Cryo-EM of nucleosome core particle interactions in trans

Nucleosomes, the basic unit of chromatin, are repetitively spaced along DNA and regulate genome expression and maintenance. The long linear chromatin molecule is extensively condensed to fit DNA inside the nucleus. How distant nucleosomes interact to build tertiary chromatin structure remains elusive. In this study, we used cryo-EM to structurally characterize different states of long range nucleosome core particle (NCP) interactions. Our structures show that NCP pairs can adopt multiple conformations, but, commonly, two NCPs are oriented with the histone octamers facing each other. In this conformation, the dyad of both nucleosome core particles is facing the same direction, however, the NCPs are laterally shifted and tilted. The histone octamer surface and histone tails in trans NCP pairs remain accessible to regulatory proteins. The overall conformational flexibility of the NCP pair suggests that chromatin tertiary structure is dynamic and allows access of various chromatin modifying machineries to nucleosomes

Structural rearrangements of the histone octamer translocate DNA

Nucleosomes, the basic unit of chromatin, package and regulate expression of eukaryotic genomes. Nucleosomes are highly dynamic and are remodeled with the help of ATP-dependent remodeling factors. Yet, the mechanism of DNA translocation around the histone octamer is poorly understood. In this study, we present several nucleosome structures showing histone proteins and DNA in different organizational states. We observe that the histone octamer undergoes conformational changes that distort the overall nucleosome structure. As such, rearrangements in the histone core a-helices and DNA induce strain that distorts and moves DNA at SHL 2. Distortion of the nucleosome structure detaches histone a-helices from the DNA, leading to their rearrangement and DNA translocation. Biochemical assays show that cross-linked histone octamers are immobilized on DNA, indicating that structural changes in the octamer move DNA. This intrinsic plasticity of the nucleosome is exploited by chromatin remodelers and might be used by other chromatin machineries

The Cost of Superconducting Magnets as a Function of Stored Energy and Design Magnetic Induction Times the Field Volume

By various theorems one can relate the capital cost of superconducting magnets to the magnetic energy stored within that magnet. This is particularly true for magnet where the cost is dominated by the structure needed to carry the magnetic forces. One can also relate the cost of the magnet to the product of the magnetic induction and the field volume. The relationship used to estimate the cost the magnet is a function of the type of magnet it is. This paper updates the cost functions given in two papers that were published in the early 1990 s. The costs (escalated to 2007 dollars) of large numbers of LTS magnets are plotted against stored energy and magnetic field time field volume. Escalated costs for magnets built since the early 1990 s are added to the plots

A Catalogue of Morphologically Classified Galaxies from the Sloan Digital Sky Survey: North Equatorial Region

We present a catalogue of morphologically classified bright galaxies in the north equatorial stripe (230 deg$^2$) derived from the Third Data Release of the Sloan Digital Sky Survey (SDSS). Morphological classification is performed by visual inspection of images in the $g$ band. The catalogue contains 2253 galaxies complete to a magnitude limit of $r=16$ after Galactic extinction correction, selected from 2658 objects that are judged as extended in the photometric catalogue in the same magnitude limit. 1866 galaxies in our catalogue have spectroscopic information. A brief statistical analysis is presented for the frequency of morphological types and mean colours in the catalogue. A visual inspection of the images reveals that the rate of interacting galaxies in the local Universe is approximately 1.5% in the $r\le16$ sample. A verification is made for the photometric catalogue generated by the SDSS, especially as to its bright end completeness.Comment: Accepted for publication in Astronomical Journal. Table 2 available at http://www.icrr.u-tokyo.ac.jp/~fukugita/MCGpaper/table2.tx

Using Technology to Serve the Agricultural Community in the Western Cape Province of South Africa

Abstract The Western Cape Department of Agriculture has a team of agricultural experts using novel approaches to address the challenges faced by South African agriculture. The objective of this paper is to describe some of the innovative research and technologies, and methods of technology transfer, used to better serve the agricultural community. The spectrum of technologies implemented includes new research on breeding (biotechnology); new approaches to conservation agriculture; remote sensing satellite and spatial information for improved decision making, such as the spatial intelligence project and FruitLook; Agricultural Integrated Management System; and technology to manage and disseminate information, such as smart (digital) pen and paper technology and Agri-Touch. The paper is an introduction to some of the cutting-edge research and technologies and new methods of communication, information dissemination and decision making support that serves the agricultural community in a tangible way. Keywords: Technology, Biotechnology, Conservation Agriculture, Remote Sensing, Information Disseminatio

HI Selected Galaxies in the Sloan Digital Sky Survey I: Optical Data

We present the optical data for 195 HI-selected galaxies that fall within both the Sloan Digital Sky Survey (SDSS) and the Parkes Equatorial Survey (ES). The photometric quantities have been independently recomputed for our sample using a new photometric pipeline optimized for large galaxies, thus correcting for SDSS's limited reliability for automatic photometry of angularly large or low surface brightness (LSB) galaxies. We outline the magnitude of the uncertainty in the SDSS catalog-level photometry and derive a quantitative method for correcting the over-sky subtraction in the SDSS photometric pipeline. The main thrust of this paper is to present the ES/SDSS sample and discuss the methods behind the improved photometry, which will be used in future scientific analysis. We present the overall optical properties of the sample and briefly compare to a volume-limited, optically-selected sample. Compared to the optically-selected SDSS sample (in the similar volume), HI-selected galaxies are bluer and more luminous (fewer dwarf ellipticals and more star formation). However, compared to typical SDSS galaxy studies, which have their own selection effects, our sample is bluer, fainter and less massive.Comment: 14 pages, 8 Figures, accepted for publication in AJ. Complete tables will be available in the AJ electronic version and on the Vizier sit

