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.
Topics: Population, Malaria, Poison control, Gene, Antigen
Papers published on a yearly basis
Papers
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TL;DR: The Pre-Linguistic Autism Diagnostic Observation Schedule (PL-ADOS) is a semistructured observation scale designed for use as a diagnostic tool for children less than 6 years old who are not yet using phrase speech and are suspected of having autism.
Abstract: The Pre-Linguistic Autism Diagnostic Observation Schedule (PL-ADOS) is a semistructured observation scale designed for use as a diagnostic tool for children less than 6 years old who are not yet using phrase speech and are suspected of having autism. The PL-ADOS takes approximately 30 minutes to administer and is appropriate for use with this population because of its emphasis on playful interactions and the use of toys designed for young children. Reliability studies indicated that both individual activity ratings and summary ratings could be reliably scored from videotaped assessments by naive raters. Additionally, PL-ADOS scores of nonverbal preschool-aged children referred for clinical diagnosis and classified on the basis of a diagnostic team's clinical judgment, clearly discriminated between autistic and nonautistic developmentally disabled children. The resulting diagnostic algorithm is theoretically linked to diagnostic constructs associated with ICD-10 and DSM-IV criteria for autism.
331 citations
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Centre national de la recherche scientifique1, university of lille2, Paris Descartes University3, French Institute of Health and Medical Research4, Wellcome Trust Sanger Institute5, Claude Bernard University Lyon 16, Institut national de la recherche agronomique7, IRSA8, Medical Research Council9, Université de Montréal10, McGill University11, Wellcome Trust Centre for Human Genetics12, University of Oxford13, University of Nantes14, University of Cambridge15, Imperial College London16
TL;DR: A firm functional link between MTNR1B and T2D risk is established and four complete loss-of-function variants are identified with complete loss of melatonin binding and signaling capabilities.
Abstract: Genome-wide association studies have revealed that common noncoding variants in MTNR1B (encoding melatonin receptor 1B, also known as MT(2)) increase type 2 diabetes (T2D) risk(1,2). Although the strongest association signal was highly significant (P < 1 × 10(-20)), its contribution to T2D risk was modest (odds ratio (OR) of ∼1.10-1.15)(1-3). We performed large-scale exon resequencing in 7,632 Europeans, including 2,186 individuals with T2D, and identified 40 nonsynonymous variants, including 36 very rare variants (minor allele frequency (MAF) <0.1%), associated with T2D (OR = 3.31, 95% confidence interval (CI) = 1.78-6.18; P = 1.64 × 10(-4)). A four-tiered functional investigation of all 40 mutants revealed that 14 were non-functional and rare (MAF < 1%), and 4 were very rare with complete loss of melatonin binding and signaling capabilities. Among the very rare variants, the partial- or total-loss-of-function variants but not the neutral ones contributed to T2D (OR = 5.67, CI = 2.17-14.82; P = 4.09 × 10(-4)). Genotyping the four complete loss-of-function variants in 11,854 additional individuals revealed their association with T2D risk (8,153 individuals with T2D and 10,100 controls; OR = 3.88, CI = 1.49-10.07; P = 5.37 × 10(-3)). This study establishes a firm functional link between MTNR1B and T2D risk.
331 citations
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TL;DR: It is confirmed that reliable Phi values can be derived from the recommended mutations in suitable proteins with 0.6 < DeltaDeltaG(D-N) < 1.7 kcal/mol, and there are many reliable high Phi values.
Abstract: Phi values are used to map structures of protein-folding transition states from changes in free energies of denaturation (DeltaDeltaG(D-N)) and activation on mutation. A recent reappraisal proposed that Phi values for DeltaDeltaG(D-N) 1.7 kcal/mol are often found for large side chains that make dispersed tertiary interactions, especially in hydrophobic cores that are in the process of being formed in the transition state. Conversely, specific local interactions that probe secondary structure tend to have DeltaDeltaG(D-N) approximately 0.5-2 kcal/mol. Discarding Phi values from lower-energy changes discards the crucial information about local interactions and makes transition states appear uniformly diffuse by overemphasizing the dispersed tertiary interactions. The evidence for the 1.7 kcal/mol cutoff was based on mutations that had been deliberately designed to be unsuitable for Phi-value analysis because they are structurally disruptive. We confirm that reliable Phi values can be derived from the recommended mutations in suitable proteins with 0.6 > 2 kcal/mol and that protein-folding transition states do move on the energy surface on mutation.
331 citations
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TL;DR: Overall, age and seizure type had little effect on the chances of achieving remission and this study confirms the good outcome for seizure control in the majority of patients.
331 citations
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TL;DR: The genome sequence of Theileria parva is reported, an apicomplexan pathogen causing economic losses to smallholder farmers in Africa, and its plastid-like genome represents the first example where all apicoplast genes are encoded on one DNA strand.
Abstract: We report the genome sequence of Theileria parva, an apicomplexan pathogen causing economic losses to smallholder farmers in Africa. The parasite chromosomes exhibit limited conservation of gene synteny with Plasmodium falciparum, and its plastid-like genome represents the first example where all apicoplast genes are encoded on one DNA strand. We tentatively identify proteins that facilitate parasite segregation during host cell cytokinesis and contribute to persistent infection of transformed host cells. Several biosynthetic pathways are incomplete or absent, suggesting substantial metabolic dependence on the host cell. One protein family that may generate parasite antigenic diversity is not telomere-associated.
331 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 |