Group B Strep Infection in Newborns

MedlinePlus

... Active Bacterial Core surveillance (ABCs) CDC Streptococcus Laboratory Sepsis Group B Strep Disease in Newborns Language: English ( ... Active Bacterial Core surveillance (ABCs) CDC Streptococcus Laboratory Sepsis Language: English (US) Español (Spanish) File Formats Help: ...

A computer program for the generation of logic networks from task chart data

NASA Technical Reports Server (NTRS)

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.

International Futures (IFs): A Global Issues Simulation for Teaching and Research.

ERIC Educational Resources Information Center

Hughes, Barry B.

This paper describes the International Futures (IFs) computer assisted simulation game for use with undergraduates. Written in Standard Fortran IV, the model currently runs on mainframe or mini computers, but has not been adapted for micros. It has been successfully installed on Harris, Burroughs, Telefunken, CDC, Univac, IBM, and Prime machines.…

Computer program for post-flight evaluation of a launch vehicle upper-stage on-off reaction control system

NASA Technical Reports Server (NTRS)

Knauber, R. N.

1982-01-01

This report describes a FORTRAN IV coded computer program for post-flight evaluation of a launch vehicle upper stage on-off reaction control system. Aerodynamic and thrust misalignment disturbances are computed as well as the total disturbing moments in pitch, yaw, and roll. Effective thrust misalignment angle time histories of the rocket booster motor are calculated. Disturbing moments are integrated and used to estimate the required control system total inpulse. Effective control system specific inpulse is computed for the boost and coast phases using measured control fuel useage. This method has been used for more than fifteen years for analyzing the NASA Scout launch vehicle second and third-stage reaction control system performance. The computer program is set up in FORTRAN IV for a CDC CYBER 175 system. With slight modification it can be used on other machines having a FORTRAN compiler. The program has optional CALCOMP plotting output. With this option the program requires 19K words of memory and has 786 cards. Running time on a CDC CYBER 175 system is less than three (3) seconds for a typical problem.

Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion

PubMed Central

Horsthemke, Markus; Bachg, Anne C.; Groll, Katharina; Moyzio, Sven; Müther, Barbara; Hemkemeyer, Sandra A.; Wedlich-Söldner, Roland; Sixt, Michael; Tacke, Sebastian; Bähler, Martin; Hanley, Peter J.

2017-01-01

Macrophage filopodia, finger-like membrane protrusions, were first implicated in phagocytosis more than 100 years ago, but little is still known about the involvement of these actin-dependent structures in particle clearance. Using spinning disk confocal microscopy to image filopodial dynamics in mouse resident Lifeact-EGFP macrophages, we show that filopodia, or filopodia-like structures, support pathogen clearance by multiple means. Filopodia supported the phagocytic uptake of bacterial (Escherichia coli) particles by (i) capturing along the filopodial shaft and surfing toward the cell body, the most common mode of capture; (ii) capturing via the tip followed by retraction; (iii) combinations of surfing and retraction; or (iv) sweeping actions. In addition, filopodia supported the uptake of zymosan (Saccharomyces cerevisiae) particles by (i) providing fixation, (ii) capturing at the tip and filopodia-guided actin anterograde flow with phagocytic cup formation, and (iii) the rapid growth of new protrusions. To explore the role of filopodia-inducing Cdc42, we generated myeloid-restricted Cdc42 knock-out mice. Cdc42-deficient macrophages exhibited rapid phagocytic cup kinetics, but reduced particle clearance, which could be explained by the marked rounded-up morphology of these cells. Macrophages lacking Myo10, thought to act downstream of Cdc42, had normal morphology, motility, and phagocytic cup formation, but displayed markedly reduced filopodia formation. In conclusion, live-cell imaging revealed multiple mechanisms involving macrophage filopodia in particle capture and engulfment. Cdc42 is not critical for filopodia or phagocytic cup formation, but plays a key role in driving macrophage lamellipodial spreading. PMID:28289096

Does familiarity with CDC guidelines, continuing education, and provider characteristics influence adherence to chronic pain management practices and opioid prescribing?

PubMed

McCalmont, Jean C; Jones, Kim D; Bennett, Robert M; Friend, Ronald

(1) To assess providers' experience and knowledge of chronic noncancer pain (CNCP) management. (2) To assess providers' utilization of the Centers for Disease Control and Prevention (CDC) 2016 Guideline for Prescribing Opioids for Chronic Pain. (3) To assess the influence of the 2016 CDC guideline on provider confidence in managing CNCP and adherence to the CDC recommendations. A cross-sectional, web-based survey conducted with 417 Oregon prescribing providers, divided into three continuing medical education (CME) groups composed of minimal (0-3), moderate (4-10), and high (≥11) hours of training. The three CME groups were associated with increased use of CDC opioid recommended practices (29.4, 34.2, 38.8; p = 0.001; scale 0-50), opioid conversion confidence (5.5, 6.5, 7.4; p < 0.001; scale 0-9), and confidence in pain management (5.5, 5.9, 6.9; p < 0.001, scale 0-9). Slightly more providers utilized CDC recommended practices than did not (57 vs 43 percent). However, CME groups differed substantially in utilization of CDC practices (42 vs 57 vs 72 percent; p < 0.001). Neither providers' profession (physician vs nurse practitioner [NP]) nor geographic setting (urban vs rural) showed differences in use of recommended practices or general confident in pain management (all p > 0.05); however, physicians were slightly more confident in opioid dose conversion than NPs (6.9 vs 5.9; p < 0. 001, scale 0-9). Higher hours of recent CME positively benefit provider confidence in pain management and utilization of CDC recommended practices. NPs and rural providers were equivalent to their physician and urban counterparts on confidence and adherence to CDC practices, with minor exceptions.

78 FR 27391 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-10

... Materials for the Division of Blood Disorders (0920-0915, Expired 01/31/2013)--Reinstatement--National... messages and materials, CDC will conduct formative focus groups with people with SCD across the country... the formative focus groups, CDC will develop and test draft messages. A total of 10 focus groups will...

User Delay Cost Model and Facilities Maintenance Cost Model for a Terminal Control Area : Volume 3. User's Manual and Program Documentation for the Facilities Maintenance Cost Model

DOT National Transportation Integrated Search

1978-05-01

The Facilities Maintenance Cost Model (FMCM) is an analytic model designed to calculate expected annual labor costs of maintenance within a given FAA maintenance sector. The model is programmed in FORTRAN IV and has been demonstrated on the CDC Krono...

SU-F-T-675: Down-Regulating the Expression of Cdc42 and Inhibition of Migration of A549 with Combined Treatment of Ionizing Radiation and Sevoflurane

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feng, Y; Feng, J; Huang, Z

Purpose: Cdc42 is involved in cell transformation, proliferation, invasion and metastasis of human cancer cells. Cdc42 overexpression has been reported in several types of cancers. This study investigated the combined treatment effects of ionizing radiation and sevoflurane on down-regulating Cdc42 expression and suppressing migration of human adenocarcinoma cell line A549. Methods: Samples of A549 cells with Cdc42 overexpression were created and Cdc42 expression was determined by Western blotting. Increase of migration speed by Cdc42-HA overexpression was confirmed with an initial in-vitro scratch assay. The cells grown in culture media were separated into 2 groups of 6 samples: one for themore » control and the other was treated with 4% sevoflurane for 5hrs prior to a single-fraction radiation of 4Gy using a 6MV beam. Cell migration speeds of the 2 groups were measured with an initial in-vitro scratch assay. The scratch was created with a pipette tip immediately after treatment and images at 4 post-treatment time points (0h, 3h, 6h, 12h) were acquired. The distance between the two separated sides at 0h was used as reference and subsequent changes of the distance over time was defined as the cell migration speed. Image processing and measurement were performed with an in-house software. The experiment was repeated three times independently to evaluate the repeatability and reliability. Statistical analysis was performed with SPSS 19.0. Results: Western blotting showed the treatment down-regulated Cdc42 overexpression. Quantitative analysis and two-tailed t-test showed that cell migration speed of the treated group was higher than the control group at all time points after treatment (p < 0.02). Conclusion: Combined treatment of 6MV photon and sevoflurane can cause the effects of down-regulating Cdc42 overexpression and decrease of migration speed of A549 cells which provides potential of clinical benefit for the cancer therapy. More investigation is needed to further quantify the benefits of the combined therapy.« less

Blastomyces dermatitidis septins CDC3, CDC10, and CDC12 impact the morphology of yeast and hyphae, but are not required for the phase transition.

PubMed

Marty, Amber J; Gauthier, Gregory M

2013-01-01

Blastomyces dermatitidis, the etiologic agent of blastomycosis, belongs to a group of thermally dimorphic fungi that change between mold (22°C) and yeast (37°C) in response to temperature. The contribution of structural proteins such as septins to this phase transition in these fungi remains poorly understood. Septins are GTPases that serve as a scaffold for proteins involved with cytokinesis, cell polarity, and cell morphology. In this study, we use a GFP sentinel RNA interference system to investigate the impact of CDC3, CDC10, CDC12, and ASPE on the morphology and phase transition of B. dermatitidis. Targeting CDC3, CDC10, and CDC12 by RNA interference resulted in yeast with aberrant morphology at 37°C with defects in cytokinesis. Downshifting the temperature to 22°C promoted the conversion to the mold phase, but did not abrogate the morphologic defects. CDC3, CDC10, and CDC12 knockdown strains grew as mold with curved, thickened hyphae. Knocking down ASPE transcript did not alter morphology of yeast at 37°C or mold at 22°C. Following an increase in temperature from 22°C to 37°C, all septin knockdown strains were able to revert to yeast. In conclusion, CDC3, CDC10, and CDC12 septin- encoding genes are required for proper morphology of yeast and hyphae, but are dispensable for the phase transition.

Clostridium difficile colonization and infection in patients with hepatic cirrhosis.

PubMed

Yan, Dong; Chen, Yunbo; Lv, Tao; Huang, Yandi; Yang, Jiezuan; Li, Yongtao; Huang, Jianrong; Li, Lanjuan

2017-10-01

The aim of this study was to investigate the toxigenic Clostridium difficile colonization (CDC, colonization with toxigenic C. difficile but without symptoms) and C. difficile infection (CDI, active C. difficile infection resulting in disease symptoms) in hepatic cirrhosis patients, identify the risk factors of CDC, and determine the correlation between CDC and CDI. The strains of toxigenic C. difficile were isolated from patients with hepatic cirrhosis within 48 h after admission, followed by multilocus sequence typing (MLST). Patients were divided into toxigenic CDC group and noncolonized (NC) group according to the colonization. Logistic regression analysis was performed to analyse the risk factors for the CDC. Besides, the CDI incidence was compared between the two groups. Colonization of toxigenic C. difficile was identified in 104 cases (19.8 %). Eighteen sequence types (STs) were identified, among which ST-3, ST-54, ST-35 and ST-37 were the predominant types. Child-Pugh class C(relative risk, RR, 3.025; 95 % CI: 1.410-6.488), decrease of prothrombin time activity (PTA) (RR 2.180; 95 % CI: 1.368-3.476), decrease of platelet (RR 2.746; 95 % CI: 0.931-8.103) and concurrent hepatic encephalopathy (RR 1.740; 95 % CI: 1.012-2.990) were identified as the risk factors for the hepatic cirrhosis patients with CDC. The CDI incidence in the CDC group was also significantly higher than that of the NC group (26.0 % vs 1.7 %, P<0.001). An carriage rate of 19.8 % was reported in the hepatic cirrhosis patients with C. difficile colonization. Child's class C, decrease of PTA and platelet, and concurrent hepatic encephalopathy were the risk factors for the hepatic cirrhosis patients with C. difficile colonization. Hepatic cirrhosis patients with C. difficile colonization were more susceptible to CDI.

Synapse Formation in Monosynaptic Sensory–Motor Connections Is Regulated by Presynaptic Rho GTPase Cdc42

PubMed Central

Imai, Fumiyasu; Ladle, David R.; Leslie, Jennifer R.; Duan, Xin; Rizvi, Tilat A.; Ciraolo, Georgianne M.; Zheng, Yi

2016-01-01

Spinal reflex circuit development requires the precise regulation of axon trajectories, synaptic specificity, and synapse formation. Of these three crucial steps, the molecular mechanisms underlying synapse formation between group Ia proprioceptive sensory neurons and motor neurons is the least understood. Here, we show that the Rho GTPase Cdc42 controls synapse formation in monosynaptic sensory–motor connections in presynaptic, but not postsynaptic, neurons. In mice lacking Cdc42 in presynaptic sensory neurons, proprioceptive sensory axons appropriately reach the ventral spinal cord, but significantly fewer synapses are formed with motor neurons compared with wild-type mice. Concordantly, electrophysiological analyses show diminished EPSP amplitudes in monosynaptic sensory–motor circuits in these mutants. Temporally targeted deletion of Cdc42 in sensory neurons after sensory–motor circuit establishment reveals that Cdc42 does not affect synaptic transmission. Furthermore, addition of the synaptic organizers, neuroligins, induces presynaptic differentiation of wild-type, but not Cdc42-deficient, proprioceptive sensory neurons in vitro. Together, our findings demonstrate that Cdc42 in presynaptic neurons is required for synapse formation in monosynaptic sensory–motor circuits. SIGNIFICANCE STATEMENT Group Ia proprioceptive sensory neurons form direct synapses with motor neurons, but the molecular mechanisms underlying synapse formation in these monosynaptic sensory–motor connections are unknown. We show that deleting Cdc42 in sensory neurons does not affect proprioceptive sensory axon targeting because axons reach the ventral spinal cord appropriately, but these neurons form significantly fewer presynaptic terminals on motor neurons. Electrophysiological analysis further shows that EPSPs are decreased in these mice. Finally, we demonstrate that Cdc42 is involved in neuroligin-dependent presynaptic differentiation of proprioceptive sensory neurons in vitro. These data suggest that Cdc42 in presynaptic sensory neurons is essential for proper synapse formation in the development of monosynaptic sensory–motor circuits. PMID:27225763

User's manual for a computer program for simulating intensively managed allowable cut.

Treesearch

Robert W. Sassaman; Ed Holt; Karl Bergsvik

1972-01-01

Detailed operating instructions are described for SIMAC, a computerized forest simulation model which calculates the allowable cut assuming volume regulation for forests with intensively managed stands. A sample problem illustrates the required inputs and expected output. SIMAC is written in FORTRAN IV and runs on a CDC 6400 computer with a SCOPE 3.3 operating system....

33 CFR 160.206 - Information required in an NOA.

Code of Federal Regulations, 2010 CFR

2010-07-01

... CDC (1) Vessel Information: (i) Name; X X X (ii) Name of the registered owner; X X X (iii) Country of registry; X X X (iv) Call sign; X X X (v) International Maritime Organization (IMO) international number or... (vi) Name of the operator; X X X (vii) Name of the charterer; and X X X (viii) Name of classification...

78 FR 3429 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-16

... Disease Educational Messages and Materials for the Division of Blood Disorders (0920-0915, Expiration 01... sickle cell disease. To develop valuable messages and materials, CDC will conduct formative focus groups... remote, rural areas. Based on the findings from the formative focus groups, CDC will develop and test...

