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. 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.)

  3. 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.

  4. 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...

  5. 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

  6. 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)

  7. 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.

  8. 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)

  9. 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

  10. ACORN: a computer program for plotting fault trees. [In FORTRAN for CDC Cyber 74

    Energy Technology Data Exchange (ETDEWEB)

    Carter, J.L.

    1977-11-01

    A description and user instructions are presented for ACORN, a FORTRAN computer program for drawing fault trees. ACORN analyzes the input logical structure of a fault tree and provides data for CalComp plot of the tree. AND, OR, and INHIBIT gates are permitted, and basic events are drawn as diamonds, circles, or houses. Each component (gate or basic event) can have a descriptive label within a rectangle attached to the top of its respective symbol. Tree logic is input as a set of FORTRAN statements, each defining a gate in terms of logical operations of the components input to it. ACORN develops the logical structure of the tree from the input statements. The tree's physical structure is developed by assigning relative spatial coordinates to the logical relationships between a gate and its inputs. ACORN provides input data checking, a printer plot of the fault tree, and plotting data for a CalComp model 763 plotter. The program is operational on a CONTROL DATA CYBER 74 computer. 2 figures, 1 table.

  11. 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.

  12. 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.

  13. 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.

  14. Performance evaluation of linear algebra software in parallel architectures. [FPS, CDC, Cray, Burroughs, ICL, and TI computers

    Energy Technology Data Exchange (ETDEWEB)

    Jordan, T.L.

    1979-10-01

    Performance data of parallel computers on several of the problems of linear algebra using direct methods are provided. The computers considered include software pipeline, hardware pipeline, single-instruction multiple-data, and multiple-instruction multiple-data. Special features of each architecture are considered. Factors such as start-up time, scalar-vector break-even points, consistency in operation count, parallel steps required, and speed-up and efficiency of the hardware are discussed. A reasonably broad comparison is given for LU factorization without pivoting. A less extensive comparison is given for LU factorization with pivoting. Also various intracomputer comparisons are presented to show the performance of different implementations of a particcular algorithm as well as the performance of different algorithms for solving the same problem. Data were collected for the linear algebraic problems of matrix multiplication, regular sparse systems (including tridiagonal systems and dissection techniques), and random sparse systems. The eigenvalue problem is not addressed. 15 figures, 7 tables.

  15. 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...

  16. 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....

  17. 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.)

  18. 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.

  19. 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

  20. 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.

  1. 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...

  2. 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,...

  3. 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,...

  4. 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,...

  5. 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,...

  6. 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,...

  7. 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,...

  8. 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,...

  9. 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,...

  10. 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,...

  11. 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,...

  12. 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,...

  13. 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,...

  14. 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.

  15. 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.

  16. 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 ...

  17. Phosphorylation of Cdc5 regulates its accumulation

    Directory of Open Access Journals (Sweden)

    Simpson-Lavy Kobi J

    2011-12-01

    Full Text Available Abstract Background Cdc5 (polo kinase/Plk1 is a highly conserved key regulator of the S. cerevisiae cell cycle from S-phase until cytokinesis. However, much of the regulatory mechanisms that govern Cdc5 remain to be determined. Cdc5 is phosphorylated on up to 10 sites during mitosis. In this study, we investigated the function of phosphorylation site T23, the only full consensus Cdk1 (Cdc28 phosphorylation site present. Findings Cdc5T23A introduces a degron that reduces its cellular amount to undetectable levels, which are nevertheless sufficient for normal cell proliferation. The degron acts in cis and is reversed by N-terminal GFP-tagging. Cdk1 kinase activity is required to maintain Cdc5 levels during G2. This, Cdk1 inhibited, Cdc5 degradation is APC/CCdh1 independent and requires new protein synthesis. Cdc5T23E is hyperactive, and reduces the levels of Cdc5 (in trans and drastically reduces Clb2 levels. Conclusions Phosphorylation of Cdc5 by Cdk1 is required to maintain Cdc5 levels during G2. However, phosphorylation of T23 (probably by Cdk1 caps Cdc5 and other CLB2 cluster protein accumulation, preventing potential protein toxicity, which may arise from their overexpression or from APC/CCdh1 inactivation.

  18. 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).

  19. 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).

  20. 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.

  1. 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...

  2. Cdc25 and Wee1: analogous opposites?

    Directory of Open Access Journals (Sweden)

    Kornbluth Sally

    2007-05-01

    Full Text Available Abstract Movement through the cell cycle is controlled by the temporally and spatially ordered activation of cyclin-dependent kinases paired with their respective cyclin binding partners. Cell cycle events occur in a stepwise fashion and are monitored by molecular surveillance systems to ensure that each cell cycle process is appropriately completed before subsequent events are initiated. Cells prevent entry into mitosis while DNA replication is ongoing, or if DNA is damaged, via checkpoint mechanisms that inhibit the activators and activate the inhibitors of mitosis, Cdc25 and Wee1, respectively. Once DNA replication has been faithfully completed, Cdc2/Cyclin B is swiftly activated for a timely transition from interphase into mitosis. This sharp transition is propagated through both positive and negative feedback loops that impinge upon Cdc25 and Wee1 to ensure that Cdc2/Cyclin B is fully activated. Recent reports from a number of laboratories have revealed a remarkably complex network of kinases and phosphatases that coordinately control Cdc25 and Wee1, thereby precisely regulating the transition into mitosis. Although not all factors that inhibit Cdc25 have been shown to activate Wee1 and vice versa, a number of regulatory modules are clearly shared in common. Thus, studies on either the Cdc25 or Wee1-regulatory arm of the mitotic control pathway should continue to shed light on how both arms are coordinated to smoothly regulate mitotic entry.

  3. 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...

  4. 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....

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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 ...

  13. 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,...

  14. 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,...

  15. 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,...

  16. 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...

  17. 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 ...

  18. 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 ...

  19. 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...

  20. 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 ...

  1. 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...

  2. 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....

  3. 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...

  4. CDC Updates Spending Plans to Combat Zika

    Science.gov (United States)

    ... 161541.html CDC Updates Spending Plans to Combat Zika Some goals: prepare states for future outbreaks, and ... dollars to prepare states and cities for future Zika virus outbreaks, and to track the effects of ...

  5. 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

  6. Regulated degradation of the APC coactivator Cdc20

    Directory of Open Access Journals (Sweden)

    Robbins Jonathan A

    2010-09-01

    Full Text Available Abstract Background Cdc20 is a highly conserved activator of the anaphase-promoting complex (APC, promoting cell-cycle-regulated ubiquitination and proteolysis of a number of critical cell-cycle-regulatory targets including securin and mitotic cyclins. APC-Cdc20 activity is tightly regulated, and this regulation is likely important for accurate cell cycle control. One significant component of Cdc20 regulation is thought to be Cdc20 proteolysis. However, published literature suggests different mechanisms and requirements for Cdc20 proteolysis. The degree to which Cdc20 proteolysis is cell-cycle regulated, the dependence of Cdc20 proteolysis on Cdc20 destruction boxes (recognition sequences for APC-mediated ubiqutination, either by Cdc20 or by the related Cdh1 APC activator, and the need for APC itself for Cdc20 proteolysis all have been disputed to varying extents. In animals, Cdc20 proteolysis is thought to be mediated by Cdh1, contributing an intrinsic order of APC activation by Cdc20 and then by Cdh1. One report suggests a Cdh1 requirement for Cdc20 proteolysis in budding yeast; this idea has not been tested further. Results We characterized Cdc20 proteolysis using Cdc20 expressed from its endogenous locus; previous studies generally employed strongly overexpressed Cdc20, which can cause significant artifacts. We analyzed Cdc20 proteolysis with or without mutations in previously identified destruction box sequences, using varying methods of cell cycle synchronization, and in the presence or absence of Cdh1. Cdc20 instability is only partially dependent on destruction boxes. A much stronger dependence on Cdh1 for Cdc20 proteolysis was observed, but Cdh1-independent proteolysis was also clearly observed. Cdc20 proteolysis independent of both destruction boxes and Cdh1 was especially detectable around the G1/S transition; Cdh1-dependent proteolysis was most notable in late mitosis and G1. Conclusions Cdc20 proteolysis is under complex control

  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......, 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 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 Supplemental Data...

  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. On-Line Help: Design Issues for Authoring Systems. CDC Technical Report No. 18.

    Science.gov (United States)

    Duffy, Thomas M.; Langston, M. Diane

    Part of the Communications Design Center's (CDC) on-going research on communication and document design, this report emphasizes the importance of a multi-level computer help system that goes beyond simple command descriptions to include assistance with goals and strategies within the application domain--in this case, automated authoring. The help…

  11. 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

  12. 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...

  13. 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...

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 13 CFR 120.851 - CDC ethical requirements.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false CDC ethical requirements. 120.851 Section 120.851 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Other Cdc Requirements § 120.851 CDC ethical requirements. CDCs and...

  19. Cdc48: A Swiss Army Knife of Cell Biology

    Directory of Open Access Journals (Sweden)

    Guem Hee Baek

    2013-01-01

    Full Text Available Cdc48 (also called VCP and p97 is an abundant protein that plays essential regulatory functions in a broad array of cellular processes. Working with various cofactors, Cdc48 utilizes its ATPase activity to promote the assembly and disassembly of protein complexes. Here, we review key biological functions and regulation of Cdc48 in ubiquitin-related events. Given the broad employment of Cdc48 in cell biology and its intimate ties to human diseases (e.g., amyotrophic lateral sclerosis, studies of Cdc48 will bring significant insights into the mechanism and function of ubiquitin in health and diseases.

  20. Human Cdc14B promotes progression through mitosis by dephosphorylating Cdc25 and regulating Cdk1/cyclin B activity.

    Directory of Open Access Journals (Sweden)

    Indra Tumurbaatar

    Full Text Available Entry into and progression through mitosis depends on phosphorylation and dephosphorylation of key substrates. In yeast, the nucleolar phosphatase Cdc14 is pivotal for exit from mitosis counteracting Cdk1-dependent phosphorylations. Whether hCdc14B, the human homolog of yeast Cdc14, plays a similar function in mitosis is not yet known. Here we show that hCdc14B serves a critical role in regulating progression through mitosis, which is distinct from hCdc14A. Unscheduled overexpression of hCdc14B delays activation of two master regulators of mitosis, Cdc25 and Cdk1, and slows down entry into mitosis. Depletion of hCdc14B by RNAi prevents timely inactivation of Cdk1/cyclin B and dephosphorylation of Cdc25, leading to severe mitotic defects, such as delay of metaphase/anaphase transition, lagging chromosomes, multipolar spindles and binucleation. The results demonstrate that hCdc14B-dependent modulation of Cdc25 phosphatase and Cdk1/cyclin B activity is tightly linked to correct chromosome segregation and bipolar spindle formation, processes that are required for proper progression through mitosis and maintenance of genomic stability.

  1. Psychometric properties of the Centers for Disease Control and Prevention Health-Related Quality of Life (CDC HRQOL items in adults with arthritis

    Directory of Open Access Journals (Sweden)

    DeVellis Robert

    2006-09-01

    Full Text Available Abstract Background Measuring health-related quality of life (HRQOL is important in arthritis and the SF-36v2 is the current state-of-the-art. It is only emerging how well the Centers for Disease Control and Prevention (CDC HRQOL measures HRQOL for people with arthritis. This study's purpose is to assess the psychometric properties of the 9-item CDC HRQOL (4-item Healthy Days Core Module and 5-item Healthy Days Symptoms Module in an arthritis sample using the SF-36v2 as a comparison. Methods In Fall 2002, a cross-sectional study acquired survey data including the CDC HRQOL and SF-36v2 from 2 North Carolina populations of adult patients reporting osteoarthritis, rheumatoid arthritis, and fibromyalgia; 2182 (52% responded. The first item of both the CDC HRQOL and the SF-36v2 was general health (GEN. All 8 other CDC HRQOL items ask for the number of days in the past 30 days that respondents experienced various aspects of HRQOL. Exploratory principal components analyses (PCA were conducted on each sample and the combined samples of the CDC HRQOL. The multitrait-multimethod matrix (MTMM was used to compute correlations between each trait (physical health and mental health and between each method of measurement (CDC HRQOL and SF36v2. The relative contribution of the CDC HRQOL in predicting the physical component summary (PCS and the mental component summary (MCS was determined by regressing the CDC HRQOL items on the PCS and MCS scales. Results All 9 CDC HRQOL items loaded primarily onto 1 factor (explaining 57% of the item variance representing a reasonable solution for capturing overall HRQOL. After rotation a 2 factor interpretation for the 9 items was clear, with 4 items capturing physical health (physical, activity, pain, and energy days and 3 items capturing mental health (mental, depression, and anxiety days. All of the loadings for these two factors were greater than 0.70. The CDC HRQOL physical health factor correlated with PCS (r = -.78, p 2

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Cdc6 ATPase activity disengages Cdc6 from the pre-replicative complex to promote DNA replication.

    Science.gov (United States)

    Chang, FuJung; Riera, Alberto; Evrin, Cecile; Sun, Jingchuan; Li, Huilin; Speck, Christian; Weinreich, Michael

    2015-08-25

    To initiate DNA replication, cells first load an MCM helicase double hexamer at origins in a reaction requiring ORC, Cdc6, and Cdt1, also called pre-replicative complex (pre-RC) assembly. The essential mechanistic role of Cdc6 ATP hydrolysis in this reaction is still incompletely understood. Here, we show that although Cdc6 ATP hydrolysis is essential to initiate DNA replication, it is not essential for MCM loading. Using purified proteins, an ATPase-defective Cdc6 mutant 'Cdc6-E224Q' promoted MCM loading on DNA. Cdc6-E224Q also promoted MCM binding at origins in vivo but cells remained blocked in G1-phase. If after loading MCM, Cdc6-E224Q was degraded, cells entered an apparently normal S-phase and replicated DNA, a phenotype seen with two additional Cdc6 ATPase-defective mutants. Cdc6 ATP hydrolysis is therefore required for Cdc6 disengagement from the pre-RC after helicase loading to advance subsequent steps in helicase activation in vivo.

  7. 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…

  8. 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 ...

  9. Cdc42 deficiency causes ciliary abnormalities and cystic kidneys.

    Science.gov (United States)

    Choi, Soo Young; Chacon-Heszele, Maria F; Huang, Liwei; McKenna, Sarah; Wilson, F Perry; Zuo, Xiaofeng; Lipschutz, Joshua H

    2013-09-01

    Ciliogenesis and cystogenesis require the exocyst, a conserved eight-protein trafficking complex that traffics ciliary proteins. In culture, the small GTPase Cdc42 co-localizes with the exocyst at primary cilia and interacts with the exocyst component Sec10. The role of Cdc42 in vivo, however, is not well understood. Here, knockdown of cdc42 in zebrafish produced a phenotype similar to sec10 knockdown, including tail curvature, glomerular expansion, and mitogen-activated protein kinase (MAPK) activation, suggesting that cdc42 and sec10 cooperate in ciliogenesis. In addition, cdc42 knockdown led to hydrocephalus and loss of photoreceptor cilia. Furthermore, there was a synergistic genetic interaction between zebrafish cdc42 and sec10, suggesting that cdc42 and sec10 function in the same pathway. Mice lacking Cdc42 specifically in kidney tubular epithelial cells died of renal failure within weeks of birth. Histology revealed cystogenesis in distal tubules and collecting ducts, decreased ciliogenesis in cyst cells, increased tubular cell proliferation, increased apoptosis, increased fibrosis, and led to MAPK activation, all of which are features of polycystic kidney disease, especially nephronophthisis. Taken together, these results suggest that Cdc42 localizes the exocyst to primary cilia, whereupon the exocyst targets and docks vesicles carrying ciliary proteins. Abnormalities in this pathway result in deranged ciliogenesis and polycystic kidney disease.

  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...... in Cdc20 protein levels, rather than mutations in checkpoint genes, could affect cell fate during prolonged mitotic arrest. This hypothesis is supported by experiments where manipulation of Cdc20 levels affects the response to antimitotic compounds. The observed differences in Cdc20 levels between cell...

  11. Cdc42 deficiency causes ciliary abnormalities and cystic kidneys.

    Science.gov (United States)

    Choi, Soo Young; Chacon-Heszele, Maria F; Huang, Liwei; McKenna, Sarah; Wilson, F Perry; Zuo, Xiaofeng; Lipschutz, Joshua H

    2013-09-01

    Ciliogenesis and cystogenesis require the exocyst, a conserved eight-protein trafficking complex that traffics ciliary proteins. In culture, the small GTPase Cdc42 co-localizes with the exocyst at primary cilia and interacts with the exocyst component Sec10. The role of Cdc42 in vivo, however, is not well understood. Here, knockdown of cdc42 in zebrafish produced a phenotype similar to sec10 knockdown, including tail curvature, glomerular expansion, and mitogen-activated protein kinase (MAPK) activation, suggesting that cdc42 and sec10 cooperate in ciliogenesis. In addition, cdc42 knockdown led to hydrocephalus and loss of photoreceptor cilia. Furthermore, there was a synergistic genetic interaction between zebrafish cdc42 and sec10, suggesting that cdc42 and sec10 function in the same pathway. Mice lacking Cdc42 specifically in kidney tubular epithelial cells died of renal failure within weeks of birth. Histology revealed cystogenesis in distal tubules and collecting ducts, decreased ciliogenesis in cyst cells, increased tubular cell proliferation, increased apoptosis, increased fibrosis, and led to MAPK activation, all of which are features of polycystic kidney disease, especially nephronophthisis. Taken together, these results suggest that Cdc42 localizes the exocyst to primary cilia, whereupon the exocyst targets and docks vesicles carrying ciliary proteins. Abnormalities in this pathway result in deranged ciliogenesis and polycystic kidney disease. PMID:23766535

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 13 CFR 120.823 - CDC Board of Directors.

    Science.gov (United States)

    2010-01-01

    ... the CDC manager must possess commercial lending experience. The Board must meet at least quarterly and shall be responsible for CDC staff decisions and actions. A quorum shall require at least 5 Directors... Committee members must include at least one member with commercial lending experience acceptable to SBA....

  1. 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.

  2. Vectorizing the Monte Carlo algorithm for lattice gauge theory calculations on the CDC cyber 205

    Science.gov (United States)

    Barkai, D.; Moriarty, K. J. M.

    1982-06-01

    Lattice gauge theory is a technique for studying quantum field theory free of divergences. All the Monte Carlo computer calculations up to now have been performed on scalar machines. A technique has been developed for effectively vectorizing this class of Monte Carlo problems. The key for vectorizing is in finding groups in finding groups of points on the space-time lattice which are independent of each other. This requires a particular ordering of points along diagonals. A technique for matrix multiply is used which enables one to get the whole of the result matrix in one pass. The CDC CYBER 205 is most suitable for this class of problems using random "index-lists" (arising from the ordering algorithm and the use of random numbers) due to the hardware implementation of "GATHER" and "SCATTER" operations performing at a streaming-rate. A preliminary implementation of this method has executed 5 times faster than on the CDC 7600 system.

  3. Cat Scratch Can Sometimes Lead to Serious Illness: CDC

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_161086.html Cat Scratch Can Sometimes Lead to Serious Illness: CDC But ... Fluffy the cat gets out of sorts and scratches you, it's possible you could get a bacterial ...

  4. 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...

  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. Smoking Rates Still High in Some Racial Groups, CDC Reports

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_160256.html Smoking Rates Still High in Some Racial Groups, CDC ... lot of progress in getting Americans to stop smoking, some groups still have high smoking rates, a ...

  7. 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....

  8. 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...

  9. 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...

  10. Smoking Losing Its Cool with Kids, CDC Says

    Science.gov (United States)

    ... finds. The same can't be said of e-cigarettes. Fewer students reported trying cigarettes or cigars between ... still showing a worrisome level of interest in e-cigarettes. The CDC released a survey in June that ...

