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Institution

University of Copenhagen

EducationCopenhagen, Denmark
About: University of Copenhagen is a education organization based out in Copenhagen, Denmark. It is known for research contribution in the topics: Population & Medicine. The organization has 57645 authors who have published 149740 publications receiving 5903093 citations. The organization is also known as: Copenhagen University & Københavns Universitet.


Papers
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Journal ArticleDOI
15 Jul 2016-Science
TL;DR: It is estimated that land use and related pressures have already reduced local biodiversity intactness—the average proportion of natural biodiversity remaining in local ecosystems—beyond its recently proposed planetary boundary across 58.1% of the world’s land surface, where 71.4%) of the human population live.
Abstract: Land use and related pressures have reduced local terrestrial biodiversity, but it is unclear how the magnitude of change relates to the recently proposed planetary boundary (“safe limit”). We estimate that land use and related pressures have already reduced local biodiversity intactness—the average proportion of natural biodiversity remaining in local ecosystems—beyond its recently proposed planetary boundary across 58.1% of the world’s land surface, where 71.4% of the human population live. Biodiversity intactness within most biomes (especially grassland biomes), most biodiversity hotspots, and even some wilderness areas is inferred to be beyond the boundary. Such widespread transgression of safe limits suggests that biodiversity loss, if unchecked, will undermine efforts toward long-term sustainable development.

714 citations

Journal ArticleDOI
TL;DR: The observed reduction in CSF clearance was associated with increasing grey-matter concentrations of Aβ in the human brain, consistent with findings in mice showing that decreased glymphatic function leads to Aβ accumulation and the development of neurodegenerative diseases.
Abstract: Summary Background The glymphatic (glial-lymphatic) pathway is a fluid-clearance pathway identified in the rodent brain in 2012. This pathway subserves the flow of CSF into the brain along arterial perivascular spaces and subsequently into the brain interstitium, facilitated by aquaporin 4 (AQP4) water channels. The pathway then directs flow towards the venous perivascular and perineuronal spaces, ultimately clearing solutes from the neuropil into meningeal and cervical lymphatic drainage vessels. In rodents, the glymphatic pathway is predominantly active during sleep, when the clearance of harmful metabolites such as amyloid β (Aβ) increases two-fold relative to the waking state. Glymphatic dysfunction, probably related to perturbed AQP4 expression, has been shown in animal models of traumatic brain injury, Alzheimer's disease, and stroke. The recent characterisations of the glymphatic and meningeal lymphatic systems in rodents and in humans call for revaluation of the anatomical routes for CSF–interstitial fluid flow and the physiological role that these pathways play in CNS health. Recent developments Several features of the glymphatic and meningeal lymphatic systems have been shown to be present in humans. MRI scans with intrathecally administered contrast agent show that CSF flows along pathways that closely resemble the glymphatic system outlined in rodents. Furthermore, PET studies have revealed that Aβ accumulates in the healthy brain after a single night of sleep deprivation, suggesting that the human glymphatic pathway might also be primarily active during sleep. Other PET studies have shown that CSF clearance of Aβ and tau tracers is reduced in patients with Alzheimer's disease compared with healthy controls. The observed reduction in CSF clearance was associated with increasing grey-matter concentrations of Aβ in the human brain, consistent with findings in mice showing that decreased glymphatic function leads to Aβ accumulation. Altered AQP4 expression is also evident in brain tissue from patients with Alzheimer's disease or normal pressure hydrocephalus; glymphatic MRI scans of patients with normal pressure hydrocephalus show reduced CSF tracer entry and clearance. Where next? Research is needed to confirm whether specific factors driving glymphatic flow in rodents also apply to humans. Longitudinal imaging studies evaluating human CSF dynamics will determine whether a causal link exists between reduced brain solute clearance and the development of neurodegenerative diseases. Assessment of glymphatic function after stroke or traumatic brain injury could identify whether this function correlates with neurological recovery. New insights into how behaviour and genetics modify glymphatic function, and how this function decompensates in disease, should lead to the development of new preventive and diagnostic tools and novel therapeutic targets.

713 citations

Journal ArticleDOI
27 Jul 2000-Nature
TL;DR: Evidence is presented that Fringe acts in the Golgi as a glycosyltransferase enzyme that modifies the epidermal growth factor modules of Notch and alters the ability of notch to bind its ligand Delta, and it is suggested that cell-type-specific modification of Glycosylation may provide a general mechanism to regulate ligand–receptor interactions in vivo.
Abstract: Ligands that are capable of activating Notch family receptors are broadly expressed in animal development, but their activity is tightly regulated to allow formation of tissue boundaries. Members of the fringe gene family have been implicated in limiting Notch activation during boundary formation, but the mechanism of Fringe function has not been determined. Here we present evidence that Fringe acts in the Golgi as a glycosyltransferase enzyme that modifies the epidermal growth factor (EGF) modules of Notch and alters the ability of Notch to bind its ligand Delta. Fringe catalyses the addition of N-acetylglucosamine to fucose, which is consistent with a role in the elongation of O-linked fucose O-glycosylation that is associated with EGF repeats. We suggest that cell-type-specific modification of glycosylation may provide a general mechanism to regulate ligand-receptor interactions in vivo.

712 citations

Journal Article
TL;DR: The 2002 OMERACT rheumatoid arthritis magnetic resonance image scoring system (RAMRIS) for evaluation of inflammatory and destructive changes in RA hands and wrists is described, developed by an international MRI-OMERACT group.
Abstract: This article describes the 2002 OMERACT rheumatoid arthritis magnetic resonance image scoring system (RAMRIS) for evaluation of inflammatory and destructive changes in RA hands and wrists, which was developed by an international MRI-OMERACT group. MRI definitions of important RA joint pathologies, and a "core set" of basic MRI sequences for use in RA are also suggested.

712 citations

Journal ArticleDOI
TL;DR: Among men with nonmetastatic, castration‐resistant prostate cancer with a rapidly rising PSA level, enzalutamide treatment led to a clinically meaningful and significant 71% lower risk of metastasis or death than placebo.
Abstract: Background Men with nonmetastatic, castration-resistant prostate cancer and a rapidly rising prostate-specific antigen (PSA) level are at high risk for metastasis. We hypothesized that enz...

711 citations


Authors

Showing all 58387 results

NameH-indexPapersCitations
Michael Karin236704226485
Matthias Mann221887230213
Peer Bork206697245427
Ronald Klein1941305149140
Kenneth S. Kendler1771327142251
Dorret I. Boomsma1761507136353
Ramachandran S. Vasan1721100138108
Unnur Thorsteinsdottir167444121009
Mika Kivimäki1661515141468
Jun Wang1661093141621
Anders Björklund16576984268
Gerald I. Shulman164579109520
Jaakko Kaprio1631532126320
Veikko Salomaa162843135046
Daniel J. Jacob16265676530
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023370
20221,266
202110,694
20209,956
20199,190
20188,620