Detection of Ser/Thr protein phosphatases in Neurospora crassa

Protein phosphorylation is a frequent posttranslational modification regulating cellular processes in eukaryotes. The phosphate content of a protein is determined by the conflicting activities of protein kinases and phosphatases. Protein phosphatases were divided into Ser/Thr and Tyr specific groups, depending on the phosphorylated residue in the substrate molecules. The former group was further classified based on enzymatic criteria (reviewed in Cohen 1989 Ann. Rev. Biochem. 58:453-508). Protein phosphatase 1 (PP1) is inhibited by two heat stable proteins termed inhibitor-1 and -2. Protein phosphatase 2A is inhibited by nanomolar concentration of the tumor promoter okadaic acid. Protein phosphatase 2B (PP2B) - also called calcineurin - is stimulated by Ca-calmodulin, and protein phosphatase 2C (PP2C) is a Mg2+ dependent enzyme. Molecular cloning of the catalytic subunits revealed that PP1-PP2A-PP2B consist of a highly conserved superfamily of proteins

Value-based genomic screening. Exploring genomic screening for chronic diseases using triple value principles

Background: Genomic screening has unique challenges which makes it difficult to easily implement on a wide scale. If the costs, benefits and tradeoffs of investing in genomic screening are not evaluated properly, there is a risk of wasting finite healthcare resources and also causing avoidable harm. Main text: If healthcare professionals - including policy makers, payers and providers - wish to incorporate genomic screening into healthcare while minimizing waste, maximizing benefits, and considering results that matter to patients, using the principles of triple value (allocative, technical, and personal value) could help them to evaluate tough decisions and tradeoffs. Allocative value focuses on the optimal distribution of limited healthcare resources to maximize the health benefits to the entire population while also accounting for all the costs of care delivery. Technical value ensures that for any given condition, the right intervention is chosen and delivered in the right way. Various methods (e.g. ACCE, HTA, and Wilson and Jungner screening criteria) exist that can help identify appropriate genomic applications. Personal value incorporates preference based informed decision making to ensure that patients are informed about the benefits and harms of the choices available to them and to ensure they make choices based on their values and preferences. Conclusions: Using triple value principles can help healthcare professionals make reasoned and tough judgements about benefits and tradeoffs when they are exploring the role genomic screening for chronic diseases could play in improving the health of their patients and populations

Lithologic Control on the Scaling Properties of the First-Order Streams of Drainage Networks: A Monofractal Analysis

The movement of water through the landscape can be investigated at different scales. This study dealt with the interrelation between bedrock lithology and the geometry of the overlying drainage systems. Parameters of fractal analysis, such as fractal dimension and lacunarity, were used to measure and quantify this relationship. The interrelation between bedrock lithology and the geometry of the drainage systems has been widely studied in the last decades. The quantification of this linkage has not yet been clearly established. Several studies have selected river basins or regularly shaped areas as study units, assuming them to be lithologically homogeneous. This study considered irregular distributions of rock types, establishing areas of the soil map (1:25,000) with the same lithologic information as study units. The tectonic stability and the low climatic variability of the study region allowed effective investigation of the lithologic controls on the drainage networks developed on the plutonic rocks, the metamorphic rocks, and the sedimentary materials existing in the study area. To exclude the effect of multiple in- and outflows in the lithologically homogeneous units, we focused this study on the first-order streams of the drainage networks. The geometry of the hydrologic features was quantified through traditional metrics of fluvial geomorphology and scaling parameters of fractal analysis, such as the fractal dimension, the reference density, and the lacunarity. The results demonstrate the scale invariance of both the drainage networks and the set of first-order streams at the study scale and a relationship between scaling in the lithology and the drainage network

Drosophila Uri, a PP1α binding protein, is essential for viability, maintenance of DNA integrity and normal transcriptional activity