A Brief Description of the Purposes and Concepts of the Coursewriter II Preprocessor. System Memo Number Four.

ERIC Educational Resources Information Center

Mitchell, Ron; Conner Michael

A brief description of the Coursewriter II preprocessor is provided. This preprocessor, a program written in FORTRAN IV on the CDC 6600 computer, is designed to reduce the repetition of effort that takes place from the time of the author's conception of a course to the time of its availability for on-line student instruction. The programer deals…

Log-normal spray drop distribution...analyzed by two new computer programs

Treesearch

Gerald S. Walton

1968-01-01

Results of U.S. Forest Service research on chemical insecticides suggest that large drops are not as effective as small drops in carrying insecticides to target insects. Two new computer programs have been written to analyze size distribution properties of drops from spray nozzles. Coded in Fortran IV, the programs have been tested on both the CDC 6400 and the IBM 7094...

Who is at Risk for Down Syndrome?

MedlinePlus

... of the Scientific Director (OSD) Affinity Groups & Labs (AG&L) Scientists Emeriti National Center for Medical Rehabilitation ... at https://www.cdc.gov/ncbddd/birthdefects/downsyndrome/data.html . CDC. (2012). World Down syndrome day . Retrieved ...

Estimates of CDC-Funded and National HIV Diagnoses: A Comparison by Demographic and HIV-related Factors.

PubMed

Krueger, Amy; Dietz, Patricia; Van Handel, Michelle; Belcher, Lisa; Johnson, Anna Satcher

2016-12-01

To determine whether CDC-funded HIV testing programs are reaching persons disproportionately affected by HIV infection. The percentage distribution for HIV testing and diagnoses by demographics and transmission risk group (diagnoses only) were calculated using 2013 data from CDC's National HIV Surveillance System and CDC's national HIV testing program data. In 2013, nearly 3.2 million CDC-funded tests were provided to persons aged 13 years and older. Among persons who received a CDC-funded test, 41.1 % were aged 20-29 years; 49.2 % were male, 46.2 % were black/African American, and 56.2 % of the tests were conducted in the South. Compared with the characteristics of all persons diagnosed with HIV in the United States in 2013, among persons diagnosed as a result of CDC-funded tests, a higher percentage were aged 20-29 years (40.3 vs 33.7 %) and black/African American (55.3 vs 46.0 %). CDC-funded HIV testing programs are reaching young people and blacks/African Americans.

DNA–DNA hybridization study of strains of Chryseobacterium, Elizabethkingia and Empedobacter and of other usually indole-producing non-fermenters of CDC groups IIc, IIe, IIh and IIi, mostly from human clinical sources, and proposals of Chryseobacterium bernardetii sp. nov., Chryseobacterium carnis sp. nov., Chryseobacterium lactis sp. nov., Chryseobacterium nakagawai sp. nov. and Chryseobacterium taklimakanense comb. nov

PubMed Central

Holmes, B.; Steigerwalt, A. G.; Nicholson, A. C.

2015-01-01

The taxonomic classification of 182 phenotypically similar isolates was evaluated using DNA–DNA hybridization and 16S rRNA gene sequence analysis. These bacterial isolates were mainly derived from clinical sources; all were Gram-negative non-fermenters and most were indoleproducing. Phenotypically, they resembled species from the genera Chryseobacterium, Elizabethkingia or Empedobacter or belonged to CDC groups IIc, IIe, IIh and IIi. Based on these analyses, four novel species are described: Chryseobacterium bernardetii sp. nov. (type strain NCTC 13530T=CCUG 60564T=CDC G229T), Chryseobacterium carnis sp. nov. (type strain NCTC 13525T=CCUG 60559T=CDC G81T), Chryseobacterium lactis sp. nov. (type strain NCTC 11390T=CCUG 60566T=CDC KC1864T) and Chryseobacterium nakagawai sp. nov. (type strain NCTC 13529T=CCUG 60563T=CDC G41T). The new combination Chryseobacterium taklimakanense comb. nov. (type strain NCTC 13490T=X-65T=CCTCC AB 208154T=NRRL B-51322T) is also proposed to accommodate the reclassified Planobacterium taklimakanense. PMID:23934253

A computer program for the calculation of thermal stratification and self-pressurization in a liquid hydrogen tank

NASA Technical Reports Server (NTRS)

Arnett, R. W.; Voth, R. O.

1972-01-01

An analysis and computer program are described for calculating the thermal stratification and the associated self-pressurization of a closed liquid hydrogen tank. FORTRAN-IV language is used and runs were made on IBM 360/65 and CDC 3600 computers. Comparisons are made between the program calculations and test results from both ground and orbital coast tests of a Centaur space vehicle.

Impact on CDC Guideline Compliance After Incorporating Pharmacy in a Pneumococcal Vaccination Screening Process.

PubMed

Pickren, Elizabeth; Crane, Brad

2016-12-01

Background: Centers for Disease Control and Prevention (CDC) guidelines for pneumococcal vaccinations were updated in 2014. Given the complexity of the guidelines and the fact that hospitals are no longer required to keep records for pneumococcal vaccinations, many hospitals are determining whether to continue this service. Objective: The primary objective of this study was to determine the impact on compliance with the revised pneumococcal vaccination guidelines from the CDC after involving pharmacy in the screening and selection processes. Secondary objectives were to determine the impact of the new process on inappropriate vaccination duplications, the time spent by pharmacy on assessments, and financial outcomes. Methods: This institutional review board (IRB)-approved, retrospective, cohort study examined all patients who received a pneumococcal vaccination from January to February 2016 after implementing a new process whereby pharmacy performed pneumococcal vaccination screening and selection (intervention group). These patients were compared to patients who received a pneumococcal vaccination from January to February 2015 (control group). Results: Of 274 patients who received a pneumococcal vaccine, 273 were included in the study. Compliance to CDC guidelines increased from 42% to 97%. Noncompliant duplications decreased from 16% to 2%. In the intervention group, labor cost for assessments and expenditure for vaccines increased. For Medicare patients, the increased reimbursement balanced the increased expenditure in the intervention group. Conclusions: Involving pharmacy in the pneumococcal vaccine screening and selection process improves compliance to CDC guidelines, but further clinical and financial analysis is needed to determine financial sustainability of the new process.

Notes from the Field: Fungal Bloodstream Infections Associated with a Compounded Intravenous Medication at an Outpatient Oncology Clinic - New York City, 2016.

PubMed

Vasquez, Amber M; Lake, Jason; Ngai, Stephanie; Halbrook, Megan; Vallabhaneni, Snigdha; Keckler, M Shannon; Moulton-Meissner, Heather; Lockhart, Shawn R; Lee, Christopher T; Perkins, Kiran; Perz, Joseph F; Antwi, Mike; Moore, Miranda S; Greenko, Jane; Adams, Eleanor; Haas, Janet; Elkind, Sandra; Berman, Marjorie; Zavasky, Dani; Chiller, Tom; Ackelsberg, Joel

2016-11-18

On May 24, 2016, the New York City Department of Health and Mental Hygiene notified CDC of two cases of Exophiala dermatitidis bloodstream infections among patients with malignancies who had received care from a single physician at an outpatient oncology facility (clinic A). Review of January 1-May 31, 2016 microbiology records identified E. dermatitidis bloodstream infections in two additional patients who also had received care at clinic A. All four patients had implanted vascular access ports and had received intravenous (IV) medications, including a compounded IV flush solution containing saline, heparin, vancomycin, and ceftazidime, compounded and administered at clinic A.

Men who have sex with men and women (MSMW), biphobia and the CDC: A bridge ignored?!

PubMed

Fernando, Daniel

2017-12-01

This is a letter to the editor on a Short Communication by a group of CDC researchers. It speaks of the importance of bisexual behavior in the transmission of HIV to heterosexual females. In this letter, I demonstrate that the differences between MSM only and MSMW have been discussed by CDC researchers and CDC collaborative researchers previously, although the CDC continues to maintain its original risk category classification, which undermines the role of bisexuals in HIV transmission to heterosexual females. In the CDC risk category classification where men who have sex with men and women (MSMW) are subsumed under the MSM category, it is impossible to know the extent of HIV transmission from MSMW to heterosexual women. Since more Blacks and Hispanics admit to bisexual behavior, the original CDC risk category classification has had a more serious adverse impact on minority communities. I argue that the CDC should change its risk category classification to include MSM only and MSMW as well as women who have sex with men only (WSM) and women who have sex with men and women (WSMW), even at this late stage. Copyright © 2017 Elsevier Inc. All rights reserved.

DNA-DNA hybridization study of strains of Chryseobacterium, Elizabethkingia and Empedobacter and of other usually indole-producing non-fermenters of CDC groups IIc, IIe, IIh and IIi, mostly from human clinical sources, and proposals of Chryseobacterium bernardetii sp. nov., Chryseobacterium carnis sp. nov., Chryseobacterium lactis sp. nov., Chryseobacterium nakagawai sp. nov. and Chryseobacterium taklimakanense comb. nov.

PubMed

Holmes, B; Steigerwalt, A G; Nicholson, A C

2013-12-01

The taxonomic classification of 182 phenotypically similar isolates was evaluated using DNA-DNA hybridization and 16S rRNA gene sequence analysis. These bacterial isolates were mainly derived from clinical sources; all were Gram-negative non-fermenters and most were indole-producing. Phenotypically, they resembled species from the genera Chryseobacterium, Elizabethkingia or Empedobacter or belonged to CDC groups IIc, IIe, IIh and IIi. Based on these analyses, four novel species are described: Chryseobacterium bernardetii sp. nov. (type strain NCTC 13530(T) = CCUG 60564(T) = CDC G229(T)), Chryseobacterium carnis sp. nov. (type strain NCTC 13525(T) = CCUG 60559(T) = CDC G81(T)), Chryseobacterium lactis sp. nov. (type strain NCTC 11390(T) = CCUG 60566(T) = CDC KC1864(T)) and Chryseobacterium nakagawai sp. nov. (type strain NCTC 13529(T) = CCUG 60563(T) = CDC G41(T)). The new combination Chryseobacterium taklimakanense comb. nov. (type strain NCTC 13490(T) = X-65(T) = CCTCC AB 208154(T) = NRRL B-51322(T)) is also proposed to accommodate the reclassified Planobacterium taklimakanense.

Evaluation of the applicability of amplified rDNA-restriction analysis (ARDRA) to identification of species of the genus Corynebacterium.

PubMed

Vaneechoutte, M; Riegel, P; de Briel, D; Monteil, H; Verschraegen, G; De Rouck, A; Claeys, G

1995-10-01

The 16S rRNA genes (rDNA) of 50 strains belonging to 26 different coryneform bacterial species and genomospecies and of the type strain of Rhodococcus equi were enzymatically amplified. Amplified rDNA restriction analysis (ARDRA) with the enzymes AluI, CfoI and RsaI was carried out. The combination of the ARDRA patterns obtained after restriction with these three different enzymes enabled the differentiation between the following species: Corynebacterium accolens (number of strains = 2), C. afermentans subsp. afermentans (2), C. afermentans subsp. lipophilum (2), C. amycolatum (3), CDC coryneform group ANF-1-like (1), CDC coryneform group ANF-3-like (1), C. cystitidis (1), C. diphtheriae (4), C. jeikeium (3), C. macginleyi (2), C. minutissimum (1), C. pilosum (1), C. pseudotuberculosis (2), C. renale (2), C. striatum (2), C. urealyticum (3), C. xerosis (1), CDC coryneform groups B-1 (2), B-3 (2), F-1, genomospecies 1 and 2 (6), G, genomospecies 1 (1) and G, genomospecies 2 (2). The following strains or species could not be differentiated from each other: C. pseudodiphtheriticum (2) from C. propinquum (former CDC coryneform group ANF-3) (2), CDC coryneform group F-1, genomospecies 1 (4) from genomospecies 2 (2) and C. jeikeium genomospecies A (1) from genomospecies C (2). ARDRA may represent a possible alternative for identification of coryneforms, since this technique enabled the identification of most coryneforms tested and since DNA extraction (i.e. cell lysis by boiling), amplification, restriction and electrophoresis can be carried out within 8 hours. This might allow quick identification of C. diphtheriae and other possible pathogens of the genus Corynebacterium.

A risk/cost analysis of alternative screening intervals for occupational tuberculosis infection.

PubMed

Nicas, M

1998-02-01

The Centers for Disease Control and Prevention (CDC) recommends that new health care employees receive a baseline skin test for Mycobacterium tuberculosis (M. tb) infection and that testing be repeated periodically. However, CDC does not explain the quantitative basis for its suggested screening intervals. This article examines the efficacy of alternative screening intervals for workers subject to different annual rates of M. tb infection and estimates the costs. An equation is developed for the cumulative risk of tuberculosis (TB) at 12 years given a specified annual rate of infection (ARI), screening interval, and a combined proportion (p) of successful skin testing and antibiotic prophylaxis. Equations for total cost of screening and cost per disease case prevented are provided. Results assume: (a) costs of $10 per skin test and $10,000 per TB disease case; (b) p = 0.88; and (c) and acceptable cumulative TB risk of 1 per 1000. For ARIs that might be deemed low (0.2% to 0.5%) and medium (1%), CDC screening intervals of 12 months and 6-12 months, respectively, minimize the cost per disease case prevented but permit residual disease risks greater than 1 per 1000. Recommended screening intervals are (i) 6 months for low-risk employee groups and (ii) 3 months for medium- and high-risk (e.g., ARIs of > or = 5%) groups. Interval (i) limits risk to 1 per 1000 and is approximately 50% shorter than the CDC interval for a low-risk group. Interval (ii), which is 67% shorter than the CDC interval for medium-risk groups but equal to that recommended for high-risk groups, permits a risk above 1 per 1000, but is likely the shortest feasible interval.

EMERGING INFECTIOUS DISEASES. Actions Needed to Address the Challenges of Responding to Zika Virus Disease Outbreaks

DTIC Science & Technology

2017-05-01

Department of Health and Human Services 81 Appendix IV Zika Virus Case Definitions for National Notifiable Disease Reporting 86 Appendix V...Insecticide, Fungicide, and Rodenticide Act HHS Department of Health and Human Services IgG immunoglobulin G IgM immunoglobulin M IMM...Agency (EPA), and Department of Health and Human Services (HHS) including CDC, FDA and National Institutes of Health (NIH). We also convened, with

Computer Center CDC Libraries/NSRDC (Subprograms).

DTIC Science & Technology

1981-02-01

TRANSFORM." COMM, OF THE ACM, VOL, 10, NO. 10, OCTOBER 1967. 3. SYSTEM/360 SCIENTIFIC SUBROUTINE PACKAGE, IBM TECHNICAL PUBLICATONS DEPARTMENT, 1967...VARIABLE 3) UP TO 9 DEPENDENT VARIABLES PER PLOT. FUNCTIONAL CATEGORIES: J5 LANGUAGE: FORTRAN IV USAGE COMMON /PLO/ NRUN, NPLOT, ITP .6), ITY(6), ITX(61...PLO/ NRUN - NUMBER OF THIS RUN iDEFAULT: 1) NPLOT - NUMBER OF PLOT (DEFAULT: 1 ITP - PAGE TITLE (DEFAULT: BLANK) ITY - Y TITLE (DEFAULT: BLANK) ITX - X

A practical approach to implementing new CDC GBS guidelines.

