WorldWideScience

Sample records for cdc computers

  1. Finite element dynamic analysis on CDC STAR-100 computer

    Science.gov (United States)

    Noor, A. K.; Lambiotte, J. J., Jr.

    1978-01-01

    Computational algorithms are presented for the finite element dynamic analysis of structures on the CDC STAR-100 computer. The spatial behavior is described using higher-order finite elements. The temporal behavior is approximated by using either the central difference explicit scheme or Newmark's implicit scheme. In each case the analysis is broken up into a number of basic macro-operations. Discussion is focused on the organization of the computation and the mode of storage of different arrays to take advantage of the STAR pipeline capability. The potential of the proposed algorithms is discussed and CPU times are given for performing the different macro-operations for a shell modeled by higher order composite shallow shell elements having 80 degrees of freedom.

  2. Sorting on STAR. [CDC computer algorithm timing comparison

    Science.gov (United States)

    Stone, H. S.

    1978-01-01

    Timing comparisons are given for three sorting algorithms written for the CDC STAR computer. One algorithm is Hoare's (1962) Quicksort, which is the fastest or nearly the fastest sorting algorithm for most computers. A second algorithm is a vector version of Quicksort that takes advantage of the STAR's vector operations. The third algorithm is an adaptation of Batcher's (1968) sorting algorithm, which makes especially good use of vector operations but has a complexity of N(log N)-squared as compared with a complexity of N log N for the Quicksort algorithms. In spite of its worse complexity, Batcher's sorting algorithm is competitive with the serial version of Quicksort for vectors up to the largest that can be treated by STAR. Vector Quicksort outperforms the other two algorithms and is generally preferred. These results indicate that unusual instruction sets can introduce biases in program execution time that counter results predicted by worst-case asymptotic complexity analysis.

  3. Experience in programming Assembly language of CDC CYBER 170/750 computer

    International Nuclear Information System (INIS)

    Aiming to optimize processing time of BCG computer code in the CDC CYBER 170/750 computer, the FORTRAN-V language of INTERP subroutine was converted to Assembly language. The BCG code was developed for solving neutron transport equation by iterative method, and the INTERP subroutine is innermost loop of the code carrying out 5 interpolation types. The central processor unit Assembly language of the CDC CYBER 170/750 computer and its application in implementing the interpolation subroutine of BCG code are described. (M.C.K.)

  4. Remote operation of DOE-1 on the Lawrence Berkeley Laboratory CDC 7600, 6600, and 6400 computers

    Energy Technology Data Exchange (ETDEWEB)

    1978-03-01

    How to run the DOE-1 building energy analysis program on the Lawrence Berkeley Laboratory CDC computers is described. An overview of the LBL operating system and how to run a job on the 7600 are presented. The DOE-1 program, a control card sequence for running the program, and how to store input, output, and intermediate files are discussed. A detailed description is given of the DOE-1 Weather Package.

  5. Subsonic flutter analysis addition to NASTRAN. [for use with CDC 6000 series digital computers

    Science.gov (United States)

    Doggett, R. V., Jr.; Harder, R. L.

    1973-01-01

    A subsonic flutter analysis capability has been developed for NASTRAN, and a developmental version of the program has been installed on the CDC 6000 series digital computers at the Langley Research Center. The flutter analysis is of the modal type, uses doublet lattice unsteady aerodynamic forces, and solves the flutter equations by using the k-method. Surface and one-dimensional spline functions are used to transform from the aerodynamic degrees of freedom to the structural degrees of freedom. Some preliminary applications of the method to a beamlike wing, a platelike wing, and a platelike wing with a folded tip are compared with existing experimental and analytical results.

  6. Installation of the CDC 7600 supercomputer system in the computer centre in 1972

    CERN Multimedia

    Nettz, William

    1972-01-01

    The CDC 7600 was installed in 1972 in the newly built computer centre. It was said to be the largest and most powerful computer system in Europe at that time and remained the fastest machine at CERN for 9 years. It was replaced after 12 years. Dr. Julian Blake (CERN), Dr. Tor Bloch (CERN), Erwin Gasser (Control Data Corporation), Jean-Marie LaPorte (Control Data Corporation), Peter McWilliam (Control Data Corporation), Hans Oeshlein (Control Data Corporation), and Peter Warn (Control Data Corporation) were heavily involved in this project and may appear on the pictures. William Nettz (who took the pictures) was in charge of the installation. Excerpt from CERN annual report 1972: 'Data handling and evaluation is becoming an increasingly important part of physics experiments. In order to meet these requirements a new central computer system, CDC 7600/6400, has been acquired and it was brought into more or less regular service during the year. Some initial hardware problems have disappeared but work has still to...

  7. The use of the processor communication of the CDC-1604A/1 and CDC-1604A/2 computers for observation of scanning process on the HPD device by means of display

    International Nuclear Information System (INIS)

    On a particular example of film data processing from the Dubna Magnetic Spectrometer the possibility is shown for using the communication between CDC-1604A/1 and CDC-1604A/2 computers for the joint working of two logically communicated programs. Combination of HPD and graphic display software by means of the processors communication channel provides an opportunity to have a visual display of the film during its scanning, without restrictions on the time of processing. Thus, using the communication between two computers one can gain conditions for handling new tasks unrealizable with one CDC-1604A computer

  8. A system for communication between a CDC 6000 and a PDP 11 computer

    International Nuclear Information System (INIS)

    A description is given of the hardware and software employed for the interchange of binary data between a PDP 11 and a CDC 6000 computer, for the bibliographic-data acquisition system of the CERN Library. The data is transmitted as buffers of 8-bit bytes with sequence and checksum verification. Initially tested under standard Intercom, the software was subsequently updated to communicate with CERN's programmable front-end concentrator Supermux. For this, a special interface was designed, providing full-duplex transmission and capable of distinguishing between the pure binary computer data and terminal-oriented system messages. The various stages in the development are briefly described and a more detailed account is given of the current system, particularly the discrimination between data and system messages and the use of DMA channels. A complete set of circuit diagrams is included. (author)

  9. Inhibitors of the Cdc34 acidic loop: A computational investigation integrating molecular dynamics, virtual screening and docking approaches

    Directory of Open Access Journals (Sweden)

    Alberto Arrigoni

    2014-01-01

    Here, we carried out a computational study based on molecular dynamics, virtual screening and docking to identify potential inhibitory compounds of Cdc34, modulating the acidic loop conformation. The molecules identified in this study have been designed to act as molecular hinges that can bind the acidic loop in its closed conformation, thus inhibiting the Cdc34-mediated ubiquitination cascade at the ubiquitin-charging step. In particular, we proposed a pharmacophore model featuring two amino groups in the central part of the model and two lateral aromatic chains, which respectively establish electrostatic interactions with the acidic loop (Asp 108 and Glu 109 and a hydrogen bond with Ser 139, which is one of the key residues for Cdc34 activity.

  10. The implementation of the CDC version of RELAP5/MOD1/019 on an IBM compatible computer system (AMDAHL 470/V8)

    International Nuclear Information System (INIS)

    RELAP5/MOD1 is an advanced one-dimensional best estimate system code, which is used for safety analysis studies of nuclear pressurized water reactor systems and related integral and separate effect test facilities. The program predicts the system response for large break, small break LOCA and special transients. To a large extent RELAP5/MOD1 is written in Fortran, only a small part of the program is coded in CDC assembler. RELAP5/MOD1 was developed on the CDC CYBER 176 at INEL*. The code development team made use of CDC system programs like the CDC UPDATE facility and incorporated in the program special purpose software packages. The report describes the problems which have been encountered when implementing the CDC version of RELAP5/MOD1 on an IBM compatible computer systems (AMDAHL 470/V8)

  11. Conversion and improvement of the Rutherford Laboratory's magnetostatic computer code GFUN3D to the NMFECC CDC 7600

    International Nuclear Information System (INIS)

    The implementation of a version of the Rutherford Laboratory's magnetostatic computer code GFUN3D on the CDC 7600 at the National Magnetic Fusion Energy Computer Center is reported. A new iteration technique that greatly increases the probability of convergence and reduces computation time by about 30% for calculations with nonlinear, ferromagnetic materials is included. The use of GFUN3D on the NMFE network is discussed, and suggestions for future work are presented. Appendix A consists of revisions to the GFUN3D User Guide (published by Rutherford Laboratory( that are necessary to use this version. Appendix B contains input and output for some sample calculations. Appendix C is a detailed discussion of the old and new iteration techniques

  12. Computer graphics by example. Part 1. FTE: how to produce resource-allocation charts. [In LRLTRAN for CDC 7600

    Energy Technology Data Exchange (ETDEWEB)

    O' Hair, K.

    1978-05-10

    FTE creates charts that show quickly how time and resources are being allocated. The FTE chart is an easy-to-digest chart showing trends and relationships. It is a useful tool for the planning and communication of ideas at all levels of management in private industry and government. Although it does not replace the detailed analysis of data needed for accurate planning, it shows the big picture, which must first be understood before the details can be accurately interpreted. This report, written for the new user, shows by example how to use the FTE program and edit FTE files. FTE is written in LRLTRAN and runs on the CDC-7600 computers of the Livermore Time-Sharing System (the Octopus Network).

  13. ESECT/EMAP: mapping algorithm for computing intersection volumes of overlaid meshes in cylindrical geometry. [In FORTRAN for CDC 6600 and 7600 computers

    Energy Technology Data Exchange (ETDEWEB)

    Wienke, B.R.; O' Dell, R.D.

    1976-12-01

    ESECT and EMAP are subroutines which provide a computer algorithm for mapping arbitrary meshes onto rectangular meshes in cylindrical (r,z) geometry. Input consists of the lines defining the rectangular mesh and the coordinates of the arbitrary mesh, which are assumed to be joined by straight lines. Output consists of the intersection volumes with designation of common mesh zones. The ESECT and EMAP routines do not comprise a ''free-standing'' code but, instead, are intended for inclusion in existing codes for which one mesh structure (typically Lagrangian) needs to be mapped onto an Eulerian mesh. Such mappings are of interest in coupled hydrodynamic and neutronic calculations. Exact expressions for the volumes of rotation (about z-axis) generated by the planar mesh intersection areas are used. Intersection points of the two meshes are computed and mapped onto corresponding regions on the rectangular mesh. Intersection points with the same regional indices are recorded into multilaterals, and the multilaterals are triangulated to facilitate computation of the intersection volumes. Dimension statements within ESECT/EMAP presently allow for rectangular and arbitrary meshes of 10k and 3.6k grid points. Scaling of all arrays to suit individual applications is easily effected. Computations of intersection volumes generated by overlapping 10k rectangular and 2.2k radial meshes require an average of 18 s computer time, while computation times for the same meshes scaled by a factor of /sup 1///sub 4/ in number of grid points average 3 s on the CDC 7600. Generally, cases of small cell rectangular meshes overlaid on large cell arbitrary meshes require the longer running times. 10 figures, 2 tables.

  14. Interactive computer graphics displays for hierarchical data structures. [Description of THESGRAF, in FORTRAN IV for CDC and IBM computers

    Energy Technology Data Exchange (ETDEWEB)

    Cahn, D.F.; Murano, C.V.

    1980-05-01

    An interactive computer graphical display program was developed as an aid to user visualization and manipulation of hierarchically structured data systems such as thesauri. In the present configuration, a thesaurus term and its primary and secondary conceptual neighbors are presented to the user in tree graph form on a CRT; the user then designates, via light pen or keyboard, any of the neighbors as the next term of interest and receives a new display centered on this term. By successive specification of broader, narrower, and related terms, the user can course rapidly through the thesaurus space and refine his search file. At any stage, he deals with a term-centered, conceptually meaningful picture of a localized portion of the thesaurus, and is freed from the artificial difficulties of handling the traditional alphabetized thesaurus. Intentional limitation of the associative range of each display frame, and the use of color, case, and interconnecting vectors to encode relationships among terms, enhance interpretability of the display. Facile movement through the term space, provided by interactive computation, allows the display to remain simple, and is an essential element of the system. 3 figures.

  15. User's guide to SUBWAR 1. [Kinematically tracks torpedo and target and shows distribution of hits; in LRLTRAN for CDC 7600 computer

    Energy Technology Data Exchange (ETDEWEB)

    Stratton, S.D.

    1976-09-27

    SUBWAR 1, a digital computer program which kinematically tracks the movements of a torpedo and its target and shows the distribution of hits on the target is described. The program is written in LRLTRAN for compilation by CHAT and execution on a CDC 7600. Output is graphical as well as numerical. Torpedo and submarine target characteristics, parameters, modeling, and simulation are briefly outlined, and a line-by-line description of the program's input file is given. Some suggestions are also provided on how SUBWAR 1 can be used to study effects of underwater weapons characteristics. 10 figures, 3 tables.

  16. CDC Disease Detective Camp

    Centers for Disease Control (CDC) Podcasts

    2010-08-02

    The CDC Disease Detective Camp gives rising high school juniors and seniors exposure to key aspects of the CDC, including basic epidemiology, infectious and chronic disease tracking, public health law, and outbreak investigations. The camp also helps students explore careers in public health.  Created: 8/2/2010 by Centers for Disease Control and Prevention (CDC).   Date Released: 8/2/2010.

  17. CDC Vital Signs: Binge Drinking

    Science.gov (United States)

    ... Search The CDC Cancel Submit Search The CDC Vital Signs Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Vital Signs Current issue Infographic Topics Covered Alcohol Cancer Cardiovascular ...

  18. CDC Vital Signs: Child Injury

    Science.gov (United States)

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  19. Computational solution of nonlinear two-point boundary-value problems. [SUPOR Q, in FORTRAN for CDC 6600

    Energy Technology Data Exchange (ETDEWEB)

    Scott, M.R.; Watts, H.A.

    1977-01-01

    A working computer code, called SUPOR Q, which solves quite general nonlinear two-point boundary value problems is described. The nonlinear problem is replaced by a sequence of linear problems by applying quasilinearization (Newton's method) to the nonlinear differential operator. Each linear two-point boundary value problem is solved by an initial-value procedure which combines the well-known technique of superposition with a process called orthonormalization. 3 tables.

  20. CDC Child Growth Charts

    Data.gov (United States)

    U.S. Department of Health & Human Services — CDC child growth charts consist of a series of percentile curves that illustrate the distribution of selected body measurements in U.S. children. Pediatric growth...

  1. CDC WONDER: Births

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Births (Natality) online databases in CDC WONDER report birth rates, fertility rates and counts of live births occurring within the United States to U.S....

  2. ECIS - Adaptation to CDC CYBER system

    International Nuclear Information System (INIS)

    The implantation of ECIS computer code, elaborated for BOURROUGHS 6700 computer of USP (Universidade de Sao Paulo), in the CDC CYBER 170/730 computer is presented. The ECIS code calculates cross section by coupled channel method. Some problems were calculated to verify the compactibility of results obtained from BOURROUGHS 6700 version with the version. The problems calculated by new version and the carried out modifications, are described (M.C.K.)

  3. Survey of new vector computers: The CRAY 1S from CRAY research; the CYBER 205 from CDC and the parallel computer from ICL - architecture and programming

    Science.gov (United States)

    Gentzsch, W.

    1982-01-01

    Problems which can arise with vector and parallel computers are discussed in a user oriented context. Emphasis is placed on the algorithms used and the programming techniques adopted. Three recently developed supercomputers are examined and typical application examples are given in CRAY FORTRAN, CYBER 205 FORTRAN and DAP (distributed array processor) FORTRAN. The systems performance is compared. The addition of parts of two N x N arrays is considered. The influence of the architecture on the algorithms and programming language is demonstrated. Numerical analysis of magnetohydrodynamic differential equations by an explicit difference method is illustrated, showing very good results for all three systems. The prognosis for supercomputer development is assessed.

  4. Computer-aided Fault Tree Analysis. [FTAP, in FORTRAN for CDC 6600/7600 and IBM 360/370 series computers

    Energy Technology Data Exchange (ETDEWEB)

    Willie, R.R.

    1978-08-01

    A computer-oriented methodology for deriving minimal cut and path set families associated with arbitrary fault trees is discussed first. Then the use of the Fault Tree Analysis Program (FTAP), an extensive FORTRAN computer package that implements the methodology is described. An input fault tree to FTAP may specify the system state as any logical function of subsystem or component state variables or complements of these variables. When fault tree logical relations involve complements of state variables, the analyst may instruct FTAP to produce a family of prime implicants, a generalization of the minimal cut set concept. FTAP can also identify certain subsystems associated with the tree as system modules and provide a collection of minimal cut set families that essentially expresses the state of the system as a function of these module state variables. Another FTAP feature allows a subfamily to be obtained when the family of minimal cut sets or prime implicants is too large to be found in its entirety; this subfamily consists only of sets that are interesting to the analyst in a special sense.

  5. Announcement: CDC's 70th Anniversary.

    Science.gov (United States)

    2016-01-01

    July 1, 2016, marks the 70th anniversary of the establishment of CDC. Since the agency's launch as the Communicable Disease Center on July 1, 1946, CDC's primary mission has been improving public health in the United States and around the world through prevention and preparedness. In the seven decades since CDC's founding, the agency has grown in size and mission and is recognized as the nation's premiere health promotion, disease prevention, and emergency preparedness agency, and a global leader in public health. CDC's mission has progressed beyond communicable disease control and now encompasses noninfectious diseases, injury prevention, and environmental and occupational health. PMID:27362420

  6. CDC Lab Values

    Centers for Disease Control (CDC) Podcasts

    2015-02-02

    More than fifteen hundred scientists fill the lab benches at CDC, logging more than four million hours each year. CDC’s laboratories play a critical role in the agency’s ability to find, stop, and prevent disease outbreaks. This podcast provides a brief overview of what goes on inside CDC’s labs, and why this work makes a difference in American’s health.  Created: 2/2/2015 by Office of the Associate Director for Communication (OADC).   Date Released: 2/2/2015.

  7. CDC Vital Signs: Prescription Painkiller Overdoses

    Science.gov (United States)

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  8. CDC Vital Signs: Alcohol and Pregnancy

    Science.gov (United States)

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  9. CDC Vital Signs: Asthma in the US

    Science.gov (United States)

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  10. CDC Vital Signs: Making Health Care Safer

    Science.gov (United States)

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  11. CDC Vital Signs: Preventing Norovirus Outbreaks

    Science.gov (United States)

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  12. CDC PRAMStat Data for 2002

    Data.gov (United States)

    U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). PRAMS, the Pregnancy Risk Assessment Monitoring System, is a surveillance system collecting state-specific,...

  13. CDC PRAMStat Data for 2010

    Data.gov (United States)

    U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). PRAMS, the Pregnancy Risk Assessment Monitoring System, is a surveillance system collecting state-specific,...

  14. CDC PRAMStat Data for 2011

    Data.gov (United States)

    U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). PRAMS, the Pregnancy Risk Assessment Monitoring System, is a surveillance system collecting state-specific,...

  15. CDC PRAMStat Data for 2000

    Data.gov (United States)

    U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). PRAMS, the Pregnancy Risk Assessment Monitoring System, is a surveillance system collecting state-specific,...

  16. CDC PRAMStat Data for 2001

    Data.gov (United States)

    U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). PRAMS, the Pregnancy Risk Assessment Monitoring System, is a surveillance system collecting state-specific,...

  17. CDC PRAMStat Data for 2006

    Data.gov (United States)

    U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). PRAMS, the Pregnancy Risk Assessment Monitoring System, is a surveillance system collecting state-specific,...

  18. CDC PRAMStat Data for 2003

    Data.gov (United States)

    U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). PRAMS, the Pregnancy Risk Assessment Monitoring System, is a surveillance system collecting state-specific,...

  19. CDC PRAMStat Data for 2004

    Data.gov (United States)

    U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). PRAMS, the Pregnancy Risk Assessment Monitoring System, is a surveillance system collecting state-specific,...

  20. CDC PRAMStat Data for 2007

    Data.gov (United States)

    U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). PRAMS, the Pregnancy Risk Assessment Monitoring System, is a surveillance system collecting state-specific,...

  1. CDC PRAMStat Data for 2008

    Data.gov (United States)

    U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). PRAMS, the Pregnancy Risk Assessment Monitoring System, is a surveillance system collecting state-specific,...

  2. CDC PRAMStat Data for 2009

    Data.gov (United States)

    U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). PRAMS, the Pregnancy Risk Assessment Monitoring System, is a surveillance system collecting state-specific,...

  3. CDC PRAMStat Data for 2005

    Data.gov (United States)

    U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). PRAMS, the Pregnancy Risk Assessment Monitoring System, is a surveillance system collecting state-specific,...

  4. CDC WONDER: Mortality - Infant Deaths

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Mortality - Infant Deaths (from Linked Birth / Infant Death Records) online databases on CDC WONDER provide counts and rates for deaths of children under 1 year...

  5. ABCXYZ: vector potential (A) and magnetic field (B) code (C) for Cartesian (XYZ) geometry using general current elements. [In LRL TRAN for CDC > 600 computer

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, D.V.; Breazeal, J.; Finan, C.H.; Johnston, B.M.

    1976-09-14

    ABCXYZ is a computer code for obtaining the Cartesian components of the vector potential and the magnetic field on an observed grid from an arrangement of current-carrying wires. Arbitrary combinations of straight line segments, arcs, and loops are allowed in the specification of the currents. Arbitrary positions and orientations of the current-carrying elements are also allowed. Specification of the wire diameter permits the computation of well-defined fields, even in the interiors of the conductors. An optical feature generates magnetic field lines. Extensive graphical and printed output is available to the user including contour, grid-line, and field-line plots. 12 figures, 1 table.

  6. CDC Kerala - The Untold Story.

    Science.gov (United States)

    Nair, M K C; Leela, Leena Mundapalliyil; George, Babu; Bhaskaran, Deepa; Pillai, Asokan Nataraja; Sarasamma, Harikumaran Nair Gopinathan Nair

    2016-05-01

    This article is our life time experience in conceptualizing and systematically developing Child Development Centre (CDC) Kerala in the last 25 years, from a research project to a national training centre in child and adolescent development and premarital counseling. CDC Kerala's major contribution was in creating a 'conceptual framework' of a valid link between childhood disability, low birth weight, adolescent girls' nutrition and fetal onset adult lifestyle diseases. It all started with a randomized controlled trial (RCT) proving beyond doubt that early stimulation is effective in improving the neurodevelopmental status of high risk babies at one and two years and the same cohort was followed-up in detail at 5, 13, 16, 19 and 24 completed years. The process of establishing CDC Kerala is being presented under (i) clinical child development, (ii) adolescent care counseling, (iii) young adults and premarital counseling and (iv) institution building. PMID:26988580

  7. Stalking SARS: CDC at Work

    Centers for Disease Control (CDC) Podcasts

    2014-05-22

    In this podcast for kids, the Kidtastics talk about the SARS outbreak and how CDC worked to solve the mystery.  Created: 5/22/2014 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 5/22/2014.

  8. CDC Vital Signs: Legionnaires' Disease

    Science.gov (United States)

    ... Overview CDC investigated the first outbreak of Legionnaires’ disease, a serious lung infection (pneumonia), in 1976. An increasing number ... they develop symptoms of pneumonia. Test for Legionnaires’ disease in people with serious pneumonia, especially those requiring intensive care or who ...

  9. The polo-like kinase Cdc5 interacts with FEAR network components and Cdc14

    OpenAIRE

    Rahal, Rami; Amon, Angelika

    2008-01-01

    Exit from mitosis in Saccharomyces cerevisiae is triggered by activation of the phosphatase Cdc14. Throughout interphase and early mitosis, Cdc14 is sequestered in the nucleolus by its inhibitor Cfi1/Net1. In anaphase, the Cdc Fourteen Early Anaphase Release (FEAR) network and the Mitotic Exit Network (MEN) coordinately trigger the release of Cdc14 from the nucleolus. Here we show that the FEAR network component Cdc5 physically associates with two other members of the pathway, the Separase Es...

  10. Working at a Ferranti-Argus graphics display linked to a CDC 6600

    CERN Multimedia

    1975-01-01

    The photo shows a Ferranti-Argus graphics display linked to a CDC 6600 computer running one of the first interactive graphics packages for physics analysis. The people around are Jean-Claude Marin, Harry Renshall and Emilio Pagiola (right).

  11. SIMWEST: A simulation model for wind and photovoltaic energy storage systems (CDC user's manual), volume 1

    Science.gov (United States)

    Warren, A. W.; Esinger, A. W.

    1979-01-01

    Procedures are given for using the SIMWEST program on CDC 6000 series computers. This expanded software package includes wind and/or photovoltaic systems utilizing any combination of five types of storage (pumped hydro, battery, thermal, flywheel, and pneumatic).

  12. Functional characterization and cellular dynamics of the CDC-42 - RAC - CDC-24 module in Neurospora crassa.

    Directory of Open Access Journals (Sweden)

    Cynthia L Araujo-Palomares

    Full Text Available Rho-type GTPases are key regulators that control eukaryotic cell polarity, but their role in fungal morphogenesis is only beginning to emerge. In this study, we investigate the role of the CDC-42 - RAC - CDC-24 module in Neurospora crassa. rac and cdc-42 deletion mutants are viable, but generate highly compact colonies with severe morphological defects. Double mutants carrying conditional and loss of function alleles of rac and cdc-42 are lethal, indicating that both GTPases share at least one common essential function. The defects of the GTPase mutants are phenocopied by deletion and conditional alleles of the guanine exchange factor (GEF cdc-24, and in vitro GDP-GTP exchange assays identify CDC-24 as specific GEF for both CDC-42 and RAC. In vivo confocal microscopy shows that this module is organized as membrane-associated cap that covers the hyphal apex. However, the specific localization patterns of the three proteins are distinct, indicating different functions of RAC and CDC-42 within the hyphal tip. CDC-42 localized as confined apical membrane-associated crescent, while RAC labeled a membrane-associated ring excluding the region labeled by CDC42. The GEF CDC-24 occupied a strategic position, localizing as broad apical membrane-associated crescent and in the apical cytosol excluding the Spitzenkörper. RAC and CDC-42 also display distinct localization patterns during branch initiation and germ tube formation, with CDC-42 accumulating at the plasma membrane before RAC. Together with the distinct cellular defects of rac and cdc-42 mutants, these localizations suggest that CDC-42 is more important for polarity establishment, while the primary function of RAC may be maintaining polarity. In summary, this study identifies CDC-24 as essential regulator for RAC and CDC-42 that have common and distinct functions during polarity establishment and maintenance of cell polarity in N. crassa.

  13. An adolescent case of familial hyperparathyroidism with a germline frameshift mutation of the CDC73 gene

    OpenAIRE

    Takeuchi, Takako; Yoto, Yuko; Tsugawa, Takeshi; Kamasaki, Hotaka; Kondo, Atsushi; OGINO, JIRO; Hasegawa, Tadashi; Yama, Naoya; Anan, Sawa; Uchino, Shinya; Ishikawa, Aki; Sakurai, Akihiro; Tsutsumi, Hiroyuki

    2015-01-01

    Abstract. A 13-yr-old boy who complained of persistent nausea, vomiting and weight loss had hypercalcemia and an elevated intact PTH level. Computed tomography confirmed two tumors in the thyroid gland. The tumors were surgically removed and pathologically confirmed as parathyroid adenoma. Because his maternal aunt and grandmother both had histories of parathyroid tumors, genetic investigation was undertaken for him, and a germline frameshift mutation of the CDC73 gene was identified. CDC73 g...

  14. CDC Vital Signs: More People Walk to Better Health

    Science.gov (United States)

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  15. CDC Vital Signs: Adult Smoking among People with Mental Illness

    Science.gov (United States)

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  16. CDC Vital Signs: Colorectal Cancer Tests Save Lives

    Science.gov (United States)

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  17. CDC Vital Signs: Prescription Painkiller Overdoses in the US

    Science.gov (United States)

    ... Search The CDC Cancel Submit Search The CDC Vital Signs Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Vital Signs Current issue Infographic Topics Covered Alcohol Cancer Cardiovascular ...

  18. CDC Vital Signs: Getting Blood Pressure under Control

    Science.gov (United States)

    ... Search The CDC Cancel Submit Search The CDC Vital Signs Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Vital Signs Current issue Infographic Topics Covered Alcohol Cancer Cardiovascular ...

  19. CDC Vital Signs: Adult Seat Belt Use in the US

    Science.gov (United States)

    ... Search The CDC Cancel Submit Search The CDC Vital Signs Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Vital Signs Current issue Infographic Topics Covered Alcohol Cancer Cardiovascular ...

  20. 13 CFR 120.851 - CDC ethical requirements.

    Science.gov (United States)

    2010-01-01

    ... Company Loan Program (504) Other Cdc Requirements § 120.851 CDC ethical requirements. CDCs and their... § 120.140. In addition, they are subject to the following: (a) Any benefit flowing to a CDC's...

  1. User's manual for preprocessor computer programs for preparing input data for the finite element structural analysis program SAPIV (programs SPREP, COMBINE, FINAL8). [For CDC computers

    Energy Technology Data Exchange (ETDEWEB)

    Goodzeit, C.L.

    1977-03-01

    A finite element structural analysis program such as SAPIV can require a large amount of effort in data preparation, particularly for three-dimensional structural models and two-dimensional cases of complicated geometry. The development of a self-organizing quadrilateral mesh generator such as QMESH has made it possible to reduce significantly the amount of manual data preparation for SAPIV. The mesh description generated by QMESH can be transformed into appropriate card images for input to SAPIV by means of the preprocessor, SPREP. Two types of element generation are available in SPREP: quadrilateral elements for two-dimensional plane or axisymetric problems (Type 4), and 8- or 12-mode three-dimensional elements (Type 8). The Type 8 elements can be generated for the following geometrical cases: a plate, a cylindrical shell section, a spherical shell section, or a toroidal shell section. SPREP can be readily modified by the user to include additional features that are desired. The program produces the bulk of the input data for SAPIV, which includes the nodal point coordinate card images and the element numbering card images. Additional data such as boundary conditions, loads, load multipliers, material properties, etc., are added to the data file by the user. Two other pre-processors described in this manual can be used as an adjunct to SPREP. FINAL8 is used to add boundary elements (Type 7) to the SAPIV input data file. This is particularly useful in the case of three-dimensional structures.FINAL8 will compute and add nodes for boundary elements along the edges of the model specified by the user and will merge all of the boundary element input data into the file. The pre-processor COMBINE is used to integrate SAPIV input data. 6 figures, 10 tables. (RWR)

  2. 13 CFR 120.823 - CDC Board of Directors.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false CDC Board of Directors. 120.823... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.823 CDC Board of Directors. The CDC must have a Board of Directors chosen from the membership by the members,...

  3. Fast Action Can Prevent Sepsis Death: CDC

    Science.gov (United States)

    ... fullstory_160574.html Fast Action Can Prevent Sepsis Death: CDC Know the signs of extreme response to ... treated long before it causes severe illness or death, U.S. health officials report. Sepsis, or septicemia, occurs ...

  4. CDC WONDER: Daily Fine Particulate Matter

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Daily Fine Particulate Matter data available on CDC WONDER are geographically aggregated daily measures of fine particulate matter in the outdoor air, spanning...

  5. Obesity Rates Rising Among Women: CDC

    Science.gov (United States)

    ... nlm.nih.gov/medlineplus/news/fullstory_159239.html Obesity Rates Rising Among Women: CDC Though a major ... are another group that continues to struggle with obesity. "Obesity remains a public health concern," said Cynthia ...

  6. Obesity Rates Rising Among Women: CDC

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_159239.html Obesity Rates Rising Among Women: CDC Though a major ... are another group that continues to struggle with obesity. "Obesity remains a public health concern," said Cynthia ...

  7. CDC Vital Signs: Prescription Painkiller Overdoses

    Science.gov (United States)

    ... What Can Be Done The US government is Enforcing federal laws to prevent nonmedical use of methadone. ... RSS ABOUT About CDC Jobs Funding LEGAL Policies Privacy FOIA No Fear Act OIG 1600 Clifton Road ...

  8. CDC WONDER: AIDS Public Use Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — The AIDS Public Information Data Set (APIDS) for years 1981-2002 on CDC WONDER online database contains counts of AIDS (Acquired Immune Deficiency Syndrome) cases...

  9. CDC STATE System Tobacco Legislation - Licensure

    Data.gov (United States)

    U.S. Department of Health & Human Services — 1995-2016. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. Legislation—Licensure. The STATE...

  10. CDC WONDER: Mortality - Multiple Cause of Death

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Mortality - Multiple Cause of Death data on CDC WONDER are county-level national mortality and population data spanning the years 1999-2006. These data are...

  11. CDC WONDER: Sexually Transmitted Disease (STD) morbidity

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Sexually Transmitted Disease (STD) Morbidity online databases on CDC WONDER contain case reports reported from the 50 United States and D.C., Puerto Rico,...

  12. CDC WONDER: Sexually Transmitted Disease (STD) Morbidity

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Sexually Transmitted Disease (STD) Morbidity online databases on CDC WONDER contain case reports reported from the 50 United States and D.C., Puerto Rico,...

  13. CDC STATE System Tobacco Legislation - Preemption

    Data.gov (United States)

    U.S. Department of Health & Human Services — 1995-2016. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. Legislation—Preemption. The STATE...

  14. CDC STATE System Tobacco Legislation - Advertising

    Data.gov (United States)

    U.S. Department of Health & Human Services — 1995-2015. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. Legislation – Advertising. The STATE...

  15. CDC STATE System Tobacco Legislation - Smokefree Campus

    Data.gov (United States)

    U.S. Department of Health & Human Services — 1995-2016. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. Legislation – Smokefree Campuses....

  16. CDC STATE System Tobacco Legislation - Preemption Summary

    Data.gov (United States)

    U.S. Department of Health & Human Services — 1995-2016. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. Legislation—Preemption. The STATE...

  17. CDC STATE System Tobacco Legislation - Fire Safety

    Data.gov (United States)

    U.S. Department of Health & Human Services — 1995-2016. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. Legislation – Fire-Safety. The STATE...

  18. CDC STATE System Tobacco Legislation - Youth Access

    Data.gov (United States)

    U.S. Department of Health & Human Services — 1995-2016. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. Legislation—Youth Access. The STATE...

  19. CDC Wonder Vaccine Adverse Event Reporting System

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Vaccine Adverse Event Reporting System (VAERS) online database on CDC WONDER provides counts and percentages of adverse event case reports after vaccination,...

  20. CDC WONDER: Mortality - Multiple Cause of Death

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Mortality - Multiple Cause of Death data on CDC WONDER are county-level national mortality and population data spanning the years 1999-2009. Data are based on...

  1. CDC WONDER: Online Tuberculosis Information System (OTIS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Online Tuberculosis Information System (OTIS) on CDC WONDER contains information on verified tuberculosis (TB) cases reported to the Centers for Disease Control...

  2. Zika Spreading Rapidly Through Puerto Rico: CDC

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_159430.html Zika Spreading Rapidly Through Puerto Rico: CDC Possibly hundreds ... 2016 FRIDAY, June 17, 2016 (HealthDay News) -- The Zika virus is spreading fast through Puerto Rico, placing ...

  3. CDC STATE System Tobacco Legislation - Tax

    Data.gov (United States)

    U.S. Department of Health & Human Services — 1995-2016. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. Legislation-Tax. The STATE System...

  4. CDC WONDER: Mortality - Underlying Cause of Death

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CDC WONDER Mortality - Underlying Cause of Death online database is a county-level national mortality and population database spanning the years since 1979....

  5. CDC Vital Signs: HIV Care Saves Lives

    Science.gov (United States)

    ... your zip code to KnowIt (566948) on your smart phone to locate an HIV testing site near ... Communications (OADC) Email Recommend Tweet YouTube Instagram Listen Watch RSS ABOUT About CDC Jobs Funding LEGAL Policies ...

  6. CDC Climat - 2011 Sustainable Development Report

    International Nuclear Information System (INIS)

    CDC Climat is the Caisse des Depots (CDC) subsidiary that is dedicated to combating climate change. Its activities aim to support the transition towards a low resource and low greenhouse gas emission (GHG) economy, through services that are cutting-edge, pro table, and in line with CDC's public policy goals. Through its corporate purpose, CDC Climat embodies the CDC's commitments in the sustainable development field. CDC Climat supports the implementation of public GHG emission reduction policies, primarily through emission trading schemes at the European and international level. Since it was founded in 2010, and throughout 2011, its strategic priorities have consisted in: - developing a long-term policy for investing in carbon credits generated by environmental initiatives, as part of the project mechanisms set up by the Kyoto Protocol, and used in the European Emission Trading Scheme; - supporting the development of its investments in carbon finance operators, like BlueNext, the European carbon exchange, for instance; - broadening the scope of its research into climate economics, which is supported by CDC and available to everyone, in order to serve the public and private players concerned. Its teams have supported French and European governments, international organisations and the United Nations, and various NGOs in their work and thinking on the future of tools for combating climate change. They have specifically contributed reports based on their research and operational feedback. When it was founded, CDC Climat was closely linked to public policies aimed at combating climate change via allowance and carbon trading mechanisms. The difficulties encountered by international negotiations, together with the effects of the economic and financial downturn in Europe, have resulted in a very pronounced fall in the price of carbon assets on these markets since the summer of 2011, with no prospect of recovery for several years. This environment is calling some of the

  7. The role of CDC42 in cancer%CDC42与癌症

    Institute of Scientific and Technical Information of China (English)

    徐永茹; 徐平; 徐锋; 李湘萍

    2016-01-01

    Cell division cycle 42 (CDC42)is a member of Rho guanosine triphosphatase (GTPase) family,which plays an important role in cell proliferation , cell migration and cell transformation .The activity of CDC42 can be regulated by guanine nucleotide exchange factors (GEFs),GTPase activating proteins (GAPs) and guanine nucleotide-dissociation inhib-itors (GDIs).Recently,CDC42 has been reported as abnormally expressed in many human cancers ,suggesting that CDC42 performs complex functions in tumorigenesis .Therefore,this paper aims to shed light on the functions of CDC 42 in cancers in terms of the alteration of CDC42 activity,CDC42 regulators,as well as its effectors.%细胞分裂周期蛋白42(cell division cycle 42,CDC42)是Rho蛋白鸟苷三磷酸酶(guanosine triphosphatase, GTPase)家族成员之一,在细胞增殖、迁移、转化等过程发挥重要作用。与大多数GTPase一样,CDC42的活性受到鸟嘌呤核苷酸转换因子( guanine nucleotide exchange factors , GEF )、GTP 酶激活蛋白( GTPase activating proteins , GAP)和鸟苷酸解离抑制因子( guanine nucleotide-dissociation inhibitors ,GDI)的调控。目前研究表明,CDC42在大多数人癌症组织中表达异常,对癌症的发生发展具有复杂而重要的调控作用。该文就CDC42自身活性变化、CDC42调节因子的变化及其下游效应因子的变化在癌症中的作用进行综述,旨在深入理解CDC42在人类癌症中的作用机制。

  8. Cdc42-mediated tubulogenesis controls cell specification

    DEFF Research Database (Denmark)

    Kesavan, Gokul; Sand, Fredrik Wolfhagen; Greiner, Thomas Uwe;

    2009-01-01

    Understanding how cells polarize and coordinate tubulogenesis during organ formation is a central question in biology. Tubulogenesis often coincides with cell-lineage specification during organ development. Hence, an elementary question is whether these two processes are independently controlled...... later for maintaining apical cell polarity. Finally, we show that Cdc42 controls cell specification non-cell-autonomously by providing the correct microenvironment for proper control of cell-fate choices of multipotent progenitors. For a video summary of this article, see the PaperFlick file with the......, or whether proper cell specification depends on formation of tubes. To address these fundamental questions, we have studied the functional role of Cdc42 in pancreatic tubulogenesis. We present evidence that Cdc42 is essential for tube formation, specifically for initiating microlumen formation and...

  9. January 21, 2015 CDC Ebola Response Update

    Centers for Disease Control (CDC) Podcasts

    2015-01-21

    The latest numbers from CDC show more than 20,000 people in West Africa have been sick with Ebola, and more than 8,000 have died. As Dr. Tom Frieden explains, some areas may be starting to see a decrease in cases, but that does not mean the fight is over. CDC will continue its work in West Africa until we get to zero new cases.  Created: 1/21/2015 by CDC’s Office of the Associate Director for Communication.   Date Released: 1/21/2015.

  10. An adolescent case of familial hyperparathyroidism with a germline frameshift mutation of the CDC73 gene.

    Science.gov (United States)

    Takeuchi, Takako; Yoto, Yuko; Tsugawa, Takeshi; Kamasaki, Hotaka; Kondo, Atsushi; Ogino, Jiro; Hasegawa, Tadashi; Yama, Naoya; Anan, Sawa; Uchino, Shinya; Ishikawa, Aki; Sakurai, Akihiro; Tsutsumi, Hiroyuki

    2015-10-01

    A 13-yr-old boy who complained of persistent nausea, vomiting and weight loss had hypercalcemia and an elevated intact PTH level. Computed tomography confirmed two tumors in the thyroid gland. The tumors were surgically removed and pathologically confirmed as parathyroid adenoma. Because his maternal aunt and grandmother both had histories of parathyroid tumors, genetic investigation was undertaken for him, and a germline frameshift mutation of the CDC73 gene was identified. CDC73 gene analysis should be done on individuals who are at risk of familial hyperparathyroidism, including those who are asymptomatic, and they should be followed for potential primary hyperparathyroidism and associated disorders including resultant parathyroid carcinoma. PMID:26568659

  11. CDC Best Practices for Comprehensive Tobacco Control Programs - 2007

    Data.gov (United States)

    U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). Best Practices for Comprehensive Tobacco Control Programs. Funding. CDC's Best Practices for Comprehensive Tobacco...

  12. CDC Best Practices for Comprehensive Tobacco Control Programs - 2014

    Data.gov (United States)

    U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). Best Practices for Comprehensive Tobacco Control Programs. Funding. CDC's Best Practices for Comprehensive Tobacco...

  13. Characterization and Expression of Mouse Cdc50c during Spermatogenesis

    Institute of Scientific and Technical Information of China (English)

    Peng XU; Xiaoyan DING

    2007-01-01

    Cdc50p is a transmembrane protein required for polarized growth in Saccharomyces cerevisiae.The knowledge on physiological functions of its mammalian homologs, however, is limited. Using database analysis, we identified one mouse testis expressed sequence tag, named Cdc50c, encoding a previously uncharacterized homolog of Cdc50p. Similar to yeast Cdc50p, the putative Cdc50c protein contains three transmembrane spanning regions. Its orthologs are present in many species such as fish, avian and human,suggesting its evolutionary conservation. In multitissue reverse transcription-polymerase chain reaction analyses the mRNA for Cdc50c was predominately detected in testis. The onset of the gene expression coincides with the first appearance of spermatocytes during testicular development. In situ hybridization analyses revealed that Cdc50c mRNA localized in pachytene spermatocytes and round and elongated spermatids. Our data suggest that Cdc50c might play important roles during spermatogenesis.

  14. June 2, 2015 CDC Ebola Response Update

    Centers for Disease Control (CDC) Podcasts

    2015-06-02

    In this podcast, CDC's Dr. Jane Seward discusses the Ebola vaccine trial known as STRIVE, which began in April 2015.  Created: 6/2/2015 by Office of the Associate Director for Communication (OADC).   Date Released: 6/2/2015.

  15. December 17, 2014 CDC Ebola Response Update

    Centers for Disease Control (CDC) Podcasts

    2014-12-17

    This podcast provides an update on the Ebola response, as of December 17, 2014. It briefly describes CDC's "Operation Care Package.".  Created: 12/17/2014 by CDC’s Office of the Associate Director for Communication.   Date Released: 12/17/2014.

  16. User's guide to program RCN. [Set of 3 FORTRAN IV programs, RCN29, HFMOD7, and RCN229, for SCF calculations of radial wave functions; for CDC 7600 computer

    Energy Technology Data Exchange (ETDEWEB)

    Cowan, R. D.; Rajnak, K.; Renard, P.

    1976-06-01

    This is a set of three Fortran IV programs, RCN29, HFMOD7, and RCN229, based on the Herman--Skillman and Charlotte Froese Fischer programs, with extensive modifications and additions. The programs compute self-consistent-field radial wave functions and the various radial integrals involved in the computation of atomic energy levels and spectra.

  17. February 20, 2015 CDC Ebola Response Update

    Centers for Disease Control (CDC) Podcasts

    2015-02-20

    A strategy to rapidly identify and respond to cases of Ebola in remote areas in Liberia led to a drastic reduction in Ebola cases and cut the duration of these cluster outbreaks in half. Learn how CDC responders and their partners trekked through the jungle in their efforts to quickly stop the spread of the virus.  Created: 2/20/2015 by Office of the Associate Director for Communication (OADC).   Date Released: 2/20/2015.

  18. CDC Vital Signs-Preventing Melanoma

    Centers for Disease Control (CDC) Podcasts

    2015-06-02

    This podcast is based on the June 2015 CDC Vital Signs report. Skin cancer is the most common form of cancer in the U.S. In 2011, there were more than 65,000 cases of melanoma, the most deadly form of skin cancer. Learn how everyone can help prevent skin cancer.  Created: 6/2/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 6/2/2015.

  19. CDC Vital Signs-Heroin Epidemic

    Centers for Disease Control (CDC) Podcasts

    2015-07-07

    This podcast is based on the July 2015 CDC Vital Signs report. Heroin use and heroin-related overdose deaths are increasing. Most people are using it with other drugs, especially prescription opioid painkillers. Learn what can be done to prevent and treat the problem.  Created: 7/7/2015 by National Center for Injury Prevention and Control (NCIPC).   Date Released: 7/7/2015.

  20. September 24, 2015 CDC Ebola Response Update

    Centers for Disease Control (CDC) Podcasts

    2015-09-24

    In this podcast, CDC medical officer Alyson Goodman describes how CDC’s Children’s Health Team worked with partners to help U.S. hospitals prepare for a potential case of Ebola in a child.  Created: 9/24/2015 by Office of the Associate Director for Communication (OADC).   Date Released: 9/24/2015.

  1. A Child Development Centre (C.D.C.) Based on the World of Work and Everyday Life: A Case of Quality Education Provision for 2.5-5 Year Old Children.

    Science.gov (United States)

    Frangos, Christos

    1993-01-01

    Outlines the organization and activities of the Child Development Centre (CDC) of Aristotle University in Thessaloniki, which operates as a model preschool and kindergarten for over 300 similar institutions throughout Greece. The CDC utilizes art, music, visits to workplaces, movement activities, foreign languages and customs, computers,and free…

  2. Analysis list: Cdc73 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Cdc73 Muscle + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Cdc73.1.ts...v http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Cdc73.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Cd...c73.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Cdc73.Muscle.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Muscle.gml ...

  3. CDC Vital Signs-Hispanic Health

    Centers for Disease Control (CDC) Podcasts

    2015-05-05

    This podcast is based on the May 2015 CDC Vital Signs report. About one in six people living in the U.S. are Hispanic. The two leading causes of death in this group are heart disease and cancer, accounting for two out of five deaths. Unfortunately, many Hispanics face considerable barriers to getting high quality health care, including language and low income. Learn what can be done to reduce the barriers.  Created: 5/5/2015 by Office of Minority Health & Health Equity (OMHHE).   Date Released: 5/5/2015.

  4. April 28, 2015 CDC Ebola Response Update

    Centers for Disease Control (CDC) Podcasts

    2015-04-28

    In any disease outbreak, misinformation, a lack of understanding, and fear can lead to unfortunate side effects, like stigma. Stigma presents a challenge for communities during a time when they need to be strong to fight the disease. In this podcast, Molly Gaines-McCollom, CDC Health Communication Specialist, discusses the impact of stigma in the current Ebola outbreak and why it’s so important to fight it.  Created: 4/28/2015 by Office of the Associate Director for Communication (OADC).   Date Released: 4/28/2015.

  5. CDC Vital Signs-Heart Age

    Centers for Disease Control (CDC) Podcasts

    2015-09-01

    This podcast is based on the September 2015 CDC Vital Signs report. Your heart age is the age of your heart and blood vessels as a result of your risk factors for heart attack and stroke. If you smoke or have high blood pressure, your heart age will be much higher than your actual age. Learn what you can do to lower your heart age and keep it low.  Created: 9/1/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 9/1/2015.

  6. March 19, 2015 CDC Ebola Response Update

    Centers for Disease Control (CDC) Podcasts

    2015-03-19

    The Ebola outbreak has caused many people to ask whether animals, or specifically pets, are at risk of getting and spreading Ebola in the United States. In this podcast, Drs. Casey Barton Behravesh and Heather Bair-Brake, veterinarians at CDC, discuss how Ebola can affect animals, whether pets in the U.S. are at risk, and what people being monitored for Ebola should do if they have pets at home.  Created: 3/19/2015 by Office of the Associate Director for Communication (OADC).   Date Released: 3/19/2015.

  7. January 8, 2015 CDC Ebola Response Update

    Centers for Disease Control (CDC) Podcasts

    2015-01-08

    CDC scientists, recently returned from Guinea, recount their infection control training course for Guinean healthcare workers who work in health facilities other than Ebola Treatment Units. These workers treat anyone from pregnant women to suspected Ebola cases. It’s critical they be able to recognize and properly treat Ebola patients, not only to protect their own health, but that of their patients.  Created: 1/8/2015 by CDC’s Office of the Associate Director for Communication.   Date Released: 1/8/2015.

  8. Perseguir al SRAG: CDC en acción (Stalking SARS: CDC at Work)

    Centers for Disease Control (CDC) Podcasts

    2013-04-29

    En este podcast los niños de Kidtastics hablan sobre el brote del SRAS y cómo trabajaron los CDC para resolver el misterio.  Created: 4/29/2013 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 8/10/2016.

  9. Overexpression of CDC25B, CDC25C and phospho-CDC25C (Ser216) in vulvar squamous cell carcinomas are associated with malignant features and aggressive cancer phenotypes

    International Nuclear Information System (INIS)

    CDC25 phosphatases are important regulators of the cell cycle. Their abnormal expression detected in a number of tumors implies that their dysregulation is involved in malignant transformation. However, the role of CDC25s in vulvar cancer is still unknown. To shed light on their roles in the pathogenesis and to clarify their prognostic values, expression of CDC25A, CDC25B and CDC25C in a large series of vulvar squamous cell carcinomas were examined. Expression of CDC25A, CDC25B, CDC25C and phosphorylated (phospho)-CDC25C (Ser216) were examined in 300 vulvar carcinomas using immunohistochemistry. Western blot analysis was utilized to demonstrate CDC25s expression in vulvar cancer cell lines. Kinase and phosphatase assays were performed to exclude cross reactivity among CDC25s isoform antibodies. High nuclear CDC25A and CDC25B expression were observed in 51% and 16% of the vulvar carcinomas, respectively, whereas high cytoplasmic CDC25C expression was seen in 63% of the cases. In cytoplasm, nucleus and cytoplasm/nucleus high phospho-CDC25C (Ser216) expression was identified in 50%, 70% and 77% of the carcinomas, respectively. High expression of CDC25s correlated significantly with malignant features, including poor differentiation and infiltration of vessel for CDC25B, high FIGO stage, presence of lymph node metastases, large tumor diameter, poor differentiation for CDC25C and high FIGO stage, large tumor diameter, deep invasion and poor differentiation for phospho-CDC25C (Ser216). In univariate analysis, high expression of phospho-CDC25C (Ser216) was correlated with poor disease-specific survival (p = 0.04). However, such an association was annulled in multivariate analysis. Our results suggest that CDC25C and phospho-CDC25C (Ser216) play a crucial role and CDC25B a minor role in the pathogenesis and/or progression of vulvar carcinomas. CDC25B, CDC25C and phospho-CDC25C (Ser216) were associated with malignant features and aggressive cancer phenotypes. However, the

  10. CDC Vital Signs: Making Health Care Safer -- Protect Patients from Antibiotic Resistance

    Science.gov (United States)

    ... Search The CDC Cancel Submit Search The CDC Vital Signs Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Vital Signs Current issue Infographic Topics Covered Alcohol Cancer Cardiovascular ...

  11. CDC Vital Signs: Heart Age - Is Your Heart Older Than You?

    Science.gov (United States)

    ... Search The CDC Cancel Submit Search The CDC Vital Signs Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Vital Signs Current issue Infographic Topics Covered Alcohol Cancer Cardiovascular ...

  12. CDC Vital Signs: Making Health Care Safer -- Stop Infections from Lethal CRE Germs Now

    Science.gov (United States)

    ... Search The CDC Cancel Submit Search The CDC Vital Signs Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Vital Signs Current issue Infographic Topics Covered Alcohol Cancer Cardiovascular ...

  13. At the Computer Centre

    CERN Multimedia

    1983-01-01

    In preparation for the removal of of the ageing CDC 7600, a 1 megaword CYBER 170/835 and 1 megaword twin processor CYBER 170/875 were installed. The CYBER 835 was moved into production in August replacing the CYBER 720. On the successful introduction of the CYBER 875, the CYBER 720 was removed from service. (See Annual Report 1983 p.67.) The photo shows on foreground the two CDC computers, and on background the IBM 3081.

  14. Roles of the CDK Phosphorylation Sites of Yeast Cdc6 in Chromatin Binding and Rereplication

    OpenAIRE

    Honey, Sangeet; Futcher, Bruce

    2007-01-01

    The Saccharomyces cerevisiae Cdc6 protein is crucial for DNA replication. In the absence of cyclin-dependent kinase (CDK) activity, Cdc6 binds to replication origins, and loads Mcm proteins. In the presence of CDK activity, Cdc6 does not bind to origins, and this helps prevent rereplication. CDK activity affects Cdc6 function by multiple mechanisms: CDK activity affects transcription of CDC6, degradation of Cdc6, nuclear import of Cdc6, and binding of Cdc6 to Clb2. Here we examine some of the...

