Institution
University of Aberdeen
Education•Aberdeen, United Kingdom•
About: University of Aberdeen is a education organization based out in Aberdeen, United Kingdom. It is known for research contribution in the topics: Population & Health care. The organization has 21174 authors who have published 49962 publications receiving 2105479 citations. The organization is also known as: Aberdeen University.
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TL;DR: Overall, these data identify fibrillar Aβ as a pathogenic entity powerfully altering neuronal membrane properties such that hyperexcitability of pyramidal cells culminates in epileptiform activity.
Abstract: Alzheimer's disease is associated with an increased risk of unprovoked seizures. However, the underlying mechanisms of seizure induction remain elusive. Here, we performed video-EEG recordings in mice carrying mutant human APPswe and PS1dE9 genes (APdE9 mice) and their wild-type littermates to determine the prevalence of unprovoked seizures. In two recording episodes at the onset of amyloid beta (Abeta) pathogenesis (3 and 4.5 months of age), at least one unprovoked seizure was detected in 65% of APdE9 mice, of which 46% had multiple seizures and 38% had a generalized seizure. None of the wild-type mice had seizures. In a subset of APdE9 mice, seizure phenotype was associated with a loss of calbindin-D28k immunoreactivity in dentate granular cells and ectopic expression of neuropeptide Y in mossy fibers. In APdE9 mice, persistently decreased resting membrane potential in neocortical layer 2/3 pyramidal cells and dentate granule cells underpinned increased network excitability as identified by patch-clamp electrophysiology. At stimulus strengths evoking single-component EPSPs in wild-type littermates, APdE9 mice exhibited decreased action potential threshold and burst firing of pyramidal cells. Bath application (1 h) of Abeta1-42 or Abeta25-35 (proto-)fibrils but not oligomers induced significant membrane depolarization of pyramidal cells and increased the activity of excitatory cell populations as measured by extracellular field recordings in the juvenile rodent brain, confirming the pathogenic significance of bath-applied Abeta (proto-)fibrils. Overall, these data identify fibrillar Abeta as a pathogenic entity powerfully altering neuronal membrane properties such that hyperexcitability of pyramidal cells culminates in epileptiform activity.
543 citations
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TL;DR: Gooday et al. as discussed by the authors showed that the (1→4)-β-linked homopolymer of N-acetyl-D-glucosamine can be stabilised as a rigid ribbon by a statistical mixture of CH2OH orientations, equivalent to half oxygens on each residue.
Abstract: Chitin is the (1→4)-β-linked homopolymer of N-acetyl-D-glucosamine (Fig. 1). The individual polymer chains can be thought of as helices, as each sugar unit is inverted with respect to its neighbors. This leads to their stabilization as rigid ribbons by 03—H … 05 and 06—H … 07 hydrogen bonds. The commonest form of chitin is α-chitin. Its unit cell is of two N,N‵-diacetylchitobiose units of two chains in an antiparallel arrangement. Thus, adjacent polymer chains run in opposite directions, held together by 06—H … 06 hydrogen bonds, and the chains are held in sheets by 07 … H—N hydrogen bonds (Minke and Blackwell, 1978). This gives a statistical mixture of CH2OH orientations, equivalent to half oxygens on each residue, each forming inter- and intramolecular hydrogen bonds. This results in two types of amide groups; all are involved in the interchain C=O … H—N bonds, while half of the groups also serve as acceptors for 06—H … O=C intramolecular bonds. This extensive intermolecular hydrogen bonding leads to a very stable structure, the individual polymer chains eventually giving rise to microfibrils if allowed to crystallize (Gooday, 1983). A less common form of chitin is β-chitin, in which the unit cell is of one N,N‵diacetylchitobiose unit, giving a polymer stabilized as a rigid ribbon, as for α-chitin, by 03—H … 05 intramolecular bonds (Gardner and Blackwell, 1975). Chains are then held together in sheets by C=O … H—N hydrogen bonding of the amide groups and by the CH2OH side chains, forming intersheet hydrogen bonds to the carbonyl oxygens on the next chains (06—H … 07). This gives a structure of parallel poly-N-acetylglucosamine chains with no intersheet hydrogen bonds.