  11. 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 ...

  12. 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....

  13. 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....

  14. CDC Ends Zika Travel Advisory for Miami Neighborhood

    Science.gov (United States)

    ... medlineplus.gov/news/fullstory_161032.html CDC Ends Zika Travel Advisory for Miami Neighborhood Pregnant women still ... News) -- U.S. health officials on Monday lifted the Zika virus travel advisory that urged pregnant women to ...

  15. 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...

  16. 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...

  17. 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...

  18. 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 ...

  19. Synthetic Fentanyl Fueling Surge in Overdose Deaths: CDC

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_160618.html Synthetic Fentanyl Fueling Surge in Overdose Deaths: CDC U.S. Surgeon ... News) -- Deaths from overdoses of the synthetic narcotic fentanyl have surged in recent years, U.S. health officials ...

  20. 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...

  1. 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...

  2. 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....

  3. CDC Awards $16M in Fight Against Zika

    Science.gov (United States)

    ... 160203.html CDC Awards $16M in Fight Against Zika Health experts warn pregnant women to avoid downtown ... where mosquitoes are apparently infecting people with the Zika virus. The number of local transmissions of the ...

  4. Heart Surgery Devices May Have Been Contaminated: CDC

    Science.gov (United States)

    ... 161469.html Heart Surgery Devices May Have Been Contaminated: CDC Patients who experience night sweats, fever, weight ... used during open heart surgery may have been contaminated with bacteria that puts patients at risk for ...

  5. 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...

  6. 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

  7. 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

  8. CDC25A phosphatase controls meiosis I progression in mouse oocytes.

    Science.gov (United States)

    Solc, Petr; Saskova, Adela; Baran, Vladimir; Kubelka, Michal; Schultz, Richard M; Motlik, Jan

    2008-05-01

    CDK1 is a pivotal regulator of resumption of meiosis and meiotic maturation of oocytes. CDC25A/B/C are dual-specificity phosphatases and activate cyclin-dependent kinases (CDKs). Although CDC25C is not essential for either mitotic or meiotic cell cycle regulation, CDC25B is essential for CDK1 activation during resumption of meiosis. Cdc25a -/- mice are embryonic lethal and therefore a role for CDC25A in meiosis is unknown. We report that activation of CDK1 results in a maturation-associated decrease in the amount of CDC25A protein, but not Cdc25a mRNA, such that little CDC25A is present by metaphase I. In addition, expression of exogenous CDC25A overcomes cAMP-mediated maintenance of meiotic arrest. Microinjection of Gfp-Cdc25a and Gpf-Cdc25b mRNAs constructs reveals that CDC25A is exclusively localized to the nucleus prior to nuclear envelope breakdown (NEBD). In contrast, CDC25B localizes to cytoplasm in GV-intact oocytes and translocates to the nucleus shortly before NEBD. Over-expressing GFP-CDC25A, which compensates for the normal maturation-associated decrease in CDC25A, blocks meiotic maturation at MI. This MI block is characterized by defects in chromosome congression and spindle formation and a transient reduction in both CDK1 and MAPK activities. Lastly, RNAi-mediated reduction of CDC25A results in fewer oocytes resuming meiosis and reaching MII. These data demonstrate that CDC25A behaves differently during female meiosis than during mitosis, and moreover, that CDC25A has a function in resumption of meiosis, MI spindle formation and the MI-MII transition. Thus, both CDC25A and CDC25B are critical for meiotic maturation of oocytes.

  9. Decreased uv mutagenesis in cdc8, a DNA replication mutant of Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Prakash, L.; Hinkle, D.; Prakash, S.

    1978-01-01

    A DNA replication mutant of yeast, cdc8, was found to decrease uv-induced reversion of lys2-1, arg4-17, tryl and ural. This effect was observed with all three alleles of cdc8 tested. Survival curves obtained following uv irradiation in cdc8 rad double mutants show that cdc8 is epistatic to rad6, as well as to rad1; cdc8 rad51 double mutants seem to be more sensitive than the single mutants. Since uv-induced reversion in cdc8 rad1 and cdc8 rad51 double mutants is like that of the cdc8 single mutants, we conclude that CDC8 plays a direct role in error-prone repair. To test whether CDC8 codes for a DNA polymerase, we have purified both DNA polymerase I and DNA polymerase II from cdc8 and CDC+ cells. The purified DNA polymerases from cdc8 were no more heat labile than those from CDC+, suggesting that CDC8 is not a structural gene for either enzyme.

  10. 爪形大分子CDC-SO的研究%Claw Type Macromolecule of CDC-SO

    Institute of Scientific and Technical Information of China (English)

    陈玲玲; 龙小柱; 高锦鹏; 王长松; 郭瓦力; 宗学军

    2011-01-01

    选用一缩二乙二醇、柠檬酸、硬脂酸和十八醇为原料,利用酯化反应设计并合成了新的低温流动改性剂:一缩二乙二醇-柠檬酸-硬脂酸-十八醇(CDC-SO).通过单因素试验和正交试验得到了制备CDC-SO的最适宜工艺条件:n(CDC):,n(硬脂酸)为1:1.00;n(CDC-S):n(十八醇)为1:4.0;催化剂用量(以总原料的酸醇总量计)为1.00%;溶剂用量(以总原料的酸醇总量计)为35%;酯化反应时间8 h.将合成的爪形大分子CDC-SO按2.5 mg/g的加剂量添加到沈阳石蜡化工有限公司生产的0#柴油中,冷滤点可降低5℃.%With the diethylene glycol, citric acid, stearic acid and octadeeyl alcohol as raw materials,using the esterification, a new low-temperature flow improver, citric acid-diethylene glycol-citric acidstearic acid-octadecyl alcohol (CDC-SO), was synthesized. Through the single factor and orthogonal experiments, the suitable conditions for preparing CDC-SO were obtained: The mole ratio of CDC to stearic acid was 1: 1.00, the mole ratio of CDC-S to octadecyl alcohol was 1: 4. 0, the dosage of the catalyst was 1.00% based on the total mass of acid and alcohol of the total raw materials, the dosage of the solvent was 35% based on the total mass of acid and alcohol of the total raw materials, the time of the esterification reaction was 8 h. When CDC-SO was added with the dosage of 2.5 mg/g, in 0# diesel oil which was produced by the Shenyang Paraffin Wax Chemical Corporation, thecold filter plugging point could drop 5℃.

  11. The dual specificity phosphatase Cdc14B bundles and stabilizes microtubules

    Energy Technology Data Exchange (ETDEWEB)

    Plumley, Hyekyung [ORNL; Liu, Yie [ORNL; Gomez, Marla V [ORNL; Wang, Yisong [ORNL

    2005-01-01

    The Cdc14 dual-specificity phosphatases regulate key events in the eukaryotic cell cycle. However, little is known about the function of mammalian CDC14B family members. Here, we demonstrate that subcellular localization of CDC14B protein is cell cycle regulated. CDC14B can bind, bundle, and stabilize microtubules in vitro independently of its catalytic activity. Basic amino acid residues within the nucleolar targeting domain are important for both retaining CDC14B in the nucleolus and preventing microtubule bundling. Overexpression of CDC14B resulted in the formation of cytoplasmic CDC14B and microtubule bundles in interphase cells. These microtubule bundles were resistant to microtubule depolymerization reagents and enriched in acetylated -tubulin. Expression of cytoplasmic forms of CDC14B impaired microtubule nucleation from the microtubule organization center. CDC14B is thus a novel microtubule-bundling and -stabilizing protein, whose regulated subcellular localization may help modulate spindle and microtubule dynamics in mitosis.

  12. 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.

  13. 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

  14. 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...

  15. 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.

  16. 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.

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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)

  2. 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$_{60}$.

  3. 77 FR 23733 - CDC/HRSA Advisory Committee on HIV and STD Prevention and Treatment

    Science.gov (United States)

    2012-04-20

    ... CDC/HRSA Advisory Committee on HIV and STD Prevention and Treatment In accordance with section 10(a)(2..., CDC, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, 1600 Clifton Road,...

  4. 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...

  5. COMPUTING

    CERN Document Server

    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 ...

  6. 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 ...

  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. Child Passenger Safety (A Cup of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    2016-09-29

    Proper installation and use of car seats and booster seats for child passengers can save their lives. CDC recommends drivers ensure children are always buckled up. In this podcast, Bethany West discusses how to keep young passengers as safe as possible.  Created: 9/29/2016 by MMWR.   Date Released: 9/29/2016.

  9. CDC WONDER: a cooperative processing architecture for public health.

    Science.gov (United States)

    Friede, A; Rosen, D H; Reid, J A

    1994-01-01

    CDC WONDER is an information management architecture designed for public health. It provides access to information and communications without the user's needing to know the location of data or communication pathways and mechanisms. CDC WONDER users have access to extractions from some 40 databases; electronic mail (e-mail); and surveillance data processing. System components include the Remote Client, the Communications Server, the Queue Managers, and Data Servers and Process Servers. The Remote Client software resides in the user's machine; other components are at the Centers for Disease Control and Prevention (CDC). The Remote Client, the Communications Server, and the Applications Server provide access to the information and functions in the Data Servers and Process Servers. The system architecture is based on cooperative processing, and components are coupled via pure message passing, using several protocols. This architecture allows flexibility in the choice of hardware and software. One system limitation is that final results from some subsystems are obtained slowly. Although designed for public health, CDC WONDER could be useful for other disciplines that need flexible, integrated information exchange.

  10. 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.

  11. 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 ...

  12. 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.

  13. 77 FR 12845 - Centers for Disease Control and Prevention (CDC)

    Science.gov (United States)

    2012-03-02

    ... HUMAN SERVICES Centers for Disease Control and Prevention (CDC) Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns... Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry...

  14. Data communication at the CERN computer centre

    CERN Document Server

    Bruins, T; Pieters, R; Slettenhaar, Hendrik J; Van de Kerk, P

    1972-01-01

    The growing interest for on-line computer service and process control at CERN decentralises certain computer activities. Small process computers, remote batch stations and user terminals are to be backed by a powerful central computer. The present data network is principally star shaped. At the centre of it is a CDC 6600-6500 computer combination. It has a front end CDC 3100 computer with a Hewlett Packard 2116 as multiplexer. Some details about the fast parallel connections between the CDC 3100 and the HP 2116B are given in the paper, as well as descriptions of some computer simulation techniques used to test the present systems. Finally some plans on a future network are given. (12 refs).

  15. 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

  16. CDC2/SPDY transiently associates with endoplasmic reticulum exit sites during oocyte maturation

    NARCIS (Netherlands)

    Holzenspies, Jurriaan J.; Stoorvogel, Willem; Colenbrander, Ben; Roelen, Bernard A. J.; Gutknecht, Dagmar R.; van Haeften, Theo

    2009-01-01

    Background: Mammalian oocytes acquire competence to be fertilized during meiotic maturation. The protein kinase CDC2 plays a pivotal role in several key maturation events, in part through controlled changes in CDC2 localization. Although CDC2 is involved in initiation of maturation, a detailed analy

  17. Modeling the fission yeast cell cycle: Quantized cycle times in wee1 cdc25 mutant cells

    Science.gov (United States)

    Sveiczer, Akos; Csikasz-Nagy, Attila; Gyorffy, Bela; Tyson, John J.; Novak, Bela

    2000-07-01

    A detailed mathematical model for the fission yeast mitotic cycle is developed based on positive and negative feedback loops by which Cdc13/Cdc2 kinase activates and inactivates itself. Positive feedbacks are created by Cdc13/Cdc2-dependent phosphorylation of specific substrates: inactivating its negative regulators (Rum1, Ste9 and Wee1/Mik1) and activating its positive regulator (Cdc25). A slow negative feedback loop is turned on during mitosis by activation of Slp1/anaphase-promoting complex (APC), which indirectly re-activates the negative regulators, leading to a drop in Cdc13/Cdc2 activity and exit from mitosis. The model explains how fission yeast cells can exit mitosis in the absence of Ste9 (Cdc13 degradation) and Rum1 (an inhibitor of Cdc13/Cdc2). We also show that, if the positive feedback loops accelerating the G2/M transition (through Wee1 and Cdc25) are weak, then cells can reset back to G2 from early stages of mitosis by premature activation of the negative feedback loop. This resetting can happen more than once, resulting in a quantized distribution of cycle times, as observed experimentally in wee1- cdc25 mutant cells. Our quantitative description of these quantized cycles demonstrates the utility of mathematical modeling, because these cycles cannot be understood by intuitive arguments alone.

  18. 13 CFR 120.820 - CDC non-profit status and good standing.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false CDC non-profit status and good... CDC non-profit status and good standing. A CDC must be a non-profit corporation, except that for-profit CDCs certified by SBA prior to January 1, 1987 may retain their certifications. An SBIC may...

  19. 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...

  20. 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...

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

    Directory of Open Access Journals (Sweden)

    Jose-Antonio Rodriguez-Rodriguez

    2016-05-01

    Full Text Available 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.

  2. 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...

  3. 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 ...

  4. 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...

  5. COMPUTING

    CERN Document Server

    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...

  6. 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...

  7. COMPUTING

    CERN Document Server

    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...

  8. COMPUTING

    CERN Document Server

    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. 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...

  10. Quantitative analysis of membrane trafficking in regulation of Cdc42 polarity.

    Science.gov (United States)

    Watson, Leah J; Rossi, Guendalina; Brennwald, Patrick

    2014-12-01

    Vesicle delivery of Cdc42 has been proposed as an important mechanism for generating and maintaining Cdc42 polarity at the plasma membrane. This mechanism requires the density of Cdc42 on secretory vesicles to be equal to or higher than the plasma membrane polarity cap. Using a novel method to estimate Cdc42 levels on post-Golgi secretory vesicles in intact yeast cells, we: (1) determined that endocytosis plays an important role in Cdc42's association with secretory vesicles (2) found that a GFP-tag placed on the N-terminus of Cdc42 negatively impacts this vesicle association and (3) quantified the surface densities of Cdc42 on post-Golgi vesicles which revealed that the vesicle density of Cdc42 is three times more dilute than that at the polarity cap. This work suggests that the immediate consequence of secretory vesicle fusion with the plasma membrane polarity cap is to dilute the local Cdc42 surface density. This provides strong support for the model in which vesicle trafficking acts to negatively regulate Cdc42 polarity on the cell surface while also providing a means to recycle Cdc42 between the cell surface and internal membrane locations.

  11. 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...

  12. COMPUTING

    CERN Document Server

    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...

  13. 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...

  14. 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...

  15. 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 ...

  16. 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...

  17. 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...

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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...

  4. 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...

  5. 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...

  6. 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

  7. Enhanced membrane fluorescence of CDC-labelled paramecium subsequent to removal of surface components.

    Science.gov (United States)

    Wyroba, E; Bottiroli, G; Giordano, P

    1983-01-01

    Cytofluorimetric analysis of cycloheptaamylose-dansyl chloride (CDC) labelled Paramecium indicates that after mild trypsin removal of surface components the localization of CDC on the outer surface of living cells was not modified by the treatment. After such treatment the intensity of fluorescence emission was found about 3-fold higher in treated single cell than in the untreated one. These findings indicate that CDC labelling can be used to follow alteration occurred on the membrane of the living cell prior to labelling.

  8. 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...

  9. 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...

  10. Role of Cdc42-Cla4 interaction in the pheromone response of Saccharomyces cerevisiae.

    Science.gov (United States)

    Heinrich, Melanie; Köhler, Tim; Mösch, Hans-Ulrich

    2007-02-01

    In Saccharomyces cerevisiae, the highly conserved Rho-type GTPase Cdc42 is essential for cell division and controls cellular development during mating and invasive growth. The role of Cdc42 in mating has been controversial, but a number of previous studies suggest that the GTPase controls the mitogen-activated protein (MAP) kinase cascade by activating the p21-activated protein kinase (PAK) Ste20. To further explore the role of Cdc42 in pheromone-stimulated signaling, we isolated novel alleles of CDC42 that confer resistance to pheromone. We find that in CDC42(V36A) and CDC42(V36A, I182T) mutant strains, the inability to undergo pheromone-induced cell cycle arrest correlates with reduced phosphorylation of the mating MAP kinases Fus3 and Kss1 and with a decrease in mating efficiency. Furthermore, Cdc42(V36A) and Cdc42(V36A, I182T) proteins show reduced interaction with the PAK Cla4 but not with Ste20. We also show that deletion of CLA4 in a CDC42(V36A, I182T) mutant strain suppresses pheromone resistance and that overexpression of CLA4 interferes with pheromone-induced cell cycle arrest and MAP kinase phosphorylation in CDC42 wild-type strains. Our data indicate that Cla4 has the potential to act as a negative regulator of the mating pathway and that this function of the PAK might be under control of Cdc42. In conclusion, our study suggests that control of pheromone signaling by Cdc42 not only depends on Ste20 but also involves interaction of the GTPase with Cla4. PMID:17189484

  11. Screening the active constituents of Chinese medicinal herbs as potent inhibitors of Cdc25 tyrosine phosphatase, an activator of the mitosis-inducing p34cdc2 kinase

    Institute of Scientific and Technical Information of China (English)

    YANG Hua; ZHENG Shu; MEIJER Laurent; LI Shi-min; LECLERC Sophie; YU Lin-lin; CHENG Jin-quan; ZHANG Su-zhan

    2005-01-01

    Objective: To screen and evaluate the active constituents of Chinese medicinal herbs as potent inhibitors of Cdc25phosphatase. Methods: The affinity chromatography purified glutashione-S-transferase/Cdc25A phosphatase fusion protein and Cdc2/cyclin B from the extracts of starfish M phase oocytes are used as the cell cycle-specific targets for screening the antimitotic constituents. We tested 9 extracts isolated from the Chinese medicinal herbs and vegetables including the agents currently used in cancer treatment by measuring the inhibition of Cdc25A phosphatase and Cdc2 kinase activity. The antitumor activity of the extracts was also evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and flow cytometry.Results: Cdc25A inhibitory activity and antitumor activity are detected in the extracts isolated from three Chinese medicinal herbs Agrimonapilosa; Herba solani lyrati; Galla chinesis. Conclusion: We found three extracts isolated from Chinese medicinal herbs have potential inhibitory activity of Cdc25 phosphatase using a highly specific mechanism-based screen assay for antimitotic drug discovery.

  12. 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

  13. 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...

  14. 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...

  15. 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...

  16. 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.

  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. 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.

  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. 光滑念珠菌 Cdc42基因生物信息分析%Bioinformatics Analysis of Cdc42 Gene from Candida Glabrata

    Institute of Scientific and Technical Information of China (English)

    赵静; 黄怀球; 袁立燕; 钟毅; 张静; 张晓辉

    2013-01-01

    目的:分析和预测光滑念珠菌Cdc42基因及其编码蛋白的结构和特性。方法:利用NCBI、Ex-PASy和CBS网站中的各种信息分析工具,并结合Vector NTI suite 8.0生物信息学分析软件包,分析预测光滑念珠菌Cdc42基因并预测该基因编码蛋白结构的特征和功能。结果:Cdc42基因全长为576 bp,编码区具有191个氨基酸,在GenBank同源序列中,其与酵母 Cdc42氨基酸序列一致性达到99%,且有Cdc42保守域。 Cdc42蛋白相对分子量预测为21420.83,理论等电点为6.31。预测Cdc42编码蛋白ɑ螺旋(H)、β折叠(E)、无规则卷(L)的比例分别是29.84%、28.70%、41.88%,1个GTP/ATP结合位点。 Cdc42蛋白为疏水蛋白,无跨膜区,无信号肽。结论:成功预测Cdc42基因及编码蛋白生化及结构特征,为下一步对其进行克隆和表达奠定基础。%Objective:To analyze and predict the structure and properties about encoding pro-tein of cell division cycle 42(Cdc42) from Candida glabrata by bioinformatics.Methods:A full-length cDNA sequence encoding Cdc 42 from Candida glabrata was identified by using tools of bioinformatics at webs sites of NCBI , ExPASy, CBS and software Vector NTI suite 8.0.The char-acteristics of the protein were predicted by employing bioinformatics software package supplied by the website of ExPaSy .Results:The full length of Cdc42 is 576 bp, and its ORF encodes 191 ami-no acid.The relationship of phylogenesis between Candida glabrata and other fungus is close .The prediction shows that Cdc 42 had a Cdc42 conserved domain , the molecular weight and theoretical pI of Cg.Cdc42 was 21 420.83 and 6.31 respectively, and the coding protein contains 29.84%ɑ-helix, 28.70%extended strand,41.88% random coil,and one GTP/ATP motif.Cdc42 enco-ding protein is hydrophobic , extra-membrane protein , without signal peptide .Conclusion:The structure and characteristics of the gene and protein of Cg .Cdc42 was

  1. 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.