  15. March 11, 2015 CDC Ebola Response Update

    Centers for Disease Control (CDC) Podcasts

    2015-03-11

    CDC’s Eric Dziuban explains key messages CDC developed with UNICEF and the World Health Organization (WHO) on safe school operations in Guinea, Liberia, and Sierra Leone. After being closed for months due to the Ebola outbreak, schools in these countries are reopening – an important step in helping children and their communities return to normal. The key messages offer a tool that each country’s government can use to develop their own approach on safely reopening schools.  Created: 3/11/2015 by Office of the Associate Director for Communication (OADC).   Date Released: 3/11/2015.

  16. 13 CFR 120.857 - Voluntary transfer and surrender of CDC certification.

    Science.gov (United States)

    2010-01-01

    ... of CDC certification. 120.857 Section 120.857 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Other Cdc Requirements § 120.857 Voluntary transfer and surrender of CDC certification. A CDC may not transfer its certification or withdraw from...

  17. The Role of Cdc2 and Other Genes in Meiosis in Schizosaccharomyces Pombe

    OpenAIRE

    Iino, Y.; Hiramine, Y.; Yamamoto, M.

    1995-01-01

    The requirement of the cdc2, cdc13 and cdc25 genes for meiosis in Schizosaccharomyces pombe was investigated using three different conditions to induce meiosis. These genes were known to be required for meiosis II. cdc13 and cdc25 are essential for meiosis I. The cdc2 gene, which is required for the initiation of both mitotic S-phase and M-phase, is essential for premeiotic DNA synthesis and meiosis II. The requirement of cdc2 for meiosis I was unclear. This contrasts with Saccharomyces cerev...

  18. Zika Virus Causes Brain Defects in Babies: CDC

    Science.gov (United States)

    ... nih.gov/medlineplus/news/fullstory_158287.html Zika Virus Causes Brain Defects in Babies: CDC Agency says ... 2016 WEDNESDAY, April 13, 2016 (HealthDay News) -- Zika virus is a definite and direct cause of microcephaly ...

  19. Tuberculosis Decline in U.S. Has Stalled, CDC Reports

    Science.gov (United States)

    ... nlm.nih.gov/medlineplus/news/fullstory_157951.html Tuberculosis Decline in U.S. Has Stalled, CDC Reports Agency ... HealthDay News) -- Two decades of progress toward eliminating tuberculosis in the United States has stalled, with incidence ...

  20. Cdc42 promotes host defenses against fatal infection

    DEFF Research Database (Denmark)

    Lee, Keunwook; Boyd, Kelli L; Parekh, Diptiben V;

    2013-01-01

    The small Rho GTPase, Cdc42, regulates key signaling pathways required for multiple cell functions including maintenance of shape, polarity, proliferation, invasion, migration, differentiation and morphogenesis. As the role of Cdc42-dependent signaling in fibroblasts in vivo is unknown, we...... attempted to specifically delete it in these cells by crossing the Cdc42(fl/fl) mouse with a FSP-1 cre mouse, which is thought to mediate recombination exclusively in fibroblasts. Surprisingly, the FSP-1cre;Cdc42(fl/fl) mice died at 3 weeks of age due to overwhelming suppurative upper airway infections that...... were associated with neutrophilia and lymphopenia. Even though major aberrations in lymphoid tissue development were present in the mice, the principal cause of death was severe migration and killing abnormalities of the neutrophil population resulting in an inability to control infection. We also...

  1. CDC STATE System E-Cigarette Legislation - Youth Access

    Data.gov (United States)

    U.S. Department of Health & Human Services — 1995-2016. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. E-Cigarette Legislation—Youth...

  2. Southern States Lagging in Tough Smoking Bans, CDC Says

    Science.gov (United States)

    ... 159529.html Southern States Lagging in Tough Smoking Bans, CDC Says Only 6 in 10 Americans covered ... federal government report says. This type of law bans smoking in all indoor areas of workplaces, restaurants ...

  3. CDC Warns of Dangers of Plastic Surgery in Dominican Republic

    Science.gov (United States)

    ... a very mutilating infection. They're going for cosmetic surgery, and they will be scarred. It's a terrible ... postoperative infections, particularly ones that are related to cosmetic surgery," Daley said. The CDC report warns about the ...

  4. CDC STATE System E-Cigarette Legislation - Preemption

    Data.gov (United States)

    U.S. Department of Health & Human Services — 1995-2016. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. E-Cigarette Legislation—Preemption....

  5. CDC STATE System E-Cigarette Legislation - Tax

    Data.gov (United States)

    U.S. Department of Health & Human Services — 1995-2016. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. E-Cigarette Legislation—Tax. The...

  6. CDC STATE System E-Cigarette Legislation - Smokefree Indoor Air

    Data.gov (United States)

    U.S. Department of Health & Human Services — 1995-2016. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. E-Cigarette Legislation—Smokefree...

  7. CDC STATE System Tobacco Legislation - Smokefree Indoor Air Summary

    Data.gov (United States)

    U.S. Department of Health & Human Services — 1995-2016. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. Legislation – Smokefree Indoor Air....

  8. CDC STATE System E-Cigarette Legislation - Smokefree Campus

    Data.gov (United States)

    U.S. Department of Health & Human Services — 1995-2016. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. E-Cigarette Legislation—Smokefree...

  9. CDC STATE System E-Cigarette Legislation - Licensure

    Data.gov (United States)

    U.S. Department of Health & Human Services — 1995-2016. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. E-Cigarette Legislation—Licensure....

  10. CDC STATE System Tobacco Legislation - Smokefree Indoor Air

    Data.gov (United States)

    U.S. Department of Health & Human Services — 1995-2016. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. Legislation – Smokefree Indoor Air....

  11. CDC WONDER: Vaccine Adverse Event Reporting System (VAERS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Vaccine Adverse Event Reporting System (VAERS) online database on CDC WONDER provides counts and percentages of adverse event case reports after vaccination, by...

  12. CDC WONDER: Compressed Mortality - Underlying Cause of Death

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CDC WONDER Mortality - Underlying Cause of Death online database is a county-level national mortality and population database spanning the years since 1979...

  13. Cell cycle sibling rivalry: Cdc2 vs. Cdk2.

    Science.gov (United States)

    Kaldis, Philipp; Aleem, Eiman

    2005-11-01

    It has been long believed that the cyclin-dependent kinase 2 (Cdk2) binds to cyclin E or cyclin A and exclusively promotes the G1/S phase transition and that Cdc2/cyclin B complexes play a major role in mitosis. We now provide evidence that Cdc2 binds to cyclin E (in addition to cyclin A and B) and is able to promote the G1/S transition. This new concept indicates that both Cdk2 and/or Cdc2 can drive cells through G1/S phase in parallel. In this review we discuss the classic cell cycle model and how results from knockout mice provide new evidence that refute this model. We focus on the roles of Cdc2 and p27 in regulating the mammalian cell cycle and propose a new model for cell cycle regulation that accommodates these novel findings. PMID:16258277

  14. CDC WONDER: Daily Air Temperatures and Heat Index

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Daily Air Temperature and Heat Index data available on CDC WONDER are county-level daily average air temperatures and heat index measures spanning the years...

  15. CDC WONDER: Detailed Mortality - Underlying Cause of Death

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Detailed Mortality - Underlying Cause of Death data on CDC WONDER are county-level national mortality and population data spanning the years 1999-2009. Data are...

  16. Cdc42 is critical for cartilage development during endochondral ossification.

    Science.gov (United States)

    Suzuki, Wataru; Yamada, Atsushi; Aizawa, Ryo; Suzuki, Dai; Kassai, Hidetoshi; Harada, Takeshi; Nakayama, Mutsuko; Nagahama, Ryo; Maki, Koutaro; Takeda, Shu; Yamamoto, Matsuo; Aiba, Atsu; Baba, Kazuyoshi; Kamijo, Ryutaro

    2015-01-01

    Cdc42 is a widely expressed protein that belongs to the family of Rho GTPases and controls a broad variety of signal transduction pathways in a variety of cell types. To investigate the physiological functions of Cdc42 during cartilage development, we generated chondrocyte-specific inactivated Cdc42 mutant mice (Cdc42(fl/fl); Col2-Cre). The gross morphology of mutant neonates showed shorter limbs and body as compared with the control mice (Cdc42(fl/fl)). Skeletal preparations stained with alcian blue and alizarin red also revealed that the body and the long bone length of the mutants were shorter than those of the control mice. Furthermore, severe defects were found in growth plate chondrocytes in the femur sections of mutant mice, characterized by a reduced proliferating zone height, wider hypertrophic zone, and loss of columnar organization in proliferating chondrocytes. The expression levels of chondrocyte marker genes, such as Col2, Col10, and Mmp13, in mutant mice were decreased as compared with the control mice. Mineralization of trabecular bones in the femur sections was also decreased in the mutants as compared with control mice, whereas osteoid volume was increased. Together these results suggested that chondrocyte proliferation and differentiation in growth plates in the present mutant mice were not normally organized, which contributed to abnormal bone formation. We concluded that Cdc42 is essential for cartilage development during endochondral bone formation. PMID:25343271

  17. Role of AtCDC48 & the AtCDC48 Regulatory Protein Family, PUX, in Plant Cell Morphogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Bednarek, Sebastian, Y.

    2009-11-08

    The long-term objective of this work is to understand the molecular events and mechanisms involved in secretory membrane trafficking and organelle biogenesis, which are crucial for normal plant growth and development. Our studies have suggested a vital role for the cytosolic chaperone Cdc48p/p97 during cytokinesis and cell expansion which are highly dependent upon secretory membrane trafficking. Localization studies have shown that the plant Cdc48p/p97, AtCDC48, and the Arabidopsis ortholog of the ER- and Golgi-associated SNARE, syntaxin 5, (referred to as SYP31) are targeted to the division plane during cytokinesis. In addition, AtCDC48 and SYP31 were shown to interact in vitro and in vivo. To characterize further the function of AtCDC48 and SYP31 we have utilized affinity chromatography and MALDI-MS to identify several plant-specific proteins that interact with SYP31 and/or modulate the activity of AtCDC48 including two UBX (i.e. ubiquitin-like) domain containing proteins, PUX1 and PUX2 (Proteins containing UBX domain). These proteins define a plant protein family consisting of 15 uncharacterized members that we postulate interact with AtCDC48. Biochemical studies have demonstrated that PUX2 is a novel membrane adapter for AtCDC48 that mediates AtCDC48/SYP31 interaction and is likely to control AtCDC48-dependent membrane fusion. In contrast, PUX1 negatively regulates AtCDC48 by inhibiting its ATPase activity and by promoting the disassembly of the active hexamer. These findings provide the first evidence that the assembly and disassembly of the CDC48/p97complex is actually a dynamic process. This new unexpected level of regulation for CDC48/p97 was demonstrated to be critical in vivo as pux1 loss-of-function mutants grow faster than wild-type plants. These studies suggest a role for AtCDC48 in plant cell cycle progression including cytokinesis and/or cell expansion. The proposed studies are designed to: 1) characterize further the localization and function of AtCDC

  18. Structure and Expression of Several Putative Cdc42-Interacting Proteins in Magnaporthe grisea

    Institute of Scientific and Technical Information of China (English)

    ZHENG Wu; CHEN Ji-sheng; ZHENG Shi-qin; LU Guo-dong; WANG Zong-hua

    2006-01-01

    MgCdc42 (Cdc42 in Magnaporthe grisea), with high homology to ScCdc42 (Cdc42 in Saccharomyces cerevisiae), has been demonstrated to involve in the morphogenesis and infection process. To further understand the signaling network,the putative MgCdc42-interacting proteins were analyzed. ScCdc42-interacting protein sequences were first used to BLAST against the M. grisea genome database to retrieve their corresponding analogs. Subsequently, conserved domains of these proteins were compared and expression patterns of their encoding genes in different MgCdc42 mutation states were analyzed by semiquantitative RT-PCR. All retrieved analogs of ScCdc42-interacting proteins from the M.grisea database have conserved domains as those in S. cerevisiae. Expression of their encoding genes increased in MgCdc42CA mutant and decreased in MgCdc42KO mutant. However, MgBem1, Chm1, and MgGic1 in MgCdc42DN mutant had the same expression level as that in the wild type, although MgBem4, MgBoi2, MgCdc24, MgGic2, MgRga1,and Mst20 had decreased expression level, as expected. Overall, it is concluded that there may exist a similar Cdc42 signal pathway in M. grisea as in S. cerevisiae and MgCdc42 plays a key role in the pathway.

  19. User's guide to REVERT. A CDC 7600 program for converting Spent Fuel Test - Climax data to engineering units, with corrections

    International Nuclear Information System (INIS)

    A CDC 7600 computer program, REVERT, can revise Spent Fuel Test - Climax data files using one of several algorithms, depending on the type of data. The algorithms use coefficients from a separate file organized by data type identifiers. REVERT can also make that file of coefficients, using data from tapes made by Hewlett-Packard equipment employed for data acquisition on the spent Fuel Test - Climax at NTS. 12 references

  20. Insights into Cdc13 Dependent Telomere Length Regulation

    Energy Technology Data Exchange (ETDEWEB)

    M Mason; E Skordalakes

    2011-12-31

    Cdc13 is a single stranded telomere binding protein that specifically localizes to the telomere ends of budding yeasts and is essential for cell viability. It caps the ends of chromosomes thus preventing chromosome end-to-end fusions and exonucleolytic degradation, events that could lead to genomic instability and senescence, the hallmark of aging. Cdc13 is also involved in telomere length regulation by recruiting or preventing access of telomerase to the telomeric overhang. Recruitment of telomerase to the telomeres for G-strand extension is required for continuous cell division, while preventing its access to the telomeres through capping the chromosome ends prevents mitotic events that could lead to cell immortality, the hall mark of carcinogenesis. Cdc13 and its putative homologues human CTC1 and POT1 are therefore key to many biological processes directly associated with life extension and cancer prevention and can be viewed as an ideal target for cancer and age related therapies.

  1. Cdc42 regulates cofilin during the establishment of neuronal polarity

    DEFF Research Database (Denmark)

    Garvalov, Boyan K; Flynn, Kevin C; Neukirchen, Dorothee;

    2007-01-01

    The establishment of polarity is an essential process in early neuronal development. Although a number of molecules controlling neuronal polarity have been identified, genetic evidence about their physiological roles in this process is mostly lacking. We analyzed the consequences of loss of Cdc42......, a central regulator of polarity in multiple systems, on the polarization of mammalian neurons. Genetic ablation of Cdc42 in the brain led to multiple abnormalities, including striking defects in the formation of axonal tracts. Neurons from the Cdc42 null animals sprouted neurites but had a strongly...... suppressed ability to form axons both in vivo and in culture. This was accompanied by disrupted cytoskeletal organization, enlargement of the growth cones, and inhibition of filopodial dynamics. Axon formation in the knock-out neurons was rescued by manipulation of the actin cytoskeleton, indicating that the...

  2. Informe Signos Vitales de los CDC Obesidad infantil - (Childhood Obesity)

    Centers for Disease Control (CDC) Podcasts

    2013-08-06

    Este podcast se basa en el informe Signos Vitales de los CDC de agosto del 2013. La tasa de obesidad entre los niños en edad prescolar de bajos ingresos ha disminuido, pero todavía uno de cada seis niños hispanos es obeso. Este programa habla brevemente sobre lo que se puede hacer.  Created: 8/6/2013 by Centers for Disease Control and Prevention (CDC).   Date Released: 8/6/2013.

  3. Photoionization of bonding and antibonding-type atom-fullerene hybrid states in Cd@C$_{60}$ vs Zn@C$_{60}$60

    CERN Document Server

    Javani, Mohammad H; Madjet, Mohamed E; Manson, Steven T; Chakraborty, Himadri S

    2014-01-01

    Powerful hybridization of the Cd 4$d$ state with the $d$-angular momentum state of C$_{60}$ $\\pi$ symmetry is found in the local density approximation (LDA) structure of Cd@C$_{60}$ ground state. The photoionization of the resulting symmetric and antisymmetric levels are computed using the time dependent LDA method to include electron correlations. Cross sections exhibit effects of the C$_{60}$ plasmonic motion coherently coupled to the diffraction-type cavity oscillations induced by local emissions from C$_{60}$. The Cd@C$_{60}$ results exhibit a substantial difference from our previous results for Zn@C$_{60}$.

  4. Photoionization of bonding and antibonding-type atom-fullerene hybrid states in Cd@C60 vs Zn@C60

    International Nuclear Information System (INIS)

    Powerful hybridization of the Cd 4d state with the d-angular momentum state of C60 π symmetry is found in the local density approximation (LDA) structure of Cd@C60 ground state. The photoionization of the resulting symmetric and antisymmetric levels are computed using the time dependent LDA method to include electron correlations. Cross sections exhibit effects of the C60 plasmonic motion coherently coupled to the diffraction-type cavity oscillations induced by local emissions from C60. The Cd@C60 results exhibit a substantial difference from our previous results for Zn@C60. (paper)

  5. Continuous cell injury promotes hepatic tumorigenesis in cdc42-deficient mouse liver

    DEFF Research Database (Denmark)

    van Hengel, Jolanda; D'Hooge, Petra; Hooghe, Bart;

    2008-01-01

    BACKGROUND & AIMS: The Rho small guanosine triphosphatase Cdc42 is critical for diverse cellular functions, including regulation of actin organization, cell polarity, intracellular membrane trafficking, transcription, cell-cycle progression, and cell transformation. This implies that Cdc42 might be...

  6. Cdc42 overexpression induces hyperbranching in the developing mammary gland by enhancing cell migration

    OpenAIRE

    Bray, Kristi; Gillette, Melissa; Young, Jeanette; Loughran, Elizabeth; Hwang, Melissa; Sears, James Cooper; Vargo-Gogola, Tracy

    2013-01-01

    Introduction The Rho GTPase Cdc42 is overexpressed and hyperactivated in breast tumors compared to normal breast tissue. Cdc42 regulates key processes that are critical for mammary gland morphogenesis and become disrupted during the development, progression, and metastasis of breast cancer. However, the contribution of Cdc42 to normal and neoplastic mammary gland development in vivo remains poorly understood. We were therefore interested in investigating the effects of Cdc42 overexpression on...

  7. CDC 24/7: Saving Lives, Protecting People

    Centers for Disease Control (CDC) Podcasts

    2012-06-04

    24/7, CDC provides health information, responds to public health emergencies and natural disasters, and monitors disease.  Created: 6/4/2012 by Office of the Associate Director of Communciation (OADC).   Date Released: 6/4/2012.

  8. CDC Vital Signs: High Blood Pressure and Cholesterol

    Science.gov (United States)

    ... 1.36 MB] Read the MMWR Science Clips High Blood Pressure and Cholesterol Out of Control Recommend on Facebook ... by County http://apps.nccd.cdc.gov/GISCVH2/ High Blood Pressure and High Cholesterol Among US Adults SOURCES: National ...

  9. CDC Reports Link Between Zika Virus and Microcephaly in Brazil

    Science.gov (United States)

    ... news/fullstory_157213.html CDC Reports Link Between Zika Virus and Microcephaly in Brazil And two U.S. women ... Feb. 11, 2016 (HealthDay News) -- Traces of the Zika virus have been identified in the tissue of two ...

  10. Cdc20 control of cell fate during prolonged mitotic arrest

    DEFF Research Database (Denmark)

    Nilsson, Jakob

    2011-01-01

    The fate of cells arrested in mitosis by antimitotic compounds is complex but is influenced by competition between pathways promoting cell death and pathways promoting mitotic exit. As components of both of these pathways are regulated by Cdc20-dependent degradation, I hypothesize that variations...

  11. 13 CFR 120.830 - Reports a CDC must submit.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Reports a CDC must submit. 120.830 Section 120.830 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development... in organizational status; (e) Changes in any condition that affects its eligibility to continue...

  12. Sex Partner with No Zika Symptoms Transmits Virus: CDC

    Science.gov (United States)

    ... news/fullstory_160643.html Sex Partner With No Zika Symptoms Transmits Virus: CDC New report also highlights ties between Zika ... HealthDay News) -- U.S. health officials report that the Zika virus can be spread sexually even when a partner ...

  13. Dangerous Creatures - A Visit to the CDC Insectary

    Centers for Disease Control (CDC) Podcasts

    2012-11-07

    Tour CDC’s insectary with Sofi, a young host, and learn from CDC researchers about mosquitoes and insecticide resistance.  Created: 11/7/2012 by Center for Global Health (CGH).   Date Released: 12/20/2012.

  14. Vaccines for Teens (A Minute of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    2016-08-25

    CDC recommends children aged 11 to 12 get three vaccines to protect from meningitis; cancers caused by human papillomavirus infections; and tetanus, diphtheria, and pertussis. This podcast discusses vaccination of adolescents.  Created: 8/25/2016 by MMWR.   Date Released: 8/25/2016.

  15. 77 FR 23733 - CDC/HRSA Advisory Committee on HIV and STD Prevention and Treatment

    Science.gov (United States)

    2012-04-20

    ... Care Data Systems; (3) External Peer Review of CDC Youth HIV/STI Prevention and Sexual Health..., CDC, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, 1600 Clifton Road, NE... CDC/HRSA Advisory Committee on HIV and STD Prevention and Treatment In accordance with section...

  16. 13 CFR 120.810 - Applications for certification as a CDC.

    Science.gov (United States)

    2010-01-01

    ... LOANS Development Company Loan Program (504) Certification Procedures to Become A Cdc § 120.810 Applications for certification as a CDC. (a) An applicant for certification as a CDC must apply to the SBA... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Applications for certification...

  17. Expression of CDC5L is associated with tumor progression in gliomas.

    Science.gov (United States)

    Chen, Wenjuan; Zhang, Li; Wang, Yan; Sun, Jie; Wang, Donglin; Fan, Shaochen; Ban, Na; Zhu, Junya; Ji, Bin; Wang, Yuchan

    2016-03-01

    Cell division cycle 5-like (CDC5L) protein is a cell cycle regulator of the G2/M transition and has been reported to participate in the catalytic step of pre-messenger RNA (mRNA) splicing and DNA damage repair. Recently, it was also found to act as a candidate oncogene in osteosarcoma and cervical tumors. However, the role of CDC5L expression in tumor biology was still unclear. Here, we analyzed the expression and clinical significance of CDC5L in gliomas. The expression of CDC5L in fresh glioma tissues and paraffin-embedded slices was evaluated by western blot and immunohistochemistry, respectively. We found that CDC5L was highly expressed in glioma tissues. The expression of CDC5L was significantly associated with glioma pathology grade and Ki-67 expression. Univariate and multivariate analyses showed that high CDC5L expression was an independent prognostic factor for glioma patients' survival. To determine whether CDC5L could regulate the proliferation of glioma cells, we transfected glioma cells with interfering RNA target CDC5L, then investigated cell proliferation with cell counting kit (CCK)-8, flow cytometry assays and colony formation analyses. Our results indicated that knockdown of CDC5L would inhibit proliferation of glioma cells. Besides, reduced expression of CDC5L could induce the apoptosis of glioma cells. These findings suggested that CDC5L might play an important role in glioma and thus be a promising therapeutic target of glioma. PMID:26490980

  18. Overexpression of CDC2/CyclinB1 in gliomas, and CDC2 depletion inhibits proliferation of human glioma cells in vitro and in vivo

    International Nuclear Information System (INIS)

    Gliomas are the most common and aggressive primary brain tumors for which unfortunately no effective treatment modalities exist despite advances in molecular biology as the knowledge base to unravel the extremely complex molecular mechanisms of tumorigenesis is limited. In this study an attempt has been made to understand the molecular pathological basis of tumorigenesis which led to an identification of an oncogene, CDC2, and an epigenetic strategy has been evaluated to control the tumorigensis by downregulating this oncogene. Tissue microarrays were utilized to investigate the expression of genes in a large number of tumor samples and to identify overexpressed genes which could be potentially causing tumorigenesis. Retroviral vectors expressing short hairpin RNAs (shRNAs) targeted against CDC2 were designed and transducted into human glioma cell line ex vivo in order to downregulate the expression of CDC2. Real-Time PCR was used to determine the level of CDC2 mRNA. Western Blotting was used to determine the level of expression of CDC2 protein as measure to quantify down regulation of CDC2 expression along with use of flow cytometry to investigate effect of shRNAs on cell cycles and detection of apoptosis. Following ex vivo study, viral particles containing small interfering RNA for CDC2 were subsequently injected into xenogeneic graft tumor of nude mice and the weight of human glioma xenografts, survival and resulting phenotypic changes of target gene were investigated. Human glioma tissue microarrays indicated the positive expression rates of CDC2/CyclinB1 with a positive correlation with pathologic grades (r = 0.982, r = 0.959, respectively). Retroviral vectors expressing short hairpin RNAs (shRNAs) against CDC2 caused efficient deletion of CDC2, cellular G2/M arrest concluding in apoptosis and inhibition of proliferation in human glioma cells U251 and SHG-44 cell lines ex vivo. And the viral particles containing small interfering RNA for CDC2 were subsequently

  19. Overexpression of CDC2/CyclinB1 in gliomas, and CDC2 depletion inhibits proliferation of human glioma cells in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Wang Ai-Dong

    2008-01-01

    Full Text Available Abstract Background Gliomas are the most common and aggressive primary brain tumors for which unfortunately no effective treatment modalities exist despite advances in molecular biology as the knowledge base to unravel the extremely complex molecular mechanisms of tumorigenesis is limited. In this study an attempt has been made to understand the molecular pathological basis of tumorigenesis which led to an identification of an oncogene, CDC2, and an epigenetic strategy has been evaluated to control the tumorigensis by downregulating this oncogene. Methods Tissue microarrays were utilized to investigate the expression of genes in a large number of tumor samples and to identify overexpressed genes which could be potentially causing tumorigenesis. Retroviral vectors expressing short hairpin RNAs (shRNAs targeted against CDC2 were designed and transducted into human glioma cell line ex vivo in order to downregulate the expression of CDC2. Real-Time PCR was used to determine the level of CDC2 mRNA. Western Blotting was used to determine the level of expression of CDC2 protein as measure to quantify down regulation of CDC2 expression along with use of flow cytometry to investigate effect of shRNAs on cell cycles and detection of apoptosis. Following ex vivo study, viral particles containing small interfering RNA for CDC2 were subsequently injected into xenogeneic graft tumor of nude mice and the weight of human glioma xenografts, survival and resulting phenotypic changes of target gene were investigated. Results Human glioma tissue microarrays indicated the positive expression rates of CDC2/CyclinB1 with a positive correlation with pathologic grades (r = 0.982, r = 0.959, respectively. Retroviral vectors expressing short hairpin RNAs (shRNAs against CDC2 caused efficient deletion of CDC2, cellular G2/M arrest concluding in apoptosis and inhibition of proliferation in human glioma cells U251 and SHG-44 cell lines ex vivo. And the viral particles

  20. Mitotic Exit Function of Polo-like Kinase Cdc5 Is Dependent on Sequential Activation by Cdk1.

    Science.gov (United States)

    Rodriguez-Rodriguez, Jose-Antonio; Moyano, Yolanda; Játiva, Soraya; Queralt, Ethel

    2016-05-31

    To complete mitosis, Saccharomyces cerevisiae needs to activate the mitotic phosphatase Cdc14. Two pathways contribute to Cdc14 regulation: FEAR (Cdc14 early anaphase release) and MEN (mitotic exit network). Cdc5 polo-like kinase was found to be an important mitotic exit component. However, its specific role in mitotic exit regulation and its involvement in Cdc14 release remain unclear. Here, we provide insight into the mechanism by which Cdc5 contributes to the timely release of Cdc14. Our genetic and biochemical data indicate that Cdc5 acts in parallel with MEN during anaphase. This MEN-independent Cdc5 function requires active separase and activation by Cdk1-dependent phosphorylation. Cdk1 first phosphorylates Cdc5 to activate it in early anaphase, and then, in late anaphase, further phosphorylation of Cdc5 by Cdk1 is needed to promote its MEN-related functions. PMID:27210759

  1. Draft Genome Assemblies of Enterobacter aerogenes CDC 6003-71, Enterobacter cloacae CDC 442-68, and Pantoea agglomerans UA 0804-01.

    Science.gov (United States)

    Minogue, T D; Daligault, H E; Davenport, K W; Bishop-Lilly, K A; Bruce, D C; Chain, P S; Coyne, S R; Chertkov, O; Freitas, T; Frey, K G; Jaissle, J; Koroleva, G I; Ladner, J T; Palacios, G F; Redden, C L; Xu, Y; Johnson, S L

    2014-01-01

    The Enterobacteriaceae are environmental and enteric microbes. We sequenced the genomes of two Enterobacter reference strains, E. aerogenes CDC 6003-71 and E. cloacae CDC 442-68, as well as one near neighbor used as an exclusionary reference for diagnostics, Pantoea agglomerans CDC UA0804-01. The genome sizes range from 4.72 to 5.55 Mbp and have G+C contents from 54.6 to 55.1%. PMID:25342683

  2. Draft Genome Assemblies of Enterobacter aerogenes CDC 6003-71, Enterobacter cloacae CDC 442-68, and Pantoea agglomerans UA 0804-01

    OpenAIRE

    Minogue, T. D.; Daligault, H. E.; Davenport, K. W.; Bishop-Lilly, K. A.; Bruce, D. C.; Chain, P. S.; Coyne, S. R.; Chertkov, O.; Freitas, T.; Frey, K. G.; Jaissle, J.; Koroleva, G. I.; Ladner, J. T.; Palacios, G. F.; Redden, C. L.

    2014-01-01

    The Enterobacteriaceae are environmental and enteric microbes. We sequenced the genomes of two Enterobacter reference strains, E. aerogenes CDC 6003-71 and E. cloacae CDC 442-68, as well as one near neighbor used as an exclusionary reference for diagnostics, Pantoea agglomerans CDC UA0804-01. The genome sizes range from 4.72 to 5.55 Mbp and have G+C contents from 54.6 to 55.1%.

  3. Basic JCL for the CRAY-1 operating system (COS) with emphasis on making the transition from CDC 7600/SCOPE

    Science.gov (United States)

    Howe, G.; Saunders, D.

    1983-01-01

    Users of the CDC 7600 at Ames are assisted in making the transition to the CRAY-1. Similarities and differences in the basic JCL are summarized, and a dozen or so examples of typical batch jobs for the two systems are shown in parallel. Some changes to look for in FORTRAN programs and in the use of UPDATE are also indicated. No attempt is made to cover magnetic tape handling. The material here should not be considered a substitute for reading the more conventional manuals or the User's Guide for the Advanced Computational Facility, available from the Computer Information Center.

  4. COMPUTING

    CERN Multimedia

    M. Kasemann

    Overview In autumn the main focus was to process and handle CRAFT data and to perform the Summer08 MC production. The operational aspects were well covered by regular Computing Shifts, experts on duty and Computing Run Coordination. At the Computing Resource Board (CRB) in October a model to account for service work at Tier 2s was approved. The computing resources for 2009 were reviewed for presentation at the C-RRB. The quarterly resource monitoring is continuing. Facilities/Infrastructure operations Operations during CRAFT data taking ran fine. This proved to be a very valuable experience for T0 workflows and operations. The transfers of custodial data to most T1s went smoothly. A first round of reprocessing started at the Tier-1 centers end of November; it will take about two weeks. The Computing Shifts procedure was tested full scale during this period and proved to be very efficient: 30 Computing Shifts Persons (CSP) and 10 Computing Resources Coordinators (CRC). The shift program for the shut down w...

  5. Cdc18 transcription and proteolysis couple S phase to passage through mitosis.

    OpenAIRE

    Baum, B.; Nishitani, H; Yanow, S; Nurse, P

    1998-01-01

    In fission yeast, cdc18p plays a critical role in bringing about the onset of S phase. We show that cdc18p expression is subject to a complex sequence of cell cycle controls which ensure that cdc18p levels rise dramatically as cells exit mitosis, before the appearance of CDK activity in G1. We find that transcription of cdc18, together with the transcription of other cdc10p/res1p targets, is first initiated as cells enter mitosis and continues even in cells arrested in mitosis with highly con...

  6. Expression of CDc6 after acute spinal cord injury in adult rats.

    Science.gov (United States)

    Chen, Chen; Lu, Jian; Yu, Qin; Xiao, Jian-Ru; Wei, Hai-Feng; Song, Xin-Jian; Ge, Jian-Bing; Tao, Wei-Dong; Qian, Rong; Yu, Xiao-Wei; Zhao, Jian

    2016-04-01

    The cell division cycle 6 (CDc6) protein has been primarily investigated as a component of the pre-replicative complex for the initiation of DNA replication. Some studies have shown that CDc6 played a critical role in the development of human carcinoma. However, the expression and roles of CDc6 in the central nervous system remain unknown. We have performed an acute spinal cord injury (SCI) model in adult rats and investigated the dynamic changes of CDc6 expression in spinal cord. Western blot have found that CDc6 protein levels first significantly increase, reach a peak at day 3, and then gradually return to normal level at day 14 after SCI. Double immunofluorescence staining showed that CDc6 immunoreactivity was found in neurons, astrocytes, and microglia. Additionally, colocalization of CDc6/active caspase-3 has been detected in neurons and colocalization of CDc6/proliferating cell nuclear antigen has been detected in astrocytes and microglial. In vitro, CDc6 depletion by short interfering RNA inhibits astrocyte proliferation and reduces cyclin A and cyclin D1 protein levels. CDc6 knockdown also decreases neuronal apoptosis. We speculate that CDc6 might play crucial roles in CNS pathophysiology after SCI. PMID:26899166

  7. COMPUTING

    CERN Multimedia

    P. McBride

    The Computing Project is preparing for a busy year where the primary emphasis of the project moves towards steady operations. Following the very successful completion of Computing Software and Analysis challenge, CSA06, last fall, we have reorganized and established four groups in computing area: Commissioning, User Support, Facility/Infrastructure Operations and Data Operations. These groups work closely together with groups from the Offline Project in planning for data processing and operations. Monte Carlo production has continued since CSA06, with about 30M events produced each month to be used for HLT studies and physics validation. Monte Carlo production will continue throughout the year in the preparation of large samples for physics and detector studies ramping to 50 M events/month for CSA07. Commissioning of the full CMS computing system is a major goal for 2007. Site monitoring is an important commissioning component and work is ongoing to devise CMS specific tests to be included in Service Availa...

  8. COMPUTING

    CERN Multimedia

    I. Fisk

    2011-01-01

    Introduction CMS distributed computing system performed well during the 2011 start-up. The events in 2011 have more pile-up and are more complex than last year; this results in longer reconstruction times and harder events to simulate. Significant increases in computing capacity were delivered in April for all computing tiers, and the utilisation and load is close to the planning predictions. All computing centre tiers performed their expected functionalities. Heavy-Ion Programme The CMS Heavy-Ion Programme had a very strong showing at the Quark Matter conference. A large number of analyses were shown. The dedicated heavy-ion reconstruction facility at the Vanderbilt Tier-2 is still involved in some commissioning activities, but is available for processing and analysis. Facilities and Infrastructure Operations Facility and Infrastructure operations have been active with operations and several important deployment tasks. Facilities participated in the testing and deployment of WMAgent and WorkQueue+Request...

  9. COMPUTING

    CERN Multimedia

    M. Kasemann

    Overview During the past three months activities were focused on data operations, testing and re-enforcing shift and operational procedures for data production and transfer, MC production and on user support. Planning of the computing resources in view of the new LHC calendar in ongoing. Two new task forces were created for supporting the integration work: Site Commissioning, which develops tools helping distributed sites to monitor job and data workflows, and Analysis Support, collecting the user experience and feedback during analysis activities and developing tools to increase efficiency. The development plan for DMWM for 2009/2011 was developed at the beginning of the year, based on the requirements from the Physics, Computing and Offline groups (see Offline section). The Computing management meeting at FermiLab on February 19th and 20th was an excellent opportunity discussing the impact and for addressing issues and solutions to the main challenges facing CMS computing. The lack of manpower is particul...

  10. Two Cdc2 Kinase Genes with Distinct Functions in Vegetative and Infectious Hyphae in Fusarium graminearum.

    Directory of Open Access Journals (Sweden)

    Huiquan Liu

    2015-06-01

    Full Text Available Eukaryotic cell cycle involves a number of protein kinases important for the onset and progression through mitosis, most of which are well characterized in the budding and fission yeasts and conserved in other fungi. However, unlike the model yeast and filamentous fungi that have a single Cdc2 essential for cell cycle progression, the wheat scab fungus Fusarium graminearum contains two CDC2 orthologs. The cdc2A and cdc2B mutants had no obvious defects in growth rate and conidiation but deletion of both of them is lethal, indicating that these two CDC2 orthologs have redundant functions during vegetative growth and asexual reproduction. However, whereas the cdc2B mutant was normal, the cdc2A mutant was significantly reduced in virulence and rarely produced ascospores. Although deletion of CDC2A had no obvious effect on the formation of penetration branches or hyphopodia, the cdc2A mutant was limited in the differentiation and growth of infectious growth in wheat tissues. Therefore, CDC2A plays stage-specific roles in cell cycle regulation during infectious growth and sexual reproduction. Both CDC2A and CDC2B are constitutively expressed but only CDC2A was up-regulated during plant infection and ascosporogenesis. Localization of Cdc2A- GFP to the nucleus but not Cdc2B-GFP was observed in vegetative hyphae, ascospores, and infectious hyphae. Complementation assays with chimeric fusion constructs showed that both the N- and C-terminal regions of Cdc2A are important for its functions in pathogenesis and ascosporogenesis but only the N-terminal region is important for its subcellular localization. Among the Sordariomycetes, only three Fusarium species closely related to F. graminearum have two CDC2 genes. Furthermore, F. graminearum uniquely has two Aurora kinase genes and one additional putative cyclin gene, and its orthologs of CAK1 and other four essential mitotic kinases in the budding yeast are dispensable for viability. Overall, our data

  11. COMPUTING

    CERN Multimedia

    I. Fisk

    2013-01-01

    Computing activity had ramped down after the completion of the reprocessing of the 2012 data and parked data, but is increasing with new simulation samples for analysis and upgrade studies. Much of the Computing effort is currently involved in activities to improve the computing system in preparation for 2015. Operations Office Since the beginning of 2013, the Computing Operations team successfully re-processed the 2012 data in record time, not only by using opportunistic resources like the San Diego Supercomputer Center which was accessible, to re-process the primary datasets HTMHT and MultiJet in Run2012D much earlier than planned. The Heavy-Ion data-taking period was successfully concluded in February collecting almost 500 T. Figure 3: Number of events per month (data) In LS1, our emphasis is to increase efficiency and flexibility of the infrastructure and operation. Computing Operations is working on separating disk and tape at the Tier-1 sites and the full implementation of the xrootd federation ...

  12. QMESH/RHENUM/QPLOT mainframe and plotter conversion: CDC6600 to IBM 360/370 and SC4020 to Calcomp

    International Nuclear Information System (INIS)

    A code conversion project to modify an existing set of FORTRAN computer programs to run on a different mainframe and to drive a different plotter is discussed. The mainframe conversion was from a CDC6600 to an IBM360; the plotter conversion was from an SC4020 (driven by calls to SCORS library subroutines) to a Calcomp. The changes made because of differences between the FORTRAN compliers were relatively minor. IBM ASSEMBLER source decks were acquired to replace all of the CDC special features (such as ENCODE/DECODE) which have no direct IBM equivalents. The plotter call conversion was more difficult, but was still relatively straightforward. By far the most difficult part of the conversion effort involved converting the file-handling protocol from default-tolerant SCOPE on the CDC6600 to explicit JCL (Job Control Language) on the IBM360; listings of all the IBM deck setups used are included in the Appendix. The programs converted were QMESH, RENUM, QPLOT, RENUM8, and QPLOT8, which together constitute a general-purpose quadrilateral-element mesh generation preprocessor to a variety of finite-element stress analysis programs. 7 figs., 2 tables

  13. Computer

    CERN Document Server

    Atkinson, Paul

    2011-01-01

    The pixelated rectangle we spend most of our day staring at in silence is not the television as many long feared, but the computer-the ubiquitous portal of work and personal lives. At this point, the computer is almost so common we don't notice it in our view. It's difficult to envision that not that long ago it was a gigantic, room-sized structure only to be accessed by a few inspiring as much awe and respect as fear and mystery. Now that the machine has decreased in size and increased in popular use, the computer has become a prosaic appliance, little-more noted than a toaster. These dramati

  14. CDC Vital Signs-Communication Can Save Lives

    Centers for Disease Control (CDC) Podcasts

    2015-08-04

    This podcast is based on the August 2015 CDC Vital Signs report. Antibiotic-resistant germs cause at least 23,000 deaths each year. Learn how public health authorities and health care facilities can work together to save lives.  Created: 8/4/2015 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 8/4/2015.

  15. CDC Vital Signs-Hospital Actions Affect Breastfeeding

    Centers for Disease Control (CDC) Podcasts

    2015-10-06

    This podcast is based on the October 2015 CDC Vital Signs report. Hospitals can implement the Ten Steps to Successful Breastfeeding to be designated as "Baby-Friendly" and support more moms in a decision to breastfeed.  Created: 10/6/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/6/2015.

  16. CDC Vital Signs-Safer Food Saves Lives

    Centers for Disease Control (CDC) Podcasts

    2015-11-03

    This podcast is based on the November 2015 CDC Vital Signs report. Contaminated food sent to several states can cause multistate outbreaks of foodborne illness and make a lot of people seriously ill. Learn what can be done to prevent and stop outbreaks.  Created: 11/3/2015 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 11/3/2015.

  17. CDC Vital Signs-Protect Patients from Antibiotic Resistance

    Centers for Disease Control (CDC) Podcasts

    2016-03-03

    This podcast is based on the March 2016 CDC Vital Signs report. Patients can get serious healthcare-associated infections, or HAIs, while receiving medical treatment in a healthcare facility. Learn how to prevent healthcare-associated infections.  Created: 3/3/2016 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 3/3/2016.

  18. Health communication takes on new dimensions at CDC.

    OpenAIRE

    Roper, W L

    1993-01-01

    Actions by the Centers for Disease Control and Prevention (CDC) to integrate health communication into overall prevention programs as a means of influencing individual behavior to reduce risks to health are described. These actions include a set of 5-year goals for the Agency; a proposal to establish an Office of Health Communication to provide leadership and support for accomplishing the goals; and establishment of a working group to create the proposed Office of Health Communication and to ...

  19. Cyclin-dependent kinase CDK1/CDC28 and checkpoints

    International Nuclear Information System (INIS)

    The genetic instability induced by defects in the cell cycle progression contributes to different human diseases, particularly neoplastic transformation. The control mechanisms of correct cell cycle progression are the most studied in the yeast Saccharomyces cerevisiae, in which checkpoint was first discovered. Many components of these processes have been identified by now. Here, the role of the central kinase of cell cycle CDK1/CDC28 is considered in checkpoint in different phases.

  20. COMPUTING

    CERN Multimedia

    I. Fisk

    2010-01-01

    Introduction It has been a very active quarter in Computing with interesting progress in all areas. The activity level at the computing facilities, driven by both organised processing from data operations and user analysis, has been steadily increasing. The large-scale production of simulated events that has been progressing throughout the fall is wrapping-up and reprocessing with pile-up will continue. A large reprocessing of all the proton-proton data has just been released and another will follow shortly. The number of analysis jobs by users each day, that was already hitting the computing model expectations at the time of ICHEP, is now 33% higher. We are expecting a busy holiday break to ensure samples are ready in time for the winter conferences. Heavy Ion An activity that is still in progress is computing for the heavy-ion program. The heavy-ion events are collected without zero suppression, so the event size is much large at roughly 11 MB per event of RAW. The central collisions are more complex and...

  1. COMPUTING

    CERN Multimedia

    M. Kasemann P. McBride Edited by M-C. Sawley with contributions from: P. Kreuzer D. Bonacorsi S. Belforte F. Wuerthwein L. Bauerdick K. Lassila-Perini M-C. Sawley

    Introduction More than seventy CMS collaborators attended the Computing and Offline Workshop in San Diego, California, April 20-24th to discuss the state of readiness of software and computing for collisions. Focus and priority were given to preparations for data taking and providing room for ample dialog between groups involved in Commissioning, Data Operations, Analysis and MC Production. Throughout the workshop, aspects of software, operating procedures and issues addressing all parts of the computing model were discussed. Plans for the CMS participation in STEP’09, the combined scale testing for all four experiments due in June 2009, were refined. The article in CMS Times by Frank Wuerthwein gave a good recap of the highly collaborative atmosphere of the workshop. Many thanks to UCSD and to the organizers for taking care of this workshop, which resulted in a long list of action items and was definitely a success. A considerable amount of effort and care is invested in the estimate of the comput...

  2. 13 CFR 120.837 - SBA decision on application for a new CDC or for an existing CDC to expand Area of Operations.

    Science.gov (United States)

    2010-01-01

    ... benchmarks, including pre-approval and annual review by SBA of any management or staff contracts, and the... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false SBA decision on application for a new CDC or for an existing CDC to expand Area of Operations. 120.837 Section 120.837 Business...

  3. Oxidative stress-induced DNA damage of mouse zygotes triggers G2/M checkpoint and phosphorylates Cdc25 and Cdc2.

    Science.gov (United States)

    Zhang, Yuting; Qian, Diting; Li, Zhiling; Huang, Yue; Wu, Que; Ru, Gaizhen; Chen, Man; Wang, Bin

    2016-07-01

    In vitro fertilized (IVF) embryos show both cell cycle and developmental arrest. We previously showed oxidative damage activates the ATM → Chk1 → Cdc25B/Cdc25C cascade to mediate G2/M cell cycle arrest for repair of hydrogen peroxide (H2O2)-induced oxidative damage in sperm. However, the mechanisms underlying the developmental delay of zygotes are unknown. To develop a model of oxidative-damaged zygotes, we treated mouse zygotes with different concentrations of H2O2 (0, 0.01, 0.02, 0.03, 0.04, 0.05 mM), and evaluated in vitro zygote development, BrdU incorporation to detect the duration of S phase. We also examined reactive oxygen species level and used immunofluorescence to detect activation of γH2AX, Cdc2, and Cdc25. Oxidatively damaged zygotes showed a delay in G2/M phase and produced a higher level of ROS. At the same time, γH2AX was detected in oxidatively damaged zygotes as well as phospho-Cdc25B (Ser323), phospho-Cdc25C (Ser216), and phospho-Cdc2 (Tyr15). Our study indicates that oxidative stress-induced DNA damage of mouse zygotes triggers the cell cycle checkpoint, which results in G2/M cell cycle arrest, and that phospho-Cdc25B (Ser323), phospho-Cdc25C (Ser216), and phospho-Cdc2 (Tyr15) participate in activating the G2/M checkpoint. PMID:27117522

  4. COMPUTING

    CERN Multimedia

    I. Fisk

    2010-01-01

    Introduction The first data taking period of November produced a first scientific paper, and this is a very satisfactory step for Computing. It also gave the invaluable opportunity to learn and debrief from this first, intense period, and make the necessary adaptations. The alarm procedures between different groups (DAQ, Physics, T0 processing, Alignment/calibration, T1 and T2 communications) have been reinforced. A major effort has also been invested into remodeling and optimizing operator tasks in all activities in Computing, in parallel with the recruitment of new Cat A operators. The teams are being completed and by mid year the new tasks will have been assigned. CRB (Computing Resource Board) The Board met twice since last CMS week. In December it reviewed the experience of the November data-taking period and could measure the positive improvements made for the site readiness. It also reviewed the policy under which Tier-2 are associated with Physics Groups. Such associations are decided twice per ye...

  5. COMPUTING

    CERN Multimedia

    M. Kasemann

    CCRC’08 challenges and CSA08 During the February campaign of the Common Computing readiness challenges (CCRC’08), the CMS computing team had achieved very good results. The link between the detector site and the Tier0 was tested by gradually increasing the number of parallel transfer streams well beyond the target. Tests covered the global robustness at the Tier0, processing a massive number of very large files and with a high writing speed to tapes.  Other tests covered the links between the different Tiers of the distributed infrastructure and the pre-staging and reprocessing capacity of the Tier1’s: response time, data transfer rate and success rate for Tape to Buffer staging of files kept exclusively on Tape were measured. In all cases, coordination with the sites was efficient and no serious problem was found. These successful preparations prepared the ground for the second phase of the CCRC’08 campaign, in May. The Computing Software and Analysis challen...

  6. COMPUTING

    CERN Multimedia

    I. Fisk

    2011-01-01

    Introduction It has been a very active quarter in Computing with interesting progress in all areas. The activity level at the computing facilities, driven by both organised processing from data operations and user analysis, has been steadily increasing. The large-scale production of simulated events that has been progressing throughout the fall is wrapping-up and reprocessing with pile-up will continue. A large reprocessing of all the proton-proton data has just been released and another will follow shortly. The number of analysis jobs by users each day, that was already hitting the computing model expectations at the time of ICHEP, is now 33% higher. We are expecting a busy holiday break to ensure samples are ready in time for the winter conferences. Heavy Ion The Tier 0 infrastructure was able to repack and promptly reconstruct heavy-ion collision data. Two copies were made of the data at CERN using a large CASTOR disk pool, and the core physics sample was replicated ...

  7. COMPUTING

    CERN Multimedia

    M. Kasemann

    Introduction During the past six months, Computing participated in the STEP09 exercise, had a major involvement in the October exercise and has been working with CMS sites on improving open issues relevant for data taking. At the same time operations for MC production, real data reconstruction and re-reconstructions and data transfers at large scales were performed. STEP09 was successfully conducted in June as a joint exercise with ATLAS and the other experiments. It gave good indication about the readiness of the WLCG infrastructure with the two major LHC experiments stressing the reading, writing and processing of physics data. The October Exercise, in contrast, was conducted as an all-CMS exercise, where Physics, Computing and Offline worked on a common plan to exercise all steps to efficiently access and analyze data. As one of the major results, the CMS Tier-2s demonstrated to be fully capable for performing data analysis. In recent weeks, efforts were devoted to CMS Computing readiness. All th...

  8. COMPUTING

    CERN Multimedia

    I. Fisk

    2012-01-01

    Introduction Computing continued with a high level of activity over the winter in preparation for conferences and the start of the 2012 run. 2012 brings new challenges with a new energy, more complex events, and the need to make the best use of the available time before the Long Shutdown. We expect to be resource constrained on all tiers of the computing system in 2012 and are working to ensure the high-priority goals of CMS are not impacted. Heavy ions After a successful 2011 heavy-ion run, the programme is moving to analysis. During the run, the CAF resources were well used for prompt analysis. Since then in 2012 on average 200 job slots have been used continuously at Vanderbilt for analysis workflows. Operations Office As of 2012, the Computing Project emphasis has moved from commissioning to operation of the various systems. This is reflected in the new organisation structure where the Facilities and Data Operations tasks have been merged into a common Operations Office, which now covers everything ...

  9. COMPUTING

    CERN Multimedia

    P. McBride

    It has been a very active year for the computing project with strong contributions from members of the global community. The project has focused on site preparation and Monte Carlo production. The operations group has begun processing data from P5 as part of the global data commissioning. Improvements in transfer rates and site availability have been seen as computing sites across the globe prepare for large scale production and analysis as part of CSA07. Preparations for the upcoming Computing Software and Analysis Challenge CSA07 are progressing. Ian Fisk and Neil Geddes have been appointed as coordinators for the challenge. CSA07 will include production tests of the Tier-0 production system, reprocessing at the Tier-1 sites and Monte Carlo production at the Tier-2 sites. At the same time there will be a large analysis exercise at the Tier-2 centres. Pre-production simulation of the Monte Carlo events for the challenge is beginning. Scale tests of the Tier-0 will begin in mid-July and the challenge it...

  10. COMPUTING

    CERN Multimedia

    M. Kasemann

    Introduction More than seventy CMS collaborators attended the Computing and Offline Workshop in San Diego, California, April 20-24th to discuss the state of readiness of software and computing for collisions. Focus and priority were given to preparations for data taking and providing room for ample dialog between groups involved in Commissioning, Data Operations, Analysis and MC Production. Throughout the workshop, aspects of software, operating procedures and issues addressing all parts of the computing model were discussed. Plans for the CMS participation in STEP’09, the combined scale testing for all four experiments due in June 2009, were refined. The article in CMS Times by Frank Wuerthwein gave a good recap of the highly collaborative atmosphere of the workshop. Many thanks to UCSD and to the organizers for taking care of this workshop, which resulted in a long list of action items and was definitely a success. A considerable amount of effort and care is invested in the estimate of the co...