Mobilizing management knowledge in healthcare : institutional imperatives and professional and organizational mediating effects

Recent changes within UK healthcare have had dramatic consequences for management and put managerial capabilities firmly under the spotlight. Yet, despite extensive research on managers, comparatively little is known about how they acquire and apply their management knowledge and how this is influenced by their professional background and organizational context. Drawing upon work that distinguishes between different forms of knowledge, managers’ mobilization of management knowledge is examined in the light of recent changes in healthcare. Case study evidence is presented from diverse managerial groups across three types of hospital trust (acute, care and specialist). The analysis demonstrates the mediating effects of interactions between professional background and organizational context on knowledge mobilization and highlights how current pressures on public services are reinforcing a reliance on existing management practices, creating enormous challenges for management learning in this sector

New Insulin Delivery Recommendations

Many primary care professionals manage injection or infusion therapies in patients with diabetes. Few published guidelines have been available to help such professionals and their patients manage these therapies. Herein, we present new, practical, and comprehensive recommendations for diabetes injections and infusions. These recommendations were informed by a large international survey of current practice and were written and vetted by 183 diabetes experts from 54 countries at the Forum for Injection Technique and Therapy: Expert Recommendations (FITTER) workshop held in Rome, Italy, in 2015. Recommendations are organized around the themes of anatomy, physiology, pathology, psychology, and technology. Key among the recommendations are that the shortest needles (currently the 4-mm pen and 6-mm syringe needles) are safe, effective, and less painful and should be the first-line choice in all patient categories; intramuscular injections should be avoided, especially with long-acting insulins, because severe hypoglycemia may result; lipohypertrophy is a frequent complication of therapy that distorts insulin absorption, and, therefore, injections and infusions should not be given into these lesions and correct site rotation will help prevent them; effective long-term therapy with insulin is critically dependent on addressing psychological hurdles upstream, even before insulin has been started; inappropriate disposal of used sharps poses a risk of infection with blood-borne pathogens; and mitigation is possible with proper training, effective disposal strategies, and the use of safety devices. Adherence to these new recommendations should lead to more effective therapies, improved outcomes, and lower costs for patients with diabetes. (C) 2016 Mayo Foundation for Medical Education and Research.BD, a manufacturer of injecting devicesSCI(E)[email protected]

Reduced thymic output, cell cycle abnormalities, and increased apoptosis of T lymphocytes in patients with cartilage-hair hypoplasia

Producción CientíficaBackground: Cartilage-hair hypoplasia (CHH) is characterized by metaphyseal dysplasia, bone marrow failure, increased risk of malignancies, and a variable degree of immunodeficiency. CHH is caused by mutations in the RNA component of the mitochondrial RNA processing (RMRP) endoribonuclease gene, which is involved in ribosomal assembly, telomere function, and cell cycle control. Objectives: We aimed to define thymic output and characterize immune function in a cohort of patients with molecularly defined CHH with and without associated clinical immunodeficiency. Methods: We studied the distribution of B and T lymphocytes (including recent thymic emigrants), in vitro lymphocyte proliferation, cell cycle, and apoptosis in 18 patients with CHH compared with controls. Results: Patients with CHH have a markedly reduced number of recent thymic emigrants, and their peripheral T cells show defects in cell cycle control and display increased apoptosis, resulting in poor proliferation on activation. Conclusion: These data confirm that RMRP mutations result in significant defects of cell-mediated immunity and provide a link between the cellular phenotype and the immunodeficiency in CH

The Ternary Rab27a–Myrip–Myosin VIIa Complex Regulates Melanosome Motility in the Retinal Pigment Epithelium

The retinal pigment epithelium (RPE) contains melanosomes similar to those found in the skin melanocytes, which undergo dramatic light-dependent movements in fish and amphibians. In mammals, those movements are more subtle and appear to be regulated by the Rab27a GTPase and the unconventional myosin, Myosin VIIa (MyoVIIa). Here we address the hypothesis that a recently identified Rab27a- and MyoVIIa-interacting protein, Myrip, promotes the formation of a functional tripartite complex. In heterologous cultured cells, all three proteins co-immunoprecipitated following overexpression. Rab27a and Myrip localize to the peripheral membrane of RPE melanosomes as observed by immunofluorescence and immunoelectron microscopy. Melanosome dynamics were studied using live-cell imaging of mouse RPE primary cultures. Wild-type RPE melanosomes exhibited either stationary or slow movement interrupted by bursts of fast movement, with a peripheral directionality trend. Nocodazole treatment led to melanosome paralysis, suggesting that movement requires microtubule motors. Significant and similar alterations in melanosome dynamics were observed when any one of the three components of the complex was missing, as studied in ashen- (Rab27a defective) and shaker-1 (MyoVIIa mutant)-derived RPE cells, and in wild-type RPE cells transduced with adenovirus carrying specific sequences to knockdown Myrip expression. We observed a significant increase in the number of motile melanosomes, exhibiting more frequent and prolonged bursts of fast movement, and inversion of directionality. Similar alterations were observed upon cytochalasin D treatment, suggesting that the Rab27a–Myrip–MyoVIIa complex regulates tethering of melanosomes onto actin filaments, a process that ensures melanosome movement towards the cell periphery