PubMed

Hill, Shawna M; Bridges, Margie A; Knudsen, Alexis L; Vezeau, Toni M

2013-01-01

Group beta streptococcus (GBS) is a well-documented pathogen causing serious maternal and fetal morbidity and mortality. The CDC guidelines for managing clients who test positive for GBS in pregnancy were revised and published in 2010. However, CDC and extant literature provide limited guidance on implementation strategies for these new recommendations. Although several algorithms are included in the CDC (2010) document, none combine the maternal risk factors for practical and consistent implementation from pregnancy to newborn. In response to confusion upon initial education of these guidelines, we developed an algorithm for maternal intrapartum management. In addition, we clarified the CDC (2010) newborn algorithm in response to provider request. Without altering the recommendations, both algorithms provide clarification of the CDC (2010) guidelines. The nursing process provides an organizational structure for the discussion of our efforts to translate the complex guidelines into practice. This article could provide other facilities with tools for dealing with specific aspects of the complex clinical management of perinatal GBS.

Cable delay compensator for microwave signal distribution over optical fibers

NASA Astrophysics Data System (ADS)

Primas, Lori E.

1990-12-01

The basic principles of microwave fiber-optic systems are outlined with emphasis on fiber-optic cable delay compensators (CDC). Degradation of frequency and phase stability is considered, and it is pointed out that the long-term stability of a fiber-optic link is degraded by group delay variations due to temperature fluctuations in the optical fiber and low-frequency noise characteristics of the laser. A CDC employing a voltage-controlled oscillator to correct for phase variations in the optical fiber is presented, and the static as well as dynamic closed-loop analyses of the fiber-optic CDC are discussed. A constructed narrow-band fiber-optic CDC is shown to reduce phase variations caused by temperature fluctuations by a factor of 400. A wide-band CDC utilizing a temperature-controlled coil of fiber to compensate for phase delay is also proposed.

2-Aminomethylthieno[3,2-d]pyrimidin-4(3H)-ones bearing 3-methylpyrazole hinge binding moiety: Highly potent, selective, and time-dependent inhibitors of Cdc7 kinase.

PubMed

Kurasawa, Osamu; Homma, Misaki; Oguro, Yuya; Miyazaki, Tohru; Mori, Kouji; Uchiyama, Noriko; Iwai, Kenichi; Ohashi, Akihiro; Hara, Hideto; Yoshida, Sei; Cho, Nobuo

2017-07-15

In order to increase the success rate for developing new Cdc7 inhibitors for cancer therapy, we explored a new chemotype which can comply with the previously-constructed pharmacophore model. Substitution of a pyridine ring of a serendipitously-identified Cdc7 inhibitor 2b with a 3-methylpyrazole resulted in a 4-fold increase in potency and acceptable kinase selectivity, leading to the identification of thieno[3,2-d]pyrimidin-4(3H)-one as an alternative scaffold. Structure-activity relationship (SAR) study revealed that incorporation of a substituted aminomethyl group into the 2-position improved kinase selectivity. Indeed, a pyrrolidinylmethyl derivative 10c was a potent Cdc7 inhibitor (IC 50 =0.70nM) with high selectivity (Cdk2/Cdc7≥14,000, ROCK1/Cdc7=200). It should be noted that 10c exhibited significant time-dependent Cdc7 inhibition with slow dissociation kinetics, cellular pharmacodynamic (PD) effects, and COLO205 growth inhibition. Additionally, molecular basis of high kinase selectivity of 10c is discussed by using the protein structures of Cdc7 and Cdk2. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cultural adaptation and the Clavien-Dindo surgical complications classification translated to Brazilian Portuguese.

PubMed

Moreira, Luis Fernando; Pessôa, Marcelo Castro Marçal; Mattana, Diego Sachet; Schmitz, Fernando Fernandes; Volkweis, Bernardo Silveira; Antoniazzi, Jorge Luiz; Ribeiro, Liacyr

2016-01-01

to generate a translated and validated version of the Clavien-Dindo Classification of Surgical Complications (CDC) to Brazilian Portuguese (CDC-BR). the process of translation and adaptation followed the guideline of Beaton et al., 2000. We divided 76 participating surgeons, in different levels of experience, from the Department Surgery of the Hospital de Clínicas de Porto Alegre, into two groups: Group I applied the original version (CDC, n=36);r Group II used the modified version (CDC-BR, n=40). Each group classified 15 clinical cases of surgical complications. We compared performance between the groups (Mann-Whitney test) relating to the level of experience of the surgeon (Kruskal-Wallis test), considering p value <0.05 as significant. the performance of the Group II (CDC-BR) was higher, with 85% accuracy, compared with 79% of Group I (CDC), p-value =0.012. The performance of the groups as for surgeons experience displayed p=0.171 for Group I, p=0.528 for Group II, and p=0.135 for overall performance. we produced a translated and validated version of the CDC for Brazilian Portuguese. The instrument will be a useful tool in the production of evidence on surgical outcomes. gerar uma versão traduzida e validada da Classificação de Complicações Cirúrgicas de Clavien-Dindo (CCD) para o Português-Brasileiro (CCD-BR). o processo de tradução e adaptação seguiu a diretriz de Beaton et al., de 2000. Formaram-se dois grupos, Grupo I, que utilizou a versão original (CCD, n=36) testado em relação ao Grupo II, com a versão modificada (CCD-BR, n=40), com um total de 76 cirurgiões participantes em níveis de experiência distintos do Departamento de Cirurgia do Hospital de Clínicas de Porto Alegre. Quinze casos clínicos de complicações cirúrgicas foram classificados em cada grupo. Comparou-se o desempenho entre grupos (teste de Mann-Whitney) relacionando ao nível de experiência dos cirurgiões (teste de Kruskal-Wallis). Valor de p<0,05 como significativo. o desempenho do Grupo II (CCD-BR) foi superior, com 85% de acertos, contra 79% do Grupo I (CCD), p-valor=0,012 do teste de Mann-Whitney. O desempenho dos grupos em relação à experiência dos cirurgiões foi p-valor=0,171 para o Grupo I, p-valor=0,528 para o Grupo II, e p-valor=0,135 para o desempenho geral, teste de Kruskal-Wallis. foi produzida uma versão traduzida e validada da CCD para o Português-Brasileiro. O instrumento produzido será ferramenta útil na produção de evidências sobre os resultados cirúrgicos.

Analysis of septins across kingdoms reveals orthology and new motifs.

PubMed

Pan, Fangfang; Malmberg, Russell L; Momany, Michelle

2007-07-01

Septins are cytoskeletal GTPase proteins first discovered in the fungus Saccharomyces cerevisiae where they organize the septum and link nuclear division with cell division. More recently septins have been found in animals where they are important in processes ranging from actin and microtubule organization to embryonic patterning and where defects in septins have been implicated in human disease. Previous studies suggested that many animal septins fell into independent evolutionary groups, confounding cross-kingdom comparison. In the current work, we identified 162 septins from fungi, microsporidia and animals and analyzed their phylogenetic relationships. There was support for five groups of septins with orthology between kingdoms. Group 1 (which includes S. cerevisiae Cdc10p and human Sept9) and Group 2 (which includes S. cerevisiae Cdc3p and human Sept7) contain sequences from fungi and animals. Group 3 (which includes S. cerevisiae Cdc11p) and Group 4 (which includes S. cerevisiae Cdc12p) contain sequences from fungi and microsporidia. Group 5 (which includes Aspergillus nidulans AspE) contains sequences from filamentous fungi. We suggest a modified nomenclature based on these phylogenetic relationships. Comparative sequence alignments revealed septin derivatives of already known G1, G3 and G4 GTPase motifs, four new motifs from two to twelve amino acids long and six conserved single amino acid positions. One of these new motifs is septin-specific and several are group specific. Our studies provide an evolutionary history for this important family of proteins and a framework and consistent nomenclature for comparison of septin orthologs across kingdoms.

Percentage of Children Aged 5--17 Years Ever Receiving a Diagnosis of Learning Disability, United States, 2007--2009

MedlinePlus

... Ethnicity † and Family Income Group § --- National Health Interview Survey, ¶ United States, 2007--2009 * Based on parental response ... cdc.gov/nchs/hdi.htm . National Health Interview Survey 2007--2009 data. Available at http://www.cdc. ...

Histomorphometry and expression of Cdc47 and caspase-3 in hyperthyroid rat uteri and placentas during gestation and postpartum associated with fetal development.

PubMed

Freitas, E S; Leite, E D; Souza, C A; Ocarino, N M; Ferreira, E; Cassali, G D; Gomes, M G; Serakides, R

2007-01-01

In two different experiments, the effects of hyperthyroidism on the histomorphometry and expression of Cdc47 and caspase-3 were evaluated in the uteri and placentas during gestation and postpartum. Fetal development was also evaluated during gestation. In the first experiment, 36 adult female Wistar rats were divided into two groups of 18 animals each: (1) hyperthyroid; and (2) euthyroid (control). Female rats were mated and killed at 7, 14 and 19 days of gestation. Uteri and placentas were weighed and subjected to histomorphometric and immunohistochemical evaluation to determine the expression of Cdc47 and caspase-3. Ovaries were also evaluated for weight and subjected to morphometric analysis. Fetuses were quantified and weighed individually. In the second experiment, 12 adult female Wistar rats were divided into two groups of six animals each: (1) hyperthyroid; and (2) euthyroid (control). Female rats were mated and killed 2 days postpartum. Uteri were evaluated in the same way as for the first experiment. Hyperthyroidism increased ovulation and conception rates without disturbing the size and viability of the fetuses. In the pregnant uteri, hyperthyroidism did not change the thickness of the layers or the expression of Cdc47 and caspase-3. However, in the placentas, hyperthyroidism increased the medium diameter of trophoblast cells, as well as the thickness and the expression of Cdc47 of spongiotrophoblast cells, at 14 days of gestation. During uterine involution, hyperthyroidism significantly increased the expression of Cdc47 and reduced the expression of caspase-3 in the uterine layers. In conclusion, hyperthyroidism increased the conception rate because of an ovulation gain, induced significant placental changes during pregnancy and, in the uterus, increased Cdc47 expression and decreased caspase-3 expression after parturition.

Genotypes of Candida albicans involved in development of candidiasis and their distribution in oral cavity of non-candidiasis individuals.

PubMed

Takagi, Yuki; Hattori, Hisao; Adachi, Hidesada; Takakura, Shunji; Horii, Toshinobu; Chindamporn, Ariya; Kitai, Hiroki; Tanaka, Reiko; Yaguchi, Takashi; Fukano, Hideo; Kawamoto, Fumihiko; Shimozato, Kazuo; Kanbe, Toshio

2011-01-01

Genotype characteristics and distribution of commensal Candida albicans should be studied to predict the development of candidiasis, however, extensive genotype analysis of commensal C. albicans has not been made. In this study, 508 C. albicans isolates were collected from patients with/without candidiasis and divided into 4 isolate groups (SG-1, oral cavity of non-candidiasis patients; SG-2, patients with cutaneous candidiasis; SG-3, patients with vaginal candidiasis; SG-4, patients with candidemia). These isolates were characterized to study the relationship between genotypes and pathogenicity using microsatellite analysis. Using CDC3 and CAI, 5 genotypes (I, 111: 115/33: 41; II, 115: 119/23: 23; III, 115: 123/18: 27; IV, 115: 123/33: 40; and V, 123: 127/32: 41) were found in 4.2%, 8.9%, 7.1%, 2.2% and 3.1% of the isolates, respectively. Genotypes II and III were commonly found in all isolate groups. These genotypes were further divided into 28 types by additional HIS3 and CAIII microsatellite markers. In this analysis, C. albicans with type 6 and type 23 was widely distributed as a commensal species in the oral cavity of non-candidiasis patients and found to be related with candidiasis development. Additionally, genotypes I and IV were found in SG-2 and/or SG-4, suggesting that the fungus with those genotypes is also involved in this development. In contrast, genotype V was not identified in any infective isolates.

CDC Kerala 14: Early child care practices at home among children (2-6 y) with autism--a case control study.

PubMed

George, Babu; Padmam, M S Razeena; Nair, M K C; Leena, M L; Russell, Paul Swamidhas Sudhakar

2014-12-01

To compare early child care practices at home as possible risk factors among children between 2 and 6 y of age with autism and a control group of normal children without any symptom of autism, presenting at the well-baby/immunization clinic. This case control study was undertaken at the autism clinic of CDC Kerala, comparing possible risk factors for autism among 143 children between 2 and 6 y with autism as per CARS criteria and a control group of 200 normal children of the same age from well-baby/immunization clinic of SAT hospital. The data was collected using a structured pre-piloted questionnaire, which included 11 questions administered by the same senior social scientist, on early child care practices at home that have been universally considered as important for child development. On multivariate analysis on early child care practices at home as possible risk factors for autism, it was observed that statistically significant high odds ratios were present for (i) no outings (OR = 3.36; 95% CI: 1.39-8.16; p 0.007); (ii) child does not play with children of same age (OR = 19.57; 95% CI: 9.50-40.32); (iii) do not tell stories/sing songs to the child (OR = 3.21; 9 % CI: 1.61-6.41); and (iv) breastfeeding duration nil/ < 6 mo (OR = 3.40; 95% CI: 1.28-8.99). This case control study involving 143 children between 2 and 6 y with autism as per CARS criteria and a control group of 200 normal children has shown that early child care practices at home, specifically breastfeeding duration nil/ < 6 mo, child does not play with children of same age, do not tell stories/sing songs to the child and no outings for the child are possible risk factors for autism.

Histomorphometry and expression of CDC-47 and caspase-3 in mammary glands of pregnant female rats with artificial hyperthyroidism.

PubMed

Leite, Eveline Dias; de Freitas, Edmilson Santos; de Almeida Souza, Cintia; de Melo Ocarino, Natalia; Cassali, Geovanni Dantas; Serakides, Rogéria

2008-01-01

The purpose of this study was to evaluate the effect of hyperthyroidism on mammary gland development and expression of two protein markers, CDC-47 for proliferation and caspase-3 for apoptosis in pregnant female rats. Thirty-six adult female Wistar rats were used in two groups: hyperthyroid and control. Rats were mated 60 days after the onset of thyroxine administration. Six animals/group were sacrificed on gestation days 7, 14, and 19. Artificial hyperthyroidism was induced by daily administration of thyroxine in the drinking water until the end of gestation. At the end of each period, rats were sacrificed, and their inguinal mammary glands were collected and processed for morphometric analysis. The percentages of epithelium, stroma, adipose tissue, and lacteal secretion were determined. Immunohistochemical analysis was also carried out using anti-CDC-47 and anti-caspase-3 antibodies to study proliferation and apoptosis, respectively. On the 19th day of gestation, thyroxine treatment significantly increased the percentage of mammary epithelium. Hyperthyroidism, however, did not change CDC-47 expression. The hyperthyroid group presented early lactogenesis and significantly larger lacteal secretion on the 19th day of gestation. There was no significant difference in caspase-3 expression between groups in any period. We may conclude that hyperthyroidism accelerates mammary gland development and increases lacteal secretion during gestation without increasing the proliferation rate and the expression of caspase-3.

