Institution
Medical Research Council
Government•London, United Kingdom•
About: Medical Research Council is a government organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Malaria. The organization has 16430 authors who have published 19150 publications receiving 1475494 citations.
Papers published on a yearly basis
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TL;DR: Assessments of monthly fecundity with life table analysis techniques revealed a highly significant, positive relationship between fertility and hamster-oocyte fusion rates that were measured in the presence of the ionophore, A23187, and reactive oxygen species generation was shown to be negatively associated with both the outcome of the sperm-oocytes fusion assay and fertility in vivo.
327 citations
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TL;DR: The results indicate that, in macrophages, HIV-1 exploits a previously undescribed intracellular plasma membrane domain to assemble infectious particles.
Abstract: In macrophages, HIV-1 has been shown to bud into intracellular structures that contain the late endosome marker CD63. We show that these organelles are not endosomes, but an internally sequestered plasma membrane domain. Using immunofluorescence microscopy and immunoelectron microscopy, we find that HIV-1 buds into a compartment that contains the tetraspanins CD81, CD9, and CD53. On uninfected macrophages, these proteins are seen at the cell surface and in intracellular vacuole-like structures with a complex content of vesicles and interconnected membranes that lack endosome markers, including CD63. Significantly, these structures are accessible to small tracers (horseradish peroxidase or ruthenium red) applied to cells at 4°C, indicating that they are connected to the cell surface. HIV assembles on, and accumulates within, these intracellular compartments. Furthermore, CD63 is recruited to the virus-containing structures and incorporated into virions. These results indicate that, in macrophages, HIV-1 exploits a previously undescribed intracellular plasma membrane domain to assemble infectious particles.
327 citations
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Institute of Molecular Pathology and Immunology of the University of Porto1, University of Turin2, Lund University3, Umeå University4, Andalusian School of Public Health5, Cancer Epidemiology Unit6, Medical Research Council7, Aarhus University Hospital8, Utrecht University9, Institut Gustave Roussy10, University of Ioannina11, National and Kapodistrian University of Athens12, University of Tromsø13, International Agency for Research on Cancer14
TL;DR: This study supports a possible protective role of vegetable intake in the intestinal type of GC and the ACO and finds a negative but non significant association between citrus fruit intake and the cardia site while no association was observed with the non‐cardia site.
Abstract: It is considered that fruit and vegetable (FV 95% CI 0.35-1.22 per 100 g increase) and onion and garlic intake (calibrated HR 0.70; 95% CI 0.38-1.29 per 10 g increase). No evidence of association between fresh fruit intake and GC risk was observed. We found a negative but non significant association between citrus fruit intake and the cardia site (calibrated HR 0.77; 95% CI 0.47-1.22 per 100 g increase) while no association was observed with the non-cardia site. Regarding ACO, we found a non significant negative association for vegetable intake and for citrus intake (calibrated HRs 0.72; 95% CI 0.32-1.64 and 0.77; 95% CI 0.46-1.28 per 100 and 50 g increase, respectively). It seems that Hp infection does not modify the effect of F&V intake. Our study supports a possible protective role of vegetable intake in the intestinal type of GC and the ACO. Citrus fruit consumption may have a role in the protection against cardia GC and ACO.
327 citations
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TL;DR: The data show that SOX2 is necessary for the normal development and function of the hypothalamo-pituitary and reproductive axes in both humans and mice.
Abstract: The transcription factor SOX2 is expressed most notably in the developing CNS and placodes, where it plays critical roles in embryogenesis. Heterozygous de novo mutations in SOX2 have previously been associated with bilateral anophthalmia/microphthalmia, developmental delay, short stature, and male genital tract abnormalities. Here we investigated the role of Sox2 in murine pituitary development. Mice heterozygous for a targeted disruption of Sox2 did not manifest eye defects, but showed abnormal anterior pituitary development with reduced levels of growth hormone, luteinizing hormone, and thyroid-stimulating hormone. Consequently, we identified 8 individuals (from a cohort of 235 patients) with heterozygous sequence variations in SOX2. Six of these were de novo mutations, predicted to result in truncated protein products, that exhibited partial or complete loss of function (DNA binding, nuclear translocation, or transactivation). Clinical evaluation revealed that, in addition to bilateral eye defects, SOX2 mutations were associated with anterior pituitary hypoplasia and hypogonadotropic hypogonadism, variable defects affecting the corpus callosum and mesial temporal structures, hypothalamic hamartoma, sensorineural hearing loss, and esophageal atresia. Our data show that SOX2 is necessary for the normal development and function of the hypothalamo-pituitary and reproductive axes in both humans and mice.
326 citations
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University of Sheffield1, University of California, San Francisco2, Medical Research Council3, French Institute of Health and Medical Research4, Tufts University5, Erasmus University Rotterdam6, St. Vincent's Health System7, Stockholm School of Economics8, Mayo Clinic9, Leiden University10, University of Geneva11, University of Manchester12, McGill University13
TL;DR: A further challenge for the future will be to identify risk factors that predict fracture with high validity in different regions of the world and their independent contributions, so that models of risk prediction can be constructed and ultimately validated in independent cohorts.
Abstract: The diagnosis of osteoporosis is made from the measurement of BMD. DXA at the hip is the appropriate diagnostic site. Current clinical guidelines follow the principle that BMD measurements are indicated in individuals with risk factors for fracture and that treatment is recommended in those with a BMD below a critical value. In some countries reimbursement for the costs of treatment depend upon such thresholds for BMD. In Europe the critical value corresponds to a T-score of-2.5 SD, whereas in the USA less stringent criteria are used. It is evident, however, that fracture risk at any given T-score varies markedly according to age and other risk factors. This has led to the view that interventions should be targeted to those at high risk, irrespective of a fixed BMD threshold. In this sense, BMD is utlized as a risk assessment, since in many instances intervention thresholds will be less stringent than the diagnostic threshold. Thus, intervention thresholds need to differ from diagnostic thresholds and be based on fracture probabilities. A 10-year fracture probability appears to be an appropriate time frame. There are a number of problems to be overcome in the development of assessment guidelines. They need to take account of not only the risk of hip fracture but also that of other fractures which contribute significantly to morbidity, particularly in younger individuals. A promising approach is to weight fracture probabilities according to the disutility incurred compared with hip fracture probability. Account also needs to be taken of the large geographic variation in fracture probabilities worldwide. A further challenge for the future will be to identify risk factors that predict fracture with high validity in different regions of the world and their independent contributions, so that models of risk prediction can be constructed and ultimately validated in independent cohorts.
326 citations
Authors
Showing all 16441 results
Name | H-index | Papers | Citations |
---|---|---|---|
Shizuo Akira | 261 | 1308 | 320561 |
Trevor W. Robbins | 231 | 1137 | 164437 |
Richard A. Flavell | 231 | 1328 | 205119 |
George Davey Smith | 224 | 2540 | 248373 |
Nicholas J. Wareham | 212 | 1657 | 204896 |
Cyrus Cooper | 204 | 1869 | 206782 |
Martin White | 196 | 2038 | 232387 |
Frank E. Speizer | 193 | 636 | 135891 |
Michael Rutter | 188 | 676 | 151592 |
Richard Peto | 183 | 683 | 231434 |
Terrie E. Moffitt | 182 | 594 | 150609 |
Kay-Tee Khaw | 174 | 1389 | 138782 |
Chris D. Frith | 173 | 524 | 130472 |
Phillip A. Sharp | 172 | 614 | 117126 |
Avshalom Caspi | 170 | 524 | 113583 |