https://www.repository.cam.ac.uk/handle/1810/368689Test

الإتاحة: https://www.repository.cam.ac.uk/handle/1810/368689Test

المؤلفون: Congreve, JVJ, Shi, Y, Druiff, H, Dennis, AR, Taylor, RW, Bumby, CW, Cardwell, DA, Durrell, JH

مصطلحات موضوعية: 40 Engineering, 51 Physical Sciences, 5104 Condensed Matter Physics

الوصف: Abstract High-strength permanent magnets are essential for a wide range of technologies, including levitation devices, motors, generators and magnetic separators. Replacing permanent magnets with single grain, bulk superconductors will enable a step-change in the performance of these technologies by providing an order-of-magnitude increase in magnetic field. However, there remain many key challenges to the practical implementation of bulk superconductors, of which size and geometry are the most fundamental. The current limits to the size and geometry of (RE)-Ba–Cu–O single grain, bulk superconductors would be overcome substantially by the ability to fabricate high-quality joints between these technologically important materials. In this work we present new insights into the creation of superconducting joints between single grain bulk YBCO superconductors using a YBCO-Ag intermediate composition. We have investigated the effect of the joint fabrication temperature on the quality of the joint in order to begin to optimise the joint fabrication route for YBCO. We report on 35 joints produced at different joining temperatures as part of this study. The trapped field properties of the resulting joined samples were measured and the microstructure at each joint was examined. We show that this simple and rapid joining technique is robust to small changes in joint fabrication temperature and suggest routes to further optimise this potentially transformative technique.

وصف الملف: text/xml; application/pdf

العلاقة: https://www.repository.cam.ac.uk/handle/1810/364187Test

الإتاحة: https://www.repository.cam.ac.uk/handle/1810/364187Test

المؤلفون: Bisschoff, M, Smuts, I, Dercksen, M, Schoonen, M, Vorster, BC, van der Watt, G, Spencer, C, Naidu, K, Henning, F, Meldau, S, McFarland, R, Taylor, RW, Patel, K, Fassad, MR, Vandrovcova, J, Wanders, RJA, van der Westhuizen, FH

المصدر: Orphanet Journal of Rare Diseases , 19 (1) , Article 15. (2024)

مصطلحات موضوعية: Multiple acyl-CoA dehydrogenase defciency, MADD, Glutaric aciduria type II, ETFDH, Ribofavin, South Africa, International Centre for Genomic Medicine in Neuromuscular Diseases, ICGNMD

الوصف: BACKGROUND: Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder resulting from pathogenic variants in three distinct genes, with most of the variants occurring in the electron transfer flavoprotein-ubiquinone oxidoreductase gene (ETFDH). Recent evidence of potential founder variants for MADD in the South African (SA) population, initiated this extensive investigation. As part of the International Centre for Genomic Medicine in Neuromuscular Diseases study, we recruited a cohort of patients diagnosed with MADD from academic medical centres across SA over a three-year period. The aim was to extensively profile the clinical, biochemical, and genomic characteristics of MADD in this understudied population. METHODS: Clinical evaluations and whole exome sequencing were conducted on each patient. Metabolic profiling was performed before and after treatment, where possible. The recessive inheritance and phase of the variants were established via segregation analyses using Sanger sequencing. Lastly, the haplotype and allele frequencies were determined for the two main variants in the four largest SA populations. RESULTS: Twelve unrelated families (ten of White SA and two of mixed ethnicity) with clinically heterogeneous presentations in 14 affected individuals were observed, and five pathogenic ETFDH variants were identified. Based on disease severity and treatment response, three distinct groups emerged. The most severe and fatal presentations were associated with the homozygous c.[1067G > A];c.[1067G > A] and compound heterozygous c.[976G > C];c.[1067G > A] genotypes, causing MADD types I and I/II, respectively. These, along with three less severe compound heterozygous genotypes (c.[1067G > A];c.[1448C > T], c.[740G > T];c.[1448C > T], and c.[287dupA*];c.[1448C > T]), resulting in MADD types II/III, presented before the age of five years, depending on the time and maintenance of intervention. By contrast, the homozygous c.[1448C > T];c.[1448C > T] ...