  11. Comparing Prescription Sales, Google Trends and CDC Data as Flu Activity Indicators

    Science.gov (United States)

    Patwardhan, Avinash; Lorber, David

    2013-01-01

    Objective To examine if the prescription sales data from a large retail pharmacy chain in the US were comparable to Google Flu trends and CDC’s US ILI Network data as flu activity indicator. Introduction In a 2007 survey of public health officials in the United States, International Society for Disease Surveillance found that only 7% used pharmacy prescription sales data for surveillance (1). There have been many reports suggesting effective use of prescription sales data in syndromic surveillance (2, 3, 4, 5). Community pharmacies can provide a valuable supplementary tool for syndromic surveillance of infectious diseases. Methods We extracted five years of de-identified prescription sales data from the proprietary pharmacy computer system of a large retail pharmacy chain in the United States. The prescriptions were written for the common drugs for the treatment of influenza: Amantadine, Os-eltamivir, Rimantadine, and Zanamivir. We acquired Google Flu trends national aggregate counts data that represented the estimates of the ILI cases per 100,000 physician visits. We acquired CDC ILINET data for 2007. We calculated Pearson ‘r’ between our data and Google and CDC data. We also created comparable trends graphs after converting the counts of the influenza scripts and the counts of the Google estimated ILI cases to logarithmic scale. Results The Pearson ‘r’ between the aggregate counts of scripts for all the four drugs and the Google estimates of the ILI cases for years 2007, 2008, 2009, 2010, and 2011 were 0.85 (95% CI, 0.75–0.91), 0.92 (95% CI, 0.86–0.95), 0.91(95% CI, 0.85–0.95), 0.88 (95% CI, 0.80–0.93), and 0.87 (95% CI, 0.78–0.92) and 0.92 (95% CI, 0.90–0.94) for years 2007 through 2011 together. The Pearson ‘r’ between the aggregate counts of scripts and the CDC % unweighted ILI (2007) was 0.97 (95% CI, 0.95–0.98). Conclusions A strong to very strong correlation between prescription sales data and Google Flu trends and CDC’s ILI

  12. Identification of a novel protein interaction between Elmo1 and Cdc27.

    Science.gov (United States)

    Lee, Juyeon; Moon, Byeongjin; Lee, Dae-Hee; Lee, Gwangrog; Park, Daeho

    2016-03-18

    Elmo has no intrinsic catalytic activity but coordinate multiple cellular processes via their interactions with other proteins. Studies thus have been focused on identifying Elmo binding partners, but the number of characterized Elmo-interacting proteins remains limited. Here, we report Cdc27 as a novel Elmo1-interacting protein. In yeast and mammalian cells, Cdc27 specifically interacted with the C-terminal region of Elmo1 essential for Dock1 association and function. The interaction of Elmo1 with Dock1 abrogated binding between Elmo1 and Cdc27, but the Dock1-Elmo1 interaction was unaffected by Cdc27. Similarly, cellular phagocytotic functions mediated by the Elmo1-Dock1-Rac module were unaffected by Cdc27 levels. In summary, a novel binding partner, Cdc27, was identified for Elmo1 and they appear to be independent of Elmo-Dock1-Rac-mediated processes. PMID:26882976

  13. COMPUTING

    CERN Multimedia

    P. MacBride

    The Computing Software and Analysis Challenge CSA07 has been the main focus of the Computing Project for the past few months. Activities began over the summer with the preparation of the Monte Carlo data sets for the challenge and tests of the new production system at the Tier-0 at CERN. The pre-challenge Monte Carlo production was done in several steps: physics generation, detector simulation, digitization, conversion to RAW format and the samples were run through the High Level Trigger (HLT). The data was then merged into three "Soups": Chowder (ALPGEN), Stew (Filtered Pythia) and Gumbo (Pythia). The challenge officially started when the first Chowder events were reconstructed on the Tier-0 on October 3rd. The data operations teams were very busy during the the challenge period. The MC production teams continued with signal production and processing while the Tier-0 and Tier-1 teams worked on splitting the Soups into Primary Data Sets (PDS), reconstruction and skimming. The storage sys...

  14. COMPUTING

    CERN Multimedia

    Matthias Kasemann

    Overview The main focus during the summer was to handle data coming from the detector and to perform Monte Carlo production. The lessons learned during the CCRC and CSA08 challenges in May were addressed by dedicated PADA campaigns lead by the Integration team. Big improvements were achieved in the stability and reliability of the CMS Tier1 and Tier2 centres by regular and systematic follow-up of faults and errors with the help of the Savannah bug tracking system. In preparation for data taking the roles of a Computing Run Coordinator and regular computing shifts monitoring the services and infrastructure as well as interfacing to the data operations tasks are being defined. The shift plan until the end of 2008 is being put together. User support worked on documentation and organized several training sessions. The ECoM task force delivered the report on “Use Cases for Start-up of pp Data-Taking” with recommendations and a set of tests to be performed for trigger rates much higher than the ...

  15. COMPUTING

    CERN Multimedia

    M. Kasemann

    Introduction A large fraction of the effort was focused during the last period into the preparation and monitoring of the February tests of Common VO Computing Readiness Challenge 08. CCRC08 is being run by the WLCG collaboration in two phases, between the centres and all experiments. The February test is dedicated to functionality tests, while the May challenge will consist of running at all centres and with full workflows. For this first period, a number of functionality checks of the computing power, data repositories and archives as well as network links are planned. This will help assess the reliability of the systems under a variety of loads, and identifying possible bottlenecks. Many tests are scheduled together with other VOs, allowing the full scale stress test. The data rates (writing, accessing and transfer¬ring) are being checked under a variety of loads and operating conditions, as well as the reliability and transfer rates of the links between Tier-0 and Tier-1s. In addition, the capa...

  16. COMPUTING

    CERN Multimedia

    Contributions from I. Fisk

    2012-01-01

    Introduction The start of the 2012 run has been busy for Computing. We have reconstructed, archived, and served a larger sample of new data than in 2011, and we are in the process of producing an even larger new sample of simulations at 8 TeV. The running conditions and system performance are largely what was anticipated in the plan, thanks to the hard work and preparation of many people. Heavy ions Heavy Ions has been actively analysing data and preparing for conferences.  Operations Office Figure 6: Transfers from all sites in the last 90 days For ICHEP and the Upgrade efforts, we needed to produce and process record amounts of MC samples while supporting the very successful data-taking. This was a large burden, especially on the team members. Nevertheless the last three months were very successful and the total output was phenomenal, thanks to our dedicated site admins who keep the sites operational and the computing project members who spend countless hours nursing the...

  17. COMPUTING

    CERN Multimedia

    I. Fisk

    2012-01-01

      Introduction Computing activity has been running at a sustained, high rate as we collect data at high luminosity, process simulation, and begin to process the parked data. The system is functional, though a number of improvements are planned during LS1. Many of the changes will impact users, we hope only in positive ways. We are trying to improve the distributed analysis tools as well as the ability to access more data samples more transparently.  Operations Office Figure 2: Number of events per month, for 2012 Since the June CMS Week, Computing Operations teams successfully completed data re-reconstruction passes and finished the CMSSW_53X MC campaign with over three billion events available in AOD format. Recorded data was successfully processed in parallel, exceeding 1.2 billion raw physics events per month for the first time in October 2012 due to the increase in data-parking rate. In parallel, large efforts were dedicated to WMAgent development and integrati...

  18. COMPUTING

    CERN Multimedia

    I. Fisk

    2013-01-01

    Computing operation has been lower as the Run 1 samples are completing and smaller samples for upgrades and preparations are ramping up. Much of the computing activity is focusing on preparations for Run 2 and improvements in data access and flexibility of using resources. Operations Office Data processing was slow in the second half of 2013 with only the legacy re-reconstruction pass of 2011 data being processed at the sites.   Figure 1: MC production and processing was more in demand with a peak of over 750 Million GEN-SIM events in a single month.   Figure 2: The transfer system worked reliably and efficiently and transferred on average close to 520 TB per week with peaks at close to 1.2 PB.   Figure 3: The volume of data moved between CMS sites in the last six months   The tape utilisation was a focus for the operation teams with frequent deletion campaigns from deprecated 7 TeV MC GEN-SIM samples to INVALID datasets, which could be cleaned up...

  19. COMPUTING

    CERN Multimedia

    2010-01-01

    Introduction Just two months after the “LHC First Physics” event of 30th March, the analysis of the O(200) million 7 TeV collision events in CMS accumulated during the first 60 days is well under way. The consistency of the CMS computing model has been confirmed during these first weeks of data taking. This model is based on a hierarchy of use-cases deployed between the different tiers and, in particular, the distribution of RECO data to T1s, who then serve data on request to T2s, along a topology known as “fat tree”. Indeed, during this period this model was further extended by almost full “mesh” commissioning, meaning that RECO data were shipped to T2s whenever possible, enabling additional physics analyses compared with the “fat tree” model. Computing activities at the CMS Analysis Facility (CAF) have been marked by a good time response for a load almost evenly shared between ALCA (Alignment and Calibration tasks - highest p...

  20. Implementation experiences of NASTRAN on CDC CYBER 74 SCOPE 3.4 operating system

    Science.gov (United States)

    Go, J. C.; Hill, R. G.

    1973-01-01

    The implementation of the NASTRAN system on the CDC CYBER 74 SCOPE 3.4 Operating System is described. The flexibility of the NASTRAN system made it possible to accomplish the change with no major problems. Various sizes of benchmark and test problems, ranging from two hours to less than one minute CP time were run on the CDC CYBER SCOPE 3.3, Univac EXEC-8, and CDC CYBER SCOPE 3.4. The NASTRAN installation deck is provided.

  1. Polo kinase Cdc5 is a central regulator of meiosis I

    OpenAIRE

    Attner, Michelle A.; Miller, Matthew P.; Ee, Ly-Sha; Elkin, Sheryl K; Amon, Angelika

    2013-01-01

    During meiosis, two consecutive rounds of chromosome segregation yield four haploid gametes from one diploid cell. The Polo kinase Cdc5 is required for meiotic progression, but how Cdc5 coordinates multiple cell-cycle events during meiosis I is not understood. Here we show that CDC5-dependent phosphorylation of Rec8, a subunit of the cohesin complex that links sister chromatids, is required for efficient cohesin removal from chromosome arms, which is a prerequisite for meiosis I chromosome se...

  2. A national, geographic database of CDC-funded HIV prevention services: development challenges and potential applications

    OpenAIRE

    Fogarty Kieran J; Gilliam Aisha; Gibbs Deborah A; Hanchette Carol L; Bruhn Mark

    2005-01-01

    Abstract Background From 2000–2002, the Centers for Disease Control and Prevention (CDC) funded a study that was designed to improve the information available to program planners about the geographic distribution of CDC-funded HIV prevention services provided by community-based organizations (CBOs). Program managers at CDC recognized the potential of a geographic information system (GIS) to organize and analyze information about HIV prevention services and they made GIS a critical component o...

  3. FMNL2 drives actin-based protrusion and migration downstream of Cdc42

    DEFF Research Database (Denmark)

    Block, Jennifer; Breitsprecher, Dennis; Kühn, Sonja;

    2012-01-01

    -guanosine triphosphatase Cdc42. Abolition of myristoylation or Cdc42 binding interferes with proper FMNL2 activation, constituting an essential prerequisite for subcellular targeting. In vitro, C-terminal FMNL2 drives elongation rather than nucleation of actin filaments in the presence of profilin. In addition, filament...... establish that the FMNL subfamily member FMNL2 is a novel elongation factor of actin filaments that constitutes the first Cdc42 effector promoting cell migration and actin polymerization at the tips of lamellipodia....

  4. Opposing Roles for Actin in Cdc42p PolarizationD⃞

    OpenAIRE

    Irazoqui, Javier E.; Howell, Audrey S.; Theesfeld, Chandra L.; Lew, Daniel J.

    2005-01-01

    In animal and fungal cells, the monomeric GTPase Cdc42p is a key regulator of cell polarity that itself exhibits a polarized distribution in asymmetric cells. Previous work showed that in budding yeast, Cdc42p polarization is unaffected by depolymerization of the actin cytoskeleton (Ayscough et al., J. Cell Biol. 137, 399–416, 1997). Surprisingly, we now report that unlike complete actin depolymerization, partial actin depolymerization leads to the dispersal of Cdc42p from the polarization si...

  5. miR-330 regulates the proliferation of colorectal cancer cells by targeting Cdc42

    International Nuclear Information System (INIS)

    Highlights: ► miR-330 was inversely correlated with Cdc42 in colorectal cancer cells. ► Elevated miR-330 suppressed cell proliferation in vivo and in vitro. ► Elevated miR-330 mimicked the effect of Cdc42 knockdown. ► Restoration of Cdc42 could partially attenuate the effects of miR-330. -- Abstract: MicroRNAs are small non-coding RNA molecules that play important roles in the multistep process of colorectal carcinoma (CRC) development. However, the miRNA–mRNA regulatory network is far from being fully understood. The objective of this study was to investigate the expression and the biological roles of miR-330 in colorectal cancer cells. Cdc42, one of the best characterized members of the Rho GTPase family, was found to be up-regulated in several types of human tumors including CRC and has been implicated in cancer initiation and progression. In the present study, we identified miR-330, as a potential regulator of Cdc42, was found to be inversely correlated with Cdc42 expression in colorectal cancer cell lines. Ectopic expression of miR-330 down-regulated Cdc42 expression at both protein and mRNA level, mimicked the effect of Cdc42 knockdown in inhibiting proliferation, inducing G1 cell cycle arrest and apoptosis of the colorectal cancer cells, whereas restoration of Cdc42 could partially attenuate the effects of miR-330. In addition, elevated expression of miR-330 could suppress the immediate downstream effectors of Cdc42 and inhibit the growth of colorectal cancer cells in vivo. To sum up, our results establish a role of miR-330 in negatively regulating Cdc42 expression and colorectal cancer cell proliferation. They suggest that manipulating the expression level of Cdc42 by miR-330 has the potential to influence colorectal cancer progression

  6. Rho GTPase protein Cdc42 is critical for postnatal cartilage development.

    Science.gov (United States)

    Nagahama, Ryo; Yamada, Atsushi; Tanaka, Junichi; Aizawa, Ryo; Suzuki, Dai; Kassai, Hidetoshi; Yamamoto, Matsuo; Mishima, Kenji; Aiba, Atsu; Maki, Koutaro; Kamijo, Ryutaro

    2016-02-19

    Cdc42, a small Rho GTPase family member, has been shown to regulate multiple cellular functions in vitro, including actin cytoskeletal reorganization, cell migration, proliferation, and gene expression. However, its tissue-specific roles in vivo remain largely unknown, especially in postnatal cartilage development, as cartilage-specific Cdc42 inactivated mice die within a few days after birth. In this study, we investigated the physiological functions of Cdc42 during cartilage development after birth using tamoxifen-induced cartilage-specific inactivated Cdc42 conditional knockout (Cdc42 (fl/fl); Col2-CreERT) mice, which were generated by crossing Cdc42 flox mice (Cdc42 (fl/fl)) with tamoxifen-induced type II collagen (Col2) Cre transgenic mice using a Cre/loxP system. The gross morphology of the Cdc42 cKO mice was shorter limbs and body, as well as reduced body weight as compared with the controls. In addition, severe defects were found in growth plate chondrocytes of the long bones, characterized by a shorter proliferating zone (PZ), wider hypertrophic zone (HZ), and loss of columnar organization of proliferating chondrocytes, resulting in delayed endochondral bone formation associated with abnormal bone growth. Our findings demonstrate the importance of Cdc42 for cartilage development during both embryonic and postnatal stages. PMID:26820532

  7. Low cdc27 and high securin expression predict short survival for breast cancer patients.

    Science.gov (United States)

    Talvinen, Kati; Karra, Henna; Pitkänen, Reino; Ahonen, Ilmari; Nykänen, Marjukka; Lintunen, Minnamaija; Söderström, Mirva; Kuopio, Teijo; Kronqvist, Pauliina

    2013-10-01

    Cell cycle regulators cdc27 and securin participate in control of the mitotic checkpoint and survey the mitotic spindle to maintain chromosomal integrity. This is achieved by their functions in metaphase-anaphase transition, DNA damage repair, enhancement of mitotic arrest and apoptosis. We report on the roles of cdc27 and securin in aneuploidy and prognosis of breast cancer. The study comprises 429 breast cancer patients with up to 22 years of follow-up. DNA content was determined by image cytometry, and immunopositivity for cdc27 and securin was based on tissue microarrays. An inverse association between cdc27 and securin expression was observed in both image cytometric and immunohistochemical analyses. Low cdc27 and high securin expression identified patients with significant difference in disease outcome. Cdc27 and securin immunoexpression identified patients at risk of early cancer death within five years from diagnosis. In multivariate analysis, the combination of cdc27 and securin immunohistochemistry was the strongest predictor of cancer death after lymph node status. We demonstrate, for the first time in human breast cancer, the prognostic value of cdc27 and securin immunohistochemistry. Cdc27 and securin appear promising biomarkers for applications in predicting disease progression, prognostication of individual patients and potential in anti-mitotic drug development. PMID:23755904

  8. Cdc20 and securin overexpression predict short-term breast cancer survival

    Science.gov (United States)

    Karra, H; Repo, H; Ahonen, I; Löyttyniemi, E; Pitkänen, R; Lintunen, M; Kuopio, T; Söderström, M; Kronqvist, P

    2014-01-01

    Background: Cdc20 is an essential component of cell division and responsible for anaphase initiation regulated by securin degradation. Cdc20 function is strongly regulated by the spindle assembly checkpoint to ensure the timely separation of sister chromatids and integrity of the genome. We present the first results on Cdc20 in a large clinical breast cancer material. Methods: The study was based on 445 breast cancer patients with up to 20 years of follow-up (mean 10.0 years). DNA content was determined by image cytometry on cell imprints, and Cdc20 and securin immunohistochemistry on tissue microarrays of breast cancer tissue. Results: In our results, high Cdc20 and securin expression was associated with aneuploid DNA content. In prognostic analyses, high Cdc20 immunoexpression alone and in combination with high securin immunoexpression indicated aggressive course of disease and up to 6.8-fold (P<0.001) risk of breast cancer death. Particularly, high Cdc20 and securin immunoexpression identified a patient subgroup with extremely short, on average 2.4 years, breast cancer survival and triple-negative breast cancer (TNBC) subtype. Conclusions: We report for the first time the association of high Cdc20 and securin immunoexpression with extremely poor outcome of breast cancer patients. Our experience indicates that Cdc20 and securin are promising candidates for clinical applications in breast cancer prognostication, especially in the challenging prognostic decisions of TNBC. PMID:24853182

  9. Telomerase Recruitment in Saccharomyces cerevisiae Is Not Dependent on Tel1-Mediated Phosphorylation of Cdc13

    Science.gov (United States)

    Gao, Hua; Toro, Tasha B.; Paschini, Margherita; Braunstein-Ballew, Bari; Cervantes, Rachel B.; Lundblad, Victoria

    2010-01-01

    In Saccharomyces cerevisiae, association between the Est1 telomerase subunit and the telomere-binding protein Cdc13 is essential for telomerase to be recruited to its site of action. A current model proposes that Tel1 binding to telomeres marks them for elongation, as the result of phosphorylation of a proposed S/TQ cluster in the telomerase recruitment domain of Cdc13. However, three observations presented here argue against one key aspect of this model. First, the pattern of Cdc13 phosphatase-sensitive isoforms is not altered by loss of Tel1 function or by mutations introduced into two conserved serines (S249 and S255) in the Cdc13 recruitment domain. Second, an interaction between Cdc13 and Est1, as monitored by a two-hybrid assay, is dependent on S255 but Tel1-independent. Finally, a derivative of Cdc13, cdc13–(S/TQ)11→(S/TA)11, in which every potential consensus phosphorylation site for Tel1 has been eliminated, confers nearly wild-type telomere length. These results are inconsistent with a model in which the Cdc13–Est1 interaction is regulated by Tel1-mediated phosphorylation of the Cdc13 telomerase recruitment domain. We propose an alternative model for the role of Tel1 in telomere homeostasis, which is based on the assumption that Tel1 performs the same molecular task at double-strand breaks (DSBs) and chromosome termini. PMID:20837994

  10. Cdc13 N-Terminal Dimerization DNA Binding and Telomere Length Regulation

    Energy Technology Data Exchange (ETDEWEB)

    M Mitchell; J Smith; M Mason; S Harper; D Speicher; F Johnson; E Skordalakes

    2011-12-31

    The essential yeast protein Cdc13 facilitates chromosome end replication by recruiting telomerase to telomeres, and together with its interacting partners Stn1 and Ten1, it protects chromosome ends from nucleolytic attack, thus contributing to genome integrity. Although Cdc13 has been studied extensively, the precise role of its N-terminal domain (Cdc13N) in telomere length regulation remains unclear. Here we present a structural, biochemical, and functional characterization of Cdc13N. The structure reveals that this domain comprises an oligonucleotide/oligosaccharide binding (OB) fold and is involved in Cdc13 dimerization. Biochemical data show that Cdc13N weakly binds long, single-stranded, telomeric DNA in a fashion that is directly dependent on domain oligomerization. When introduced into full-length Cdc13 in vivo, point mutations that prevented Cdc13N dimerization or DNA binding caused telomere shortening or lengthening, respectively. The multiple DNA binding domains and dimeric nature of Cdc13 offer unique insights into how it coordinates the recruitment and regulation of telomerase access to the telomeres.

  11. Septin ring assembly involves cycles of GTP loading and hydrolysis by Cdc42p

    OpenAIRE

    Gladfelter, Amy S.; Bose, Indrani; Zyla, Trevin R.; Bardes, Elaine S.G.; Lew, Daniel J.

    2002-01-01

    At the beginning of the budding yeast cell cycle, the GTPase Cdc42p promotes the assembly of a ring of septins at the site of future bud emergence. Here, we present an analysis of cdc42 mutants that display specific defects in septin organization, which identifies an important role for GTP hydrolysis by Cdc42p in the assembly of the septin ring. The mutants show defects in basal or stimulated GTP hydrolysis, and the septin misorganization is suppressed by overexpression of a Cdc42p GTPase-act...

  12. Amino acid residues in the CDC25 guanine nucleotide exchange factor critical for interaction with Ras.

    OpenAIRE

    Park, W.; Mosteller, R D; Broek, D.

    1994-01-01

    Previously we found that negatively charged residues at positions 62, 63, and 69 of H-Ras are involved in binding to the CDC25 guanine nucleotide exchange factor (GEF). Using site-directed mutagenesis, we have changed conserved, positively charged residues of CDC25GEF to glutamic acid. We find the nonfunctional CDC25R1374E mutant and the nonfunctional H-RasE63K mutant cooperate in suppression of the loss of CDC25 function in Saccharomyces cerevisiae. Also, peptides corresponding to residues 1...

  13. The CDC25 protein of Saccharomyces cerevisiae promotes exchange of guanine nucleotides bound to ras.

    OpenAIRE

    Jones, S; Vignais, M L; Broach, J R

    1991-01-01

    The product of the CDC25 gene of Saccharomyces cerevisiae, in its capacity as an activator of the RAS/cyclic AMP pathway, is required for initiation of the cell cycle. In this report, we provide an identification of Cdc25p, the product of the CDC25 gene, and evidence that it promotes exchange of guanine nucleotides bound to Ras in vitro. Extracts of strains containing high levels of Cdc25p catalyze both removal of GDP from and the concurrent binding of GTP to Ras. This same activity is also o...

  14. Telomerase recruitment in Saccharomyces cerevisiae is not dependent on Tel1-mediated phosphorylation of Cdc13.

    Science.gov (United States)

    Gao, Hua; Toro, Tasha B; Paschini, Margherita; Braunstein-Ballew, Bari; Cervantes, Rachel B; Lundblad, Victoria

    2010-12-01

    In Saccharomyces cerevisiae, association between the Est1 telomerase subunit and the telomere-binding protein Cdc13 is essential for telomerase to be recruited to its site of action. A current model proposes that Tel1 binding to telomeres marks them for elongation, as the result of phosphorylation of a proposed S/TQ cluster in the telomerase recruitment domain of Cdc13. However, three observations presented here argue against one key aspect of this model. First, the pattern of Cdc13 phosphatase-sensitive isoforms is not altered by loss of Tel1 function or by mutations introduced into two conserved serines (S249 and S255) in the Cdc13 recruitment domain. Second, an interaction between Cdc13 and Est1, as monitored by a two-hybrid assay, is dependent on S255 but Tel1-independent. Finally, a derivative of Cdc13, cdc13-(S/TQ)11→(S/TA)11, in which every potential consensus phosphorylation site for Tel1 has been eliminated, confers nearly wild-type telomere length. These results are inconsistent with a model in which the Cdc13-Est1 interaction is regulated by Tel1-mediated phosphorylation of the Cdc13 telomerase recruitment domain. We propose an alternative model for the role of Tel1 in telomere homeostasis, which is based on the assumption that Tel1 performs the same molecular task at double-strand breaks (DSBs) and chromosome termini. PMID:20837994

  15. COMPUTING

    CERN Multimedia

    I. Fisk

    2011-01-01

    Introduction The Computing Team successfully completed the storage, initial processing, and distribution for analysis of proton-proton data in 2011. There are still a variety of activities ongoing to support winter conference activities and preparations for 2012. Heavy ions The heavy-ion run for 2011 started in early November and has already demonstrated good machine performance and success of some of the more advanced workflows planned for 2011. Data collection will continue until early December. Facilities and Infrastructure Operations Operational and deployment support for WMAgent and WorkQueue+Request Manager components, routinely used in production by Data Operations, are provided. The GlideInWMS and components installation are now deployed at CERN, which is added to the GlideInWMS factory placed in the US. There has been new operational collaboration between the CERN team and the UCSD GlideIn factory operators, covering each others time zones by monitoring/debugging pilot jobs sent from the facto...

  16. CDC Vital Signs-Daily Pill Can Prevent HIV

    Centers for Disease Control (CDC) Podcasts

    2015-11-24

    This podcast is based on the November 24, 2015 CDC Vital Signs report. Preexposure prophylaxis, or PrEP, is a daily medicine that can be used to prevent getting HIV. PrEP is for people who don’t have HIV but who are at very high risk for getting it from sex or injection drug use. Unfortunately, many people who can benefit from PrEP aren’t taking it.  Created: 11/24/2015 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 11/24/2015.

  17. CDC Vital Signs-E-cigarette Ads and Youth

    Centers for Disease Control (CDC) Podcasts

    2016-01-05

    This podcast is based on the January 2016 CDC Vital Signs report. Most electronic cigarettes, or e-cigarettes, contain nicotine, which is highly addictive and may harm brain development. More than 18 million middle and high school students were exposed to e-cigarette ads. Exposure to these ads may be contributing to an increase in e-cigarette use among youth. Learn what can be done to keep our youth safe and healthy.  Created: 1/5/2016 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 1/5/2016.

  18. AROMA-AIRWICK: a CHLOE/CDC-3600 system for the automatic identification of spark images and their association into tracks

    Energy Technology Data Exchange (ETDEWEB)

    Clark, R K

    1980-06-26

    The AROMA-AIRWICK System for CHLOE, an automatic film scanning equipment built at Argonne by Donald Hodges, and the CDC-3600 computer is a system for the automatic identification of spark images and their association into tracks. AROMA-AIRWICK has been an outgrowth of the generally recognized need for the automatic processing of high energy physics data and the fact that the Argonne National Laboratory has been a center of serious spark chamber development in recent years.

  19. AROMA-AIRWICK: a CHLOE/CDC-3600 system for the automatic identification of spark images and their association into tracks

    International Nuclear Information System (INIS)

    The AROMA-AIRWICK System for CHLOE, an automatic film scanning equipment built at Argonne by Donald Hodges, and the CDC-3600 computer is a system for the automatic identification of spark images and their association into tracks. AROMA-AIRWICK has been an outgrowth of the generally recognized need for the automatic processing of high energy physics data and the fact that the Argonne National Laboratory has been a center of serious spark chamber development in recent years

  20. COMPUTING

    CERN Multimedia

    M. Kasemann

    CMS relies on a well functioning, distributed computing infrastructure. The Site Availability Monitoring (SAM) and the Job Robot submission have been very instrumental for site commissioning in order to increase availability of more sites such that they are available to participate in CSA07 and are ready to be used for analysis. The commissioning process has been further developed, including "lessons learned" documentation via the CMS twiki. Recently the visualization, presentation and summarizing of SAM tests for sites has been redesigned, it is now developed by the central ARDA project of WLCG. Work to test the new gLite Workload Management System was performed; a 4 times increase in throughput with respect to LCG Resource Broker is observed. CMS has designed and launched a new-generation traffic load generator called "LoadTest" to commission and to keep exercised all data transfer routes in the CMS PhE-DEx topology. Since mid-February, a transfer volume of about 12 P...

  1. Multisite phosphorylation of the guanine nucleotide exchange factor Cdc24 during yeast cell polarization.

    Directory of Open Access Journals (Sweden)

    Stephanie C Wai

    Full Text Available BACKGROUND: Cell polarization is essential for processes such as cell migration and asymmetric cell division. A common regulator of cell polarization in most eukaryotic cells is the conserved Rho GTPase, Cdc42. In budding yeast, Cdc42 is activated by a single guanine nucleotide exchange factor, Cdc24. The mechanistic details of Cdc24 activation at the onset of yeast cell polarization are unclear. Previous studies have suggested an important role for phosphorylation of Cdc24, which may regulate activity or function of the protein, representing a key step in the symmetry breaking process. METHODOLOGY/PRINCIPAL FINDINGS: Here, we directly ask whether multisite phosphorylation of Cdc24 plays a role in its regulation. We identify through mass spectrometry analysis over thirty putative in vivo phosphorylation sites. We first focus on sites matching consensus sequences for cyclin-dependent and p21-activated kinases, two kinase families that have been previously shown to phosphorylate Cdc24. Through site-directed mutagenesis, yeast genetics, and light and fluorescence microscopy, we show that nonphosphorylatable mutations of these consensus sites do not lead to any detectable consequences on growth rate, morphology, kinetics of polarization, or localization of the mutant protein. We do, however, observe a change in the mobility shift of mutant Cdc24 proteins on SDS-PAGE, suggesting that we have indeed perturbed its phosphorylation. Finally, we show that mutation of all identified phosphorylation sites does not cause observable defects in growth rate or morphology. CONCLUSIONS/SIGNIFICANCE: We conclude that lack of phosphorylation on Cdc24 has no overt functional consequences in budding yeast. Yeast cell polarization may be more tightly regulated by inactivation of Cdc42 by GTPase activating proteins or by alternative methods of Cdc24 regulation, such as conformational changes or oligomerization.

  2. CDC Signos Vitales: Enfermedad del legionario (CDC Vital Signs–Legionnaires’ Disease)

    Centers for Disease Control (CDC) Podcasts

    2016-06-07

    Este podcast se basa en la edición de junio del 2016 del informe Signos Vitales de los CDC. Las personas pueden contraer la enfermedad del legionario, un tipo grave de infección pulmonar, al inhalar pequeñas gotitas de agua contaminada con bacterias Legionella. Obtenga más información sobre lo que se puede hacer para ayudar a prevenir brotes de enfermedad del legionario y mantener seguras a las personas.  Created: 6/7/2016 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 6/7/2016.

  3. The human homolog of S. cerevisiae CDC27, CDC27 Hs, is encoded by a highly conserved intronless gene present in multiple copies in the human genome

    Energy Technology Data Exchange (ETDEWEB)

    Devor, E.J.; Dill-Devor, R.M. [Univ. of Iowa College of Medicine, Iowa City (United States)

    1994-09-01

    We have obtained a number of unique sequences via PCR amplification of human genomic DNA using degenerate primers under low stringency (42{degrees}C). One of these, an 853 bp product, has been identified as a partial genomic sequence of the human homolog of the S. cerevisiae CDC27 gene, CDC27Hs (GenBank No. U00001). This gene, reported by Turgendreich et al. is also designated EST00556 from Adams et al. We have undertaken a more detailed examination of our sequence, MCP34N, and have found that: 1. the genomic sequence is nearly identical to CDC27Hs over its entire 853 bp length; 2. an MCP34N-specific PCR assay of several non-human primate species reveals amplification products in chimpanzee and gorilla genomes having greater than 90% sequence identity with CDC27Hs; and 3. an MCP34N-specific PCR assay of the BIOS hybrid cell line panel gives a discordancy pattern suggesting multiple loci. Based upon these data, we present the following initial characterization: 1. the complete MCP34N sequence identity with CDC27Hs indicates that the latter is encoded by an intronless gene; 2. CDC27Hs is highly conserved among higher primates; and 3. CDC27Hs is present in multiple copies in the human genome. These characteristics, taken together with those initially reported for CDC27Hs, suggest that this is an old gene that carries out an important but, as yet, unknown function in the human brain.

  4. The Rho-GTPase cdc42 regulates neural progenitor fate at the apical surface

    DEFF Research Database (Denmark)

    Cappello, Silvia; Attardo, Alessio; Wu, Xunwei; Iwasato, Takuji; Itohara, Shigeyoshi; Wilsch-Bräuninger, Michaela; Eilken, Hanna M; Rieger, Michael A; Schroeder, Timm T; Huttner, Wieland B; Brakebusch, Cord; Götz, Magdalena

    2006-01-01

    fundamental difference between these progenitors. Here we show that the conditional deletion of the small Rho-GTPase cdc42 at different stages of neurogenesis in mouse telencephalon results in an immediate increase in basal mitoses. Whereas cdc42-deficient progenitors have normal cell cycle length...

  5. Cdc42 expression in keratinocytes is required for the maintenance of the basement membrane in skin

    DEFF Research Database (Denmark)

    Wu, Xunwei; Quondamatteo, Fabio; Brakebusch, Cord

    2006-01-01

    , structure and number of hemidesomosomes were not significantly changed in the Cdc42 mutant skin compared with the control mice and no blister formation was observed in mutant skin. These data indicate that Cdc42 in keratinocytes is important for maintenance of the basement membrane of skin....

  6. CDC's Response to the 2014-2016 Ebola Epidemic - Guinea, Liberia, and Sierra Leone.

    Science.gov (United States)

    Dahl, Benjamin A; Kinzer, Michael H; Raghunathan, Pratima L; Christie, Athalia; De Cock, Kevin M; Mahoney, Frank; Bennett, Sarah D; Hersey, Sara; Morgan, Oliver W

    2016-01-01

    CDC's response to the 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa was the largest in the agency's history and occurred in a geographic area where CDC had little operational presence. Approximately 1,450 CDC responders were deployed to Guinea, Liberia, and Sierra Leone since the start of the response in July 2014 to the end of the response at the end of March 2016, including 455 persons with repeat deployments. The responses undertaken in each country shared some similarities but also required unique strategies specific to individual country needs. The size and duration of the response challenged CDC in several ways, particularly with regard to staffing. The lessons learned from this epidemic will strengthen CDC's ability to respond to future public health emergencies. These lessons include the importance of ongoing partnerships with ministries of health in resource-limited countries and regions, a cadre of trained CDC staff who are ready to be deployed, and development of ongoing working relationships with U.S. government agencies and other multilateral and nongovernment organizations that deploy for international public health emergencies. CDC's establishment of a Global Rapid Response Team in June 2015 is anticipated to meet some of these challenges. The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html). PMID:27388930

  7. 13 CFR 120.820 - CDC non-profit status and good standing.

    Science.gov (United States)

    2010-01-01

    ..., as determined by SBA in its discretion. The CDC's Risk Rating, among other factors, will be... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false CDC non-profit status and good standing. 120.820 Section 120.820 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION...

  8. Cell cycle-dependent mobility of Cdc45 determined in vivo by fluorescence correlation spectroscopy.

    Directory of Open Access Journals (Sweden)

    Ronan Broderick

    Full Text Available Eukaryotic DNA replication is a dynamic process requiring the co-operation of specific replication proteins. We measured the mobility of eGFP-Cdc45 by Fluorescence Correlation Spectroscopy (FCS in vivo in asynchronous cells and in cells synchronized at the G1/S transition and during S phase. Our data show that eGFP-Cdc45 mobility is faster in G1/S transition compared to S phase suggesting that Cdc45 is part of larger protein complex formed in S phase. Furthermore, the size of complexes containing Cdc45 was estimated in asynchronous, G1/S and S phase-synchronized cells using gel filtration chromatography; these findings complemented the in vivo FCS data. Analysis of the mobility of eGFP-Cdc45 and the size of complexes containing Cdc45 and eGFP-Cdc45 after UVC-mediated DNA damage revealed no significant changes in diffusion rates and complex sizes using FCS and gel filtration chromatography analyses. This suggests that after UV-damage, Cdc45 is still present in a large multi-protein complex and that its mobility within living cells is consistently similar following UVC-mediated DNA damage.

  9. 77 FR 58847 - Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)

    Science.gov (United States)

    2012-09-24

    ... HUMAN SERVICES Centers for Disease Control and Prevention Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC) In accordance with section 10(a)(2) of the Federal... enable CDC to fulfill its mission of protecting health through health promotion, prevention,...

  10. Multiple alterations of platelet functions dominated by increased secretion in mice lacking Cdc42 in platelets

    DEFF Research Database (Denmark)

    Pleines, Irina; Eckly, Anita; Elvers, Margitta; Hagedorn, Ina; Eliautou, Sandra; Bender, Markus; Wu, Xunwei; Lanza, Francois; Gachet, Christian; Brakebusch, Cord; Nieswandt, Bernhard

    2010-01-01

    (ADP)/adenosine triphosphate (ATP) content, increased aggregation at low agonist concentrations, and enhanced aggregate formation on collagen under flow. In vivo, lack of Cdc42 resulted in faster occlusion of ferric chloride-injured arterioles. The life span of Cdc42-deficient platelets was markedly...

  11. Cdc42 Controls Vascular Network Assembly Through Protein Kinase C{iota} During Embryonic Vasculogenesis

    DEFF Research Database (Denmark)

    Qi, Yanmei; Liu, Jie; Wu, Xunwei; Brakebusch, Cord; Leitges, Michael; Han, Yaling; Corbett, Siobhan A; Lowry, Stephen F; Graham, Alan M; Li, Shaohua

    2011-01-01

    The goal of this study was to determine the role of Cdc42 in embryonic vasculogenesis and the underlying mechanisms.......The goal of this study was to determine the role of Cdc42 in embryonic vasculogenesis and the underlying mechanisms....

  12. High expression of CDC6 is associated with accelerated cell proliferation and poor prognosis of epithelial ovarian cancer.

    Science.gov (United States)

    Deng, Yan; Jiang, Lifei; Wang, Yingying; Xi, Qinghua; Zhong, Jianxin; Liu, Jian; Yang, Shuyun; Liu, Rong; Wang, Juan; Huang, Menghui; Tang, Chunhui; Su, Min

    2016-04-01

    Cell division cycle 6 (CDC6) is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle. CDC6 has been associated with the oncogenic activities in human cancers, but the biological function and clinical significance of CDC6 in EOC remain unclear. The aim of the present study is to examine the effect of CDC6 on epithelial ovarian cancer (EOC) cells proliferation. We found that CDC6 protein level was up-regulated in EOC tissues compared with the normal ovary tissues. CDC6 expression correlated significantly with FIGO stage (plymph node status (pformation. HO8910 cells transfected with sh CDC6#1 underwent G1 phase cell cycle arrest. Collectively, this study provides a novel regulatory signaling pathway of CDC6-regulated EOC growth and a new potential therapeutic target for EOC patients. PMID:26920249

  13. Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization

    DEFF Research Database (Denmark)

    Petersen, B O; Lukas, J; Sørensen, Claus Storgaard;

    1999-01-01

    CDKs. CDC6 interacts specifically with the active Cyclin A/CDK2 complex in vitro and in vivo, but not with Cyclin E or Cyclin B kinase complexes. The cyclin binding domain of CDC6 was mapped to an N-terminal Cy-motif that is similar to the cyclin binding regions in p21(WAF1/SDI1) and E2F-1. The in vivo...... relocalizes to the cytoplasm when Cyclin A/CDK2 is activated. In agreement with CDC6 phosphorylation being specifically mediated by Cyclin A/CDK2, we show that ectopic expression of Cyclin A, but not of Cyclin E, leads to rapid relocalization of CDC6 from the nucleus to the cytoplasm. Based on our data we...... suggest that the phosphorylation of CDC6 by Cyclin A/CDK2 is a negative regulatory event that could be implicated in preventing re-replication during S phase and G2....

  14. Inhibition of CDC25B Phosphatase Through Disruption of Protein-Protein Interaction

    Energy Technology Data Exchange (ETDEWEB)

    Lund, George; Dudkin, Sergii; Borkin, Dmitry; Ni, Wendi; Grembecka, Jolanta; Cierpicki, Tomasz [Michigan

    2015-04-29

    CDC25 phosphatases are key cell cycle regulators and represent very attractive but challenging targets for anticancer drug discovery. Here, we explored whether fragment-based screening represents a valid approach to identify inhibitors of CDC25B. This resulted in identification of 2-fluoro-4-hydroxybenzonitrile, which directly binds to the catalytic domain of CDC25B. Interestingly, NMR data and the crystal structure demonstrate that this compound binds to the pocket distant from the active site and adjacent to the protein–protein interaction interface with CDK2/Cyclin A substrate. Furthermore, we developed a more potent analogue that disrupts CDC25B interaction with CDK2/Cyclin A and inhibits dephosphorylation of CDK2. Based on these studies, we provide a proof of concept that targeting CDC25 phosphatases by inhibiting their protein–protein interactions with CDK2/Cyclin A substrate represents a novel, viable opportunity to target this important class of enzymes.

  15. Implatation of MC2 computer code

    International Nuclear Information System (INIS)

    The implantation of MC2 computer code in the CDC system is presented. The MC2 computer code calculates multigroup cross sections for tipical compositions of fast reactors. The multigroup constants are calculated using solutions of PI or BI approximations for determined buckling value as weighting function. (M.C.K.)

  16. The Ubx2 and Ubx3 cofactors direct Cdc48 activity to proteolytic and nonproteolytic ubiquitin-dependent processes

    DEFF Research Database (Denmark)

    Hartmann-Petersen, Rasmus; Wallace, Mairi; Hofmann, Kay;

    2004-01-01

    Valosin-containing protein, VCP/p97 or Cdc48, is a eukaryotic ATPase involved in membrane fusion, protein transport, and protein degradation. We describe two proteins, Ubx2 and Ubx3, which interact with Cdc48 in fission yeast. Ubx3 is the ortholog of p47/Shp1, a previously described Cdc48 cofactor...

  17. The internal Cdc20 binding site in BubR1 facilitates both spindle assembly checkpoint signalling and silencing

    DEFF Research Database (Denmark)

    Lischetti, Tiziana; Zhang, Gang; Sedgwick, Garry G; Bolanos-Garcia, Victor M; Nilsson, Jakob

    2014-01-01

    in the SAC, we delineate the molecular details of its interaction with kinetochores. We find that BubR1 recruits the bulk of Cdc20 to kinetochores through its internal Cdc20 binding domain (IC20BD). We show that preventing Cdc20 kinetochore localization by removal of the IC20BD has a limited effect...

  18. Announcing the CDC guideline for prescribing opioids for chronic pain.

    Science.gov (United States)

    Houry, Debra; Baldwin, Grant

    2016-06-01

    This guideline provides recommendations for primary care providers who are prescribing opioids for chronic pain outside of active cancer treatment, palliative care, and end-of-life care. The guideline addresses: (a) when to initiate or continue opioids for chronic pain; (b) opioid selection, dosage, duration, follow-up, and discontinuation; and (c) assessing risk and addressing harms of opioid use. This guideline is intended to improve communication between providers and patients about the risks and benefits of opioid therapy for chronic pain, improve the safety and effectiveness of pain treatment, and reduce the risks associated with long-term opioid therapy, including abuse, dependence, overdose, and death (Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016. MMWR Recomm Rep 2016;65:1-49. DOI: http://dx.doi.org/10.15585/mmwr.rr6501e1.). PMID:27178083

  19. Androgens upregulate Cdc25C protein by inhibiting its proteasomal and lysosomal degradation pathways.

    Directory of Open Access Journals (Sweden)

    Yu-Wei Chou

    Full Text Available Cdc25C is a cell cycle protein of the dual specificity phosphatase family essential for activating the cdk1/Cyclin B1 complex in cells entering into mitosis. Since altered cell cycle is a hallmark of human cancers, we investigated androgen regulation of Cdc25C protein in human prostate cancer (PCa cells, including androgen-sensitive (AS LNCaP C-33 cells and androgen-independent (AI LNCaP C-81 as well as PC-3 cells. In the regular culture condition containing fetal bovine serum (FBS, Cdc25C protein levels were similar in these PCa cells. In a steroid-reduced condition, Cdc25C protein was greatly decreased in AS C-33 cells but not AI C-81 or PC-3 cells. In androgen-treated C-33 cells, the Cdc25C protein level was greatly elevated, following a dose- and a time-dependent manner, correlating with increased cell proliferation. This androgen effect was blocked by Casodex, an androgen receptor blocker. Nevertheless, epidermal growth factor (EGF, a growth stimulator of PCa cells, could only increase Cdc25C protein level by about 1.5-fold. Altered expression of Cdc25C in C-33 cells and PC-3 cells by cDNA and/or shRNA transfection is associated with the corresponding changes of cell growth and Cyclin B1 protein level. Actinomycin D and cycloheximide could only partially block androgen-induced Cdc25C protein level. Treatments with both proteasomal and lysosomal inhibitors resulted in elevated Cdc25C protein levels. Immunoprecipitation revealed that androgens reduced the ubiquitination of Cdc25C proteins. These results show for the first time that Cdc25C protein plays a role in regulating PCa cell growth, and androgen treatments, but not EGF, greatly increase Cdc25C protein levels in AS PCa cells, which is in part by decreasing its degradation. These results can lead to advanced PCa therapy via up-regulating the degradation pathways of Cdc25C protein.

  20. An Essential Role for Cdc42 in the Functioning of the Adult Mammary Gland.

    Science.gov (United States)

    Druso, Joseph E; Endo, Makoto; Lin, Miao-Chong Joy; Peng, Xu; Antonyak, Marc A; Meller, Stephanie; Cerione, Richard A

    2016-04-22

    The Rho family small GTPase Cdc42 has been implicated in a wide range of cellular functions including the establishment of cell polarity and the remodeling of the actin cytoskeletal architecture, resulting in the tight regulation of cell growth and survival during developmental processes. The complete knock-out of Cdc42 in the mouse is embryonic-lethal, and its targeted deletion in various tissues has been shown to disrupt tissue homeostasis. Thus far, in most studies, the targeted deletion of Cdc42 occurred during embryogenesis. Here, we have used a conditional gene deletion strategy in mice to probe the specific role of Cdc42 during adult mammary gland function. Cdc42 conditional-knock-out females were unable to adequately nourish their pups, due to a disorganized epithelial compartment within their mammary glands. A closer examination showed that their mammary epithelial cells were not able to maintain functional alveolar lumens, due to an inability to establish normal apical/basal epithelial polarity, as well as proper cell-cell contacts. Loss of these essential epithelial characteristics led to a premature sloughing off of the Cdc42-null epithelial cells. Overall our findings demonstrate that Cdc42 plays essential roles in mammary gland function post pregnancy, where it helps to establish proper epithelial cell polarity and tissue homeostasis during lactation. PMID:26912661

  1. Cdc37 is essential for chromosome segregation and cytokinesis in higher eukaryotes

    Science.gov (United States)

    Lange, Bodo M.H.; Rebollo, Elena; Herold, Andrea; González, Cayetano

    2002-01-01

    Cdc37 has been shown to be required for the activity and stability of protein kinases that regulate different stages of cell cycle progression. However, little is known so far regarding interactions of Cdc37 with kinases that play a role in cell division. Here we show that the loss of function of Cdc37 in Drosophila leads to defects in mitosis and male meiosis, and that these phenotypes closely resemble those brought about by the inactivation of Aurora B. We provide evidence that Aurora B interacts with and requires the Cdc37/Hsp90 complex for its stability. We conclude that the Cdc37/Hsp90 complex modulates the function of Aurora B and that most of the phenotypes brought about by the loss of Cdc37 function can be explained by the inactivation of this kinase. These observations substantiate the role of Cdc37 as an upstream regulatory element of key cell cycle kinases. PMID:12374737

  2. Opposing Roles for Actin in Cdc42p PolarizationD⃞

    Science.gov (United States)

    Irazoqui, Javier E.; Howell, Audrey S.; Theesfeld, Chandra L.; Lew, Daniel J.

    2005-01-01

    In animal and fungal cells, the monomeric GTPase Cdc42p is a key regulator of cell polarity that itself exhibits a polarized distribution in asymmetric cells. Previous work showed that in budding yeast, Cdc42p polarization is unaffected by depolymerization of the actin cytoskeleton (Ayscough et al., J. Cell Biol. 137, 399–416, 1997). Surprisingly, we now report that unlike complete actin depolymerization, partial actin depolymerization leads to the dispersal of Cdc42p from the polarization site in unbudded cells. We provide evidence that dispersal is due to endocytosis associated with cortical actin patches and that actin cables are required to counteract the dispersal and maintain Cdc42p polarity. Thus, although Cdc42p is initially polarized in an actin-independent manner, maintaining that polarity may involve a reinforcing feedback between Cdc42p and polarized actin cables to counteract the dispersing effects of actin-dependent endocytosis. In addition, we report that once a bud has formed, polarized Cdc42p becomes more resistant to dispersal, revealing an unexpected difference between unbudded and budded cells in the organization of the polarization site. PMID:15616194

  3. Cdc6 is a rate-limiting factor for proliferative capacity during HL60 cell differentiation

    International Nuclear Information System (INIS)

    The DNA replication (or origin) licensing pathway represents a critical step in cell proliferation control downstream of growth signalling pathways. Repression of origin licensing through down-regulation of the MCM licensing factors (Mcm2-7) is emerging as a ubiquitous route for lowering proliferative capacity as metazoan cells exit the cell division cycle into quiescent, terminally differentiated and senescent 'out-of-cycle' states. Using the HL60 monocyte/macrophage differentiation model system and a cell-free DNA replication assay, we have undertaken direct biochemical investigations of the coupling of origin licensing to the differentiation process. Our data show that down-regulation of the MCM loading factor Cdc6 acts as a molecular switch that triggers loss of proliferative capacity during early engagement of the somatic differentiation programme. Consequently, addition of recombinant Cdc6 protein to in vitro replication reactions restores DNA replication competence in nuclei prepared from differentiating cells. Differentiating HL60 cells over-expressing either wild-type Cdc6 or a CDK phosphorylation-resistant Cdc6 mutant protein (Cdc6A4) exhibit an extended period of cell proliferation compared to mock-infected cells. Notably, differentiating HL60 cells over-expressing the Cdc6A4 mutant fail to down-regulate Cdc6 protein levels, suggesting that CDK phosphorylation of Cdc6 is linked to its down-regulation during differentiation and the concomitant decrease in cell proliferation. In this experimental model, Cdc6 therefore plays a key role in the sequential molecular events leading to repression of origin licensing and loss of proliferative capacity during execution of the differentiation programme

  4. Essential roles of Cdc42 and MAPK in cadmium-induced apoptosis in Litopenaeus vannamei

    International Nuclear Information System (INIS)

    Highlights: • Cd2+ induces Cdc42 and MAPKs pathway related gene of Litopenaeus vannamei up-regulation. • Reduction of THC, increase of ROS production and apoptotic cell rate were observed when the shrimps exposure to Cd2+. • DsRNA-suppression of LvCdc42 and MAPKs during Cd2+ stress reduces the ROS production and apoptosis. • We conclude that LvCdc42 and MAPKs play key roles in Cd2+ stress responses of shrimps. - Abstract: Cadmium, one of the most toxic heavy metals in aquatic environments, has severe effects on marine invertebrates and fishes. The MAPK signaling pathway plays a vital role in stress responses of animals. The mitogen-activated protein kinase (MAPK) signaling pathway plays a vital role in animals’ stress responses, including mediation of apoptosis induced by the Rho GTPase Cdc42. However, there is limited knowledge about its function in shrimps, although disorders exacerbated by environmental stresses (including heavy metal pollution) have caused serious mortality in commercially cultured shrimps. Thus, we probed roles of Cdc42 in Litopenaeus vannamei shrimps (LvCdc42) during cadmium exposure by inhibiting its expression using dsRNA-mediated RNA interference. The treatment successfully reduced expression levels of MAPKs (including p38, JNK, and ERK). Cadmium exposure induced significant increases in expression levels of LvCdc42 and MAPKs, accompanied by reductions in total hemocyte counts (THC) and increases in apoptotic hemocyte ratios and ROS production. However, all of these responses were much weaker in LvCdc42-suppressed shrimps, in which mortality rates were higher than in controls. Our results suggest that the MAPK pathway plays a vital role in shrimps’ responses to Cd2+. They also indicate that LvCdc42 in shrimps participates in its regulation, and thus plays key roles in ROS production, regulation of apoptosis and associated stress responses

  5. Essential roles of Cdc42 and MAPK in cadmium-induced apoptosis in Litopenaeus vannamei

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Ting; Wang, Wei-Na, E-mail: weina63@aliyun.com; Gu, Mei-Mei; Xie, Chen-Ying; Xiao, Yu-Chao; Liu, Yuan; Wang, Lei

    2015-06-15

    Highlights: • Cd{sup 2+} induces Cdc42 and MAPKs pathway related gene of Litopenaeus vannamei up-regulation. • Reduction of THC, increase of ROS production and apoptotic cell rate were observed when the shrimps exposure to Cd{sup 2+}. • DsRNA-suppression of LvCdc42 and MAPKs during Cd{sup 2+} stress reduces the ROS production and apoptosis. • We conclude that LvCdc42 and MAPKs play key roles in Cd{sup 2+} stress responses of shrimps. - Abstract: Cadmium, one of the most toxic heavy metals in aquatic environments, has severe effects on marine invertebrates and fishes. The MAPK signaling pathway plays a vital role in stress responses of animals. The mitogen-activated protein kinase (MAPK) signaling pathway plays a vital role in animals’ stress responses, including mediation of apoptosis induced by the Rho GTPase Cdc42. However, there is limited knowledge about its function in shrimps, although disorders exacerbated by environmental stresses (including heavy metal pollution) have caused serious mortality in commercially cultured shrimps. Thus, we probed roles of Cdc42 in Litopenaeus vannamei shrimps (LvCdc42) during cadmium exposure by inhibiting its expression using dsRNA-mediated RNA interference. The treatment successfully reduced expression levels of MAPKs (including p38, JNK, and ERK). Cadmium exposure induced significant increases in expression levels of LvCdc42 and MAPKs, accompanied by reductions in total hemocyte counts (THC) and increases in apoptotic hemocyte ratios and ROS production. However, all of these responses were much weaker in LvCdc42-suppressed shrimps, in which mortality rates were higher than in controls. Our results suggest that the MAPK pathway plays a vital role in shrimps’ responses to Cd{sup 2+}. They also indicate that LvCdc42 in shrimps participates in its regulation, and thus plays key roles in ROS production, regulation of apoptosis and associated stress responses.