  2. 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.

  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. Distinct roles of Cdc42 in thymopoiesis and effector and memory T cell differentiation.

    Directory of Open Access Journals (Sweden)

    Fukun Guo

    Full Text Available Cdc42 of the Rho GTPase family has been implicated in cell actin organization, proliferation, survival, and migration but its physiological role is likely cell-type specific. By a T cell-specific deletion of Cdc42 in mouse, we have recently shown that Cdc42 maintains naïve T cell homeostasis through promoting cell survival and suppressing T cell activation. Here we have further investigated the involvement of Cdc42 in multiple stages of T cell differentiation. We found that in Cdc42(-/- thymus, positive selection of CD4(+CD8(+ double-positive thymocytes was defective, CD4(+ and CD8(+ single-positive thymocytes were impaired in migration and showed an increase in cell apoptosis triggered by anti-CD3/-CD28 antibodies, and thymocytes were hyporesponsive to anti-CD3/-CD28-induced cell proliferation and hyperresponsive to anti-CD3/-CD28-stimulated MAP kinase activation. At the periphery, Cdc42-deficient naive T cells displayed an impaired actin polymerization and TCR clustering during the formation of mature immunological synapse, and showed an enhanced differentiation to Th1 and CD8(+ effector and memory cells in vitro and in vivo. Finally, Cdc42(-/- mice exhibited exacerbated liver damage in an induced autoimmune disease model. Collectively, these data establish that Cdc42 is critically involved in thymopoiesis and plays a restrictive role in effector and memory T cell differentiation and autoimmunity.

  5. 76 FR 66721 - CDC/HRSA Advisory Committee on HIV and STD Prevention and Treatment

    Science.gov (United States)

    2011-10-27

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention CDC/HRSA Advisory Committee on HIV and STD...-Cseh, CDC, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, 1600 Clifton Road,...

  6. 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.

  7. 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,...

  8. 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

  9. Testing public health ethics: why the CDC's HIV screening recommendations may violate the least infringement principle.

    Science.gov (United States)

    Pierce, Matthew W; Maman, Suzanne; Groves, Allison K; King, Elizabeth J; Wyckoff, Sarah C

    2011-01-01

    The CDC's HIV screening recommendations for health care settings advocate abandoning two important autonomy protections: (1) pretest counseling and (2) the requirement that providers obtain affirmative agreement from patients prior to testing. The recommendations may violate the least infringement principle because there is insufficient evidence to conclude that abandoning pretest counseling or affirmative agreement requirements will further the CDC's stated public health goals.

  10. "Working Together, Unlimited Things Can Happen": CDC, Tribes, Colleges Strive to Improve Native Health

    Science.gov (United States)

    Selden, Ron

    2004-01-01

    The article focuses on the overall health of American Indians. Native people living on reservations and in urban areas face a broad array of health problems. Centers for Disease Control and Prevention (CDC) in Atlanta is committed to improving the health of Native Americans. CDC is one of the agencies within the U.S. Department of Health and Human…

  11. Do the benefits of male circumcision outweigh the risks? A critique of the proposed CDC guidelines

    Directory of Open Access Journals (Sweden)

    Brian D. Earp

    2015-03-01

    Full Text Available The Centers for Disease Control and Prevention (CDC have announced a set of provisional guidelines concerning male circumcision, in which they suggest that the benefits of the surgery outweigh the risks. In this perspective article, I highlight a few of the key scientific and ethical issues worth considering in interpreting the new CDC recommendations.

  12. Birth and rapid subcellular adaptation of a hominoid-specific CDC14 protein.

    Directory of Open Access Journals (Sweden)

    Lia Rosso

    2008-06-01

    Full Text Available Gene duplication was prevalent during hominoid evolution, yet little is known about the functional fate of new ape gene copies. We characterized the CDC14B cell cycle gene and the functional evolution of its hominoid-specific daughter gene, CDC14Bretro. We found that CDC14B encodes four different splice isoforms that show different subcellular localizations (nucleus or microtubule-associated and functional properties. A microtubular CDC14B variant spawned CDC14Bretro through retroposition in the hominoid ancestor 18-25 million years ago (Mya. CDC14Bretro evolved brain-/testis-specific expression after the duplication event and experienced a short period of intense positive selection in the African ape ancestor 7-12 Mya. Using resurrected ancestral protein variants, we demonstrate that by virtue of amino acid substitutions in distinct protein regions during this time, the subcellular localization of CDC14Bretro progressively shifted from the association with microtubules (stabilizing them to an association with the endoplasmic reticulum. CDC14Bretro evolution represents a paradigm example of rapid, selectively driven subcellular relocalization, thus revealing a novel mode for the emergence of new gene function.

  13. Characterization of centralizers on CDC-algebras%CDC-代数上中心化子的刻画

    Institute of Scientific and Technical Information of China (English)

    马飞; 张建华; 尹琳娟

    2015-01-01

    设 A lg L是Hilbert空间 H 上的一个CDC-代数,φ:A lg L ® A lg L是一可加映射。证明了如果存在正整数m'n1,满足对于任意的a Î A lg L'有φ(am+n+1)=amφ(a)an ,那么存在 A lg L的中心中的元素λÎ Z(A lg L),使得对于任意的a Î A lg L'有φ(a)=λa。%Let A lg L be a CDC-algebra on a Hilbert space H,and φ:A lg L ® A lg L be an additive mapping. This paper proves that if for some positive integer numbers m'n1, φ(am+n+1)=amφ(a)an hold for all a Î A lg L, then there exists some λÎ Z(A lg L)' such thatφ(a)=λa' for all a Î A lg L.

  14. 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....

  15. 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.

  16. 75 FR 63844 - Health Resources and Services Administration CDC/HRSA Advisory Committee on HIV and STD...

    Science.gov (United States)

    2010-10-18

    ... CDC/HRSA Advisory Committee on HIV and STD Prevention and Treatment (CHACHSPT) In accordance with... Person for More Information: Margie Scott-Cseh, CDC, National Center for HIV/AIDS, Viral Hepatitis,...

  17. The small GTPase Cdc42 is necessary for primary ciliogenesis in renal tubular epithelial cells.

    Science.gov (United States)

    Zuo, Xiaofeng; Fogelgren, Ben; Lipschutz, Joshua H

    2011-06-24

    Primary cilia are found on many epithelial cell types, including renal tubular epithelial cells, where they participate in flow sensing. Disruption of cilia function has been linked to the pathogenesis of polycystic kidney disease. We demonstrated previously that the exocyst, a highly conserved eight-protein membrane trafficking complex, localizes to primary cilia of renal tubular epithelial cells, is required for ciliogenesis, biochemically and genetically interacts with polycystin-2 (the protein product of the polycystic kidney disease 2 gene), and, when disrupted, results in MAPK pathway activation both in vitro and in vivo. The small GTPase Cdc42 is a candidate for regulation of the exocyst at the primary cilium. Here, we demonstrate that Cdc42 biochemically interacts with Sec10, a crucial component of the exocyst complex, and that Cdc42 colocalizes with Sec10 at the primary cilium. Expression of dominant negative Cdc42 and shRNA-mediated knockdown of both Cdc42 and Tuba, a Cdc42 guanine nucleotide exchange factor, inhibit ciliogenesis in Madin-Darby canine kidney cells. Furthermore, exocyst Sec8 and polycystin-2 no longer localize to primary cilia or the ciliary region following Cdc42 and Tuba knockdown. We also show that Sec10 directly interacts with Par6, a member of the Par complex that itself directly interacts with Cdc42. Finally, we show that Cdc42 knockdown results in activation of the MAPK pathway, something observed in cells with dysfunctional primary cilia. These data support a model in which Cdc42 localizes the exocyst to the primary cilium, whereupon the exocyst then targets and docks vesicles carrying proteins necessary for ciliogenesis.

  18. The Small GTPase Cdc42 Is Necessary for Primary Ciliogenesis in Renal Tubular Epithelial Cells*

    Science.gov (United States)

    Zuo, Xiaofeng; Fogelgren, Ben; Lipschutz, Joshua H.

    2011-01-01

    Primary cilia are found on many epithelial cell types, including renal tubular epithelial cells, where they participate in flow sensing. Disruption of cilia function has been linked to the pathogenesis of polycystic kidney disease. We demonstrated previously that the exocyst, a highly conserved eight-protein membrane trafficking complex, localizes to primary cilia of renal tubular epithelial cells, is required for ciliogenesis, biochemically and genetically interacts with polycystin-2 (the protein product of the polycystic kidney disease 2 gene), and, when disrupted, results in MAPK pathway activation both in vitro and in vivo. The small GTPase Cdc42 is a candidate for regulation of the exocyst at the primary cilium. Here, we demonstrate that Cdc42 biochemically interacts with Sec10, a crucial component of the exocyst complex, and that Cdc42 colocalizes with Sec10 at the primary cilium. Expression of dominant negative Cdc42 and shRNA-mediated knockdown of both Cdc42 and Tuba, a Cdc42 guanine nucleotide exchange factor, inhibit ciliogenesis in Madin-Darby canine kidney cells. Furthermore, exocyst Sec8 and polycystin-2 no longer localize to primary cilia or the ciliary region following Cdc42 and Tuba knockdown. We also show that Sec10 directly interacts with Par6, a member of the Par complex that itself directly interacts with Cdc42. Finally, we show that Cdc42 knockdown results in activation of the MAPK pathway, something observed in cells with dysfunctional primary cilia. These data support a model in which Cdc42 localizes the exocyst to the primary cilium, whereupon the exocyst then targets and docks vesicles carrying proteins necessary for ciliogenesis. PMID:21543338

  19. Technical Review of SRS Dose Reconstrruction Methods Used By CDC

    Energy Technology Data Exchange (ETDEWEB)

    Simpkins, Ali, A

    2005-07-20

    At the request of the Centers for Disease Control and Prevention (CDC), a subcontractor Advanced Technologies and Laboratories International, Inc.(ATL) issued a draft report estimating offsite dose as a result of Savannah River Site operations for the period 1954-1992 in support of Phase III of the SRS Dose Reconstruction Project. The doses reported by ATL differed than those previously estimated by Savannah River Site SRS dose modelers for a variety of reasons, but primarily because (1) ATL used different source terms, (2) ATL considered trespasser/poacher scenarios and (3) ATL did not consistently use site-specific parameters or correct usage parameters. The receptors with the highest dose from atmospheric and liquid pathways were within about a factor of four greater than dose values previously reported by SRS. A complete set of technical comments have also been included.

  20. 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

    Proper cell-cycle progression requires tight temporal control of the Anaphase Promoting Complex/Cyclosome (APC/C), a large ubiquitin ligase that is activated by one of two co-activators, Cdh1 or Cdc20. APC/C and Cdc20 are already present during interphase but APC/C-Cdc20 regulation during...

  1. 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...

  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;

    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...

  3. ATP8B1-mediated spatial organization of Cdc42 signaling maintains singularity during enterocyte polarization

    Science.gov (United States)

    Bruurs, Lucas J.M.; Donker, Lisa; Zwakenberg, Susan; Zwartkruis, Fried J.; Begthel, Harry; Knisely, A.S.; Posthuma, George; van de Graaf, Stan F.J.; Paulusma, Coen C.

    2015-01-01

    During yeast cell polarization localization of the small GTPase, cell division control protein 42 homologue (Cdc42) is clustered to ensure the formation of a single bud. Here we show that the disease-associated flippase ATPase class I type 8b member 1 (ATP8B1) enables Cdc42 clustering during enterocyte polarization. Loss of this regulation results in increased apical membrane size with scattered apical recycling endosomes and permits the formation of more than one apical domain, resembling the singularity defect observed in yeast. Mechanistically, we show that to become apically clustered, Cdc42 requires the interaction between its polybasic region and negatively charged membrane lipids provided by ATP8B1. Disturbing this interaction, either by ATP8B1 depletion or by introduction of a Cdc42 mutant defective in lipid binding, increases Cdc42 mobility and results in apical membrane enlargement. Re-establishing Cdc42 clustering, by tethering it to the apical membrane or lowering its diffusion, restores normal apical membrane size in ATP8B1-depleted cells. We therefore conclude that singularity regulation by Cdc42 is conserved between yeast and human and that this regulation is required to maintain healthy tissue architecture. PMID:26416959

  4. CDC27 protein is involved in radiation response in squamous cell cervix carcinoma.

    Science.gov (United States)

    Rajkumar, T; Gopal, G; Selvaluxmi, G; Rajalekshmy, K R

    2005-10-01

    In the present study, an attempt was made to identify genes involved in radiation response in cervix carcinoma. Differential display technique was used to study the expression profiles of tumour biopsy samples obtained from patients, responding and not responding to treatment. The samples were obtained prior to radiotherapy and subsequent to treatment with Tele-radiation at 10 Gray (Gy). One of the differentially expressed cDNAs, when sequenced was identified to be CDC27. Immuno-histochemical analysis of pre- and post-treated tumour samples from fifteen patients showed the downregulation of expression of CDC27 protein in seven patients. Down-regulation was associated with poorer response to radiotherapy. Cervical cancer cell lines SiHa and C33A were irradiated and their nuclei were stained for expression of CDC27 and analyzed using fluorescent-activated cell sorting (FACS). Down-regulation of CDC27 protein in the irradiated SiHa cell line was associated with greater survival fraction, compared to the irradiated C33A cell line, which had only slight fall in the level of CDC27 protein. This is the first study to suggest a role for CDC27 in radiation response. However, a larger cohort is needed to further confirm the value of CDC27 protein as a predictive marker, for radiation response in cervix cancer.

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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...

  11. 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...... is 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...

  12. 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

  13. 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 ...

  14. 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

  15. 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.

  16. Kids 14 and Younger Only Need 2 HPV Vaccine Shots: CDC

    Science.gov (United States)

    ... html Kids 14 and Younger Only Need 2 HPV Vaccine Shots: CDC But agency's revised guidelines still recommend ... and younger require only two doses of the HPV vaccine rather than the previously recommended three shots, U.S. ...

  17. 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...

  18. 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 ...

  19. 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 ...

  20. CDC25B overexpression stabilises centrin 2 and promotes the formation of excess centriolar foci.

    Directory of Open Access Journals (Sweden)

    Rose Boutros

    Full Text Available CDK-cyclin complexes regulate centriole duplication and microtubule nucleation at specific cell cycle stages, although their exact roles in these processes remain unclear. As the activities of CDK-cyclins are themselves positively regulated by CDC25 phosphatases, we investigated the role of centrosomal CDC25B during interphase. We report that overexpression of CDC25B, as is commonly found in human cancer, results in a significant increase in centrin 2 at the centrosomes of interphase cells. Conversely, CDC25B depletion causes a loss of centrin 2 from the centrosome, which can be rescued by treatment with the proteasome inhibitor MG132. CDC25B overexpression also promotes the formation of excess centrin 2 "foci". These foci can accumulate other centrosome proteins, including γ-tubulin and PCM-1, and can function as microtubule organising centres, indicating that these represent functional centrosomes. Formation of centrin 2 foci can be blocked by specific inhibition of CDK2 but not CDK1. CDK2-mediated phosphorylation of Monopolar spindle 1 (Mps1 at the G1/S transition is essential for the initiation of centrosome duplication, and Mps1 is reported to phosphorylate centrin 2. Overexpression of wild-type or non-degradable Mps1 exacerbated the formation of excess centrin 2 foci induced by CDC25B overexpression, while kinase-dead Mps1 has a protective effect. Together, our data suggest that CDC25B, through activation of a centrosomal pool of CDK2, stabilises the local pool of Mps1 which in turn regulates the level of centrin 2 at the centrosome. Overexpression of CDC25B may therefore contribute to tumourigenesis by perturbing the natural turnover of centrosome proteins such as Mps1 and centrin 2, thus resulting in the de novo assembly of extra-numerary centrosomes and potentiating chromosome instability.

  1. 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...

  2. Human Cdc14A regulates Wee1 stability by counteracting CDK-mediated phosphorylation

    OpenAIRE

    Ovejero, Sara; Ayala, Patricia; Bueno, Avelino; Sacristán, María P.

    2012-01-01

    The activity of Cdk1–cyclin B1 mitotic complexes is regulated by the balance between the counteracting activities of Wee1/Myt1 kinases and Cdc25 phosphatases. These kinases and phosphatases must be strictly regulated to ensure proper mitotic timing. One masterpiece of this regulatory network is Cdk1, which promotes Cdc25 activity and suppresses inhibitory Wee1/Myt1 kinases through direct phosphorylation. The Cdk1-dependent phosphorylation of Wee1 primes phosphorylation by additional kinases s...

  3. 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...

  4. A Synthetic Interaction between CDC20 and RAD4 in Saccharomyces cerevisiae upon UV Irradiation

    Directory of Open Access Journals (Sweden)

    Bernadette Connors

    2014-01-01

    Full Text Available Regulation of DNA repair can be achieved through ubiquitin-mediated degradation of transiently induced proteins. In Saccharomyces cerevisiae, Rad4 is involved in damage recognition during nucleotide excision repair (NER and, in conjunction with Rad23, recruits other proteins to the site of damage. We identified a synthetic interaction upon UV exposure between Rad4 and Cdc20, a protein that modulates the activity of the anaphase promoting complex (APC/C, a multisubunit E3 ubiquitin ligase complex. The moderately UV sensitive Δrad4 strain became highly sensitive when cdc20-1 was present, and was rescued by overexpression of CDC20. The double mutant is also deficient in elicting RNR3-lacZ transcription upon exposure to UV irradiation or 4-NQO compared with the Δrad4 single mutant. We demonstrate that the Δrad4/cdc20-1 double mutant is defective in double strand break repair by way of a plasmid end-joining assay, indicating that Rad4 acts to ensure that damaged DNA is repaired via a Cdc20-mediated mechanism. This study is the first to present evidence that Cdc20 may play a role in the degradation of proteins involved in nucleotide excision repair.

  5. Cdc7p-Dbf4p regulates mitotic exit by inhibiting Polo kinase.

    Directory of Open Access Journals (Sweden)

    Charles T Miller

    2009-05-01

    Full Text Available Cdc7p-Dbf4p is a conserved protein kinase required for the initiation of DNA replication. The Dbf4p regulatory subunit binds Cdc7p and is essential for Cdc7p kinase activation, however, the N-terminal third of Dbf4p is dispensable for its essential replication activities. Here, we define a short N-terminal Dbf4p region that targets Cdc7p-Dbf4p kinase to Cdc5p, the single Polo kinase in budding yeast that regulates mitotic progression and cytokinesis. Dbf4p mediates an interaction with the Polo substrate-binding domain to inhibit its essential role during mitosis. Although Dbf4p does not inhibit Polo kinase activity, it nonetheless inhibits Polo-mediated activation of the mitotic exit network (MEN, presumably by altering Polo substrate targeting. In addition, although dbf4 mutants defective for interaction with Polo transit S-phase normally, they aberrantly segregate chromosomes following nuclear misorientation. Therefore, Cdc7p-Dbf4p prevents inappropriate exit from mitosis by inhibiting Polo kinase and functions in the spindle position checkpoint.

