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Cell-specific responses to loss of cyclin-dependent kinases

Inactivation of cyclin-dependent kinases (Cdks) and/or cyclins in mice has changed our view of cell cycle regulation. In general, cells are far more resistant to the loss of Cdks than originally anticipated, suggesting widespread compensation among the Cdks. Early embryonic cells are, so far, not sensitive to the lack of multiple Cdks or cyclins. In contrast, differentiated cells are more dependen

Identification of Yin-Yang regulators and a phosphorylation consensus for male germ cell-associated kinase (MAK)-related kinase

MAK (male germ cell-associated protein kinase) and MRK/ICK (MAK-related kinase/intestinal cell kinase) are human homologs of Ime2p in Saccharomyces cerevisiae and of Mde3 and Pit1 in Schizosaccharomyces pombe and are similar to human cyclin-dependent kinase 2 (CDK2) and extracellular signal-regulated kinase 2 (ERK2). MAK and MRK require dual phosphorylation in a TDY motif catalyzed by an unidentif

The CDK-activating kinase (Cak1p) from budding yeast has an unusual ATP binding pocket

Cak1p is an essential protein kinase that phosphorylates and thereby activates the major cyclin-dependent kinase in budding yeast, Cdc28p. The sequence of Cak1p differs from other members of the protein kinase superfamily in several conserved regions. Cak1p lacks the highly conserved glycine loop motif (GXGXXG) that is found in the nucleotide binding fold of virtually all protein kinases and also

Expression of active-octameric chicken cardiac mitochondrial creatine kinase in Escherichia coli

Sarcomeric mitochondrial creatine kinase (Mi(b)-CK) of chicken was expressed in Escherichia coli as a soluble enzyme by using an inducible phage-T7 promoter. Up to one third of the protein in E. coli extracts consisted of soluble recombinant Mi(b)-CK in an enzymically active form. Approx. 20 mg of nearly-homogenous Mi(b)-CK was isolated in a two-step isolation procedure starting with 1 litre of is

Car free urban districts – Interactions between measures, implementation and experience

Cities and car traffic does not always fit well together. Apart from the well-knownenvironmental problems associated with traffic congestion (e.g. air pollution and noise,climate change and global warming), there are also negative local effects in the form ofincreased risk of traffic accidents, abuse of key resources (energy and time), gender issues interms of accessibility, security and power ove

Slower Skeletal Muscle Oxygenation Kinetics in Adults With Complex Congenital Heart Disease

Background: Adults with complex congenital heart disease (CHD) show reduced aerobic exercise capacity and impaired skeletal muscle function compared with healthy peers. Peripheral muscle factors are presumed to be important contributors to the aerobic capacity, but the mechanisms are poorly understood. The aim of the present study was to investigate differences between adults with CHD and controls

Social capital and knowledge contribution in online user communities : One-way or two-way relationship?

Firms have been increasingly relying on online user communities to access external, distant knowledge and expertise. Previous research on online user communities has largely investigated the influence of users' social capital on their knowledge sharing behavior. In this study, we propose a two-way relationship between social capital and knowledge contribution of users in online user communities. T

Building Knowledge Graphs : Processing Infrastructure and Named Entity Linking

Things such as organizations, persons, or locations are ubiquitous in all texts circulating on the internet, particularly in the news, forum posts, and social media. Today, there is more written material than any single person can read through during a typical lifespan. Automatic systems can help us amplify our abilities to find relevant information, where, ideally, a system would learn knowledge

Magnetic field-assisted chain formation of aerosol nanoparticles

We will present the formation of nanoparticle chains by deposit magnetic iron oxide aerosol nanoparticles in a combined electric and magnetic field. Aerosol methods, in particular spark ablation, provides a good means to produce magnetic nanoparticles with a controllable size and concentration in a broad size range without agglomeration. These aerosol nanoparticles are usually deposited using an e

Building superlattices from aerosol nanoparticles via evaporative self-assembly

Nanoparticle superlattices consisting of densely packed particles with periodic arrangements can exhibit interesting collective properties different from those of individual nanoparticles and thus have attracted great interest in research due to their potential applications in optoelectronic, plasmonic, and magnetic devices. Evaporation-induced self-assembly on solid substrates which employs nanop

Starten på det yrkeslivslånga lärandet som läkare - Den nya svenska grundutbildningen i ett internationellt perspektiv

The Swedish Parliament and Government has recently sanctioned a new 6 year undergraduate medical degree leading directly to license, followed by a 12 month introduction to work as a certified doctor. The undergraduate education is internationally harmonized and the 23 learning outcomes address competence needs in future Swedish and international health-care. Particular attention is given to profes

Effect of epinephrine and mannoheptulose on early and late phases of glucose-stimulated insulin release

Previous studies have revealed the existence of two separate phases in the glucose-stimulated insulin release. Exposure of microdissected mouse islets to mannoheptulose or epinephrine effectively inhibited both the initial transient release and the second persistent phase of insulin secretion. These results suggest that metabolism of glucose is a prerequisite for both phases of insulin release. Th

Loss of Cdk2 and cyclin A2 impairs cell proliferation and tumorigenesis

Cell-cycle inhibition has yet to offer a generally effective approach to cancer treatment, but a full evaluation of different combinations of cell-cycle inhibitors has not been evaluated. Cyclin A2, a core component of the cell cycle, is often aberrantly expressed in cancer where it may impact cell proliferation. In this study, we investigated the role of cyclin A2 in tumorigenesis using a conditi

Cdk2-null mice are resistant to ErbB-2-induced mammary tumorigenesis

The concept of targeting G1 cyclin-dependent kinases (CDKs) in breast cancer treatments is supported by the fact that the genetic ablation of Cdk4 had minimal impacts on normal cell proliferation in majority of cell types, resulting in near-normal mouse development, whereas such loss of Cdk4 completely abrogated ErbB-2/neu-induced mammary tumorigenesis in mice. In most human breast cancer tissues,

Another piece of the p27Kip1 puzzle

How extracellular signals communicate with the cell cycle is poorly understood. In this issue, two papers (Grimmler et al., 2007; Chu et al., 2007) address this problem by reporting phosphorylation of the cyclin-dependent kinase inhibitor p27Kip1 on a tyrosine residue by nonreceptor tyrosine kinases, which decreases p27 stability. This new mechanism could explain how cells enter the cell cycle fro