  6. Cytoplasmic Localization of Human cdc25C during Interphase Requires an Intact 14-3-3 Binding Site

    OpenAIRE

    Dalal, Sorab N.; Schweitzer, Colleen M.; Gan, Jianmin; DeCaprio, James A.

    1999-01-01

    cdc25C induces mitosis by activating the cdc2-cyclin B complex. The intracellular localization of cyclin B1 is regulated in a cell cycle-specific manner, and its entry into the nucleus may be required for the initiation of mitosis. To determine the cellular localization of cdc25C, monoclonal antibodies specific for cdc25C were developed and used to demonstrate that in human cells, cdc25C is retained in the cytoplasm during interphase. A deletion analysis identified a 58-amino-acid region (ami...

  7. NEK11: linking CHK1 and CDC25A in DNA damage checkpoint signaling

    DEFF Research Database (Denmark)

    Sørensen, Claus Storgaard; Melixetian, Marina; Klein, Ditte Kjaersgaard;

    2010-01-01

    The DNA damage induced G(2)/M checkpoint is an important guardian of the genome that prevents cell division when DNA lesions are present. The checkpoint prevents cells from entering mitosis by degrading CDC25A, a key CDK activator. CDC25A proteolysis is controlled by direct phosphorylation events...... required for beta-TrCP mediated CDC25A polyubiquitylation and degradation. The activity of NEK11 is in turn controlled by CHK1 that activates NEK11 via phosphorylation on serine 273. Since inhibition of NEK11 activity forces checkpoint-arrested cells into mitosis and cell death, NEK11 is, like CHK1, a...

  8. Cdc20 mediates D-box-dependent degradation of Sp100

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ran; Li, Ke-min; Zhou, Cai-hong; Xue, Jing-lun [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai (China); Ji, Chao-neng, E-mail: Chnji@fudan.edu.cn [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai (China); Chen, Jin-zhong, E-mail: kingbellchen@fudan.edu.cn [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai (China)

    2011-12-02

    Highlights: Black-Right-Pointing-Pointer Cdc20 is a co-activator of APC/C complex. Black-Right-Pointing-Pointer Cdc20 recruits Sp100 and mediates its degradation. Black-Right-Pointing-Pointer The D-box of Sp100 is required for Cdc20-mediated degradation. Black-Right-Pointing-Pointer Sp100 expresses consistently at both the mRNA and protein levels in cell cycle. -- Abstract: Cdc20 is a co-activator of the anaphase-promoting complex/cyclosome (APC/C complex), which recruits substrates at particular phases of the cell cycle and mediates their degradation. Sp100 is a PML-NB scaffold protein, which localizes to nuclear particles during interphase and disperses from them during mitosis, participates in viral resistance, transcriptional regulation, and apoptosis. However, its metabolism during the cell cycle has not yet been fully characterized. We found a putative D-box in Sp100 using the Eukaryotic Linear Motif (ELM) predictor database. The putative D-box of Sp100 was verified by mutational analysis. Overexpression of Cdc20 resulted in decreased levels of both endogenous Sp100 protein and overexpressed Sp100 mRNA in HEK 293 cells. Only an overexpressed D-box deletion mutant of Sp100 accumulated in HEK293 cells that also overexpressed Cdc20. Cdc20 knockdown by cdc20 specific siRNA resulted in increased Sp100 protein levels in cells. Furthermore, we discovered that the Cdc20 mediated degradation of Sp100 is diminished by the proteasome inhibitor MG132, which suggests that the ubiquitination pathway is involved in this process. However, unlike the other Cdc20 substrates, which display oscillating protein levels, the level of Sp100 protein remains constant throughout the cell cycle. Additionally, both overexpression and knockdown of endogenous Sp100 had no effect on the cell cycle. Our results suggested that sp100 is a novel substrate of Cdc20 and it is degraded by the ubiquitination pathway. The intact D-box of Sp100 was necessary for this process. These findings expand

  9. CDC25A governs proliferation and differentiation of FLT3-ITD acute myeloid leukemia

    OpenAIRE

    Bertoli, Sarah; Boutzen, Helena; David, Laure; Larrue, Clément; Vergez, François; Fernandez-Vidal, Anne; Yuan, Lingli; Hospital, Marie-Anne; Tamburini, Jérôme; Demur, Cecile; Delabesse, Eric; Saland, Estelle; Sarry, Jean-Emmanuel; Galcera, Marie-Odile; Mansat-De Mas, Véronique

    2015-01-01

    We investigated cell cycle regulation in acute myeloid leukemia cells expressing the FLT3-ITD mutated tyrosine kinase receptor, an underexplored field in this disease. Upon FLT3 inhibition, CDC25A mRNA and protein were rapidly down-regulated, while levels of other cell cycle proteins remained unchanged. This regulation was dependent on STAT5, arguing for FLT3-ITD-dependent transcriptional regulation of CDC25A. CDC25 inhibitors triggered proliferation arrest and cell death of FLT3-ITD as well ...

  10. Automatic neutron PSD transmission from a process computer to a timeshare system

    Energy Technology Data Exchange (ETDEWEB)

    Bullock, J.B.; Sides, W.H. Jr.

    1977-04-01

    A method for automatically telephoning, connecting, and transmitting neutron power-spectral density data from a CDC-1700 process control computer to a PDP-10 time-share system is described. Detailed program listings and block diagrams are included.

  11. Automatic neutron PSD transmission from a process computer to a timeshare system

    International Nuclear Information System (INIS)

    A method for automatically telephoning, connecting, and transmitting neutron power-spectral density data from a CDC-1700 process control computer to a PDP-10 time-share system is described. Detailed program listings and block diagrams are included

  12. ORACLS- OPTIMAL REGULATOR ALGORITHMS FOR THE CONTROL OF LINEAR SYSTEMS (CDC VERSION)

    Science.gov (United States)

    Armstrong, E. S.

    1994-01-01

    , formulates and selects the routines to be used to solve the problem, and specifies the desired output. There are three versions of ORACLS source code available for implementation: CDC, IBM, and DEC. The CDC version has been implemented on a CDC 6000 series computer with a central memory of approximately 13K (octal) of 60 bit words. The CDC version is written in FORTRAN IV, was developed in 1978, and last updated in 1989. The IBM version has been implemented on an IBM 370 series computer with a central memory requirement of approximately 300K of 8 bit bytes. The IBM version is written in FORTRAN IV and was generated in 1981. The DEC version has been implemented on a VAX series computer operating under VMS. The VAX version is written in FORTRAN 77 and was generated in 1986.

  13. Characterization of a Dual CDC7/CDK9 Inhibitor in Multiple Myeloma Cellular Models

    International Nuclear Information System (INIS)

    Two key features of myeloma cells are the deregulation of the cell cycle and the dependency on the expression of the BCL2 family of anti-apoptotic proteins. The cell division cycle 7 (CDC7) is an essential S-phase kinase and emerging CDC7 inhibitors are effective in a variety of preclinical cancer models. These compounds also inhibit CDK9 which is relevant for MCL-1 expression. The activity and mechanism of action of the dual CDC7/CDK9 inhibitor PHA-767491 was assessed in a panel of multiple myeloma cell lines, in primary samples from patients, in the presence of stromal cells and in combination with drugs used in current chemotherapeutic regimens. We report that in all conditions myeloma cells undergo cell death upon PHA-767491 treatment and we report an overall additive effect with melphalan, bortezomib and doxorubicin, thus supporting further assessment of targeting CDC7 and CDK9 in multiple myeloma

  14. Businesses Should Be Mindful of Zika Danger to Workers, CDC Says

    Science.gov (United States)

    ... nih.gov/medlineplus/news/fullstory_158458.html Businesses Should Be Mindful of Zika Danger to Workers, CDC ... a news release. As for travel protocols, "employers should consider allowing flexibility in required travel to areas ...

  15. 75 FR 39264 - CDC/HRSA Advisory Committee on HIV and STD Prevention and Treatment

    Science.gov (United States)

    2010-07-08

    ... CDC/HRSA Advisory Committee on HIV and STD Prevention and Treatment In accordance with section 10(a)(2..., Viral Hepatitis, STD, and TB ] Prevention, 1600 Clifton Road, NE., Mailstop E-07, Atlanta, Georgia...

  16. 76 FR 66721 - CDC/HRSA Advisory Committee on HIV and STD Prevention and Treatment

    Science.gov (United States)

    2011-10-27

    ... Prevention and Treatment In accordance with section l0(a)(2) of the Federal Advisory Committee Act (Pub. L...-Cseh, CDC, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, 1600 Clifton Road,...

  17. Characterization of a Dual CDC7/CDK9 Inhibitor in Multiple Myeloma Cellular Models

    Energy Technology Data Exchange (ETDEWEB)

    Natoni, Alessandro [Centre for Chromosome Biology, School of Natural Sciences National University of Ireland Galway, Galway (Ireland); Coyne, Mark R. E. [Centre for Chromosome Biology, School of Natural Sciences National University of Ireland Galway, Galway (Ireland); Department of Medicine, National University of Ireland Galway, Galway (Ireland); Department of Haematology, Galway University Hospital, Galway (Ireland); Jacobsen, Alan; Rainey, Michael D.; O’Brien, Gemma; Healy, Sandra [Centre for Chromosome Biology, School of Natural Sciences National University of Ireland Galway, Galway (Ireland); Montagnoli, Alessia; Moll, Jürgen [Nerviano Medical Sciences S.r.l., Via Pasteur 10, Nerviano 20014 (Italy); O’Dwyer, Michael, E-mail: michael.odwyer@nuigalway.ie [Department of Medicine, National University of Ireland Galway, Galway (Ireland); Department of Haematology, Galway University Hospital, Galway (Ireland); Santocanale, Corrado, E-mail: michael.odwyer@nuigalway.ie [Centre for Chromosome Biology, School of Natural Sciences National University of Ireland Galway, Galway (Ireland)

    2013-07-24

    Two key features of myeloma cells are the deregulation of the cell cycle and the dependency on the expression of the BCL2 family of anti-apoptotic proteins. The cell division cycle 7 (CDC7) is an essential S-phase kinase and emerging CDC7 inhibitors are effective in a variety of preclinical cancer models. These compounds also inhibit CDK9 which is relevant for MCL-1 expression. The activity and mechanism of action of the dual CDC7/CDK9 inhibitor PHA-767491 was assessed in a panel of multiple myeloma cell lines, in primary samples from patients, in the presence of stromal cells and in combination with drugs used in current chemotherapeutic regimens. We report that in all conditions myeloma cells undergo cell death upon PHA-767491 treatment and we report an overall additive effect with melphalan, bortezomib and doxorubicin, thus supporting further assessment of targeting CDC7 and CDK9 in multiple myeloma.

  18. Defective tubulin organization and proplatelet formation in murine megakaryocytes lacking Rac1 and Cdc42

    DEFF Research Database (Denmark)

    Pleines, Irina; Dütting, Sebastian; Cherpokova, Deya; Eckly, Anita; Meyer, Imke; Morowski, Martina; Krohne, Georg; Schulze, Harald; Gachet, Christian; Debili, Najet; Brakebusch, Cord Herbert; Nieswandt, Bernhard

    2013-01-01

    and tubulin cytoskeleton. Rho GTPases, such as RhoA, Rac1, and Cdc42, are important regulators of cytoskeletal rearrangements in platelets; however, the specific roles of these proteins during platelet production have not been established. Using conditional knockout mice, we show here that Rac1 and...... Cdc42 possess redundant functions in platelet production and function. In contrast to a single-deficiency of either protein, a double-deficiency of Rac1 and Cdc42 in MKs resulted in macrothrombocytopenia, abnormal platelet morphology, and impaired platelet function. Double-deficient bone marrow MKs...... matured normally in vivo but displayed highly abnormal morphology and uncontrolled fragmentation. Consistently, a lack of Rac1/Cdc42 virtually abrogated proplatelet formation in vitro. Strikingly, this phenotype was associated with severely defective tubulin organization, whereas actin assembly and...

  19. 13 CFR 120.972 - Third Party Lender participation fee and CDC fee.

    Science.gov (United States)

    2010-01-01

    ... BUSINESS LOANS Development Company Loan Program (504) Fees § 120.972 Third Party Lender participation fee... when the Third Party Lender occupies a senior credit position to SBA in the Project. (b) CDC fee....

  20. Breastfeeding Among U.S. Children Born 2000 - 2009, CDC National Immunization Survey

    Science.gov (United States)

    ... Their Families Communities Health Care Employment Research & Surveillance Public Health Infrastructure National Policies & Positions Healthy People 2020 Frequently Asked Questions (FAQs) Resources & Publications Breastfeeding Progress MMWR Highlights CDC Guide to Strategies to ...

  1. Fewer U.S. Kids Die from Abusive Head Trauma: CDC

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_159052.html Fewer U.S. Kids Die From Abusive Head Trauma: CDC Parent ... two years of the study, according to the U.S. Centers for Disease Control and Prevention. Experts said ...

  2. U.S. Suicide Rate Up 24 Percent Since 1999: CDC

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_158462.html U.S. Suicide Rate Up 24 Percent Since 1999: CDC ... per 100,000 people, said researchers from the U.S. Centers for Disease Control and Prevention's National Center ...

  3. U.S. Autism Rate Unchanged at 1 in 68 Kids: CDC

    Science.gov (United States)

    ... nih.gov/medlineplus/news/fullstory_158064.html U.S. Autism Rate Unchanged at 1 in 68 Kids: CDC ... 2016 THURSDAY, March 31, 2016 (HealthDay News) -- The autism rate among school-aged children in the United ...

  4. CDC Zika Summit Details Plans to Fight Mosquito-Borne Illness

    Science.gov (United States)

    ... nih.gov/medlineplus/news/fullstory_158094.html CDC Zika Summit Details Plans to Fight Mosquito-Borne Illness ... the continental United States braces itself for the Zika virus, federal, state and local health officials gathered ...

  5. U.S. Suicide Rate Up 24 Percent Since 1999: CDC

    Science.gov (United States)

    ... nih.gov/medlineplus/news/fullstory_158462.html U.S. Suicide Rate Up 24 Percent Since 1999: CDC Rates ... 22, 2016 FRIDAY, April 22, 2016 (HealthDay News) -- Suicide rates in the United States rose 24 percent ...

  6. 78 FR 60876 - Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)

    Science.gov (United States)

    2013-10-02

    ... the next day. Number for Technical Support: (404) 639-3737 The deadline for notification of attendance...: Carmen Villar, MSW, Designated Federal Officer, Advisory Committee to the Director, CDC, 1600...

  7. Characteristics of CDC group 1 and group 1-like coryneform bacteria isolated from clinical specimens.

    OpenAIRE

    Funke, G; Lucchini, G M; Pfyffer, G E; Marchiani, M; von Graevenitz, A

    1993-01-01

    Fifteen strains of CDC group 1 coryneform and biochemically similar bacteria were isolated from clinical specimens. Of the 15 strains isolated, 11 were derived from abscesses and purulent lesions, mostly from the upper part of the body, and 3 were grown from blood cultures. Nine strains were associated with mixed anaerobic but no other aerobic flora. Seven strains exhibited the classical biochemical profile of CDC coryneform group 1; however, eight strains were unable to reduce nitrate and we...

  8. Glucose-stimulated Cdc42 Signaling Is Essential for the Second Phase of Insulin Secretion*

    OpenAIRE

    Wang, Zhanxiang; Oh, Eunjin; Thurmond, Debbie C.

    2007-01-01

    The small Rho family GTPases Cdc42 and Rac1 have each been shown to function in insulin exocytosis and are presumed to function in actin remodeling and insulin granule mobilization. However, whether either GTPase is required for the mobilization phase of insulin release (second phase) and are linked in a common signaling pathway has remained unknown. Here we demonstrate that small interfering RNA-mediated depletion of Cdc42 from isolated islets results in the selective loss of second-phase in...

  9. NCAR Johns Hopkins/CDC Climate and Health Summer Institute

    Science.gov (United States)

    Mearns, Linda O.

    2005-01-01

    The interactions between climate and health are rife with complexity and present many conceptual and methodological challenges. Possible effects of climate change on health are considered some of the most sensitive impacts of climate change and are a high priority for policy-makers and the public. As a first step toward improving tlit: quality of research, we developed a Climate and Health Workshop (Institute), geared toward teaching students various aspects of how to conduct integrated climate and health research. At the workshop scientists presented selected case studies of climate and health (e.g., heat mortality, vector-borne diseases), thus demonstrating a subset of key analytical tools and databases most useful to researchers in this field. Key research gaps in this research area were discussed. In this six-day Institute (21-28 July 2004, Boulder, Colorado), health scientists and students benefited from lectures and hands-on tools taught by top NCAR scientists. The attendees learned about health databases and epidemiologic methods from leading health scientists from CDC, Johns Hopkins, and other institutions from around the globe.

  10. CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016.

    Science.gov (United States)

    Dowell, Deborah; Haegerich, Tamara M; Chou, Roger

    2016-01-01

    This guideline provides recommendations for primary care clinicians who are prescribing opioids for chronic pain outside of active cancer treatment, palliative care, and end-of-life care. The guideline addresses 1) when to initiate or continue opioids for chronic pain; 2) opioid selection, dosage, duration, follow-up, and discontinuation; and 3) assessing risk and addressing harms of opioid use. CDC developed the guideline using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, and recommendations are made on the basis of a systematic review of the scientific evidence while considering benefits and harms, values and preferences, and resource allocation. CDC obtained input from experts, stakeholders, the public, peer reviewers, and a federally chartered advisory committee. It is important that patients receive appropriate pain treatment with careful consideration of the benefits and risks of treatment options. This guideline is intended to improve communication between clinicians and patients about the risks and benefits of opioid therapy for chronic pain, improve the safety and effectiveness of pain treatment, and reduce the risks associated with long-term opioid therapy, including opioid use disorder, overdose, and death. CDC has provided a checklist for prescribing opioids for chronic pain (http://stacks.cdc.gov/view/cdc/38025) as well as a website (http://www.cdc.gov/drugoverdose/prescribingresources.html) with additional tools to guide clinicians in implementing the recommendations. PMID:26987082

  11. A novel E2 box-GATA element modulates Cdc6 transcription during human cells polyploidization.

    Science.gov (United States)

    Vilaboa, Nuria; Bermejo, Rodrigo; Martinez, Pilar; Bornstein, Rafael; Calés, Carmela

    2004-01-01

    Cdc6 is a key regulator of the strict alternation of S and M phases during the mitotic cell cycle. In mammalian and plant cells that physiologically become polyploid, cdc6 is transcriptionally and post-translationally regulated. We have recently reported that Cdc6 levels are maintained in megakaryoblastic HEL cells, but severely downregulated by ectopic expression of transcriptional repressor Drosophila melanogaster escargot. Here, we show that cdc6 promoter activity is upregulated during megakaryocytic differentiation of HEL endoreplicating cells, and that Escargot interferes with such activation. Transactivation experiments showed that a 1.7 kb region located at 2800 upstream cdc6 transcription initiation site behaved as a potent enhancer in endoreplicating cells only. This activity was mainly dependent on a novel cis-regulatory element composed by an E2 box overlapping a GATA motif. Ectopic Escargot could bind this regulatory element in vitro and endogenous GATA-1 and E2A formed specific complexes in megakaryoblastic cells as well as in primary megakaryocytes. Chromatin Immunoprecipitation analysis revealed that both transcription factors were occupying the E2 box/GATA site in vivo. Altogether, these data suggest that cdc6 expression could be actively maintained during megakaryocytic differentiation through transcriptional mechanisms involving specific cis- and trans-regulatory elements. PMID:15590906

  12. Roles of Aspergillus nidulans Cdc42/Rho GTPase regulators in hyphal morphogenesis and development.

    Science.gov (United States)

    Si, Haoyu; Rittenour, William R; Harris, Steven D

    2016-01-01

    The Rho-related family of GTPases are pivotal regulators of morphogenetic processes in diverse eukaryotic organisms. In the filamentous fungi two related members of this family, Cdc42 and Rac1, perform particularly important roles in the establishment and maintenance of hyphal polarity. The activity of these GTPases is tightly controlled by two sets of regulators: guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Despite the importance of Cdc42 and Rac1 in polarized hyphal growth, the morphogenetic functions of their cognate GEFs and GAPs have not been widely characterized in filamentous fungi outside the Saccharomycotina. Here we present a functional analysis of the Aspergillus nidulans homologs of the yeast GEF Cdc24 and the yeast GAP Rga1. We show that Cdc24 is required for the establishment of hyphal polarity and localizes to hyphal tips. We also show that Rga1 is necessary for the suppression of branching in developing conidiophores. During asexual development Rga1 appears to act primarily via Cdc42 and in doing so serves as a critical determinant of conidiophore architecture. Our results provide new insight into the roles of Cdc42 during development in A nidulans. PMID:26932184

  13. Cellular localization and biochemical analysis of mammalian CDC50A, a glycosylated β-subunit for P4 ATPases.

    Science.gov (United States)

    Folmer, Dineke E; Mok, Kam S; de Wee, Sebastiaan W; Duijst, Suzanne; Hiralall, Johan K; Seppen, Jurgen; Oude Elferink, Ronald P J; Paulusma, Coen C

    2012-03-01

    CDC50 proteins are β-subunits for P4 ATPases, which upon heterodimerization form a functional phospholipid translocation complex. Emerging evidence in mouse models and men links mutations in P4 ATPase genes with human disease. This study analyzed the tissue distribution and cellular localization of CDC50A, the most abundant and ubiquitously expressed CDC50 homologue in the mouse. The authors have raised antibodies that detect mouse and human CDC50A and studied CDC50A localization and glycosylation status in mouse liver cells. CDC50A is a terminal-glycosylated glycoprotein and is expressed in hepatocytes and liver sinusoidal endothelial cells, where it resides in detergent-resistant membranes. In pancreas and stomach, CDC50A localized to secretory vesicles, whereas in the kidney, CDC50A localized to the apical region of proximal convoluted tubules of the cortex. In WIF-B9 cells, CDC50A partially costains with the trans-Golgi network. Data suggest that CDC50A is present as a fully glycosylated protein in vivo, which presumes interaction with distinct P4 ATPases. PMID:22253360

  14. Human TRIB2 Oscillates during the Cell Cycle and Promotes Ubiquitination and Degradation of CDC25C.

    Science.gov (United States)

    Liang, Kai Ling; Paredes, Roberto; Carmody, Ruaidhri; Eyers, Patrick A; Meyer, Stefan; McCarthy, Tommie V; Keeshan, Karen

    2016-01-01

    Tribbles homolog 2 (TRIB2) is a member of the mammalian Tribbles family of serine/threonine pseudokinases (TRIB1-3). Studies of TRIB2 indicate that many of the molecular interactions between the single Drosophila Tribbles (Trbl) protein and interacting partners are evolutionary conserved. In this study, we examined the relationship between TRIB2 and cell division cycle 25 (CDC25) family of dual-specificity protein phosphatases (mammalian homologues of Drosophila String), which are key physiological cell cycle regulators. Using co-immunoprecipitation we demonstrate that TRIB2 interacts with CDC25B and CDC25C selectively. Forced overexpression of TRIB2 caused a marked decrease in total CDC25C protein levels. Following inhibition of the proteasome, CDC25C was stabilized in the nuclear compartment. This implicates TRIB2 as a regulator of nuclear CDC25C turnover. In complementary ubiquitination assays, we show that TRIB2-mediated degradation of CDC25C is associated with lysine-48-linked CDC25C polyubiquitination driven by the TRIB2 kinase-like domain. A cell cycle associated role for TRIB2 is further supported by the cell cycle regulated expression of TRIB2 protein levels. Our findings reveal mitotic CDC25C as a new target of TRIB2 that is degraded via the ubiquitin proteasome system. Inappropriate CDC25C regulation could mechanistically underlie TRIB2 mediated regulation of cellular proliferation in neoplastic cells. PMID:27563873

  15. Cdc6 localizes to S- and G2-phase centrosomes in a cell cycle-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Gwang Su; Kang, Jeeheon; Bang, Sung Woong; Hwang, Deog Su, E-mail: dshwang@snu.ac.kr

    2015-01-16

    Highlights: • Cdc6 protein is a component of the pre-replicative complex required for chromosomal replication initiation. • Cdc6 localized to centrosomes of S and G2 phases in a cell cycle-dependent manner. • The centrosomal localization was governed by centrosomal localization signal sequences of Cdc6. • Deletions or substitution mutations on the centrosomal localization signal interfered with centrosomal localization of the Cdc6 proteins. - Abstract: The Cdc6 protein has been primarily investigated as a component of the pre-replicative complex for the initiation of chromosome replication, which contributes to maintenance of chromosomal integrity. Here, we show that Cdc6 localized to the centrosomes during S and G2 phases of the cell cycle. The centrosomal localization was mediated by Cdc6 amino acid residues 311–366, which are conserved within other Cdc6 homologues and contains a putative nuclear export signal. Deletions or substitutions of the amino acid residues did not allow the proteins to localize to centrosomes. In contrast, DsRed tag fused to the amino acid residues localized to centrosomes. These results indicated that a centrosome localization signal is contained within amino acid residues 311–366. The cell cycle-dependent centrosomal localization of Cdc6 in S and G2 phases suggest a novel function of Cdc6 in centrosomes.

  16. The small GTPase Cdc42 modulates the number of exocytosis-competent dense-core vesicles in PC12 cells

    International Nuclear Information System (INIS)

    Highlights: ► Regulation of exocytosis by Rho GTPase Cdc42. ► Cdc42 increases the number of fusion events from newly recruited vesicles. ► Cdc42 increases the number of exocytosis-competent dense-core vesicles. -- Abstract: Although the small GTPase Rho family Cdc42 has been shown to facilitate exocytosis through increasing the amount of hormones released, the precise mechanisms regulating the quantity of hormones released on exocytosis are not well understood. Here we show by live cell imaging analysis under TIRF microscope and immunocytochemical analysis under confocal microscope that Cdc42 modulated the number of fusion events and the number of dense-core vesicles produced in the cells. Overexpression of a wild-type or constitutively-active form of Cdc42 strongly facilitated high-KCl-induced exocytosis from the newly recruited plasma membrane vesicles in PC12 cells. By contrast, a dominant-negative form of Cdc42 inhibited exocytosis from both the newly recruited and previously docked plasma membrane vesicles. The number of intracellular dense-core vesicles was increased by the overexpression of both a wild-type and constitutively-active form of Cdc42. Consistently, activation of Cdc42 by overexpression of Tuba, a Golgi-associated guanine nucleotide exchange factor for Cdc42 increased the number of intracellular dense-core vesicles, whereas inhibition of Cdc42 by overexpression of the Cdc42/Rac interactive binding domain of neuronal Wiskott–Aldrich syndrome protein decreased the number of them. These findings suggest that Cdc42 facilitates exocytosis by modulating both the number of exocytosis-competent dense-core vesicles and the production of dense-core vesicles in PC12 cells.

  17. Therapeutic Targeting the Cell Division Cycle 25 (CDC25 Phosphatases in Human Acute Myeloid Leukemia — The Possibility to Target Several Kinases through Inhibition of the Various CDC25 Isoforms

    Directory of Open Access Journals (Sweden)

    Annette K. Brenner

    2014-11-01

    Full Text Available The cell division cycle 25 (CDC25 phosphatases include CDC25A, CDC25B and CDC25C. These three molecules are important regulators of several steps in the cell cycle, including the activation of various cyclin-dependent kinases (CDKs. CDC25s seem to have a role in the development of several human malignancies, including acute myeloid leukemia (AML; and CDC25 inhibition is therefore considered as a possible anticancer strategy. Firstly, upregulation of CDC25A can enhance cell proliferation and the expression seems to be controlled through PI3K-Akt-mTOR signaling, a pathway possibly mediating chemoresistance in human AML. Loss of CDC25A is also important for the cell cycle arrest caused by differentiation induction of malignant hematopoietic cells. Secondly, high CDC25B expression is associated with resistance against the antiproliferative effect of PI3K-Akt-mTOR inhibitors in primary human AML cells, and inhibition of this isoform seems to reduce AML cell line proliferation through effects on NFκB and p300. Finally, CDC25C seems important for the phenotype of AML cells at least for a subset of patients. Many of the identified CDC25 inhibitors show cross-reactivity among the three CDC25 isoforms. Thus, by using such cross-reactive inhibitors it may become possible to inhibit several molecular events in the regulation of cell cycle progression and even cytoplasmic signaling, including activation of several CDKs, through the use of a single drug. Such combined strategies will probably be an advantage in human cancer treatment.

  18. Thyroid bud morphogenesis requires CDC42- and SHROOM3-dependent apical constriction

    Science.gov (United States)

    Loebel, David A. F.; Plageman, Timothy F.; Tang, Theresa L.; Jones, Vanessa J.; Muccioli, Maria; Tam, Patrick P. L.

    2016-01-01

    ABSTRACT Early development of the gut endoderm and its subsequent remodeling for the formation of organ buds are accompanied by changes to epithelial cell shape and polarity. Members of the Rho-related family of small GTPases and their interacting proteins play multiple roles in regulating epithelial morphogenesis. In this study we examined the role of Cdc42 in foregut development and organ bud formation. Ablation of Cdc42 in post-gastrulation mouse embryos resulted in a loss of apical-basal cell polarity and columnar epithelial morphology in the ventral pharyngeal endoderm, in conjunction with a loss of apical localization of the known CDC42 effector protein PARD6B. Cell viability but not proliferation in the foregut endoderm was impaired. Outgrowth of the liver, lung and thyroid buds was severely curtailed in Cdc42-deficient embryos. In particular, the thyroid bud epithelium did not display the apical constriction that normally occurs concurrently with the outgrowth of the bud into the underlying mesenchyme. SHROOM3, a protein that interacts with Rho GTPases and promotes apical constriction, was strongly expressed in the thyroid bud and its sub-cellular localization was disrupted in Cdc42-deficient embryos. In Shroom3 gene trap mutant embryos, the thyroid bud epithelium showed no apical constriction, while the bud continued to grow and protruded into the foregut lumen. Our findings indicate that Cdc42 is required for epithelial polarity and organization in the endoderm and for apical constriction in the thyroid bud. It is possible that the function of CDC42 is partly mediated by SHROOM3. PMID:26772200

  19. Hepatocyte-specific deletion of Cdc42 results in delayed liver regeneration after partial hepatectomy in mice

    DEFF Research Database (Denmark)

    Yuan, Haixin; Zhang, Hong; Wu, Xunwei;

    2009-01-01

    Cdc42, a member of the Rho guanosine triphosphatase (GTPase) family, plays important roles in the regulation of the cytoskeleton, cell proliferation, cell polarity, and cellular transport, but little is known about its specific function in mammalian liver. We investigated the function of Cdc42 in...... regeneration, which may result from impaired cytoskeletal organization and intracellular trafficking in hepatocytes. Conclusion: Our results revealed important roles of Cdc42 in the regulation of proliferative signaling during liver regeneration....

  20. The F-box protein Cdc4/Fbxw7 is a novel regulator of neural crest development in Xenopus laevis

    Directory of Open Access Journals (Sweden)

    Hartley Rebecca S

    2010-01-01

    Full Text Available Abstract Background The neural crest is a unique population of cells that arise in the vertebrate ectoderm at the neural plate border after which they migrate extensively throughout the embryo, giving rise to a wide range of derivatives. A number of proteins involved in neural crest development have dynamic expression patterns, and it is becoming clear that ubiquitin-mediated protein degradation is partly responsible for this. Results Here we demonstrate a novel role for the F-box protein Cdc4/Fbxw7 in neural crest development. Two isoforms of Xenopus laevis Cdc4 were identified, and designated xCdc4α and xCdc4β. These are highly conserved with vertebrate Cdc4 orthologs, and the Xenopus proteins are functionally equivalent in terms of their ability to degrade Cyclin E, an established vertebrate Cdc4 target. Blocking xCdc4 function specifically inhibited neural crest development at an early stage, prior to expression of c-Myc, Snail2 and Snail. Conclusions We demonstrate that Cdc4, an ubiquitin E3 ligase subunit previously identified as targeting primarily cell cycle regulators for proteolysis, has additional roles in control of formation of the neural crest. Hence, we identify Cdc4 as a protein with separable but complementary functions in control of cell proliferation and differentiation.

  1. Anti-CDC25B autoantibody predicts poor prognosis in patients with advanced esophageal squamous cell carcinoma

    OpenAIRE

    Dong Jun; Zeng Bo-hang; Xu Li-hua; Wang Jun-ye; Li Man-Zhi; Zeng Mu-sheng; Liu Wan-li

    2010-01-01

    Abstract Background The oncogene CDC25B phosphatase plays an important role in cancer cell growth. We have recently reported that patients with esophageal squamous cell carcinoma (ESCC) have significantly higher serum levels of CDC25B autoantibodies (CDC25B-Abs) than both healthy individuals and patients with other types of cancer; however, the potential diagnostic or prognostic significance of CDC25B-Abs is not clear. The aim of this study is to evaluate the clinical significance of serum CD...

  2. The small G-proteins Rac1 and Cdc42 are essential for myoblast fusion in the mouse

    DEFF Research Database (Denmark)

    Vasyutina, Elena; Martarelli, Benedetta; Brakebusch, Cord; Wende, Hagen; Birchmeier, Carmen

    2009-01-01

    Rac1 and Cdc42 are small G-proteins that regulate actin dynamics and affect plasma membrane protrusion and vesicle traffic. We used conditional mutagenesis in mice to demonstrate that Rac1 and Cdc42 are essential for myoblast fusion in vivo and in vitro. The deficit in fusion of Rac1 or Cdc42...... genetic analysis demonstrates thus that the function of Rac in myoblast fusion is evolutionarily conserved from insects to mammals and that Cdc42, a molecule hitherto not implicated in myoblast fusion, is essential for the fusion of murine myoblasts....

  3. Drug design with Cdc7 kinase: a potential novel cancer therapy target

    Directory of Open Access Journals (Sweden)

    Masaaki Sawa

    2008-11-01

    Full Text Available Masaaki Sawa1, Hisao Masai21Carna Biosciences, Inc., Kobe, Japan; 2Genome Dynamics Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, JapanAbstract: Identification of novel molecular targets is critical in development of new and efficient cancer therapies. Kinases are one of the most common drug targets with a potential for cancer therapy. Cell cycle progression is regulated by a number of kinases, some of which are being developed to treat cancer. Cdc7 is a serine-threonine kinase originally discovered in budding yeast, which has been shown to be necessary to initiate the S phase. Inhibition of Cdc7 in cancer cells retards the progression of the S phase, accumulates DNA damage, and induces p53-independent cell death, but the same treatment in normal cells does not significantly affect viability. Low-molecular-weight compounds that inhibit Cdc7 kinase with an IC50 of less than 10 nM have been identified, and shown to be effective in the inhibition of tumor growth in animal models. Thus Cdc7 kinase can be recognized as a novel molecular target for cancer therapy.Keywords: Cdc7 kinase, cell cycle, replication fork, genome stability, DNA damages, ATP-binding pocket, kinase inhibitor

  4. Temperature dependent expression of cdc2 and cyclin B1 in spermatogenic cells during spermatogenesis

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    p34cdc2 and Cyclin Bi are key components of cell cycle controlling machine and are believed to play a fundamental role in gametogenesis. It is also well known that, in scrotal mammals, spermatogenesis depends greatly on the maintenance of comparatively low temperature in the scrotum. To investigate whether the expression of cdc2 and cyclin B1 in spermatogenic cells during spermatogenesis is actually a temperature dependent event, in situ hybridization, Western blotting and immunohistochemistry analysis were used to study the expression of cdc2 and cyclin B1 in normal and cryptorchid testis. Results showed that the abdominal temperature had no significant influence on the transcription of cdc2 and cyclin B1 in the spermatogonia and pachytene/diplotene primary spermatocytes, but it blocked the translation of them. Due to the deficiency of p34cdc2 and Cyclin B1, the spermatogonia and pachytene/diplotene primary spermatocytes were unable to form MPF, hence, they couldn't undergo karyokinesis. The development of primary spermato cytes was arrested at the G2 to M phase transition. We also found that testosterone could regulate the Cyclin B1 expression in spermatogenic cells. Muscular injection of testosterone could recover spermatogenesis in the unilateral scrotal testis which was influenced by the contralateral cryptorchid testis, but it could not salvage the spermatogenesis block in the cryptorchid testis.

  5. Isolation and Characterization of New Alleles of the Cyclin-Dependent Kinase Gene CDC28 with Cyclin-Specific Functional and Biochemical Defects

    OpenAIRE

    Levine, Kristi; Oehlen, L. J. W. M.; Cross, Frederick R.

    1998-01-01

    The G1 cyclin Cln2 negatively regulates the mating-factor pathway. In a genetic screen to identify factors required for this regulation, we identified an allele of CDC28 (cdc28-csr1) that blocked this function of Cln2. Cln2 immunoprecipitated from cdc28-csr1 cells was completely defective in histone H1 kinase activity, due to defects in Cdc28 binding and activation by Cln2. In contrast, Clb2-associated H1 kinase and Cdc28 binding was normal in immunoprecipitates from these cells. cdc28-csr1 w...

  6. 超表达Cdc20基因不影响牛卵母细胞第一极体排出%Over-expression of Cdc20 Gene Has No Effect on Bovine Oocytes First Polar Body Extrusion

    Institute of Scientific and Technical Information of China (English)

    杨文琳; 安鹏; 李伟; 赵贵民; 史芸安; 雷安民

    2012-01-01

    As one of the co-activator of anaphase-promoting complex ( APC) , cell division cycle 20 (CDC20) protein also functions as the target of the spindle assembly checkpoint ( SAC), which is essential for the cell cycle regulation. To investigate the function of Cdc20 during the first polar body extrusion ( PBE I) , Cdc20 CDS was cloned and eukaryotic expression vector pCdc20-Venus was constructed. Using the linear pCdc20-Venus as template, the capped Cdc20-Venus mRNA was synthesized via T7 Mmessage Mmachine Kit ( Ambion). Cdc20 over-expression was performed by microinjection of Cdc20-Venus mRNA into the cytoplasm of bovine oocytes. The results showed that Venus tagged Cdc20 dispersed around the nucleus in HeLa cells. In bovine oocytes, the fluorescence appeared in the whole cytoplasm. However, the PBE I rate in over-expressed group (48. 9% ) is not significant, compared to Venus mRNA injection group (50.9%) and non-injection group (51.1%). Our study demonstrated that the over-expression of Cdc20 in bovine oocytes does not affect the PBE I rate ( P > 0.05).%CDC20(cell division cycle 20)是后期促进复合物(anaphase-promoting complex,APC)的共激活剂之一,也是纺锤体组装检查点(spindle assembly checkpoint,SAC)的靶点,在细胞周期调控中扮演重要角色.为探讨Cdc20在第一极体排出(first polar body extrusion,PBE I)中的作用,Cdc20基因被成功克隆并构建了真核表达载体pCdc20-Venus,随后用T7 Mmessage Mmachine Kit(Ambion)以线性化pCdc20-Venus为模板体外转录(in vitro transcription)获得带帽的Cdc20-Venus mRNA,将Ccdc20-Venus mRNA显微注射到体外培养的牛卵母细胞胞质中进行超量表达.结果表明,真核表达载体pCdc20-Venus转染HeLa细胞后能够正常表达,绿色荧光在细胞核周围呈弥散状分布;将Cdc20-Venus mRNA注射到牛卵母细胞胞质后,胞质内有绿色荧光出现.Cdc20-Venus mRNA注射组卵母细胞的PBE I率(48.9%)与Venus mRNA注射组卵母细胞的PBE I率(50

  7. Conserved CDC20 cell cycle functions are carried out by two of the five isoforms in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Zoltán Kevei

    Full Text Available BACKGROUND: The CDC20 and Cdh1/CCS52 proteins are substrate determinants and activators of the Anaphase Promoting Complex/Cyclosome (APC/C E3 ubiquitin ligase and as such they control the mitotic cell cycle by targeting the degradation of various cell cycle regulators. In yeasts and animals the main CDC20 function is the destruction of securin and mitotic cyclins. Plants have multiple CDC20 gene copies whose functions have not been explored yet. In Arabidopsis thaliana there are five CDC20 isoforms and here we aimed at defining their contribution to cell cycle regulation, substrate selectivity and plant development. METHODOLOGY/PRINCIPAL FINDINGS: Studying the gene structure and phylogeny of plant CDC20s, the expression of the five AtCDC20 gene copies and their interactions with the APC/C subunit APC10, the CCS52 proteins, components of the mitotic checkpoint complex (MCC and mitotic cyclin substrates, conserved CDC20 functions could be assigned for AtCDC20.1 and AtCDC20.2. The other three intron-less genes were silent and specific for Arabidopsis. We show that AtCDC20.1 and AtCDC20.2 are components of the MCC and interact with mitotic cyclins with unexpected specificity. AtCDC20.1 and AtCDC20.2 are expressed in meristems, organ primordia and AtCDC20.1 also in pollen grains and developing seeds. Knocking down both genes simultaneously by RNAi resulted in severe delay in plant development and male sterility. In these lines, the meristem size was reduced while the cell size and ploidy levels were unaffected indicating that the lower cell number and likely slowdown of the cell cycle are the cause of reduced plant growth. CONCLUSIONS/SIGNIFICANCE: The intron-containing CDC20 gene copies provide conserved and redundant functions for cell cycle progression in plants and are required for meristem maintenance, plant growth and male gametophyte formation. The Arabidopsis-specific intron-less genes are possibly "retrogenes" and have hitherto undefined

  8. Dynamics of Cdc42 network embodies a Turing-type mechanism of yeast cell polarity.

    Science.gov (United States)

    Goryachev, Andrew B; Pokhilko, Alexandra V

    2008-04-30

    Complex biochemical networks can be understood by identifying their principal regulatory motifs and mode of action. We model the early phase of budding yeast cellular polarization and show that the biochemical processes in the presumptive bud site comprise a Turing-type mechanism. The roles of the prototypical activator and substrate are played by GTPase Cdc42 in its active and inactive states, respectively. We demonstrate that the nucleotide cycling of Cdc42 converts cellular energy into a stable cluster of activated Cdc42. This energy drives a continuous membrane-cytoplasmic exchange of the cluster components to counteract diffusive spread of the cluster. This exchange explains why only one bud forms per cell cycle, because the winner-takes-all competition of candidate sites inevitably selects a single site. PMID:18381072

  9. Podocyte-specific loss of cdc42 leads to congenital nephropathy

    DEFF Research Database (Denmark)

    Scott, Rizaldy P; Hawley, Steve P; Ruston, Julie; Du, Jianmei; Brakebusch, Cord; Jones, Nina; Pawson, Tony

    2012-01-01

    Rho family GTPases are molecular switches best known for their pivotal role in dynamic regulation of the actin cytoskeleton. The prototypic members of this family are Cdc42, Rac1, and RhoA; these GTPases contribute to the breakdown of glomerular filtration and the resultant proteinuria, but their...... functions in normal podocyte physiology remain poorly understood. Here, mice lacking Cdc42 in podocytes developed congenital nephropathy and died as a result of renal failure within 2 weeks after birth. In contrast, mice lacking Rac1 or RhoA in podocytes were overtly normal and lived to adulthood. Kidneys...... from Cdc42-mutant mice exhibited protein-filled microcysts with hallmarks of collapsing glomerulopathy, as well as extensive effacement of podocyte foot processes with abnormal junctional complexes. Furthermore, we observed aberrant expression of several podocyte markers and cell polarity proteins in...

  10. KEG, an Eulerian configuration generator for BBC and VOA. [For CDC 7600 and STAR computers

    Energy Technology Data Exchange (ETDEWEB)

    Warshaw, S.I.

    1977-05-01

    KEG is an extremely flexible generator for BBC, a two-dimensional multifluid Eulerian hydrodynamics code, and for VOA, a plasma version of BBC. This document describes the operating details for the use of KEG, the contents of the input deck required to set up a problem to be calculated on the BBC or VOA, and other miscellanea related to output and file handling. Matters relevant to the actual calculations of the hydrodynamics are found elsewhere. 19 figures. (RWR)

  11. High selectivity of TiC-CDC for CO2/N2 separation

    OpenAIRE

    Silvestre Albero, Ana; Rico Francés, Soledad; Rodríguez Reinoso, Francisco; Kern, Andreas M.; Klumpp, Michael; Etzold, Bastian J. M.; Silvestre Albero, Joaquín

    2013-01-01

    A series of carbide-derived carbons (CDC) have been prepared starting from TiC and using different chlorine treatment temperatures (500–1200 °C). Contrary to N2 adsorption measurements at −196 °C, CO2 adsorption measurements at room temperature and high pressure (up to 1 MPa) together with immersion calorimetry measurements into dichloromethane suggest that the synthesized CDC exhibit a similar porous structure, in terms of narrow pore volume, independently of the temperature of the reactive ...

  12. Cdc42 is not essential for filopodium formation, directed migration, cell polarization, and mitosis in fibroblastoid cells

    DEFF Research Database (Denmark)

    Czuchra, Aleksandra; Wu, Xunwei; Meyer, Hannelore;

    2005-01-01

    of Cdc42 did not affect filopodium or lamellipodium formation and had no significant influence on the speed of directed migration nor on mitosis. Cdc42-deficient cells displayed a more elongated cell shape and had a reduced area. Furthermore, directionality during migration and reorientation of the...

  13. 77 FR 66469 - CDC/HRSA Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment

    Science.gov (United States)

    2012-11-05

    ... Client Level Data Update; (3) Viral Hepatitis Action Plan and Implementation Update; (4) Update on... Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC, 1600 Clifton Road NE., Mailstop E-07... HUMAN SERVICES Centers for Disease Control and Prevention CDC/HRSA Advisory Committee on HIV,...

  14. 76 FR 29755 - Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)-Ethics...

    Science.gov (United States)

    2011-05-23

    ...), Centers for Disease Control and Prevention (CDC)--Ethics Subcommittee (ES) In accordance with section 10(a.... Purpose: The ES will provide counsel to the ACD, CDC, regarding a broad range of public health ethics... meeting; discussion of next steps on addressing potential public health ethical issues associated...

  15. 75 FR 57044 - Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)-Ethics...

    Science.gov (United States)

    2010-09-17

    ...), Centers for Disease Control and Prevention (CDC)--Ethics Subcommittee (ES) In accordance with section 10(a..., CDC, regarding a broad range of public health ethics questions and issues arising from programs..., local and territorial health departments address ethical issues in the practice of public health;...

  16. 77 FR 2549 - Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)-Ethics...

    Science.gov (United States)

    2012-01-18

    ...), Centers for Disease Control and Prevention (CDC)--Ethics Subcommittee (ES) In accordance with section 10(a... provide counsel to the ACD, CDC, regarding a broad range of public health ethics questions and issues... health departments in their efforts to address public health ethics challenges, approaches for...

  17. Cold-sensitive mutants of p34cdc2 that suppress a mitotic catastrophe phenotype in fission yeast.

    Science.gov (United States)

    Ayscough, K; Hayles, J; MacNeill, S A; Nurse, P

    1992-04-01

    The p34cdc2 protein kinase plays a central role in the regulation of the eukaryotic cell cycle, being required both in late G1 for the commitment to S-phase and in late G2 for the initiation of mitosis. p34cdc2 also determines the precise timing of entry into mitosis in fission yeast, where a number of gene products that regulate p34cdc2 activity have been identified and characterised. To investigate further the mitotic role of p34cdc2 in this organism we have isolated new cold-sensitive p34cdc2 mutants. These are defective only in their G2 function and are extragenic suppressors of the lethal premature entry into mitosis brought about by mutating the mitotic inhibitor p107wee1 and overproducing the mitotic activator p80cdc25. One of the mutant proteins p34cdc2-E8 is only functional in the absence of p107wee1, and all the mutant strains have reduced histone H1 kinase activity in vitro. Each mutant allele has been cloned and sequenced, and the lesions responsible for the cold-sensitive phenotypes identified. All the mutations were found to map to regions that are conserved between the fission yeast p34cdc2 and functional homologues from higher eukaryotes. PMID:1316996

  18. Interphase APC/C-Cdc20 inhibition by cyclin A2-Cdk2 ensures efficient mitotic entry

    DEFF Research Database (Denmark)

    Hein, Jamin B; Nilsson, Jakob

    2016-01-01

    window of the cell cycle, if any, is unknown. Here we show that cyclin A2-Cdk2 binds and phosphorylates Cdc20 in interphase and this inhibits APC/C-Cdc20 activity. Preventing Cdc20 phosphorylation results in pre-mature activation of the APC/C-Cdc20 and several substrates, including cyclin B1 and A2, are...... destabilized which lengthens G2 and slows mitotic entry. Expressing non-degradable cyclin A2 but not cyclin B1 restores mitotic entry in these cells. We have thus uncovered a novel positive feedback loop centred on cyclin A2-Cdk2 inhibition of interphase APC/C-Cdc20 to allow further cyclin A2 accumulation and...

  19. A novel functional polymorphism in the Cdc6 promoter is associated with the risk for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Cdc6 is essential for DNA replication and its deregulation is involved in carcinogenesis. To date, the biological significance of the polymorphism in Cdc6 promoter is still unknown. In this study, we aimed to evaluate the influence of the Cdc6 -515A>G polymorphism (rs4134994) on the individual's susceptibility to cancer and on the function of Cdc6. The Cdc6 -515A>G polymorphism was genotyped in 387 hepatocellular carcinoma (HCC) and 389 age- and sex-matched healthy subjects. The association between the genotypes and the risk for HCC was then estimated by unconditional logistic regression analysis with adjustment for age, sex and HBV status. Compared with the AA homozygotes, the homozygous GG genotype (adjusted OR = 0.36, 95% confidence interval (CI) = 0.18-0.72, P = 0.004) or the combined AG/GG genotypes (adjusted OR = 0.56, 95% CI = 0.36-0.86, P = 0.008) were statistically significantly associated with the reduced risk for HCC. Moreover, the analysis using luciferase reporter system showed that the G-allelic Cdc6 promoter displayed a decreased transcriptional activity compared with the A-allelic one. These results indicate that the individuals with G allele may have reduced Cdc6 expression and are therefore in reduced risk for HCC. Further investigation using electrophoretic mobility shift assay (EMSA) revealed that the G allele had a stronger binding strength to nuclear protein(s) which might function as negative regulator(s) for Cdc6 transcription. Our findings suggest that the -515A>G polymorphism may affect the Cdc6 promoter binding affinity with nuclear protein(s) and in turn the Cdc6 expression, which consequently modulates the individual's susceptibility to HCC

  20. CDC28 phosphorylates Cac1p and regulates the association of chromatin assembly factor I with chromatin.

    Science.gov (United States)

    Jeffery, Daniel C B; Kakusho, Naoko; You, Zhiying; Gharib, Marlene; Wyse, Brandon; Drury, Erin; Weinreich, Michael; Thibault, Pierre; Verreault, Alain; Masai, Hisao; Yankulov, Krassimir

    2015-01-01

    Chromatin Assembly Factor I (CAF-I) plays a key role in the replication-coupled assembly of nucleosomes. It is expected that its function is linked to the regulation of the cell cycle, but little detail is available. Current models suggest that CAF-I is recruited to replication forks and to chromatin via an interaction between its Cac1p subunit and the replication sliding clamp, PCNA, and that this interaction is stimulated by the kinase CDC7. Here we show that another kinase, CDC28, phosphorylates Cac1p on serines 94 and 515 in early S phase and regulates its association with chromatin, but not its association with PCNA. Mutations in the Cac1p-phosphorylation sites of CDC28 but not of CDC7 substantially reduce the in vivo phosphorylation of Cac1p. However, mutations in the putative CDC7 target sites on Cac1p reduce its stability. The association of CAF-I with chromatin is impaired in a cdc28-1 mutant and to a lesser extent in a cdc7-1 mutant. In addition, mutations in the Cac1p-phosphorylation sites by both CDC28 and CDC7 reduce gene silencing at the telomeres. We propose that this phosphorylation represents a regulatory step in the recruitment of CAF-I to chromatin in early S phase that is distinct from the association of CAF-I with PCNA. Hence, we implicate CDC28 in the regulation of chromatin reassembly during DNA replication. These findings provide novel mechanistic insights on the links between cell-cycle regulation, DNA replication and chromatin reassembly. PMID:25602519

  1. Super-computer architecture

    CERN Document Server

    Hockney, R W

    1977-01-01

    This paper examines the design of the top-of-the-range, scientific, number-crunching computers. The market for such computers is not as large as that for smaller machines, but on the other hand it is by no means negligible. The present work-horse machines in this category are the CDC 7600 and IBM 360/195, and over fifty of the former machines have been sold. The types of installation that form the market for such machines are not only the major scientific research laboratories in the major countries-such as Los Alamos, CERN, Rutherford laboratory-but also major universities or university networks. It is also true that, as with sports cars, innovations made to satisfy the top of the market today often become the standard for the medium-scale computer of tomorrow. Hence there is considerable interest in examining present developments in this area. (0 refs).

  2. Fewer U.S. Kids Die from Abusive Head Trauma: CDC

    Science.gov (United States)

    ... U.S. Kids Die From Abusive Head Trauma: CDC Parent training helps prevent shaken baby syndrome, other forms of ... agencies that can help." Briggs said that adding behavioral health ... including parent-child interventions that build on strengths and resilience, ...