  6. 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

  7. 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

  8. Functional roles of PC-PLC and Cdc20 in the cell cycle, proliferation, and apoptosis.

    Science.gov (United States)

    Chen, Zhiwei; Yu, Yongfeng; Fu, Da; Li, Ziming; Niu, Xiaoming; Liao, Meilin; Lu, Shun

    2010-06-01

    Phosphatidylcholine-specific phospholipase C (PC-PLC) is the major enzyme in the Phosphatidylcholine (PC) cycle and is involved in many long-term cellular responses such as activation, proliferation, and differentiation events. Cell division cycle 20 homolog (Cdc20) is an essential cell-cycle regulator required for the completion of mitosis. Our previous studies identified the interaction between PC-PLC and Cdc20. Through the interaction, Cdc20 could mediate the degradation of PC-PLC by Cdc20-mediated ubiquitin proteasome pathway (UPP). In this study, we found that PC-PLC might not be involved in cancer metastasis. Inhibition of PC-PLC by D609 could cause cell proliferation inhibition and apoptosis inhibition in CBRH-7919 cells. Inhibition of PC-PLC could also influence the cell cycle by arresting the cells in G1 phase, and Cdc20 might be involved in these processes. Taken together, in this report, we provided new evidence for the functional roles of PC-PLC and Cdc20 in the cell cycle, proliferation, and apoptosis in CBRH-7919 cells.

  9. Large computer systems and new architectures addendum

    Science.gov (United States)

    Bloch, T.

    1982-05-01

    This addendum brings the paper referenced up-to-date as of January 1981. The new market situation in the area of super computers is reviewed and the only really new machine, the CDC CYBER 205, is described. The CRAY-1S series is briefly described and the FPS-164 is mentioned. The fact that Burroughs discontinued the BSP project is mentioned.

  10. 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

  11. 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

  12. 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

  13. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Mai [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902 (Japan); Kitaguchi, Tetsuya [Cell Signaling Group, Waseda Bioscience Research Institute in Singapore (WABOIS), Waseda University, 11 Biopolis Way, 05-01/02 Helios, Singapore 138667 (Singapore); Numano, Rika [The Electronics-Inspired Interdisciplinary Research Institute (EIIRIS), Toyohashi University of Technology, 1-1 Hibarigaoka, Tennpaku-cho, Toyohashi, Aichi 441-8580 (Japan); Ikematsu, Kazuya [Forensic Pathology and Science, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Kakeyama, Masaki [Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033 (Japan); Murata, Masayuki; Sato, Ken [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902 (Japan); Tsuboi, Takashi, E-mail: takatsuboi@bio.c.u-tokyo.ac.jp [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902 (Japan)

    2012-04-06

    Highlights: Black-Right-Pointing-Pointer Regulation of exocytosis by Rho GTPase Cdc42. Black-Right-Pointing-Pointer Cdc42 increases the number of fusion events from newly recruited vesicles. Black-Right-Pointing-Pointer 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.

  15. 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.

  16. 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....

  17. 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.

  18. Redundant and nonredundant roles for Cdc42 and Rac1 in lymphomas developed in NPM-ALK transgenic mice.

    Science.gov (United States)

    Choudhari, Ramesh; Minero, Valerio Giacomo; Menotti, Matteo; Pulito, Roberta; Brakebusch, Cord; Compagno, Mara; Voena, Claudia; Ambrogio, Chiara; Chiarle, Roberto

    2016-03-10

    Increasing evidence suggests that Rho family GTPases could have a critical role in the biology of T-cell lymphoma. In ALK-rearranged anaplastic large cell lymphoma (ALCL), a specific subtype of T-cell lymphoma, the Rho family GTPases Cdc42 and Rac1 are activated by the ALK oncogenic activity. In vitro studies have shown that Cdc42 and Rac1 control rather similar phenotypes of ALCL biology such as the proliferation, survival, and migration of lymphoma cells. However, their role and possible redundancy in ALK-driven lymphoma development in vivo are still undetermined. We genetically deleted Cdc42 or Rac1 in a mouse model of ALK-rearranged ALCL to show that either Cdc42 or Rac1 deletion impaired lymphoma development, modified lymphoma morphology, actin filament distribution, and migration properties of lymphoma cells. Cdc42 or Rac1 deletion primarily affected survival rather than proliferation of lymphoma cells. Apoptosis of lymphoma cells was equally induced following Cdc42 or Rac1 deletion, was associated with upregulation of the proapoptotic molecule Bid, and was blocked by Bcl2 overexpression. Remarkably, Cdc42/Rac1 double deletion, but not Cdc42 or Rac1 single deletions, completely prevented NPM-ALK lymphoma dissemination in vivo. Thus, Cdc42 and Rac1 have nonredundant roles in controlling ALK-rearranged lymphoma survival and morphology but are redundant for lymphoma dissemination, suggesting that targeting both GTPases could represent a preferable therapeutic option for ALCL treatment.

  19. 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...

  20. Staphylococcus aureus recruits Cdc42GAP through recycling endosomes and the exocyst to invade human endothelial cells.

    Science.gov (United States)

    Rauch, Liane; Hennings, Kirsten; Trasak, Claudia; Röder, Anja; Schröder, Barbara; Koch-Nolte, Friedrich; Rivera-Molina, Felix; Toomre, Derek; Aepfelbacher, Martin

    2016-08-01

    Activation and invasion of the vascular endothelium by Staphylococcus aureus is a major cause of sepsis and endocarditis. For endothelial cell invasion, S. aureus triggers actin polymerization through Cdc42, N-WASp (also known as WASL) and the Arp2/3 complex to assemble a phagocytic cup-like structure. Here, we show that after stimulating actin polymerization staphylococci recruit Cdc42GAP (also known as ARHGAP1) which deactivates Cdc42 and terminates actin polymerization in the phagocytic cups. Cdc42GAP is delivered to the invading bacteria on recycling endocytic vesicles in concert with the exocyst complex. When Cdc42GAP recruitment by staphylococci was prevented by blocking recycling endocytic vesicles or the exocyst complex, or when Cdc42 was constitutively activated, phagocytic cup closure was impaired and endothelial cell invasion was inhibited. Thus, to complete invasion of the endothelium, staphylococci reorient recycling endocytic vesicles to recruit Cdc42GAP, which terminates Cdc42-induced actin polymerization in phagocytic cups. Analogous mechanisms might govern other Cdc42-dependent cell functions.

  1. 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

  2. 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.

  3. 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...

  4. 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

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

    Science.gov (United States)

    Lee, Seung Baek; Kim, Jung Jin; Nam, Hyun-Ja; Gao, Bowen; Yin, Ping; Qin, Bo; Yi, Sang-Yeop; Ham, Hyoungjun; Evans, Debra; Kim, Sun-Hyun; Zhang, Jun; Deng, Min; Liu, Tongzheng; Zhang, Haoxing; Billadeau, Daniel D; Wang, Liewei; Giaime, Emilie; Shen, Jie; Pang, Yuan-Ping; Jen, Jin; van Deursen, Jan M; Lou, Zhenkun

    2015-10-01

    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 the degradation of several key mitotic regulators independent of APC/C. We demonstrate that ordered progression through mitosis is orchestrated by two distinct E3 ligases through the shared use of Cdc20 and Cdh1. Furthermore, Parkin is phosphorylated and activated by polo-like kinase 1 (Plk1) during mitosis. Parkin deficiency results in overexpression of its substrates, mitotic defects, genomic instability, and tumorigenesis. These results suggest that the Parkin-Cdc20/Cdh1 complex is an important regulator of mitosis.

  6. 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

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

    Directory of Open Access Journals (Sweden)

    Dong Jun

    2010-09-01

    Full Text Available 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 CDC25B-Abs in patients with ESCC. Methods CDC25B autoantibodies were measured in sera from both 134 patients with primary ESCC and 134 healthy controls using a reverse capture enzyme-linked immunosorbent assay (ELISA in which anti-CDC25B antibodies bound CDC25B antigen purified from Eca-109 ESCC tumor cells. The clinicopathologic significance of CDC25B serum autoantibodies was compared to that of the tumor markers carcinoembryonic antigen (CEA, squamous cell carcinoma antigen (SCC-Ag and cytokeratin 19 fragment antigen 21-1(CYFRA21-1. Results Higher levels of CDC25B autoantibodies were present in sera from patients with ESCC (A450 = 0.917, SD = 0.473 than in sera from healthy control subjects (A450 = 0.378, SD = 0.262, P 450 greater than the cut-off value of 0.725. Relatively few patients tested positive for the tumor markers CEA, SCC-Ag and CYFRA21-1 (13.4%, 17.2%, and 32.1%, respectively. A significantly higher number of patients with ESCC tested positive for a combination of CEA, SCC, CYFRA21-1 and CDC25B-Abs (64.2% than for a combination of CEA, SCC-Ag and CYFRA21-1 (41.0%, P P P = 0.001, log-rank. In the N1 subgroup, the cumulative five-year survival rate of CDC25B-seropositive patients was 13.6%, while that of CDC25B-seronegative patients was 54.5% (P = 0.040, log-rank. Conclusions Detection of serum CDC25B-Abs is superior to detection of the tumor markers CEA, SCC-Ag and CYFRA21-1 for diagnosis of ESCC, and CDC25B-Abs are a potential prognostic

  8. 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

  9. 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).

  10. 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...

  11. 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;...

  12. 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...

  13. 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 Golgi...

  14. Cell cycle- and cell growth-regulated proteolysis of mammalian CDC6 is dependent on APC-CDH1

    DEFF Research Database (Denmark)

    Petersen, B O; Wagener, C; Marinoni, F;

    2000-01-01

    CDC6 is conserved during evolution and is essential and limiting for the initiation of eukaryotic DNA replication. Human CDC6 activity is regulated by periodic transcription and CDK-regulated subcellular localization. Here, we show that, in addition to being absent from nonproliferating cells, CD...... proteolysis of CDC6 in early G(1) and in quiescent cells suggests that this process is part of a mechanism that ensures the timely licensing of replication origins during G(1).......CDC6 is conserved during evolution and is essential and limiting for the initiation of eukaryotic DNA replication. Human CDC6 activity is regulated by periodic transcription and CDK-regulated subcellular localization. Here, we show that, in addition to being absent from nonproliferating cells, CDC6...... is targeted for ubiquitin-mediated proteolysis by the anaphase promoting complex (APC)/cyclosome in G(1). A combination of point mutations in the destruction box and KEN-box motifs in CDC6 stabilizes the protein in G(1) and in quiescent cells. Furthermore, APC, in association with CDH1, ubiquitinates CDC6...

  15. Cdc7-Dbf4 Kinase Overexpression in Multiple Cancers and Tumor Cell Lines Is Correlated with p53 Inactivation

    Directory of Open Access Journals (Sweden)

    Dorine Bonte

    2008-09-01

    Full Text Available Cdc7 is a conserved serine/threonine kinase essential for the initiation of DNA replication, likely by activating the MCM DNA helicase at the G1- to S-phase transition. Cdc7 kinase activity requires association with its regulatory subunit Dbf4/activator of S-phase kinase. Cdc7-Dbf4 is also downstream of the conserved Ataxia telangectasia and RAD3-related kinase that responds to stalled replication forks or DNA damage. In this study, we found that Cdc7 protein was very low or undetectable in normal tissues and cell lines but had increased expression in ∼50% of the 62 human tumor cell lines we examined. Most cell lines with increased Cdc7 protein levels also had increased Dbf4 abundance, and some tumor cell lines had extra copies of the DBF4 gene. A high expression of Cdc7 protein was also detected in primary breast, colon, and lung tumors but not in the matched normal tissues. We also found a high correlation between p53 loss and increased CDC7 and DBF4 expression in primary breast cancers (P = 3.6 × 10−9 and 1.8 × 10−10, respectively and in the cancer cell lines we studied. Therefore, increased Cdc7-Dbf4 abundance may be a common occurrence in human malignancies.

  16. Make a Difference at Your School! CDC Resources Can Help You Implement Strategies to Prevent Obesity Among Children and Adolescents

    Science.gov (United States)

    Centers for Disease Control and Prevention, 2008

    2008-01-01

    The Centers for Disease Control and Prevention (CDC) reviews scientific evidence to determine which school-based policies and practices are most likely to improve key health behaviors among young people, including physical activity and healthy eating. In this document, the CDC identifies ten strategies to help schools prevent obesity by promoting…

  17. 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.

  18. Dbf4 regulates the Cdc5 Polo-like kinase through a distinct non-canonical binding interaction.

    Science.gov (United States)

    Chen, Ying-Chou; Weinreich, Michael

    2010-12-31

    Cdc7-Dbf4 is a conserved, two-subunit kinase required for initiating eukaryotic DNA replication. Recent studies have shown that Cdc7-Dbf4 also regulates the mitotic exit network (MEN) and monopolar homolog orientation in meiosis I (Matos, J., Lipp, J. J., Bogdanova, A., Guillot, S., Okaz, E., Junqueira, M., Shevchenko, A., and Zachariae, W. (2008) Cell 135, 662-678 and Miller, C. T., Gabrielse, C., Chen, Y. C., and Weinreich, M. (2009) PLoS Genet. 5, e1000498). Both activities likely involve a Cdc7-Dbf4 interaction with Cdc5, the single Polo-like kinase in budding yeast. We previously showed that Dbf4 binds the Cdc5 polo-box domain (PBD) via an ∼40-residue N-terminal sequence, which lacks a PBD consensus binding site (S(pS/pT)(P/X)), and that Dbf4 inhibits Cdc5 function during mitosis. Here we identify a non-consensus PBD binding site within Dbf4 and demonstrate that the PBD-Dbf4 interaction occurs via a distinct PBD surface from that used to bind phosphoproteins. Genetic and biochemical analysis of multiple dbf4 mutants indicate that Dbf4 inhibits Cdc5 function through direct binding. Surprisingly, mutation of invariant Cdc5 residues required for binding phosphorylated substrates has little effect on yeast viability or growth rate. Instead, cdc5 mutants defective for binding phosphoproteins exhibit enhanced resistance to microtubule disruption and an increased rate of spindle elongation. This study, therefore, details the molecular nature of a new type of PBD binding and reveals that Cdc5 targeting to phosphorylated substrates likely regulates spindle dynamics.

  19. CDC28 phosphorylates Cac1p and regulates the association of chromatin assembly factor i with chromatin

    Science.gov (United States)

    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, 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

  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. 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

  2. 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

  3. 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

    Podocytes are highly specialized epithelial cells with complex actin cytoskeletal architecture crucial for maintenance of the glomerular filtration barrier. The mammalian Rho GTPases Rac1 and Cdc42 are molecular switches that control many cellular processes, but are best known for their roles in ...

  4. 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

  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. 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... health and STD disparities among racial and ethnic minorities. The objectives of the workgroup are: (1..., Viral Hepatitis, STD, and TB ] Prevention, 1600 Clifton Road, NE., Mailstop E-07, Atlanta, Georgia...

  8. 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.

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

    DEFF Research Database (Denmark)

    Pleines, Irina; Dütting, Sebastian; Cherpokova, Deya;

    2013-01-01

    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 structure were...

  10. 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...

  11. 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-actin belts...

  12. 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

  13. Opioid Epidemic Costs U.S. $78.5 Billion Annually: CDC

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_161089.html Opioid Epidemic Costs U.S. $78.5 Billion Annually: CDC ... HealthDay News) -- Abuse of powerful prescription painkillers called opioids costs the U.S. economy $78.5 billion a ...

  14. 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…

  15. 76 FR 62071 - Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)

    Science.gov (United States)

    2011-10-06

    ... 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..., for both the Centers for Disease Control and Prevention and the Agency for Toxic Substances...

  16. 77 FR 19018 - Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)

    Science.gov (United States)

    2012-03-29

    ... 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... and other committee management activities, for both the Centers for Disease Control and Prevention...

  17. Modulation of yeast telomerase activity by Cdc13 and Est1 in vitro

    Science.gov (United States)

    Chen, Yu-Fan; Lu, Chia-Ying; Lin, Yi-Chien; Yu, Tai-Yuan; Chang, Chun-Ping; Li, Jing-Ru; Li, Hung-Wen; Lin, Jing-Jer

    2016-01-01

    Telomerase is the enzyme involved in extending telomeric DNA. Control of telomerase activity by modulating its access to chromosome ends is one of the most important fundamental mechanisms. This study established an in vitro yeast telomerase reconstitution system that resembles telomere replication in vivo. In this system, a tailed-duplex DNA formed by telomeric DNA was employed to mimic the structure of telomeres. The core catalytic components of telomerase Est2/Tlc1 RNA were used as the telomeric DNA extension machinery. Using the reconstituted systems, this study found that binding of Cdc13 to telomeric DNA inhibited the access of telomerase to its substrate. The result was further confirmed by a single-molecule approach using the tethered-particle motion (TPM)-based telomerase assay. The findings also showed that the inhibitory effect can be relieved by telomerase-associated protein Est1, consistent with the role of Cdc13 and Est1 in regulating telomere extension in vivo. Significantly, this study found that the DNA binding property of Cdc13 was altered by Est1, providing the first mechanistic evidence of Est1 regulating the access of telomerase to its substrate. Thus, the roles of Cdc13 and Est1 in modulating telomerase activity were clearly defined using the in vitro reconstituted system. PMID:27659693

  18. 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, ...

  19. Frequent alterations of SLIT2-ROBO1-CDC42 signalling pathway in breast cancer: clinicopathological correlation.

    Science.gov (United States)

    Bhattacharya, Rittwika; Mukherjee, Nupur; Dasgupta, Hemantika; Islam, Md Saimul; Alam, Neyaz; Roy, Anup; Das, Priyobrata; Roychoudhury, Susanta; Panda, Chinmay Kumar

    2016-09-01

    The aim of the study was to understand the role of SLIT2-ROBO1/2-CDC42 signalling pathways in development of breast cancer (BC). Primary BC samples (n = 150), comprising of almost equal proportion of four subtypes were tested for molecular alterations of SLIT2, ROBO1, ROBO2 and CDC42, the key regulator genes of this pathway. Deletion and methylation frequencies of the candidate genes were seen in the following order: deletion, SLIT2 (38.6%) > ROBO1 (30%) > ROBO2 (7.3%); methylation, SLIT2 (63.3%) > ROBO1 (26.6%) >ROBO2 (9.3%). Majority (80%, 120/150) of the tumours showed alterations (deletion/methylation) in at least one of the candidate genes. Overall, alterations of the candidate genes were as follows: SLIT2, 75.3% (101/150); ROBO1, 45.3% (68/150); ROBO2, 15.3% (23/150). Significantly, higher alteration of SLIT2 locus was observed in triple negative breast cancer (TNBC) over HER2 subtype (P = 0.0014). Similar trend is also seen in overall alterations of SLIT2 and/or ROBO1, in TNBC than HER2 subtype (P = 0.0012); of SLIT2 and/or ROBO2 in TNBC than luminal A (P = 0.014) and HER2 subtype (P = 0.048). Immunohistochemical analysis of SLIT2, ROBO1/2 showed reduced expression, concordant with their molecular alterations. Also, high expression of total CDC42 (49/52; 94.2%) and reduced expression of phospho Serine-71 CDC42 (41/52; 78.8%) was observed. Coalterations of SLIT2 and/or ROBO1, SLIT2 and/or ROBO2 had significant association with reduced expression of phospho Serine-71 CDC42 (P = 0.0012-0.0038). Alterations of SLIT2 and/or ROBO1, reduced expression of phospho Serine-71 CDC42 predicted poor survival of BC patients. Results indicate the importance of SLIT2-ROBO1-CDC42 signalling pathway in predicting tumour progression.