What Can a Woman Do to Promote a Healthy Pregnancy Before She Gets Pregnant?

MedlinePlus

... report of the CDC/ATSDR Preconception Care Work Group and the Select Panel on Preconception Care. Retrieved May 18, 2012, from http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5506a1.htm Zhang, C., Liu, S., Solomon, C. G., & Hu, F. B. (2006). Dietary fiber ...

CDC 2004 Programs in Brief.

ERIC Educational Resources Information Center

US Department of Health and Human Services, 2004

2004-01-01

Grouped in 16 categories, the 2004 Programs in Brief illustrates the scope of Centers for Disease Control and Prevention (CDC) and the Agency for Toxic Substances and Disease Registry (ATSDR) activities, as well as their shared goals of safer, healthier people here and around the world. Each description includes a statement of the public health…

Defective homing is associated with altered Cdc42 activity in cells from patients with Fanconi anemia group A

PubMed Central

Zhang, Xiaoling; Shang, Xun; Guo, Fukun; Murphy, Kim; Kirby, Michelle; Kelly, Patrick; Reeves, Lilith; Smith, Franklin O.; Williams, David A.

2008-01-01

Previous studies showed that Fanconi anemia (FA) murine stem cells have defective reconstitution after bone marrow (BM) transplantation. The mechanism underlying this defect is not known. Here, we report defective homing of FA patient BM progenitors transplanted into mouse models. Using cells from patients carrying mutations in FA complementation group A (FA-A), we show that when transplanted into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) recipient mice, FA-A BM cells exhibited impaired homing activity. FA-A cells also showed defects in both cell-cell and cell-matrix adhesion. Complementation of FA-A deficiency by reexpression of FANCA readily restored adhesion of FA-A cells. A significant decrease in the activity of the Rho GTPase Cdc42 was found associated with these defective functions in patient-derived cells, and expression of a constitutively active Cdc42 mutant was able to rescue the adhesion defect of FA-A cells. These results provide the first evidence that FA proteins influence human BM progenitor homing and adhesion via the small GTPase Cdc42-regulated signaling pathway. PMID:18565850

Optimal allocation of HIV prevention funds for state health departments.

PubMed

Yaylali, Emine; Farnham, Paul G; Cohen, Stacy; Purcell, David W; Hauck, Heather; Sansom, Stephanie L

2018-01-01

To estimate the optimal allocation of Centers for Disease Control and Prevention (CDC) HIV prevention funds for health departments in 52 jurisdictions, incorporating Health Resources and Services Administration (HRSA) Ryan White HIV/AIDS Program funds, to improve outcomes along the HIV care continuum and prevent infections. Using surveillance data from 2010 to 2012 and budgetary data from 2012, we divided the 52 health departments into 5 groups varying by number of persons living with diagnosed HIV (PLWDH), median annual CDC HIV prevention budget, and median annual HRSA expenditures supporting linkage to care, retention in care, and adherence to antiretroviral therapy. Using an optimization and a Bernoulli process model, we solved for the optimal CDC prevention budget allocation for each health department group. The optimal allocation distributed the funds across prevention interventions and populations at risk for HIV to prevent the greatest number of new HIV cases annually. Both the HIV prevention interventions funded by the optimal allocation of CDC HIV prevention funds and the proportions of the budget allocated were similar across health department groups, particularly those representing the large majority of PLWDH. Consistently funded interventions included testing, partner services and linkage to care and interventions for men who have sex with men (MSM). Sensitivity analyses showed that the optimal allocation shifted when there were differences in transmission category proportions and progress along the HIV care continuum. The robustness of the results suggests that most health departments can use these analyses to guide the investment of CDC HIV prevention funds into strategies to prevent the most new cases of HIV.

Optimal allocation of HIV prevention funds for state health departments

PubMed Central

Farnham, Paul G.; Cohen, Stacy; Purcell, David W.; Hauck, Heather; Sansom, Stephanie L.

2018-01-01

Objective To estimate the optimal allocation of Centers for Disease Control and Prevention (CDC) HIV prevention funds for health departments in 52 jurisdictions, incorporating Health Resources and Services Administration (HRSA) Ryan White HIV/AIDS Program funds, to improve outcomes along the HIV care continuum and prevent infections. Methods Using surveillance data from 2010 to 2012 and budgetary data from 2012, we divided the 52 health departments into 5 groups varying by number of persons living with diagnosed HIV (PLWDH), median annual CDC HIV prevention budget, and median annual HRSA expenditures supporting linkage to care, retention in care, and adherence to antiretroviral therapy. Using an optimization and a Bernoulli process model, we solved for the optimal CDC prevention budget allocation for each health department group. The optimal allocation distributed the funds across prevention interventions and populations at risk for HIV to prevent the greatest number of new HIV cases annually. Results Both the HIV prevention interventions funded by the optimal allocation of CDC HIV prevention funds and the proportions of the budget allocated were similar across health department groups, particularly those representing the large majority of PLWDH. Consistently funded interventions included testing, partner services and linkage to care and interventions for men who have sex with men (MSM). Sensitivity analyses showed that the optimal allocation shifted when there were differences in transmission category proportions and progress along the HIV care continuum. Conclusion The robustness of the results suggests that most health departments can use these analyses to guide the investment of CDC HIV prevention funds into strategies to prevent the most new cases of HIV. PMID:29768489

Logistics Support Analysis Techniques Guide

DTIC Science & Technology

1985-03-15

LANGUAGE (DATA RECORDS) FORTRAN CDC 6600 D&V FSD P/D A H REMA-RKS: Program n-s-ists of F PLIATIffIONS, approx 4000 line of coding , 3 Safegard, AN/FSC... FORTRAN IV -EW-RAK9-- The model consz.sts of IT--k-LIC- I-U-0NS: approximately 367 lines of SiNCGARS, PERSHING II coding . %.’. ~ LSA TASK INTERFACE...system supported by Computer’ Systems Command. The current version of LADEN is coded totally in FORTRAN 󈧕 for virtual memory operating system

Optimization of thermal protection systems for the space vehicle. Volume 2: User's manual

NASA Technical Reports Server (NTRS)

1972-01-01

The development of the computational techniques for the design optimization of thermal protection systems for the space shuttle vehicle are discussed. The resulting computer program was then used to perform initial optimization and sensitivity studies on a typical thermal protection system (TPS) to demonstrate its application to the space shuttle TPS design. The program was developed in FORTRAN IV for CDC 6400 computer, but it was subsequently converted to the FORTRAN V language to be used on the Univac 1108.

Relationship of carbohydrates and lignin molecular structure spectral profiles to nutrient profile in newly developed oats cultivars and barley grain

NASA Astrophysics Data System (ADS)

Prates, Luciana Louzada; Refat, Basim; Lei, Yaogeng; Louzada-Prates, Mariana; Yu, Peiqiang

2018-01-01

The objectives of this study were to quantify the chemical profile and the magnitude of differences in the oat and barley grain varieties developed by Crop Development Centre (CDC) in terms of Cornell Net Carbohydrate Protein System (CNCPS) carbohydrate sub-fractions: CA4 (sugars), CB1 (starch), CB2 (soluble fibre), CB3 (available neutral detergent fibre - NDF), and CC (unavailable carbohydrate); to estimate the energy values; to detect the lignin and carbohydrate (CHO) molecular structure profiles in CDC Nasser and CDC Seabiscuit oat and CDC Meredith barley grains by using Fourier transform infrared attenuated total reflectance (FTIR-ATR); to develop a model to predict nutrient supply based on CHO molecular profile. Results showed that NDF, ADF and CHO were greater (P < 0.05) in oat than in barley. The starch content was greater (P < 0.05) in barley than in oat. The CDC Meredith showed greater total rumen degradable carbohydrate (RDC), intestinal digestible fraction carbohydrate (FC) and lower total rumen undegradable carbohydrate (RUC). However, the estimated milk production did not differ for CDC Nasser oat and CDC Meredith barley. Lignin peak area and peak height did not differ (P > 0.05) for oat and barley grains as well as non-structural CHO. However, cellulosic compounds peak area and height were greater (P < 0.05) in oat than barley grains. Multiple regressions were determined to predict nutrient supply by using lignin and CHO molecular profiles. It was concluded that although there were some differences between oat and barley grains, CDC Nasser and CDC Meredith presented similarities related to chemical and molecular profiles, indicating that CDC Meredith barley could be replaced for CDC Nasser as ruminant feed. The FTIR was able to identify functional groups related to CHO molecular spectral in oat and barley grains and FTIR-ATR results could be used to predict nutrient supply in ruminant livestock systems.

Role of mitochondrial DNA damage and dysfunction in veterans with Gulf War Illness.

PubMed

Chen, Yang; Meyer, Joel N; Hill, Helene Z; Lange, Gudrun; Condon, Michael R; Klein, Jacquelyn C; Ndirangu, Duncan; Falvo, Michael J

2017-01-01

Gulf War Illness (GWI) is a chronic multi-symptom illness not currently diagnosed by standard medical or laboratory test that affects 30% of veterans who served during the 1990-1991 Gulf War. The clinical presentation of GWI is comparable to that of patients with certain mitochondrial disorders-i.e., clinically heterogeneous multisystem symptoms. Therefore, we hypothesized that mitochondrial dysfunction may contribute to both the symptoms of GWI as well as its persistence over time. We recruited 21 cases of GWI (CDC and Kansas criteria) and 7 controls to participate in this study. Peripheral blood samples were obtained in all participants and a quantitative polymerase chain reaction (QPCR) based assay was performed to quantify mitochondrial and nuclear DNA lesion frequency and mitochondrial DNA (mtDNA) copy number (mtDNAcn) from peripheral blood mononuclear cells. Samples were also used to analyze nuclear DNA lesion frequency and enzyme activity for mitochondrial complexes I and IV. Both mtDNA lesion frequency (p = 0.015, d = 1.13) and mtDNAcn (p = 0.001; d = 1.69) were elevated in veterans with GWI relative to controls. Nuclear DNA lesion frequency was also elevated in veterans with GWI (p = 0.344; d = 1.41), but did not reach statistical significance. Complex I and IV activity (p > 0.05) were similar between groups and greater mtDNA lesion frequency was associated with reduced complex I (r2 = -0.35, p = 0.007) and IV (r2 = -0.28, p < 0.01) enzyme activity. In conclusion, veterans with GWI exhibit greater mtDNA damage which is consistent with mitochondrial dysfunction.

An experimental and theoretical study of the adsorption removal of toluene and chlorobenzene on coconut shell derived carbon.

PubMed

Zhao, Xiaoyan; Zeng, Xiaolan; Qin, Yu; Li, Xiang; Zhu, Tianle; Tang, Xiaolong

2018-04-26

The adsorption performance of toluene and chlorobenzene on prepared coconut shell derived carbon (CDC) is investigated and compared with commercial activated carbon (CAC) by experiment and theory calculation. Textural properties of prepared adsorbents are characterized by N 2 adsorption, infrared spectra (FT-IR), Raman spectra and X-ray photoelectron spectra (XPS). Adsorption isotherms of toluene and chlorobenzene are obtained and fitted using structure optimizations, Grand Canonical Monte Carlo (GCMC) simulation and thermodynamic models. The results indicate that CDC shows better volatile organic compounds (VOCs) removal performance than CAC, and chlorobenzene is easily adsorbed than toluene. On the aspect of textural characteristics, CDC possesses more micropores ratio and narrower pore size distribution than CAC. Furthermore, amounts of electron-withdrawing carbonyl groups on the CAC surface reduce the electron density of adsorbents, thus weakening the interaction between VOCs and adsorbents. On the aspect of model fitting, the Yoon and Nelson (Y-N) and Dubinin-Astakhov (D-A) models can well describe the dynamic adsorption and the adsorption equilibrium of toluene and chlorobenzene on CDC respectively. It is believed that substituent groups of adsorbates, making the charge distribution deviate, lead to adsorption potentials of chlorobenzene larger than toluene. In general, both the pore structure and the surface property of adsorbents affect the VOCs adsorption behaviors on CDC. Copyright © 2018. Published by Elsevier Ltd.

Comprehensive disease control (CDC): what does achieving CDC mean for patients with rheumatoid arthritis?

PubMed

Emery, Paul; Kavanaugh, Arthur; Bao, Yanjun; Ganguli, Arijit; Mulani, Parvez

2015-12-01

This study assessed the impact of simultaneous achievement of clinical, functional and structural efficacy, herein referred to as comprehensive disease control (CDC), on short-term and long-term work-related outcomes, health-related quality of life (HRQoL), pain and fatigue. Data were pooled from three randomised trials of adalimumab plus methotrexate for treatment of early-stage or late-stage rheumatoid arthritis (RA). CDC was defined as 28-joint Disease Activity Score using C reactive protein <2.6, Health Assessment Questionnaire <0.5 and change from baseline in modified Total Sharp Score ≤0.5. Changes in scores at weeks 26 and 52 for work-related outcomes, Short Form 36 (SF-36) physical (PCS) and mental component scores (MCS), a Visual Analogue Scale measuring pain (VAS-Pain) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were compared between patient groups defined by achievement of CDC at week 26 using linear regression with adjustment for baseline scores. Patients with RA who achieved CDC at week 26 (n=200) had significantly greater improvements in VAS-Pain (46.9 vs 26.9; p<0.0001), FACIT-F (13.3 vs 7.5; p<0.0001), SF-36 PCS (19.7 vs 8.9; p<0.0001) and SF-36 MCS (8.1 vs 5.0; p=0.0004) than those who did not (n=1267). Results were consistent at week 52 and among methotrexate-naive patients with early RA, methotrexate-experienced patients with late-stage RA and patients with inadequate response to methotrexate. Patients with RA who achieved CDC at week 26 had improved short-term and long-term HRQoL, pain, fatigue and work-related outcomes compared with patients who do not. These results demonstrate that the joint achievement of all CDC components provides meaningful benefits to patients. DE019: NCT00195702, PREMIER: NCT00195702, OPTIMA: NCT00195702. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Improving integration and coordination of funding, technical assistance, and reporting/data collection: recommendations from CDC and USAPI stakeholders.