  3. Potential utility of cinacalcet as a treatment for CDC73-related primary hyperparathyroidism: a case report

    Science.gov (United States)

    Sato, Takeshi; Muroya, Koji; Hanakawa, Junko; Yamashita, Sumimasa; Nozawa, Kumiko; Masudo, Katsuhiko; Yamakawa, Tadashi; Asakura, Yumi; Hasegawa, Tomonobu; Adachi, Masanori

    2016-01-01

    Abstract. We report a Japanese pedigree with familial primary hyperparathyroidism due to a CDC73 mutation. To our knowledge, this is the first report of cinacalcet as a treatment for CDC73-related primary hyperparathyroidism. The proband had severe psychomotor retardation and received laryngotracheal separation surgery. At 19 yr of age, he developed acute pancreatitis. Hypercalcemia (12.2–13.8 mg/dL), elevated levels of intact PTH (86–160 pg/mL), and a tumor detected upon neck ultrasonography led to the diagnosis of primary hyperparathyroidism. Family history and biochemical examinations revealed that three family members (the proband’s mother, elder brother, and maternal grandfather) had primary hyperparathyroidism. We identified a novel heterozygous mutation, c.240delT, p.Glu81Lysfs*28, in the CDC73 gene in three affected family members, excluding the proband’s elder brother who refused genetic testing. Parathyroidectomy for the proband was considered as high-risk, because the tumor was located close to the tracheostomy orifice. After receiving approval from the institutional review board and obtaining the consent, we initiated cinacalcet treatment. At 22 yr of age, treatment with 100 mg of cinacalcet maintained serum calcium levels below 11.0 mg/dL with no apparent side effects. Our report presents the potential efficacy of cinacalcet as a treatment for CDC73-related primary hyperparathyroidism, in particularly inoperative cases. PMID:27507909

  4. Differential impact of diverse anticancer chemotherapeutics on the Cdc25A-degradation checkpoint pathway

    International Nuclear Information System (INIS)

    When exposed to DNA-damaging insults such as ionizing radiation (IR) or ultraviolet light (UV), mammalian cells activate checkpoint pathways to halt cell cycle progression or induce cell death. Here we examined the ability of five commonly used anticancer drugs with different mechanisms of action to activate the Chk1/Chk2-Cdc25A-CDK2/cyclin E cell cycle checkpoint pathway, previously shown to be induced by IR or UV. Whereas exposure of human cells to topoisomerase inhibitors camptothecin, etoposide, or adriamycin resulted in rapid (within 1 h) activation of the pathway including degradation of the Cdc25A phosphatase and inhibition of cyclin E/CDK2 kinase activity, taxol failed to activate this checkpoint even after a prolonged treatment. Unexpectedly, although the alkylating agent cisplatin also induced degradation of Cdc25A (albeit delayed, after 8-12 h), cyclin E/CDK2 activity was elevated and DNA synthesis continued, a phenomena that correlated with increased E2F1 protein levels and consequently enhanced expression of cyclin E. These results reveal a differential impact of various classes of anticancer chemotherapeutics on the Cdc25A-degradation pathway, and indicate that the kinetics of checkpoint induction, and the relative balance of key components within the DNA damage response network may dictate whether the treated cells arrest their cell cycle progression

  5. Cdc20 and Cks direct the spindle checkpoint-independent destruction of cyclin A

    NARCIS (Netherlands)

    Wolthuis, Rob; Clay-Farrace, Lori; van Zon, Wouter; Yekezare, Mona; Koop, Lars; Ogink, Janneke; Medema, Rene; Pines, Jonathon

    2008-01-01

    Successful mitosis requires the right protein be degraded at the right time. Central to this is the spindle checkpoint that prevents the destruction of securin and cyclin 131 when there are improperly attached chromosomes. The principal target of the checkpoint is Cdc20, which activates the anaphase

  6. Parkin Regulates Mitosis and Genomic Stability through Cdc20/Cdh1

    NARCIS (Netherlands)

    Lee, S.B.; Kim, J.J.; Nam, H.J.; Gao, B.; Yin, P.; Qin, B.; Yi, S.Y.; Ham, H.; Evans, D.; Kim, S.H.; Zhang, Jun; Deng, M.; Liu, T.; Zhang, H.; Billadeau, D.D.; Wang, L.; Giaime, E.; Shen, J.; Pang, Y.P.; Jen, J.; Deursen, J.M.A. van; Lou, Z.

    2015-01-01

    Mutations in the E3 ubiquitin ligase Parkin have been linked to familial Parkinson's disease. Parkin has also been implicated in mitosis through mechanisms that are unclear. Here we show that Parkin interacts with anaphase promoting complex/cyclosome (APC/C) coactivators Cdc20 and Cdh1 to mediate th

  7. Cdc42-dependent structural development of auditory supporting cells is required for wound healing at adulthood

    DEFF Research Database (Denmark)

    Anttonen, Tommi; Kirjavainen, Anna; Belevich, Ilya;

    2012-01-01

    of a basolateral membrane protein in the apical domain were observed. These defects and changes in aPKCλ/ι expression suggested that apical polarization is impaired. Following a lesion at adulthood, supporting cells with Cdc42 loss-induced maturational defects collapsed and failed to remodel F...

  8. Cdc42 controls progenitor cell differentiation and beta-catenin turnover in skin

    DEFF Research Database (Denmark)

    Wu, Xunwei; Quondamatteo, Fabio; Lefever, Tine;

    2006-01-01

    Differentiation of skin stem cells into hair follicles (HFs) requires the inhibition of beta-catenin degradation, which is controlled by a complex containing axin and the protein kinase GSK3beta. Using conditional gene targeting in mice, we show now that the small GTPase Cdc42 is crucial for...

  9. 1 in 8 U.S. Workers Has Some Hearing Loss: CDC

    Science.gov (United States)

    ... gov/news/fullstory_158434.html 1 in 8 U.S. Workers Has Some Hearing Loss: CDC Survey finds ... 21, 2016 (HealthDay News) -- Nearly 13 percent of U.S. workers suffer from at least some hearing loss, ...

  10. Abortion surveillance at CDC: creating public health light out of political heat.

    Science.gov (United States)

    Cates, W; Grimes, D A; Schulz, K F

    2000-07-01

    In the late 1960s, states began to liberalize their abortion laws, and a new era in women's health began. Under the leadership of Jack Smith, the Centers for Disease Control and Prevention (CDC) established a voluntary abortion surveillance system that provided the first nationwide information on the numbers and characteristics of women having abortions. Studies of abortion morbidity done by the CDC revealed that suction curettage was safer than sharp curettage, local anesthesia was safer than general anesthesia, free-standing clinics were safer than hospitals, and dilation and evacuation (D&E) was safer than the alternative of labor induction for early second-trimester abortions. This evidence, which contradicted traditional medical tenets, rapidly changed the practice of abortion in the United States. CDC also established a surveillance system for abortion deaths. This demonstrated a rapid improvement in the safety of abortion in the early 1970s. Lessons learned from mortality investigations helped to change practice as well.Today, more is known about the epidemiology of abortion than any other operation in the history of medicine. In the midst of strident debate over the abortion issue, CDC abortion surveillance data have helped to guide judicial rulings, legislative actions, and Surgeon General's reports, which have supported safer choices for women of reproductive age. When medical historians of the future look back on this century, the increasing availability of safe, legal abortion will stand out as a public health triumph. PMID:10863125

  11. Potential utility of cinacalcet as a treatment for CDC73-related primary hyperparathyroidism: a case report.

    Science.gov (United States)

    Sato, Takeshi; Muroya, Koji; Hanakawa, Junko; Yamashita, Sumimasa; Nozawa, Kumiko; Masudo, Katsuhiko; Yamakawa, Tadashi; Asakura, Yumi; Hasegawa, Tomonobu; Adachi, Masanori

    2016-07-01

    We report a Japanese pedigree with familial primary hyperparathyroidism due to a CDC73 mutation. To our knowledge, this is the first report of cinacalcet as a treatment for CDC73-related primary hyperparathyroidism. The proband had severe psychomotor retardation and received laryngotracheal separation surgery. At 19 yr of age, he developed acute pancreatitis. Hypercalcemia (12.2-13.8 mg/dL), elevated levels of intact PTH (86-160 pg/mL), and a tumor detected upon neck ultrasonography led to the diagnosis of primary hyperparathyroidism. Family history and biochemical examinations revealed that three family members (the proband's mother, elder brother, and maternal grandfather) had primary hyperparathyroidism. We identified a novel heterozygous mutation, c.240delT, p.Glu81Lysfs*28, in the CDC73 gene in three affected family members, excluding the proband's elder brother who refused genetic testing. Parathyroidectomy for the proband was considered as high-risk, because the tumor was located close to the tracheostomy orifice. After receiving approval from the institutional review board and obtaining the consent, we initiated cinacalcet treatment. At 22 yr of age, treatment with 100 mg of cinacalcet maintained serum calcium levels below 11.0 mg/dL with no apparent side effects. Our report presents the potential efficacy of cinacalcet as a treatment for CDC73-related primary hyperparathyroidism, in particularly inoperative cases. PMID:27507909

  12. Using Evidence-Based Parenting Programs to Advance CDC Efforts in Child Maltreatment Prevention. Research Brief

    Science.gov (United States)

    Valle, Linda Anne; Whitaker, Daniel J.; Lutzker, John R.; Filene, Jill H.; Wyatt, Jennifer M.; Cephas, Kendell C.; Hoover, D. Michele

    2004-01-01

    The Centers for Disease Control and Prevention (CDC) recognize child maltreatment as a serious public health problem with extensive short- and long-term health effects. In addition to the immediate physical and emotional effects of maltreatment, children who have experienced abuse and neglect are at increased risk of adverse health effects and…

  13. CDC Vital Signs–Think Sepsis. Time Matters.

    Centers for Disease Control (CDC) Podcasts

    2016-08-23

    This podcast is based on the August 2016 CDC Vital Signs report. Sepsis is a medical emergency and can happen quickly. Learn the signs of sepsis and how to prevent it.  Created: 8/23/2016 by National Center for Injury Prevention and Control (NCIPC).   Date Released: 8/23/2016.

  14. 13 CFR 120.826 - Basic requirements for operating a CDC.

    Science.gov (United States)

    2010-01-01

    ... Board of the American Institute of Certified Public Accountants (AICPA). The auditor must be independent, as defined by the AICPA, of the CDC. Annually, the auditor must issue an opinion as to the fairness... to SBA must be reviewed by an independent CPA in accordance with GAAP. (d) Auditor...

  15. Sequencing analysis of mutant allele cdc28-srm of protein kinase CDC28 and molecular dynamics study of glycine-rich loop in wild-type and mutant allele G16S of CDK2 as model

    International Nuclear Information System (INIS)

    The central role that cyclin-dependent kinases play in the timing of cell division and the high incidence of genetic alteration of CDKs or deregulation of CDK inhibitors in a number of cancers make CDC28 of the yeast Saccharomyces cerevisiae a very attractive model for studies of mechanisms of CDK regulation. Earlier it was found that certain gene mutations including cdc28-srm affect cell cycle progression, maintenance of different genetic structures and increase cell sensitivity to ionizing radiation. A cdc28-srm mutation is not a temperature-sensitive mutation and differs from the known cdc28-ts mutations because it has the evident phenotypic manifestations at 30 deg C. Sequencing analysis of cdc28-srm revealed a single nucleotide substitution G20S. This is a third glycine in a conserved sequence GxGxxG in the G-rich loop positioned opposite the activation T-loop. Despite its demonstrated importance, the role of the G-loop has remained unclear. The crystal structure of the human CDK2 has served as a model for the catalytic core of other CDKs, including CDC28. Nanoseconds long molecular dynamics (MD) trajectories of the CDK2/ATP complex were analyzed. The MD simulations of CDK2-G16S (CDC28-G20S) substitution show conformational changes of CDK2 structure resulting in the moving of the G-loop away from ATP and a new rearrangement of amino acids in the T-loop

  16. Cdc20 is critical for meiosis I and fertility of female mice.

    Directory of Open Access Journals (Sweden)

    Fang Jin

    2010-09-01

    Full Text Available Chromosome missegregation in germ cells is an important cause of unexplained infertility, miscarriages, and congenital birth defects in humans. However, the molecular defects that lead to production of aneuploid gametes are largely unknown. Cdc20, the activating subunit of the anaphase-promoting complex/cyclosome (APC/C, initiates sister-chromatid separation by ordering the destruction of two key anaphase inhibitors, cyclin B1 and securin, at the transition from metaphase to anaphase. The physiological significance and full repertoire of functions of mammalian Cdc20 are unclear at present, mainly because of the essential nature of this protein in cell cycle progression. To bypass this problem we generated hypomorphic mice that express low amounts of Cdc20. These mice are healthy and have a normal lifespan, but females produce either no or very few offspring, despite normal folliculogenesis and fertilization rates. When mated with wild-type males, hypomorphic females yield nearly normal numbers of fertilized eggs, but as these embryos develop, they become malformed and rarely reach the blastocyst stage. In exploring the underlying mechanism, we uncover that the vast majority of these embryos have abnormal chromosome numbers, primarily due to chromosome lagging and chromosome misalignment during meiosis I in the oocyte. Furthermore, cyclin B1, cyclin A2, and securin are inefficiently degraded in metaphase I; and anaphase I onset is markedly delayed. These results demonstrate that the physiologically effective threshold level of Cdc20 is high for female meiosis I and identify Cdc20 hypomorphism as a mechanism for chromosome missegregation and formation of aneuploid gametes.

  17. Functional mapping of the fission yeast DNA polymerase δ B-subunit Cdc1 by site-directed and random pentapeptide insertion mutagenesis

    Directory of Open Access Journals (Sweden)

    Gray Fiona C

    2009-08-01

    Full Text Available Abstract Background DNA polymerase δ plays an essential role in chromosomal DNA replication in eukaryotic cells, being responsible for synthesising the bulk of the lagging strand. In fission yeast, Pol δ is a heterotetrameric enzyme comprising four evolutionarily well-conserved proteins: the catalytic subunit Pol3 and three smaller subunits Cdc1, Cdc27 and Cdm1. Pol3 binds directly to the B-subunit, Cdc1, which in turn binds the C-subunit, Cdc27. Human Pol δ comprises the same four subunits, and the crystal structure was recently reported of a complex of human p50 and the N-terminal domain of p66, the human orthologues of Cdc1 and Cdc27, respectively. Results To gain insights into the structure and function of Cdc1, random and directed mutagenesis techniques were used to create a collection of thirty alleles encoding mutant Cdc1 proteins. Each allele was tested for function in fission yeast and for binding of the altered protein to Pol3 and Cdc27 using the two-hybrid system. Additionally, the locations of the amino acid changes in each protein were mapped onto the three-dimensional structure of human p50. The results obtained from these studies identify amino acid residues and regions within the Cdc1 protein that are essential for interaction with Pol3 and Cdc27 and for in vivo function. Mutations specifically defective in Pol3-Cdc1 interactions allow the identification of a possible Pol3 binding surface on Cdc1. Conclusion In the absence of a three-dimensional structure of the entire Pol δ complex, the results of this study highlight regions in Cdc1 that are vital for protein function in vivo and provide valuable clues to possible protein-protein interaction surfaces on the Cdc1 protein that will be important targets for further study.

  18. Data processing in high energy physics and vector processing computers

    International Nuclear Information System (INIS)

    The data handling done in high energy physics in order to extract the results from the large volumes of data collected in typical experiments is a very large consumer of computing capacity. More than 70 vector processing computers have now been installed and many fields of applications have been tried on such computers as the ILLIAC IV, the TI ASC, the CDC STAR-100 and more recently on the CRAY-1, the CDC Cyber 205, the ICL DAP and the CRAY X-MP. This paper attempts to analyze the reasons for the lack of use of these computers in processing results from high energy physics experiments. Little work has been done to look at the possible vectorisation of the large codes in this field, but the motivation to apply vector processing computers in high energy physics data handling may be increasing as the gap between the scalar performance and the vector performance offered by large computers available on the market widens

  19. FLIM FRET Visualization of Cdc42 Activation by Netrin-1 in Embryonic Spinal Commissural Neuron Growth Cones

    Science.gov (United States)

    Rappaz, Benjamin; Lai Wing Sun, Karen; Correia, James P.; Wiseman, Paul W.; Kennedy, Timothy E.

    2016-01-01

    Netrin-1 is an essential extracellular chemoattractant that signals through its receptor DCC to guide commissural axon extension in the embryonic spinal cord. DCC directs the organization of F-actin in growth cones by activating an intracellular protein complex that includes the Rho GTPase Cdc42, a critical regulator of cell polarity and directional migration. To address the spatial distribution of signaling events downstream of netrin-1, we expressed the FRET biosensor Raichu-Cdc42 in cultured embryonic rat spinal commissural neurons. Using FLIM-FRET imaging we detected rapid activation of Cdc42 in neuronal growth cones following application of netrin-1. Investigating the signaling mechanisms that control Cdc42 activation by netrin-1, we demonstrate that netrin-1 rapidly enriches DCC at the leading edge of commissural neuron growth cones and that netrin-1 induced activation of Cdc42 in the growth cone is blocked by inhibiting src family kinase signaling. These findings reveal the activation of Cdc42 in embryonic spinal commissural axon growth cones and support the conclusion that src family kinase activation downstream of DCC is required for Cdc42 activation by netrin-1. PMID:27482713

  20. An ALS disease mutation in Cdc48/p97 impairs 20S proteasome binding and proteolytic communication.

    Science.gov (United States)

    Barthelme, Dominik; Jauregui, Ruben; Sauer, Robert T

    2015-09-01

    Cdc48 (also known as p97 or VCP) is an essential and highly abundant, double-ring AAA+ ATPase, which is ubiquitous in archaea and eukaryotes. In archaea, Cdc48 ring hexamers play a direct role in quality control by unfolding and translocating protein substrates into the degradation chamber of the 20S proteasome. Whether Cdc48 and 20S cooperate directly in protein degradation in eukaryotic cells is unclear. Two regions of Cdc48 are important for 20S binding, the pore-2 loop at the bottom of the D2 AAA+ ring and a C-terminal tripeptide. Here, we identify an aspartic acid in the pore-2 loop as an important element in 20S recognition. Importantly, mutation of this aspartate in human Cdc48 has been linked to familial amyotrophic lateral sclerosis (ALS). In archaeal or human Cdc48 variants, we find that mutation of this pore-2 residue impairs 20S binding and proteolytic communication but does not affect the stability of the hexamer or rates of ATP hydrolysis and protein unfolding. These results suggest that human Cdc48 interacts functionally with the 20S proteasome. PMID:26134898

  1. The Rho GTPase Cdc42 regulates hair cell planar polarity and cellular patterning in the developing cochlea

    Directory of Open Access Journals (Sweden)

    Anna Kirjavainen

    2015-03-01

    Full Text Available Hair cells of the organ of Corti (OC of the cochlea exhibit distinct planar polarity, both at the tissue and cellular level. Planar polarity at tissue level is manifested as uniform orientation of the hair cell stereociliary bundles. Hair cell intrinsic polarity is defined as structural hair bundle asymmetry; positioning of the kinocilium/basal body complex at the vertex of the V-shaped bundle. Consistent with strong apical polarity, the hair cell apex displays prominent actin and microtubule cytoskeletons. The Rho GTPase Cdc42 regulates cytoskeletal dynamics and polarization of various cell types, and, thus, serves as a candidate regulator of hair cell polarity. We have here induced Cdc42 inactivation in the late-embryonic OC. We show the role of Cdc42 in the establishment of planar polarity of hair cells and in cellular patterning. Abnormal planar polarity was displayed as disturbances in hair bundle orientation and morphology and in kinocilium/basal body positioning. These defects were accompanied by a disorganized cell-surface microtubule network. Atypical protein kinase C (aPKC, a putative Cdc42 effector, colocalized with Cdc42 at the hair cell apex, and aPKC expression was altered upon Cdc42 depletion. Our data suggest that Cdc42 together with aPKC is part of the machinery establishing hair cell planar polarity and that Cdc42 acts on polarity through the cell-surface microtubule network. The data also suggest that defects in apical polarization are influenced by disturbed cellular patterning in the OC. In addition, our data demonstrates that Cdc42 is required for stereociliogenesis in the immature cochlea.

  2. Genetic deletion of cdc42 reveals a crucial role for astrocyte recruitment to the injury site in vitro and in vivo

    DEFF Research Database (Denmark)

    Robel, Stefanie; Bardehle, Sophia; Lepier, Alexandra; Brakebusch, Cord; Götz, Magdalena

    2011-01-01

    signals, the small RhoGTPase Cdc42, selectively in mouse astrocytes in vitro and in vivo. We used an in vitro scratch assay as a minimal wounding model and found that astrocytes lacking Cdc42 (Cdc42Δ) were still able to form protrusions, although in a nonoriented way. Consequently, they failed to migrate...... in a directed manner toward the scratch. When animals were injured in vivo through a stab wound, Cdc42Δ astrocytes developed protrusions properly oriented toward the lesion, but the number of astrocytes recruited to the lesion site was significantly reduced. Surprisingly, however, lesions in Cdc42Δ...

  3. The current status of super computers

    Science.gov (United States)

    Knight, J. C.

    1978-01-01

    In this paper, commercially available super computers are surveyed. Computer performance in general is limited by circuit speeds and physical size. Assuming the use of the fastest technology, super computers typically use parallelism in the form of either vector processing or array processing to obtain performance. The Burroughs Scientific Processor is an array computer with 16 separate processors, the Cray-1 and CDC STAR-100 are vector processors, the Goodyear Aerospace STARAN is an array processor with up to 8192 single bit processors, and the Systems Development Corporation PEPE is a collection of up to 288 separate processors.

  4. Cdc25B Dual-Specificity Phosphatase Inhibitors Identified in a High-Throughput Screen of the NIH Compound Library

    OpenAIRE

    Johnston, Paul A.; Foster, Caleb A.; Tierno, Marni Brisson; Shun, Tong Ying; Shinde, Sunita N.; Paquette, William D.; Brummond, Kay M.; Wipf, Peter; Lazo, John S.

    2009-01-01

    The University of Pittsburgh Molecular Library Screening Center (Pittsburgh, PA) conducted a screen with the National Institutes of Health compound library for inhibitors of in vitro cell division cycle 25 protein (Cdc25) B activity during the pilot phase of the Molecular Library Screening Center Network. Seventy-nine (0.12%) of the 65,239 compounds screened at 10 μM met the active criterion of ≥50% inhibition of Cdc25B activity, and 25 (31.6%) of these were confirmed as Cdc25B inhibitors wit...

  5. The Tea4-PP1 landmark promotes local growth by dual Cdc42 GEF recruitment and GAP exclusion.

    OpenAIRE

    Kokkoris K.; Gallo Castro D.; Martin S.G.

    2014-01-01

    Cell polarization relies on small GTPases, such as Cdc42, which can break symmetry through self-organizing principles, and landmarks that define the axis of polarity. In fission yeast, microtubules deliver the Tea1-Tea4 complex to mark cell poles for growth, but how this complex activates Cdc42 is unknown. Here, we show that ectopic targeting of Tea4 to cell sides promotes the local activation of Cdc42 and cell growth. This activity requires that Tea4 binds the type I phosphatase (PP1) cataly...

  6. PP2A(Cdc55)'s role in reductional chromosome segregation during achiasmate meiosis in budding yeast is independent of its FEAR function.

    Science.gov (United States)

    Kerr, Gary W; Wong, Jin Huei; Arumugam, Prakash

    2016-01-01

    PP2A(Cdc55) is a highly conserved serine-threonine protein phosphatase that is involved in diverse cellular processes. In budding yeast, meiotic cells lacking PP2A(Cdc55) activity undergo a premature exit from meiosis I which results in a failure to form bipolar spindles and divide nuclei. This defect is largely due to its role in negatively regulating the Cdc Fourteen Early Anaphase Release (FEAR) pathway. PP2A(Cdc55) prevents nucleolar release of the Cdk (Cyclin-dependent kinase)-antagonising phosphatase Cdc14 by counteracting phosphorylation of the nucleolar protein Net1 by Cdk. CDC55 was identified in a genetic screen for monopolins performed by isolating suppressors of spo11Δ spo12Δ lethality suggesting that Cdc55 might have a role in meiotic chromosome segregation. We investigated this possibility by isolating cdc55 alleles that suppress spo11Δ spo12Δ lethality and show that this suppression is independent of PP2A(Cdc55)'s FEAR function. Although the suppressor mutations in cdc55 affect reductional chromosome segregation in the absence of recombination, they have no effect on chromosome segregation during wild type meiosis. We suggest that Cdc55 is required for reductional chromosome segregation during achiasmate meiosis and this is independent of its FEAR function. PMID:27455870

  7. Purification of MPF from starfish: identification as the H1 histone kinase p34cdc2 and a possible mechanism for its periodic activation.

    Science.gov (United States)

    Labbe, J C; Picard, A; Peaucellier, G; Cavadore, J C; Nurse, P; Doree, M

    1989-04-21

    MPF extracted from starfish oocytes copurifies with an M phase-specific H1 histone kinase encoded by a homolog of the fission yeast cell cycle control gene cdc2+. The most purified preparations contain p34cdc2 as the only major protein. Activation of the p34cdc2 kinase is correlated with appearance of the MPF activity both in vivo and in vitro. The increase in protein kinase activity is associated with p34cdc2 dephosphorylation and the decrease in protein kinase activity on leaving M phase with rephosphorylation. Microinjection of a peptide perfectly conserved in p34cdc2 from yeast to humans induces meiotic maturation, suggesting that an inhibitory component in G2 arrested oocytes interacts with this region of the p34cdc2 kinase. We propose that initiation of M phase is brought about by the dephosphorylation of p34cdc2, leading to increase in its protein kinase activity. PMID:2649251

  8. Prominin-2 expression increases protrusions, decreases caveolae and inhibits Cdc42 dependent fluid phase endocytosis

    International Nuclear Information System (INIS)

    Highlights: •Prominin-2 expression induced protrusions that co-localized with lipid raft markers. •Prominin-2 expression decreased caveolae, caveolar endocytosis and increased pCav1. •Prominin-2 expression inhibited fluid phase endocytosis by inactivation of Cdc42. •These endocytic effects can be reversed by adding exogenous cholesterol. •Caveolin1 knockdown restored fluid phase endocytosis in Prominin2 expressing cells. -- Abstract: Background: Membrane protrusions play important roles in biological processes such as cell adhesion, wound healing, migration, and sensing of the external environment. Cell protrusions are a subtype of membrane microdomains composed of cholesterol and sphingolipids, and can be disrupted by cholesterol depletion. Prominins are pentaspan membrane proteins that bind cholesterol and localize to plasma membrane (PM) protrusions. Prominin-1 is of great interest as a marker for stem and cancer cells, while Prominin-2 (Prom2) is reportedly restricted to epithelial cells. Aim: To characterize the effects of Prom-2 expression on PM microdomain organization. Methods: Prom2-fluorescent protein was transfected in human skin fibroblasts (HSF) and Chinese hamster ovary (CHO) cells for PM raft and endocytic studies. Caveolae at PM were visualized using transmission electron microscopy. Cdc42 activation was measured and caveolin-1 knockdown was performed using siRNAs. Results: Prom2 expression in HSF and CHO cells caused extensive Prom2-positive protrusions that co-localized with lipid raft markers. Prom2 expression significantly decreased caveolae at the PM, reduced caveolar endocytosis and increased caveolin-1 phosphorylation. Prom2 expression also inhibited Cdc42-dependent fluid phase endocytosis via decreased Cdc42 activation. Effects on endocytosis were reversed by addition of cholesterol. Knockdown of caveolin-1 by siRNA restored Cdc42 dependent fluid phase endocytosis in Prom2-expressing cells. Conclusions: Prom2 protrusions primarily

  9. Prominin-2 expression increases protrusions, decreases caveolae and inhibits Cdc42 dependent fluid phase endocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Raman Deep, E-mail: Takhter.Ramandeep@mayo.edu; Schroeder, Andreas S.; Scheffer, Luana; Holicky, Eileen L.; Wheatley, Christine L.; Marks, David L., E-mail: Marks.david@mayo.edu; Pagano, Richard E.

    2013-05-10

    Highlights: •Prominin-2 expression induced protrusions that co-localized with lipid raft markers. •Prominin-2 expression decreased caveolae, caveolar endocytosis and increased pCav1. •Prominin-2 expression inhibited fluid phase endocytosis by inactivation of Cdc42. •These endocytic effects can be reversed by adding exogenous cholesterol. •Caveolin1 knockdown restored fluid phase endocytosis in Prominin2 expressing cells. -- Abstract: Background: Membrane protrusions play important roles in biological processes such as cell adhesion, wound healing, migration, and sensing of the external environment. Cell protrusions are a subtype of membrane microdomains composed of cholesterol and sphingolipids, and can be disrupted by cholesterol depletion. Prominins are pentaspan membrane proteins that bind cholesterol and localize to plasma membrane (PM) protrusions. Prominin-1 is of great interest as a marker for stem and cancer cells, while Prominin-2 (Prom2) is reportedly restricted to epithelial cells. Aim: To characterize the effects of Prom-2 expression on PM microdomain organization. Methods: Prom2-fluorescent protein was transfected in human skin fibroblasts (HSF) and Chinese hamster ovary (CHO) cells for PM raft and endocytic studies. Caveolae at PM were visualized using transmission electron microscopy. Cdc42 activation was measured and caveolin-1 knockdown was performed using siRNAs. Results: Prom2 expression in HSF and CHO cells caused extensive Prom2-positive protrusions that co-localized with lipid raft markers. Prom2 expression significantly decreased caveolae at the PM, reduced caveolar endocytosis and increased caveolin-1 phosphorylation. Prom2 expression also inhibited Cdc42-dependent fluid phase endocytosis via decreased Cdc42 activation. Effects on endocytosis were reversed by addition of cholesterol. Knockdown of caveolin-1 by siRNA restored Cdc42 dependent fluid phase endocytosis in Prom2-expressing cells. Conclusions: Prom2 protrusions primarily

  10. MRG15 activates the cdc2 promoter via histone acetylation in human cells

    International Nuclear Information System (INIS)

    Chromatin remodeling is required for transcriptional activation and repression. MRG15 (MORF4L1), a chromatin modulator, is a highly conserved protein and is present in complexes containing histone acetyltransferases (HATs) as well as histone deacetylases (HDACs). Loss of expression of MRG15 in mice and Drosophila results in embryonic lethality and fibroblast and neural stem/progenitor cells cultured from Mrg15 null mouse embryos exhibit marked proliferative defects when compared with wild type cells. To determine the role of MRG15 in cell cycle progression we performed chromatin immunoprecipitation with an antibody to MRG15 on normal human fibroblasts as they entered the cell cycle from a quiescent state, and analyzed various cell cycle gene promoters. The results demonstrated a 3-fold increase in MRG15 occupancy at the cdc2 promoter during S phase of the cell cycle and a concomitant increase in acetylated histone H4. H4 lysine 12 was acetylated at 24 h post-serum stimulation while there was no change in acetylation of lysine 16. HDAC1 and 2 were decreased at this promoter during cell cycle progression. Over-expression of MRG15 in HeLa cells activated a cdc2 promoter-reporter construct in a dose-dependent manner, whereas knockdown of MRG15 resulted in decreased promoter activity. In order to implicate HAT activity, we treated cells with the HAT inhibitor anacardic acid and determined that HAT inhibition results in loss of expression of cdc2 mRNA. Further, chromatin immunoprecipitation with Tip60 localizes the protein to the same 110 bp stretch of the cdc2 promoter pulled down by MRG15. Additionally, we determined that cotransfection of MRG15 with the known associated HAT Tip60 had a cooperative effect in activating the cdc2 promoter. These results suggest that MRG15 is acting in a HAT complex involving Tip60 to modify chromatin via acetylation of histone H4 at the cdc2 promoter to activate transcription.

  11. Isolation and characterization of new alleles of the cyclin-dependent kinase gene CDC28 with cyclin-specific functional and biochemical defects.

    Science.gov (United States)

    Levine, K; Oehlen, L J; Cross, F R

    1998-01-01

    The G1 cyclin Cln2 negatively regulates the mating-factor pathway. In a genetic screen to identify factors required for this regulation, we identified an allele of CDC28 (cdc28-csr1) that blocked this function of Cln2. Cln2 immunoprecipitated from cdc28-csr1 cells was completely defective in histone H1 kinase activity, due to defects in Cdc28 binding and activation by Cln2. In contrast, Clb2-associated H1 kinase and Cdc28 binding was normal in immunoprecipitates from these cells. cdc28-csr1 was significantly deficient in other aspects of genetic interaction with Cln2. The cdc28-csr1 mutation was determined to be Q188P, in the T loop distal to most of the probable Cdk-cyclin interaction regions. We performed random mutagenesis of CDC28 to identify additional alleles incapable of causing CLN2-dependent mating-factor resistance but capable of complementing cdc28 temperature-sensitive and null alleles. Two such mutants had highly defective Cln2-associated kinase, but, surprisingly, two other mutants had levels of Cln2-associated kinase near to wild-type levels. We performed a complementary screen for CDC28 mutants that could cause efficient Cln2-dependent mating-factor resistance but not complement a cdc28 null allele. Most such mutants were found to alter residues essential for kinase activity; the proteins had little or no associated kinase activity in bulk or in association with Cln2. Several of these mutants also functioned in another assay for CLN2-dependent function not involving the mating-factor pathway, complementing the temperature sensitivity of a cln1 cln3 cdc28-csr1 strain. These results could indicate that Cln2-Cdc28 kinase activity is not directly relevant to some CLN2-mediated functions. Mutants of this sort should be useful in differentiating the function of Cdc28 complexed with different cyclin regulatory subunits. PMID:9418876

  12. Cdc42 and PI(4,5)P2-induced actin assembly in Xenopus egg extracts.

    Science.gov (United States)

    Lebensohn, Andres M; Ma, Le; Ho, Hsin-Yi Henry; Kirschner, Marc W

    2006-01-01

    Xenopus egg cytoplasmic extracts have been used to study a variety of complex cellular processes. Given their amenability to biochemical manipulation and physiological balance of regulatory proteins, these extracts are an ideal system to dissect signal transduction pathways leading to actin assembly. We have developed methods to study Cdc42 and PI(4,5)P2-induced actin assembly in Xenopus egg extracts. In this chapter, we describe detailed procedures to prepare Xenopus egg extracts, Cdc42, and PI(4,5)P2 for use in actin assembly experiments. We also describe a fluorometric pyrene actin assay for quantitative kinetic analysis of actin polymerization and a microscopic rhodamine actin assay for quick measurement of actin rearrangements in extracts. Finally we provide a protocol for immunodepletion of proteins and discuss the use of immunodepletion and rescue experiments for functional analysis of components in the extracts. PMID:16472657

  13. Cdc42/N-WASP signaling links actin dynamics to pancreatic beta cell delamination and differentiation

    DEFF Research Database (Denmark)

    Kesavan, Gokul; Lieven, Oliver; Mamidi, Anant;

    2014-01-01

    Delamination plays a pivotal role during normal development and cancer. Previous work has demonstrated that delamination and epithelial cell movement within the plane of an epithelium are associated with a change in cellular phenotype. However, how this positional change is linked to differentiat......Delamination plays a pivotal role during normal development and cancer. Previous work has demonstrated that delamination and epithelial cell movement within the plane of an epithelium are associated with a change in cellular phenotype. However, how this positional change is linked to...... differentiation remains unknown. Using the developing mouse pancreas as a model system, we show that β cell delamination and differentiation are two independent events, which are controlled by Cdc42/N-WASP signaling. Specifically, we show that expression of constitutively active Cdc42 in β cells inhibits β cell...

  14. Ebola in West Africa--CDC's Role in Epidemic Detection, Control, and Prevention.

    Science.gov (United States)

    Frieden, Thomas R; Damon, Inger K

    2015-11-01

    Since Ebola virus disease was identified in West Africa on March 23, 2014, the Centers for Disease Control and Prevention (CDC) has undertaken the most intensive response in the agency's history; >3,000 staff have been involved, including >1,200 deployed to West Africa for >50,000 person workdays. Efforts have included supporting incident management systems in affected countries; mobilizing partners; and strengthening laboratory, epidemiology, contact investigation, health care infection control, communication, and border screening in West Africa, Nigeria, Mali, Senegal, and the United States. All efforts were undertaken as part of national and global response activities with many partner organizations. CDC was able to support community, national, and international health and public health staff to prevent an even worse event. The Ebola virus disease epidemic highlights the need to strengthen national and international systems to detect, respond to, and prevent the spread of future health threats. PMID:26484940

  15. A Decision Processing Algorithm for CDC Location Under Minimum Cost SCM Network

    Science.gov (United States)

    Park, N. K.; Kim, J. Y.; Choi, W. Y.; Tian, Z. M.; Kim, D. J.

    Location of CDC in the matter of network on Supply Chain is becoming on the high concern these days. Present status of methods on CDC has been mainly based on the calculation manually by the spread sheet to achieve the goal of minimum logistics cost. This study is focused on the development of new processing algorithm to overcome the limit of present methods, and examination of the propriety of this algorithm by case study. The algorithm suggested by this study is based on the principle of optimization on the directive GRAPH of SCM model and suggest the algorithm utilizing the traditionally introduced MST, shortest paths finding methods, etc. By the aftermath of this study, it helps to assess suitability of the present on-going SCM network and could be the criterion on the decision-making process for the optimal SCM network building-up for the demand prospect in the future.

  16. 75 FR 4830 - Advisory Committee to the Director (ACD), Centers for Disease Control (CDC) and Prevention-Ethics...

    Science.gov (United States)

    2010-01-29

    ...), Centers for Disease Control (CDC) and Prevention--Ethics Subcommittee (ES) In accordance with section 10(a... health ethics questions and issues arising from programs, scientists, and practitioners. Matter to...

  17. 75 FR 7483 - Advisory Committee to the Director (ACD), Centers for Disease Control (CDC) and Prevention-Ethics...

    Science.gov (United States)

    2010-02-19

    ... February 18, 2010, meeting published at 75 FR 4830, January 29, 2010, is 1 p.m.-5 p.m. FOR FURTHER...), Centers for Disease Control (CDC) and Prevention--Ethics Subcommittee (ES); Correction AGENCY: Centers...

  18. No Drop in Teen Use of Tobacco Products, CDC Says, and E-Cigs May Be Why

    Science.gov (United States)

    ... nih.gov/medlineplus/news/fullstory_158315.html No Drop in Teen Use of Tobacco Products, CDC Says, ... to the study. While there was a significant drop in cigarette smoking between 2011 and 2015, there ...

  19. Single site suppressors of a fission yeast temperature-sensitive mutant in cdc48 identified by whole genome sequencing.

    Directory of Open Access Journals (Sweden)

    Irina N Marinova

    Full Text Available The protein called p97 in mammals and Cdc48 in budding and fission yeast is a homo-hexameric, ring-shaped, ubiquitin-dependent ATPase complex involved in a range of cellular functions, including protein degradation, vesicle fusion, DNA repair, and cell division. The cdc48+ gene is essential for viability in fission yeast, and point mutations in the human orthologue have been linked to disease. To analyze the function of p97/Cdc48 further, we performed a screen for cold-sensitive suppressors of the temperature-sensitive cdc48-353 fission yeast strain. In total, 29 independent pseudo revertants that had lost the temperature-sensitive growth defect of the cdc48-353 strain were isolated. Of these, 28 had instead acquired a cold-sensitive phenotype. Since the suppressors were all spontaneous mutants, and not the result of mutagenesis induced by chemicals or UV irradiation, we reasoned that the genome sequences of the 29 independent cdc48-353 suppressors were most likely identical with the exception of the acquired suppressor mutations. This prompted us to test if a whole genome sequencing approach would allow us to map the mutations. Indeed genome sequencing unambiguously revealed that the cold-sensitive suppressors were all second site intragenic cdc48 mutants. Projecting these onto the Cdc48 structure revealed that while the original temperature-sensitive G338D mutation is positioned near the central pore in the hexameric ring, the suppressor mutations locate to subunit-subunit and inter-domain boundaries. This suggests that Cdc48-353 is structurally compromized at the restrictive temperature, but re-established in the suppressor mutants. The last suppressor was an extragenic frame shift mutation in the ufd1 gene, which encodes a known Cdc48 co-factor. In conclusion, we show, using a novel whole genome sequencing approach, that Cdc48-353 is structurally compromized at the restrictive temperature, but stabilized in the suppressors.

  20. Activated Cdc42-associated kinase Ack1 promotes prostate cancer progression via androgen receptor tyrosine phosphorylation

    OpenAIRE

    Mahajan, Nupam P.; Liu, Yuanbo; Majumder, Samarpan; Warren, Maria R.; Parker, Carol E.; Mohler, James L.; Earp, H. Shelton; Whang, Young E.

    2007-01-01

    Activation of the androgen receptor (AR) may play a role in androgen-independent progression of prostate cancer. Multiple mechanisms of AR activation, including stimulation by tyrosine kinases, have been postulated. We and others have recently shown involvement of activated Cdc42-associated tyrosine kinase Ack1 in advanced human prostate cancer. Here we provide the molecular basis for interplay between Ack1 and AR in prostate cancer cells. Activated Ack1 promoted androgen-independent growth o...

  1. Cdc42p and Fus2p act together late in yeast cell fusion

    OpenAIRE

    Ydenberg, Casey A.; Stein, Richard A; Rose, Mark D.

    2012-01-01

    Cell fusion is the key event of fertilization that gives rise to the diploid zygote and is a nearly universal aspect of eukaryotic biology. In the yeast Saccharomyces cerevisiae, several mutants have been identified that are defective for cell fusion, and yet the molecular mechanism of this process remains obscure. One obstacle has been that genetic screens have mainly focused on mating-specific factors, whereas the process likely involves housekeeping proteins as well. Here we implicate Cdc4...

  2. Cdc7-Dbf4 Is a Gene-Specific Regulator of Meiotic Transcription in Yeast

    OpenAIRE

    Lo, Hsiao-Chi; Kunz, Ryan C.; Chen, Xiangyu; Marullo, Allison; Steven P Gygi; Hollingsworth, Nancy M.

    2012-01-01

    Meiosis divides the chromosome number of the cell in half by having two rounds of chromosome segregation follow a single round of chromosome duplication. The first meiotic division is unique in that homologous pairs of sister chromatids segregate to opposite poles. Recent work in budding and fission yeast has shown that the cell cycle kinase, Cdc7-Dbf4, is required for many meiosis-specific chromosomal functions necessary for proper disjunction at meiosis I. This work reveals another role for...

  3. CDC28, NETI, and HFII are required for checkpoints in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    The involvement of SRM genes selected as genes affecting genetic stability and radiosensitivity in a cell cycle arrest under the action of damaging agents was studied. It was shown that the srm5/cdc28-srm, srm8/netI-srm, and srmI2/hfiI-srm mutations prevent checkpoint activation by DNA damage, particularly the G0/S (srm5, srm8), G1/S (srm5, srm8, srm12), S (srm8, srm12) and S/G2 (srm5) checkpoints. It seems that in budding yeast the CDC28, HFII/ADAI, and NETI genes mediate cellular response induced by DNA damage with checkpoint control. The well-known checkpoint-genes RAD9, RAD17, RAD24, and RAD53, and the genes CDC28, and NETI have been found to belong to one epistasis group named RAD9-group as regards cell sensitivity to γ radiation. An analysis of the radiosensitivity of double mutants has revealed that the mutation cdc-28-srm is hypostatic to each of mutations rad9Δ, and rad24Δ, and additive to rad17Δ. The mutation netI-srm is hypostatic to the mutations rad9Δ but additive to rad17Δ, rad24Δ, and rad53. The mutation hfiI-srm has an additive effect in compound with the mutations rad24Δ and rad9Δ. So, investigations of epistatic interactions have demonstrated a branched RAD9-dependent pathway. The analyzed genes can also participate in a minor mechanism involved in determining cell radiation sensitivity independently of the mentioned RAD9-dependent pathway

  4. Microbiological characteristics of Weeksella virosa (formerly CDC group IIf) isolated from the human genitourinary tract.

    OpenAIRE

    Reina, J; Gil, J.; Salva, F; J. Gomez; Alomar, P

    1990-01-01

    Weeksella virosa (formerly CDC group IIf) is a nonsaccharolytic, oxidase- and catalase-positive, gram-negative rod which is unable to grow on MacConkey agar. At 48 h of incubation on blood or chocolate agar, the colonies present a characteristic appearance: intensely mucoid, adherent, and cream colored as a result of the production of a nondiffusible yellow pigment. This microorganism has been isolated predominantly from the female genitourinary tract, which indicates the opportunity for sexu...

  5. Cdc42 and noncanonical Wnt signal transduction pathways cooperate to promote cell polarity

    OpenAIRE

    Schlessinger, Karni; McManus, Edward J.; Hall, Alan

    2007-01-01

    Scratch-induced disruption of cultured monolayers induces polarity in front row cells that can be visualized by spatially localized polymerization of actin at the front of the cell and reorientation of the centrosome/Golgi to face the leading edge. We previously reported that centrosomal reorientation and microtubule polarization depend on a Cdc42-regulated signal transduction pathway involving activation of the Par6/aPKC complex followed by inhibition of GSK-3β and accumulation of the adenom...

  6. Congenital syphilis after treatment of maternal syphilis with a penicillin regimen exceeding CDC guidelines.

    OpenAIRE

    Conover, C S; Rend, C A; Miller, G B; Schmid, G P

    1998-01-01

    BACKGROUND: Although congenital syphilis usually occurs as a result of a failure to detect and treat syphilis in pregnant women, failures of the currently recommended regimen to prevent congenital syphilis have been reported. CASE: This report describes an infant with congenital syphilis despite maternal treatment with a regimen exceeding current CDC guidelines. CONCLUSION: Regardless of the regimen used to treat syphilis during pregnancy, clinicians should recognize the possibility of occasi...

  7. Addressing Poverty as Risk for Disease: Recommendations from CDC's Consultation on Microenterprise as HIV Prevention

    OpenAIRE

    Stratford, Dale; Mizuno, Yuko; Williams, Kim; Courtenay-Quirk, Cari; O'Leary, Ann

    2008-01-01

    In March 2006, the Centers for Disease Control and Prevention (CDC) convened a consultation meeting to explore microenterprise as a potential human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) prevention intervention. The impulse to link microenterprise with HIV/AIDS prevention was driven by the fact that poverty is a significant factor contributing to the risk for infection. Because increasingly high rates of HIV infection are occurring among women, particularly amo...

  8. Human infections caused by Brevibacterium casei, formerly CDC groups B-1 and B-3.

    OpenAIRE

    Gruner, E; Steigerwalt, A G; Hollis, D G; Weyant, R S; Weaver, R E; Moss, C W; M Daneshvar; J. M. Brown; Brenner, D J

    1994-01-01

    Forty-one clinical strains of CDC coryneform groups B-1 and B-3 were compared biochemically, by analysis of cell wall sugars, amino acids, and cellular fatty acids, and by DNA relatedness to the type strains of Brevibacterium casei, Brevibacterium epidermidis, and Brevibacterium linens. Twenty-two strains were shown to be B. casei, while five other strains formed a phenotypically inseparable genomospecies in the same genus. The remaining isolates were genetically heterogeneous, and most are p...

  9. CDC Signos Vitales: Piense en la septicemia. El tiempo es crucial. (Think Sepsis. Time Matters.)

    Centers for Disease Control (CDC) Podcasts

    2016-08-23

    Este podcast se basa en la edición de agosto del 2016 del informe Signos Vitales de los CDC. La septicemia es una emergencia médica y puede ocurrir rápidamente. Conozca los signos de la septicemia y la forma de prevenirla.  Created: 8/23/2016 by National Center for Injury Prevention and Control (NCIPC).   Date Released: 8/23/2016.

  10. CDC Vital Signs–Motor Vehicle Crash Deaths

    Centers for Disease Control (CDC) Podcasts

    2016-07-06

    This podcast is based on the July 2016 CDC Vital Signs report. In the U.S., about 90 people die in motor vehicle crashes each day and thousands more are injured, resulting in hundreds of millions of dollars in direct medical costs each year. Learn what you can do to stay safe.  Created: 7/6/2016 by National Center for Injury Prevention and Control (NCIPC).   Date Released: 7/6/2016.

  11. CDC Vital Signs-ADHD in Young Children: What You Should Know

    Centers for Disease Control (CDC) Podcasts

    2016-05-03

    This podcast is based on the May 2016 CDC Vital Signs report. For children ages two to five who have ADHD, behavior therapy is recommended before prescribing medicine. This therapy teaches parents ways to improve their child’s behavior and can work as well as medicine, without the risk of side effects.  Created: 5/3/2016 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 5/3/2016.

  12. CDC Vital Signs-Zika and Pregnancy: What You Should Know

    Centers for Disease Control (CDC) Podcasts

    2016-04-01

    This podcast is based on the April 2016 CDC Vital Signs report. A pregnant woman who is infected with Zika virus can pass it to her fetus which is linked to microcephaly, a serious birth defect. This podcast discusses how to protect yourself from Zika virus.  Created: 4/1/2016 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 4/1/2016.

  13. GIT1 promotes lung cancer cell metastasis through modulating Rac1/Cdc42 activity and is associated with poor prognosis

    OpenAIRE

    Chang, Jeng-Shou; Su, Chia-Yi; Yu, Wen-Hsuan; Lee, Wei-Jiunn; Liu, Yu-Peng; Lai, Tsung-Ching; Jan, Yi-Hua; Yang, Yi-Fang; Shen, Chia-Ning; Shew, Jin-Yuh; Lu, Jean; Yang, Chih-Jen; Huang, Ming-Shyan; Lu, Pei-Jung; Lin, Yuan-Feng

    2015-01-01

    G-protein-coupled receptor kinase interacting protein 1 (GIT1) is participated in cell movement activation, which is a fundamental process during tissue development and cancer progression. GIT1/PIX forming a functional protein complex that contributes to Rac1/Cdc42 activation, resulting in increasing cell mobility. Although the importance of Rac1/Cdc42 activation is well documented in cancer aggressiveness, the clinical importance of GIT1 remains largely unknown. Here, we investigated the cli...

  14. The role of nucleotide binding and hydrolysis in the function of the fission yeast cdc18(+) gene product.

    OpenAIRE

    DeRyckere, D; Smith, C.L.; Martin, G S

    1999-01-01

    The fission yeast cdc18(+) gene is required for both initiation of DNA replication and the mitotic checkpoint that normally inhibits mitosis in the absence of DNA replication. The cdc18(+) gene product contains conserved Walker A and B box motifs. Studies of other ATPases have shown that these motifs are required for nucleotide binding and hydrolysis, respectively. We have observed that mutant strains in which either of these motifs is disrupted are inviable. The effects of these mutations we...

  15. Systems-wide Analysis of K-Ras, Cdc42, and PAK4 Signaling by Quantitative Phosphoproteomics*

    OpenAIRE

    Gnad, Florian; Young, Amy; Zhou, Wei; Lyle, Karen; Ong, Christy C.; Matthew P. Stokes; Silva, Jeffrey C.; Belvin, Marcia; Friedman, Lori S.; Koeppen, Hartmut; Minden, Audrey; Hoeflich, Klaus P.

    2013-01-01

    Although K-Ras, Cdc42, and PAK4 signaling are commonly deregulated in cancer, only a few studies have sought to comprehensively examine the spectrum of phosphorylation-mediated signaling downstream of each of these key signaling nodes. In this study, we completed a label-free quantitative analysis of oncogenic K-Ras, activated Cdc42, and PAK4-mediated phosphorylation signaling, and report relative quantitation of 2152 phosphorylated peptides on 1062 proteins. We define the overlap in phosphop...

  16. P-cadherin promotes collective cell migration via a Cdc42-mediated increase in mechanical forces

    Science.gov (United States)

    Plutoni, Cédric; Bazellieres, Elsa; Le Borgne-Rochet, Maïlys; Comunale, Franck; Brugues, Agusti; Séveno, Martial; Planchon, Damien; Thuault, Sylvie; Morin, Nathalie; Bodin, Stéphane; Trepat, Xavier

    2016-01-01

    Collective cell migration (CCM) is essential for organism development, wound healing, and metastatic transition, the primary cause of cancer-related death, and it involves cell–cell adhesion molecules of the cadherin family. Increased P-cadherin expression levels are correlated with tumor aggressiveness in carcinoma and aggressive sarcoma; however, how P-cadherin promotes tumor malignancy remains unknown. Here, using integrated cell biology and biophysical approaches, we determined that P-cadherin specifically induces polarization and CCM through an increase in the strength and anisotropy of mechanical forces. We show that this mechanical regulation is mediated by the P-cadherin/β-PIX/Cdc42 axis; P-cadherin specifically activates Cdc42 through β-PIX, which is specifically recruited at cell–cell contacts upon CCM. This mechanism of cell polarization and migration is absent in cells expressing E- or R-cadherin. Thus, we identify a specific role of P-cadherin through β-PIX–mediated Cdc42 activation in the regulation of cell polarity and force anisotropy that drives CCM. PMID:26783302

  17. NRP1 Regulates CDC42 Activation to Promote Filopodia Formation in Endothelial Tip Cells

    Directory of Open Access Journals (Sweden)

    Alessandro Fantin

    2015-06-01

    Full Text Available Sprouting blood vessels are led by filopodia-studded endothelial tip cells that respond to angiogenic signals. Mosaic lineage tracing previously revealed that NRP1 is essential for tip cell function, although its mechanistic role in tip cells remains poorly defined. Here, we show that NRP1 is dispensable for genetic tip cell identity. Instead, we find that NRP1 is essential to form the filopodial bursts that distinguish tip cells morphologically from neighboring stalk cells, because it enables the extracellular matrix (ECM-induced activation of CDC42, a key regulator of filopodia formation. Accordingly, NRP1 knockdown and pharmacological CDC42 inhibition similarly impaired filopodia formation in vitro and in developing zebrafish in vivo. During mouse retinal angiogenesis, CDC42 inhibition impaired tip cell and vascular network formation, causing defects that resembled those due to loss of ECM-induced, but not VEGF-induced, NRP1 signaling. We conclude that NRP1 enables ECM-induced filopodia formation for tip cell function during sprouting angiogenesis.