543 citations
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Forschungszentrum Jülich1, University of California, Davis2, Université catholique de Louvain3, ETH Zurich4, University of Southampton5, University of Texas at Austin6, University of Bonn7, James Hutton Institute8, University of California, Irvine9, Université Paris-Saclay10, Desert Research Institute11, Ghent University12, Washington State University13, Katholieke Universiteit Leuven14, University of Aberdeen15, Institut national de la recherche agronomique16, Polish Academy of Sciences17, University of Vienna18, University of Sydney19, University of Stuttgart20, Agricultural Research Service21, University of Naples Federico II22, University of California, Riverside23, Netherlands Environmental Assessment Agency24, Monash University25, University of Tübingen26, University of New England (Australia)27
TL;DR: Key challenges in modeling soil processes are identified, including the systematic incorporation of heterogeneity and uncertainty, the integration of data and models, and strategies for effective integration of knowledge on physical, chemical, and biological soil processes.
Abstract: The remarkable complexity of soil and its importance to a wide range of ecosystem services presents major challenges to the modeling of soil processes. Although major progress in soil models has occurred in the last decades, models of soil processes remain disjointed between disciplines or ecosystem services, with considerable uncertainty remaining in the quality of predictions and several challenges that remain yet to be addressed. First, there is a need to improve exchange of knowledge and experience among the different disciplines in soil science and to reach out to other Earth science communities. Second, the community needs to develop a new generation of soil models based on a systemic approach comprising relevant physical, chemical, and biological processes to address critical knowledge gaps in our understanding of soil processes and their interactions. Overcoming these challenges will facilitate exchanges between soil modeling and climate, plant, and social science modeling communities. It will allow us to contribute to preserve and improve our assessment of ecosystem services and advance our understanding of climate-change feedback mechanisms, among others, thereby facilitating and strengthening communication among scientific disciplines and society. We review the role of modeling soil processes in quantifying key soil processes that shape ecosystem services, with a focus on provisioning and regulating services. We then identify key challenges in modeling soil processes, including the systematic incorporation of heterogeneity and uncertainty, the integration of data and models, and strategies for effective integration of knowledge on physical, chemical, and biological soil processes. We discuss how the soil modeling community could best interface with modern modeling activities in other disciplines, such as climate, ecology, and plant research, and how to weave novel observation and measurement techniques into soil models. We propose the establishment of an international soil modeling consortium to coherently advance soil modeling activities and foster communication with other Earth science disciplines. Such a consortium should promote soil modeling platforms and data repository for model development, calibration and intercomparison essential for addressing contemporary challenges.
542 citations
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TL;DR: It is postulated that Proteobacteria with adherent and invasive properties might exploit host defenses, drive proinflammatory change, alter the intestinal microbiota in favor of dysbiosis and ultimately lead to the development of IBD.
Abstract: The gastrointestinal microbiota has come to the fore in the search for the causes of IBD. This shift has largely been driven by the finding of genetic polymorphisms involved in gastrointestinal innate immunity (particularly polymorphisms in NOD2 and genes involved in autophagy) and alterations in the composition of the microbiota that might result in inflammation (so-called dysbiosis). Microbial diversity studies have continually demonstrated an expansion of the Proteobacteria phylum in patients with IBD. Individual Proteobacteria, in particular (adherent-invasive) Escherichia coli, Campylobacter concisus and enterohepatic Helicobacter, have all been associated with the pathogenesis of IBD. In this Review, we comprehensively describe the various associations of Proteobacteria and IBD. We also examine the importance of pattern recognition in the extracellular innate immune response of the host with particular reference to Proteobacteria, and postulate that Proteobacteria with adherent and invasive properties might exploit host defenses, drive proinflammatory change, alter the intestinal microbiota in favor of dysbiosis and ultimately lead to the development of IBD.
540 citations
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TL;DR: In this paper, the authors present a range of future, spatially explicit, land use change scenarios for the EU15, Norway and Switzerland based on an interpretation of the global storylines of the Intergovernmental Panel on Climate Change (IPCC) that are presented in the special report on emissions scenarios (SRES).
540 citations
Authors
Showing all 21424 results
Name | H-index | Papers | Citations |
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Paul M. Thompson | 183 | 2271 | 146736 |
Feng Zhang | 172 | 1278 | 181865 |
Ian J. Deary | 166 | 1795 | 114161 |
Peter A. R. Ade | 162 | 1387 | 138051 |
David W. Johnson | 160 | 2714 | 140778 |
Pete Smith | 156 | 2464 | 138819 |
Naveed Sattar | 155 | 1326 | 116368 |
John R. Hodges | 149 | 812 | 82709 |
Ruth J. F. Loos | 142 | 647 | 92485 |
Alan J. Silman | 141 | 708 | 92864 |
Michael J. Keating | 140 | 1169 | 76353 |
David Price | 138 | 1687 | 93535 |
John D. Scott | 135 | 625 | 83878 |
Aarno Palotie | 129 | 711 | 89975 |
Rajat Gupta | 126 | 1240 | 72881 |