PubMed

Ka'opua, Lana Sue I; White, Susan F; Rochester, Phyllis F; Holden, Debra J

2010-09-01

Current US Federal funding mechanisms may foster program silos that disable sharing of resources and information across programs within a larger system of public health services. Such silos present challenges to USAPI communities where human resources, health infrastructure, and health financing are limited. Integrative and coordinated approaches have been recommended. The CDC Pacific Islands Integration and Coordination project was initiated by the Division of Cancer Prevention and Control (DCPC). Its project aim was to identify ways for the CDC to collaborate with the USAPI in improving CDC activities and processes related to chronic disease. This article focuses on recommendations for improving coordination and integration in three core areas of health services programming: funding, program reporting/data collection and analysis, and technical assistance. Preliminary information on challenges and issues relevant to the core areas was gathered through site visits, focus groups, key informant interviews, and other sources. This information was used by stakeholder groups from the CDC and the USAPI to develop recommendations in the core programming areas. Recommendations generated at the CDC and USAPI stakeholder meetings were prepared into a single set of recommendations and stakeholders reviewed the document for accuracy prior to its dissemination to CDC's National Center for Chronic Disease Prevention and Health Promotion programs management and staff. Key recommendations, include: (1) consideration of resource s and other challenges unique to the USAPI when reviewing funding applications, (2) consideration of ways to increase flexibility in USAPI use of program funds, (3) dedicate funding and human resources for technical assistance, (4) provide opportunities for capacity-building across programs and jurisdictions, (5) consider ways to more directly link program reporting with technical assistance. This project provided a unique opportunity for CDC and USAPI stakeholders to share diverse perspectives on challenges to public health programs in the USAPI. Despite diverse experiences, the final set of recommendations reflected a high level of concordance between USAPI and CDC stakeholders on ways to improve coordination and integration of CDC processes and activities in the three core areas. Recommendations have informed some actions already initiated by the DCPC, including the dedication of funds for leadership institutes aimed at enhancing USAPI capacity for sustainable, integrated regional and jurisdictional cancer control infrastructure. Such efforts are an important beginning, but more remains to be done. Indicated is the need for continuous dialogue and collaboration. While this project focused on the USAPI, our results may be relevant to those interested in inter-organizational collaborations, medically underserved areas, public health services programs, and community-based participatory approaches.

Improving integration and coordination of funding, technical assistance, and reporting/data collection: recommendations from CDC and USAPI stakeholders.

PubMed

Ka'opua, Lana Sue I; White, Susan F; Rochester, Phyllis F; Holden, Debra J

2011-03-01

Current US Federal funding mechanisms may foster program silos that disable sharing of resources and information across programs within a larger system of public health services. Such silos present challenges to USAPI communities where human resources, health infrastructure, and health financing are limited. Integrative and coordinated approaches have been recommended. The CDC Pacific Islands Integration and Coordination project was initiated by the CDC Division of Cancer Prevention and Control (DCPC). The project aim was to identify ways for the CDC to collaborate with the USAPI in improving CDC activities and processes related to chronic disease. This article focuses on recommendations for improving coordination and integration in three core areas of health services programming: funding, program reporting/data collection and analysis, and technical assistance. Preliminary information on challenges and issues relevant to the core areas was gathered through site visits, focus groups, key informant interviews, and other sources. This information was used by stakeholder groups from the CDC and the USAPI to develop recommendations in the core programming areas. Recommendations generated at the CDC and USAPI stakeholder meetings were prepared into a single set of recommendations and stakeholders reviewed the document for accuracy prior to its dissemination to CDC's National Center for Chronic Disease Prevention and Health Promotion programs management and staff. Key recommendations, include: (1) consideration of resources and other challenges unique to the USAPI when reviewing funding applications, (2) consideration of ways to increase flexibility in USAPI use of program funds, (3) dedication of funding and human resources for technical assistance, (4) provision of opportunities for capacity-building across programs and jurisdictions, (5) consideration of ways to more directly link program reporting with technical assistance. This project provided a unique opportunity for CDC and USAPI stakeholders to share diverse perspectives on challenges to public health programs in the USAPI. Despite diverse experiences, the final set of recommendations reflected a high level of concordance between USAPI and CDC stakeholders. Recommendations have informed or reinforced actions initiated by the DCPC, including the dedication of funds for leadership institutes aimed at enhancing USAPI capacity for sustainable, integrated regional and jurisdictional cancer control infrastructure. Such efforts are an important beginning, but more remains to be done. Indicated is the need for continuous dialogue and collaboration. While this project focused on the USAPI, our results may be relevant to those interested in inter-organizational collaborations, medically underserved areas, public health services programs, and community-based participatory approaches.

Effect of dehydroleucodine on meiosis reinitiation in Bufo arenarum denuded oocytes.

PubMed

Sánchez Toranzo, G; Giordano, O S; López, L A; Bühler, M I

2007-05-01

In amphibian oocytes meiosis, the transition from G2 to M phase is regulated by the maturation promoting factor (MPF), a complex of the cyclin-dependent kinase p34/cdc2 and cyclin B. In immature oocytes there is an inactive complex (pre-MPF), in which cdc2 is phosphorylated on both Thr-161 and Thr-14/Tyr-15 residues. The dephosphorylation of Thr-14/Tyr-15 is necessary for the start of MPF activation and it is induced by the activation of cdc25 phosphatase. Late, to complete the activation, a small amount of active MPF induces an auto-amplification loop of MPF stimulation (MPF amplification). Dehydroleucodine (DhL) is a sesquiterpenic lactone that inhibits mammalian cell proliferation in G2. We asked whether DhL interferes with MPF activation. For this question, the effect of DhL (up to 30 microM) on the resumption of meiosis was evaluated, and visualized by germinal vesicle break down (GVBD), of Bufo arenarum oocytes induced in vitro by either: (i) removing follicle cells; (ii) progesterone stimulation; (iii) VG-content injection; or (iv) injection of mature cytoplasm. The results show that DhL induced GVBD inhibition, in a dose-dependent manner, in spontaneous and progesterone-induced oocyte maturation. Nevertheless, DhL at the doses assayed had no effect on GVBD induced by mature cytoplasm injection, but exerted an inhibitory effect on GVBD induced by GV content. On the basis of these results, we interpreted that DhL does not inhibit MPF amplification and that the target of DhL is any event in the early stages of the cdc25 activation cascade.

Successful management of chronic disseminated candidiasis in hematologic patients treated with high-dose liposomal amphotericin B: a retrospective study of the SEIFEM registry.

PubMed

Della Pepa, Roberta; Picardi, M; Sorà, F; Stamouli, M; Busca, A; Candoni, A; Delia, M; Fanci, R; Perriello, V; Zancanella, M; Nosari, A; Salutari, P; Marchesi, F; Pane, F; Pagano, L

2016-09-01

Chronic disseminated candidiasis (CDC) is a complication of Candida infection in immunocompromised patients, involving the liver and spleen, and rarely other organs. The aim of the study is to identify the best antifungal drug for hematologic immunocompromised patients with CDC. In this multicentric retrospective study, the charts of 20 patients with CDC following cytotoxic agent protocols for hematological malignancies, diagnosed from 2003 to 2013, were analyzed. The response to systemic antifungal therapy within 90 days from CDC diagnosis and the possible delay in chemotherapy plan, due to the infection, were evaluated. Six patients were treated with high-dose (HD; 5 mg/kg/daily) liposomal amphotericin B (L-AmB), whereas three received standard-dose (SD) L-AmB (3 mg/kg/daily). Azoles were given to six patients; the remaining five were treated with echinocandins. All patients treated with HD L-AmB (6/6-100 %) achieved complete resolution of CDC; one of them had to interrupt the chemotherapy program for the infection. In the SD L-AmB group, treatment failed in the 100 % of cases and one patient had to delay chemotherapy for the infection. Of the six patients who received azoles, two achieved complete resolution of the infection, four experienced treatment failure, and only three performed chemotherapy as planned. Echinocandins treatment resulted in complete resolution of the infection in 2/5 cases, partial response in 2/5 cases, and failure in one case. In this group, 3/5 patients completed chemotherapy as planned. This study shows that HD L-AmB was particularly effective against CDC in hematologic patients, allowing most patients to continue cytotoxic agent program.

Heart transplant outcomes in recipients of Centers for Disease Control (CDC) high risk donors.

PubMed

Tsiouris, Athanasios; Wilson, Lynn; Sekar, Rajesh B; Mangi, Abeel A; Yun, James J

2016-12-01

A lack of donor hearts remains a major limitation of heart transplantation. Hearts from Centers for Disease Control (CDC) high-risk donors can be utilized with specific recipient consent. However, outcomes of heart transplantation with CDC high-risk donors are not well known. We sought to define outcomes, including posttransplant hepatitis and human immunodeficiency virus (HIV) status, in recipients of CDC high-risk donor hearts at our institution. All heart transplant recipients from August 2010 to December 2014 (n = 74) were reviewed. Comparison of 1) CDC high-risk donor (HRD) versus 2) standard-risk donor (SRD) groups were performed using chi-squared tests for nominal data and Wilcoxon two-sample tests for continuous variables. Survival was estimated with Kaplan-Meier curves. Of 74 heart transplant recipients reviewed, 66 (89%) received a SRD heart and eight (11%) received a CDC HRD heart. We found no significant differences in recipient age, sex, waiting list 1A status, pretransplant left ventricular assist device (LVAD) support, cytomegalovirus (CMV) status, and graft ischemia times (p = NS) between the HRD and SRD groups. All of the eight HRD were seronegative at the time of transplant. Postoperatively, there was no significant difference in rejection rates at six and 12 months posttransplant. Importantly, no HRD recipients acquired hepatitis or HIV. Survival in HRD versus SRD recipients was not significantly different by Kaplan-Meier analysis (log rank p = 0.644) at five years posttransplant. Heart transplants that were seronegative at the time of transplant had similar posttransplant graft function, rejection rates, and five-year posttransplant survival versus recipients of SRD hearts. At our institution, no cases of hepatitis or HIV occurred in HRD recipients in early follow-up. © 2016 Wiley Periodicals, Inc.

Introduction: CDC Health Disparities and Inequalities Report - United States, 2013.

PubMed

Meyer, Pamela A; Yoon, Paula W; Kaufmann, Rachel B

2013-11-22

This supplement is the second CDC Health Disparities and Inequalities Report (CHDIR). The 2011 CHDIR was the first CDC report to assess disparities across a wide range of diseases, behavioral risk factors, environmental exposures, social determinants, and health-care access (CDC. CDC Health Disparities and Inequalities Report-United States, 2011. MMWR 2011;60[Suppl; January 14, 2011]). The 2013 CHDIR provides new data for 19 of the topics published in 2011 and 10 new topics. When data were available and suitable analyses were possible for the topic area, disparities were examined for population characteristics that included race and ethnicity, sex, sexual orientation, age, disability, socioeconomic status, and geographic location. The purpose of this supplement is to raise awareness of differences among groups regarding selected health outcomes and health determinants and to prompt actions to reduce disparities. The findings in this supplement can be used by practitioners in public health, academia and clinical medicine; the media; the general public; policymakers; program managers; and researchers to address disparities and help all persons in the United States live longer, healthier, and more productive lives.

CDC staging based on absolute CD4 count and CD4 percentage in an HIV-1-infected Indian population: treatment implications

PubMed Central

Vajpayee, M; Kaushik, S; Sreenivas, V; Wig, N; Seth, P

2005-01-01

CD4+ T-cell levels are an important criterion for categorizing HIV-related clinical conditions according to the CDC classification system and are therefore important in the management of HIV by initiating antiretroviral therapy and prophylaxis for opportunistic infections due to HIV among HIV-infected individuals. However, it has been observed that the CD4 counts are affected by the geographical location, race, ethnic origin, age, gender and changes in total and differential leucocyte counts. In the light of this knowledge, we classified 600 HIV seropositive antiretroviral treatment (ART)-naïve Indian individuals belonging to different CDC groups A, B and C on the basis of CDC criteria of both CD4% and CD4 counts and receiver operating characteristic (ROC) curves were generated. Importantly, CDC staging on the basis of CD4% indicated significant clinical implications, requiring an early implementation of effective antiretroviral treatment regimen in HIV-infected individuals deprived of treatment when classified on the basis of CD4 counts. PMID:16045738

ANOPP programmer's reference manual for the executive System. [aircraft noise prediction program

NASA Technical Reports Server (NTRS)

Gillian, R. E.; Brown, C. G.; Bartlett, R. W.; Baucom, P. H.

1977-01-01

Documentation for the Aircraft Noise Prediction Program as of release level 01/00/00 is presented in a manual designed for programmers having a need for understanding the internal design and logical concepts of the executive system software. Emphasis is placed on providing sufficient information to modify the system for enhancements or error correction. The ANOPP executive system includes software related to operating system interface, executive control, and data base management for the Aircraft Noise Prediction Program. It is written in Fortran IV for use on CDC Cyber series of computers.

Lessons of Risk Communication and Health Promotion - West Africa and United States.

PubMed

Bedrosian, Sara R; Young, Cathy E; Smith, Laura A; Cox, Joanne D; Manning, Craig; Pechta, Laura; Telfer, Jana L; Gaines-McCollom, Molly; Harben, Kathy; Holmes, Wendy; Lubell, Keri M; McQuiston, Jennifer H; Nordlund, Kristen; O'Connor, John; Reynolds, Barbara S; Schindelar, Jessica A; Shelley, Gene; Daniel, Katherine Lyon

2016-07-08

During the response to the 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa, CDC addressed the disease on two fronts: in the epidemic epicenter of West Africa and at home in the United States. Different needs drove the demand for information in these two regions. The severity of the epidemic was reflected not only in lives lost but also in the amount of fear, misinformation, and stigma that it generated worldwide. CDC helped increase awareness, promoted actions to stop the spread of Ebola, and coordinated CDC communication efforts with multiple international and domestic partners. CDC, with input from partners, vastly increased the number of Ebola communication materials for groups with different needs, levels of health literacy, and cultural preferences. CDC deployed health communicators to West Africa to support ministries of health in developing and disseminating clear, science-based messages and promoting science-based behavioral interventions. Partnerships in West Africa with local radio, television, and cell phone businesses made possible the dissemination of messages appropriate for maximum effect. CDC and its partners communicated evolving science and risk in a culturally appropriate way to motivate persons to adapt their behavior and prevent infection with and spread of Ebola virus. Acknowledging what is and is not known is key to effective risk communication, and CDC worked with partners to integrate health promotion and behavioral and cultural knowledge into the response to increase awareness of the actual risk for Ebola and to promote protective actions and specific steps to stop its spread. 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).

Investigating consumers' and informal carers' views and preferences for consumer directed care: A discrete choice experiment.