  18. Waist Circumferences of Chilean Students: Comparison of the CDC-2012 Standard and Proposed Percentile Curves

    Directory of Open Access Journals (Sweden)

    Rossana Gómez-Campos

    2015-07-01

    Full Text Available The measurement of waist circumference (WC is considered to be an important means to control overweight and obesity in children and adolescents. The objectives of the study were to (a compare the WC measurements of Chilean students with the international CDC-2012 standard and other international standards, and (b propose a specific measurement value for the WC of Chilean students based on age and sex. A total of 3892 students (6 to 18 years old were assessed. Weight, height, body mass index (BMI, and WC were measured. WC was compared with the CDC-2012 international standard. Percentiles were constructed based on the LMS method. Chilean males had a greater WC during infancy. Subsequently, in late adolescence, males showed values lower than those of the international standards. Chilean females demonstrated values similar to the standards until the age of 12. Subsequently, females showed lower values. The 85th and 95th percentiles were adopted as cutoff points for evaluating overweight and obesity based on age and sex. The WC of Chilean students differs from the CDC-2012 curves. The regional norms proposed are a means to identify children and adolescents with a high risk of suffering from overweight and obesity disorders.

  19. CDC-42 and RAC-1 regulate opposite chemotropisms in Neurospora crassa.

    Science.gov (United States)

    Lichius, Alexander; Goryachev, Andrew B; Fricker, Mark D; Obara, Boguslaw; Castro-Longoria, Ernestina; Read, Nick D

    2014-05-01

    Cell polarization and fusion are crucial developmental processes that occur in response to intracellular and extracellular signals. Asexual spores (conidia) of the mold Neurospora crassa differentiate two types of polarized cell protrusions, germ tubes and conidial anastomosis tubes (CATs), which exhibit negative and positive chemotropism, respectively. We provide the first evidence that shared and separate functions of the Rho-type GTPases CDC-42 and RAC-1 regulate these opposite chemotropisms. We demonstrate that RAC-1 is essential for CAT formation and cell fusion, whereas CDC-42 is necessary and sufficient for normal germ tube development. Cdc42-Rac-interactive-binding (CRIB) reporters were constructed to exclusively label locally activated GTP-bound GTPases. Time course analyses showed that repositioning of these activated GTPase clusters within germ tube and CAT tip apices controls directional growth in the absence of a tip-localized vesicle supply center (Spitzenkörper). We propose a model in which the local assembly of a plasma-membrane-associated GTPase-PAK-MAPK signaling platform regulates chemoattractant perception and secretion in order to synchronize oscillatory cell-cell communication and directional CAT tip growth. PMID:24790223

  20. Characterization of Cdc2 kinase in the red claw crayfish (Cherax quadricarinatus): evidence for its role in regulating oogenesis.

    Science.gov (United States)

    Wang, Lan-Mei; Zuo, Di; Lv, Wei-Wei; Wang, Dan-Li; Liu, A-Jing; Zhao, Yunlong

    2013-02-25

    Cdc2 kinase is a catalytic subunit of the maturation-promoting factor (MPF), a central factor for inducing the meiotic maturation of oocytes. MPF has been studied in a wide variety of animal species; however, its expression in crustaceans is poorly characterized. In this study, a complete cDNA sequence of Cdc2 kinase was cloned from the red claw crayfish, Cherax quadricarinatus, and its spatiotemporal expression profiles were analyzed. The Cdc2 cDNA (1,769 bp) encodes for a 299 amino acid protein with a calculated molecular weight of 34.7 kDa. Quantitative real-time PCR demonstrated that Cdc2 mRNA was expressed mainly in the ovary tissue and the expression decreased as the ovaries developed. Immunohistochemistry analysis revealed that the Cdc2 protein relocated from the cytoplasm to the nucleus during oogenesis. These findings suggest that Cdc2 kinase may play an important role in the gametogenesis and gonad development in C. quadricarinatus. PMID:23266620

  1. Nuclear distribution and chromatin association of DNA polymerase α-primase is affected by TEV protease cleavage of Cdc23 (Mcm10 in fission yeast

    Directory of Open Access Journals (Sweden)

    Gregan Juraj

    2005-06-01

    Full Text Available Abstract Background Cdc23/Mcm10 is required for the initiation and elongation steps of DNA replication but its biochemical function is unclear. Here, we probe its function using a novel approach in fission yeast, involving Cdc23 cleavage by the TEV protease. Results Insertion of a TEV protease cleavage site into Cdc23 allows in vivo removal of the C-terminal 170 aa of the protein by TEV protease induction, resulting in an S phase arrest. This C-terminal fragment of Cdc23 is not retained in the nucleus after cleavage, showing that it lacks a nuclear localization signal and ability to bind to chromatin. Using an in situ chromatin binding procedure we have determined how the S phase chromatin association of DNA polymerase α-primase and the GINS (Sld5-Psf1-Psf2-Psf3 complex is affected by Cdc23 inactivation. The chromatin binding and sub-nuclear distribution of DNA primase catalytic subunit (Spp1 is affected by Cdc23 cleavage and also by inactivation of Cdc23 using a degron allele, implying that DNA polymerase α-primase function is dependent on Cdc23. In contrast to the effect on Spp1, the chromatin association of the Psf2 subunit of the GINS complex is not affected by Cdc23 inactivation. Conclusion An important function of Cdc23 in the elongation step of DNA replication may be to assist in the docking of DNA polymerase α-primase to chromatin.

  2. CDC25A Protein Stability Represents a Previously Unrecognized Target of HER2 Signaling in Human Breast Cancer: Implication for a Potential Clinical Relevance in Trastuzumab Treatment

    Directory of Open Access Journals (Sweden)

    Emanuela Brunetto

    2013-06-01

    Full Text Available The CDC25A-CDK2 pathway has been proposed as critical for the oncogenic action of human epidermal growth factor receptor 2 (HER2 in mammary epithelial cells. In particular, transgenic expression of CDC25A cooperates with HER2 in promoting mammary tumors, whereas CDC25A hemizygous loss attenuates the HER2-induced tumorigenesis penetrance. On the basis of this evidence of a synergism between HER2 and the cell cycle regulator CDC25A in a mouse model of mammary tumorigenesis, we investigated the role of CDC25A in human HER2-positive breast cancer and its possible implications in therapeutic response. HER2 status and CDC25A expression were assessed in 313 breast cancer patients and we found statistically significant correlation between HER2 and CDC25A (P = .007. Moreover, an HER2-positive breast cancer subgroup with high levels of CDC25A and very aggressive phenotype was identified (P = .005. Importantly, our in vitro studies on breast cancer cell lines showed that the HER2 inhibitor efficacy on cell growth and viability relied also on CDC25A expression and that such inhibition induces CDC25A down-regulation through phosphatidylinositol 3-kinase/protein kinase B pathway and DNA damage response activation. In line with this observation, we found a statistical significant association between CDC25A overexpression and trastuzumab-combined therapy response rate in two different HER2-positive cohorts of trastuzumab-treated patients in either metastatic or neoadjuvant setting (P = .018 for the metastatic cohort and P = .021 for the neoadjuvant cohort. Our findings highlight a link between HER2 and CDC25A that positively modulates HER2- targeted therapy response, suggesting that, in HER2-positive breast cancer patients, CDC25A overexpression affects trastuzumab sensitivity.

  3. DATA-ENTRY-1: a general-purpose COBOL program for on-line data entry, formatting, and verification. [For CDC 6600

    Energy Technology Data Exchange (ETDEWEB)

    Harlow, M.V. Jr.

    1977-11-01

    The COBOL program DATA-ENTRY-1 solves a large class of elementary data-capture, data-formatting, and data-editing problems for managerial accounting. It operates on-line in the time-sharing environment of the Network Operating System (NOS) on a CDC 6600 computer. The Output Record Definition Table controls the processing and specifies such things as record and field types, data sources, prompt words, output field addresses, and instructions for formatting, truncating, and editing. Each new data-entry problem changes the contents of the table. DATA-ENTRY-1 provides for free-form entry of phrases and for a comprehensive set of reserved control words that perform utility functions and control the prompt sequence. 19 figures, 7 tables.

  4. ANISN-L, a CDC-7600 code which solves the one-dimensional, multigroup, time dependent transport equation by the method of discrete ordinates

    Energy Technology Data Exchange (ETDEWEB)

    Wilcox, T. P.

    1973-09-20

    The code ANISN-L solves the one-dimensional, multigroup, time-independent Boltzmann transport equation by the method of discrete ordinates. In problems involving a fissionable system, it can calculate the system multiplication or alpha. In such cases, it is also capable of determining isotopic concentrations, radii, zone widths, or buckling in order to achieve a given multiplication or alpha. The code may also calculate fluxes caused by a specified fixed source. Neutron, gamma, and coupled neutron--gamma problems may be solved in either the forward or adjoint (backward) modes. Cross sections describing upscatter, as well as the usual downscatter, may be employed. This report describes the use of ANISN-L; this is a revised version of ANISN which handles both large and small problems efficiently on CDC-7600 computers. (RWR)

  5. Isolation of a cdc28 mutation that abrogates the dependence of S phase on completion of M phase of the budding yeast cell cycle

    Indian Academy of Sciences (India)

    Santanu Kumar Ghosh; Pratima Sinha

    2000-01-01

    We have isolated a mutation in the budding yeast Saccharomyces cerevisisae CDC28 gene that allows cdc13 cells, carrying damaged DNA, to continue with the cell division cycle. While cdc13 mutant cells are arrested as large-budded cells at the nonpermissive temperature 37°C, the cdc13 cdc28 double mutant culture showed cells with one or more buds, most of which showed apical growth. The additional buds emerged without the intervening steps of nuclear division and cell separation. We suggest that the cdc28 mutation abrogates a checkpoint function and allows cells with damaged or incompletely replicated DNA an entry to another round of cell cycle and bypasses the mitotic phase of the cell cycle.

  6. 猪带绦虫CDC37基因的克隆、表达与组织定位研究%Prokaryotic Expression and Histolocalization of the Taenia solium CDC37 Gene

    Institute of Scientific and Technical Information of China (English)

    黄江; 李波; 戴佳琳; 张爱华

    2013-01-01

    Objective To express Taenia solium gene encoding cell division cycle 37 protein (TsCDC37) and investigate its antigenicity and localization in adults of Taenia solium. Methods The complete coding sequence of TsCDC37 was amplified by PCR based on the recombinant plasmid clone from the cDNA library of adult Taenia solium. The PCR product was cloned into a prokaryotic expression vector pET-28a(+). The recombinant expression plasmid was identified by PCR, double endonuclease digestion and sequencing. The recombinant plasmid was transformed into E. coli BL21/DE3 and followed by expression of the protein induced by IPTG. The mice were immunized subcutaneously with purified reeombinant TsCDC37 formulated in Freund's adjuvant. The antigenicity of the reeombinant protein was examined by Western blotting. The localization of TsCDC37 in adult worms was demonstrated by immunofluorescent technique. Results The reeombinant expression vector was constructed successfully. The reeombinant protein was about M, 52 000, it was then purified and specifically recognized by immunosera of SD rats and sera from patients infected with Taenia solium, Taenia saginata or Taenia asiatica. The immunofluorescence assay revealed that TsCDC37 located at the tegument of T. solium adult and the eggs. Conclusion TsCDC37 gene has been expressed with immunoreactivity. The reeombinant protein is mainly expressed in tegument and egg, and is a common antigen of the three human taenia cestodes.%目的 原核表达猪带绦虫(Taenia solium)细胞分裂周期蛋白37(cell division cycle 37,TsCDC37),并对其进行组织定位和免疫原性研究.方法 通过Blastx分析从猪带绦虫成虫cDNA质粒文库中筛选出 TsCDC37基因,PCR扩增CDC37基因,以pET-28a(+)为载体构建目的基因原核表达体系,在大肠埃希菌(E.coli)BL-21/DE3 中诱导表达,纯化的重组蛋白免疫SD大鼠制备免疫血清,Western blotting分析重组蛋白的免疫原性,免疫组织化学方法观察TsCDC37在

  7. Sequencing Analysis of Mutant Allele $cdc$28-$srm$ of Protein Kinase CDC28 and Molecular Dynamics Study of Glycine-Rich Loop in Wild-Type and Mutant Allele G16S of CDK2 as Model

    CERN Document Server

    Koltovaya, N A; Kholmurodov, Kh T; Kretov, D A

    2005-01-01

    The central role that cyclin-dependent kinases play in the timing of cell division and the high incidence of genetic alteration of CDKs or deregulation of CDK inhibitors in a number of cancers make CDC28 of the yeast \\textit{Saccharomyces cerevisiae }very attractive model for studies of mechanisms of CDK regulation. Earlier it was found that certain gene mutations including \\textit{cdc28-srm} affect cell cycle progression, maintenance of different genetic structures and increase cell sensitivity to ionizing radiation. A~\\textit{cdc28-srm} mutation is not temperature-sensitive mutation and differs from the known \\textit{cdc28-ts }mutations because it has the evident phenotypic manifestations at 30 $^{\\circ}$C. Sequencing analysis of \\textit{cdc28-srm} revealed a single nucleotide substitution G20S. This is a third glycine in a conserved sequence GxGxxG in the G-rich loop positioned opposite the activation T-loop. Despite its demonstrated importance, the role of the G-loop has remained unclear. The crystal stru...

  8. Specific deletion of Cdc42 does not affect meiotic spindle organization/migration and homologous chromosome segregation but disrupts polarity establishment and cytokinesis in mouse oocytes

    DEFF Research Database (Denmark)

    Wang, Zhen-Bo; Jiang, Zong-Zhe; Zhang, Qing-Hua;

    2013-01-01

    female infertility in mice. Cdc42 deletion has little effect on meiotic spindle organization and migration to the cortex but inhibits polar body emission, although homologous chromosome segregation occurs. The failure of cytokinesis is due to the loss of polarized Arp2/3 accumulation and actin cap...... polarized actin cap and oocyte polarity, and it determines asymmetric divisions resulting in two polar bodies. Here we investigate the functions of Cdc42 in oocyte meiotic maturation by oocyte-specific deletion of Cdc42 through Cre-loxP conditional knockout technology. We find that Cdc42 deletion causes...

  9. Cdc42 and phosphoinositide 3-kinase drive Rac-mediated actin polymerization downstream of c-Met in distinct and common pathways

    DEFF Research Database (Denmark)

    Bosse, Tanja; Ehinger, Julia; Czuchra, Aleksandra;

    2007-01-01

    Activation of c-Met, the hepatocyte growth factor (HGF)/scatter factor receptor induces reorganization of the actin cytoskeleton, which drives epithelial cell scattering and motility and is exploited by pathogenic Listeria monocytogenes to invade nonepithelial cells. However, the precise...... required the simultaneous inactivation of both Cdc42 and PI3-kinase signaling. Moreover, Cdc42 activation was fully independent of PI3-kinase activity, whereas the latter partly depended on Cdc42. Finally, Cdc42 function did not require its interaction with the actin nucleation-promoting factor N...

  10. Biochemical analysis of the interactions of IQGAP1 C-terminal domain with CDC42

    Institute of Scientific and Technical Information of China (English)

    Sarah; F; Elliott; George; Allen; David; J; Timson

    2012-01-01

    AIM:To understand the interaction of human IQGAP1 and CDC42,especially the effects of phosphorylation and a cancer-associated mutation. METHODS:Recombinant CDC42 and a novel C-termi- nal fragment of IQGAP1 were expressed in,and puri- fied from,Escherichia coli.Site directed mutagenesis was used to create coding sequences for three phos- phomimicking variants(S1441E,S1443D and S1441E/ S1443D)and to recapitulate a cancer-associated mu- tation(M1231I).These variant proteins were also ex- pressed and purified.Protein-protein crosslinking using 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide was used to investigate interactions between the C-terminal fragment and CDC42.These interactions were quanti- fied using surface plasmon resonance measurements.Molecular modelling was employed to make predictions about changes to the structure and flexibility of the protein which occur in the cancer-associated variant. RESULTS:The novel,C-terminal region of human IQGAP1 (residues 877-1558)is soluble following expression and purification.It is also capable of binding to CDC42,as judged by crosslinking experiments.Interaction appears to be strongest in the presence of added GTP.The three phosphomimicking mutants had different affini- ties for CDC42.S1441E had an approximately 200-fold reduction in affinity compared to wild type.This was caused largely by a dramatic reduction in the associa- tion rate constant.In contrast,both S1443D and the double variant S1441E/S1443D had similar affinities to the wild type.The cancer-associated variant,M1231I, also had a similar affinity to wild type.However,in the case of this variant,both the association and dis- sociation rate constants were reduced approximately 10-fold.Molecular modelling of the M1231I variant, based on the published crystal structure of part of the C-terminal region,revealed no gross structural changes compared to wild type(root mean square deviation of 0.564over 5556 equivalent atoms).However,pre- dictions of the

  11. CDC25B蛋白S149/S321位点突变对小鼠1-细胞期受精卵发育的影响%Mutation of S149 and S321 Sites of CDC25B Protein on Development of 1-Cell Stage of Fertilized Mouse Eggs

    Institute of Scientific and Technical Information of China (English)

    刘超; 肖建英; 孙小涵; 徐晓燕; 于秉治

    2012-01-01

    Objective: To investigate the role of Serl49 of CDC25B in 1-cell stage of fertilized mouse eggs and the relationship between Serl49 and Ser 321 sites. Methods: pBSK-CDC25B-S149A and pBSK-CDC25B-S149A/S321A mutants were constructed and transcribed into mRNAs in vitro. CDC25B-WT-mRNA, CDC25B-S149A-mRNA and CDC25B-S149A/S321A-mRNA were respectively microinjected into the mouse fertilized eggs in Gi phase after superovulation. Furthermore, the cleavage rate, MPF activity and phosphorylation status of CDC2-pTyrl5 in fertilized eggs were observed. Results: Cleavage rate of fertilized eggs in CDC25B-S149A-mRNA injected group was significantly higher than that of CDC25B-WT-mRNA group, and the peak of MPF activity appeared in the CDC25B-S149A-mRNA group, about 1 h early compared with the CDC25B-WT-mRNA group. While the cleavage rate in CDC25B-S149A/S321 A-mRNA group was significantly higher than that in CDC25B-S149A-mRNA group. Conclusion: PKA regulates the early development of mouse embryos by phosphorylation of S149 of CDC25B, and the residue Serl49 of CDC25B cooperates with Ser321, which plays an important role in the regulation of G2/M transition in the mitotic cell cycle of fertilized mouse eggs.%目的:研究小鼠CDC25B蛋白S149位点对小鼠1-细胞期受精卵发育的影响及S149位点与S321位点的关系.方法:构建pBSK-CDC25B-S 149A和pBSK-CDC25B-S149A/S321A突变体,体外转录成mRNA;采用小鼠超排卵技术取G1期受精卵,显微注射CDC25B-WT-mRNA和突变CDC25B-S149A-mRNA、CDC25B-S 149A/S321A-mRNA,观察其对受精卵发育、M期促进因子(MPF)活性及CDC2-pTyr 15磷酸化状态的影响.结果:CDC25B-S149A-mRNA注射组受精卵卵裂率明显高于CDC25B-WT-mRNA注射组,MPF活性提前1h达到高峰;而联合突变体CDC25B-S149A/S321A-mRNA注射组卵裂率又显著高于CDC25B-S149A-mRNA注射组.结论:在小鼠1-细胞期受精卵有丝分裂过程中,蛋白激酶A(PKA)对小鼠CDC25B蛋白S149位点的磷酸化

  12. Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC.

    Science.gov (United States)

    Schrag, Stephanie; Gorwitz, Rachel; Fultz-Butts, Kristi; Schuchat, Anne

    2002-08-16

    Group B streptococcus (GBS) remains a leading cause of serious neonatal infection despite great progress in perinatal GBS disease prevention in the 1990s. In 1996, CDC, in collaboration with other agencies, published guidelines for the prevention of perinatal group B streptococcal disease (CDC. Prevention of perinatal group B streptococcal disease: a public health perspective. MMWR 1996;45[RR-7]:1-24). Data collected after the issuance of the 1996 guidelines prompted reevaluation of prevention strategies at a meeting of clinical and public health representatives in November 2001. This report replaces CDC's 1996 guidelines. The recommendations are based on available evidence and expert opinion where sufficient evidence was lacking. Although many of the recommendations in the 2002 guidelines are the same as those in 1996, they include some key changes: * Recommendation of universal prenatal screening for vaginal and rectal GBS colonization of all pregnant women at 35-37 weeks' gestation, based on recent documentation in a large retrospective cohort study of a strong protective effect of this culture-based screening strategy relative to the risk-based strategy * Updated prophylaxis regimens for women with penicillin allergy * Detailed instruction on prenatal specimen collection and expanded methods of GBS culture processing, including instructions on antimicrobial susceptibility testing * Recommendation against routine intrapartum antibiotic prophylaxis for GBS-colonized women undergoing planned cesarean deliveries who have not begun labor or had rupture of membranes * A suggested algorithm for management of patients with threatened preterm delivery * An updated algorithm for management of newborns exposed to intrapartum antibiotic prophylaxis Although universal screening for GBS colonization is anticipated to result in further reductions in the burden of GBS disease, the need to monitor for potential adverse consequences of intrapartum antibiotic use, such as

  13. Improving effector functions of antibodies for cancer treatment: Enhancing ADCC and CDC

    Directory of Open Access Journals (Sweden)

    Akito Natsume

    2008-12-01

    Full Text Available Akito Natsume, Rinpei Niwa, Mitsuo SatohAntibody Research Laboratories, Research Division, Kyowa Hakko Kirin Co., Ltd.,/Machida-shi, Tokyo, JapanAbstract: As platforms for therapeutic agents, monoclonal antibodies (MAbs have already been approved, and several MAbs have demonstrated clinical effectiveness in a variety of malignancies. However, several issues have also been emerging in antibody therapy, such as high cost and insufficient drug action. Recently, to improve MAb activity in humans, effector functions have been subjects of focus, especially antibody-dependent cell-mediated cytotoxicity (ADCC and complement-dependent cytotoxicity (CDC. Extensive efforts have been made to enhance these effector functions of MAbs, and successful approaches have been reported by us and others, wherein the binding activity of MAbs to FcγRIIIa or C1q is increased by introducing amino acid mutations into heavy chain constant regions or through glyco-modification of Fc-linked oligosaccharides. In addition, one of the next approaches to optimizing therapeutic antibodies would be to combine multiple enhancing modifications into a single antibody platform to overcome the diverse mechanisms of clinical resistance of tumor cells. For this aim, we have recently developed a successful combination composed of ADCC-enhancing modification by the fucose depletion from Fc-linked oligosaccharides and CDC-enhancing modification by IgG1 and IgG3 isotype shuffling in heavy chains, which could be of great value for the development of third-generation antibody therapeutics.Keywords: ADCC, CDC, effector functions, Fc oligosaccharides, IgG isotypes, nonfucosylated IgG

  14. Positive feedback promotes mitotic exit via the APC/C-Cdh1-separase-Cdc14 axis in budding yeast.

    Science.gov (United States)

    Hatano, Yuhki; Naoki, Koike; Suzuki, Asuka; Ushimaru, Takashi

    2016-10-01

    The mitotic inhibitor securin is degraded via the ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C)-Cdc20 after anaphase onset. This triggers activation of the mitotic protease separase and thereby sister chromatid separation. However, only a proportion of securin molecules are degraded at metaphase-anaphase transition and the remaining molecules are still present in anaphase. The roles of securin and separase in late mitosis remain elusive. Here, we show that securin still inhibits separase to repress mitotic exit in anaphase in budding yeast. APC/C-Cdh1-mediated securin degradation at telophase further liberated separase, which promotes Cdc14 release and mitotic exit. Separase executed these events via its proteolytic action and that in the Cdc14 early release (FEAR) network. Cdc14 release further activated APC/C-Cdh1 in the manner of a positive feedback loop. Thus, the positive feedback promotes mitotic exit via the APC/C-Cdh1-separase-Cdc14 axis. This study shows the importance of the two-step degradation mode of securin and the role of separase in mitotic exit. PMID:27418100

  15. CDC Vital Signs–Legionnaires’ Disease

    Centers for Disease Control (CDC) Podcasts

    2016-06-07

    This podcast is based on the June 2016 CDC Vital Signs report. People can get Legionnaires’ disease, a serious type of lung infection, from breathing in small water droplets of water contaminated with Legionella germs. Learn what can be done to help prevent Legionnaires’ disease outbreaks and keep people safe.  Created: 6/7/2016 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 6/7/2016.

  16. Genetics, structure, and prevalence of FP967 (CDC Triffid) T-DNA in flax

    OpenAIRE

    Young, Lester; Hammerlindl, Joseph; Babic, Vivijan; McLeod, Jamille; Sharpe, Andrew; Matsalla, Chad; Bekkaoui, Faouzi; Marquess, Leigh; Booker, Helen M

    2015-01-01

    The detection of T-DNA from a genetically modified flaxseed line (FP967, formally CDC Triffid) in a shipment of Canadian flaxseed exported to Europe resulted in a large decrease in the amount of flax planted in Canada. The Canadian flaxseed industry undertook major changes to ensure the removal of FP967 from the supply chain. This study aimed to resolve the genetics and structure of the FP967 transfer DNA (T-DNA). The FP967 T-DNA is thought to be inserted in at single genomic locus. The junct...

  17. Divergent functions of the Rho GTPases Rac1 and Cdc42 in podocyte injury

    DEFF Research Database (Denmark)

    Blattner, Simone M; Hodgin, Jeffrey B; Nishio, Masashi;

    2013-01-01

    the regulation of actin cytoskeleton dynamics. Here, we employed podocyte-specific Cre-lox technology and found that mice with deletion of Rac1 display normal podocyte morphology without glomerular dysfunction well into adulthood. Using the protamine sulfate model of acute podocyte injury, podocyte...... steady state. However, Rac1 has either beneficial or deleterious effects depending on the context of podocyte impairment. Thus, our study highlights the divergent roles of Rac1 and Cdc42 function in podocyte maintenance and injury.Kidney International advance online publication, 15 May 2013; doi:10...

  18. Characterization, in vitro susceptibility, and clinical significance of CDC group HB-5 from Rwanda.

    OpenAIRE

    Bogaerts, J.; Verhaegen, J.; Martinez Tello, W.; Allen, S.; Verbist, L; Van Dyck, E; Piot, P.

    1990-01-01

    From June 1984 until July 1988, CDC group HB-5 isolates were recovered from the exudates of genital ulcers in 25 of 675 (3.6%) patients (204 women, 471 men) in Kigali, Rwanda. Among a group of 145 men presenting with urethritis but without genital ulcers, a positive culture for HB-5 of a specimen from the coronal groove of the penis of only 1 man (0.7%) was found. During the same period, the organism was not obtained in cultures of vaginal specimens from 838 women without genital ulcer diseas...

  19. CDC Signos Vitales: Mortalidad por choques automovilísticos (Motor Vehicle Crash Deaths)

    Centers for Disease Control (CDC) Podcasts

    2016-07-06

    Este podcast se basa en la edición de julio de 2016 del informe Signos Vitales de los CDC. En los Estados Unidos, aproximadamente 90 personas mueren en choques automovilísticos cada día y miles sufren lesiones, lo cual resulta en cientos de millones de dólares en costos médicos directos cada año. Sepa qué puede hacer para mantenerse seguro.  Created: 7/6/2016 by National Center for Injury Prevention and Control (NCIPC).   Date Released: 7/6/2016.

  20. Signos Vitales de los CDC-El humo de segunda mano (Secondhand Smoke)

    Centers for Disease Control (CDC) Podcasts

    2015-02-03

    Este podcast se basa en la edición de febrero del 2015 del informe de Signos Vitales de los CDC. El humo de segunda mano mata a más de 400 bebés y 41 000 adultos no fumadores al año. Sepa qué se puede hacer para prevenir la exposición al humo de segunda mano.  Created: 2/3/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 2/3/2015.

  1. CDC Signos Vitales-Las medidas hospitalarias afectan la lactancia materna (Hospital Actions Affect Breastfeeding)

    Centers for Disease Control (CDC) Podcasts

    2015-10-06

    Este podcast se basa en la edición de octubre del 2015 del informe Signos Vitales de los CDC. Los hospitales pueden implementar los "Diez Pasos hacia una Feliz Lactancia Natural" para obtener la designación de "Amigo del Niño" y así apoyar a más mamás en su decisión de amamantar.  Created: 10/6/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/6/2015.

  2. CDC: Tips from Former Smokers – Tiffany PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2013-03-28

    When Tiffany was 16, her mother—a cigarette smoker—died of lung cancer. Tiffany quit smoking at 34 because she wanted to be around for her own daughter, who had just turned 16. In this 60 second PSA from CDC's Tips From Former Smokers campaign, Tiffany offers tips on how to quit.  Created: 3/28/2013 by Office on Smoking and Health, National Center for Chronic Disease Prevention and Health Promotion.   Date Released: 8/8/2013.

  3. CDC Signos Vitales-Seguridad de los camioneros (Vital Signs-Trucker Safety)

    Centers for Disease Control (CDC) Podcasts

    2015-03-03

    Este podcast se basa en la edición de marzo del 2015 del informe Signos Vitales de los CDC. En el 2012 en los Estados Unidos, ocurrieron cerca de 317 000 choques asociados a camiones pesados. Veintiséis mil camioneros y sus pasajeros sufrieron lesiones en esos choques, y cerca de 700 murieron. Infórmese sobre lo que se puede hacer para que los camioneros estén seguros.  Created: 3/3/2015 by National Institute for Occupational Safety and Health (NIOSH).   Date Released: 3/3/2015.

  4. CDC Vital Signs-Alcohol and Pregnancy: Why Take the Risk?

    Centers for Disease Control (CDC) Podcasts

    2016-02-02

    This podcast is based on the February 2016 CDC Vital Signs report. More than three million women in the U.S. are at risk for exposing their developing baby to alcohol. Drinking alcohol during pregnancy can cause physical, behavioral, and intellectual disabilities that can affect a child’s whole life. Learn what can be done to keep developing babies healthy.  Created: 2/2/2016 by National Center on Birth Defects and Developmental Disabilities (NCBDDD).   Date Released: 2/2/2016.

  5. Jaridonin-induced G2/M phase arrest in human esophageal cancer cells is caused by reactive oxygen species-dependent Cdc2-tyr15 phosphorylation via ATM–Chk1/2–Cdc25C pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Yong-Cheng [Clinical Pharmacology Laboratory, Henan Province People' s Hospital, No. 7, Wei Wu Road, Zhengzhou, Henan (China); Su, Nan [Department of Quality Detection and Management, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan (China); Shi, Xiao-Jing; Zhao, Wen; Ke, Yu [School of Pharmaceutical Sciences, Zhengzhou University, No. 100, Science Avenue, Zhengzhou, Henan (China); Zi, Xiaolin [Department of Urology, University of California, Irvine, Orange, CA (United States); Department of Pharmacology, University of California, Irvine, Orange, CA (United States); Department of Pharmaceutical Sciences, University of California, Irvine, Orange, CA (United States); Zhao, Ning-Min; Qin, Yu-Hua; Zhao, Hong-Wei [Clinical Pharmacology Laboratory, Henan Province People' s Hospital, No. 7, Wei Wu Road, Zhengzhou, Henan (China); Liu, Hong-Min, E-mail: liuhm@zzu.edu.cn [School of Pharmaceutical Sciences, Zhengzhou University, No. 100, Science Avenue, Zhengzhou, Henan (China)

    2015-01-15

    Jaridonin, a novel diterpenoid from Isodon rubescens, has been shown previously to inhibit proliferation of esophageal squamous cancer cells (ESCC) through G2/M phase cell cycle arrest. However, the involved mechanism is not fully understood. In this study, we found that the cell cycle arrest by Jaridonin was associated with the increased expression of phosphorylation of ATM at Ser1981 and Cdc2 at Tyr15. Jaridonin also resulted in enhanced phosphorylation of Cdc25C via the activation of checkpoint kinases Chk1 and Chk2, as well as in increased phospho-H2A.X (Ser139), which is known to be phosphorylated by ATM in response to DNA damage. Furthermore, Jaridonin-mediated alterations in cell cycle arrest were significantly attenuated in the presence of NAC, implicating the involvement of ROS in Jaridonin's effects. On the other hand, addition of ATM inhibitors reversed Jaridonin-related activation of ATM and Chk1/2 as well as phosphorylation of Cdc25C, Cdc2 and H2A.X and G2/M phase arrest. In conclusion, these findings identified that Jaridonin-induced cell cycle arrest in human esophageal cancer cells is associated with ROS-mediated activation of ATM–Chk1/2–Cdc25C pathway. - Highlights: • Jaridonin induced G2/M phase arrest through induction of redox imbalance. • Jaridonin increased the level of ROS through depleting glutathione in cell. • ATM–Chk1/2–Cdc25C were involved in Jaridonin-induced cell cycle arrest. • Jaridonin selectively inhibited cancer cell viability and cell cycle progression.

  6. Jaridonin-induced G2/M phase arrest in human esophageal cancer cells is caused by reactive oxygen species-dependent Cdc2-tyr15 phosphorylation via ATM–Chk1/2–Cdc25C pathway

    International Nuclear Information System (INIS)

    Jaridonin, a novel diterpenoid from Isodon rubescens, has been shown previously to inhibit proliferation of esophageal squamous cancer cells (ESCC) through G2/M phase cell cycle arrest. However, the involved mechanism is not fully understood. In this study, we found that the cell cycle arrest by Jaridonin was associated with the increased expression of phosphorylation of ATM at Ser1981 and Cdc2 at Tyr15. Jaridonin also resulted in enhanced phosphorylation of Cdc25C via the activation of checkpoint kinases Chk1 and Chk2, as well as in increased phospho-H2A.X (Ser139), which is known to be phosphorylated by ATM in response to DNA damage. Furthermore, Jaridonin-mediated alterations in cell cycle arrest were significantly attenuated in the presence of NAC, implicating the involvement of ROS in Jaridonin's effects. On the other hand, addition of ATM inhibitors reversed Jaridonin-related activation of ATM and Chk1/2 as well as phosphorylation of Cdc25C, Cdc2 and H2A.X and G2/M phase arrest. In conclusion, these findings identified that Jaridonin-induced cell cycle arrest in human esophageal cancer cells is associated with ROS-mediated activation of ATM–Chk1/2–Cdc25C pathway. - Highlights: • Jaridonin induced G2/M phase arrest through induction of redox imbalance. • Jaridonin increased the level of ROS through depleting glutathione in cell. • ATM–Chk1/2–Cdc25C were involved in Jaridonin-induced cell cycle arrest. • Jaridonin selectively inhibited cancer cell viability and cell cycle progression

  7. The Use of Modular Computer-Based Lessons in a Modification of the Classical Introductory Course in Organic Chemistry.

    Science.gov (United States)

    Stotter, Philip L.; Culp, George H.

    An experimental course in organic chemistry utilized computer-assisted instructional (CAI) techniques. The CAI lessons provided tutorial drill and practice and simulated experiments and reactions. The Conversational Language for Instruction and Computing was used, along with a CDC 6400-6600 system; students scheduled and completed the lessons at…

  8. New role for Cdc14 phosphatase: localization to basal bodies in the oomycete phytophthora and its evolutionary coinheritance with eukaryotic flagella.

    Directory of Open Access Journals (Sweden)

    Audrey M V Ah-Fong

    Full Text Available Cdc14 protein phosphatases are well known for regulating the eukaryotic cell cycle, particularly during mitosis. Here we reveal a distinctly new role for Cdc14 based on studies of the microbial eukaryote Phytophthora infestans, the Irish potato famine agent. While Cdc14 is transcribed constitutively in yeast and animal cells, the P. infestans ortholog is expressed exclusively in spore stages of the life cycle and not in vegetative hyphae where the bulk of mitosis takes place. PiCdc14 expression is first detected in nuclei at sporulation, and during zoospore formation the protein accumulates at the basal body, which is the site from which flagella develop. The association of PiCdc14 with basal bodies was supported by co-localization studies with the DIP13 basal body protein and flagellar β-tubulin, and by demonstrating the enrichment of PiCdc14 in purified flagella-basal body complexes. Overexpressing PiCdc14 did not cause defects in growth or mitosis in hyphae, but interfered with cytoplasmic partitioning during zoosporogenesis. This cytokinetic defect might relate to its ability to bind microtubules, which was shown using an in vitro cosedimentation assay. The use of gene silencing to reveal the precise function of PiCdc14 in flagella is not possible since we showed previously that silencing prevents the formation of the precursor stage, sporangia. Nevertheless, the association of Cdc14 with flagella and basal bodies is consistent with their phylogenetic distribution in eukaryotes, as species that lack the ability to produce flagella generally also lack Cdc14. An ancestral role of Cdc14 in the flagellar stage of eukaryotes is thereby proposed.

  9. Stage-specific functions of the small Rho GTPases Cdc42 and Rac1 for adult hippocampal neurogenesis

    DEFF Research Database (Denmark)

    Vadodaria, Krishna C; Brakebusch, Cord; Suter, Ueli;

    2013-01-01

    The molecular mechanisms underlying the generation, maturation, and integration of new granule cells generated throughout life in the mammalian hippocampus remain poorly understood. Small Rho GTPases, such as Cdc42 and Rac1, have been implicated previously in neural stem/progenitor cell (NSPC......) proliferation and neuronal maturation during embryonic development. Here we used conditional genetic deletion and virus-based loss-of-function approaches to identify temporally distinct functions for Cdc42 and Rac1 in adult hippocampal neurogenesis. We found that Cdc42 is involved in mouse NSPC proliferation......, initial dendritic development, and dendritic spine maturation. In contrast, Rac1 is dispensable for early steps of neuronal development but is important for late steps of dendritic growth and spine maturation. These results establish cell-autonomous and stage-specific functions for the small Rho GTPases...

  10. Tendances Carbone no. 82 'A 2030 framework for climate and energy policies: CDC Climat Research's answer'

    International Nuclear Information System (INIS)

    Among the publications of CDC Climat Research, 'Tendances Carbone' bulletin specifically studies the developments of the European market for CO2 allowances. This issue addresses the following points: To establish a climate and energy policy in the EU in 2030, CDC Climat Research addresses three main recommendations to the European Commission: (1) Establish a binding, single and ambitious CO2 emission reduction target of at least 40% in 2030. (2) Put the EU ETS as the central and non-residual instrument aimed at promoting cost-effective reductions in Europe and other parts of the world. (3) Define a stable, predictable and flexible climate regulation to limit carbon leakage and encourage innovation. Key drivers of the European carbon price this month: - The European Parliament has adopted Back-loading: 1.85 billion EUAs will be sold at auction between now and 2015 instead of 2.75 billion; - Phase 2 compliance: a surplus of 1,742 million tonnes (excluding the aviation sector) including auctions. - Energy Efficiency Directive: 22 of the 27 Member States have forwarded indicative targets for 2020 to the European Commission; these targets will be assessed in early 2014

  11. Translation and validation of the Dutch language version of the CDC Symptom Inventory for assessment of Chronic Fatigue Syndrome (CFS

    Directory of Open Access Journals (Sweden)

    Vermeulen Ruud CW

    2006-10-01

    Full Text Available Abstract Background In a study by Wagner et al., the CDC Symptom Inventory was validated in a population selected from the inhabitants of a city in the USA, and proofed reliable for the assessment of the accompanying symptoms of CFS. The Dutch translation of the CDC Symptom Inventory is compared to the original and the psychometric properties are presented for patients in a tertiary care setting. Methods One hundred thirty-nine consecutive patients who visited the CFS Center Amsterdam for the first time were asked to complete the CDC Symptom Inventory in the Dutch Language Version (DLV together with the usual set of questionnaires. Sixty-one patients had Chronic Fatigue (CF and 78 patients fulfilled the criteria for CFS. Forty-three healthy accompanying persons completed the CDC Symptom Inventory DLV, the Physical Functioning scale of the Medical Outcome Survey Short Form-36 DLV, and the Fatigue and Concentration scales of the Checklist Individual Strength (CIS-20. Results The healthy controls group contained fewer women and was overall older than the patient groups. The influence of gender on the CDC Symptom Inventory DLV was significant but the effect of age was not. The Dutch version had a good internal consistency and convergent validity. The results were comparable to the original English version, but the sex-related difference needs further study. Conclusion The Dutch version of the CDC Symptom Inventory is a reliable tool for the assessment of the secondary criteria for CFS. The results show that it is comparable to the outcome of studies in English speaking countries.

  12. A Putative Homologue of CDC20/CDH1 in the Malaria Parasite Is Essential for Male Gamete Development

    OpenAIRE

    Guttery, David S; Ferguson, David J. P.; Benoit Poulin; Zhengyao Xu; Ursula Straschil; Onny Klop; Lev Solyakov; Sandrini, Sara M.; Declan Brady; Nieduszynski, Conrad A.; Chris J. Janse; Holder, Anthony A.; Tobin, Andrew B.; Rita Tewari

    2012-01-01

    Cell-cycle progression is governed by a series of essential regulatory proteins. Two major regulators are cell-division cycle protein 20 (CDC20) and its homologue, CDC20 homologue 1 (CDH1), which activate the anaphase-promoting complex/cyclosome (APC/C) in mitosis, and facilitate degradation of mitotic APC/C substrates. The malaria parasite, Plasmodium, is a haploid organism which, during its life-cycle undergoes two stages of mitosis; one associated with asexual multiplication and the other ...

  13. Yeast 2-microns plasmid DNA replication in vitro: purification of the CDC8 gene product by complementation assay.

    OpenAIRE

    Arendes, J; Kim, K. C.; Sugino, A

    1983-01-01

    Extracts of the yeast Saccharomyces cerevisiae support DNA replication on exogenous yeast 2-microns plasmid DNA templates. A crude extract from a S. cerevisiae cell division cycle mutant, cdc8-1, expressed the temperature-sensitive phenotype since it could be inactivated at 42 degrees C in vitro. This heat-inactivated extract was fully complemented by the addition of either wild-type or cdc8-1 single-stranded DNA binding protein (SSB). restoration by SSB of the activity of the mutant cell ext...

  14. Rac1 and Cdc42 GTPases regulate shear stress-driven β-catenin signaling in osteoblasts

    International Nuclear Information System (INIS)

    Highlights: •Shear stress increased TCF/LEF activity and stimulated β-catenin nuclear localization. •Rac1, Cdc42, and RhoA displayed distinct dynamic activity patterns under flow. •Rac1 and Cdc42, but not RhoA, regulate shear stress-driven TCF/LEF activation. •Cytoskeleton did not significantly affect shear stress-induced TCF/LEF activation. -- Abstract: Beta-catenin-dependent TCF/LEF (T-cell factor/lymphocyte enhancing factor) is known to be mechanosensitive and an important regulator for promoting bone formation. However, the functional connection between TCF/LEF activity and Rho family GTPases is not well understood in osteoblasts. Herein we investigated the molecular mechanisms underlying oscillatory shear stress-induced TCF/LEF activity in MC3T3-E1 osteoblast cells using live cell imaging. We employed fluorescence resonance energy transfer (FRET)-based and green fluorescent protein (GFP)-based biosensors, which allowed us to monitor signal transduction in living cells in real time. Oscillatory (1 Hz) shear stress (10 dynes/cm2) increased TCF/LEF activity and stimulated translocation of β-catenin to the nucleus with the distinct activity patterns of Rac1 and Cdc42. The shear stress-induced TCF/LEF activity was blocked by the inhibition of Rac1 and Cdc42 with their dominant negative mutants or selective drugs, but not by a dominant negative mutant of RhoA. In contrast, constitutively active Rac1 and Cdc42 mutants caused a significant enhancement of TCF/LEF activity. Moreover, activation of Rac1 and Cdc42 increased the basal level of TCF/LEF activity, while their inhibition decreased the basal level. Interestingly, disruption of cytoskeletal structures or inhibition of myosin activity did not significantly affect shear stress-induced TCF/LEF activity. Although Rac1 is reported to be involved in β-catenin in cancer cells, the involvement of Cdc42 in β-catenin signaling in osteoblasts has not been identified. Our findings in this study demonstrate that

  15. Rac1 and Cdc42 GTPases regulate shear stress-driven β-catenin signaling in osteoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Wan, Qiaoqiao; Cho, Eunhye [Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202 (United States); Yokota, Hiroki [Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202 (United States); Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202 (United States); Na, Sungsoo, E-mail: sungna@iupui.edu [Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202 (United States)

    2013-04-19

    Highlights: •Shear stress increased TCF/LEF activity and stimulated β-catenin nuclear localization. •Rac1, Cdc42, and RhoA displayed distinct dynamic activity patterns under flow. •Rac1 and Cdc42, but not RhoA, regulate shear stress-driven TCF/LEF activation. •Cytoskeleton did not significantly affect shear stress-induced TCF/LEF activation. -- Abstract: Beta-catenin-dependent TCF/LEF (T-cell factor/lymphocyte enhancing factor) is known to be mechanosensitive and an important regulator for promoting bone formation. However, the functional connection between TCF/LEF activity and Rho family GTPases is not well understood in osteoblasts. Herein we investigated the molecular mechanisms underlying oscillatory shear stress-induced TCF/LEF activity in MC3T3-E1 osteoblast cells using live cell imaging. We employed fluorescence resonance energy transfer (FRET)-based and green fluorescent protein (GFP)-based biosensors, which allowed us to monitor signal transduction in living cells in real time. Oscillatory (1 Hz) shear stress (10 dynes/cm{sup 2}) increased TCF/LEF activity and stimulated translocation of β-catenin to the nucleus with the distinct activity patterns of Rac1 and Cdc42. The shear stress-induced TCF/LEF activity was blocked by the inhibition of Rac1 and Cdc42 with their dominant negative mutants or selective drugs, but not by a dominant negative mutant of RhoA. In contrast, constitutively active Rac1 and Cdc42 mutants caused a significant enhancement of TCF/LEF activity. Moreover, activation of Rac1 and Cdc42 increased the basal level of TCF/LEF activity, while their inhibition decreased the basal level. Interestingly, disruption of cytoskeletal structures or inhibition of myosin activity did not significantly affect shear stress-induced TCF/LEF activity. Although Rac1 is reported to be involved in β-catenin in cancer cells, the involvement of Cdc42 in β-catenin signaling in osteoblasts has not been identified. Our findings in this study demonstrate

  16. Mechanisms controlling the temporal degradation of Nek2A and Kif18A by the APC/C-Cdc20 complex

    DEFF Research Database (Denmark)

    Sedgwick, G.G.; Hayward, D.G.; Nilsson, J.; Di Fiore, B.; Pines, J.; Pardo, Mercedes; Yu, L.

    2013-01-01

    The Anaphase Promoting Complex/Cyclosome (APC/C) in complex with its co-activator Cdc20 is responsible for targeting proteins for ubiquitin-mediated degradation during mitosis. The activity of APC/C-Cdc20 is inhibited during prometaphase by the Spindle Assembly Checkpoint (SAC) yet certain substr...

  17. 13 CFR 120.839 - Case-by-case application to make a 504 loan outside of a CDC's Area of Operations.

    Science.gov (United States)

    2010-01-01

    .... The CDC's Risk Rating, among other factors, will be considered in determining satisfactory SBA... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Case-by-case application to make a 504 loan outside of a CDC's Area of Operations. 120.839 Section 120.839 Business Credit and...

  18. The regulatory beta-subunit of protein kinase CK2 accelerates the degradation of CDC25A phosphatase through the checkpoint kinase Chk1

    DEFF Research Database (Denmark)

    Kreutzer, Jan Nicolas; Guerra, Barbara

    2007-01-01

    Human CDC25 phosphatases play an important role in cell cycle regulation by removing inhibitory phosphate groups on cyclin-CDKs. Chk1 has been shown to phosphorylate CDC25 family members down-regulating their phosphatase activity through distinct mechanisms. The kinase activity of Chk1 is evident...... cell cycle progression is shown to enhance CDC25A degradation, and this occurs in a manner similar to that by which CDC25A is down-regulated upon activation of cellular checkpoint responses. By using RNA interference to specifically deplete cells of Chk1, we demonstrate that Chk1 mediates the down-regulation...... cell cycle regulation and indicate the mechanism by which CDC25A turnover might be regulated by Chk1 in the absence of DNA damage....

  19. Proper Regulation of Cdc42 Activity is Required for Tight Actin Concentration at the Equator during Cytokinesis in Adherent Mammalian Cells

    Science.gov (United States)

    Zhu, Xiaodong; Wang, Junxia; Moriguchi, Kazuki; Liow, Lu Ting; Ahmed, Sohail; Kaverina, Irina; Murata-Hori, Maki

    2012-01-01

    Cytokinesis in mammalian cells requires actin assembly at the equatorial region. Although functions of RhoA in this process have been well established, additional mechanisms are likely involved. We have examined if Cdc42 is involved in actin assembly during cytokinesis. Depletion of Cdc42 had no apparent effects on the duration of cytokinesis, while overexpression of constitutively active Cdc42 (CACdc42) caused cytokinesis failure in normal rat kidney epithelial cells. Cells depleted of Cdc42 displayed abnormal cell morphology and caused a failure of tight accumulation of actin and RhoA at the equator. In contrast, in cells overexpressing CACdc42, actin formed abnormal bundles and RhoA was largely eliminated from the equator. Our results suggest that accurate regulation of Cdc42 activity is crucial for proper equatorial actin assembly and RhoA localization during cytokinesis. Notably, our observations also suggest that tight actin concentration is not essential for cytokinesis in adherent mammalian cells. PMID:21763307

  20. On-line satellite/central computer facility of the Multiparticle Argo Spectrometer System

    International Nuclear Information System (INIS)

    An on-line satellite/central computer facility has been developed at Brookhaven National Laboratory as part of the Multiparticle Argo Spectrometer System (MASS). This facility consisting of a PDP-9 and a CDC-6600, has been successfully used in study of proton-proton interactions at 28.5 GeV/c. (U.S.)

  1. A computer program for the generation of logic networks from task chart data

    Science.gov (United States)

    Herbert, H. E.

    1980-01-01

    The Network Generation Program (NETGEN), which creates logic networks from task chart data is presented. NETGEN is written in CDC FORTRAN IV (Extended) and runs in a batch mode on the CDC 6000 and CYBER 170 series computers. Data is input via a two-card format and contains information regarding the specific tasks in a project. From this data, NETGEN constructs a logic network of related activities with each activity having unique predecessor and successor nodes, activity duration, descriptions, etc. NETGEN then prepares this data on two files that can be used in the Project Planning Analysis and Reporting System Batch Network Scheduling program and the EZPERT graphics program.

  2. 75 FR 22145 - Health Resources and Services Administration (HRSA); CDC/HRSA Advisory Committee on HIV and STD...

    Science.gov (United States)

    2010-04-27

    ... (HRSA); CDC/HRSA Advisory Committee on HIV and STD Prevention and Treatment (CHACHSPT) In accordance... the Administrator, HRSA, regarding activities related to the prevention and control of HIV/AIDS and other STDs, the support of healthcare services to persons living with HIV/AIDS, and the education...

  3. Cdc42 is crucial for the maturation of primordial cell junctions in keratinocytes independent of Rac1

    DEFF Research Database (Denmark)

    Du, Dan; Pedersen, Esben; Wang, Zhipeng;

    2008-01-01

    -deficient immortalized and primary keratinocytes form only punctate primordial cell contacts in vitro, which cannot mature into belt-like junctions. This defect was independent of enhanced degradation of beta-catenin, but correlated to an impaired activation and localization of aPKCzeta in the Cdc42-null...

  4. 76 FR 54773 - Notice of Intent To Award Affordable Care Act Funding, Funding Opportunity Announcement CDC-RFA...

    Science.gov (United States)

    2011-09-02

    ..., for programs authorized by the public Health Services Act, for prevention, wellness and public health... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND... Prevention (CDC), Department of Health and Human Services (HHS). ACTION: Notice. SUMMARY: This...

  5. 78 FR 32392 - CDC/HRSA Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment

    Science.gov (United States)

    2013-05-30

    ... CDC/HRSA Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment In accordance... Administrator, HRSA, regarding activities related to prevention and control of HIV/AIDS, Viral Hepatitis and... professionals and the public about HIV/AIDS, Viral Hepatitis and other STDs. Matters To Be Discussed:...

  6. 78 FR 64221 - CDC/HRSA Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment; Notice of...

    Science.gov (United States)

    2013-10-28

    ... meeting. Name: CDC/HRSA Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment Dates... related to prevention and control of HIV/AIDS, Viral Hepatitis and other STDs, the support of health care.../AIDS, Viral Hepatitis, and other STDs. Agenda: Agenda items include: (1) Affordable Care Act...

  7. Chloride-dependent acceleration of cell cycle via modulation of Rb and cdc2 in osteoblastic cells

    International Nuclear Information System (INIS)

    In the present study, we investigated if Cl- regulates the proliferation of the MC3T3-E1 osteoblastic cells. The proliferation of MC3T3-E1 osteoblastic cells was diminished by lowering the extracellular Cl- concentration ([Cl-]o) in the culture medium. The lowered in [Cl-]o increased the periods of the G0/G1 and the G2/M phases in cell cycle. We further studied the effects of [Cl-]o on the key enzymes, Rb and cdc2, playing key roles in checking points of the G0/G1 and the G2/M phases in cell cycle. The lowered in [Cl-]o diminished the active forms of enzymes, Rb and cdc2. We further found that the action of lowered [Cl-]o on the cell proliferation, the cell cycle, Rb and cdc2 was abolished by the presence of 2 mM glutamine, but not by that of pyruvate as another Krebs cycle substrate. Taken together, these observations indicate here for the first time that Cl- modulates Rb and cdc2, enhancing the proliferation of the MC3T3-E1 osteoblastic cells

  8. 75 FR 63844 - Health Resources and Services Administration CDC/HRSA Advisory Committee on HIV and STD...

