University of Bergen

About: University of Bergen is a education organization based out in Bergen, Hordaland, Norway. It is known for research contribution in the topics: Population & Large Hadron Collider. The organization has 17106 authors who have published 52492 publications receiving 2009844 citations. The organization is also known as: Universitetet i Bergen & Universitas Bergensis.

Individualized Systems Medicine Strategy to Tailor Treatments for Patients with Chemorefractory Acute Myeloid Leukemia

Abstract: We present an individualized systems medicine (ISM) approach to optimize cancer drug therapies one patient at a time. ISM is based on (i) molecular profiling and ex vivo drug sensitivity and resistance testing (DSRT) of patients9 cancer cells to 187 oncology drugs, (ii) clinical implementation of therapies predicted to be effective, and (iii) studying consecutive samples from the treated patients to understand the basis of resistance. Here, application of ISM to 28 samples from patients with acute myeloid leukemia (AML) uncovered five major taxonomic drug-response subtypes based on DSRT profiles, some with distinct genomic features (e.g., MLL gene fusions in subgroup IV and FLT3 -ITD mutations in subgroup V). Therapy based on DSRT resulted in several clinical responses. After progression under DSRT-guided therapies, AML cells displayed significant clonal evolution and novel genomic changes potentially explaining resistance, whereas ex vivo DSRT data showed resistance to the clinically applied drugs and new vulnerabilities to previously ineffective drugs. Significance: Here, we demonstrate an ISM strategy to optimize safe and effective personalized cancer therapies for individual patients as well as to understand and predict disease evolution and the next line of therapy. This approach could facilitate systematic drug repositioning of approved targeted drugs as well as help to prioritize and de-risk emerging drugs for clinical testing. Cancer Discov; 3(12); 1416–29. ©2013 AACR. See related commentary by Hourigan and Karp, p. 1336 This article is highlighted in the In This Issue feature, p. 1317

Genomic Insights into Methanotrophy: The Complete Genome Sequence of Methylococcus capsulatus (Bath)

Abstract: Methanotrophs are ubiquitous bacteria that can use the greenhouse gas methane as a sole carbon and energy source for growth, thus playing major roles in global carbon cycles, and in particular, substantially reducing emissions of biologically generated methane to the atmosphere. Despite their importance, and in contrast to organisms that play roles in other major parts of the carbon cycle such as photosynthesis, no genome-level studies have been published on the biology of methanotrophs. We report the first complete genome sequence to our knowledge from an obligate methanotroph, Methylococcus capsulatus (Bath), obtained by the shotgun sequencing approach. Analysis revealed a 3.3-Mb genome highly specialized for a methanotrophic lifestyle, including redundant pathways predicted to be involved in methanotrophy and duplicated genes for essential enzymes such as the methane monooxygenases. We used phylogenomic analysis, gene order information, and comparative analysis with the partially sequenced methylotroph Methylobacterium extorquens to detect genes of unknown function likely to be involved in methanotrophy and methylotrophy. Genome analysis suggests the ability of M. capsulatus to scavenge copper (including a previously unreported nonribosomal peptide synthetase) and to use copper in regulation of methanotrophy, but the exact regulatory mechanisms remain unclear. One of the most surprising outcomes of the project is evidence suggesting the existence of previously unsuspected metabolic flexibility in M. capsulatus, including an ability to grow on sugars, oxidize chemolithotrophic hydrogen and sulfur, and live under reduced oxygen tension, all of which have implications for methanotroph ecology. The availability of the complete genome of M. capsulatus (Bath) deepens our understanding of methanotroph biology and its relationship to global carbon cycles. We have gained evidence for greater metabolic flexibility than was previously known, and for genetic components that may have biotechnological potential.

Visualization and Visual Analysis of Multifaceted Scientific Data: A Survey

Abstract: Visualization and visual analysis play important roles in exploring, analyzing, and presenting scientific data. In many disciplines, data and model scenarios are becoming multifaceted: data are often spatiotemporal and multivariate; they stem from different data sources (multimodal data), from multiple simulation runs (multirun/ensemble data), or from multiphysics simulations of interacting phenomena (multimodel data resulting from coupled simulation models). Also, data can be of different dimensionality or structured on various types of grids that need to be related or fused in the visualization. This heterogeneity of data characteristics presents new opportunities as well as technical challenges for visualization research. Visualization and interaction techniques are thus often combined with computational analysis. In this survey, we study existing methods for visualization and interactive visual analysis of multifaceted scientific data. Based on a thorough literature review, a categorization of approaches is proposed. We cover a wide range of fields and discuss to which degree the different challenges are matched with existing solutions for visualization and visual analysis. This leads to conclusions with respect to promising research directions, for instance, to pursue new solutions for multirun and multimodel data as well as techniques that support a multitude of facets.

Injected cytochrome c induces apoptosis

Abstract: Mitochondria, the cell's energy-producing organelles, are thought to play a central role in mediating apoptosis, or programmed cell death Mitochondrial morphology remains intact during the process, the apoptosis-blocking protein Bcl-2 is localized in the outer mitochondrial membrane1, several critical steps in the process require ATP2, and mitochondrial ‘megachannels’ or ‘permeability transitions’ open during apoptosis It has been suggested that mitochondrial constituents leak out through these permeability transition channels, and activate the apoptotic machinery in the cytosol3 Here we show that the injection into cells of a key mitochondrial protein, cytochrome c, activates apoptosis