PubMed

Kaambwa, Billingsley; Lancsar, Emily; McCaffrey, Nicola; Chen, Gang; Gill, Liz; Cameron, Ian D; Crotty, Maria; Ratcliffe, Julie

2015-09-01

Consumer directed care (CDC) is currently being embraced internationally as a means to promote autonomy and choice for consumers (people aged 65 and over) receiving community aged care services (CACSs). CDC involves giving CACS clients (consumers and informal carers of consumers) control over how CACSs are administered. However, CDC models have largely developed in the absence of evidence on clients' views and preferences. We explored CACS clients' preferences for a variety of CDC attributes and identified factors that may influence these preferences and potentially inform improved design of future CDC models. Study participants were clients of CACSs delivered by five Australian providers. Using a discrete choice experiment (DCE) approach undertaken in a group setting between June and December 2013, we investigated the relative importance to CACS consumers and informal (family) carers of gradations relating to six salient features of CDC (choice of service provider(s), budget management, saving unused/unspent funds, choice of support/care worker(s), support-worker flexibility and level of contact with service coordinator). The DCE data were analysed using conditional, mixed and generalised logit regression models, accounting for preference and scale heterogeneity. Mean ages for 117 study participants were 80 years (87 consumers) and 74 years (30 informal carers). All participants preferred a CDC approach that allowed them to: save unused funds from a CACS package for future use; have support workers that were flexible in terms of changing activities within their CACS care plan and; choose the support workers that provide their day-to-day CACSs. The CDC attributes found to be important to both consumers and informal carers receiving CACSs will inform the design of future CDC models of service delivery. The DCE approach used in this study has the potential for wide applicability and facilitates the assessment of preferences for elements of potential future aged care service delivery not yet available in policy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular Clustering Interrelationships and Carbohydrate Conformation in Hull and Seeds Among Barley Cultivars

DOE Office of Scientific and Technical Information (OSTI.GOV)

N Liu; P Yu

2011-12-31

The objective of this study was to use molecular spectral analyses with the diffuse reflectance Fourier transform infrared spectroscopy (DRIFT) bioanlytical technique to study carbohydrate conformation features, molecular clustering and interrelationships in hull and seed among six barley cultivars (AC Metcalfe, CDC Dolly, McLeod, CDC Helgason, CDC Trey, CDC Cowboy), which had different degradation kinetics in rumen. The molecular structure spectral analyses in both hull and seed involved the fingerprint regions of ca. 1536-1484 cm{sup -1} (attributed mainly to aromatic lignin semicircle ring stretch), ca. 1293-1212 cm{sup -1} (attributed mainly to cellulosic compounds in the hull), ca. 1269-1217 cm{sup -1}more » (attributed mainly to cellulosic compound in the seeds), and ca. 1180-800 cm{sup -1} (attributed mainly to total CHO C-O stretching vibrations) together with an agglomerative hierarchical cluster (AHCA) and principal component spectral analyses (PCA). The results showed that the DRIFT technique plus AHCA and PCA molecular analyses were able to reveal carbohydrate conformation features and identify carbohydrate molecular structure differences in both hull and seeds among the barley varieties. The carbohydrate molecular spectral analyses at the region of ca. 1185-800 cm{sup -1} together with the AHCA and PCA were able to show that the barley seed inherent structures exhibited distinguishable differences among the barley varieties. CDC Helgason had differences from AC Metcalfe, MeLeod, CDC Cowboy and CDC Dolly in carbohydrate conformation in the seed. Clear molecular cluster classes could be distinguished and identified in AHCA analysis and the separate ellipses could be grouped in PCA analysis. But CDC Helgason had no distinguished differences from CDC Trey in carbohydrate conformation. These carbohydrate conformation/structure difference could partially explain why the varieties were different in digestive behaviors in animals. The molecular spectroscopy technique used in this study could also be used for other plant-based feed and food structure studies.« less

The test characteristics of head circumference measurements for pathology associated with head enlargement: a retrospective cohort study

PubMed Central

2012-01-01

Background The test characteristics of head circumference (HC) measurement percentile criteria for the identification of previously undetected pathology associated with head enlargement in primary care are unknown. Methods Electronic patient records were reviewed to identify children age 3 days to 3 years with new diagnoses of intracranial expansive conditions (IEC) and metabolic and genetic conditions associated with macrocephaly (MGCM). We tested the following HC percentile threshold criteria: ever above the 95th, 97th, or 99.6th percentile and ever crossing 2, 4, or 6 increasing major percentile lines. The Centers for Disease Control and World Health Organization growth curves were used, as well as the primary care network (PCN) curves previously derived from this cohort. Results Among 74,428 subjects, 85 (0.11%) had a new diagnosis of IEC (n = 56) or MGCM (n = 29), and between these 2 groups, 24 received intervention. The 99.6th percentile of the PCN curve was the only threshold with a PPV over 1% (PPV 1.8%); the sensitivity of this threshold was only 15%. Test characteristics for the 95th percentiles were: sensitivity (CDC: 46%; WHO: 55%; PCN: 40%), positive predictive value (PPV: CDC: 0.3%; WHO: 0.3%; PCN: 0.4%), and likelihood ratios positive (LR+: CDC: 2.8; WHO: 2.2; PCN: 3.9). Test characteristics for the 97th percentiles were: sensitivity (CDC: 40%; WHO: 48%; PCN: 34%), PPV (CDC: 0.4%; WHO: 0.3%; PCN: 0.6%), and LR+ (CDC: 3.6; WHO: 2.7; PCN: 5.6). Test characteristics for crossing 2 increasing major percentile lines were: sensitivity (CDC: 60%; WHO: 40%; PCN: 31%), PPV (CDC: 0.2%; WHO: 0.1%; PCN: 0.2%), and LR+ (CDC: 1.3; WHO: 1.1; PCN: 1.5). Conclusions Commonly used HC percentile thresholds had low sensitivity and low positive predictive value for diagnosing new pathology associated with head enlargement in children in a primary care network. PMID:22269214

The step-wise pathway of septin hetero-octamer assembly in budding yeast.

PubMed

Weems, Andrew; McMurray, Michael

2017-05-25

Septin proteins bind guanine nucleotides and form rod-shaped hetero-oligomers. Cells choose from a variety of available septins to assemble distinct hetero-oligomers, but the underlying mechanism was unknown. Using a new in vivo assay, we find that a stepwise assembly pathway produces the two species of budding yeast septin hetero-octamers: Cdc11/Shs1-Cdc12-Cdc3-Cdc10-Cdc10-Cdc3-Cdc12-Cdc11/Shs1. Rapid GTP hydrolysis by monomeric Cdc10 drives assembly of the core Cdc10 homodimer. The extended Cdc3 N terminus autoinhibits Cdc3 association with Cdc10 homodimers until prior Cdc3-Cdc12 interaction. Slow hydrolysis by monomeric Cdc12 and specific affinity of Cdc11 for transient Cdc12•GTP drive assembly of distinct trimers, Cdc11-Cdc12-Cdc3 or Shs1-Cdc12-Cdc3. Decreasing the cytosolic GTP:GDP ratio increases the incorporation of Shs1 vs Cdc11, which alters the curvature of filamentous septin rings. Our findings explain how GTP hydrolysis controls septin assembly, and uncover mechanisms by which cells construct defined septin complexes.

Monitoring population health for Healthy People 2020: evaluation of the NIH PROMIS® Global Health, CDC Healthy Days, and satisfaction with life instruments

PubMed Central

Barile, John P.; Reeve, Bryce B.; Smith, Ashley Wilder; Zack, Matthew M.; Mitchell, Sandra A.; Kobau, Rosemarie; Cella, David F.; Luncheon, Cecily; Thompson, William W.

2015-01-01

Purpose Healthy People 2020 identified health-related quality of life and well-being (WB) as indicators of population health for the next decade. This study examined the measurement properties of the NIH PROMIS® Global Health Scale, the CDC Healthy Days items, and associations with the Satisfaction with Life Scale. Methods A total of 4,184 adults completed the Porter Novelli's HealthStyles mailed survey. Physical and mental health (9 items from PROMIS Global Scale and 3 items from CDC Healthy days measure), and 4 WB factor items were tested for measurement equivalence using multiple-group confirmatory factor analysis. Results The CDC items accounted for similar variance as the PROMIS items on physical and mental health factors; both factors were moderately correlated with WB. Measurement invariance was supported across gender and age; the magnitude of some factor loadings differed between those with and without a chronic medical condition. Conclusions The PROMIS, CDC, and WB items all performed well. The PROMIS items captured a broad range of functioning across the entire continuum of physical and mental health, while the CDC items appear appropriate for assessing burden of disease for chronic conditions and are brief and easily interpretable. All three measures under study appear to be appropriate measures for monitoring several aspects of the Healthy People 2020 goals and objectives. PMID:23404737

Monitoring population health for Healthy People 2020: evaluation of the NIH PROMIS® Global Health, CDC Healthy Days, and satisfaction with life instruments.

PubMed

Barile, John P; Reeve, Bryce B; Smith, Ashley Wilder; Zack, Matthew M; Mitchell, Sandra A; Kobau, Rosemarie; Cella, David F; Luncheon, Cecily; Thompson, William W

2013-08-01

Healthy People 2020 identified health-related quality of life and well-being (WB) as indicators of population health for the next decade. This study examined the measurement properties of the NIH PROMIS(®) Global Health Scale, the CDC Healthy Days items, and associations with the Satisfaction with Life Scale. A total of 4,184 adults completed the Porter Novelli's HealthStyles mailed survey. Physical and mental health (9 items from PROMIS Global Scale and 3 items from CDC Healthy days measure), and 4 WB factor items were tested for measurement equivalence using multiple-group confirmatory factor analysis. The CDC items accounted for similar variance as the PROMIS items on physical and mental health factors; both factors were moderately correlated with WB. Measurement invariance was supported across gender and age; the magnitude of some factor loadings differed between those with and without a chronic medical condition. The PROMIS, CDC, and WB items all performed well. The PROMIS items captured a broad range of functioning across the entire continuum of physical and mental health, while the CDC items appear appropriate for assessing burden of disease for chronic conditions and are brief and easily interpretable. All three measures under study appear to be appropriate measures for monitoring several aspects of the Healthy People 2020 goals and objectives.

Functional Dysregulation of CDC42 Causes Diverse Developmental Phenotypes.

PubMed

Martinelli, Simone; Krumbach, Oliver H F; Pantaleoni, Francesca; Coppola, Simona; Amin, Ehsan; Pannone, Luca; Nouri, Kazem; Farina, Luciapia; Dvorsky, Radovan; Lepri, Francesca; Buchholzer, Marcel; Konopatzki, Raphael; Walsh, Laurence; Payne, Katelyn; Pierpont, Mary Ella; Vergano, Samantha Schrier; Langley, Katherine G; Larsen, Douglas; Farwell, Kelly D; Tang, Sha; Mroske, Cameron; Gallotta, Ivan; Di Schiavi, Elia; Della Monica, Matteo; Lugli, Licia; Rossi, Cesare; Seri, Marco; Cocchi, Guido; Henderson, Lindsay; Baskin, Berivan; Alders, Mariëlle; Mendoza-Londono, Roberto; Dupuis, Lucie; Nickerson, Deborah A; Chong, Jessica X; Meeks, Naomi; Brown, Kathleen; Causey, Tahnee; Cho, Megan T; Demuth, Stephanie; Digilio, Maria Cristina; Gelb, Bruce D; Bamshad, Michael J; Zenker, Martin; Ahmadian, Mohammad Reza; Hennekam, Raoul C; Tartaglia, Marco; Mirzaa, Ghayda M

2018-01-17

Exome sequencing has markedly enhanced the discovery of genes implicated in Mendelian disorders, particularly for individuals in whom a known clinical entity could not be assigned. This has led to the recognition that phenotypic heterogeneity resulting from allelic mutations occurs more commonly than previously appreciated. Here, we report that missense variants in CDC42, a gene encoding a small GTPase functioning as an intracellular signaling node, underlie a clinically heterogeneous group of phenotypes characterized by variable growth dysregulation, facial dysmorphism, and neurodevelopmental, immunological, and hematological anomalies, including a phenotype resembling Noonan syndrome, a developmental disorder caused by dysregulated RAS signaling. In silico, in vitro, and in vivo analyses demonstrate that mutations variably perturb CDC42 function by altering the switch between the active and inactive states of the GTPase and/or affecting CDC42 interaction with effectors, and differentially disturb cellular and developmental processes. These findings reveal the remarkably variable impact that dominantly acting CDC42 mutations have on cell function and development, creating challenges in syndrome definition, and exemplify the importance of functional profiling for syndrome recognition and delineation. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Strategies for preventing group B streptococcal infections in newborns: a nation-wide survey of Italian policies.

PubMed

Tzialla, Chryssoula; Berardi, Alberto; Farina, Claudio; Clerici, Pierangelo; Borghesi, Alessandro; Viora, Elsa; Scollo, Paolo; Stronati, Mauro

2017-11-02

There are no Italian data regarding the strategies for preventing neonatal group B streptococcal (GBS) infection. We conducted a national survey in order to explore obstetrical, neonatal and microbiological practices for the GBS prevention. Three distinct questionnaires were sent to obstetricians, neonatologists and microbiologists. Questionnaires included data on prenatal GBS screening, maternal risk factors, intrapartum antibiotic prophylaxis, microbiological information concerning specimen processing and GBS antimicrobial susceptibility. All respondent obstetrical units used the culture-based screening approach to identify women who should receive intrapartum antibiotic prophylaxis, and more than half of the microbiological laboratories (58%) reported using specimen processing consistent with CDC guidelines. Most neonatal units (89 out of 107, 82%) reported using protocols for preventing GBS early-onset sepsis consistent with CDC guidelines. The screening-based strategy is largely prevalent in Italy, and most protocols for preventing GBS early-onset sepsis are consistent with CDC guidelines. However, we found discrepancies in practices among centers that may reflect the lack of Italian guidelines issued by public health organizations.

Effect of Low Level Subchronic Microwave Radiation on Rat Brain.

PubMed

Deshmukh, Pravin Suryakantrao; Megha, Kanu; Nasare, Namita; Banerjee, Basu Dev; Ahmed, Rafat Sultana; Abegaonkar, Mahesh Pandurang; Tripathi, Ashok Kumar; Mediratta, Pramod Kumari

2016-12-01

The present study was designed to investigate the effects of subchronic low level microwave radiation (MWR) on cognitive function, heat shock protein 70 (HSP70) level and DNA damage in brain of Fischer rats. Experiments were performed on male Fischer rats exposed to microwave radiation for 90 days at three different frequencies: 900, 1800, and 2450 MHz. Animals were divided into 4 groups: Group I: Sham exposed, Group II: animals exposed to microwave radiation at 900 MHz and specific absorption rate (SAR) 5.953 × 10-4 W/kg, Group III: animals exposed to 1800 MHz at SAR 5.835 × 10-4 W/kg and Group IV: animals exposed to 2450 MHz at SAR 6.672 × 10-4 W/kg. All the animals were tested for cognitive function using elevated plus maze and Morris water maze at the end of the exposure period and subsequently sacrificed to collect brain tissues. HSP70 levels were estimated by ELISA and DNA damage was assessed using alkaline comet assay. Microwave exposure at 900-2450 MHz with SAR values as mentioned above lead to decline in cognitive function, increase in HSP70 level and DNA damage in brain. The results of the present study suggest that low level microwave exposure at frequencies 900, 1800, and 2450 MHz may lead to hazardous effects on brain. Copyright © 2016 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Zombie Apocalypse: Can the Undead Teach the Living How to Survive an Emergency?

PubMed

Kruvand, Marjorie; Bryant, Fred B

2015-01-01

We examined whether or not CDC's zombie apocalypse campaign had the ability to achieve the agency's goals of educating young people about emergency preparedness and prompting them to get ready by developing an emergency kit and plan. While the campaign was extremely popular, we examined the question of whether the campaign had the capability to translate into knowledge and action. We conducted an online experiment with 340 undergraduate students divided randomly into two groups. One group was exposed to CDC's zombie blog post; the other to the same preparedness information presented in CDC's traditional, straightforward way. Participants then completed a survey designed to gauge their affective feelings, perceptions, retention of preparedness preparation, and intent to develop an emergency kit and plan. While participants who viewed the humorous zombie material clearly enjoyed it, their positive affect did not lead to greater retention of preparedness information or greater expressed intent to prepare, compared with participants exposed to the factual treatment. The zombie approach had no influence on retention or resulted in less retention relative to the factual approach. Also, there was no significant between-group difference in reported likelihood of developing an emergency kit or plan. While the campaign drew unprecedented traffic to CDC's website, our findings suggest that it lacked the capability to fully achieve the agency's goals of educating people about preparedness and prompting them to get ready. This finding supports previous studies concluding that it is challenging to design public health messages that evoke positive affect as well as intended changes in intentions or behaviors.