    Science.gov (United States)

    2010-10-18

    ... the National HIV/AIDS Strategy; (2) CHACHSPT Realignment Program Review Workgroup update; (3) update..., and TB Prevention, 1600 Clifton Road, NE., Mailstop E-07, Atlanta, Georgia 30333, Telephone (404) 639... CDC/HRSA Advisory Committee on HIV and STD Prevention and Treatment (CHACHSPT) In accordance...

  9. 75 FR 72831 - Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)-Ethics...

    Science.gov (United States)

    2010-11-26

    ...), Centers for Disease Control and Prevention (CDC)--Ethics Subcommittee (ES) In accordance with section 10(a... broad range of public health ethics questions and issues arising from programs, scientists and... preliminary overview to the ACD on ethical issues related to non-communicable disease prevention and...

  10. 77 FR 34046 - Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)-Ethics...

    Science.gov (United States)

    2012-06-08

    ...), Centers for Disease Control and Prevention (CDC)--Ethics Subcommittee (ES) In accordance with section 10(a... of public health ethics questions and issues arising from programs, scientists and practitioners. Matters To Be Discussed: Agenda items will include the following: Addition of ethics standards to...

  11. 76 FR 3909 - Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)-Ethics...

    Science.gov (United States)

    2011-01-21

    ...), Centers for Disease Control and Prevention (CDC)--Ethics Subcommittee (ES) In accordance with section 10(a... ethics questions and issues arising from programs, scientists and practitioners. Matter To Be Discussed: Agenda items will include the following: A review of public comments submitted on the...

  12. 76 FR 57744 - Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)-Ethics...

    Science.gov (United States)

    2011-09-16

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)--Ethics Subcommittee (ES) Correction: This notice...

  13. 76 FR 55678 - Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)-Ethics...

    Science.gov (United States)

    2011-09-08

    ...), Centers for Disease Control and Prevention (CDC)--Ethics Subcommittee (ES) In accordance with section 10(a..., regarding a broad range of public health ethics questions and issues arising from programs, scientists and... ethics challenges. The agenda is subject to change as priorities dictate. Contact Person for...

  14. Announcement: Release of CDC's 2016 Model Aquatic Health Code, Second Edition and Revised Hyperchlorination and Fecal Incident Response Recommendations.

    Science.gov (United States)

    2016-01-01

    The 2016 Model Aquatic Health Code (MAHC), Second Edition was released on July 15, 2016 (http://www.cdc.gov/mahc/editions/current.html). MAHC is national guidance that can be voluntarily adopted by state and local jurisdictions to minimize the risk for illness and injury at public aquatic facilities through facility design, construction, operation, maintenance, and management. PMID:27442593

  15. Cdc42 and Rab8a are critical for intestinal stem cell division, survival, and differentiation in mice

    DEFF Research Database (Denmark)

    Sakamori, Ryotaro; Das, Soumyashree; Yu, Shiyan; Feng, Shanshan; Stypulkowski, Ewa; Guan, Yinzheng; Douard, Veronique; Tang, Waixing; Ferraris, Ronaldo P; Harada, Akihiro; Brakebusch, Cord; Guo, Wei; Gao, Nan

    2012-01-01

    reminiscent of human microvillus inclusion disease (MVID), a devastating congenital intestinal disorder that results in severe nutrient deprivation. Further analysis revealed that Cdc42-deficient stem cells had cell division defects, reduced capacity for clonal expansion and differentiation into Paneth cells...

  16. Cdc50p plays a vital role in the ATPase reaction cycle of the putative aminophospholipid transporter Drs2p.

    Science.gov (United States)

    Lenoir, Guillaume; Williamson, Patrick; Puts, Catheleyne F; Holthuis, Joost C M

    2009-07-01

    Members of the P(4) subfamily of P-type ATPases are believed to catalyze transport of phospholipids across cellular bilayers. However, most P-type ATPases pump small cations or metal ions, and atomic structures revealed a transport mechanism that is conserved throughout the family. Hence, a challenging problem is to understand how this mechanism is adapted in P(4)-ATPases to flip phospholipids. P(4)-ATPases form heteromeric complexes with Cdc50 proteins. The primary role of these additional polypeptides is unknown. Here, we show that the affinity of yeast P(4)-ATPase Drs2p for its Cdc50-binding partner fluctuates during the transport cycle, with the strongest interaction occurring at a point where the enzyme is loaded with phospholipid ligand. We also find that specific interactions with Cdc50p are required to render the ATPase competent for phosphorylation at the catalytically important aspartate residue. Our data indicate that Cdc50 proteins are integral components of the P(4)-ATPase transport machinery. Thus, acquisition of these subunits may have been a crucial step in the evolution of flippases from a family of cation pumps. PMID:19411703

  17. CDC: Consejos de exfumadores: El Consejo de Jessica Sobre el Asma PSA (:30)

    Centers for Disease Control (CDC) Podcasts

    2012-03-19

    La exposición al humo de segunda mano puede provocar un ataque de asma que puede ser mortal. Este anuncio de servicio público de 30 segundos de la campaña de los CDC “Consejos de exfumadores”, muestra a Jessica, la madre de un niño pequeño que tiene ataques de asma por la exposición al humo de segunda mano. Su consejo es que las personas no sientan pena de decirles a otras que no fumen cerca de sus hijos.  Created: 3/19/2012 by Office on Smoking and Health, National Center for Chronic Disease Prevention and Health Promotion.   Date Released: 8/8/2013.

  18. CDC Signos Vitales-Una pastilla diaria puede prevenir el VIH (Daily Pill Can Prevent HIV)

    Centers for Disease Control (CDC) Podcasts

    2015-11-24

    Este podcast se basa en la edición del 24 de noviembre del 2015 del informe Signos Vitales de los CDC. La profilaxis prexposición, o PrEP, es un medicamento diario que se puede usar para prevenir contraer el VIH. La PrEP es para las personas que no tienen el VIH, pero que están en alto riesgo de contraerlo mediante las relaciones sexuales o el consumo de drogas inyectables. Desafortunadamente, muchas de las personas que se pueden beneficiar de la PrEP no la están tomando.  Created: 11/24/2015 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 11/24/2015.

  19. Signos Vitales de los CDC-Epidemia de heroína (Heroin Epidemic)

    Centers for Disease Control (CDC) Podcasts

    2015-07-07

    Este podcast se basa en la edición de julio del informe Signos Vitales de los CDC. El consumo de heroína y las muertes por sobredosis relacionadas con esta droga están aumentando. La mayoría de las personas están consumiendo heroína con otras drogas, especialmente analgésicos opioides recetados. Sepa qué se puede hacer para prevenir y tratar el problema.  Created: 7/7/2015 by National Center for Injury Prevention and Control (NCIPC).   Date Released: 7/7/2015.

  20. CDC Signos Vitales-La prevención del melanoma (Preventing Melanoma)

    Centers for Disease Control (CDC) Podcasts

    2015-06-02

    Este podcast se basa en la edición de junio del 2015 del informe Signos Vitales de los CDC. El cáncer de piel es el tipo de cáncer más común en los Estados Unidos. En el 2011, hubo más de 65 000 casos de melanoma, el tipo de cáncer de piel más mortal. Sepa cómo todos pueden ayudar a prevenir el cáncer de piel.  Created: 6/2/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 6/2/2015.

  1. CDC Signos Vitales-La salud de los hispanos (Hispanic Health)

    Centers for Disease Control (CDC) Podcasts

    2015-05-05

    Este podcast se basa en la edición de mayo del 2015 del informe Signos Vitales de los CDC. Cerca de una de cada seis personas que viven en los EE. UU. son hispanas. Las dos causas principales de muerte en este grupo son las enfermedades cardiacas y el cáncer, lo que representa dos de cada cinco muertes. Desafortunadamente, muchos hispanos enfrentan barreras considerables para obtener atención médica de alta calidad, como las barreras del idioma y los bajos ingresos. Sepa qué se puede hacer para reducirlas.  Created: 5/5/2015 by Office of Minority Health & Health Equity (OMHHE).   Date Released: 5/5/2015.

  2. CDC Signos Vitales-Edad del corazón (Heart Age)

    Centers for Disease Control (CDC) Podcasts

    2015-09-01

    Este podcast se basa en la edición de septiembre del 2015 del informe Signos Vitales de los CDC. La "edad del corazón" es la edad que tienen su corazón y vasos sanguíneos como resultado de sus factores de riesgo de ataque cardiaco y accidente cerebrovascular. Si usted fuma o tiene la presión arterial alta, la edad de su corazón será mucho mayor que su edad real. Sepa qué puede hacer para disminuir la edad de su corazón y mantenerla baja.  Created: 9/1/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 9/1/2015.

  3. Psychometric properties of the CDC Symptom Inventory for assessment of Chronic Fatigue Syndrome

    Directory of Open Access Journals (Sweden)

    Unger Elizabeth R

    2005-07-01

    Full Text Available Abstract Objectives Validated or standardized self-report questionnaires used in research studies and clinical evaluation of chronic fatigue syndrome (CFS generally focus on the assessment of fatigue. There are relatively few published questionnaires that evaluate case defining and other accompanying symptoms in CFS. This paper introduces the self-report CDC CFS Symptom Inventory and analyzes its psychometric properties. Methods One hundred sixty-four subjects (with CFS, other fatiguing illnesses and non fatigued controls identified from the general population of Wichita, Kansas were enrolled. Evaluation included a physical examination, a standardized psychiatric interview, three previously validated self-report questionnaires measuring fatigue and illness impact (Medical Outcomes Survey Short-Form-36 [MOS SF-36], Multidimensional Fatigue Inventory [MFI], Chalder Fatigue Scale, and the CDC CFS Symptom Inventory. Based on theoretical assumptions and statistical analyses, we developed several different Symptom Inventory scores and evaluated them on their ability to differentiate between participants with CFS and non-fatigued controls. Results The Symptom Inventory had good internal consistency and excellent convergent validity. A Total score (all symptoms, Case Definition score (CFS case defining symptoms and Short Form score (6 symptoms with minimal correlation differentiated CFS cases from controls. Furthermore, both the Case Definition and Short Form scores distinguished people with CFS from fatigued subjects who did not meet criteria for CFS. Conclusion The Symptom Inventory appears to be a reliable and valid instrument to assess symptoms that accompany CFS. It is a positive addition to existing instruments measuring fatigue because it allows other dimensions of the illness to be assessed. Further research is needed to confirm and replicate the current findings in a normative population.

  4. Crystal structure of the karyopherin Kap121p bound to the extreme C-terminus of the protein phosphatase Cdc14p

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Junya [Division of Biological Science, Graduate School of Science, Nagoya University (Japan); Hirano, Hidemi [Division of Biological Science, Graduate School of Science, Nagoya University (Japan); Structural Biology Research Center, Graduate School of Science, Nagoya University (Japan); Matsuura, Yoshiyuki, E-mail: matsuura.yoshiyuki@d.mbox.nagoya-u.ac.jp [Division of Biological Science, Graduate School of Science, Nagoya University (Japan); Structural Biology Research Center, Graduate School of Science, Nagoya University (Japan)

    2015-07-31

    In Saccharomyces cerevisiae, the protein phosphatase Cdc14p is an antagonist of mitotic cyclin-dependent kinases and is a key regulator of late mitotic events such as chromosome segregation, spindle disassembly and cytokinesis. The activity of Cdc14p is controlled by cell-cycle dependent changes in its association with its competitive inhibitor Net1p (also known as Cfi1p) in the nucleolus. For most of the cell cycle up to metaphase, Cdc14p is sequestered in the nucleolus in an inactive state. During anaphase, Cdc14p is released from Net1p, spreads into the nucleus and cytoplasm, and dephosphorylates key mitotic targets. Although regulated nucleocytoplasmic shuttling of Cdc14p has been suggested to be important for exit from mitosis, the mechanism underlying Cdc14p nuclear trafficking remains poorly understood. Here we show that the C-terminal region (residues 517–551) of Cdc14p can function as a nuclear localization signal (NLS) in vivo and also binds to Kap121p (also known as Pse1p), an essential nuclear import carrier in yeast, in a Gsp1p-GTP-dependent manner in vitro. Moreover we report a crystal structure, at 2.4 Å resolution, of Kap121p bound to the C-terminal region of Cdc14p. The structure and structure-based mutational analyses suggest that either the last five residues at the extreme C-terminus of Cdc14p (residues 547–551; Gly-Ser-Ile-Lys-Lys) or adjacent residues with similar sequence (residues 540–544; Gly-Gly-Ile-Arg-Lys) can bind to the NLS-binding site of Kap121p, with two residues (Ile in the middle and Lys at the end of the five residues) of Cdc14p making key contributions to the binding specificity. Based on comparison with other structures of Kap121p-ligand complexes, we propose “IK-NLS” as an appropriate term to refer to the Kap121p-specific NLS. - Highlights: • The C-terminus of Cdc14p binds to Kap121p in a Gsp1p-GTP-dependent manner. • The crystal structure of Kap121p-Cdc14p complex is determined. • The structure reveals how

  5. Crystal structure of the karyopherin Kap121p bound to the extreme C-terminus of the protein phosphatase Cdc14p

    International Nuclear Information System (INIS)

    In Saccharomyces cerevisiae, the protein phosphatase Cdc14p is an antagonist of mitotic cyclin-dependent kinases and is a key regulator of late mitotic events such as chromosome segregation, spindle disassembly and cytokinesis. The activity of Cdc14p is controlled by cell-cycle dependent changes in its association with its competitive inhibitor Net1p (also known as Cfi1p) in the nucleolus. For most of the cell cycle up to metaphase, Cdc14p is sequestered in the nucleolus in an inactive state. During anaphase, Cdc14p is released from Net1p, spreads into the nucleus and cytoplasm, and dephosphorylates key mitotic targets. Although regulated nucleocytoplasmic shuttling of Cdc14p has been suggested to be important for exit from mitosis, the mechanism underlying Cdc14p nuclear trafficking remains poorly understood. Here we show that the C-terminal region (residues 517–551) of Cdc14p can function as a nuclear localization signal (NLS) in vivo and also binds to Kap121p (also known as Pse1p), an essential nuclear import carrier in yeast, in a Gsp1p-GTP-dependent manner in vitro. Moreover we report a crystal structure, at 2.4 Å resolution, of Kap121p bound to the C-terminal region of Cdc14p. The structure and structure-based mutational analyses suggest that either the last five residues at the extreme C-terminus of Cdc14p (residues 547–551; Gly-Ser-Ile-Lys-Lys) or adjacent residues with similar sequence (residues 540–544; Gly-Gly-Ile-Arg-Lys) can bind to the NLS-binding site of Kap121p, with two residues (Ile in the middle and Lys at the end of the five residues) of Cdc14p making key contributions to the binding specificity. Based on comparison with other structures of Kap121p-ligand complexes, we propose “IK-NLS” as an appropriate term to refer to the Kap121p-specific NLS. - Highlights: • The C-terminus of Cdc14p binds to Kap121p in a Gsp1p-GTP-dependent manner. • The crystal structure of Kap121p-Cdc14p complex is determined. • The structure reveals how

  6. Overview, Control Strategies, and Lessons Learned in the CDC Response to the 2014-2016 Ebola Epidemic.

    Science.gov (United States)

    Bell, Beth P; Damon, Inger K; Jernigan, Daniel B; Kenyon, Thomas A; Nichol, Stuart T; O'Connor, John P; Tappero, Jordan W

    2016-01-01

    During 2014-2016, CDC, working with U.S. and international partners, mounted a concerted response to end the unprecedented epidemic of Ebola virus disease (Ebola) in West Africa. CDC's response, which was the largest in the agency's history, was directed simultaneously at controlling the epidemic in West Africa and strengthening preparedness for Ebola in the United States. Although experience in responding to approximately 20 Ebola outbreaks since 1976 had provided CDC and other international responders an understanding of the disease and how to stop its spread, the epidemic in West Africa presented new and formidable challenges. The initial response was slow and complicated for several reasons, including wide geographic spread of cases, poor public health and societal infrastructure, sociodemographic factors, local unfamiliarity with Ebola, and distrust of government and health care workers. In the United States, widespread public alarm erupted after Ebola cases were diagnosed in Dallas, Texas, and New York City, New York. CDC, in collaboration with its U.S. and international counterparts, applied proven public health strategies as well as innovative new approaches to help control the Ebola epidemic in West Africa and strengthen public health readiness in the United States. Lessons learned include the recognition that West African and other countries need effective systems to detect and stop infectious disease threats, the need for stronger international surge capacity for times when countries are overwhelmed by an outbreak, and the importance of improving infection prevention and control in health care settings. The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html). PMID:27389903

  7. 细胞周期蛋白依赖性激酶cdc2与恶性肿瘤发生发展的研究

    Institute of Scientific and Technical Information of China (English)

    翟德忠; 黄强

    2006-01-01

    cdc2在细胞周期调控中起着调控G2至M期的作用.在G2期后期,cyclinB与cdc2结合,形成有丝分裂促进因子(MPF),再由cdc25、cyclin H、cdk7等一些磷酸酶和激酶作用,使其激活,活化的MPF通过cdc2对细胞核内组蛋白H1、核纤维层蛋白A、B、C、核仁蛋白nucleolin等蛋白发生直接或间接磷酸化作用,从而诱导产生一系列变化,使细胞发生有丝分裂.cdc2的过度表达或缺乏,可使细胞周期进程发生紊乱,不能正常生长、分化.cdc2过表达往往导致细胞恶性增殖,形成肿瘤.现已证明cdc2过度表达与许多恶性肿瘤的发生、发展、预后有关,但与神经干细胞、胶质瘤干细胞之间的关系尚待阐明.

  8. Morphological Analysis of CDC2 and Glycogen Synthase Kinase 3β Phosphorylation as Markers of G2 → M Transition in Glioma

    Directory of Open Access Journals (Sweden)

    José Javier Otero

    2011-01-01

    Full Text Available G2 → M transition is a strategic target for glioma chemotherapy. Key players in G2 → M transition include CDC2 and glycogen synthase kinase 3β (GSK3β, which are highly regulated by posttranslational phosphorylation. This report is a morphological analysis of CDC2 and GSK3β phosphorylation using immunohistochemistry in gliomas with different biological properties. GBM showed a 2.8-fold and 5.6-fold increase in number of cells positive for pThr161CDC2 and a 4.2- and 6.9-fold increase in number of cells positive for pTyr15CDC2 relative to oligodendroglioma and ependymoma, respectively. Elevated labeling for inhibited phospho-CDC2 (pTyr15CDC correlates with elevated levels of phosphorylated glycogen synthase kinase 3β (GSK3β. 71% of the GBM cases showed intermediate to high intensity staining for pSer9SGK3β 53% of oligodendroglioma, and 73% of ependymoma showed low intensity staining. CDC2 gene amplification correlates with increased survival in glioblastoma multiforme (GBM and astrocytoma WHO grades II-III, but not in oligodendroglioma WHO grades II-III.

  9. Brine: a computer program to compute brine migration adjacent to a nuclear waste canister in a salt repository

    International Nuclear Information System (INIS)

    This report presents a mathematical model used to predict brine migration toward a nuclear waste canister in a bedded salt repository. The mathematical model is implemented in a computer program called BRINE. The program is written in FORTRAN and executes in the batch mode on a CDC 7600. A description of the program input requirements and output available is included. Samples of input and output are given

  10. A comprehensive analysis of CDC20 overexpression in common malignant tumors from multiple organs: its correlation with tumor grade and stage.

    Science.gov (United States)

    Gayyed, Mariana F; El-Maqsoud, Nehad M R Abd; Tawfiek, Ehab Rifat; El Gelany, Saad Abdelnaby A; Rahman, Mohamed Fathy Abdel

    2016-01-01

    High expression of cell division cycle 20 homolog (CDC20), a key component of the spindle assembly checkpoint (SAC), has been reported in various malignancies and plays a vital role in tumorigenesis and progression. The goal of this study was to evaluate the utility of CDC20 immunostaining in a wide range of malignant tumors. CDC20 immunohistochemistry was evaluated in normal tissues and compared to the most frequently occurring malignant tumors in these tissues (bladder, breast, cervical, colonic, endometrial, gastric, head and neck, liver, lung, ovarian, pancreatic, prostatic, renal, thyroid carcinomas, and testicular seminoma). Normal/non-neoplastic tissues showed positive CDC20 expression in 19.44 % of all examined cases. CDC20 staining was negative in normal and non-neoplastic tissues from the bladder, cervix, liver, stomach, and thyroid. From the all malignant tumors examined 55.7 % showed high CDC20 expression while low expression was found in 44.3 %. High expression of CDC20 was associated with high tumor grade in the bladder (p = 0.027), cervical (p = 0.032), colonic (p = 0.026), endometrial (p = 0.016), gastric (p = 0.033), liver (p = 0.028), ovarian (p = 0.044), prostatic (p = 0.040), and renal (p = 0.048) carcinomas. There was a significant correlation between high CDC20 expression and advanced tumor stage in carcinoma of the breast, colon, endometrium, and prostate (p = 0.021, p = 0.040, p = 0.047, p = 0.031, respectively). CDC20 expression may be useful as a biomarker of tumor prognosis and as a therapeutic target of human cancer. PMID:26245990

  11. National MFE computer center: increased capability in 1978

    International Nuclear Information System (INIS)

    The National Magnetic Fusion Energy Computer Center at Livermore is greatly increasing its computing power and versatility through hardware acquisitions and concurrent software development. Most significant has been the arrival of the Cray-1 computer in April 1978, with its one-million-word semiconductor memory and vector processing rate of up to 250 million floating-point operations per second. Additional equipment now being installed includes a new 500-billion-bit CDC 38500 mass storage device, a Dicomed D48 graphic film recorder, and Systems Concepts 3350 staging disks

  12. User's manual for computer code SOLTES-1 (simulator of large thermal energy systems). [For CDC 6600

    Energy Technology Data Exchange (ETDEWEB)

    Fewell, M.E.; Grandjean, N.R.; Dunn, J.C.; Edenburn, M.W.

    1978-09-01

    SOLTES simulates the steady-state response of thermal energy systems to time-varying data such as weather and loads. Thermal energy system models of both simple and complex systems can easily be modularly constructed from a library of routines. These routines mathematically model solar collectors, pumps, switches, thermal energy storage, thermal boilers, auxiliary boilers, heat exchangers, extraction turbines, extraction turbine/generators, condensers, regenerative heaters, air conditioners, heating and cooling of buildings, process vapor, etc.; SOLTES also allows user-supplied routines. The analyst need only specify fluid names to obtain readout of property data for heat-transfer fluids and constants that characterize power-cycle working fluids from a fluid property data bank. A load management capability allows SOLTES to simulate total energy systems that simultaneously follow heat and power loads and demands. Generalized energy accounting is available, and values for system performance parameters may be automatically determined by SOLTES. Because of its modularity and flexibility, SOLTES can be used to simulate a wide variety of thermal energy systems such as solar power/total energy, fossil fuel power plants/total energy, nuclear power plants/total energy, solar energy heating and cooling, geothermal energy, and solar hot water heaters.

  13. [PKA-regulated phosphorylation status of S149 and S321 sites of CDC25B inhibits mitosis of fertilized mouse eggs].

    Science.gov (United States)

    Xiao, Jian-Ying; Liu, Chao; Sun, Xiao-Han; Yu, Bing-Zhi

    2012-02-25

    To further test whether protein kinase A (PKA) can affect the mitotic cell cycle, one-cell stage mouse embryos at S phase (22 h after hCG injection) were incubated in M16 medium containing various concentrations of H-89, a PKA inhibitor. With increasing concentrations of H-89 (0-50 μmol/L), the G(2) phase of eggs was decreased and the cleavage rate was accelerated. A concentration of 40 μmol/L H-89 led to all of the mouse eggs entering the M phase of mitosis. Furthermore, to study the role of PKA in regulating the phosphorylation status of S149 and S321 sites of cell division cycle 25B (CDC25B) on one-cell stage fertilized mouse eggs, pBSK-CDC25B-WT, pBSK-CDC25B-S149A, pBSK-CDC25B-S321A and pBSK-CDC25B-S149A/S321A were transcribed into mRNAs in vitro, then mRNAs were microinjected into S phase of mouse fertilized eggs and cultured in M16 medium pretreated with H-89. Then, the cleavage of fertilized eggs, maturation promoting factor (MPF) activity and phosphorylation status of CDC2-Tyr15 were observed. In the presence of 40 μmol/L H-89, the cleavage rate of fertilized eggs in CDC25B-S/A-mRNAs and CDC25B-WT-mRNA injected groups was significantly higher than that in the control groups, and the peak of MPF activity appeared in the CDC25B-S/A-mRNAs and CDC25B-WT-mRNA injected groups earlier than that in the control groups. CDC2-Tyr15 phosphorylation state was consistent with MPF activity. In conclusion, the present study suggests that PKA regulates the early development of mouse embryos by phosphorylation of S149 and S321 of CDC25B, which plays an important role in the regulation of G(2)/M transition in the mitotic cell cycle of fertilized mouse eggs. PMID:22348958

  14. Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A

    DEFF Research Database (Denmark)

    Sørensen, Claus Storgaard; Syljuåsen, Randi G; Falck, Jacob;

    2003-01-01

    Chk1 kinase coordinates cell cycle progression and preserves genome integrity. Here, we show that chemical or genetic ablation of human Chk1 triggered supraphysiological accumulation of the S phase-promoting Cdc25A phosphatase, prevented ionizing radiation (IR)-induced degradation of Cdc25A, and...... by a combined action of Chk1 and Chk2 kinases. Finally, phosphorylation of Chk1 by ATM was required to fully accelerate the IR-induced degradation of Cdc25A. Our results provide evidence that the mammalian S phase checkpoint functions via amplification of physiologically operating, Chk1-dependent...

  15. Suppression of the Schizosaccharomyces pombe cut12.1 Cell-Cycle Defect by Mutations in cdc25 and Genes Involved in Transcriptional and Translational Control

    OpenAIRE

    Tallada, Victor A.; Alan J Bridge; Emery, Patrick A.; Iain M Hagan

    2007-01-01

    Cdc25 phosphatase primes entry to mitosis by removing the inhibitory phosphate that is transferred to mitosis promoting factor (MPF) by Wee1 related kinases. A positive feedback loop then boosts Cdc25 and represses Wee1 activities to drive full-scale MPF activation and commitment to mitosis. Dominant mutations in the Schizosaccharomyces pombe spindle pole body (SPB) component Cut12 enable cdc25.22 mutants to overcome a G2 arrest at 36° and enter mitosis. The recessive temperature-sensitive cu...

  16. Health and Environment Linked for Information Exchange (HELIX)-Atlanta: A CDC-NASA Joint Environmental Public Health Tracking Collaborative Project

    Science.gov (United States)

    Al-Hamdan, Mohammad; Luvall, Jeff; Crosson, Bill; Estes, Maury; Limaye, Ashutosh; Quattrochi, Dale; Rickman, Doug

    2008-01-01

    HELIX-Atlanta was developed to support current and future state and local EPHT programs to implement data linking demonstration projects which could be part of the CDC EPHT Network. HELIX-Atlanta is a pilot linking project in Atlanta for CDC to learn about the challenges the states will encounter. NASA/MSFC and the CDC are partners in linking environmental and health data to enhance public health surveillance. The use of NASA technology creates value added geospatial products from existing environmental data sources to facilitate public health linkages. Proving the feasibility of the approach is the main objective

  17. MicroRNA-141 is downregulated in human renal cell carcinoma and regulates cell survival by targeting CDC25B

    Directory of Open Access Journals (Sweden)

    Yu XY

    2013-04-01

    Full Text Available Xiu-yue Yu, Zhe Zhang, Jiao Liu, Bo Zhan, Chui-ze Kong Department of Urology, the First Hospital of China Medical University, Shenyang, People’s Republic of China Background/objective: MicroRNAs (miRNAs are small noncoding RNAs (ribonucleic acids, approximately 22 nucleotides in length, that function as regulators of gene expression. Dysregulation of miRNAs has been associated with the initiation and progression of oncogenesis in humans. The cell division cycle (CDC25 phosphatases are important regulators of the cell cycle. Their abnormal expression detected in a number of tumors implies that their dysregulation is involved in malignant transformation. Methods: Using miRNA target prediction software, we found that miR-141 could target the 3´ untranslated region (3´UTR sequence of CDC25B. To shed light on the role of miR-141 in renal cell carcinogenesis, the expression of miR-141 was examined by real-time polymerase chain reaction (RT-PCR in renal cell carcinoma and normal tissues. The impact of miR-141 re-expression on 769-P cells was analyzed using 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT and colony-forming assay. A luciferase reporter assay was applied to prove the functionality of the miR-141 binding site. Results: miR-141 is significantly downregulated in renal cell carcinoma. miR-141 re-expression suppressed cell growth in 769-P cells. Luciferase expression from a reporter vector containing the CDC25B-3'UTR was decreased when this construct was transfected with miR-141 in 769-P cells. The overexpression of miR-141 suppressed the endogenous CDC25B protein level in 769-P cells. Conclusion: For the first time, we demonstrated that CDC25B is a direct target of miR-141 in renal cell carcinoma. The transcriptional loss of miR-141 and the resultant increase in CDC25B expression facilitates increased genomic instability at an early stage of renal cell carcinoma development. Keywords: carcinogenesis, 769-P, target, Micro

  18. "Know More Hepatitis:" CDC's National Education Campaign to Increase Hepatitis C Testing Among People Born Between 1945 and 1965.

    Science.gov (United States)

    Jorgensen, Cynthia; Carnes, C Amanda; Downs, Alycia

    2016-01-01

    In 2012, CDC issued recommendations calling for those born between 1945 and 1965, or baby boomers, to get tested for the hepatitis C virus. To help implement this recommendation, CDC developed "Know More Hepatitis," a multimedia national education campaign. Guided by behavioral science theories and formative research, the campaign used multiple strategies to reach baby boomers and health-care providers with messages encouraging baby boomers to get tested for hepatitis C. With a limited campaign budget, the "Know More Hepatitis" campaign relied mostly on donated time and space from broadcast and print outlets. Donated placements totaled approximately $14.7 million, which reflected a more than 12-to-1 return on the campaign investment. This effort was supplemented with a small, paid digital advertising campaign. Combining audience impressions from both paid and donated campaign efforts resulted in more than 1.2 billion audience impressions. PMID:27168658

  19. Molecular mechanisms of hypoxic responses via unique roles of Ras1, Cdc24 and Ptp3 in a human fungal pathogen Cryptococcus neoformans.

    Directory of Open Access Journals (Sweden)

    Yun C Chang

    2014-04-01

    Full Text Available Cryptococcus neoformans encounters a low oxygen environment when it enters the human host. Here, we show that the conserved Ras1 (a small GTPase and Cdc24 (the guanine nucleotide exchange factor for Cdc42 play an essential role in cryptococcal growth in hypoxia. Suppressor studies indicate that PTP3 functions epistatically downstream of both RAS1 and CDC24 in regulating hypoxic growth. Ptp3 shares sequence similarity to the family of phosphotyrosine-specific protein phosphatases and the ptp3Δ strain failed to grow in 1% O2. We demonstrate that RAS1, CDC24 and PTP3 function in parallel to regulate thermal tolerance but RAS1 and CDC24 function linearly in regulating hypoxic growth while CDC24 and PTP3 reside in compensatory pathways. The ras1Δ and cdc24Δ strains ceased to grow at 1% O2 and became enlarged but viable single cells. Actin polarization in these cells, however, was normal for up to eight hours after transferring to hypoxic conditions. Double deletions of the genes encoding Rho GTPase Cdc42 and Cdc420, but not of the genes encoding Rac1 and Rac2, caused a slight growth retardation in hypoxia. Furthermore, growth in hypoxia was not affected by the deletion of several central genes functioning in the pathways of cAMP, Hog1, or the two-component like phosphorylation system that are critical in the cryptococcal response to osmotic and genotoxic stresses. Interestingly, although deletion of HOG1 rescued the hypoxic growth defect of ras1Δ, cdc24Δ, and ptp3Δ, Hog1 was not hyperphosphorylated in these three mutants in hypoxic conditions. RNA sequencing analysis indicated that RAS1, CDC24 and PTP3 acted upon the expression of genes involved in ergosterol biosynthesis, chromosome organization, RNA processing and protein translation. Moreover, growth of the wild-type strain under low oxygen conditions was affected by sub-inhibitory concentrations of the compounds that inhibit these biological processes, demonstrating the importance of these

  20. School Bullying, Cyberbullying, or both: Correlates of Teen Suicidality in the 2011 CDC Youth Risk Behavior Survey

    OpenAIRE

    Messias, Erick; Kindrick, Kristi; Castro, Juan

    2014-01-01

    While school bullying has been shown to be associated with depression and suicidality among teens, the relationship between these outcomes and cyberbullying has not been studied in nationally representative samples. Data came from the 2011 CDC Youth Risk Behavior Survey (YRBS), a nationally representative sample of high-school students (N=15,425). We calculated weighted estimates representative of all students in grades 9-12 attending school in the US. Logistic regression was used to calculat...

  1. Cdc28–Cln3 phosphorylation of Sla1 regulates actin patch dynamics in different modes of fungal growth

    OpenAIRE

    Zeng, Guisheng; Wang, Yan-Ming; Wang, Yue

    2012-01-01

    A dynamic balance between targeted transport and endocytosis is critical for polarized cell growth. However, how actin-mediated endocytosis is regulated in different growth modes remains unclear. Here we report differential regulation of cortical actin patch dynamics between the yeast and hyphal growth in Candida albicans. The mechanism involves phosphoregulation of the endocytic protein Sla1 by the cyclin-dependent kinase (CDK) Cdc28–Cln3 and the actin-regulating kinase Prk1. Mutational stud...

  2. Cdc42 and Rac1 activity is reduced in human pheochromocytoma and correlates with FARP1 and ARHGEF1 expression.

    Science.gov (United States)

    Croisé, Pauline; Houy, Sébastien; Gand, Mathieu; Lanoix, Joël; Calco, Valérie; Tóth, Petra; Brunaud, Laurent; Lomazzi, Sandra; Paramithiotis, Eustache; Chelsky, Daniel; Ory, Stéphane; Gasman, Stéphane

    2016-04-01

    Among small GTPases from the Rho family, Cdc42, RAC, and Rho are well known to mediate a large variety of cellular processes linked with cancer biology through their ability to cycle between an inactive (GDP-bound) and an active (GTP-bound) state. Guanine nucleotide exchange factors (GEFs) stimulate the exchange of GDP for GTP to generate the activated form, whereas the GTPase-activating proteins (GAPs) catalyze GTP hydrolysis, leading to the inactivated form. Modulation of Rho GTPase activity following altered expression of RHO-GEFs and/or RHO-GAPs has already been reported in various human tumors. However, nothing is known about the Rho GTPase activity or the expression of their regulators in human pheochromocytomas, a neuroendocrine tumor (NET) arising from chromaffin cells of the adrenal medulla. In this study, we demonstrate, through an ELISA-based activity assay, that Rac1 and Cdc42 activities decrease in human pheochromocytomas (PCCs) compared with the matched adjacent non-tumor tissue. Furthermore, through quantitative mass spectrometry (MS) approaches, we show that the expression of two RHO-GEF proteins, namely ARHGEF1 and FARP1, is significantly reduced in tumors compared with matched non-tumor tissue, whereas ARHGAP36 expression is increased. Moreover, siRNA-based knockdown of ARHGEF1 and FARP1 in PC12 cells leads to a significant inhibition of Rac1 and Cdc42 activities, respectively. Finally, a principal component analysis (PCA) of our dataset was able to discriminate PCC from non-tumor tissue and indicates a close correlation between Cdc42/Rac1 activity and FARP1/ARHGEF1 expression. Altogether, our findings reveal for the first time the importance of modulation of Rho GTPase activities and expression of their regulators in human PCCs. PMID:26911374

  3. Cell cycle-dependent deposition of CENP-A requires the Dos1/2-Cdc20 complex.

    Science.gov (United States)

    Gonzalez, Marlyn; He, Haijin; Sun, Siyu; Li, Chen; Li, Fei

    2013-01-01

    Centromeric histone CENP-A, a variant of canonical histone H3, plays a central role in proper chromosome segregation. Loading of CENP-A at centromeres is cell cycle-regulated: parental CENP-A is deposited at centromeres during S phase, whereas newly synthesized CENP-A is deposited during later stages of the cell cycle. The mechanisms involved in deposition of CENP-A at centromeres during S phase remain poorly understood. In fission yeast, loading of CENP-A during S phase is regulated by the GATA-type factor, Ams2. Here we show that the Dos1/2-Cdc20 complex, previously characterized as a silencing complex essential for inheritance of H3K9 methylation during S phase, is also required for localization of CENP-A(cnp1) at centromeres at this stage. Disruption of Dos1 (also known as Raf1/Clr8/Cmc1), Dos2 (also known as Raf2/Clr7/Cmc2), or Cdc20, a DNA polymerase epsilon subunit, results in dissociation of CENP-A from centromeres and mislocalization of the protein to noncentromeric sites. All three mutants display spindle disorganization and mitotic defects. Inactivation of Dos1 or Cdc20 also results in accumulation of noncoding RNA transcripts from centromeric cores, a feature common to mutants affecting kinetochore integrity. We further find that Dos1 physically associates with Ams2 and is required for the association of Ams2 with centromeric cores during S phase. Finally, we show that Dos2 associates with centromeric cores during S phase and that its recruitment to centromeric cores depends on Cdc20. This study identifies a physical link between DNA replication and CENP-A assembly machinery and provides mechanistic insight into how CENP-A is faithfully inherited during S phase. PMID:23267073

  4. Rif-mDia1 Interaction Is Involved in Filopodium Formation Independent of Cdc42 and Rac Effectors

    OpenAIRE

    Goh, Wah Ing; Sudhaharan, Thankiah; Lim, Kim Buay; Sem, Kai Ping; Lau, Chew Ling; Ahmed, Sohail

    2011-01-01

    Filopodia are cellular protrusions important for axon guidance, embryonic development, and wound healing. The Rho GTPase Cdc42 is the best studied inducer of filopodium formation, and several of its effectors and their interacting partners have been linked to the process. These include IRSp53, N-WASP, Mena, and Eps8. The Rho GTPase, Rif, also drives filopodium formation. The signaling pathway by which Rif induces filopodia is poorly understood, with mDia2 being the only protein implicated to ...

  5. AtCDC5 regulates the G2 to M transition of the cell cycle and is critical for the function of Arabidopsis shoot apical meristem

    Institute of Scientific and Technical Information of China (English)

    Zhiqiang Lin; Kangquan Yin; Danling Zhu; Zhangliang Chen; Hongya Gu; LiJia Qu

    2007-01-01

    As a cell cycle regulator, the Myb-related CDC5 protein was reported to be essential for the G2 phase of the cell cycle in yeast and animals, but little is known about its function in plants. Here we report the functional characterization of the CDC5 gene in Arabidopsis thaliana. Arabidopsis CDC5 {AtCDCS) is mainly expressed in tissues with high cell division activity, and is expressed throughout the entire process of embryo formation. The AtCDCS loss-of-function mutant is embryonic lethal. In order to investigate the function of AtCDCS in vivo, we generated AtCDC5-RNAi plants in which the expression of AtCDCS was reduced by RNA interference. We found that the G2 to M (G2/M) phase transition was affected in the AtCDC5-RNAi plants, and that endoreduplication was increased. Additionally, the maintenance of shoot apical meristem (SAM) function was disturbed in the AtCDC5-KNAi plants, in which both the WUSCHEL (WUS)-CLAVATA (CLV) and the SHOOT MERISTEMLESS (STM) pathways were impaired. In situ hybridization analysis showed that the expression of STM was greatly reduced in the shoot apical cells of the AtCDC5-KNAi plants. Moreover, cyclinBl or Histone4 was found to be expressed in some of these cells when the transcript of STM was undetectable. These results suggest that AtCDC5 is essential for the G2/M phase transition and may regulate the function of SAM by controlling the expression of STM and WUS.

  6. Assignment of Neisseria meningitidis serogroup A and C class-specific anticapsular antibody concentrations to the new standard reference serum CDC1992.

    OpenAIRE

    Holder, P K; Maslanka, S E; Pais, L B; Dykes, J; Plikaytis, B D; Carlone, G M

    1995-01-01

    A new standard meningococcal reference serum designated CDC1992 was prepared to replace meningococcal reference sera ECG and PB-2, which are not available in sufficient quantities for continued use as primary reference sera. CDC1992 was prepared from 14 healthy adult volunteers who underwent plasmapheresis 4 to 12 weeks postvaccination with a single dose of a Neisseria meningitidis quadrivalent polysaccharide vaccine. Total and/or class-specific meningococcal serogroup A and C anticapsular an...

  7. Proteomic and Phosphoproteomic Insights into a Signaling Hub Role for Cdc14 in Asexual Development and Multiple Stress Responses in Beauveria bassiana

    Science.gov (United States)

    Wang, Zhi-Kang; Wang, Jie; Liu, Jing; Ying, Sheng-Hua; Peng, Xiao-Jun; Feng, Ming-Guang

    2016-01-01

    Cdc14 is a dual-specificity phosphatase that regulates nuclear behavior by dephosphorylating phosphotyrosine and phosphoserine/phosphothreonine in fungi. Previously, Cdc14 was shown to act as a positive regulator of cytokinesis, asexual development and multiple stress responses in Beauveria bassiana, a fungal insect pathogen. This study seeks to gain deep insight into a pivotal role of Cdc14 in the signaling network of B. bassiana by analyzing the Cdc14-specific proteome and phosphoproteome generated by the 8-plex iTRAQ labeling and MS/MS analysis of peptides and phosphopeptides. Under normal conditions, 154 proteins and 86 phosphorylation sites in 67 phosphoproteins were upregulated in Δcdc14 versus wild-type, whereas 117 proteins and 85 phosphorylation sites in 58 phosphoproteins were significantly downregulated. Co-cultivation of Δcdc14 with NaCl (1 M), H2O2 (3 mM) and Congo red (0.15 mg/ml) resulted in the upregulation / downregulation of 23/63, 41/39 and 79/79 proteins and of 127/112, 52/47 and 105/226 phosphorylation sites in 85/92, 45/36 and 79/146 phosphoproteins, respectively. Bioinformatic analyses revealed that Cdc14 could participate in many biological and cellular processes, such as carbohydrate metabolism, glycerophospholipid metabolism, the MAP Kinase signaling pathway, and DNA conformation, by regulating protein expression and key kinase phosphorylation in response to different environmental cues. These indicate that in B. bassiana, Cdc14 is a vital regulator of not only protein expression but also many phosphorylation events involved in developmental and stress-responsive pathways. Fourteen conserved and novel motifs were identified in the fungal phosphorylation events. PMID:27055109

  8. Survival and growth of yeast without telomere capping by Cdc13 in the absence of Sgs1, Exo1, and Rad9.

    Directory of Open Access Journals (Sweden)

    Hien-Ping Ngo

    2010-08-01

    Full Text Available Maintenance of telomere capping is absolutely essential to the survival of eukaryotic cells. Telomere capping proteins, such as Cdc13 and POT1, are essential for the viability of budding yeast and mammalian cells, respectively. Here we identify, for the first time, three genetic modifications that allow budding yeast cells to survive without telomere capping by Cdc13. We found that simultaneous inactivation of Sgs1, Exo1, and Rad9, three DNA damage response (DDR proteins, is sufficient to allow cell division in the absence of Cdc13. Quantitative amplification of ssDNA (QAOS was used to show that the RecQ helicase Sgs1 plays an important role in the resection of uncapped telomeres, especially in the absence of checkpoint protein Rad9. Strikingly, simultaneous deletion of SGS1 and the nuclease EXO1, further reduces resection at uncapped telomeres and together with deletion of RAD9 permits cell survival without CDC13. Pulsed-field gel electrophoresis studies show that cdc13-1 rad9Delta sgs1Delta exo1Delta strains can maintain linear chromosomes despite the absence of telomere capping by Cdc13. However, with continued passage, the telomeres of such strains eventually become short and are maintained by recombination-based mechanisms. Remarkably, cdc13Delta rad9Delta sgs1Delta exo1Delta strains, lacking any Cdc13 gene product, are viable and can grow indefinitely. Our work has uncovered a critical role for RecQ helicases in limiting the division of cells with uncapped telomeres, and this may provide one explanation for increased tumorigenesis in human diseases associated with mutations of RecQ helicases. Our results reveal the plasticity of the telomere cap and indicate that the essential role of telomere capping is to counteract specific aspects of the DDR.

  9. Epi Info™: Now an Open-source application that continues a long and productive “life” through CDC support and funding

    OpenAIRE

    Nieves, Enrique; Jones, Jay

    2009-01-01

    About the authors: Enrique Nieves Jr is the Acting Director of the Division of Integrated Surveillance Systems and Services (DISSS), National Center for Public for Health Informatics (NCPHI), Coordinating Center for Health information and Service (CCHIS), Centers for Disease Control and Prevention (CDC), Atlanta, USA. Jay Jones is a BearingPoint Consultant to the CDC/NCPHI Division of Alliance Management and Consultation (DAMC), National Center for Public for Health Informatics (NCPHI), Coord...

  10. Essential and distinct roles for cdc42 and rac1 in the regulation of Schwann cell biology during peripheral nervous system development

    OpenAIRE

    Benninger, Yves; Thurnherr, Tina; Pereira, Jorge A.; Krause, Sven; Wu, Xunwei; Chrostek-Grashoff, Anna; Herzog, Dominik; Nave, Klaus-Armin; Franklin, Robin J. M.; Meijer, Dies; Brakebusch, Cord; Suter, Ueli; Relvas, João B.

    2007-01-01

    During peripheral nervous system (PNS) myelination, Schwann cells must interpret extracellular cues to sense their environment and regulate their intrinsic developmental program accordingly. The pathways and mechanisms involved in this process are only partially understood. We use tissue-specific conditional gene targeting to show that members of the Rho GTPases, cdc42 and rac1, have different and essential roles in axon sorting by Schwann cells. Our results indicate that although cdc42 is re...

  11. Proteomic and Phosphoproteomic Insights into a Signaling Hub Role for Cdc14 in Asexual Development and Multiple Stress Responses in Beauveria bassiana.

    Science.gov (United States)

    Wang, Zhi-Kang; Wang, Jie; Liu, Jing; Ying, Sheng-Hua; Peng, Xiao-Jun; Feng, Ming-Guang

    2016-01-01

    Cdc14 is a dual-specificity phosphatase that regulates nuclear behavior by dephosphorylating phosphotyrosine and phosphoserine/phosphothreonine in fungi. Previously, Cdc14 was shown to act as a positive regulator of cytokinesis, asexual development and multiple stress responses in Beauveria bassiana, a fungal insect pathogen. This study seeks to gain deep insight into a pivotal role of Cdc14 in the signaling network of B. bassiana by analyzing the Cdc14-specific proteome and phosphoproteome generated by the 8-plex iTRAQ labeling and MS/MS analysis of peptides and phosphopeptides. Under normal conditions, 154 proteins and 86 phosphorylation sites in 67 phosphoproteins were upregulated in Δcdc14 versus wild-type, whereas 117 proteins and 85 phosphorylation sites in 58 phosphoproteins were significantly downregulated. Co-cultivation of Δcdc14 with NaCl (1 M), H2O2 (3 mM) and Congo red (0.15 mg/ml) resulted in the upregulation / downregulation of 23/63, 41/39 and 79/79 proteins and of 127/112, 52/47 and 105/226 phosphorylation sites in 85/92, 45/36 and 79/146 phosphoproteins, respectively. Bioinformatic analyses revealed that Cdc14 could participate in many biological and cellular processes, such as carbohydrate metabolism, glycerophospholipid metabolism, the MAP Kinase signaling pathway, and DNA conformation, by regulating protein expression and key kinase phosphorylation in response to different environmental cues. These indicate that in B. bassiana, Cdc14 is a vital regulator of not only protein expression but also many phosphorylation events involved in developmental and stress-responsive pathways. Fourteen conserved and novel motifs were identified in the fungal phosphorylation events. PMID:27055109

  12. Cross-cultural adaptation of the CDC Worksite Health ScoreCard questionnaire into Portuguese

    Directory of Open Access Journals (Sweden)

    Patrícia Coelho de Soárez

    2016-06-01

    Full Text Available SUMMARY Objective: Despite the progress in the implementation of health promotion programs in the workplace, there are no questionnaires in Brazil to assess the scope of health promotion interventions adopted and their scientific basis. This study aimed to translate into Brazilian Portuguese and culturally adapt the CDC Worksite Health ScoreCard (HSC questionnaire. Method: The HSC has 100 questions grouped into twelve domains. The steps are as follows: translation, reconciliation, back-translation, review by expert panel, pretesting, and final revision. The convenience sample included 27 individuals from health insurance providers and companies of various sizes, types and industries in São Paulo. Data were analyzed using descriptive statistics. Results: The average age of the sample was 38 years, most of the subjects were female (21 of 27, and were responsible for programs to promote health in these workplaces. Most questions were above the minimum value of understanding set at 90%. The participants found the questionnaire very useful to determine the extent of existing health promotion programs and to pinpoint areas that could be developed. Conclusion: The Brazilian Portuguese version of the HSC questionnaire may be a valid measure and useful to assess the degree of implementation of health promotion interventions based on evidence in local health organizations.

  13. Summary of data reported to CDC's national automated biosurveillance system, 2008

    Directory of Open Access Journals (Sweden)

    McMurray Paul

    2010-05-01

    Full Text Available Abstract Background BioSense is the US national automated biosurveillance system. Data regarding chief complaints and diagnoses are automatically pre-processed into 11 broader syndromes (e.g., respiratory and 78 narrower sub-syndromes (e.g., asthma. The objectives of this report are to present the types of illness and injury that can be studied using these data and the frequency of visits for the syndromes and sub-syndromes in the various data types; this information will facilitate use of the system and comparison with other systems. Methods For each major data source, we summarized information on the facilities, timeliness, patient demographics, and rates of visits for each syndrome and sub-syndrome. Results In 2008, the primary data sources were the 333 US Department of Defense, 770 US Veterans Affairs, and 532 civilian hospital emergency department facilities. Median times from patient visit to record receipt at CDC were 2.2 days, 2.0 days, and 4 hours for these sources respectively. Among sub-syndromes, we summarize mean 2008 visit rates in 45 infectious disease categories, 11 injury categories, 7 chronic disease categories, and 15 other categories. Conclusions We present a systematic summary of data that is automatically available to public health departments for monitoring and responding to emergencies.

  14. Identification of the C. elegans anaphase promoting complex subunit Cdc26 by phenotypic profiling and functional rescue in yeast

    Directory of Open Access Journals (Sweden)

    Zachariae Wolfgang

    2007-03-01

    Full Text Available Abstract Background RNA interference coupled with videorecording of C. elegans embryos is a powerful method for identifying genes involved in cell division processes. Here we present a functional analysis of the gene B0511.9, previously identified as a candidate cell polarity gene in an RNAi videorecording screen of chromosome I embryonic lethal genes. Results Whereas weak RNAi inhibition of B0511.9 causes embryonic cell polarity defects, strong inhibition causes embryos to arrest in metaphase of meiosis I. The range of defects induced by RNAi of B0511.9 is strikingly similar to those displayed by mutants of anaphase-promoting complex/cyclosome (APC/C components. Although similarity searches did not reveal any obvious homologue of B0511.9 in the non-redundant protein database, we found that the N-terminus shares a conserved sequence pattern with the N-terminus of the small budding yeast APC/C subunit Cdc26 and its orthologues from a variety of other organisms. Furthermore, we show that B0511.9 robustly complements the temperature-sensitive growth defect of a yeast cdc26Δ mutant. Conclusion These data demonstrate that B0511.9 encodes the C. elegans APC/C subunit CDC-26.

