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Institution

University of East Anglia

EducationNorwich, Norfolk, United Kingdom
About: University of East Anglia is a(n) education organization based out in Norwich, Norfolk, United Kingdom. It is known for research contribution in the topic(s): Population & Climate change. The organization has 13250 authors who have published 37504 publication(s) receiving 1669060 citation(s). The organization is also known as: UEA.


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Paul Burton1, David Clayton2, Lon R. Cardon, Nicholas John Craddock3  +192 moreInstitutions (4)
07 Jun 2007-Nature
TL;DR: This study has demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in theBritish population is generally modest.
Abstract: There is increasing evidence that genome-wide association ( GWA) studies represent a powerful approach to the identification of genes involved in common human diseases. We describe a joint GWA study ( using the Affymetrix GeneChip 500K Mapping Array Set) undertaken in the British population, which has examined similar to 2,000 individuals for each of 7 major diseases and a shared set of similar to 3,000 controls. Case-control comparisons identified 24 independent association signals at P < 5 X 10(-7): 1 in bipolar disorder, 1 in coronary artery disease, 9 in Crohn's disease, 3 in rheumatoid arthritis, 7 in type 1 diabetes and 3 in type 2 diabetes. On the basis of prior findings and replication studies thus-far completed, almost all of these signals reflect genuine susceptibility effects. We observed association at many previously identified loci, and found compelling evidence that some loci confer risk for more than one of the diseases studied. Across all diseases, we identified a large number of further signals ( including 58 loci with single-point P values between 10(-5) and 5 X 10(-7)) likely to yield additional susceptibility loci. The importance of appropriately large samples was confirmed by the modest effect sizes observed at most loci identified. This study thus represents a thorough validation of the GWA approach. It has also demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; has generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in the British population is generally modest. Our findings offer new avenues for exploring the pathophysiology of these important disorders. We anticipate that our data, results and software, which will be widely available to other investigators, will provide a powerful resource for human genetics research.

8,858 citations

Journal ArticleDOI

[...]

23 Sep 2009-Nature
TL;DR: Identifying and quantifying planetary boundaries that must not be transgressed could help prevent human activities from causing unacceptable environmental change, argue Johan Rockstrom and colleagues.
Abstract: Identifying and quantifying planetary boundaries that must not be transgressed could help prevent human activities from causing unacceptable environmental change, argue Johan Rockstrom and colleagues.

7,735 citations

Journal ArticleDOI

[...]

22 Jun 2000-Nature
TL;DR: The present genetic structure of populations, species and communities has been mainly formed by Quaternary ice ages, and genetic, fossil and physical data combined can greatly help understanding of how organisms were so affected.
Abstract: Global climate has fluctuated greatly during the past three million years, leading to the recent major ice ages. An inescapable consequence for most living organisms is great changes in their distribution, which are expressed differently in boreal, temperate and tropical zones. Such range changes can be expected to have genetic consequences, and the advent of DNA technology provides most suitable markers to examine these. Several good data sets are now available, which provide tests of expectations, insights into species colonization and unexpected genetic subdivision and mixture of species. The genetic structure of human populations may be viewed in the same context. The present genetic structure of populations, species and communities has been mainly formed by Quaternary ice ages, and genetic, fossil and physical data combined can greatly help our understanding of how organisms were so affected.

5,877 citations

Journal ArticleDOI

[...]

TL;DR: In this paper, an updated gridded climate dataset (referred to as CRU TS3.10) from monthly observations at meteorological stations across the world's land areas is presented.
Abstract: This paper describes the construction of an updated gridded climate dataset (referred to as CRU TS3.10) from monthly observations at meteorological stations across the world's land areas. Station anomalies (from 1961 to 1990 means) were interpolated into 0.5° latitude/longitude grid cells covering the global land surface (excluding Antarctica), and combined with an existing climatology to obtain absolute monthly values. The dataset includes six mostly independent climate variables (mean temperature, diurnal temperature range, precipitation, wet-day frequency, vapour pressure and cloud cover). Maximum and minimum temperatures have been arithmetically derived from these. Secondary variables (frost day frequency and potential evapotranspiration) have been estimated from the six primary variables using well-known formulae. Time series for hemispheric averages and 20 large sub-continental scale regions were calculated (for mean, maximum and minimum temperature and precipitation totals) and compared to a number of similar gridded products. The new dataset compares very favourably, with the major deviations mostly in regions and/or time periods with sparser observational data. CRU TS3.10 includes diagnostics associated with each interpolated value that indicates the number of stations used in the interpolation, allowing determination of the reliability of values in an objective way. This gridded product will be publicly available, including the input station series (http://www.cru.uea.ac.uk/ and http://badc.nerc.ac.uk/data/cru/). © 2013 Royal Meteorological Society

4,840 citations

Journal ArticleDOI

[...]

Daniel J. Klionsky1, Kotb Abdelmohsen2, Akihisa Abe3, Joynal Abedin4  +2519 moreInstitutions (695)
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

4,756 citations


Authors

Showing all 13250 results

NameH-indexPapersCitations
George Davey Smith2242540248373
Nicholas J. Wareham2121657204896
Cyrus Cooper2041869206782
Kay-Tee Khaw1741389138782
Phillip A. Sharp172614117126
Rory Collins162489193407
William J. Sutherland14896694423
Shah Ebrahim14673396807
Kenneth M. Yamada13944672136
Martin McKee1381732125972
David Price138168793535
Sheila Bingham13651967332
Philip Jones13564490838
Peter M. Rothwell13477967382
Ivan Reid131131885123
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202226
20212,200
20202,121
20191,957
20181,798
20171,865