  20. Molecular and structural insight into lysine selection on substrate and ubiquitin lysine 48 by the ubiquitin-conjugating enzyme Cdc34

    DEFF Research Database (Denmark)

    Suryadinata, Randy; Holien, Jessica K; Yang, George;

    2013-01-01

    the native salt-bridge interactions in Ub and Cdc34, resulting in misplacement of Sic1 lysine 50 in the Cdc34 catalytic cleft. During polyubiquitination, Cdc34 showed a strong preference for Ub lysine 48 (K48), with lower activity towards lysine 11 (K11) and lysine 63 (K63). Mutating the -2, -1, +1 and +2...

  1. 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.

  2. Use of CYBER 203 and CYBER 205 computers for three-dimensional transonic flow calculations

    Science.gov (United States)

    Melson, N. D.; Keller, J. D.

    1983-04-01

    Experiences are discussed for modifying two three-dimensional transonic flow computer programs (FLO 22 and FLO 27) for use on the CDC CYBER 203 computer system. Both programs were originally written for use on serial machines. Several methods were attempted to optimize the execution of the two programs on the vector machine: leaving the program in a scalar form (i.e., serial computation) with compiler software used to optimize and vectorize the program, vectorizing parts of the existing algorithm in the program, and incorporating a vectorizable algorithm (ZEBRA I or ZEBRA II) in the program. Comparison runs of the programs were made on CDC CYBER 175. CYBER 203, and two pipe CDC CYBER 205 computer systems.

  3. The tenacious recognition of yeast telomere sequence by Cdc13 is fully exerted by a single OB-fold domain.

    Science.gov (United States)

    Lewis, Karen A; Pfaff, Danielle A; Earley, Jennifer N; Altschuler, Sarah E; Wuttke, Deborah S

    2014-01-01

    Cdc13, the telomere end-binding protein from Saccharomyces cerevisiae, is a multidomain protein that specifically binds telomeric single-stranded DNA (ssDNA) with exquisitely high affinity to coordinate telomere maintenance. Recent structural and genetic data have led to the proposal that Cdc13 is the paralog of RPA70 within a telomere-specific RPA complex. Our understanding of Cdc13 structure and biochemistry has been largely restricted to studies of individual domains, precluding analysis of how each domain influences the activity of the others. To better facilitate a comparison to RPA70, we evaluated the ssDNA binding of full-length S. cerevisiae Cdc13 to its minimal substrate, Tel11. We found that, unlike RPA70 and the other known telomere end-binding proteins, the core Cdc13 ssDNA-binding activity is wholly contained within a single tight-binding oligosaccharide/oligonucleotide/oligopeptide binding (OB)-fold. Because two OB-folds are implicated in dimerization, we also evaluated the relationship between dimerization and ssDNA-binding activity and found that the two activities are independent. We also find that Cdc13 binding exhibits positive cooperativity that is independent of dimerization. This study reveals that, while Cdc13 and RPA70 share similar domain topologies, the corresponding domains have evolved different and specialized functions.

  4. Cdc42-dependent Modulation of Tight Junctions and Membrane Protein Traffic in Polarized Madin-Darby Canine Kidney Cells

    Science.gov (United States)

    Rojas, Raul; Ruiz, Wily G.; Leung, Som-Ming; Jou, Tzuu-Shuh; Apodaca, Gerard

    2001-01-01

    Polarized epithelial cells maintain the asymmetric composition of their apical and basolateral membrane domains by at least two different processes. These include the regulated trafficking of macromolecules from the biosynthetic and endocytic pathway to the appropriate membrane domain and the ability of the tight junction to prevent free mixing of membrane domain-specific proteins and lipids. Cdc42, a Rho family GTPase, is known to govern cellular polarity and membrane traffic in several cell types. We examined whether this protein regulated tight junction function in Madin-Darby canine kidney cells and pathways that direct proteins to the apical and basolateral surface of these cells. We used Madin-Darby canine kidney cells that expressed dominant-active or dominant-negative mutants of Cdc42 under the control of a tetracycline-repressible system. Here we report that expression of dominant-active Cdc42V12 or dominant-negative Cdc42N17 altered tight junction function. Expression of Cdc42V12 slowed endocytic and biosynthetic traffic, and expression of Cdc42N17 slowed apical endocytosis and basolateral to apical transcytosis but stimulated biosynthetic traffic. These results indicate that Cdc42 may modulate multiple cellular pathways required for the maintenance of epithelial cell polarity. PMID:11514615

  5. 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

  6. An Armadillo Motif in Ufd3 Interacts with Cdc48 and is Involved in Ubiquitin Homeostasis and Protein Degradation

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, G.; Li, G; Schindelin, H; Lennarz, W

    2009-01-01

    The yeast AAA-ATPase Cdc48 and the ubiquitin fusion degradation (UFD) proteins play important, evolutionarily conserved roles in ubiquitin dependent protein degradation. The N-terminal domain of Cdc48 interacts with substrate-recruiting cofactors, whereas the C terminus of Cdc48 binds to proteins such as Ufd3 that process substrates. Ufd3 is essential for efficient protein degradation and for maintaining cellular ubiquitin levels. This protein contains an N-terminal WD40 domain, a central ubiquitin-binding domain, and a C-terminal Cdc48-binding PUL domain. The crystal structure of the PUL domain reveals an Armadillo repeat with high structural similarity to importin-a, and the Cdc48-binding site could be mapped to the concave surface of the PUL domain by biochemical studies. Alterations of the Cdc48 binding site of Ufd3 by site-directed mutagenesis resulted in a depletion of cellular ubiquitin pools and reduced activity of the ubiquitin fusion degradation pathway. Therefore, our data provide direct evidence that the functions of Ufd3 in ubiquitin homeostasis and protein degradation depend on its interaction with the C terminus of Cdc48.

  7. 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.

  8. 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.

  9. 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...

  10. 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;

    2014-01-01

    Improperly attached kinetochores activate the spindle assembly checkpoint (SAC) and by an unknown mechanism catalyse the binding of two checkpoint proteins, Mad2 and BubR1, to Cdc20 forming the mitotic checkpoint complex (MCC). Here, to address the functional role of Cdc20 kinetochore localization...... on the SAC because the IC20BD is also required for efficient SAC silencing. Indeed, the IC20BD can disrupt the MCC providing a mechanism for its role in SAC silencing. We thus uncover an unexpected dual function of the second Cdc20 binding site in BubR1 in promoting both efficient SAC signalling and SAC...

  11. The cell cycle rallies the transcription cycle: Cdc28/Cdk1 is a cell cycle-regulated transcriptional CDK.

    Science.gov (United States)

    Chymkowitch, Pierre; Enserink, Jorrit M

    2013-01-01

    In the budding yeast Saccharomyces cerevisiae, the cyclin-dependent kinases (CDKs) Kin28, Bur1 and Ctk1 regulate basal transcription by phosphorylating the carboxyl-terminal domain (CTD) of RNA polymerase II. However, very little is known about the involvement of the cell cycle CDK Cdc28 in the transcription process. We have recently shown that, upon cell cycle entry, Cdc28 kinase activity boosts transcription of a subset of genes by directly stimulating the basal transcription machinery. Here, we discuss the biological significance of this finding and give our view of the kinase-dependent role of Cdc28 in regulation of RNA polymerase II.

  12. 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

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

    Directory of Open Access Journals (Sweden)

    Fogarty Kieran J

    2005-11-01

    Full Text Available 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 of the study design. The primary objective of this study was to construct a national, geographically-referenced database of HIV prevention services provided by CDC-funded CBOs. We designed a survey instrument to collect information about the geographic service areas where CBOs provided HIV prevention services, then collected data from CBOs that received CDC funding for these services during fiscal year 2000. We developed a GIS database to link questionnaire responses with GIS map layers in a manner that would incorporate overlapping geographies, risk populations and prevention services. We collected geographic service area data in two formats: 1 geopolitical boundaries and 2 geographic distance. Results The survey response rate was 70.3%, i.e. 1,020 of 1,450 community-based organizations responded. The number of HIV prevention programs administered by each CBO ranged from 1 to 23. The survey provided information about 3,028 prevention programs, including descriptions of intervention types, risk populations, race and ethnicity, CBO location and geographic service area. We incorporated this information into a large GIS database, the HIV Prevention Services Database. The use of geopolitical boundaries provided more accurate results than geographic distance. The use of a reference map with the questionnaire improved completeness, accuracy and precision of service area data. Conclusion The survey instrument design and database development procedures that we used

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

    Energy Technology Data Exchange (ETDEWEB)

    Pena, AndreAna N., E-mail: andreana.pena@gmail.com [Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX (United States); Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX (United States); Tominaga, Kaoru; Pereira-Smith, Olivia M. [Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX (United States); Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX (United States)

    2011-07-01

    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.

  15. 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

  16. Structural bases of dimerization of yeast telomere protein Cdc13 and its interaction with the catalytic subunit of DNA polymerase α

    Institute of Scientific and Technical Information of China (English)

    Jia Sun; Neal F Lue; Ming Lei; Yuting Yang; Ke Wan; Ninghui Mao; Tai-Yuan Yu; Yi-Chien Lin; Diane C DeZwaan; Brian C Freeman; Jing-Jer Lin

    2011-01-01

    Budding yeast Cdc13-Stnl-Tenl (CST) complex plays an essential role in telomere protection and maintenance, and has been proposed to be a telomere-specific replication protein A (RPA)-like complex. Previous genetic and structural studies revealed a close resemblance between Stn1-Ten1 and RPA32-RPA14. However, the relationship between Cdc13 and RPA70, the largest subunit of RPA, has remained unclear. Here, we report the crystal structure of the N-terminal OB (oligonucleotide/oligosaccharide binding) fold of Cdc13. Although Cdc13 has an RPA70-like domain organization, the structures of Cdc13 OB folds are significantly different from their counterparts in RPA70, suggesting that they have distinct evolutionary origins. Furthermore, our structural and biochemical analyses revealed unexpected dimerization by the N-terminal OB fold and showed that homodimerization is probably a conserved feature of all Cdc13 proteins. We also uncovered the structural basis of the interaction between the Cdc13 N-terminal OB ' fold and the catalytic subunit of DNA polymerase a (Pol1), and demonstrated a role for Cdc13 dimerization in Pol1 binding. Analysis of the phenotypes of mutants defective in Cdc13 dimerization and Cdc13-Pol1 interaction revealed multiple mechanisms by which dimerization regulates telomere lengths in vivo. Collectively, our findings provide novel insights into the mechanisms and evolution of Cdc13.

  17. 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

  18. 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...

  19. A Review of the CDC Recommendations for Prevention of HAIs in Outpatient Settings.

    Science.gov (United States)

    Garrett, J Hudson

    2015-05-01

    According to the Centers for Disease Control and Prevention (CDC), most health care-associated infections (HAIs) are caused by contamination from the hands of health care providers or patients, contamination from the environment, and contamination from the patient's own skin. To mitigate common sources of infection transmission, frontline health care providers must be compliant with basic infection-prevention interventions, including hand hygiene, environmental cleaning and disinfection, safe injection practices, and designation of a trained health care professional to be responsible for the infection prevention and control program. Integration of CDC recommendations should incorporate a bundled approach to these interventions and should be part of a comprehensive approach to infection prevention and control. Effective infection-prevention practices in outpatient settings are critical for reducing the risk of infection transmission, improving patient safety and patient outcomes, and reducing costs associated with health care delivery.

  20. 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.

  1. 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...

  2. 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...

  3. 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

    ... Hepatitis and STD Prevention and Treatment; Notice of Meeting In accordance with section l0(a)(2) of the... meeting. Name: CDC/HRSA Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment...

  4. 77 FR 66469 - CDC/HRSA Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment

    Science.gov (United States)

    2012-11-05

    ... Hepatitis and STD Prevention and Treatment In accordance with section 10(a)(2) of the Federal Advisory... Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC, 1600 Clifton Road NE., Mailstop...

  5. 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...

  6. 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...

  7. CDC Vital Signs–Dental Sealants Prevent Cavities

    Centers for Disease Control (CDC) Podcasts

    2016-10-18

    This podcast is based on the October 2016 CDC Vital Signs report. Dental sealants, applied soon after a child's permanent molars come in, can protect against cavities for up to nine years. Applying sealants in schools for low-income children could save millions in dental treatment costs.  Created: 10/18/2016 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/18/2016.

  8. 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.

  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-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.

  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. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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...

  1. 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...

  2. Diferencias en magnitud de estado nutricional en escolares chilenos según la referencia CDC y OMS 2005-2008

    Directory of Open Access Journals (Sweden)

    Fabián Vásquez

    2013-02-01

    Full Text Available Introducción: Es necesario realizar nuevas discusiones respecto a la magnitud de los problemas nutricionales diagnosticados, al usar CDC u OMS, frente a la existencia de nuevas definiciones biológicas o estadísticas de obesidad. Objetivo: Comparar la evolución de la prevalencia de estado nutricional en escolares de primero básico, desde el año 2005 al 2008, según CDC y OMS. Métodos: Cohorte retrospectiva, de 140.265 escolares de ambos sexos de primero básico, evaluados entre 2005-2008, cuyos datos antropométricos (peso y talla, se obtuvieron del sistema anual de registro del estado nutricional escolar. Para clasificar el estado nutricional, se utilizaron los patrones CDC y OMS. Resultados: Los promedios de IMC fueron levemente diferentes y menores en la niñas que en los niños, en 2005 y 2006. Durante el 2007 y 2008 el promedio de IMC en las niñas alcanzó la cifra observada en los varones. Hubo mayor prevalencia de bajo peso según OMS (p=0,03, con una tendencia a la disminución en los años posteriores. La prevalencia de normalidad fue mayor según el criterio CDC, con una reducción entre el 2005 y 2007 y un incremento 2008 (p<0,001. Hubo una menor prevalencia de sobrepeso según el criterio CDC (p<0,001, con aumento entre el 2005 y 2007, tanto CDC como OMS. La prevalencia de obesidad fue menor según el criterio OMS, no encontrándose diferencia estadísticamente significativa al comparar con el patrón CDC. Conclusiones: Al comparar ambos patrones, CDC tiende a sobreestimar la normalidad y subestimar el sobrepeso, mientras que en obesidad no se encontraron diferencias significativas.

  3. Correlation between δ-catenin and Cdc42 expression in non-small cell lung cancer%δ-catenin与Cdc42在非小细胞肺癌中表达的相关性

    Institute of Scientific and Technical Information of China (English)

    张迪; 王恩华

    2016-01-01

    背景与目的:δ-catenin是p120 catenin亚家族中的成员,可与细胞膜上的E-cadherin直接结合,形成E-cadherin/catenin复合体。δ-catenin还可以通过调节Cdc42(Small GTP酶)活性以影响细胞骨架装配。该研究检测非小细胞肺癌(non-small cell lung cancer,NSCLC)中δ-catenin及Cdc42的表达情况并探讨了二者表达的相关性。方法:采用免疫组织化学方法检测122例NSCLC标本中δ-catenin与Cdc42的表达。采用蛋白[质]印迹法(Western blot)及逆转录聚合酶链反应(reverse transcription polymerase chain reaction,RT-PCR)法检测肺癌组织中δ-catenin及Cdc42的蛋白及mRNA表达情况。在肺癌细胞系中,分别上调或干扰δ-catenin的表达后,利用G-LISA及Transwell小室法检测Cdc42活性以及肺癌细胞侵袭能力的改变。结果:δ-catenin和Cdc42在肺癌组织中其蛋白及mRNA表达明显高于正常肺组织。而在122例NSCLC病例中,δ-catenin阳性表达率为65.57%(80/122),Cdc42过表达率为68.03%(83/122)。δ-catenin阳性表达和Cdc42的过表达具有较好的相关性(P<0.001)。δ-catenin和Cdc42的协同表达与肺癌的高临床分期、低分化、病理类型为腺癌和淋巴结转移相关(P<0.05),并且与肺癌患者的不良预后明显相关。在肺癌细胞系中通过调节δ-catenin表达,改变Cdc42的表达及活性,影响肺癌细胞的侵袭能力。结论:在肺癌组织中δ-catenin和Cdc42的表达具有相关性,而二者协同表达与患者不良预后相关。%Background and purpose:δ-catenin is a member of the p120 catenin subfamily, which can directly bind to E-cadherin on the cell membrane, forming E-cadherin/catenin complex. δ-catenin can also affect the cytoskeleton assembly by regulating the activity of Cdc42 (Small GTPase). Therefore, this study detected the expression of δ-catenin and Cdc42 in non-small cell lung cancer (NSCLC) and investigated the relationship between them

  4. 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.

  5. 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)

  6. 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.

  7. 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.

  8. 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

  9. 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...

  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. 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

  12. Slit2 inhibits glioma cell invasion in the brain by suppression of Cdc42 activity.

    Science.gov (United States)

    Yiin, Jia-Jean; Hu, Bo; Jarzynka, Michael J; Feng, Haizhong; Liu, Kui-Wei; Wu, Jane Y; Ma, Hsin-I; Cheng, Shi-Yuan

    2009-12-01

    Acquisition of insidious invasiveness by malignant glioma cells involves multiple genetic alterations in signaling pathways. Slit2, a chemorepulsive factor, controls cell migration of neuronal and glial cells during development and inhibits chemotaxic migration of various types of cells in vitro. However, the role of Slit2 in vitro remains controversial, and the biological significance of Slit2 expression in cancer cell invasion in vivo has not yet been determined. In the present study, we characterized the effects of Slit2 expression on the migration and invasion of invasive glioma cells in vitro and in vivo. By reverse transcriptase polymerase chain reaction (PCR) analyses, Slit2 was found to be expressed at lower levels in primary glioma specimens and invasive glioma cells compared with normal human brain cells and astrocytes. Ectopic expression of Slit2 or treatment with recombinant Slit2 on glioma cells attenuates cell migration and invasion through inhibition of Cdc42 activity in vitro. Cellular depletion of Robo1, a cognate receptor for Slit2, prevented Slit2 inhibition of Cdc42 activity and glioma cell migration. In vivo, expression of Slit2 by invasive SNB19 glioma cells markedly inhibited glioma cell infiltration into the brain of mice. Moreover, impediment of glioma cell invasion by Slit2 did not affect the expression of N-cadherin and beta-catenin in glioma cells. These results provide the first evidence demonstrating that Slit2-Robo1 inhibits glioma invasion through attenuating Cdc42 activity in vitro and in the brain. Understanding the mechanisms of Slit2-Robo1 inhibition of glioma cell invasion will foster new treatments for malignant gliomas.

  13. 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…

  14. Ten1p promotes the telomeric DNA-binding activity of Cdc13p: implication for its function in telomere length regulation

    Institute of Scientific and Technical Information of China (English)

    Wei Qian; Jianyong Wang; Na-Na Jin; Xiao-Hong Fu; Yi-Chien Lin; Jing-Jer Lin; Jin-Qiu Zhou

    2009-01-01

    In Saccharomyces cerevisiae, the essential gene CDC13 encodes a telomeric single-stranded DNA-binding protein that interacts with Stnlp and Tenlp genetically and physically, and is required for telomere end protection and te-Iomere length control. The molecular mechanism by which Ten1 participates in telomere length regulation and chro-mosome end protection remains elusive. In this work, we observed a weak interaction of Cdc13p and Tenlp in a gel-filtration analysis using purified recombinant Cdc13p and Ten lp. Ten 1p itself exhibits a weak DNA-binding activity, but enhances the telomeric TG1-3 DNA-binding ability of Cdc13p. Cdc13p is co-immunoprecipitated with Ten1p. In the mutant ten1-55 or ten1-66 cells, the impaired interaction between Ten1p and Cdc13p results in much longer telomeres, as well as a decreased association of Cdc13p with telomeric DNA. Consistently, the Ten1-55 and Ten1-66 mutant proteins fail to stimulate the telomeric DNA-binding activity of Cdc13p in vitro. These results suggest that Ten1p enhances the telomeric DNA-binding activity of Cdc13p to negatively regulate telomere length.

