Institution
University of Birmingham
Education•Birmingham, United Kingdom•
About: University of Birmingham is a education organization based out in Birmingham, United Kingdom. It is known for research contribution in the topics: Population & Context (language use). The organization has 51794 authors who have published 115304 publications receiving 4335316 citations. The organization is also known as: Birmingham University & Uni of Birmingham.
Topics: Population, Context (language use), Health care, Randomized controlled trial, Poison control
Papers published on a yearly basis
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TL;DR: It is shown in an in vitro system that EBV, through expression of the full set of eight virus-coded 'latent' proteins, can protect human B cells from programmed cell death (apoptosis), the deletion mechanism which normally restricts entry into memory.
Abstract: Epstein-Barr virus (EBV), a human herpesvirus, establishes a persistent asymptomatic infection of the circulating B-lymphocyte pool. The mechanism of virus persistence is not understood but, given the limited lifespan of most B cells in vivo, it seems most likely that EBV-infected cells must gain access to the long-lived memory B-cell pool. Here we show in an in vitro system that EBV, through expression of the full set of eight virus-coded 'latent' proteins, can protect human B cells from programmed cell death (apoptosis), the deletion mechanism which normally restricts entry into memory. We have found that EBV-positive Burkitt's lymphoma (BL) cell clones retaining the original tumour cell phenotype and expressing only one of the virus latent proteins, the nuclear antigen EBNA 1, are extremely sensitive to apoptosis; in this respect they resemble the tumour's normal cell of origin found in the germinal centres of lymphoid tissue. By contrast, isogenic BL cell clones which have activated expression of all eight EBV latent proteins are resistant to the induction of apoptosis. The EBV latent proteins should therefore be seen not just as activators of B-cell proliferation but, perhaps more importantly, as mediators of enhanced B-cell survival.
527 citations
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A. Abada1, Marcello Abbrescia2, Marcello Abbrescia3, Shehu S. AbdusSalam4 +1491 more•Institutions (239)
TL;DR: In this article, the authors present the second volume of the Future Circular Collider Conceptual Design Report, devoted to the electron-positron collider FCC-ee, and present the accelerator design, performance reach, a staged operation scenario, the underlying technologies, civil engineering, technical infrastructure, and an implementation plan.
Abstract: In response to the 2013 Update of the European Strategy for Particle Physics, the Future Circular Collider (FCC) study was launched, as an international collaboration hosted by CERN. This study covers a highest-luminosity high-energy lepton collider (FCC-ee) and an energy-frontier hadron collider (FCC-hh), which could, successively, be installed in the same 100 km tunnel. The scientific capabilities of the integrated FCC programme would serve the worldwide community throughout the 21st century. The FCC study also investigates an LHC energy upgrade, using FCC-hh technology. This document constitutes the second volume of the FCC Conceptual Design Report, devoted to the electron-positron collider FCC-ee. After summarizing the physics discovery opportunities, it presents the accelerator design, performance reach, a staged operation scenario, the underlying technologies, civil engineering, technical infrastructure, and an implementation plan. FCC-ee can be built with today’s technology. Most of the FCC-ee infrastructure could be reused for FCC-hh. Combining concepts from past and present lepton colliders and adding a few novel elements, the FCC-ee design promises outstandingly high luminosity. This will make the FCC-ee a unique precision instrument to study the heaviest known particles (Z, W and H bosons and the top quark), offering great direct and indirect sensitivity to new physics.
526 citations
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University of Southern California1, University of Oslo2, Oslo University Hospital3, University of Pittsburgh4, Oxford Health NHS Foundation Trust5, University of Cape Town6, University of Texas Health Science Center at Houston7, Heidelberg University8, Neuroscience Research Australia9, Karolinska Institutet10, City University London11, King's College London12, University of Münster13, Icahn School of Medicine at Mount Sinai14, University of Barcelona15, Brown University16, French Institute of Health and Medical Research17, University of Pennsylvania18, Utrecht University19, University of Göttingen20, University of Amsterdam21, Yale University22, Hartford Hospital23, National University of Ireland, Galway24, University of São Paulo25, University of Edinburgh26, West Los Angeles College27, University of California, Los Angeles28, University of California, Irvine29, Medical College of Wisconsin30, McGovern Institute for Brain Research31, Radboud University Nijmegen32, Northumberland, Tyne and Wear NHS Foundation Trust33, National Institutes of Health34, University of California, San Diego35, Dresden University of Technology36, University of Adelaide37, Semel Institute for Neuroscience and Human Behavior38, Pasteur Institute39, University of Birmingham40, VU University Medical Center41, University of Cincinnati Academic Health Center42, University of New South Wales43, Poznan University of Medical Sciences44, Dalhousie University45, Karolinska University Hospital46, University of Gothenburg47, University of Exeter48, Janssen Pharmaceutica49, Cardiff University50
TL;DR: The largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of bipolar disorder patients is performed, revealing previously undetected associations and providing an extensive analysis of potential confounding variables in neuroimaging studies of BD.
