University of Copenhagen

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.

Human circulatory and thermoregulatory adaptations with heat acclimation and exercise in a hot, dry environment.

Abstract: 1. Heat acclimation was induced in eight subjects by asking them to exercise until exhaustion at 60% of maximum oxygen consumption rate (VO2) for 9-12 consecutive days at an ambient temperature of 40 degrees C, with 10% relative humidity (RH). Five control subjects exercised similarly in a cool environment, 20 degrees C, for 90 min for 9-12 days; of these, three were exposed to exercise at 40 degrees C on the first and last day. 2. Acclimation had occurred as seen by the increased average endurance from 48 min to 80 min, the lower rate of rise in the heart rate (HR) and core temperature and the increased sweating. 3. Cardiac output increased significantly from the first to the final heat exposure from 19.6 to 21.4 l min-1; this was possibly due to an increased plasma volume and stroke volume. 4. The mechanism for the increased plasma volume may be an isosmotic volume expansion caused by influx of protein to the vascular compartment, and a sodium retention induced by a significant increase in aldosterone. 5. The exhaustion coincided with, or was elicited when, core temperature reached 39.7 +/- 0.15 degrees C; with progressing acclimation processes it took progressively longer to reach this level. However, at this point we found no reduction in cardiac output, muscle (leg) blood flow, no changes in substrate utilization or availability, and no recognized accumulated 'fatigue' substances. 6. It is concluded that the high core temperature per se, and not circulatory failure, is the critical factor for the exhaustion during exercise in heat stress.

Primary Hepatocytes: Current Understanding of the Regulation of Metabolic Enzymes and Transporter Proteins, and Pharmaceutical Practice for the Use of Hepatocytes in Metabolism, Enzyme Induction, Transporter, Clearance, and Hepatotoxicity Studies

Abstract: This review brings you up-to-date with the hepatocyte research on: 1) in vitro-in vivo correlations of metabolism and clearance; 2) CYP enzyme induction, regulation, and cross-talk using human hepatocytes and hepatocyte-like cell lines; 3) the function and regulation of hepatic transporters and models used to elucidate their role in drug clearance; 4) mechanisms and examples of idiosyncratic and intrinsic hepatotoxicity; and 5) alternative cell systems to primary human hepatocytes. We also report pharmaceutical perspectives of these topics and compare methods and interpretations for the drug development process.

The whole-genome landscape of medulloblastoma subtypes

Abstract: Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.

The oral microbiome – an update for oral healthcare professionals

Abstract: For millions of years, our resident microbes have coevolved and coexisted with us in a mostly harmonious symbiotic relationship. We are not distinct entities from our microbiome, but together we form a 'superorganism' or holobiont, with the microbiome playing a significant role in our physiology and health. The mouth houses the second most diverse microbial community in the body, harbouring over 700 species of bacteria that colonise the hard surfaces of teeth and the soft tissues of the oral mucosa. Through recent advances in technology, we have started to unravel the complexities of the oral microbiome and gained new insights into its role during both health and disease. Perturbations of the oral microbiome through modern-day lifestyles can have detrimental consequences for our general and oral health. In dysbiosis, the finely-tuned equilibrium of the oral ecosystem is disrupted, allowing disease-promoting bacteria to manifest and cause conditions such as caries, gingivitis and periodontitis. For practitioners and patients alike, promoting a balanced microbiome is therefore important to effectively maintain or restore oral health. This article aims to give an update on our current knowledge of the oral microbiome in health and disease and to discuss implications for modern-day oral healthcare.

Formal subdivision of the Holocene Series/Epoch: a Discussion Paper by a Working Group of INTIMATE (Integration of ice‐core, marine and terrestrial records) and the Subcommission on Quaternary Stratigraphy (International Commission on Stratigraphy)

Abstract: This discussion paper, by a Working Group of INTIMATE (Integration of ice-core, marine and terrestrial records) and the Subcommision on Quaternary Stratigraphy (SQS) of the International Commission on Stratigraphy (ICS), considers the prospects for a formal subdivision of the Holocene Series/Epoch. Although previous attempts to subdivide the Holocene have proved inconclusive, recent developments in Quaternary stratigraphy, notably the definition of the Pleistocene-Holocene boundary and the emergence of formal subdivisions of the Pleistocene Series/ Epoch, mean that it may be timely to revisit this matter. The Quaternary literature reveals a widespread but variable informal usage of a tripartite division of the Holocene ('early', 'middle' or 'mid', and 'late'), and we argue that this de facto subdivision should now be formalized to ensure consistency in stratigraphic terminology. We propose an Early-Middle Holocene Boundary at 8200 a BP and a Middle-Late Holocene Boundary at 4200 a BP, each of which is linked to a Global Stratotype Section and Point (GSSP). Should the proposal find a broad measure of support from the Quaternary community, a submission will be made to the International Union of Geological Sciences (IUGS), via the SQS and the ICS, for formal ratification of this subdivision of the Holocene Series/Epoch. Copyright# 2012 John Wiley & Sons, Ltd.