  15. Hyphal growth in Candida albicans requires the phosphorylation of Sec2 by the Cdc28-Ccn1/Hgc1 kinase.

    Science.gov (United States)

    Bishop, Amy; Lane, Rachel; Beniston, Richard; Chapa-y-Lazo, Bernardo; Smythe, Carl; Sudbery, Peter

    2010-09-01

    Polarized growth is a fundamental property of cell growth and development. It requires the delivery of post-Golgi secretory vesicles to the site of polarized growth. This process is mediated by Rab GTPases activated by their guanine exchange factors (GEFs). The human fungal pathogen, Candida albicans, can grow in a budded yeast form or in a highly polarized hyphal form, and thus provides a model to study this phenomenon. During hyphal, but not yeast growth, secretory vesicles accumulate in an apical body called a Spitzenkörper, which acts to focus delivery of the vesicles to the tip. Post-Golgi transport of secretory vesicles is mediated by the Rab GTPase Sec4, activated by its GEF Sec2. Using a combination of deletion mapping, in vitro mutagenesis, an analogue-sensitive allele of Cdc28 and an in vitro kinase assay, we show that localization of Sec2 to the Spitzenkörper and normal hyphal development requires phosphorylation of Serine 584 by the cyclin-dependent kinase Cdc28. Thus, as well as controlling passage through the cell cycle, Cdc28 has an important function in controlling polarized secretion. PMID:20639857

  16. Conversion tool for the LWR transient analysis code RELAP5 from the CDC version to the FACOM version

    International Nuclear Information System (INIS)

    The LWR transient analysis code RELAP5 has been developed on the CDC-CYBER 176 at Idaho National Engineering Laboratory (INEL), the RELAP5 code has been often updated in order to extend the analyzing model and correct the errors. At Japan Atomic Energy Research Institute the code has been converted from the CDC version to the FACOM version and the converted code has been used. The conversion is the task which consumes a lot of time, because the code is large and there is the difference between CDC's machines and FACOM's ones. In order to convert the RELAP5 code automatically, the software tool has been developed. By using this tools the efficiency for converting the RELAP5 code has been improved. Productivity of the conversion is increased about 2.0 to 2.6 times by the tools in comparison with in manual. The procedure of conversion by using the tools and the option parameters of each tool are described. (author)

  17. Endogenous Hot Spots of De Novo Telomere Addition in the Yeast Genome Contain Proximal Enhancers That Bind Cdc13.

    Science.gov (United States)

    Obodo, Udochukwu C; Epum, Esther A; Platts, Margaret H; Seloff, Jacob; Dahlson, Nicole A; Velkovsky, Stoycho M; Paul, Shira R; Friedman, Katherine L

    2016-06-15

    DNA double-strand breaks (DSBs) pose a threat to genome stability and are repaired through multiple mechanisms. Rarely, telomerase, the enzyme that maintains telomeres, acts upon a DSB in a mutagenic process termed telomere healing. The probability of telomere addition is increased at specific genomic sequences termed sites of repair-associated telomere addition (SiRTAs). By monitoring repair of an induced DSB, we show that SiRTAs on chromosomes V and IX share a bipartite structure in which a core sequence (Core) is directly targeted by telomerase, while a proximal sequence (Stim) enhances the probability of de novo telomere formation. The Stim and Core sequences are sufficient to confer a high frequency of telomere addition to an ectopic site. Cdc13, a single-stranded DNA binding protein that recruits telomerase to endogenous telomeres, is known to stimulate de novo telomere addition when artificially recruited to an induced DSB. Here we show that the ability of the Stim sequence to enhance de novo telomere addition correlates with its ability to bind Cdc13, indicating that natural sites at which telomere addition occurs at high frequency require binding by Cdc13 to a sequence 20 to 100 bp internal from the site at which telomerase acts to initiate de novo telomere addition. PMID:27044869

  18. In situ biosynthesis of Ag, Au and bimetallic nanoparticles using Piper pedicellatum C.DC: green chemistry approach.

    Science.gov (United States)

    Tamuly, Chandan; Hazarika, Moushumi; Borah, Sarat Ch; Das, Manash R; Boruah, Manas P

    2013-02-01

    The synthesis of Ag, Au and Ag-Au bimetallic nanoparticles using Piper pedicellatum C.DC leaf extract is demonstrated here. The rapid formation of stable Ag and Au nanoparticles has been found using P. pedicellatum C.DC leaf extract in aqueous medium at normal atmospheric condition. Competitive reduction of Ag(+) and Au(3+) ions present simultaneously in solution during exposure to P. pedicellatum C.DC leaf extract leads to the synthesis of bimetallic Ag-Au nanoparticles in solution. Transmission electron microscopy (TEM) analysis revealed that the Ag nanoparticles predominantly form spherical in shape with the size range of 2.0±0.5-30.0±1.2 nm. In case of Au nanoparticles, the particles are spherical in shape along with few triangular, hexagonal and pentagonal shaped nanoparticles also observed. X-ray diffraction (XRD) studies revealed that the nanoparticles were face centered cubic (fcc) in shape. Fourier transform infrared spectroscopy (FTIR) showed nanoparticles were capped with plant compounds. The chemical constituents, viz. catechin, gallic acid, courmaric acid and protocatechuic acid of the leaf extract were identified which may act as a reducing, stabilizing and capping agent. The expected reaction mechanism in the formation of Ag and Au nanoparticles is also reported. PMID:23107941

  19. Stability of the Human Hsp90-p50Cdc37 Chaperone Complex against Nucleotides and Hsp90 Inhibitors, and the Influence of Phosphorylation by Casein Kinase 2

    Directory of Open Access Journals (Sweden)

    Sanne H. Olesen

    2015-01-01

    Full Text Available The molecular chaperone Hsp90 is regulated by co-chaperones such as p50Cdc37, which recruits a wide selection of client protein kinases. Targeted disruption of the Hsp90-p50Cdc37 complex by protein–protein interaction (PPI inhibitors has emerged as an alternative strategy to treat diseases characterized by aberrant Hsp90 activity. Using isothermal microcalorimetry, ELISA and GST-pull down assays we evaluated reported Hsp90 inhibitors and nucleotides for their ability to inhibit formation of the human Hsp90β-p50Cdc37 complex, reconstituted in vitro from full-length proteins. Hsp90 inhibitors, including the proposed PPI inhibitors gedunin and H2-gamendazole, did not affect the interaction of Hsp90 with p50Cdc37 in vitro. Phosphorylation of Hsp90 and p50Cdc37 by casein kinase 2 (CK2 did not alter the thermodynamic signature of complex formation. However, the phosphorylated complex was vulnerable to disruption by ADP (IC50 = 32 µM, while ATP, AMPPNP and Hsp90 inhibitors remained largely ineffective. The differential inhibitory activity of ADP suggests that phosphorylation by CK2 primes the complex for dissociation in response to a drop in ATP/ADP levels. The approach applied herein provides robust assays for a comprehensive biochemical evaluation of potential effectors of the Hsp90-p50Cdc37 complex, such as phosphorylation by a kinase or the interaction with small molecule ligands.

  20. Synchronizing Progression of Schizosaccharomyces pombe Cells from G2 through Repeated Rounds of Mitosis and S Phase with cdc25-22 Arrest Release.

    Science.gov (United States)

    Hagan, Iain M; Grallert, Agnes; Simanis, Viesturs

    2016-01-01

    Transient inactivation of the cdc25(+) gene product by manipulation of the culture temperature for cdc25-22 cells is the most commonly exploited approach to mitotic synchronization in fission yeast. Because Cdc25 removes the inhibitory phosphate placed on Cdk1 by Wee1, inactivation of Cdc25 arrests cells at the G2/M boundary. Incubation at the restrictive temperature of 36°C for just over one generation time forces all cells in the culture to accumulate at the G2/M boundary. Restoration of Cdc25 function via a return to the permissive temperature or chemical inhibition of Wee1 activity at 36°C can then promote a highly synchronous wave of cell division throughout the culture. These approaches can be performed on any scale and thus support simultaneous assessment of numerous events within a single culture. After describing this simple and widely applicable procedure, we discuss frequently overlooked issues that can have a considerable impact on the interpretation of data from cdc25-22 induction-synchronized cultures. PMID:27480720

  1. Involvement of cdc25c in cell cycle alteration of a radioresistant lung cancer cell line established with fractionated ionizing radiation.

    Science.gov (United States)

    Li, Jie; Yang, Chun-Xu; Mei, Zi-Jie; Chen, Jing; Zhang, Shi-Min; Sun, Shao-Xing; Zhou, Fu-Xiang; Zhou, Yun-Feng; Xie, Cong-Hua

    2013-01-01

    Cancer patients often suffer from local tumor recurrence after radiation therapy. Cell cycling, an intricate sequence of events which guarantees high genomic fidelity, has been suggested to affect DNA damage responses and eventual radioresistant characteristics of cancer cells. Here, we established a radioresistant lung cancer cell line, A549R , by exposing the parental A549 cells to repeated γ-ray irradiation with a total dose of 60 Gy. The radiosensitivity of A549 and A549R was confirmed using colony formation assays. We then focused on examination of the cell cycle distribution between A549 and A549R and found that the proportion of cells in the radioresistant S phase increased, whereas that in the radiosensitive G1 phase decreased. When A549 and A549R cells were exposed to 4 Gy irradiation the total differences in cell cycle redistribution suggested that G2-M cell cycle arrest plays a predominant role in mediating radioresistance. In order to further explore the possible mechanisms behind the cell cycle related radioresistance, we examined the expression of Cdc25 proteins which orchestrate cell cycle transitions. The results showed that expression of Cdc25c increased accompanied by the decrease of Cdc25a and we proposed that the quantity of Cdc25c, rather than activated Cdc25c or Cdc25a, determines the radioresistance of cells. PMID:24289569

  2. Structural Bioinformatics and Protein Docking Analysis of the Molecular Chaperone-Kinase Interactions: Towards Allosteric Inhibition of Protein Kinases by Targeting the Hsp90-Cdc37 Chaperone Machinery

    Directory of Open Access Journals (Sweden)

    Gennady Verkhivker

    2013-11-01

    Full Text Available A fundamental role of the Hsp90-Cdc37 chaperone system in mediating maturation of protein kinase clients and supporting kinase functional activity is essential for the integrity and viability of signaling pathways involved in cell cycle control and organism development. Despite significant advances in understanding structure and function of molecular chaperones, the molecular mechanisms and guiding principles of kinase recruitment to the chaperone system are lacking quantitative characterization. Structural and thermodynamic characterization of Hsp90-Cdc37 binding with protein kinase clients by modern experimental techniques is highly challenging, owing to a transient nature of chaperone-mediated interactions. In this work, we used experimentally-guided protein docking to probe the allosteric nature of the Hsp90-Cdc37 binding with the cyclin-dependent kinase 4 (Cdk4 kinase clients. The results of docking simulations suggest that the kinase recognition and recruitment to the chaperone system may be primarily determined by Cdc37 targeting of the N-terminal kinase lobe. The interactions of Hsp90 with the C-terminal kinase lobe may provide additional “molecular brakes” that can lock (or unlock kinase from the system during client loading (release stages. The results of this study support a central role of the Cdc37 chaperone in recognition and recruitment of the kinase clients. Structural analysis may have useful implications in developing strategies for allosteric inhibition of protein kinases by targeting the Hsp90-Cdc37 chaperone machinery.

  3. The signaling pathway of Campylobacter jejuni-induced Cdc42 activation: Role of fibronectin, integrin beta1, tyrosine kinases and guanine exchange factor Vav2

    LENUS (Irish Health Repository)

    Krause-Gruszczynska, Malgorzata

    2011-12-28

    Abstract Background Host cell invasion by the foodborne pathogen Campylobacter jejuni is considered as one of the primary reasons of gut tissue damage, however, mechanisms and key factors involved in this process are widely unclear. It was reported that small Rho GTPases, including Cdc42, are activated and play a role during invasion, but the involved signaling cascades remained unknown. Here we utilised knockout cell lines derived from fibronectin-\\/-, integrin-beta1-\\/-, focal adhesion kinase (FAK)-\\/- and Src\\/Yes\\/Fyn-\\/- deficient mice, and wild-type control cells, to investigate C. jejuni-induced mechanisms leading to Cdc42 activation and bacterial uptake. Results Using high-resolution scanning electron microscopy, GTPase pulldowns, G-Lisa and gentamicin protection assays we found that each studied host factor is necessary for induction of Cdc42-GTP and efficient invasion. Interestingly, filopodia formation and associated membrane dynamics linked to invasion were only seen during infection of wild-type but not in knockout cells. Infection of cells stably expressing integrin-beta1 variants with well-known defects in fibronectin fibril formation or FAK signaling also exhibited severe deficiencies in Cdc42 activation and bacterial invasion. We further demonstrated that infection of wild-type cells induces increasing amounts of phosphorylated FAK and growth factor receptors (EGFR and PDGFR) during the course of infection, correlating with accumulating Cdc42-GTP levels and C. jejuni invasion over time. In studies using pharmacological inhibitors, silencing RNA (siRNA) and dominant-negative expression constructs, EGFR, PDGFR and PI3-kinase appeared to represent other crucial components upstream of Cdc42 and invasion. siRNA and the use of Vav1\\/2-\\/- knockout cells further showed that the guanine exchange factor Vav2 is required for Cdc42 activation and maximal bacterial invasion. Overexpression of certain mutant constructs indicated that Vav2 is a linker

  4. Genetics, structure, and prevalence of FP967 (CDC Triffid) T-DNA in flax.

    Science.gov (United States)

    Young, Lester; Hammerlindl, Joseph; Babic, Vivijan; McLeod, Jamille; Sharpe, Andrew; Matsalla, Chad; Bekkaoui, Faouzi; Marquess, Leigh; Booker, Helen M

    2015-01-01

    The detection of T-DNA from a genetically modified flaxseed line (FP967, formally CDC Triffid) in a shipment of Canadian flaxseed exported to Europe resulted in a large decrease in the amount of flax planted in Canada. The Canadian flaxseed industry undertook major changes to ensure the removal of FP967 from the supply chain. This study aimed to resolve the genetics and structure of the FP967 transfer DNA (T-DNA). The FP967 T-DNA is thought to be inserted in at single genomic locus. The junction between the T-DNA and genomic DNA consisted of two inverted Right Borders with no Left Border (LB) flanking genomic DNA sequences recovered. This information was used to develop an event-specific quantitative PCR (qPCR) assay. This assay and an existing assay specific to the T-DNA construct were used to determine the genetics and prevalence of the FP967 T-DNA. These data supported the hypothesis that the T-DNA is present at a single location in the genome. The FP967 T-DNA is present at a low level (between 0.01 and 0.1%) in breeder seed lots from 2009 and 2010. None of the 11,000 and 16,000 lines selected for advancement through the Flax Breeding Program in 2010 and 2011, respectively, tested positive for the FP967 T-DNA, however. Most of the FP967 T-DNA sequence was resolved via PCR cloning and next generation sequencing. A 3,720 bp duplication of an internal portion of the T-DNA (including a Right Border) was discovered between the flanking genomic DNA and the LB. An event-specific assay, SAT2-LB, was developed for the junction between this repeat and the LB. PMID:25883881

  5. Design of dashboard audio module based on Micronas CDC3207G microcontroller%基于Micronas CDC3207G微控制器的汽车仪表盘音频模块设计

    Institute of Scientific and Technical Information of China (English)

    黄甜; 吴志红; 朱元

    2007-01-01

    介绍了德国Micronas公司生产的CDC3207G微控制器音频模块的原理及应用设计.该音频模块含有脉宽调制单元(PWM),产生由PWM控制的声音方波信号,因此除了生成普通的声音信号,还可产生振幅逐次衰减的锣声信号.

  6. Guide to the TYNMET/TELENET Computer Network for IIASA Users

    OpenAIRE

    Sebestyen, I.

    1980-01-01

    IIASA's computing power is basically built upon two main sources. The first, and obviously most important, of these sources for all IIASA users is the internal computer resource of the Institute based mainly on the PDP 11/70, which is run on the UNIX operating system of Bell Labs. The second major source of satisfying IIASA's user demand is based on external computer resources, such as the large IBM computers at CNUCE in Pisa, the CDC-CYBER 74 of the Technical University, Vienna, and the IBM ...

  7. Proteomics Analysis Reveals Stable Multiprotein Complexes in Both Fission and Budding Yeasts Containing Myb-Related Cdc5p/Cef1p, Novel Pre-mRNA Splicing Factors, and snRNAs

    OpenAIRE

    Ohi, Melanie D.; Link, Andrew J.; Ren, Liping; Jennings, Jennifer L.; McDonald, W. Hayes; Gould, Kathleen L.

    2002-01-01

    Schizosaccharomyces pombe Cdc5p and its Saccharomyces cerevisiae ortholog, Cef1p, are essential Myb-related proteins implicated in pre-mRNA splicing and contained within large multiprotein complexes. Here we describe the tandem affinity purification (TAP) of Cdc5p- and Cef1p-associated complexes. Using transmission electron microscopy, we show that the purified Cdc5p complex is a discrete structure. The components of the S. pombe Cdc5p/S. cerevisiae Cef1p complexes (termed Cwfs or Cwcs, respe...

  8. A comprehensive genome-wide analysis of melanoma Breslow thickness identifies interaction between CDC42 and SCIN genetic variants.

    Science.gov (United States)

    Vaysse, Amaury; Fang, Shenying; Brossard, Myriam; Wei, Qingyi; Chen, Wei V; Mohamdi, Hamida; Vincent-Fetita, Lynda; Margaritte-Jeannin, Patricia; Lavielle, Nolwenn; Maubec, Eve; Lathrop, Mark; Avril, Marie-Françoise; Amos, Christopher I; Lee, Jeffrey E; Demenais, Florence

    2016-11-01

    Breslow thickness (BT) is a major prognostic factor of cutaneous melanoma (CM), the most fatal skin cancer. The genetic component of BT has only been explored by candidate gene studies with inconsistent results. Our objective was to uncover the genetic factors underlying BT using an hypothesis-free genome-wide approach. Our analysis strategy integrated a genome-wide association study (GWAS) of single nucleotide polymorphisms (SNPs) for BT followed by pathway analysis of GWAS outcomes using the gene-set enrichment analysis (GSEA) method and epistasis analysis within BT-associated pathways. This strategy was applied to two large CM datasets with Hapmap3-imputed SNP data: the French MELARISK study for discovery (966 cases) and the MD Anderson Cancer Center study (1,546 cases) for replication. While no marginal effect of individual SNPs was revealed through GWAS, three pathways, defined by gene ontology (GO) categories were significantly enriched in genes associated with BT (false discovery rate ≤5% in both studies): hormone activity, cytokine activity and myeloid cell differentiation. Epistasis analysis, within each significant GO, identified a statistically significant interaction between CDC42 and SCIN SNPs (pmeta-int =2.2 × 10(-6) , which met the overall multiple-testing corrected threshold of 2.5 × 10(-6) ). These two SNPs (and proxies) are strongly associated with CDC42 and SCIN gene expression levels and map to regulatory elements in skin cells. This interaction has important biological relevance since CDC42 and SCIN proteins have opposite effects in actin cytoskeleton organization and dynamics, a key mechanism underlying melanoma cell migration and invasion. PMID:27347659

  9. Integrin α PAT-2/CDC-42 signaling is required for muscle-mediated clearance of apoptotic cells in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Hsiao-Han Hsieh

    Full Text Available Clearance of apoptotic cells by engulfment plays an important role in the homeostasis and development of multicellular organisms. Despite the fact that the recognition of apoptotic cells by engulfment receptors is critical in inducing the engulfment process, the molecular mechanisms are still poorly understood. Here, we characterize a novel cell corpse engulfment pathway mediated by the integrin α subunit PAT-2 in Caenorhabditis elegans and show that it specifically functions in muscle-mediated engulfment during embryogenesis. Inactivation of pat-2 results in a defect in apoptotic cell internalization. The PAT-2 extracellular region binds to the surface of apoptotic cells in vivo, and the intracellular region may mediate signaling for engulfment. We identify essential roles of small GTPase CDC-42 and its activator UIG-1, a guanine-nucleotide exchange factor, in PAT-2-mediated cell corpse removal. PAT-2 and CDC-42 both function in muscle cells for apoptotic cell removal and are co-localized in growing muscle pseudopods around apoptotic cells. Our data suggest that PAT-2 functions through UIG-1 for CDC-42 activation, which in turn leads to cytoskeletal rearrangement and apoptotic cell internalization by muscle cells. Moreover, in contrast to PAT-2, the other integrin α subunit INA-1 and the engulfment receptor CED-1, which signal through the conserved signaling molecules CED-5 (DOCK180/CED-12 (ELMO or CED-6 (GULP respectively, preferentially act in epithelial cells to mediate cell corpse removal during mid-embryogenesis. Our results show that different engulfing cells utilize distinct repertoires of receptors for engulfment at the whole organism level.

  10. Caveolin-1 and CDC42 mediated endocytosis of silica-coated iron oxide nanoparticles in HeLa cells

    Directory of Open Access Journals (Sweden)

    Nils Bohmer

    2015-01-01

    Full Text Available Nanomedicine is a rapidly growing field in nanotechnology, which has great potential in the development of new therapies for numerous diseases. For example iron oxide nanoparticles are in clinical use already in the thermotherapy of brain cancer. Although it has been shown, that tumor cells take up these particles in vitro, little is known about the internalization routes. Understanding of the underlying uptake mechanisms would be very useful for faster and precise development of nanoparticles for clinical applications. This study aims at the identification of key proteins, which are crucial for the active uptake of iron oxide nanoparticles by HeLa cells (human cervical cancer as a model cell line. Cells were transfected with specific siRNAs against Caveolin-1, Dynamin 2, Flotillin-1, Clathrin, PIP5Kα and CDC42. Knockdown of Caveolin-1 reduces endocytosis of superparamagnetic iron oxide nanoparticles (SPIONs and silica-coated iron oxide nanoparticles (SCIONs between 23 and 41%, depending on the surface characteristics of the nanoparticles and the experimental design. Knockdown of CDC42 showed a 46% decrease of the internalization of PEGylated SPIONs within 24 h incubation time. Knockdown of Dynamin 2, Flotillin-1, Clathrin and PIP5Kα caused no or only minor effects. Hence endocytosis in HeLa cells of iron oxide nanoparticles, used in this study, is mainly mediated by Caveolin-1 and CDC42. It is shown here for the first time, which proteins of the endocytotic pathway mediate the endocytosis of silica-coated iron oxide nanoparticles in HeLa cells in vitro. In future studies more experiments should be carried out with different cell lines and other well-defined nanoparticle species to elucidate possible general principles.

  11. Clinical inquiries regarding Ebola virus disease received by CDC--United States, July 9-November 15, 2014.

    Science.gov (United States)

    Karwowski, Mateusz P; Meites, Elissa; Fullerton, Kathleen E; Ströher, Ute; Lowe, Luis; Rayfield, Mark; Blau, Dianna M; Knust, Barbara; Gindler, Jacqueline; Van Beneden, Chris; Bialek, Stephanie R; Mead, Paul; Oster, Alexandra M

    2014-12-12

    Since early 2014, there have been more than 6,000 reported deaths from Ebola virus disease (Ebola), mostly in Guinea, Liberia, and Sierra Leone. On July 9, 2014, CDC activated its Emergency Operations Center for the Ebola outbreak response and formalized the consultation service it had been providing to assist state and local public health officials and health care providers evaluate persons in the United States thought to be at risk for Ebola. During July 9-November 15, CDC responded to clinical inquiries from public health officials and health care providers from 49 states and the District of Columbia regarding 650 persons thought to be at risk. Among these, 118 (18%) had initial signs or symptoms consistent with Ebola and epidemiologic risk factors placing them at risk for infection, thereby meeting the definition of persons under investigation (PUIs). Testing was not always performed for PUIs because alternative diagnoses were made or symptoms resolved. In total, 61 (9%) persons were tested for Ebola virus, and four, all of whom met PUI criteria, had laboratory-confirmed Ebola. Overall, 490 (75%) inquiries concerned persons who had neither traveled to an Ebola-affected country nor had contact with an Ebola patient. Appropriate medical evaluation and treatment for other conditions were noted in some instances to have been delayed while a person was undergoing evaluation for Ebola. Evaluating and managing persons who might have Ebola is one component of the overall approach to domestic surveillance, the goal of which is to rapidly identify and isolate Ebola patients so that they receive appropriate medical care and secondary transmission is prevented. Health care providers should remain vigilant and consult their local and state health departments and CDC when assessing ill travelers from Ebola-affected countries. Most of these persons do not have Ebola; prompt diagnostic assessments, laboratory testing, and provision of appropriate care for other conditions are

  12. Mapping and mutation of the conserved DNA polymerase interaction motif (DPIM located in the C-terminal domain of fission yeast DNA polymerase δ subunit Cdc27

    Directory of Open Access Journals (Sweden)

    Warbrick Emma

    2004-12-01

    Full Text Available Abstract Background DNA polymerases α and δ play essential roles in the replication of chromosomal DNA in eukaryotic cells. DNA polymerase α (Pol α-primase is required to prime synthesis of the leading strand and each Okazaki fragment on the lagging strand, whereas DNA polymerase δ (Pol δ is required for the elongation stages of replication, a function it appears capable of performing on both leading and lagging strands, at least in the absence of DNA polymerase ε (Pol ε. Results Here it is shown that the catalytic subunit of Pol α, Pol1, interacts with Cdc27, one of three non-catalytic subunits of fission yeast Pol δ, both in vivo and in vitro. Pol1 interacts with the C-terminal domain of Cdc27, at a site distinct from the previously identified binding sites for Cdc1 and PCNA. Comparative protein sequence analysis identifies a protein sequence motif, called the DNA polymerase interaction motif (DPIM, in Cdc27 orthologues from a wide variety of eukaryotic species, including mammals. Mutational analysis shows that the DPIM in fission yeast Cdc27 is not required for effective DNA replication, repair or checkpoint function. Conclusions The absence of any detectable phenotypic consequences arising from mutation of the DPIM suggests that despite its evolutionary conservation, the interaction between the two polymerases mediated by this motif is a non-essential one.

  13. Huge enhancement of energy storage capacity and power density of supercapacitors based on the carbon dioxide activated microporous SiC-CDC

    International Nuclear Information System (INIS)

    Nanostructured carbide-derived carbons (CDC) were synthesized from SiC powders (SiC-CDC) via gas phase chlorination within the temperature range from 1000 °C to 1100 °C. Thereafter the CDCs were additionally activated by CO2 treatment method, resulting in nearly two-fold increase in specific surface area. The results of X-ray diffraction, high-resolution transmission electron microscopy and Raman spectroscopy showed that the synthesized CDC materials are mainly amorphous, however containing small graphitic crystallites. The low-temperature N2 sorption experiments were performed and the specific micropore surface areas from 1100 m2 g−1 up to 2270 m2 g−1 were obtained, depending on the extent of CO2 activation. The energy and power density characteristics of the supercapacitors based on 1 M (C2H5)3CH3NBF4 solution in acetonitrile and SiC-CDC as an electrode material were investigated using the cyclic voltammetry, electrochemical impedance spectroscopy, galvanostatic charge/discharge and constant power discharge methods. The electrochemical data indicated two-times increase in specific capacitance. Most importantly, the activation of SiC-CDC with CO2 significantly increases the performance (energy density, power density, etc.) of the supercapacitors especially at higher potential scan rates and at higher power loads

  14. p53 negativity, CDC25B positivity, and metallothionein negativity are predictors of a response of esophageal squamous cell carcinoma to chemoradiotherapy

    Institute of Scientific and Technical Information of China (English)

    Fumiko Sunada; Masayuki Itabashi; Hisanao Ohkura; Toshiyuki Okumura

    2005-01-01

    AIM: Esophageal squamous cell carcinoma is generally sensitive to chemoradiotherapy (CRT), but some cases are not. Using a retrospective analysis, we aimed to identify the predictors of the response by esophageal squamous cell carcinoma to definitive CRT.METHODS: The intensities of expression of p53, Ki67,Bcl-2, Bax, cyclin D1, VEGF, CDC25B, and metallothionein (MT)were evaluated immunohistochemically in the biopsy specimens obtained before CRT, and the intensities of their expression were tested for correlations with the clinical effects of CRT.RESULTS: The esophageal squamous cell carcinomas with negative p53, positive CDC25B, and negative MT expression were found to be significantly more sensitive to CRT. In addition, p53 positivity and CDC25B positivity respomd well to CRT.CONCLUSION: Esophageal squamous cell carcinomas with negative p53,positive CDC25B, and negative MT expressions respond well to CRT. Even with p53 positivity,if with CDC25B positivity, CRT can be expected.

  15. Leveraging geospatial data, technology, and methods for improving the health of communities: priorities and strategies from an expert panel convened by the CDC.

    Science.gov (United States)

    Elmore, Kim; Flanagan, Barry; Jones, Nicholas F; Heitgerd, Janet L

    2010-04-01

    In 2008, CDC convened an expert panel to gather input on the use of geospatial science in surveillance, research and program activities focused on CDC's Healthy Communities Goal. The panel suggested six priorities: spatially enable and strengthen public health surveillance infrastructure; develop metrics for geospatial categorization of community health and health inequity; evaluate the feasibility and validity of standard metrics of community health and health inequities; support and develop GIScience and geospatial analysis; provide geospatial capacity building, training and education; and, engage non-traditional partners. Following the meeting, the strategies and action items suggested by the expert panel were reviewed by a CDC subcommittee to determine priorities relative to ongoing CDC geospatial activities, recognizing that many activities may need to occur either in parallel, or occur multiple times across phases. Phase A of the action items centers on developing leadership support. Phase B focuses on developing internal and external capacity in both physical (e.g., software and hardware) and intellectual infrastructure. Phase C of the action items plan concerns the development and integration of geospatial methods. In summary, the panel members provided critical input to the development of CDC's strategic thinking on integrating geospatial methods and research issues across program efforts in support of its Healthy Communities Goal. PMID:20012474

  16. Mutations in CDC14A, Encoding a Protein Phosphatase Involved in Hair Cell Ciliogenesis, Cause Autosomal-Recessive Severe to Profound Deafness.

    Science.gov (United States)

    Delmaghani, Sedigheh; Aghaie, Asadollah; Bouyacoub, Yosra; El Hachmi, Hala; Bonnet, Crystel; Riahi, Zied; Chardenoux, Sebastien; Perfettini, Isabelle; Hardelin, Jean-Pierre; Houmeida, Ahmed; Herbomel, Philippe; Petit, Christine

    2016-06-01

    By genetic linkage analysis in a large consanguineous Iranian family with eleven individuals affected by severe to profound congenital deafness, we were able to define a 2.8 Mb critical interval (at chromosome 1p21.2-1p21.1) for an autosomal-recessive nonsyndromic deafness locus (DFNB). Whole-exome sequencing allowed us to identify a CDC14A biallelic nonsense mutation, c.1126C>T (p.Arg376(∗)), which was present in the eight clinically affected individuals still alive. Subsequent screening of 115 unrelated individuals affected by severe or profound congenital deafness of unknown genetic cause led us to identify another CDC14A biallelic nonsense mutation, c.1015C>T (p.Arg339(∗)), in an individual originating from Mauritania. CDC14A encodes a protein tyrosine phosphatase. Immunofluorescence analysis of the protein distribution in the mouse inner ear showed a strong labeling of the hair cells' kinocilia. By using a morpholino strategy to knockdown cdc14a in zebrafish larvae, we found that the length of the kinocilia was reduced in inner-ear hair cells. Therefore, deafness caused by loss-of-function mutations in CDC14A probably arises from a morphogenetic defect of the auditory sensory cells' hair bundles, whose differentiation critically depends on the proper growth of their kinocilium. PMID:27259055

  17. Assignment of CDC Weak Oxidizer Group 2 (WO-2) to the Genus Pandoraea and Characterization of Three New Pandoraea Genomospecies

    OpenAIRE

    Daneshvar, Maryam I.; Hollis, Dannie G.; Steigerwalt, Arnold G.; Whitney, Anne M.; Spangler, Laura; Douglas, Michael P.; Jordan, Jean G.; MacGregor, John P.; Hill, Bertha C.; Tenover, Fred C.; Brenner, Don J.; Weyant, Robbin S.

    2001-01-01

    CDC weak oxidizer group 2 (WO-2) consists of nine phenotypically similar human clinical isolates received by the Centers for Disease Control and Prevention between 1989 and 1998. Four of the isolates were from blood, three were from sputum, and one each was from bronchial fluid and maxillary sinus. All are aerobic nonfermentative, motile gram-negative rods with one to eight polar flagella per cell. All grew at 25 and 35°C and were positive for catalase, urease (usually delayed 3 to 7 days), c...

  18. RNAi screen of Salmonella invasion shows role of COPI in membrane targeting of cholesterol and Cdc42

    OpenAIRE

    Misselwitz, Benjamin; Dilling, Sabrina; Vonaesch, Pascale; Sacher, Raphael; Snijder, Berend; Schlumberger, Markus; Rout, Samuel; Stark, Manuel; Mering, Christian von; Pelkmans, Lucas; Hardt, Wolf-Dietrich

    2011-01-01

    Pathogens are not only a menace to public health, but they also provide excellent tools for probing host cell function. Thus, studying infection mechanisms has fueled progress in cell biology (Ridley et al, 1992; Welch et al, 1997). In the presented study, we have performed an RNAi screen to identify host cell genes required for Salmonella host cell invasion. This screen identified proteins known to contribute to Salmonella-induced actin rearrangements (e.g., Cdc42 and the Arp2/3 complex; rev...

  19. CDC Signos Vitales: El zika y el embarazo Lo que debe saber (Zika and Pregnancy: What You Should Know)

    Centers for Disease Control (CDC) Podcasts

    2016-04-01

    Este podcast se basa en el informe de Signos Vitales de los CDC de abril del 2016. Una mujer embarazada infectada por el virus del Zika puede pasar el virus a su feto. El virus se ha vinculado a la microcefalia, un defecto congénito grave. Este podcast trata sobre cómo protegerse del virus del Zika.  Created: 4/1/2016 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 4/1/2016.

  20. Perception, attitude and behavior in relation to climate change: A survey among CDC health professionals in Shanxi province, China

    International Nuclear Information System (INIS)

    Background: A better understanding of public perceptions, attitude and behavior in relation to climate change will provide an important foundation for government's policy-making, service provider's guideline development and the engagement of local communities. The purpose of this study was to assess the perception towards climate change, behavior change, mitigation and adaptation measures issued by the central government among the health professionals in the Centres for Disease Control and Prevention (CDC) in China. Methods: In 2013, a cross-sectional questionnaire survey was undertaken among 314 CDC health professionals in various levels of CDC in Shanxi Province, China. Descriptive analyses were performed. Results: More than two thirds of the respondents believed that climate change has happened at both global and local levels, and climate change would lead to adverse impacts to human beings. Most respondents (74.8%) indicated the emission of greenhouse gases was the cause of climate change, however there was a lack of knowledge about greenhouse gases and their sources. Media was the main source from which respondents obtained the information about climate change. A majority of respondents showed that they were willing to change behavior, but their actions were limited. In terms of mitigation and adaptation measures issued by the Chinese Government, respondents' perception showed inconsistency between strategies and relevant actions. Moreover, although the majority of respondents believed some strategies and measures were extremely important to address climate change, they were still concerned about economic development, energy security, and local environmental protection. Conclusion: There are gaps between perceptions and actions towards climate change among these health professionals. Further efforts need to be made to raise the awareness of climate change among health professionals, and to promote relevant actions to address climate change in

  1. CDC28 phosphorylates Cac1p and regulates the association of chromatin assembly factor i with chromatin

    OpenAIRE

    Jeffery, Daniel CB; Kakusho, Naoko; You, Zhiying; Gharib, Marlene; Wyse, Brandon; Drury, Erin; Weinreich, Michael; Thibault, Pierre; Verreault, Alain; Masai, Hisao; Yankulov, Krassimir

    2015-01-01

    Chromatin Assembly Factor I (CAF-I) plays a key role in the replication-coupled assembly of nucleosomes. It is expected that its function is linked to the regulation of the cell cycle, but little detail is available. Current models suggest that CAF-I is recruited to replication forks and to chromatin via an interaction between its Cac1p subunit and the replication sliding clamp, PCNA, and that this interaction is stimulated by the kinase CDC7. Here we show that another kinase, ...

  2. CDC Signos Vitales- Los alimentos más seguros salvan vidas (Safer Food Saves Lives)

    Centers for Disease Control (CDC) Podcasts

    2015-11-03

    Este podcast se basa en la edición de noviembre del 2015 del informe Signos Vitales de los CDC. Los alimentos contaminados que se envían a múltiples estados pueden causar brotes de enfermedades y enfermar gravemente a muchas personas. Sepa lo que se puede hacer para prevenir y detener los brotes.  Created: 11/3/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 11/3/2015.

  3. Signos Vitales de los CDC-Muertes por intoxicación por alcohol (Alcohol Poisoning Deaths)

    Centers for Disease Control (CDC) Podcasts

    2015-01-06

    Este podcast se basa en la edición de enero del 2015 del informe Signos Vitales de los CDC. En los Estados Unidos, mueren en promedio seis personas cada día debido a la intoxicación por alcohol. Infórmese sobre lo que puede hacer para prevenir los atracones de alcohol y las intoxicaciones por alcohol.  Created: 1/6/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 1/6/2015.

  4. Signos Vitales de los CDC-La comunicación puede salvar vidas (Communication Can Save Lives)

    Centers for Disease Control (CDC) Podcasts

    2015-08-04

    Este podcast se basa en la edición de agosto del 2015 del informe Signos Vitales de los CDC. Las bacterias resistentes a los antibióticos causan por lo menos 23 000 muertes anuales. Infórmese sobre cómo pueden las autoridades de salud pública y los establecimientos de atención médica colaborar para salvar vidas.  Created: 8/4/2015 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 8/4/2015.

  5. Signos Vitales de los CDC Cómo prevenir los brotes de norovirus (Vital Signs-Preventing Norovirus Outbreaks)

    Centers for Disease Control (CDC) Podcasts

    2014-06-03

    Este podcast se basa en la edición de junio del 2014 del informe Signos Vitales de los CDC. Los norovirus infectan cada año a cerca de 20 millones de personas en los Estados Unidos. Sepa cómo protegerse y proteger a su familia de esta enfermedad que es muy contagiosa y potencialmente grave.  Created: 6/3/2014 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 6/3/2014.

  6. Signos Vitales de los CDC Prevención de las sobredosis de medicamentos recetados (Preventing Prescription Drug Overdose)

    Centers for Disease Control (CDC) Podcasts

    2014-07-01

    Este podcast se basa en la edición de julio del informe Signos Vitales de los CDC. Todos los días, 46 personas mueren en los EE. UU. de una sobredosis de analgésicos opioides recetados. Infórmese sobre lo que se puede hacer para que la prescripción de analgésicos sea segura y para ayudar a prevenir las sobredosis.  Created: 7/1/2014 by National Center for Injury Prevention and Control (NCIPC).   Date Released: 7/1/2014.

  7. Perception, attitude and behavior in relation to climate change: A survey among CDC health professionals in Shanxi province, China

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Junni, E-mail: junxinni@163.com [Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, Shanxi (China); Hansen, Alana, E-mail: alana.hansen@adelaide.edu.au [Discipline of Public Health, School of Population Health, The University of Adelaide, Adelaide 5005 (Australia); Zhang, Ying, E-mail: ying.zhang@sydney.edu.au [Sydney School of Public Health, The University of Sydney, NSW 2006 (Australia); Li, Hong [Shanxi Center for Disease Control and Prevention, Taiyuan 030001 Shanxi (China); Liu, Qiyong, E-mail: liuqiyong@icdc.cn [State Key Laboratory for Infectious Diseases Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206 (China); Shandong University Climate Change and Health Center, Jinan 250012, Shandong (China); Sun, Yehuan, E-mail: yhsun@sina.com [Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei 230032, Anhui (China); Bi, Peng, E-mail: peng.bi@adelaide.edu.au [Discipline of Public Health, School of Population Health, The University of Adelaide, Adelaide 5005 (Australia)

    2014-10-15

    Background: A better understanding of public perceptions, attitude and behavior in relation to climate change will provide an important foundation for government's policy-making, service provider's guideline development and the engagement of local communities. The purpose of this study was to assess the perception towards climate change, behavior change, mitigation and adaptation measures issued by the central government among the health professionals in the Centres for Disease Control and Prevention (CDC) in China. Methods: In 2013, a cross-sectional questionnaire survey was undertaken among 314 CDC health professionals in various levels of CDC in Shanxi Province, China. Descriptive analyses were performed. Results: More than two thirds of the respondents believed that climate change has happened at both global and local levels, and climate change would lead to adverse impacts to human beings. Most respondents (74.8%) indicated the emission of greenhouse gases was the cause of climate change, however there was a lack of knowledge about greenhouse gases and their sources. Media was the main source from which respondents obtained the information about climate change. A majority of respondents showed that they were willing to change behavior, but their actions were limited. In terms of mitigation and adaptation measures issued by the Chinese Government, respondents' perception showed inconsistency between strategies and relevant actions. Moreover, although the majority of respondents believed some strategies and measures were extremely important to address climate change, they were still concerned about economic development, energy security, and local environmental protection. Conclusion: There are gaps between perceptions and actions towards climate change among these health professionals. Further efforts need to be made to raise the awareness of climate change among health professionals, and to promote relevant actions to address climate change in

  8. PKA-regulated phosphorylation status of S149 and S321 sites of CDC25B inhibits mitosis of fertilized mouse eggs%蛋白激酶A对CDC25B蛋白S149与S321位点磷酸化的修饰抑制小鼠1-细胞期受精卵有丝分裂

    Institute of Scientific and Technical Information of China (English)

    肖建英; 刘超; 孙小涵; 于秉治

    2012-01-01

    To further test whether protein kinase A (PKA) can affect the mitotic cell cycle, one-cell stage mouse embryos at S phase (22 h after hCG injection) were incubated in M16 medium containing various concentrations of H-89, a PKA inhibitor. With increasing concentrations of H-89 (0-50 μmol/L), the G2 phase of eggs was decreased and the cleavage rate was accelerated. A concentration of 40 μmol/L H-89 led to all of the mouse eggs entering the M phase of mitosis. Furthermore, to study the role of PKA in regulating the phosphorylation status of S149 and S321 sites of cell division cycle 25B (CDC25B) on one-cell stage fertilized mouse eggs, pBSK-CDC25B-WT, pBSK-CDC25B-S149A, pBSK-CDC25B-S321A and pBSK-CDC25B-S149A/S321A were transcribed into mRNAs in vitro, then mRNAs were microinjected into S phase of mouse fertilized eggs and cultured in M16 medium pretreated with H-89. Then, the cleavage of fertilized eggs, maturation promoting factor (MPF) activity and phosphorylation status of CDC2-Tyr15 were observed. In the presence of 40 umol/L H-89, the cleavage rate of fertilized eggs in CDC25B-S/A-mRNAs and CDC25B-WT-mRNA injected groups was significantly higher than that in the control groups, and the peak of MPF activity appeared in the CDC25B-S/A-mRNAs and CDC25B-WT-mRNA injected groups earlier than that in the control groups. CDC2-Tyr15 phosphorylation state was consistent with MPF activity. In conclusion, the present study suggests that PKA regulates the early development ofmouse embryos by phosphorylation of S149 and S321 of CDC25B, which plays an important role in the regulation of G2/M transition in the mitotic cell cycle of fertilized mouse eggs.%在小鼠1-细胞期受精卵,蛋白激酶A (protein kinase A,PKA)可通过磷酸化细胞分裂周期25B (cell division cycle 25B,CDC25B)的321位Ser引起受精卵分裂阻滞.本文旨在研究PKA对CDC25B 149位点Ser的磷酸化对小鼠受精卵发育的影响,及其与321位点的关系.质粒pBSK-CDC25B-WT (野生型)、pBSK-CDC

  9. Cloud Computing Vs. Grid Computing

    OpenAIRE

    Seyyed Mohsen Hashemi; Amid Khatibi Bardsiri

    2012-01-01

    Cloud computing emerges as one of the hottest topic in field of information technology. Cloud computing is based on several other computing research areas such as HPC, virtualization, utility computing and grid computing. In order to make clear the essential of cloud computing, we propose the characteristics of this area which make cloud computing being cloud computing and distinguish it from other research areas. The service oriented, loose coupling, strong fault tolerant, business model and...

  10. Involvement of the Cdc42 pathway in CFTR post-translational turnover and in its plasma membrane stability in airway epithelial cells.

    Directory of Open Access Journals (Sweden)

    Romain Ferru-Clément

    Full Text Available Cystic fibrosis transmembrane conductance regulator (CFTR is a chloride channel that is expressed on the apical plasma membrane (PM of epithelial cells. The most common deleterious allele encodes a trafficking-defective mutant protein undergoing endoplasmic reticulum-associated degradation (ERAD and presenting lower PM stability. In this study, we investigated the involvement of the Cdc42 pathway in CFTR turnover and trafficking in a human bronchiolar epithelial cell line (CFBE41o- expressing wild-type CFTR. Cdc42 is a small GTPase of the Rho family that fulfils numerous cell functions, one of which is endocytosis and recycling process via actin cytoskeleton remodelling. When we treated cells with chemical inhibitors such as ML141 against Cdc42 and wiskostatin against the downstream effector N-WASP, we observed that CFTR channel activity was inhibited, in correlation with a decrease in CFTR amount at the cell surface and an increase in dynamin-dependent CFTR endocytosis. Anchoring of CFTR to the cortical cytoskeleton was then presumably impaired by actin disorganization. When we performed siRNA-mediated depletion of Cdc42, actin polymerization was not impacted, but we observed actin-independent consequences upon CFTR. Total and PM CFTR amounts were increased, resulting in greater activation of CFTR. Pulse-chase experiments showed that while CFTR degradation was slowed, CFTR maturation through the Golgi apparatus remained unaffected. In addition, we observed increased stability of CFTR in PM and reduction of its endocytosis. This study highlights the involvement of the Cdc42 pathway at several levels of CFTR biogenesis and trafficking: (i Cdc42 is implicated in the first steps of CFTR biosynthesis and processing; (ii it contributes to the stability of CFTR in PM via its anchoring to cortical actin; (iii it promotes CFTR endocytosis and presumably its sorting toward lysosomal degradation.

  11. Functional role of evolutionarily highly conserved residues, N-glycosylation level and domains of the Leishmania miltefosine transporter-Cdc50 subunit.

    Science.gov (United States)

    García-Sánchez, Sebastián; Sánchez-Cañete, María P; Gamarro, Francisco; Castanys, Santiago

    2014-04-01

    Cdc50 (cell-cycle control protein 50) is a family of conserved eukaryotic proteins that interact with P4-ATPases (phospholipid translocases). Cdc50 association is essential for the endoplasmic reticulum export of P4-ATPases and proper translocase activity. In the present study, we analysed the role of Leishmania infantum LiRos3, the Cdc50 subunit of the P4-ATPase MLF (miltefosine) transporter [LiMT (L. infantum MLF transporter)], on trafficking and complex functionality using site-directed mutagenesis and domain substitution. We identified 22 invariant residues in the Cdc50 proteins from L. infantum, human and yeast. Seven of these residues are found in the extracellular domain of LiRos3, the conservation of which is critical for ensuring that LiMT arrives at the plasma membrane. The substitution of other invariant residues affects complex trafficking to a lesser extent. Furthermore, invariant residues located in the N-terminal cytosolic domain play a role in the transport activity. Partial N-glycosylation of LiRos3 reduces MLF transport and total N-deglycosylation completely inhibits LiMT trafficking to the plasma membrane. One of the N-glycosylation residues is invariant along the Cdc50 family. The transmembrane and exoplasmic domains are not interchangeable with the other two L. infantum Cdc50 proteins to maintain LiMT interaction. Taken together, these findings indicate that both invariant and N-glycosylated residues of LiRos3 are implicated in LiMT trafficking and transport activity. PMID:24447089

  12. Inter-kingdom Signaling by the Legionella Quorum Sensing Molecule LAI-1 Modulates Cell Migration through an IQGAP1-Cdc42-ARHGEF9-Dependent Pathway

    Science.gov (United States)

    Simon, Sylvia; Schell, Ursula; Heuer, Natalie; Hager, Dominik; Albers, Michael F.; Matthias, Jan; Fahrnbauer, Felix; Trauner, Dirk; Eichinger, Ludwig; Hedberg, Christian; Hilbi, Hubert

    2015-01-01

    Small molecule signaling promotes the communication between bacteria as well as between bacteria and eukaryotes. The opportunistic pathogenic bacterium Legionella pneumophila employs LAI-1 (3-hydroxypentadecane-4-one) for bacterial cell-cell communication. LAI-1 is produced and detected by the Lqs (Legionella quorum sensing) system, which regulates a variety of processes including natural competence for DNA uptake and pathogen-host cell interactions. In this study, we analyze the role of LAI-1 in inter-kingdom signaling. L. pneumophila lacking the autoinducer synthase LqsA no longer impeded the migration of infected cells, and the defect was complemented by plasmid-borne lqsA. Synthetic LAI-1 dose-dependently inhibited cell migration, without affecting bacterial uptake or cytotoxicity. The forward migration index but not the velocity of LAI-1-treated cells was reduced, and the cell cytoskeleton appeared destabilized. LAI-1-dependent inhibition of cell migration involved the scaffold protein IQGAP1, the small GTPase Cdc42 as well as the Cdc42-specific guanine nucleotide exchange factor ARHGEF9, but not other modulators of Cdc42, or RhoA, Rac1 or Ran GTPase. Upon treatment with LAI-1, Cdc42 was inactivated and IQGAP1 redistributed to the cell cortex regardless of whether Cdc42 was present or not. Furthermore, LAI-1 reversed the inhibition of cell migration by L. pneumophila, suggesting that the compound and the bacteria antagonistically target host signaling pathway(s). Collectively, the results indicate that the L. pneumophila quorum sensing compound LAI-1 modulates migration of eukaryotic cells through a signaling pathway involving IQGAP1, Cdc42 and ARHGEF9. PMID:26633832

  13. An acidic loop and cognate phosphorylation sites define a molecular switch that modulates ubiquitin charging activity in Cdc34-like enzymes

    DEFF Research Database (Denmark)

    Papaleo, Elena; Ranzani, Valeria; Tripodi, Farida; Vitriolo, Alessandro; Cirulli, Claudia; Fantucci, Piercarlo; Alberghina, Lilia; Vanoni, Marco; De Gioia, Luca; Coccetti, Paola

    2011-01-01

    mechanism for cellular regulation, which modulates protein conformation. In this contribution, we provide the first rationale, at the molecular level, of the regulatory mechanism mediated by casein kinase 2 (CK2) phosphorylation of E2 Cdc34-like enzymes. In particular, we identify two co-evolving signature...... elements in one of the larger families of E2 enzymes: an acidic insertion in β4α2 loop in the proximity of the catalytic cysteine and two conserved key serine residues within the catalytic domain, which are phosphorylated by CK2. Our investigations, using yeast Cdc34 as a model, through 2.5 µs molecular...

  14. Mum, this bud’s for you: where do you want it? Roles for Cdc42 in controlling bud site selection in Saccharomyces cerevisiae

    OpenAIRE

    Nelson, W. James

    2003-01-01

    The generation of asymmetric cell shapes is a recurring theme in biology. In budding yeast, one form of cell asymmetry occurs for division and is generated by anisotropic growth of the mother cell to form a daughter cell bud. Previous genetic studies uncovered key roles for the small GTPase Cdc42 in organizing the actin cytoskeleton and vesicle delivery to the site of bud growth,(1,2) but a recent paper has also raised questions about how control of Cdc42 activity is integrated into a propose...

  15. E2F-Rb Complexes Assemble and Inhibit cdc25A Transcription in Cervical Carcinoma Cells following Repression of Human Papillomavirus Oncogene Expression

    OpenAIRE

    Wu, Lingling; Goodwin, Edward C.; Naeger, Lisa Kay; Vigo, Elena; Galaktionov, Konstantin; Helin, Kristian; DiMaio, Daniel

    2000-01-01

    Expression of the bovine papillomavirus E2 protein in cervical carcinoma cells represses expression of integrated human papillomavirus (HPV) E6/E7 oncogenes, followed by repression of the cdc25A gene and other cellular genes required for cell cycle progression, resulting in dramatic growth arrest. To explore the mechanism of repression of cell cycle genes in cervical carcinoma cells following E6/E7 repression, we analyzed regulation of the cdc25A promoter, which contains two consensus E2F bin...

  16. Two S-phase checkpoint systems, one involving the function of both BIME and Tyr15 phosphorylation of p34cdc2, inhibit NIMA and prevent premature mitosis.

    OpenAIRE

    Ye, X S; Fincher, R R; Tang, A.; O'Donnell, K; Osmani, S A

    1996-01-01

    We demonstrate that there are at least two S-phase checkpoint mechanisms controlling mitosis in Aspergillus. The first responds to the rate of DNA replication and inhibits mitosis via tyrosine phosphorylation of p34cdc2. Cells unable to tyrosine phosphorylate p34cdc2 are therefore viable but are unable to tolerate low levels of hydroxyurea and prematurely enter lethal mitosis when S-phase is slowed. However, if the NIMA mitosis-promoting kinase is inactivated then non-tyrosine-phosphorylated ...

  17. Altered mRNA cap recognition activity of initiation factor 4E in the yeast cell cycle division mutant cdc33.

    OpenAIRE

    Altmann, M; Trachsel, H

    1989-01-01

    The mutation in the S. cerevisiae cell cycle division mutant cdc33 consists of a single G to A transition in the open reading frame encoding translation initiation factor 4E (eIF-4E). This leads to the substitution of glycine 113 by aspartic acid close to tryptophane 115 in the protein. This mutation reduces cap binding activity of eIF-4E as measured by binding of eIF-4E to m7GDP agarose columns and slows down overall protein synthesis at the non-permissive temperature. Comparison of the cdc3...

  18. A microprocessor-based single board computer for high energy physics event pattern recognition

    International Nuclear Information System (INIS)

    A single board MC 68000 based computer has been assembled and bench marked against the CDC 7600 running portions of the pattern recognition code used at the MPS. This computer has a floating coprocessor to achieve throughputs equivalent to several percent that of the 7600. A major part of this work was the construction of a FORTRAN compiler including assembler, linker and library. The intention of this work is to assemble a large number of these single board computers in a parallel FASTBUS environment to act as an on-line and off-line filter for the raw data from MPS II and ISABELLE experiments. (orig.)

  19. Microprocessor-based single board computer for high energy physics event pattern recognition

    International Nuclear Information System (INIS)

    A single board MC 68000 based computer has been assembled and bench marked against the CDC 7600 running portions of the pattern recognition code used at the MPS. This computer has a floating coprocessor to achieve throughputs equivalent to several percent that of the 7600. A major part of this work was the construction of a FORTRAN compiler including assembler, linker and library. The intention of this work is to assemble a large number of these single board computers in a parallel FASTBUS environment to act as an on-line and off-line filter for the raw data from MPS II and ISABELLE experiments

  20. REEFER: a digital computer program for the simulation of high energy electron tubes. [Reefer

    Energy Technology Data Exchange (ETDEWEB)

    Boers, J.E.

    1976-11-01

    A digital computer program for the simulation of very high-energy electron and ion beams is described. The program includes space-charge effects through the solution of Poisson's equation and magnetic effects (both induced and applied) through the relativistic trajectory equations. Relaxation techniques are employed while alternately computing electric fields and trajectories. Execution time is generally less than 15 minutes on a CDC 6600 digital computer. Either space-charge-limited or field-emission sources may be simulated. The input data is described in detail and an example data set is included.