Abstract: Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 × 10-21), left fusiform gyrus (d=-0.288; P=8.25 × 10-21) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10-19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.
525 citations
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Sergey Nejentsev1, Joanna M. M. Howson1, Neil Walker1, Jeffrey S. Szeszko1 +218 more•Institutions (26)
TL;DR: In this article, the major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune.
Abstract: The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods-recursive partitioning and regression-to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; P(combined) = 2.01 x 10(-19) and 2.35 x 10(-13), respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes.
525 citations
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TL;DR: Observations are consistent with the notion that human, and probably rabbit and rat, erythrocyte membranes possess a single polyphosphoinositide phosphodiesterase that is activated by Ca(2+) and that attacks phosphatidylinositol 4-phosphate and phosphatIDylinotol 4,5-bisph phosphate with equal facility.
Abstract: 1. A new assay procedure has been devised for measurement of the Ca2+-activated polyphosphoinositide phosphodiesterase (phosphatidylinositol polyphosphate phosphodiesterase) activity of erythrocyte ghosts. The ghosts are prepared from cells previously incubated with [32P]Pi. They are incubated under appropriate conditions for activation of the phosphodiesterase and the released 32P-labelled inositol bisphosphate and inositol trisphosphate are separated by anion-exchange chromatography on small columns of Dowex-1 (formate form). When necessary, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate can be deacylated and the released phosphodiesters separated on the same columns. 2. The release of both inositol bisphosphate and inositol trisphosphate was rapid in human ghosts, with half of the labelled membrane-bound phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate broken down in only a few minutes in the presence of 0.5mm-Ca2+. For both esters, optimum rates of release were seen at pH6.8–6.9. Mg2+ did not provoke release of either ester. 3. Ca2+ provoked rapid polyphosphoinositide breakdown in rabbit erythrocyte ghosts and a slower breakdown in rat ghosts. Erythrocyte ghosts from pig or ox showed no release of inositol phosphates when exposed to Ca2+. 4. In the presence of Mg2+, the inositol trisphosphate released from phosphatidylinositol 4,5-bisphosphate was rapidly converted into inositol bisphosphate by phosphomonoesterase activity. 5. Neomycin, an aminoglycoside antibiotic that interacts with polyphosphoinositides, inhibited the breakdown of both phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate, with the latter process being appreciably more sensitive to the drug. Phenylmethanesulphonyl fluoride, an inhibitor of serine esterases that is said to inhibit phosphatidylinositol phosphodiesterase, had no effect on the activity of the erythrocyte polyphosphoinositide phosphodiesterase. 6. These observations are consistent with the notion that human, and probably rabbit and rat, erythrocyte membranes possess a single polyphosphoinositide phosphodiesterase that is activated by Ca2+ and that attacks phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate with equal facility. Inhibition of this activity by neomycin seems likely to be due to interactions between neomycin and the polyphosphoinositides, with the greater inhibition of phosphatidylinositol 4,5-bisphosphate breakdown consistent with the greater affinity of the drug for this lipid. In addition, erythrocyte membranes possess Mg2+-dependent phosphomonoesterase that converts inositol 1,4,5-triphosphate into inositol bisphosphate.
524 citations
Authors
Showing all 52384 results
Name | H-index | Papers | Citations |
---|---|---|---|
Nicholas G. Martin | 192 | 1770 | 161952 |
Paul G. Richardson | 183 | 1533 | 155912 |
Jie Zhang | 178 | 4857 | 221720 |
David R. Williams | 178 | 2034 | 138789 |
Masayuki Yamamoto | 171 | 1576 | 123028 |
Gregory Y.H. Lip | 169 | 3159 | 171742 |
Dennis R. Burton | 164 | 683 | 90959 |
J. E. Brau | 162 | 1949 | 157675 |
L. Joseph Melton | 161 | 531 | 97861 |
Paul Emery | 158 | 1314 | 121293 |
Wolfgang Wagner | 156 | 2342 | 123391 |
David H. Adams | 155 | 1613 | 117783 |
Julian Parkhill | 149 | 759 | 104736 |
J. Fraser Stoddart | 147 | 1239 | 96083 |
Robert A. Kyle | 146 | 1221 | 89997 |