  15. 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...

  16. Cdc14 Early Anaphase Release, FEAR, Is Limited to the Nucleus and Dispensable for Efficient Mitotic Exit.

    Directory of Open Access Journals (Sweden)

    Christopher M Yellman

    Full Text Available Cdc14 phosphatase is a key regulator of exit from mitosis, acting primarily through antagonism of cyclin-dependent kinase, and is also thought to be important for meiosis. Cdc14 is released from its sequestration site in the nucleolus in two stages, first by the non-essential Cdc Fourteen Early Anaphase Release (FEAR pathway and later by the essential Mitotic Exit Network (MEN, which drives efficient export of Cdc14 to the cytoplasm. We find that Cdc14 is confined to the nucleus during early mitotic anaphase release, and during its meiosis I release. Proteins whose degradation is directed by Cdc14 as a requirement for mitotic exit (e.g. the B-type cyclin, Clb2, remain stable during mitotic FEAR, a result consistent with Cdc14 being restricted to the nucleus and not participating directly in mitotic exit. Cdc14 released by the FEAR pathway has been proposed to have a wide variety of activities, all of which are thought to promote passage through anaphase. Proposed functions of FEAR include stabilization of anaphase spindles, resolution of the rDNA to allow its segregation, and priming of the MEN so that mitotic exit can occur promptly and efficiently. We tested the model for FEAR functions using the FEAR-deficient mutation net1-6cdk. Our cytological observations indicate that, contrary to the current model, FEAR is fully dispensable for timely progression through a series of anaphase landmarks and mitotic exit, although it is required for timely rDNA segregation. The net1-6cdk mutation suppresses temperature-sensitive mutations in MEN genes, suggesting that rather than activating mitotic exit, FEAR either inhibits the MEN or has no direct effect upon it. One interpretation of this result is that FEAR delays MEN activation to ensure that rDNA segregation occurs before mitotic exit. Our findings clarify the distinction between FEAR and MEN-dependent Cdc14 activities and will help guide emerging quantitative models of this cell cycle transition.

  17. 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

  18. 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.

  19. 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.

  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 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.

  3. 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.

  4. 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.

  5. 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...

  6. 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...

  7. A genome-scale CRISPR-Cas9 screening method for protein stability reveals novel regulators of Cdc25A

    Science.gov (United States)

    Wu, Yuanzhong; Zhou, Liwen; Wang, Xin; Lu, Jinping; Zhang, Ruhua; Liang, Xiaoting; Wang, Li; Deng, Wuguo; Zeng, Yi-Xin; Huang, Haojie; Kang, Tiebang

    2016-01-01

    The regulation of stability is particularly crucial for unstable proteins in cells. However, a convenient and unbiased method of identifying regulators of protein stability remains to be developed. Recently, a genome-scale CRISPR-Cas9 library has been established as a genetic tool to mediate loss-of-function screening. Here, we developed a protein stability regulators screening assay (Pro-SRSA) by combining the whole-genome CRISPR-Cas9 library with a dual-fluorescence-based protein stability reporter and high-throughput sequencing to screen for regulators of protein stability. Using Cdc25A as an example, Cul4B-DDB1DCAF8 was identified as a new E3 ligase for Cdc25A. Moreover, the acetylation of Cdc25A at lysine 150, which was acetylated by p300/CBP and deacetylated by HDAC3, prevented the ubiquitin-mediated degradation of Cdc25A by the proteasome. This is the first study to report that acetylation, as a novel posttranslational modification, modulates Cdc25A stability, and we suggest that this unbiased CRISPR-Cas9 screening method at the genome scale may be widely used to globally identify regulators of protein stability. PMID:27462461

  8. 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.

  9. 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

  10. Cell-cycle-dependent PC-PLC regulation by APC/C(Cdc20)-mediated ubiquitin-proteasome pathway.

    Science.gov (United States)

    Fu, Da; Ma, Yushui; Wu, Wei; Zhu, Xuchao; Jia, Chengyou; Zhao, Qianlei; Zhang, Chunyi; Wu, Xing Zhong

    2009-07-01

    Phosphatidylcholine-specific phospholipase C (PC-PLC) is involved in the cell signal transduction, cell proliferation, and apoptosis. The mechanism of its action, however, has not been fully understood, particularly, the role of PC-PLC in the cell cycle. In the present study, we found that cell division cycle 20 homolog (Cdc20) and PC-PLC were co-immunoprecipitated reciprocally by either antibody in rat hepatoma cells CBRH-7919 as well as in rat liver tissue. Using confocal microscopy, we found that PC-PLC and Cdc20 were co-localized in the perinuclear endoplasmic reticulum region (the "juxtanuclear quality control" compartment, JUNQ). The expression level and activities of PC-PLC changed in a cell-cycle-dependent manner and were inversely correlated with the expression of Cdc20. Intriguingly, Cdc20 overexpression altered the subcellular localization and distribution of PC-PLC, and caused PC-PLC degradation by the ubiquitin proteasome pathway (UPP). Taken together, our data indicate that PC-PLC regulation in cell cycles is controlled by APC/C(Cdc20)-mediated UPP.

  11. CDC4及c-Myc在胃癌中的表达及临床意义%The expressions of CDC4 and c-Myc in gastric cancer and their clinical signifieance

    Institute of Scientific and Technical Information of China (English)

    黄国全; 黎晖; 张才全; 吴泉峰; 孙建华

    2015-01-01

    背景与目的:胃癌是全世界多发恶性肿瘤之一,其死亡率及术后复发率高。目前治疗胃癌的手段主要是手术及放化疗,但总体效果欠佳。随着经济及分子生物学的飞速发展,胃癌的早期诊断及分子靶向治疗成为全世界研究的热点。胃癌的发生、发展与抑癌基因的失活和癌基因的过表达相关。CDC4/Fbxw7为重要的抑癌基因。本实验通过研究CDC4(F框/WD-40Ⅱ蛋白7,也称为FBXW7、Sel-10、Ago)及c-Myc蛋白在人胃癌组织中的表达,分析两者与胃癌临床病理特征的关系。方法:应用半定量逆转录聚合酶链反应(semi-quantitative reverse transcription polymerase chain reaction,sRT-PCR)、免疫组化及蛋白[质]印迹法(Western blot)检测40例胃癌组织、癌旁组织及正常胃黏膜组织中CDC4、c-Myc的mRNA及蛋白的表达,并分析两者之间的相关性及与患者病理特征之间的关系。结果:胃癌中CDC4蛋白的表达明显低于癌旁组织及正常组织(P<0.05)。而c-Myc蛋白的表达在胃癌中显著增高,阳性率同癌旁组织及正常组织比较,差异有统计学意义(P<0.05)。CDC4、c-Myc蛋白及其mRNA的表达与胃癌患者的性别、年龄、肿瘤部位无关,而与肿瘤浸润深度、分化程度、TNM分期、有无淋巴结转移及有无远处转移有关(P<0.05)。CDC4和c-Myc在mRNA水平和蛋白水平的表达均呈负相关(P<0.05)。结论:CDC4在胃癌中表达量显著下降,可能与胃癌的浸润、分化及转移相关,其表达缺失可能导致c-Myc的过度表达。CDC4可能成为早期诊断、判断胃癌预后及浸润转移的生物学指标。%Background and purpose:The gastric cancer is the highest incidence of malignant tumors in the world. The main treatment methods for gastric cancer are operation and chemotherapy. But the effect is not good. With the rapid development of economy and molecular biology, early diagnosis and molecular

  12. 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.

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

    Science.gov (United States)

    Natsume, Akito; Niwa, Rinpei; Satoh, Mitsuo

    2009-09-21

    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 FcgammaRIIIa 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.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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...

  19. 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 ...

  20. A cyclin-abundance cycle-independent p34cdc2 tyrosine phosphorylation cycle in early sea urchin embryos.

    OpenAIRE

    Edgecombe, M; Patel, R.; Whitaker, M

    1991-01-01

    The activity of the cell cycle control protein p34cdc2 is post-translationally regulated in a variety of cell types. Using anti-phosphotyrosine antibodies, we find that p34cdc2-directed tyrosine kinase activity increases at fertilization in sea urchin eggs, leading to a gradual accumulation of phosphotyrosine on p34 during the early part of the cell cycle. Loss of phosphotyrosine from p34 accompanies entry into mitosis and phosphotyrosine reaccumulates as the embryo enters the next cell cycle...

  1. 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.)

  2. Molecular Characterization and Expression Profiles of Cyclin B1, B2 and Cdc2 Kinase during Oogenesis and Spermatogenesis in Rainbow Trout (Oncorhynchus mykiss)

    Science.gov (United States)

    The meiotic maturation of oocytes and spermatocytes is controlled by the maturation promotion factor (MPF), a complex of the Cdc2 and cyclin B proteins. To better understand the mechanism of oocyte and spermatocyte maturation in fish, the expression of cyclin B1 (CB1), cyclin B2 (CB2) and Cdc2 kinas...

  3. 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...

  4. 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...

  5. Control of the Cdc6 replication licensing factor in metazoa: the role of nuclear export and the CUL4 ubiquitin ligase.

    Science.gov (United States)

    Kim, Jihyun; Kipreos, Edward T

    2008-01-15

    A central requirement to maintain genome stability is that DNA replication must be tightly controlled so that genomic DNA is replicated only once in a single cell cycle. The prevention of DNA re-replication is achieved by restricting the assembly of pre-replicative complexes (pre-RCs) to the period prior to S phase, and ensuring that pre-RCs cannot reform during S phase. The regulation of the replication licensing factors Cdt1 and Cdc6 during S phase is critical to prevent the reformation of pre-RCs. In yeast, Cdc6 is degraded during S phase to block DNA re-replication. In mammals, Cdc6 is exported from the nucleus; however, a variable percentage of endogenous Cdc6 remains nuclear throughout S phase. The perdurance of nuclear Cdc6 has led a number of groups to question whether the nuclear export of Cdc6 is relevant in restricting its activity. A recent study in C. elegans shows that the nuclear export of Cdc6 is in fact critical to prevent DNA re-replication. This work also identifies the CUL-4 ubiquitin ligase as a master regulator that controls DNA replication by regulating both Cdt1 and Cdc6 replication licensing factors. PMID:18256526

  6. 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.

  7. 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....

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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... items include: (1) STD clinical preventive services in primary care setting and integrating STD... Hepatitis, STD, and TB Prevention, 1600 Clifton Road NE., Mailstop E-07, Atlanta, Georgia 30333,...

  15. 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... STD disparities among racial and ethnic minorities. Agenda items are subject to change as priorities... Hepatitis, STD, and TB Prevention, 1600 Clifton Road, NE., Mailstop E-07, Atlanta, Georgia 30333,...

  16. 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

  17. 75 FR 11889 - Request for Comments on Proposed NIH, AHRQ and CDC Process Change for Electronic Submission of...

    Science.gov (United States)

    2010-03-12

    ... HUMAN SERVICES Request for Comments on Proposed NIH, AHRQ and CDC Process Change for Electronic Submission of Grant Applications AGENCY: Department of Health and Human Services. ACTION: Process change. SUMMARY: The National Institutes of Health (NIH), the Agency for Healthcare Research and Quality...

  18. 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

  19. 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...

  20. 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

  1. The CDC and IOTF cut points show inconsistent prevalence of underweight and overweight in chinese, indonesian, and vietnamese children

    Science.gov (United States)

    No nationally representative data from middle and low-income countries have been analyzed to compare prevalence of underweight and overweight defined by the Centers for Disease Control and Prevention (CDC) and the International Obesity Task Force (IOTF) BMI cut points. We evaluated the consistency i...

  2. 76 FR 62071 - Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)-Health...

    Science.gov (United States)

    2011-10-06

    ... HUMAN SERVICES Centers for Disease Control and Prevention Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)--Health Disparities Subcommittee (HDS) In accordance with... and other committee management activities, for both the Centers for Disease Control and Prevention...

  3. Comparison of various configurations of CDC-type traps for the collection of Phlebotomus papatasi (Scopoli) in southern Israel

    Science.gov (United States)

    We conducted 2 experiments to determine the best configuration of CDC-trap for catching male and female Phlebotomus papatasi. Darker traps caught significantly more male sand flies; significantly more females were captured by traps with either all black or a combination of black and white features. ...

  4. A novel coumarin-quinone derivative SV37 inhibits CDC25 phosphatases, impairs proliferation, and induces cell death.

    Science.gov (United States)

    Bana, Emilie; Sibille, Estelle; Valente, Sergio; Cerella, Claudia; Chaimbault, Patrick; Kirsch, Gilbert; Dicato, Mario; Diederich, Marc; Bagrel, Denyse

    2015-03-01

    Cell division cycle (CDC) 25 proteins are key phosphatases regulating cell cycle transition and proliferation by regulating CDK/cyclin complexes. Overexpression of these enzymes is frequently observed in cancer and is related to aggressiveness, high-grade tumors and poor prognosis. Thus, targeting CDC25 by compounds, able to inhibit their activity, appears a good therapeutic approach. Here, we describe the synthesis of a new inhibitor (SV37) whose structure is based on both coumarin and quinone moieties. An analytical in vitro approach shows that this compound efficiently inhibits all three purified human CDC25 isoforms (IC50 1-9 µM) in a mixed-type mode. Moreover, SV37 inhibits growth of breast cancer cell lines. In MDA-MB-231 cells, reactive oxygen species generation is followed by pCDK accumulation, a mark of CDC25 dysfunction. Eventually, SV37 treatment leads to activation of apoptosis and DNA cleavage, underlining the potential of this new type of coumarin-quinone structure.

  5. Atomic structure of Hsp90-Cdc37-Cdk4 reveals that Hsp90 traps and stabilizes an unfolded kinase.

    Science.gov (United States)

    Verba, Kliment A; Wang, Ray Yu-Ruei; Arakawa, Akihiko; Liu, Yanxin; Shirouzu, Mikako; Yokoyama, Shigeyuki; Agard, David A

    2016-06-24

    The Hsp90 molecular chaperone and its Cdc37 cochaperone help stabilize and activate more than half of the human kinome. However, both the mechanism by which these chaperones assist their "client" kinases and the reason why some kinases are addicted to Hsp90 while closely related family members are independent are unknown. Our structural understanding of these interactions is lacking, as no full-length structures of human Hsp90, Cdc37, or either of these proteins with a kinase have been elucidated. Here we report a 3.9 angstrom cryo-electron microscopy structure of the Hsp90-Cdc37-Cdk4 kinase complex. Surprisingly, the two lobes of Cdk4 are completely separated with the β4-β5 sheet unfolded. Cdc37 mimics part of the kinase N lobe, stabilizing an open kinase conformation by wedging itself between the two lobes. Finally, Hsp90 clamps around the unfolded kinase β5 strand and interacts with exposed N- and C-lobe interfaces, protecting the kinase in a trapped unfolded state. On the basis of this structure and an extensive amount of previously collected data, we propose unifying conceptual and mechanistic models of chaperone-kinase interactions. PMID:27339980

  6. Estrogen and Resveratrol Regulate Rac and Cdc42 Signaling to the Actin Cytoskeleton of Metastatic Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Nicolas G. Azios

    2007-02-01

    Full Text Available Estrogen and structurally related molecules play critical roles in breast cancer. We reported that resveratrol (50 µM, an estrogen-like phytosterol from grapes, acts in an antiestrogenic manner in breast cancer cells to reduce cell migration and to induce a global and sustained extension of actin structures called filopodia. Herein, we report that resveratrol-induced filopodia formation is time-dependent and concentration-dependent. In contrast to resveratrol at 50 µM, resveratrol at 5 µM acts in a manner similar to estrogen by increasing lamellipodia, as well as cell migration and invasion. Because Rho GTPases regulate the extension of actin structures, we investigated a role for Rac and Cdc42 in estrogen and resveratrol signaling. Our results demonstrate that 50 µM resveratrol decreases Rac and Cdc42 activity, whereas estrogen and 5 µM resveratrol increase Rac activity in breast cancer cells. MDA-MB-231 cells expressing dominant-negative Cdc42 or dominantnegative Rac retain filopodia response to 50 µM resveratrol. Lamellipodia response to 5 µM resveratrol, estrogen, or epidermal growth factor is inhibited in cells expressing dominant-negative Rac, indicating that Rac regulates estrogen and resveratrol (5 µM signaling to the actin cytoskeleton. These results indicate that signaling to the actin cytoskeleton by low and high concentrations of resveratrol may be differentially regulated by Rac and Cdc42.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration

    DEFF Research Database (Denmark)

    Lammermann, Tim; Renkawitz, Jorg; Wu, Xunwei;

    2009-01-01

    contraction are still initiated in response to chemotactic cues. Accordingly, the cells are able to polarize and form protrusions. However, in the absence of Cdc42 the protrusions are temporally and spatially dysregulated which leads to impaired leading edge coordination. While this defect still allows...... the cells to move on two-dimensional surfaces, their in vivo motility is completely abrogated. We show that this difference is entirely caused by the geometrical complexity of the environment as multiple competing protrusions lead to instantaneous entanglement within three-dimensional extracellular matrix...... scaffolds. This demonstrates that the decisive factor for migrating DCs is not specific interaction with the extracellular environment, but adequate coordination of cytoskeletal flow....

  14. Frequent alterations of SLIT2–ROBO1–CDC42 signalling pathway in breast cancer: clinicopathological correlation

    Indian Academy of Sciences (India)

    RITTWIKA BHATTACHARYA; NUPUR MUKHERJEE; HEMANTIKA DASGUPTA; MD. SAIMUL ISLAM; NEYAZ ALAM; ANUP ROY; PRIYOBRATA DAS; SUSANTA ROY CHOUDHURY; CHINMAY KUMAR PANDA

    2016-09-01

    The aim of the study was to understand the role of SLIT2–ROBO1/2–CDC42 signalling pathways in development of breast cancer (BC). Primary BC samples (n = 150), comprising of almost equal proportion of four subtypes were tested for molecular alterations of SLIT2, ROBO1, ROBO2 and CDC42, the key regulator genes of this pathway. Deletion and methylation frequencies of the candidate genes were seen in the following order: deletion, SLIT2 (38.6%) > ROBO1 (30%)> ROBO2 (7.3%); methylation, SLIT2 (63.3%) > ROBO1 (26.6%) >ROBO2 (9.3%). Majority (80%, 120/150) of the tumours showed alterations (deletion/methylation) in at least one of the candidate genes. Overall, alterations of the candidate genes were as follows: SLIT2, 75.3% (101/150); ROBO1, 45.3% (68/150); ROBO2, 15.3% (23/150). Significantly, higher alteration of SLIT2 locus was observed in triple negative breast cancer (TNBC) over HER2 subtype (P = 0.0014). Similar trend is also seen in overall alterations of SLIT2 and/or ROBO1, in TNBC than HER2 subtype (P = 0.0012); of SLIT2 and/or ROBO2 in TNBC than luminal A (P = 0.014) and HER2 subtype (P = 0.048). Immunohistochemical analysis of SLIT2, ROBO1/2 showed reduced expression, concordant with their molecular alterations. Also, high expression of total CDC42 (49/52; 94.2%) and reduced expression of phospho Serine-71 CDC42 (41/52; 78.8%) was observed. Coalterations of SLIT2 and/or ROBO1, SLIT2 and/or ROBO2 had significant association with reduced expression of phospho Serine-71 CDC42 (P = 0.0012–0.0038). Alterations of SLIT2 and/or ROBO1, reduced expression of phospho Serine-71 CDC42 predicted poor survival of BC patients. Results indicate the importance of SLIT2–ROBO1–CDC42 signalling pathway in predicting tumour progression.

