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.

Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer

Abstract: Objective To evaluate the potential for diagnosing colorectal cancer (CRC) from faecal metagenomes. Design We performed metagenome-wide association studies on faecal samples from 74 patients with CRC and 54 controls from China, and validated the results in 16 patients and 24 controls from Denmark. We further validated the biomarkers in two published cohorts from France and Austria. Finally, we employed targeted quantitative PCR (qPCR) assays to evaluate diagnostic potential of selected biomarkers in an independent Chinese cohort of 47 patients and 109 controls. Results Besides confirming known associations of Fusobacterium nucleatum and Peptostreptococcus stomatis with CRC, we found significant associations with several species, including Parvimonas micra and Solobacterium moorei . We identified 20 microbial gene markers that differentiated CRC and control microbiomes, and validated 4 markers in the Danish cohort. In the French and Austrian cohorts, these four genes distinguished CRC metagenomes from controls with areas under the receiver-operating curve (AUC) of 0.72 and 0.77, respectively. qPCR measurements of two of these genes accurately classified patients with CRC in the independent Chinese cohort with AUC=0.84 and OR of 23. These genes were enriched in early-stage (I–II) patient microbiomes, highlighting the potential for using faecal metagenomic biomarkers for early diagnosis of CRC. Conclusions We present the first metagenomic profiling study of CRC faecal microbiomes to discover and validate microbial biomarkers in ethnically different cohorts, and to independently validate selected biomarkers using an affordable clinically relevant technology. Our study thus takes a step further towards affordable non-invasive early diagnostic biomarkers for CRC from faecal samples.

Truncated GLP-1 (proglucagon 78-107-amide) inhibits gastric and pancreatic functions in man.

Abstract: We studied the effect of intravenous infusion of synthetic truncated GLP-1 (proglucagon 78–107-amide) on fasting and postprandial gastric acid secretion, gastric emptying, and pancreatic secretion of trypsin and lipase in eight normal volunteers using marker dilution and aspiration technique. The infusion resulted in a plasma concentration of 110±14 pmol/liter (mean±SEM). Truncated GLP-1 significantly inhibited postprandial acid secretion by 43±11%, in spite of unchanged plasma gastrin concentration. Gastric emptying rate decreased significantly; 50% emptying time increased from 16±2 min to 30±5 min. Postprandial trypsin and lipase outputs were significantly inhibited by 47±17% and 40±9%, during truncated GLP-1 infusion. Pancreatic enzyme output was linearly correlated to gastric emptying, and truncated GLP-1 did not affect this relationship, suggesting that the effect on pancreatic secretion was secondary to the effect on gastric emptying. Postprandial insulin and glucagon concentrations were similar with and without truncated GLP-1 infusion in spite of significantly lower blood glucose levels (5.2 ±0.2 versus 3.7±0.3), indicating that GLP-1 stimulated insulin secretion and inhibited glucagon secretion. In conclusion, our results suggest that truncated GLP-1 act as a physiological inhibitor of gastric and pancreatic functions in man.

Allocation, plasticity and allometry in plants

Abstract: Allocation is one of the central concepts in modern ecology, providing the basis for different strategies. Allocation in plants has been conceptualized as a proportional or ratio-driven process (‘partitioning’). In this view, a plant has a given amount of resources at any point in time and it allocates these resources to different structures. But many plant ecological processes are better understood in terms of growth and size than in terms of time. In an allometric perspective, allocation is seen as a size-dependent process: allometry is the quantitative relationship between growth and allocation. Therefore most questions of allocation should be posed allometrically, not as ratios or proportions. Plants evolve allometric patterns in response to numerous selection pressures and constraints, and these patterns explain many behaviours of plant populations. In the allometric view, plasticity in allocation can be understood as a change in a plant's allometric trajectory in response to the environment. Some allocation patterns show relatively fixed allometric trajectories, varying in different environments primarily in the speed at which the trajectory is travelled, whereas other allocation patterns show great flexibility in their behaviour at a given size. Because plant growth is often indeterminate and its rate highly influenced by environmental conditions, ‘plasticity in size’ is not a meaningful concept. We need a new way to classify, describe and analyze plant allocation and plasticity because the concepts ‘trait’ and ‘plasticity’ are too broad. Three degrees of plasticity can be distinguished: (1) allometric growth (‘apparent plasticity’), (2) modular proliferation and local physiological adaptation, and (3) integrated plastic responses. Plasticity, which has evolved because it increases individual fitness, can be a disadvantage in plant production systems, where we want to optimize population, not individual, performance.

The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3

Abstract: Methylation of lysine and arginine residues on histone tails affects chromatin structure and gene transcription. Tri- and dimethylation of lysine 9 on histone H3 (H3K9me3/me2) is required for the binding of the repressive protein HP1 and is associated with heterochromatin formation and transcriptional repression in a variety of species. H3K9me3 has long been regarded as a 'permanent' epigenetic mark. In a search for proteins and complexes interacting with H3K9me3, we identified the protein GASC1 (gene amplified in squamous cell carcinoma 1), which belongs to the JMJD2 (jumonji domain containing 2) subfamily of the jumonji family, and is also known as JMJD2C. Here we show that three members of this subfamily of proteins demethylate H3K9me3/me2 in vitro through a hydroxylation reaction requiring iron and alpha-ketoglutarate as cofactors. Furthermore, we demonstrate that ectopic expression of GASC1 or other JMJD2 members markedly decreases H3K9me3/me2 levels, increases H3K9me1 levels, delocalizes HP1 and reduces heterochromatin in vivo. Previously, GASC1 was found to be amplified in several cell lines derived from oesophageal squamous carcinomas, and in agreement with a contribution of GASC1 to tumour development, inhibition of GASC1 expression decreases cell proliferation. Thus, in addition to identifying GASC1 as a histone trimethyl demethylase, we suggest a model for how this enzyme might be involved in cancer development, and propose it as a target for anti-cancer therapy.