The radioresistance to killing of A1-5 cells derives from activation of the Chk1 pathway

NASA Technical Reports Server (NTRS)

Hu, B.; Zhou, X. Y.; Wang, X.; Zeng, Z. C.; Iliakis, G.; Wang, Y.

2001-01-01

Checkpoints respond to DNA damage by arresting the cell cycle to provide time for facilitating repair. In mammalian cells, the G(2) checkpoint prevents the Cdc25C phosphatase from removing inhibitory phosphate groups from the mitosis-promoting kinase Cdc2. Both Chk1 and Chk2, the checkpoint kinases, can phosphorylate Cdc25C and inactivate its in vitro phosphatase activity. Therefore, both Chk1 and Chk2 are thought to regulate the activation of the G(2) checkpoint. Here we report that A1-5, a transformed rat embryo fibroblast cell line, shows much more radioresistance associated with a much stronger G(2) arrest response when compared with its counterpart, B4, although A1-5 and B4 cells have a similar capacity for nonhomologous end-joining DNA repair. These phenotypes of A1-5 cells are accompanied by a higher Chk1 expression and a higher phosphorylation of Cdc2. On the other hand, Chk2 expression increases slightly following radiation; however, it has no difference between A1-5 and B4 cells. Caffeine or UCN-01 abolishes the extreme radioresistance with the strong G(2) arrest and at the same time reduces the phosphorylation of Cdc2 in A1-5 cells. In addition, Chk1 but not Chk2 antisense oligonucleotide sensitizes A1-5 cells to radiation-induced killing and reduces the G(2) arrest of the cells. Taken together these results suggest that the Chk1/Cdc25C/Cdc2 pathway is the major player for the radioresistance with G(2) arrest in A1-5 cells.

Diagnostic performance of BMI percentiles to identify adolescents with metabolic syndrome.

PubMed

Laurson, Kelly R; Welk, Gregory J; Eisenmann, Joey C

2014-02-01

To compare the diagnostic performance of the Centers for Disease Control and Prevention (CDC) and FITNESSGRAM (FGram) BMI standards for quantifying metabolic risk in youth. Adolescents in the NHANES (n = 3385) were measured for anthropometric variables and metabolic risk factors. BMI percentiles were calculated, and youth were categorized by weight status (using CDC and FGram thresholds). Participants were also categorized by presence or absence of metabolic syndrome. The CDC and FGram standards were compared by prevalence of metabolic abnormalities, various diagnostic criteria, and odds of metabolic syndrome. Receiver operating characteristic curves were also created to identify optimal BMI percentiles to detect metabolic syndrome. The prevalence of metabolic syndrome in obese youth was 19% to 35%, compared with <2% in the normal-weight groups. The odds of metabolic syndrome for obese boys and girls were 46 to 67 and 19 to 22 times greater, respectively, than for normal-weight youth. The receiver operating characteristic analyses identified optimal thresholds similar to the CDC standards for boys and the FGram standards for girls. Overall, BMI thresholds were more strongly associated with metabolic syndrome in boys than in girls. Both the CDC and FGram standards are predictive of metabolic syndrome. The diagnostic utility of the CDC thresholds outperformed the FGram values for boys, whereas FGram standards were slightly better thresholds for girls. The use of a common set of thresholds for school and clinical applications would provide advantages for public health and clinical research and practice.

Comics as a Medium for Providing Information on Adult Immunizations.

PubMed

Muzumdar, Jagannath M; Pantaleo, Nicholas L

2017-10-01

This study compared the following effects of two vaccine information flyers-one developed by the Centers for Disease Control and Prevention (CDC) versus one adapted from this information to a comic medium (comic)-on adults: (a) attitude toward the flyer; (b) perceived informativeness of the flyer; (c) intention to seek more information about adult immunizations after viewing the flyer; and (d) intention to get immunized after viewing the flyer. A between-group, randomized trial was used to randomly assign adults (age 18 years or older) at an ambulatory care center to review the CDC or comic flyer. Participants were asked to complete a survey to measure several outcome variables. Items were measured using a 7-point semantic differential scale. Independent-samples t-test was used for comparisons. A total of 265 surveys (CDC n = 132 vs comic n = 133) were analyzed. The comic flyer had a statistically significant effect on participants' attitudes and their perception of the flyer's informativeness compared to the CDC flyer. Flyer type did not have a statistically significant effect on intention-related variables. The study findings showed that the comic flyer was positively evaluated compared to the CDC flyer. These findings could provide a new direction for developing adult educational materials.

Celastrol: Molecular targets of Thunder God Vine.

PubMed

Salminen, Antero; Lehtonen, Marko; Paimela, Tuomas; Kaarniranta, Kai

2010-04-09

Celastrol, a quinone methide triterpene, is a pharmacologically active compound present in Thunder God Vine root extracts used as a remedy of inflammatory and autoimmune diseases, e.g. rheumatoid arthritis. Celastrol is one of the most promising medicinal molecules isolated from the plant extracts of traditional medicines. Molecular studies have identified several molecular targets which are mostly centered on the inhibition of IKK-NF-kappaB signaling. Celastrol (i) inhibits directly the IKKalpha and beta kinases, (ii) inactivates the Cdc37 and p23 proteins which are co-chaperones of HSP90, (iii) inhibits the function of proteasomes, and (iv) activates the HSF1 and subsequently triggers the heat shock response. It seems that the quinone methide structure present in celastrol can react with the thiol groups of cysteine residues, forming covalent protein adducts. In laboratory experiments, celastrol has proved to be a potent inhibitor of inflammatory responses and cancer formation as well as alleviating diseases of proteostasis deficiency. Celastrol needs still to pass several hurdles, e.g. ADMET assays, before it can enter the armoury of western drugs. Copyright 2010 Elsevier Inc. All rights reserved.

Does symptomatic primary HIV-1 infection accelerate progression to CDC stage IV disease, CD4 count below 200 x 10(6)/l, AIDS, and death from AIDS?

PubMed Central

Lindbäck, S.; Broström, C.; Karlsson, A.; Gaines, H.

1994-01-01

OBJECTIVE--To investigate the prognostic significance of symptomatic primary HIV-1 infection. DESIGN--Prospective study of homosexual men seroconverting to HIV in 1985 and 1986. Patients were followed up at least three times yearly with clinical examinations and T cell subset determinations for an average of 7.2 years. SETTING--Research project centred on attenders for treatment and screening for HIV at the Karolinska Institute, Stockholm. SUBJECTS--19 patients presenting with a glandular-fever-like illness associated with seroconversion to HIV and 29 asymptomatic seroconverters. MAIN OUTCOME MEASURES--Progression to Centers for Disease Control and Prevention stage IV disease, CD4 cell count below 200 x 10(6)/l, AIDS, and death from AIDS. RESULTS--Symptomatic seroconverters were significantly more likely to develop Centers for Disease Control and Prevention stage IV disease (95% v 66%), CD4 cell counts below 200 x 10(6)/l (84% v 55%), and AIDS (58% v 28%) and die of AIDS (53% v 7%). CONCLUSION--A glandular-fever-like illness associated with seroconversion to HIV-1 predicts accelerated progression to AIDS and other HIV related diseases. PMID:7819891

Risk of fetal mortality after exposure to Listeria monocytogenes based on dose-response data from pregnant guinea pigs and primates.

PubMed

Williams, Denita; Castleman, Jennifer; Lee, Chi-Ching; Mote, Beth; Smith, Mary Alice

2009-11-01

One-third of the annual cases of listeriosis in the United States occur during pregnancy and can lead to miscarriage or stillbirth, premature delivery, or infection of the newborn. Previous risk assessments completed by the Food and Drug Administration/the Food Safety Inspection Service of the U.S. Department of Agriculture/the Centers for Disease Control and Prevention (FDA/USDA/CDC) and Food and Agricultural Organization/the World Health Organization (FAO/WHO) were based on dose-response data from mice. Recent animal studies using nonhuman primates and guinea pigs have both estimated LD(50)s of approximately 10(7) Listeria monocytogenes colony forming units (cfu). The FAO/WHO estimated a human LD(50) of 1.9 x 10(6) cfu based on data from a pregnant woman consuming contaminated soft cheese. We reevaluated risk based on dose-response curves from pregnant rhesus monkeys and guinea pigs. Using standard risk assessment methodology including hazard identification, exposure assessment, hazard characterization, and risk characterization, risk was calculated based on the new dose-response information. To compare models, we looked at mortality rate per serving at predicted doses ranging from 10(-4) to 10(12) L. monocytogenes cfu. Based on a serving of 10(6) L. monocytogenes cfu, the primate model predicts a death rate of 5.9 x 10(-1) compared to the FDA/USDA/CDC (fig. IV-12) predicted rate of 1.3 x 10(-7). Based on the guinea pig and primate models, the mortality rate calculated by the FDA/USDA/CDC is underestimated for this susceptible population.

Elimination of cdc2 phosphorylation sites in the cdc25 phosphatase blocks initiation of M-phase.

PubMed Central

Izumi, T; Maller, J L

1993-01-01

The cdc25 phosphatase is a mitotic inducer that activates p34cdc2 at the G2/M transition by dephosphorylation of Tyr15 in p34cdc2. cdc25 itself is also regulated through periodic changes in its phosphorylation state. To elucidate the mechanism for induction of mitosis, phosphorylation of cdc25 has been investigated using recombinant proteins. cdc25 is phosphorylated by both cyclin A/p34cdc2 and cyclin B/p34cdc2 at similar sets of multiple sites in vitro. This phosphorylation retards its electrophoretical mobility and activates its ability to increase cyclin B/p34cdc2 kinase activity three- to fourfold in vitro, as found for endogenous Xenopus cdc25 in M-phase extracts. The threonine and serine residues followed by proline that are conserved between Xenopus and human cdc25 have been mutated. Both the triple mutation of Thr48, Thr67, and Thr138 and the quintuple mutation of these three threonine residues plus Ser205 and Ser285, almost completely abolish the shift in electrophoretic mobility of cdc25 after incubation with M-phase extracts or phosphorylation by p34cdc2. These mutations inhibit the activation of cdc25 by phosphorylation with p34cdc2 by 70 and 90%, respectively. At physiological concentrations these mutants cannot activate cyclin B/p34cdc2 in cdc25-immunodepleted oocyte extracts, suggesting that a positive feed-back loop between cdc2 and cdc25 is necessary for the full activation of cyclin B/p34cdc2 that induces abrupt entry into mitosis in vivo. Images PMID:7513216

Hepatitis C Virus in the US Military Retiree Population: To Screen, or Not to Screen?

PubMed

Laufer, Christin B; Carroll, Matthew B

2015-10-01

In 2012, the Centers for Disease Control (CDC) recommended hepatitis C virus (HCV) screening for those born between 1945 and 1965. Prior recommendations endorsed screening based on risk factors (RFs). Because United States (US) military retirees have had at least 20 years of access to free comprehensive health care, mandatory physical fitness tests, periodic health assessments and mandatory drug screening, we hypothesized that the prevalence of HCV amongst military retirees is lower than the national average. Thus the new CDC screening guidelines may not be applicable or cost effective in this particular population. A quality improvement (QI) initiative implemented the new birth-cohort CDC screening guidelines for the internal medicine (IM) clinic of our hospital (QI group). An age-matched group from the same IM clinic, screened based on RFs for HCV infection, served as the comparator (RF group). The prevalence of the anti-HCV antibody and chronic infection was determined and compared with each other and with the national average. The prevalence of the HCV antibody was 2.1% and 2.3% in the QI and RF groups, respectively (odds ratio (OR): 1.08, 95% CI: 0.37 - 3.21, P = 1.000). The prevalence of chronic infection was 0.4% and 1.8% in the QI and RF groups, respectively (OR: 4.39, 95% CI: 0.80 - 24.13, P = 0.083). When our data were compared with the national average, there were no statistical differences in the prevalence of the HCV antibody; however, there was statistically more viral clearance, and subsequently less chronic infection, in the QI group versus the national average. The military retiree population did not have a lower prevalence of the HCV antibody than the American populace whether screened based on age or traditional RFs. Thus, the CDC guidelines are applicable in this population. One interesting finding of this study is the higher rate of viral clearance in military retirees when compared with the national average. It is therefore possible that military retirees may be more likely to have natural viral eradication than the civilian population.

Strategies for achieving healthy energy balance among African Americans in the Mississippi Delta.

PubMed

Parham, Groesbeck P; Scarinci, Isabel C

2007-10-01

Low-income African Americans who live in rural areas of the Deep South are particularly vulnerable to diseases associated with unhealthy energy imbalance. The Centers for Disease Control and Prevention (CDC) has suggested various physical activity strategies to achieve healthy energy balance. Our objective was to conduct formal, open-ended discussions with low-income African Americans in the Mississippi Delta to determine 1) their dietary habits and physical activity levels, 2) their attitudes toward CDC's suggested physical activity strategies, and 3) their suggestions on how to achieve CDC's strategies within their own environment. A qualitative method (focus groups) was used to conduct the study during 2005. Prestudy meetings were held with African American lay health workers to formulate a focus group topic guide, establish inclusion criteria for focus group participants, select meeting sites and times, and determine group segmentation guidelines. Focus groups were divided into two phases. All discussions and focus group meetings were held in community centers within African American neighborhoods in the Mississippi Delta and were led by trained African American moderators. Phase I focus groups identified the following themes: overeating, low self-esteem, low income, lack of physical exercise, unhealthy methods of food preparation, a poor working definition of healthy energy balance, and superficial knowledge of strategies for achieving healthy energy balance. Phase 2 focus groups identified a preference for social support-based strategies for increasing physical activity levels. Energy balance strategies targeting low-income, rural African Americans in the Deep South may be more effective if they emphasize social interaction at the community and family levels and incorporate the concept of community volunteerism.

CDC25A phosphatase controls meiosis I progression in mouse oocytes.

PubMed

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.

Kidney transplantation after desensitization in sensitized patients: a Korean National Audit.

