Institution
Laboratory of Molecular Biology
Facility•Cambridge, Cambridgeshire, United Kingdom•
About: Laboratory of Molecular Biology is a facility organization based out in Cambridge, Cambridgeshire, United Kingdom. It is known for research contribution in the topics: Gene & RNA. The organization has 19395 authors who have published 24236 publications receiving 2101480 citations.
Topics: Gene, RNA, DNA, Population, Receptor
Papers published on a yearly basis
Papers
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TL;DR: Mutation analysis indicates that excessive nucleostemin, particularly mutants that lack the GTP-regulatory domain, prevents cells from entering mitosis and causes apoptosis in a p53-dependent manner.
Abstract: The unique property of stem cells to self-renew suggests specific mechanisms that regulate their cell-cycle progression. In the present study, we identify a novel protein, nucleostemin, found in the nucleoli of CNS stem cells, embryonic stem cells, and several cancer cell lines and preferentially expressed by other stem cell-enriched populations. It contains an N-terminal basic domain and two GTP-binding motifs. When stem cells differentiate, nucleostemin expression decreases rapidly prior to cell-cycle exit both in vitro and in vivo. Depletion or overexpression of nucleostemin reduces cell proliferation in CNS stem cells and transformed cells. Mutation analysis indicates that excessive nucleostemin, particularly mutants that lack the GTP-regulatory domain, prevents cells from entering mitosis and causes apoptosis in a p53-dependent manner. The N-terminal basic domain specifies nucleolar localization, the p53 interaction, and is required for the cell death caused by overexpression. This work describes a novel nucleolar mechanism that controls the cell-cycle progression in CNS stem cells and cancer cells.
446 citations
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TL;DR: One of the first steps in segmentation of the Drosophila embryo seems to be not the formation of segments, but instead the definition of 14 domains, each of which encroaches into adjacent segments.
Abstract: One of the first steps in segmentation of the Drosophila embryo seems to be not the formation of segments, but instead the definition of 14 domains, each of which encroaches into adjacent segments. We call these domains parasegments and discuss their developmental significance.
444 citations
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TL;DR: Comparison of properties of the system regulating the synthesis of these compounds with those of the amino acid control of RNA biosynthesis suggests that the unusual compounds participate in an early step in the mechanism which leads to the slowing ofRNA biosynthesis during amino acid starvation of stringent strains.
443 citations
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TL;DR: It is reported that mutations affecting the splicing factor S RSF2 directly impair hematopoietic differentiation in vivo, which is not due to SRSF2 loss of function, and this data provide a mechanistic link between a mutant spliceosomal protein, alterations in thesplicing of key regulators, and impaired hematoiesis.
443 citations
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TL;DR: Cryo-electron microscopy structures of tau filaments from the brains of three individuals with chronic traumatic encephalopathy reveal distinct assembled tau conformers, with a novel protofilament fold enclosing hydrophobic molecules, and support the hypothesis that the formation and propagation of distinct conformers ofassembled tau underlie different neurodegenerative diseases.
Abstract: Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy that is associated with repetitive head impacts or exposure to blast waves. First described as punch-drunk syndrome and dementia pugilistica in retired boxers1–3, CTE has since been identified in former participants of other contact sports, ex-military personnel and after physical abuse4–7. No disease-modifying therapies currently exist, and diagnosis requires an autopsy. CTE is defined by an abundance of hyperphosphorylated tau protein in neurons, astrocytes and cell processes around blood vessels8,9. This, together with the accumulation of tau inclusions in cortical layers II and III, distinguishes CTE from Alzheimer’s disease and other tauopathies10,11. However, the morphologies of tau filaments in CTE and the mechanisms by which brain trauma can lead to their formation are unknown. Here we determine the structures of tau filaments from the brains of three individuals with CTE at resolutions down to 2.3 A, using cryo-electron microscopy. We show that filament structures are identical in the three cases but are distinct from those of Alzheimer’s and Pick’s diseases, and from those formed in vitro12–15. Similar to Alzheimer’s disease12,14,16–18, all six brain tau isoforms assemble into filaments in CTE, and residues K274–R379 of three-repeat tau and S305–R379 of four-repeat tau form the ordered core of two identical C-shaped protofilaments. However, a different conformation of the β-helix region creates a hydrophobic cavity that is absent in tau filaments from the brains of patients with Alzheimer’s disease. This cavity encloses an additional density that is not connected to tau, which suggests that the incorporation of cofactors may have a role in tau aggregation in CTE. Moreover, filaments in CTE have distinct protofilament interfaces to those of Alzheimer’s disease. Our structures provide a unifying neuropathological criterion for CTE, and support the hypothesis that the formation and propagation of distinct conformers of assembled tau underlie different neurodegenerative diseases. Cryo-electron microscopy structures of tau filaments from the brains of three individuals with chronic traumatic encephalopathy reveal distinct assembled tau conformers, with a novel protofilament fold enclosing hydrophobic molecules.
442 citations
Authors
Showing all 19431 results
Name | H-index | Papers | Citations |
---|---|---|---|
Robert J. Lefkowitz | 214 | 860 | 147995 |
Ronald M. Evans | 199 | 708 | 166722 |
Tony Hunter | 175 | 593 | 124726 |
Marc G. Caron | 173 | 674 | 99802 |
Mark Gerstein | 168 | 751 | 149578 |
Timothy A. Springer | 167 | 669 | 122421 |
Harvey F. Lodish | 165 | 782 | 101124 |
Ira Pastan | 160 | 1286 | 110069 |
Bruce N. Ames | 158 | 506 | 129010 |
Philip Cohen | 154 | 555 | 110856 |
Gerald M. Rubin | 152 | 382 | 115248 |
Ashok Kumar | 151 | 5654 | 164086 |
Kim Nasmyth | 142 | 294 | 59231 |
Kenneth M. Yamada | 139 | 446 | 72136 |
Harold E. Varmus | 137 | 496 | 76320 |