<p>Abstract</p> <p>Background</p> <p>Protein phosphatase 1 (PP1) is involved in diverse cellular processes, and is targeted to substrates via interaction with many different protein binding partners. PP1 catalytic subunits (PP1c) fall into PP1α and PP1β subfamilies based on sequence analysis, however very few PP1c binding proteins have been demonstrated to discriminate between PP1α and PP1β.</p> <p>Results</p> <p>URI (unconventional prefoldin RPB5 interactor) is a conserved molecular chaperone implicated in a variety of cellular processes, including the transcriptional response to nutrient signalling and maintenance of DNA integrity. We show that <it>Drosophila </it>Uri binds PP1α with much higher affinity than PP1β, and that this ability to discriminate between PP1c forms is conserved to humans. Most Uri is cytoplasmic, however we found some protein associated with active RNAPII on chromatin. We generated a <it>uri </it>loss of function allele, and show that <it>uri </it>is essential for viability in <it>Drosophila</it>. <it>uri </it>mutants have transcriptional defects, reduced cell viability and differentiation in the germline, and accumulate DNA damage in their nuclei.</p> <p>Conclusion</p> <p>Uri is the first PP1α specific binding protein to be described in <it>Drosophila</it>. Uri protein plays a role in transcriptional regulation. Activity of <it>uri </it>is required to maintain DNA integrity and cell survival in normal development.</p

Shell structure of the neutron-rich isotopes Co 69,71,73

The structures of the neutron-rich Co69,71,73 isotopes were investigated via (p,2p) knockout reactions at the Radioactive Isotope Beam Factory, RIKEN. Isotopes of interest were studied using the DALI2 γ-ray detector array combined with the MINOS target and tracker system. Level schemes were reconstructed using the γ-γ coincidence technique, with tentative spin-parity assignments based on the measured inclusive and exclusive cross sections. Comparison with shell-model calculations using the Lenzi-Nowacki-Poves-Sieja LNPS and PFSDG-U interactions suggests coexistence of spherical and deformed shapes at low excitation energies in the Co69,71,73 isotopes. The distorted-wave impulse approximation (DWIA) framework was used to calculate the single-particle cross sections. These values were compared with the experimental findings

78Ni revealed as a doubly magic stronghold against nuclear deformation

Nuclear magic numbers correspond to fully occupied energy shells of protons or neutrons inside atomic nuclei. Doubly magic nuclei, with magic numbers for both protons and neutrons, are spherical and extremely rare across the nuclear landscape. Although the sequence of magic numbers is well established for stable nuclei, experimental evidence has revealed modifications for nuclei with a large asymmetry between proton and neutron numbers. Here we provide a spectroscopic study of the doubly magic nucleus 78 Ni, which contains fourteen neutrons more than the heaviest stable nickel isotope. We provide direct evidence of its doubly magic nature, which is also predicted by ab initio calculations based on chiral effective-field theory interactions and the quasi-particle random-phase approximation. Our results also indicate the breakdown of the neutron magic number 50 and proton magic number 28 beyond this stronghold, caused by a competing deformed structure. State-of-the-art phenomenological shell-model calculations reproduce this shape coexistence, predicting a rapid transition from spherical to deformed ground states, with 78 Ni as the turning point

betabeta decay of 75Ni^75Ni and the systematics of the low-lying level structure of neutron-rich odd-AA Cu isotopes

International audienceBackground: Detailed spectroscopy of neutron-rich odd-A Cu isotopes is of great importance for studying the shell evolution in the region of Ni78. While there is experimental information on excited states in Cu69−73,77,79 isotopes, the information concerning Cu75 is very limited. Purpose: Experimentally observed single-particle, core-coupling, and proton-hole intruder states in Cu75, will complete the systematics of these states in the chain of isotopes. Method: Excited states in Cu75 were populated in the β decay of Ni75 isotopes. The Ni nuclei were produced by the in-flight fission of U238 projectiles, and were separated, identified, and implanted in a highly segmented Si detector array for the detection of the β-decay electrons. The β-delayed γ rays were detected in a HPGe cluster array. Monte Carlo shell model calculations were performed using the A3DA interaction built on the pfg9/2d5/2 model space for both neutrons and protons. Results: A level scheme of Cu75 was built up to ≈4 MeV by performing a γ-γ coincidence analysis. The excited states below 2 MeV were interpreted based on the systematics of neutron-rich odd-A Cu isotopes and the results of the shell model calculations. Conclusions: The evolution of the single-particle, core-coupling, and proton-hole intruder states in the chain of neutron-rich odd-A Cu isotopes is discussed in the present work, in connection with the newly observed level structure of Cu75