FoxK1 and FoxK2 in insulin regulation of cellular and mitochondrial metabolism

A major target of insulin signaling is the FoxO family of Forkhead transcription factors, which translocate from the nucleus to the cytoplasm following insulin-stimulated phosphorylation. Here we show that the Forkhead transcription factors FoxK1 and FoxK2 are also downstream targets of insulin action, but that following insulin stimulation, they translocate from the cytoplasm to nucleus, reciprocal to the translocation of FoxO1. FoxK1/FoxK2 translocation to the nucleus is dependent on the Akt-mTOR pathway, while its localization to the cytoplasm in the basal state is dependent on GSK3. Knockdown of FoxK1 and FoxK2 in liver cells results in upregulation of genes related to apoptosis and down-regulation of genes involved in cell cycle and lipid metabolism. This is associated with decreased cell proliferation and altered mitochondrial fatty acid metabolism. Thus, FoxK1/K2 are reciprocally regulated to FoxO1 following insulin stimulation and play a critical role in the control of apoptosis, metabolism and mitochondrial function

Proteomic maps of breast cancer subtypes

Systems-wide profiling of breast cancer has almost always entailed RNA and DNA analysis by microarray and sequencing techniques. Marked developments in proteomic technologies now enable very deep profiling of clinical samples, with high identification and quantification accuracy. We analysed 40 oestrogen receptor positive (luminal), Her2 positive and triple negative breast tumours and reached a quantitative depth of >10,000 proteins. These proteomic profiles identified functional differences between breast cancer subtypes, related to energy metabolism, cell growth, mRNA translation and cell-cell communication. Furthermore, we derived a signature of 19 proteins, which differ between the breast cancer subtypes, through support vector machine (SVM)-based classification and feature selection. Remarkably, only three proteins of the signature were associated with gene copy number variations and eleven were also reflected on the mRNA level. These breast cancer features revealed by our work provide novel insights that may ultimately translate to development of subtype-specific therapeutics

A Web-based multimedia collaboratory. Empirical work studies in film archives

This report represents the latest study in the activity on Ecological Information Systems conducted in the Center for Human Machine Interaction situated at Ris National Laboratory and the University of Aarhus. The purpose of this activity is to give a description of the characteristics of work domains that will serve to outline the general context of concern to design of collaboratories. In addition, a set of preliminary implications for the design of a collaboratory are derived from the cognitive work analysis. To anticipate, further research on this approach to the design of collaboratories will show how the preceding analysis is likely to lead to a novel theoretical framework, called Ecological Collaborative Information Systems (ECIS), required for the design of collaboratories. The intention is to illustrate how the general principles of ECIS can be instantiated to develop a concrete design product: A crossdisciplinary and cross-cultural collaboratory to support customer service and professional research in archives. A web based Collaboratory Numerous valuable historic and cultural films and their sources are scattered in various national archives. Knowledge and usage of the multinational film material are severely impeded by access problems. To fully exploit the cultural film heritage internationally, a high degree of cross-disciplinary and international collaboration among professionals working with the film media is required. The Collaboratory for Annotation, Indexing and Retrieval of Digitized Historical Archive Material (Collate) is intended to foster and support collaboration on research, cultural mediation and preservation of films through a distributed multimedia repository. The collaboratory will provide webbased tools and interfac..

Petri Dish-ELISA, a Simple and Economic Technique for Detecting Plant Viruses

A large number of microtiter plates are needed for mass testing of planting material for viruses in seed certification and plant quarantine. In the case of poorly equipped laboratories, problems with availability of microtiter plates have economic implications for the broad acceptance of enzyme-linked immunosorbent assay (ELISA) for e.g. seed health testing in developing countries. In this experiment the potential of an alternative, cheaper technique was investigated. A conventional indirect ELISA procedure was followed for comparison between the polystyrene solid phases of plastic Petri dishes and microtiter plates for detection of three viruses belonging to the Tobamovirus, Comovirus and Potyvirus genera. A wax pen was used to divide the inner surface of a polystyrene Petri dish into many circles or squares. The hydrophobic boundaries thus provided were effective in separating 50 µl-drops throughout the ELISA procedure. In comparative assays of serial dilutions of the three viruses, the ELISA in Petri dishes resulted in similar or higher A405 values than the ELISA carried out in microtiter plates, suggesting a similar or better protein binding capacity of Petri dishes. The perspectives of this alternative method are briefly discussed

Pregnancy outcome in women before and after cervical conisation: population based cohort study

Objectives To examine the consequences of cervical conisation in terms of adverse outcome in subsequent pregnancies

The role of the P1BS element containing promoter-driven genes in Pi transport and homeostasis in plants

Inorganic phosphate (Pi) is an easily accessible form of phosphorus for plants. Plant Pi uptake is usually limited by slow Pi diffusion through the soil which adsorps the Pi quite strong. That is why plants have developed mechanisms to increase Pi availability. There are abiotic (phosphate level) and biotic (mycorrhiza) factors regulating the expression of Pi-responsive genes. Transcription factors binding to the promoters of Pi-responsive genes activate different pathways of Pi transport, distribution and homeostasis maintenance. Pi metabolism involves proteins, as well as microRNAs and other noncoding RNAs

Engineering nanoscale hypersonic phonon transport

Controlling the vibrations in solids is crucial to tailor their mechanical properties and their interaction with light. Thermal vibrations represent a source of noise and dephasing for many physical processes at the quantum level. One strategy to avoid these vibrations is to structure a solid such that it possesses a phononic stop band, i.e., a frequency range over which there are no available mechanical modes. Here, we demonstrate the complete absence of mechanical vibrations at room temperature over a broad spectral window, with a 5.3 GHz wide band gap centered at 8.4 GHz in a patterned silicon nanostructure membrane measured using Brillouin light scattering spectroscopy. By constructing a line-defect waveguide, we directly measure GHz localized modes at room temperature. Our experimental results of thermally excited guided mechanical modes at GHz frequencies provides an eficient platform for photon-phonon integration with applications in optomechanics and signal processing transduction