Institution
Newcastle University
Education•Newcastle upon Tyne, United Kingdom•
About: Newcastle University is a education organization based out in Newcastle upon Tyne, United Kingdom. It is known for research contribution in the topics: Population & Context (language use). The organization has 31772 authors who have published 71187 publications receiving 2539147 citations. The organization is also known as: University of Newcastle upon Tyne.
Papers published on a yearly basis
Papers
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Newcastle University1, Imperial College London2, French Institute of Health and Medical Research3, Mayo Clinic4, Roy J. and Lucille A. Carver College of Medicine5, Mario Negri Institute for Pharmacological Research6, Spanish National Research Council7, Pierre-and-Marie-Curie University8, Paris Descartes University9, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico10
TL;DR: Recommendations for best treatment strategies were discussed at length, providing the evidence base underpinning current treatment options, and knowledge gaps were identified and a prioritized research agenda was proposed to resolve outstanding controversial issues.
462 citations
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TL;DR: This study presents the first direct experimental observations of the fate of random mtDNA mutations in the mammalian germ line and demonstrates the importance of purifying selection in shaping mitochondrial sequence diversity.
Abstract: There is an intense debate concerning whether selection or demographics has been most important in shaping the sequence variation observed in modern human mitochondrial DNA (mtDNA). Purifying selection is thought to be important in shaping mtDNA sequence evolution, but the strength of this selection has been debated, mainly due to the threshold effect of pathogenic mtDNA mutations and an observed excess of new mtDNA mutations in human population data. We experimentally addressed this issue by studying the maternal transmission of random mtDNA mutations in mtDNA mutator mice expressing a proofreading-deficient mitochondrial DNA polymerase. We report a rapid and strong elimination of nonsynonymous changes in protein-coding genes; the hallmark of purifying selection. There are striking similarities between the mutational patterns in our experimental mouse system and human mtDNA polymorphisms. These data show strong purifying selection against mutations within mtDNA protein-coding genes. To our knowledge, our study presents the first direct experimental observations of the fate of random mtDNA mutations in the mammalian germ line and demonstrates the importance of purifying selection in shaping mitochondrial sequence diversity.
462 citations
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TL;DR: This study looked for IF mutations in a panel of 76 patients with HUS, finding two patients, both of whom had reduced serum IF levels and had a history of recurrent HUS after transplantation.
Abstract: Atypical hemolytic uremic syndrome (aHUS) is a disease of complement dysregulation. In approximately 50% of patients, mutations have been described in the genes encoding the complement regulators factor H, MCP, and factor I or the activator factor B. We report here mutations in the central component of the complement cascade, C3, in association with aHUS. We describe 9 novel C3 mutations in 14 aHUS patients with a persistently low serum C3 level. We have demonstrated that 5 of these mutations are gain-of-function and 2 are inactivating. This establishes C3 as a susceptibility factor for aHUS.
461 citations
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TL;DR: It is shown that the partitioning of mtDNA molecules into different cells before and after implantation, followed by the segregation of replicating mtDNA between proliferating primordial germ cells, is responsible for the different levels of heteroplasmy seen in the offspring ofheteroplasmic female mice.
Abstract: Mammalian mitochondrial DNA (mtDNA) is inherited principally down the maternal line, but the mechanisms involved are not fully understood. Females harboring a mixture of mutant and wild-type mtDNA (heteroplasmy) transmit a varying proportion of mutant mtDNA to their offspring. In humans with mtDNA disorders, the proportion of mutated mtDNA inherited from the mother correlates with disease severity. Rapid changes in allele frequency can occur in a single generation. This could be due to a marked reduction in the number of mtDNA molecules being transmitted from mother to offspring (the mitochondrial genetic bottleneck), to the partitioning of mtDNA into homoplasmic segregating units, or to the selection of a group of mtDNA molecules to re-populate the next generation. Here we show that the partitioning of mtDNA molecules into different cells before and after implantation, followed by the segregation of replicating mtDNA between proliferating primordial germ cells, is responsible for the different levels of heteroplasmy seen in the offspring of heteroplasmic female mice.
459 citations
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TL;DR: HCC related mortality is increasing, with typical patients being elderly with metabolic risk factors, but older patients with co-morbidities can do well, managed, within a specialist multidisciplinary team if their cancer is detected pre-symptomatically.
459 citations
Authors
Showing all 32219 results
Name | H-index | Papers | Citations |
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Martin White | 196 | 2038 | 232387 |
Barry Halliwell | 173 | 662 | 159518 |
Adrian L. Harris | 170 | 1084 | 120365 |
Jorge E. Cortes | 163 | 2784 | 124154 |
Frank J. Gonzalez | 160 | 1144 | 96971 |
David W. Bates | 159 | 1239 | 116698 |
Nicholas J. Talley | 158 | 1571 | 90197 |
Hans Lassmann | 155 | 724 | 79933 |
Stephen J. O'Brien | 153 | 1062 | 93025 |
Edmund T. Rolls | 153 | 612 | 77928 |
David J. Brooks | 152 | 1056 | 94335 |
Andrew J. Lees | 140 | 877 | 91605 |
Daniel Thomas | 134 | 846 | 84224 |
Peter Hall | 132 | 1640 | 85019 |
Paul Brennan | 132 | 1221 | 72748 |