وصف الملف: application/pdf

العلاقة: https://discovery.ucl.ac.uk/id/eprint/10186147/1/s13023-023-03014-8.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10186147Test/

الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10186147/1/s13023-023-03014-8.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10186147Test/

المؤلفون: Kaiyrzhanov, R, Rad, A, Lin, S-J, Bertoli-Avella, A, Kallemeijn, WW, Godwin, A, Zaki, MS, Huang, K, Lau, T, Petree, C, Efthymiou, S, Karimiani, EG, Hempel, M, Normand, EA, Rudnik-Schöneborn, S, Schatz, UA, Baggelaar, MP, Ilyas, M, Sultan, T, Alvi, JR, Ganieva, M, Fowler, B, Aanicai, R, Tayfun, GA, Al Saman, A, Alswaid, A, Amiri, N, Asilova, N, Shotelersuk, V, Yeetong, P, Azam, M, Babaei, M, Monajemi, GB, Mohammadi, P, Samie, S, Banu, SH, Pinto Basto, J, Kortüm, F, Bauer, M, Bauer, P, Beetz, C, Garshasbi, M, Issa, AH, Eyaid, W, Ahmed, H, Hashemi, N, Hassanpour, K, Herman, I, Ibrohimov, S, Abdul-Majeed, BA, Imdad, M, Isrofilov, M, Kaiyal, Q, Khan, S, Kirmse, B, Koster, J, Lourenço, CM, Mitani, T, Moldovan, O, Murphy, D, Najafi, M, Pehlivan, D, Rocha, ME, Salpietro, V, Schmidts, M, Shalata, A, Mahroum, M, Talbeya, JK, Taylor, RW, Vazquez, D, Vetro, A, Waterham, HR, Zaman, M, Schrader, TA, Chung, WK, Guerrini, R, Lupski, JR, Gleeson, J, Suri, M, Jamshidi, Y, Bhatia, KP, Vona, B, Schrader, M, Severino, M, Guille, M, Tate, EW, Varshney, GK, Houlden, H, Maroofian, R

الوصف: The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 defects on human pathophysiology. Using exome sequencing and extensive international data sharing efforts, we identified 45 affected individuals from 28 unrelated families (consanguinity 93%) with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants in ACBD6. We generated zebrafish and Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9 and characterized the role of ACBD6 on protein N-myristoylation with myristic acid alkyne (YnMyr) chemical proteomics in the model organisms and human cells, with the latter also being subjected further to ACBD6 peroxisomal localization studies. The affected individuals (23 males and 22 females), aged 1-50 years, typically present with a complex and progressive disease involving moderate-to-severe global developmental delay/intellectual disability (100%) with significant expressive language impairment (98%), movement disorders (97%), facial dysmorphism (95%) and mild cerebellar ataxia (85%) associated with gait impairment (94%), limb spasticity/hypertonia (76%), oculomotor (71%) and behavioural abnormalities (65%), overweight (59%), microcephaly (39%) and epilepsy (33%). The most conspicuous and common movement disorder was dystonia (94%), frequently leading to early-onset progressive postural deformities (97%), limb dystonia (55%) and cervical dystonia (31%). A jerky tremor in the upper limbs (63%), a mild head tremor (59%), parkinsonism/hypokinesia developing with advancing age (32%) and simple motor and vocal tics were among other frequent movement disorders. Midline brain malformations including corpus callosum abnormalities (70%), hypoplasia/agenesis of the anterior commissure (66%), short midbrain and small inferior cerebellar vermis (38% each) as ...

وصف الملف: application/pdf; application/zip

العلاقة: https://openaccess.sgul.ac.uk/id/eprint/115881/6/awad380.pdfTest; https://openaccess.sgul.ac.uk/id/eprint/115881/14/awad380_supplementary_data.zipTest; https://openaccess.sgul.ac.uk/id/eprint/115881/1/awad380.pdfTest; Kaiyrzhanov, R; Rad, A; Lin, S-J; Bertoli-Avella, A; Kallemeijn, WW; Godwin, A; Zaki, MS; Huang, K; Lau, T; Petree, C; et al. Kaiyrzhanov, R; Rad, A; Lin, S-J; Bertoli-Avella, A; Kallemeijn, WW; Godwin, A; Zaki, MS; Huang, K; Lau, T; Petree, C; Efthymiou, S; Karimiani, EG; Hempel, M; Normand, EA; Rudnik-Schöneborn, S; Schatz, UA; Baggelaar, MP; Ilyas, M; Sultan, T; Alvi, JR; Ganieva, M; Fowler, B; Aanicai, R; Tayfun, GA; Al Saman, A; Alswaid, A; Amiri, N; Asilova, N; Shotelersuk, V; Yeetong, P; Azam, M; Babaei, M; Monajemi, GB; Mohammadi, P; Samie, S; Banu, SH; Pinto Basto, J; Kortüm, F; Bauer, M; Bauer, P; Beetz, C; Garshasbi, M; Issa, AH; Eyaid, W; Ahmed, H; Hashemi, N; Hassanpour, K; Herman, I; Ibrohimov, S; Abdul-Majeed, BA; Imdad, M; Isrofilov, M; Kaiyal, Q; Khan, S; Kirmse, B; Koster, J; Lourenço, CM; Mitani, T; Moldovan, O; Murphy, D; Najafi, M; Pehlivan, D; Rocha, ME; Salpietro, V; Schmidts, M; Shalata, A; Mahroum, M; Talbeya, JK; Taylor, RW; Vazquez, D; Vetro, A; Waterham, HR; Zaman, M; Schrader, TA; Chung, WK; Guerrini, R; Lupski, JR; Gleeson, J; Suri, M; Jamshidi, Y; Bhatia, KP; Vona, B; Schrader, M; Severino, M; Guille, M; Tate, EW; Varshney, GK; Houlden, H; Maroofian, R (2024) Bi-allelic ACBD6 variants lead to a neurodevelopmental syndrome with progressive and complex movement disorders. Brain, 147 (4). pp. 1436-1456. ISSN 1460-2156 https://doi.org/10.1093/brain/awad380Test SGUL Authors: Jamshidi, Yalda