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. Hyperactive Cdc2 kinase interferes with the response to broken replication forks by trapping S.pombe Crb2 in its mitotic T215 phosphorylated state.

    Science.gov (United States)

    Mahyous Saeyd, Salah Adam; Ewert-Krzemieniewska, Katarzyna; Liu, Boyin; Caspari, Thomas

    2014-07-01

    Although it is well established that Cdc2 kinase phosphorylates the DNA damage checkpoint protein Crb2(53BP1) in mitosis, the full impact of this modification is still unclear. The Tudor-BRCT domain protein Crb2 binds to modified histones at DNA lesions to mediate the activation of Chk1 by Rad3ATR kinase. We demonstrate here that fission yeast cells harbouring a hyperactive Cdc2CDK1 mutation (cdc2.1w) are specifically sensitive to the topoisomerase 1 inhibitor camptothecin (CPT) which breaks DNA replication forks. Unlike wild-type cells, which delay only briefly in CPT medium by activating Chk1 kinase, cdc2.1w cells bypass Chk1 to enter an extended cell-cycle arrest which depends on Cds1 kinase. Intriguingly, the ability to bypass Chk1 requires the mitotic Cdc2 phosphorylation site Crb2-T215. This implies that the presence of the mitotic phosphorylation at Crb2-T215 channels Rad3 activity towards Cds1 instead of Chk1 when forks break in S phase. We also provide evidence that hyperactive Cdc2.1w locks cells in a G1-like DNA repair mode which favours non-homologous end joining over interchromosomal recombination. Taken together, our data support a model such that elevated Cdc2 activity delays the transition of Crb2 from its G1 to its G2 mode by blocking Srs2 DNA helicase and Casein Kinase 1 (Hhp1).

  3. 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

  4. Epstein-Barr virus-encoded LMP1 interacts with FGD4 to activate Cdc42 and thereby promote migration of nasopharyngeal carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Hao-Ping Liu

    Full Text Available Epstein-Barr virus (EBV is closely associated with nasopharyngeal carcinoma (NPC, a human malignancy notorious for its highly metastatic nature. Among EBV-encoded genes, latent membrane protein 1 (LMP1 is expressed in most NPC tissues and exerts oncogenicity by engaging multiple signaling pathways in a ligand-independent manner. LMP1 expression also results in actin cytoskeleton reorganization, which modulates cell morphology and cell motility- cellular process regulated by RhoGTPases, such as Cdc42. Despite the prominent association of Cdc42 activation with tumorigenesis, the molecular basis of Cdc42 activation by LMP1 in NPC cells remains to be elucidated. Here using GST-CBD (active Cdc42-binding domain as bait in GST pull-down assays to precipitate active Cdc42 from cell lysates, we demonstrated that LMP1 acts through its transmembrane domains to preferentially induce Cdc42 activation in various types of epithelial cells, including NPC cells. Using RNA interference combined with re-introduction experiments, we identified FGD4 (FYVE, RhoGEF and PH domain containing 4 as the GEF (guanine nucleotide exchange factor responsible for the activation of Cdc42 by LMP1. Serial deletion experiments and co-immunoprecipitation assays further revealed that ectopically expressed FGD4 modulated LMP1-mediated Cdc42 activation by interacting with LMP1. Moreover, LMP1, through its transmembrane domains, directly bound FGD4 and enhanced FGD4 activity toward Cdc42, leading to actin cytoskeleton rearrangement and increased motility of NPC cells. Depletion of FGD4 or Cdc42 significantly reduced (∼50% the LMP1-stimulated cell motility, an effect that was partially reversed by expression of a constitutively active mutant of Cdc42. Finally, quantitative RT-PCR and immunohistochemistry analyses showed that FGD4 and LMP1 were expressed in NPC tissues, supporting the potential physiologically relevance of this mechanism in NPC. Collectively, our results not only

  5. [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

  6. 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...

  7. 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

  8. "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

  9. Mitotic expression of Spo13 alters M-phase progression and nucleolar localization of Cdc14 in budding yeast.

    Science.gov (United States)

    Varela, Elisa; Schlecht, Ulrich; Moina, Anca; Fackenthal, James D; Washburn, Brian K; Niederhauser-Wiederkehr, Christa; Tsai-Pflugfelder, Monika; Primig, Michael; Gasser, Susan M; Esposito, Rochelle E

    2010-07-01

    Spo13 is a key meiosis-specific regulator required for centromere cohesion and coorientation, and for progression through two nuclear divisions. We previously reported that it causes a G2/M arrest and may delay the transition from late anaphase to G1, when overexpressed in mitosis. Yet its mechanism of action has remained elusive. Here we show that Spo13, which is phosphorylated and stabilized at G2/M in a Cdk/Clb-dependent manner, acts at two stages during mitotic cell division. Spo13 provokes a G2/M arrest that is reversible and largely independent of the Mad2 spindle checkpoint. Since mRNAs whose induction requires Cdc14 activation are reduced, we propose that its anaphase delay results from inhibition of Cdc14 function. Indeed, the Spo13-induced anaphase delay correlates with Cdc14 phosphatase retention in the nucleolus and with cyclin B accumulation, which both impede anaphase exit. At the onset of arrest, Spo13 is primarily associated with the nucleolus, where Cdc14 accumulates. Significantly, overexpression of separase (Esp1), which promotes G2/M and anaphase progression, suppresses Spo13 effects in mitosis, arguing that Spo13 acts upstream or parallel to Esp1. Given that Spo13 overexpression reduces Pds1 and cyclin B degradation, our findings are consistent with a role for Spo13 in regulating APC, which controls both G2/M and anaphase. Similar effects of Spo13 during meiotic MI may prevent cell cycle exit and initiation of DNA replication prior to MII, thereby ensuring two successive chromosome segregation events without an intervening S phase. PMID:20407133

  10. 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...

  11. 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

  12. 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...

  13. The impact of climate change on infectious disease transmission: perceptions of CDC health professionals in Shanxi Province, China.

    Directory of Open Access Journals (Sweden)

    Junni Wei

    Full Text Available There have been increasing concerns about the challenge of emerging and re-emerging infectious diseases due to climate change, especially in developing countries including China. Health professionals play a significant role in the battle to control and prevent infectious diseases. This study therefore aims to investigate the perceptions and attitudes of health professionals at the Centers for Disease Control and Prevention (CDC in different levels in China, and to consider adaptation measures to deal with the challenge of climate change. In 2013, a cross-sectional questionnaire survey was undertaken among 314 staff in CDCs in Shanxi Province, China, whose routine work involves disease control and prevention. Data were analyzed using descriptive methods and logistic regression. A majority of the CDC staff were aware of the health risks from climate change, especially its impacts on infectious disease transmission in their jurisdictions, and believed climate change might bring about both temporal and spatial change in transmission patterns. It was thought that adaptation measures should be established including: strengthening/improving currently existing disease surveillance systems and vector monitoring; building CDC capacity in terms of infrastructure and in-house health professional training; development and refinement of relevant legislation, policies and guidelines; better coordination among various government departments; the involvement of the community in infectious disease interventions; and collaborative research with other institutions. This study provides a snapshot of the understanding of CDC staff regarding climate change risks relevant to infectious diseases and adaptation in China. Results may help inform future efforts to develop adaptation measures to minimize infectious disease risks due to climate change.

  14. MicroRNA-224 Suppresses Colorectal Cancer Cell Migration by Targeting Cdc42

    Directory of Open Access Journals (Sweden)

    Tao-Wei Ke

    2014-01-01

    Full Text Available The metastatic spread of tumor cells is the major risk factor affecting the clinical prognosis of colorectal cancer (CRC patients. The metastatic phenotype can be modulated by dysregulating the synthesis of different structural and functional proteins of tumor cells. Micro(miRNAs are noncoding RNAs that recognize their cognate messenger (mRNA targets by sequence-specific interactions with the 3′ untranslated region and are involved in the multistep process of CRC development. The objective of this study was to investigate the expression and biological roles of miR-224 in CRC. The miR-224 expression level was assessed by a quantitative real-time PCR in 79 CRC and 18 nontumor tissues. Expression levels of miR-224 in CRC tissues were significantly lower than those in nontumor tissues. Its expression level was associated with the mutation status of the APC gene. Ectopic expression of miR-224 suppressed the migratory ability of CRC cell line, but cell proliferation was less affected. Increased miR-224 diminished Cdc42 and SMAD4 expressions at both the protein and mRNA levels and inhibited the formation of actin filaments. Overall, this study indicated a role of miR-224 in negatively regulating CRC cell migration. The expression level of miR-224 may be a useful predictive biomarker for CRC progression.

  15. 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.

  16. Definition of the switch surface in the solution structure of Cdc42Hs.

    Science.gov (United States)

    Feltham, J L; Dötsch, V; Raza, S; Manor, D; Cerione, R A; Sutcliffe, M J; Wagner, G; Oswald, R E

    1997-07-22

    Proteins of the rho subfamily of ras GTPases have been shown to be crucial components of pathways leading to cell growth and the establishment of cell polarity and mobility. Presented here is the solution structure of one such protein, Cdc42Hs, which provides insight into the structural basis for specificity of interactions between this protein and its effector and regulatory proteins. Standard heteronuclear NMR methods were used to assign the protein, and approximately 2100 distance and dihedral angle constraints were used to calculate a set of 20 structures using a combination of distance geometry and simulated annealing refinement. These structures show overall similarity to those of other GTP-binding proteins, with some exceptions. The regions corresponding to switch I and switch II in H-ras are disordered, and no evidence was found for an alpha-helix in switch II. The 13-residue insertion, which is only present in rho-subtype proteins and has been shown to be an important mediator of binding of regulatory and target proteins, forms a compact structure containing a short helix lying adjacent to the beta4-alpha3 loop. The insert forms one edge of a "switch surface" and, unexpectedly, does not change conformation upon activation of the protein by the exchange of GTP analogs for GDP. These studies indicate the insert region forms a stable invariant "footrest" for docking of regulatory and effector proteins.

  17. 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

  18. 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)

  19. 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.

  20. 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

  1. A Genome-wide CRISPR Screen Identifies CDC25A as a Determinant of Sensitivity to ATR Inhibitors.

    Science.gov (United States)

    Ruiz, Sergio; Mayor-Ruiz, Cristina; Lafarga, Vanesa; Murga, Matilde; Vega-Sendino, Maria; Ortega, Sagrario; Fernandez-Capetillo, Oscar

    2016-04-21

    One recurring theme in drug development is to exploit synthetic lethal properties as means to preferentially damage the DNA of cancer cells. We and others have previously developed inhibitors of the ATR kinase, shown to be particularly genotoxic for cells expressing certain oncogenes. In contrast, the mechanisms of resistance to ATR inhibitors remain unexplored. We report here on a genome-wide CRISPR-Cas9 screen that identified CDC25A as a major determinant of sensitivity to ATR inhibition. CDC25A-deficient cells resist high doses of ATR inhibitors, which we show is due to their failure to prematurely enter mitosis in response to the drugs. Forcing mitotic entry with WEE1 inhibitors restores the toxicity of ATR inhibitors in CDC25A-deficient cells. With ATR inhibitors now entering the clinic, our work provides a better understanding of the mechanisms by which these compounds kill cells and reveals genetic interactions that could be used for their rational use. PMID:27067599

  2. The Cdc42 guanine nucleotide exchange factor FGD6 coordinates cell polarity and endosomal membrane recycling in osteoclasts.

    Science.gov (United States)

    Steenblock, Charlotte; Heckel, Tobias; Czupalla, Cornelia; Espírito Santo, Ana Isabel; Niehage, Christian; Sztacho, Martin; Hoflack, Bernard

    2014-06-27

    The initial step of bone digestion is the adhesion of osteoclasts onto bone surfaces and the assembly of podosomal belts that segregate the bone-facing ruffled membrane from other membrane domains. During bone digestion, membrane components of the ruffled border also need to be recycled after macropinocytosis of digested bone materials. How osteoclast polarity and membrane recycling are coordinated remains unknown. Here, we show that the Cdc42-guanine nucleotide exchange factor FGD6 coordinates these events through its Src-dependent interaction with different actin-based protein networks. At the plasma membrane, FGD6 couples cell adhesion and actin dynamics by regulating podosome formation through the assembly of complexes comprising the Cdc42-interactor IQGAP1, the Rho GTPase-activating protein ARHGAP10, and the integrin interactors Talin-1/2 or Filamin A. On endosomes and transcytotic vesicles, FGD6 regulates retromer-dependent membrane recycling through its interaction with the actin nucleation-promoting factor WASH. These results provide a mechanism by which a single Cdc42-exchange factor controlling different actin-based processes coordinates cell adhesion, cell polarity, and membrane recycling during bone degradation. PMID:24821726

  3. The Cdc42 Guanine Nucleotide Exchange Factor FGD6 Coordinates Cell Polarity and Endosomal Membrane Recycling in Osteoclasts*

    Science.gov (United States)

    Steenblock, Charlotte; Heckel, Tobias; Czupalla, Cornelia; Espírito Santo, Ana Isabel; Niehage, Christian; Sztacho, Martin; Hoflack, Bernard

    2014-01-01

    The initial step of bone digestion is the adhesion of osteoclasts onto bone surfaces and the assembly of podosomal belts that segregate the bone-facing ruffled membrane from other membrane domains. During bone digestion, membrane components of the ruffled border also need to be recycled after macropinocytosis of digested bone materials. How osteoclast polarity and membrane recycling are coordinated remains unknown. Here, we show that the Cdc42-guanine nucleotide exchange factor FGD6 coordinates these events through its Src-dependent interaction with different actin-based protein networks. At the plasma membrane, FGD6 couples cell adhesion and actin dynamics by regulating podosome formation through the assembly of complexes comprising the Cdc42-interactor IQGAP1, the Rho GTPase-activating protein ARHGAP10, and the integrin interactors Talin-1/2 or Filamin A. On endosomes and transcytotic vesicles, FGD6 regulates retromer-dependent membrane recycling through its interaction with the actin nucleation-promoting factor WASH. These results provide a mechanism by which a single Cdc42-exchange factor controlling different actin-based processes coordinates cell adhesion, cell polarity, and membrane recycling during bone degradation. PMID:24821726

  4. 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.

  5. Activation of Cdc42 is necessary for sustained oscillations of Ca2+ and PIP2 stimulated by antigen in RBL mast cells

    Directory of Open Access Journals (Sweden)

    Marcus M. Wilkes

    2014-07-01

    Full Text Available Antigen stimulation of mast cells via FcεRI, the high-affinity receptor for IgE, triggers a signaling cascade that requires Ca2+ mobilization for exocytosis of secretory granules during the allergic response. To characterize the role of Rho GTPases in FcεRI signaling, we utilized a mutant RBL cell line, B6A4C1, that is deficient in antigen-stimulated Cdc42 activation important for these processes. Recently the importance of stimulated intracellular oscillations has emerged, and we find that B6A4C1 cells exhibit severely attenuated Ca2+ oscillations in response to antigen, which are restored to wild-type RBL-2H3 levels by expression of constitutively active Cdc42 G12V or by a GEF for Cdc42, DOCK7, but not when the C-terminal di-arginine motif of active Cdc42 is mutated to di-glutamine. We found that antigen-stimulated FcεRI endocytosis, which occurs independently of Ca2+ mobilization, is also defective in B6A4C1 cells, and Cdc42 G12V reconstitutes this response as well. Thus, activation of Cdc42 occurs prior to and is critical for antigen-stimulated pathways leading separately to both Ca2+ mobilization and receptor endocytosis. Accounting for these downstream functional consequences, we show that Cdc42 G12V reconstitutes antigen-stimulated oscillations of phosphatidylinositol 4,5-bisphosphate (PIP2 at the plasma membrane in mutant B6A4C1 cells, pointing to Cdc42 participation in the regulation of stimulated PIP2 synthesis.

  6. 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...

  7. 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.

  8. Identification of a DYRK1A Inhibitor that Induces Degradation of the Target Kinase using Co-chaperone CDC37 fused with Luciferase nanoKAZ.

    Science.gov (United States)

    Sonamoto, Rie; Kii, Isao; Koike, Yuka; Sumida, Yuto; Kato-Sumida, Tomoe; Okuno, Yukiko; Hosoya, Takamitsu; Hagiwara, Masatoshi

    2015-01-01

    The protein kinase family includes attractive targets for drug development. Methods for screening of kinase inhibitors remain largely limited to in vitro catalytic assays. It has been shown that ATP-competitive inhibitors antagonize interaction between the target kinase and kinase-specific co-chaperone CDC37 in living cells. Here we show a cell-based method to screen kinase inhibitors using fusion protein of CDC37 with a mutated catalytic 19-kDa component of Oplophorus luciferase, nanoKAZ (CDC37-nanoKAZ). A dual-specificity kinase DYRK1A, an importance of which has been highlighted in Alzheimer's disease, was targeted in this study. We established 293T cells stably expressing CDC37-nanoKAZ, and analyzed interaction between CDC37-nanoKAZ and DYRK1A. We revealed that DYRK1A interacted with CDC37-nanoKAZ. Importantly, point mutations that affect autophosphorylation strengthened the interaction, thus improving signal/noise ratio of the interaction relative to non-specific binding of CDC37-nanoKAZ. This high signal/noise ratio enabled screening of chemical library that resulted in identification of a potent inhibitor of DYRK1A, named CaNDY. CaNDY induced selective degradation of DYRK1A, and inhibited catalytic activity of recombinant DYRK1A with IC50 value of 7.9 nM by competing with ATP. This method based on a mutant target kinase and a bioluminescence-eliciting co-chaperone CDC37 could be applicable to evaluation and development of inhibitors targeting other kinases. PMID:26234946

  9. 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...

  10. 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

  11. 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

  12. Stability of the human Hsp90-p50Cdc37 chaperone complex against nucleotides and Hsp90 inhibitors, and the influence of phosphorylation by casein kinase 2.

    Science.gov (United States)

    Olesen, Sanne H; Ingles, Donna J; Zhu, Jin-Yi; Martin, Mathew P; Betzi, Stephane; Georg, Gunda I; Tash, Joseph S; Schönbrunn, Ernst

    2015-01-19

    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.

  13. 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.

  14. 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.

  15. Stability of the Human Hsp90-p50Cdc37 Chaperone Complex against Nucleotides and Hsp90 Inhibitors, and the Influence of Phosphorylation by Casein Kinase 2

    Science.gov (United States)

    Olesen, Sanne H.; Ingles, Donna J.; Zhu, Jin-Yi; Martin, Mathew P.; Betzi, Stephane; Georg, Gunda I.; Tash, Joseph S.; Schönbrunn, Ernst

    2015-01-01

    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. PMID:25608045

  16. 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

  17. 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 ...