الإتاحة: https://doi.org/10.1093/brain/awad380Test
https://openaccess.sgul.ac.uk/id/eprint/115881Test/
https://openaccess.sgul.ac.uk/id/eprint/115881/6/awad380.pdfTest
https://openaccess.sgul.ac.uk/id/eprint/115881/14/awad380_supplementary_data.zipTest
https://openaccess.sgul.ac.uk/id/eprint/115881/1/awad380.pdfTest

المؤلفون: Töpf, A, Cox, D, Zaharieva, IT, Di Leo, V, Sarparanta, J, Jonson, PH, Sealy, IM, Smolnikov, A, White, RJ, Vihola, A, Savarese, M, Merteroglu, M, Wali, N, Laricchia, KM, Venturini, C, Vroling, B, Stenton, SL, Cummings, BB, Harris, E, Marini-Bettolo, C, Diaz-Manera, J, Henderson, M, Barresi, R, Duff, J, England, EM, Patrick, J, Al-Husayni, S, Biancalana, V, Beggs, AH, Bodi, I, Bommireddipalli, S, Bönnemann, CG, Cairns, A, Chiew, M-T, Claeys, KG, Cooper, ST, Davis, MR, Donkervoort, S, Erasmus, CE, Fassad, MR, Genetti, CA, Grosmann, C, Jungbluth, H, Kamsteeg, E-J, Lornage, X, Löscher, WN, Malfatti, E, Manzur, A, Martí, P, Mongini, TE, Muelas, N, Nishikawa, A, O'Donnell-Luria, A, Ogonuki, N, O'Grady, GL, O'Heir, E, Paquay, S, Phadke, R, Pletcher, BA, Romero, NB, Schouten, M, Shah, S, Smuts, I, Sznajer, Y, Tasca, G, Taylor, RW, Tuite, A, Van den Bergh, P, VanNoy, G, Voermans, NC, Wanschitz, JV, Wraige, E, Yoshimura, K, Oates, EC, Nakagawa, O, Nishino, I, Laporte, J, Vilchez, JJ, MacArthur, DG, Sarkozy, A, Cordell, HJ, Udd, B, Busch-Nentwich, EM, Muntoni, F, Straub, V

مصطلحات موضوعية: Animals, Humans, Male, Connectin, Muscle, Skeletal, Muscular Diseases, Mutation, Zebrafish

الوصف: In digenic inheritance, pathogenic variants in two genes must be inherited together to cause disease. Only very few examples of digenic inheritance have been described in the neuromuscular disease field. Here we show that predicted deleterious variants in SRPK3, encoding the X-linked serine/argenine protein kinase 3, lead to a progressive early onset skeletal muscle myopathy only when in combination with heterozygous variants in the TTN gene. The co-occurrence of predicted deleterious SRPK3/TTN variants was not seen among 76,702 healthy male individuals, and statistical modeling strongly supported digenic inheritance as the best-fitting model. Furthermore, double-mutant zebrafish (srpk3-/-; ttn.1+/-) replicated the myopathic phenotype and showed myofibrillar disorganization. Transcriptome data suggest that the interaction of srpk3 and ttn.1 in zebrafish occurs at a post-transcriptional level. We propose that digenic inheritance of deleterious changes impacting both the protein kinase SRPK3 and the giant muscle protein titin causes a skeletal myopathy and might serve as a model for other genetic diseases.

وصف الملف: 395 - 407

العلاقة: Nat Genet; Töpf, A., Cox, D., Zaharieva, I.T. et al. Digenic inheritance involving a muscle-specific protein kinase and the giant titin protein causes a skeletal muscle myopathy. Nat Genet 56, 395–407 (2024). https://doi.org/10.1038/s41588-023-01651-0Test; https://qmro.qmul.ac.uk/xmlui/handle/123456789/96240Test

الإتاحة: https://doi.org/10.1038/s41588-023-01651-0Test
https://qmro.qmul.ac.uk/xmlui/handle/123456789/96240Test

المؤلفون: Maas, RR, Iwanicka-Pronicka, K, Ucar, SK, Alhaddad, B, AlSayed, M, Al-Owain, MA, Al-Zaidan, HI, Balasubramaniam, S, Baric, I, Bubshait, DK, Burlina, A, Christodoulou, J, Chung, WK, Colombo, R, Darin, N, Freisinger, P, Silva, MTG, Grunewald, S, Haack, TB, van Hasselt, PM, Hikmat, O, Horster, F, Isohanni, P, Ramzan, K, Kovacs-Nagy, R, Krumina, Z, Martin-Hernandez, E, Mayr, JA, McClean, P, De Meirleir, L, Naess, K, Ngu, LH, Pajdowska, M, Rahman, S, Riordan, G, Riley, L, Roeben, B, Rutsch, F, Santer, R, Schiff, M, Seders, M, Sequeira, S, Sperl, W, Staufner, C, Synofzik, M, Taylor, RW, Trubicka, J, Tsiakas, K, Unal, O, Wassmer, E, Wedatilake, Y, Wolff, T, Prokisch, H, Morava, E, Pronicka, E, Wevers, RA, de Brouwer, AP, Wortmann, SB

المصدر: Annals of neurology. 82(6):1004-1015

مصطلحات موضوعية: Medicin och hälsovetenskap

الوصول الحر: http://kipublications.ki.se/Default.aspx?queryparsed=id:137244001Test

المؤلفون: Johnson, BJ, Hunter, KE, Golley, RK, Chadwick, P, Barba, A, Aberoumand, M, Libesman, S, Askie, L, Taylor, RW, Robledo, KP, Mihrshahi, S, O'Connor, DA, Hayes, AJ, Wolfenden, L, Wood, CT, Baur, LA, Rissel, C, Staub, LP, Taki, S, Smith, W, Sue-See, M, Marschner, IC, Espinoza, D, Thomson, JL, Larsen, JK, Verbestel, V, Stough, CO, Salvy, SJ, O'Reilly, SL, Karssen, LT, Rasmussen, FE, Messito, MJ, Gross, RS, Bryant, M, Paul, IM, Wen, LM, Hesketh, KD, Acero, CG, Campbell, K, Overby, NC, Linares, AM, Wasser, HM, Joshipura, KJ, Palacios, C, Maffeis, C, Thompson, AL, Ghaderi, A, Lakshman, R, Banna, JC, Oken, E, Rivera, MC, Perez-Exposito, AB, Taylor, BJ, Savage, JS, Roed, M, Goran, M, de la Haye, K, Anzman-Frasca, S, Seidler, AL

المصدر: BMJ open. 12(1):e048165

مصطلحات موضوعية: Medicin och hälsovetenskap

الوصول الحر: http://kipublications.ki.se/Default.aspx?queryparsed=id:148693335Test

المؤلفون: Hunter, KE, Johnson, BJ, Askie, L, Golley, RK, Baur, LA, Marschner, IC, Taylor, RW, Wolfenden, L, Wood, CT, Mihrshahi, S, Hayes, AJ, Rissel, C, Robledo, KP, O'Connor, DA, Espinoza, D, Staub, LP, Chadwick, P, Taki, S, Barba, A, Libesman, S, Aberoumand, M, Smith, WA, Sue-See, M, Hesketh, KD, Thomson, JL, Bryant, M, Paul, IM, Verbestel, V, Stough, CO, Wen, LM, Larsen, JK, O'Reilly, SL, Wasser, HM, Savage, JS, Ong, KK, Salvy, SJ, Messito, MJ, Gross, RS, Karssen, LT, Rasmussen, FE, Campbell, K, Linares, AM, Overby, NC, Palacios, C, Joshipura, KJ, Acero, CG, Lakshman, R, Thompson, AL, Maffeis, C, Oken, E, Ghaderi, A, Rivera, MC, Perez-Exposito, AB, Banna, JC, de la Haye, K, Goran, M, Roed, M, Anzman-Frasca, S, Taylor, BJ, Seidler, AL

المصدر: BMJ open. 12(1):e048166

مصطلحات موضوعية: Medicin och hälsovetenskap

الوصول الحر: http://kipublications.ki.se/Default.aspx?queryparsed=id:148723237Test

المؤلفون: Tuppen, HAL, Naess, K, Kennaway, NG, Al-Dosary, M, Lesko, N, Yarham, JW, Bruhn, H, Wibom, R, Nennesmo, I, Weleber, RG, Blakely, EL, Taylor, RW, McFarland, R

المصدر: European journal of human genetics : EJHG. 20(8):897-904

مصطلحات موضوعية: Medicin och hälsovetenskap

الوصول الحر: http://kipublications.ki.se/Default.aspx?queryparsed=id:124980413Test