  18. CDC's Health Equity Resource Toolkit: disseminating guidance for state practitioners to address obesity disparities.

    Science.gov (United States)

    Payne, Gayle Holmes; James, Stephen D; Hawley, Lisa; Corrigan, Bethany; Kramer, Rachel E; Overton, Samantha N; Farris, Rosanne P; Wasilewski, Yvonne

    2015-01-01

    Obesity has been on the rise in the United States over the past three decades, and is high. In addition to population-wide trends, it is clear that obesity affects some groups more than others and can be associated with age, income, education, gender, race and ethnicity, and geographic region. To reverse the obesity epidemic, the Centers for Disease Control and Prevention) promotes evidence-based and practice-informed strategies to address nutrition and physical activity environments and behaviors. These public health strategies require translation into actionable approaches that can be implemented by state and local entities to address disparities. The Centers for Disease Control and Prevention used findings from an expert panel meeting to guide the development and dissemination of the Health Equity Resource Toolkit for State Practitioners Addressing Obesity Disparities (available at http://www.cdc.gov/obesity/health_equity/toolkit.html). The Toolkit helps public health practitioners take a systematic approach to program planning using a health equity lens. The Toolkit provides a six-step process for planning, implementing, and evaluating strategies to address obesity disparities. Each section contains (a) a basic description of the steps of the process and suggested evidence-informed actions to help address obesity disparities, (b) practical tools for carrying out activities to help reduce obesity disparities, and (c) a "real-world" case study of a successful state-level effort to address obesity with a focus on health equity that is particularly relevant to the content in that section. Hyperlinks to additional resources are included throughout.

  19. Structure and Function of the PLAA/Ufd3-p97/Cdc48 Complex

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Liyan; Pashkova, Natasha; Walker, John R.; Winistorfer, Stanley; Allali-Hassani, Abdellah; Akutsu, Masato; Piper, Robert; Dhe-Paganon, Sirano (Iowa); (Toronto)

    2010-02-11

    PLAA (ortholog of yeast Doa1/Ufd3, also know as human PLAP or phospholipase A2-activating protein) has been implicated in a variety of disparate biological processes that involve the ubiquitin system. It is linked to the maintenance of ubiquitin levels, but the mechanism by which it accomplishes this is unclear. The C-terminal PUL (PLAP, Ufd3p, and Lub1p) domain of PLAA binds p97, an AAA ATPase, which among other functions helps transfer ubiquitinated proteins to the proteasome for degradation. In yeast, loss of Doa1 is suppressed by altering p97/Cdc48 function indicating that physical interaction between PLAA and p97 is functionally important. Although the overall regions of interaction between these proteins are known, the structural basis has been unavailable. We solved the high resolution crystal structure of the p97-PLAA complex showing that the PUL domain forms a 6-mer Armadillo-containing domain. Its N-terminal extension folds back onto the inner curvature forming a deep ridge that is positively charged with residues that are phylogenetically conserved. The C terminus of p97 binds in this ridge, where the side chain of p97-Tyr805, implicated in phosphorylation-dependent regulation, is buried. Expressed in doa1{Delta} null cells, point mutants of the yeast ortholog Doa1 that disrupt this interaction display slightly reduced ubiquitin levels, but unlike doa1{Delta} null cells, showed only some of the growth phenotypes. These data suggest that the p97-PLAA interaction is important for a subset of PLAA-dependent biological processes and provides a framework to better understand the role of these complex molecules in the ubiquitin system.

  20. 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

  1. 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...

  2. Using the public health model to address unintentional injuries and TBI: A perspective from the Centers for Disease Control and Prevention (CDC).

    Science.gov (United States)

    Baldwin, Grant; Breiding, Matt; Sleet, David

    2016-06-30

    Traumatic brain injury (TBI) can have long term effects on mental and physical health, and can disrupt vocational, educational, and social functioning. TBIs can range from mild to severe and their effects can last many years after the initial injury. CDC seeks to reduce the burden of TBI from unintentional injuries through a focus on primary prevention, improved recognition and management, and intervening to improve health outcomes after TBI. CDC uses a 4-stage public health model to guide TBI prevention, moving from 1) surveillance of TBI, 2) identification of risk and protective factors for TBI, 3) development and testing of evidence-based interventions, to 4) bringing effective intervention to scale through widespread adoption. CDC's unintentional injury prevention activities focus on the prevention of sports-related concussions, motor vehicle crashes, and older adult falls. For concussion prevention, CDC developed Heads Up - an awareness initiative focusing on ways to prevent a concussion in sports, and identifying how to recognize and manage potential concussions. In motor vehicle injury prevention, CDC has developed a tool (MV PICCS) to calculate the expected number of injuries prevented and lives saved using various evidence-based motor vehicle crash prevention strategies. To help prevent TBI related to older adult falls, CDC has developed STEADI, an initiative to help primary care providers identify their patients' falls risk and provide effective interventions. In the future, CDC is focused on advancing our understanding of the public health burden of TBI through improved surveillance in order to produce more comprehensive estimates of the public health burden of TBI. PMID:27497467

  3. The budding yeast Cdc48(Shp1 complex promotes cell cycle progression by positive regulation of protein phosphatase 1 (Glc7.

    Directory of Open Access Journals (Sweden)

    Stefanie Böhm

    Full Text Available The conserved, ubiquitin-selective AAA ATPase Cdc48 regulates numerous cellular processes including protein quality control, DNA repair and the cell cycle. Cdc48 function is tightly controlled by a multitude of cofactors mediating substrate specificity and processing. The UBX domain protein Shp1 is a bona fide substrate-recruiting cofactor of Cdc48 in the budding yeast S. cerevisiae. Even though Shp1 has been proposed to be a positive regulator of Glc7, the catalytic subunit of protein phosphatase 1 in S. cerevisiae, its cellular functions in complex with Cdc48 remain largely unknown. Here we show that deletion of the SHP1 gene results in severe growth defects and a cell cycle delay at the metaphase to anaphase transition caused by reduced Glc7 activity. Using an engineered Cdc48 binding-deficient variant of Shp1, we establish the Cdc48(Shp1 complex as a critical regulator of mitotic Glc7 activity. We demonstrate that shp1 mutants possess a perturbed balance of Glc7 phosphatase and Ipl1 (Aurora B kinase activities and show that hyper-phosphorylation of the kinetochore protein Dam1, a key mitotic substrate of Glc7 and Ipl1, is a critical defect in shp1. We also show for the first time a physical interaction between Glc7 and Shp1 in vivo. Whereas loss of Shp1 does not significantly affect Glc7 protein levels or localization, it causes reduced binding of the activator protein Glc8 to Glc7. Our data suggest that the Cdc48(Shp1 complex controls Glc7 activity by regulating its interaction with Glc8 and possibly further regulatory subunits.

  4. Inhibitory effect of artesunate on human esophageal carcinoma is associated with CDC25A modulation%青蒿琥酯抗人食管癌作用与调控CDC25A表达的关系

    Institute of Scientific and Technical Information of China (English)

    王静; 刘亮; 李金梅; 刘江惠; 郭建文; 左连富

    2007-01-01

    目的 观察青蒿琥酯(artesunate, Art)对人食管癌Eca109细胞株及裸鼠移植瘤的抑瘤作用,探讨Art诱导肿瘤细胞周期阻滞是否与CDC25A表达有关.方法 MTT法测定Art对Eca109细胞及正常人外周血单个核细胞(hPBMC)增殖的影响;流式细胞术(FCM)测定肿瘤细胞的周期变化;观察Art对裸鼠人食管癌移植瘤的抑制情况; 采用RT-PCR及Western blotting方法检测CDC25A mRNA和蛋白表达情况.结果 Art能显著抑制Eca109细胞的增殖, IC50为 (68.80±0.76)μmol/L,而在刀豆蛋白A(concanavalin A, Con A)刺激下hPBMC的增殖则没有明显抑制作用.低浓度Art可将细胞阻滞于G0/G1期,S期细胞显著减少,当浓度达到100 μmol/L时,Art可将细胞阻滞于G2/M期.Art对裸鼠肿瘤的体积抑瘤率最高可达76.4%,质量抑瘤率可达33.2%.Art可显著抑制Eca109细胞CDC25A mRNA及蛋白表达.结论 Art可抑制食管癌细胞及裸鼠移植瘤的生长,且无明显毒副作用,通过下调CDC25A的表达而调控细胞周期,是Art发挥抑瘤作用的重要机制.

  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. 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

  7. 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.

  8. 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.

  9. 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

  10. Two Distinct Cdc2 Pools Regulate Cell Cycle Progression and the DNA Damage Response in the Fission Yeast S.pombe.

    Directory of Open Access Journals (Sweden)

    Thomas Caspari

    Full Text Available The activity of Cdc2 (CDK1 kinase, which coordinates cell cycle progression and DNA break repair, is blocked upon its phosphorylation at tyrosine 15 (Y15 by Wee1 kinase in the presence of DNA damage. How Cdc2 can support DNA repair whilst being inactivated by the DNA damage checkpoint remains to be explained. Human CDK1 is phosphorylated by Myt1 kinase at threonine 14 (T14 close to its ATP binding site before being modified at threonine 161 (T167Sp in its T-loop by the CDK-activating kinase (CAK. While modification of T161 promotes association with the cyclin partner, phosphorylation of T14 inhibits the CDK1-cyclin complex. This inhibition is further enforced by the modification of Y15 by Wee1 in the presence of DNA lesions. In S.pombe, the dominant inhibition of Cdc2 is provided by the phosphorylation of Y15 and only a small amount of Cdc2 is modified at T14 when cells are in S phase. Unlike human cells, both inhibitory modifications are executed by Wee1. Using the novel IEFPT technology, which combines isoelectric focusing (IEF with Phos-tag SDS electrophoresis (PT, we report here that S.pombe Cdc2 kinase exists in seven forms. While five forms are phosphorylated, two species are not. Four phospho-forms associate with cyclin B (Cdc13 of which only two are modified at Y15 by Wee1. Interestingly, only one Y15-modified species carries also the T14 modification. The fifth phospho-form has a low affinity for cyclin B and is neither Y15 nor T14 modified. The two unphosphorylated forms may contribute directly to the DNA damage response as only they associate with the DNA damage checkpoint kinase Chk1. Interestingly, cyclin B is also present in the unphosphorylated pool. We also show that the G146D mutation in Cdc2.1w, which renders Cdc2 insensitive to Wee1 inhibition, is aberrantly modified in a Wee1-dependent manner. In conclusion, our work adds support to the idea that two distinct Cdc2 pools regulate cell cycle progression and the response to DNA

  11. Two Distinct Cdc2 Pools Regulate Cell Cycle Progression and the DNA Damage Response in the Fission Yeast S.pombe.

    Science.gov (United States)

    Caspari, Thomas; Hilditch, Victoria

    2015-01-01

    The activity of Cdc2 (CDK1) kinase, which coordinates cell cycle progression and DNA break repair, is blocked upon its phosphorylation at tyrosine 15 (Y15) by Wee1 kinase in the presence of DNA damage. How Cdc2 can support DNA repair whilst being inactivated by the DNA damage checkpoint remains to be explained. Human CDK1 is phosphorylated by Myt1 kinase at threonine 14 (T14) close to its ATP binding site before being modified at threonine 161 (T167Sp) in its T-loop by the CDK-activating kinase (CAK). While modification of T161 promotes association with the cyclin partner, phosphorylation of T14 inhibits the CDK1-cyclin complex. This inhibition is further enforced by the modification of Y15 by Wee1 in the presence of DNA lesions. In S.pombe, the dominant inhibition of Cdc2 is provided by the phosphorylation of Y15 and only a small amount of Cdc2 is modified at T14 when cells are in S phase. Unlike human cells, both inhibitory modifications are executed by Wee1. Using the novel IEFPT technology, which combines isoelectric focusing (IEF) with Phos-tag SDS electrophoresis (PT), we report here that S.pombe Cdc2 kinase exists in seven forms. While five forms are phosphorylated, two species are not. Four phospho-forms associate with cyclin B (Cdc13) of which only two are modified at Y15 by Wee1. Interestingly, only one Y15-modified species carries also the T14 modification. The fifth phospho-form has a low affinity for cyclin B and is neither Y15 nor T14 modified. The two unphosphorylated forms may contribute directly to the DNA damage response as only they associate with the DNA damage checkpoint kinase Chk1. Interestingly, cyclin B is also present in the unphosphorylated pool. We also show that the G146D mutation in Cdc2.1w, which renders Cdc2 insensitive to Wee1 inhibition, is aberrantly modified in a Wee1-dependent manner. In conclusion, our work adds support to the idea that two distinct Cdc2 pools regulate cell cycle progression and the response to DNA damage. PMID

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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......, 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...

  19. 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

  20. 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...

  1. 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

  2. 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...

  3. 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, ...

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. Inlfuence of FSH Treatment on Expression of CDC25A, TSSK3 and P53in Vitro Cultured Sertoli Cells of Calf

    Institute of Scientific and Technical Information of China (English)

    Li Yu-long; Wu Qiong; Zhao Xun-wu; Zeng Yue; Elkanah Adegoke; Zhang Gui-xue

    2015-01-01

    CDC25A, TSSK3 and P53 expressionsin vitro in cultured sertoli cells after FSH treatment were studied in order to provide some data for further researches of spermatogenesis. Different concentrations of FSH (0, 0.01, 0.02, 0.04, and 0.08 IU• mL-1) were used to treat sertoli cells culturedin vitro. The expression of CDC25A, TSSK3 and P53 was determined by real-time-PCR at 6 h, 12 h and 24 h after FSH treatment of sertoli cells. The results showed that FSH had no significant effect on expression of CDC25A (p>0.05), could significantly improve the expression of TSSK3 and P53 (p<0.05), and had no significant effect on expression of CDC25A in sertoli cells, but it could significantly improve the expression of TSSK3. CDC25A was likely to play a role in other signaling pathways in sertoli cells. Within the range of certain concentration of FSH, TSSK3 in sertoli cells had the highest expression at about 24 h. TSSK3 protein produced in sertoli cells was likely to play an important role in substrate-level phosphorylationbe in meiosis and mitosis of spermatogenic cells. FSH could promote P53 expression and the highest expression was at about 12 h, and P53 might control the division of spermatogenic cells as well as sertoli cells.

  9. Cloud Computing

    OpenAIRE

    Bhavana Gupta

    2012-01-01

    Cloud computing is such a type of computing environment, where business owners outsource their computing needs including application software services to a third party and when they need to use the computing power or employees need to use the application resources like database, emails etc., they access the resources via Internet. Cloud computing the use of computing resources (hardware and software) that are delivered as a service over a (typically the Internet).

  10. Computer Music

    Science.gov (United States)

    Cook, Perry R.

    This chapter covers algorithms, technologies, computer languages, and systems for computer music. Computer music involves the application of computers and other digital/electronic technologies to music composition, performance, theory, history, and the study of perception. The field combines digital signal processing, computational algorithms, computer languages, hardware and software systems, acoustics, psychoacoustics (low-level perception of sounds from the raw acoustic signal), and music cognition (higher-level perception of musical style, form, emotion, etc.).

  11. Computer Music

    Science.gov (United States)

    Cook, Perry

    This chapter covers algorithms, technologies, computer languages, and systems for computer music. Computer music involves the application of computers and other digital/electronic technologies to music composition, performance, theory, history, and perception. The field combines digital signal processing, computational algorithms, computer languages, hardware and software systems, acoustics, psychoacoustics (low-level perception of sounds from the raw acoustic signal), and music cognition (higher-level perception of musical style, form, emotion, etc.). Although most people would think that analog synthesizers and electronic music substantially predate the use of computers in music, many experiments and complete computer music systems were being constructed and used as early as the 1950s.

  12. 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

  13. Rif1 controls DNA replication by directing Protein Phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex.

    Science.gov (United States)

    Hiraga, Shin-Ichiro; Alvino, Gina M; Chang, Fujung; Lian, Hui-Yong; Sridhar, Akila; Kubota, Takashi; Brewer, Bonita J; Weinreich, Michael; Raghuraman, M K; Donaldson, Anne D

    2014-02-15

    Initiation of eukaryotic DNA replication requires phosphorylation of the MCM complex by Dbf4-dependent kinase (DDK), composed of Cdc7 kinase and its activator, Dbf4. We report here that budding yeast Rif1 (Rap1-interacting factor 1) controls DNA replication genome-wide and describe how Rif1 opposes DDK function by directing Protein Phosphatase 1 (PP1)-mediated dephosphorylation of the MCM complex. Deleting RIF1 partially compensates for the limited DDK activity in a cdc7-1 mutant strain by allowing increased, premature phosphorylation of Mcm4. PP1 interaction motifs within the Rif1 N-terminal domain are critical for its repressive effect on replication. We confirm that Rif1 interacts with PP1 and that PP1 prevents premature Mcm4 phosphorylation. Remarkably, our results suggest that replication repression by Rif1 is itself also DDK-regulated through phosphorylation near the PP1-interacting motifs. Based on our findings, we propose that Rif1 is a novel PP1 substrate targeting subunit that counteracts DDK-mediated phosphorylation during replication. Fission yeast and mammalian Rif1 proteins have also been implicated in regulating DNA replication. Since PP1 interaction sites are evolutionarily conserved within the Rif1 sequence, it is likely that replication control by Rif1 through PP1 is a conserved mechanism.

  14. Rif1 controls DNA replication by directing Protein Phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex

    Science.gov (United States)

    Hiraga, Shin-ichiro; Alvino, Gina M.; Chang, FuJung; Lian, Hui-yong; Sridhar, Akila; Kubota, Takashi; Brewer, Bonita J.; Weinreich, Michael; Raghuraman, M.K.; Donaldson, Anne D.

    2014-01-01

    Initiation of eukaryotic DNA replication requires phosphorylation of the MCM complex by Dbf4-dependent kinase (DDK), composed of Cdc7 kinase and its activator, Dbf4. We report here that budding yeast Rif1 (Rap1-interacting factor 1) controls DNA replication genome-wide and describe how Rif1 opposes DDK function by directing Protein Phosphatase 1 (PP1)-mediated dephosphorylation of the MCM complex. Deleting RIF1 partially compensates for the limited DDK activity in a cdc7-1 mutant strain by allowing increased, premature phosphorylation of Mcm4. PP1 interaction motifs within the Rif1 N-terminal domain are critical for its repressive effect on replication. We confirm that Rif1 interacts with PP1 and that PP1 prevents premature Mcm4 phosphorylation. Remarkably, our results suggest that replication repression by Rif1 is itself also DDK-regulated through phosphorylation near the PP1-interacting motifs. Based on our findings, we propose that Rif1 is a novel PP1 substrate targeting subunit that counteracts DDK-mediated phosphorylation during replication. Fission yeast and mammalian Rif1 proteins have also been implicated in regulating DNA replication. Since PP1 interaction sites are evolutionarily conserved within the Rif1 sequence, it is likely that replication control by Rif1 through PP1 is a conserved mechanism. PMID:24532715

  15. Cloud Computing

    OpenAIRE

    Bhavana Gupta

    2012-01-01

    Cloud computing is such a type of computing environment, where business owners outsource their computing needs including application software services to a third party and when they need to use the computing power or employees need to use the application resources like database, emails etc., they access the resources via Internet

  16. Computer Virus

    Institute of Scientific and Technical Information of China (English)

    高振桥

    2002-01-01

    If you work with a computer,it is certain that you can not avoid dealing, with at least one computer virus.But how much do you know about it? Well,actually,a computer virus is not a biological' one as causes illnesses to people.It is a kind of computer program

  17. Grid Computing

    Indian Academy of Sciences (India)

    2016-05-01

    A computing grid interconnects resources such as high performancecomputers, scientific databases, and computercontrolledscientific instruments of cooperating organizationseach of which is autonomous. It precedes and is quitedifferent from cloud computing, which provides computingresources by vendors to customers on demand. In this article,we describe the grid computing model and enumerate themajor differences between grid and cloud computing.

  18. 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.

  19. Involvement of the Cdc42 pathway in CFTR post-translational turnover and in its plasma membrane stability in airway epithelial cells.

    Science.gov (United States)

    Ferru-Clément, Romain; Fresquet, Fleur; Norez, Caroline; Métayé, Thierry; Becq, Frédéric; Kitzis, Alain; Thoreau, Vincent

    2015-01-01

    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.

  20. 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