PubMed

Huh, Kyu Ha; Kim, Beom Seok; Yang, Jaeseok; Ahn, Jeongmyung; Kim, Myung-Gyu; Park, Jae Berm; Kim, Jong Man; Chung, Byung-Ha; Kim, Joong Kyung; Kong, Jin Min

2012-10-01

The number of end-stage renal disease (ESRD) patients with preformed antibodies waiting for a kidney transplant has been increasing lately. We conducted a nationwide study on the outcomes of kidney transplantation after desensitization in Korea. Six transplant centers have run desensitization programs. The patients who underwent living donor kidney transplantation after desensitization from 2002 to 2010 were retrospectively analyzed. A total of 86 cases were enrolled. Thirty-five of these were cases of re-transplantation (40.7 %). Indications of desensitization were positive complement-dependent cytotoxicity (CDC) cross-match responses (CDC(+), 36.0 %), positive flow-cytometric cross-match responses (FCX(+), 54.7 %), and positive donor-specific antibodies (DSA(+), 8.1 %). The desensitization protocols used pre-transplant plasmapheresis (95.3 %), intravenous immunoglobulin (62.8 %), and rituximab (67.4 %). Acute rejection occurred in 18 patients (20.9 %), graft failure occurred in 4 patients, and the 3-year graft survival rate was 93.8 %. The presence of DSA increased the acute rejection rate (P = 0.015) and decreased the 1-year post-transplant estimated glomerular filtration rate (P = 0.006). Although rejection-free survival rates did not differ significantly between the CDC(+) and FCX(+) groups, the 1-year estimated glomerular filtration rate was lower in the CDC(+) group (P = 0.010). Infectious and significant bleeding complications occurred in 15.5 % and 4.7 % of cases, respectively. Kidney transplantation after desensitization had good graft outcomes and tolerable complications in Korea, and therefore, this therapy can be recommended for sensitized ESRD patients.

Awareness and trust of the FDA and CDC: Results from a national sample of US adults and adolescents

PubMed Central

2017-01-01

Trust in government agencies plays a key role in advancing these organizations' agendas, influencing behaviors, and effectively implementing policies. However, few studies have examined the extent to which individuals are aware of and trust the leading United States agencies devoted to protecting the public’s health. Using two national samples of adolescents (N = 1,125) and adults (N = 5,014), we examined demographic factors, with a focus on vulnerable groups, as correlates of awareness of and trust in the Centers for Disease Control and Prevention (CDC), Food and Drug Administration (FDA), and the federal government. From nine different weighted and adjusted logistic regression models, we found high levels of awareness of the existence of the FDA and CDC (ranging from 55.7% for adolescents’ awareness of the CDC to 94.3% for adults’ awareness of the FDA) and moderate levels of trust (ranging from a low of 41.8% for adults’ trust in the federal government and a high of 78.8% for adolescents’ trust of the FDA). In the adolescent and adult samples, awareness was higher among non-Hispanic Blacks and respondents with low numeracy. With respect to trust, few consistent demographic differences emerged. Our findings provide novel insights regarding awareness and trust in the federal government and specific United States public health agencies. Our findings suggest groups to whom these agencies may want to selectively communicate to enhance trust and thus facilitate their communication and regulatory agendas. PMID:28520750

Awareness and trust of the FDA and CDC: Results from a national sample of US adults and adolescents.

PubMed

Kowitt, Sarah D; Schmidt, Allison M; Hannan, Anika; Goldstein, Adam O

2017-01-01

Trust in government agencies plays a key role in advancing these organizations' agendas, influencing behaviors, and effectively implementing policies. However, few studies have examined the extent to which individuals are aware of and trust the leading United States agencies devoted to protecting the public's health. Using two national samples of adolescents (N = 1,125) and adults (N = 5,014), we examined demographic factors, with a focus on vulnerable groups, as correlates of awareness of and trust in the Centers for Disease Control and Prevention (CDC), Food and Drug Administration (FDA), and the federal government. From nine different weighted and adjusted logistic regression models, we found high levels of awareness of the existence of the FDA and CDC (ranging from 55.7% for adolescents' awareness of the CDC to 94.3% for adults' awareness of the FDA) and moderate levels of trust (ranging from a low of 41.8% for adults' trust in the federal government and a high of 78.8% for adolescents' trust of the FDA). In the adolescent and adult samples, awareness was higher among non-Hispanic Blacks and respondents with low numeracy. With respect to trust, few consistent demographic differences emerged. Our findings provide novel insights regarding awareness and trust in the federal government and specific United States public health agencies. Our findings suggest groups to whom these agencies may want to selectively communicate to enhance trust and thus facilitate their communication and regulatory agendas.

The effect of DNA replication on mutation of the Saccharomyces cerevisiae CDC8 gene.

PubMed

Zaborowska, D; Zuk, J

1990-04-01

Incubation in YPD medium under permissive conditions when DNA replication is going on, strongly stimulates the induction of cdc+ colonies of UV-irradiated cells of yeast strains HB23 (cdc8-1/cdc8-3), HB26 (cdc8-3/cdc8-3) and HB7 (cdc8-1/cdc8-1). Inhibition of DNA replication by hydroxyurea, araCMP, cycloheximide or caffeine or else by incubation in phosphate buffer pH 7.0, abolishes this stimulation. Thus the replication of DNA is strongly correlated with the high induction of cdc+ colonies by UV irradiation. It is postulated that these UV-induced cdc+ colonies arise as the result infidelity in DNA replication.

Hospital-Acquired Pneumonia in Patients Undergoing Coronary Artery Bypass Graft; Comparison of the Center for Disease Control Clinical Criteria With Physicians’ Judgment

PubMed Central

Baghban, Mahboubeh; Paknejad, Omalbanin; Yousefshahi, Fardin; Gohari Moghadam, Keivan; Bina, Payvand; Samimi Sadeh, Saghar

2014-01-01

Background: Following coronary artery bypass graft (CABG), patients are at high risk (3.2%-8.3%) for developing hospital-acquired pneumonia (HAP) with mortality rate of 24% to 50%. Some of routine features in patients undergoing CABG are similar to clinical criteria of Center of Disease Control (CDC) for diagnosis of pneumonia. This may lead to over-diagnosis of pneumonia in these patients. Objectives: This study aimed to assess the frequency of CDC criteria for diagnosis of pneumonia in patients undergoing CABG. Patients and Methods: This study was performed on CABG candidates admitted to post cardiac surgery Intensive Care Unit (ICU) in a six-month period. Patient’s records, Chest-X-Ray, and Laboratory tests were assessed for PNU1-CDC criteria for HAP diagnosis. At the same time, a physician who was unaware of the study protocol assessed the clinical diagnosis. Then the results were compared with CDC criteria-based diagnosis. Results: Of total 300 patients, 9 (3%) met CDC criteria for diagnosis of pneumonia while none of the cases were diagnosed as HAP according to the physicians’ clinical diagnosis. All nine patients were discharged with proper general condition and no need of antibiotic therapy. This study showed that loss of consciousness, tachypnea, dyspnea, PaO2 < 60 mm Hg, PaO2/FiO2 < 240, and local infiltration in 24 hours of operation were misleading features of CDC criteria, which were not considered in physicians’ clinical judgment to establish the diagnosis. Conclusions: Our findings suggest that in Post-CABG patients, physicians could judge the occurrence of HAP more accurately in comparison to making the diagnosis based on CDC criteria alone. Expert physician may intentionally do not take some of these criteria into account according the patients’ course of disease. Therefore, it is suggested that the value of these criteria in special group of patients like those undergoing CABG should be re-evaluated. PMID:25289379

Hospital-acquired pneumonia in patients undergoing coronary artery bypass graft; comparison of the center for disease control clinical criteria with physicians' judgment.

PubMed

Baghban, Mahboubeh; Paknejad, Omalbanin; Yousefshahi, Fardin; Gohari Moghadam, Keivan; Bina, Payvand; Samimi Sadeh, Saghar

2014-08-01

Following coronary artery bypass graft (CABG), patients are at high risk (3.2%-8.3%) for developing hospital-acquired pneumonia (HAP) with mortality rate of 24% to 50%. Some of routine features in patients undergoing CABG are similar to clinical criteria of Center of Disease Control (CDC) for diagnosis of pneumonia. This may lead to over-diagnosis of pneumonia in these patients. This study aimed to assess the frequency of CDC criteria for diagnosis of pneumonia in patients undergoing CABG. This study was performed on CABG candidates admitted to post cardiac surgery Intensive Care Unit (ICU) in a six-month period. Patient's records, Chest-X-Ray, and Laboratory tests were assessed for PNU1-CDC criteria for HAP diagnosis. At the same time, a physician who was unaware of the study protocol assessed the clinical diagnosis. Then the results were compared with CDC criteria-based diagnosis. Of total 300 patients, 9 (3%) met CDC criteria for diagnosis of pneumonia while none of the cases were diagnosed as HAP according to the physicians' clinical diagnosis. All nine patients were discharged with proper general condition and no need of antibiotic therapy. This study showed that loss of consciousness, tachypnea, dyspnea, PaO2 < 60 mm Hg, PaO2/FiO2 < 240, and local infiltration in 24 hours of operation were misleading features of CDC criteria, which were not considered in physicians' clinical judgment to establish the diagnosis. Our findings suggest that in Post-CABG patients, physicians could judge the occurrence of HAP more accurately in comparison to making the diagnosis based on CDC criteria alone. Expert physician may intentionally do not take some of these criteria into account according the patients' course of disease. Therefore, it is suggested that the value of these criteria in special group of patients like those undergoing CABG should be re-evaluated.

Ubiquitination of Cdc20 by the APC occurs through an intramolecular mechanism

PubMed Central

Foe, Ian T.; Foster, Scott A.; Cheung, Stephanie K.; DeLuca, Steven Z.; Morgan, David O.; Toczyski, David P.

2012-01-01

SUMMARY Background Cells control progression through late mitosis by regulating Cdc20 and Cdh1, the two mitotic activators of the Anaphase Promoting Complex (APC). The control of Cdc20 protein levels during the cell cycle is not well understood. Results Here, we demonstrate that Cdc20 is degraded in budding yeast by multiple APC-dependent mechanisms. We find that the majority of Cdc20 turnover does not involve a second activator molecule, but instead depends on in cis Cdc20 autoubiquitination while it is bound to its activator-binding site on the APC core. Unlike in trans ubiquitination of Cdc20 substrates, the APC ubiquitinates Cdc20 independent of APC activation by Cdc20’s C-box. Cdc20 turnover by this intramolecular mechanism is cell cycle-regulated, contributing to the decline in Cdc20 levels that occurs after anaphase. Interestingly, high substrate levels in vitro significantly reduce Cdc20 autoubiquitination. Conclusion We show here that Cdc20 fluctuates through the cell cycle via a distinct form of APC-mediated ubiquitination. This in cis autoubiquitination may preferentially occur in early anaphase, following depletion of Cdc20 substrates. This suggests that distinct mechanisms are able to target Cdc20 for ubiquitination at different points during the cell cycle. PMID:22079111

Characterization of a Drosophila ortholog of the Cdc7 kinase: a role for Cdc7 in endoreplication independent of Chiffon.

PubMed

Stephenson, Robert; Hosler, Marcus R; Gavande, Navnath S; Ghosh, Arun K; Weake, Vikki M

2015-01-16

Cdc7 is a serine-threonine kinase that phosphorylates components of the pre-replication complex during DNA replication initiation. Cdc7 is highly conserved, and Cdc7 orthologs have been characterized in organisms ranging from yeast to humans. Cdc7 is activated specifically during late G1/S phase by binding to its regulatory subunit, Dbf4. Drosophila melanogaster contains a Dbf4 ortholog, Chiffon, which is essential for chorion amplification in Drosophila egg chambers. However, no Drosophila ortholog of Cdc7 has yet been characterized. Here, we report the functional and biochemical characterization of a Drosophila ortholog of Cdc7. Co-expression of Drosophila Cdc7 and Chiffon is able to complement a growth defect in yeast containing a temperature-sensitive Cdc7 mutant. Cdc7 and Chiffon physically interact and can be co-purified from insect cells. Cdc7 phosphorylates the known Cdc7 substrates Mcm2 and histone H3 in vitro, and Cdc7 kinase activity is stimulated by Chiffon and inhibited by the Cdc7-specific inhibitor XL413. Drosophila egg chamber follicle cells deficient for Cdc7 have a defect in two types of DNA replication, endoreplication and chorion gene amplification. However, follicle cells deficient for Chiffon have a defect in chorion gene amplification but still undergo endocycling. Our results show that Cdc7 interacts with Chiffon to form a functional Dbf4-dependent kinase complex and that Cdc7 is necessary for DNA replication in Drosophila egg chamber follicle cells. Additionally, we show that Chiffon is a member of an expanding subset of DNA replication initiation factors that are not strictly required for endoreplication in Drosophila. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Physical activity recommendations: an alternative approach using energy expenditure.

PubMed

Mudd, Lanay M; Rafferty, Ann P; Reeves, Mathew J; Pivarnik, James M

2008-10-01

Most adults do not meet the American College of Sports Medicine and Centers for Disease Control and Prevention (ACSM/CDC) physical activity recommendations. Even fewer meet the more extreme Institute of Medicine (IOM) physical activity recommendations. Compliance with either recommendation has been conventionally assessed by combining frequencies and durations of self-reported activities. Leisure-time energy expenditure is a cumulative measure of activity that offers an alternative method of defining compliance. To calculate the leisure-time energy expenditure of adults complying with the ACSM/CDC or the IOM physical activity recommendations determined by conventional measures and to reexamine compliance with the IOM recommendation using energy expenditure criteria. National, cross-sectional data from the 2000 Behavioral Risk Factor Surveillance System determined the mode, frequency, and duration of up to two leisure-time activities performed by adults. Four mutually exclusive activity groups (Non-, Low-, ACSM/CDC-, and IOM-Active) were defined on the basis of frequencies and durations of reported activities. Leisure-time energy expenditure (kcal x kg(-1) x wk(-1)) was calculated per respondent. The energy expenditure threshold for meeting the IOM recommendation was calculated as 21 kcal x kg(-1) x wk(-1). Of the 162,669 respondents included in the analyses, 29.9% were Nonactive, whereas 42.3%, 23.3%, and 4.5% were Low-, ACSM/CDC-, and IOM-Active, respectively. Median leisure-time energy expenditure values were 9.0, 27.4, and 63.0 kcal x kg(-1) x wk(-1) for Low-, ACSM/CDC-, and IOM-Active groups, respectively. When using energy expenditure criteria, compliance with the IOM recommendation rose to 27.7% of respondents. Compliance with the IOM physical activity recommendation dramatically increased when assessed by energy expenditure compared with conventional criteria, thereby highlighting the potential bias of conventional methods. A significant proportion of adults meet the intent but not the letter of the IOM activity recommendation.

Complement-dependent cytotoxicity (CDC) to detect Anti-HLA antibodies: old but gold.

PubMed

Saito, Patrícia Keiko; Yamakawa, Roger Haruki; Pereira, Lucieni Christina Marques da Silva; da Silva, Waldir Veríssimo; Borelli, Sueli Donizete

2014-07-01

The criterion (gold) standard to detect anti-human leukocyte antigen (HLA) antibodies is the complement-dependent cytotoxicity (CDC) assay. Recently, more sensitive methods have been used for the same purpose. This study analyzed 70 serum samples of patients with end-stage renal disease using CDC, CDC with the addition of anti-human globulin (CDC-AHG), CDC with the addition of dithiothreitol (CDC-DTT), and the recent solid-phase immunoassay (SPI; Labscreen PRA) to detect anti-HLA antibodies. Mean percent panel reactive antibodies (PRA) detected by SPI was 37.5% (±34.2) higher than the values detected by the other methods. Comparative analyses revealed significant difference between CDC and CDC-AHG, and between CDC and SPI (P < 0.0001), but not between CDC-AHG and SPI (P = 0.8026). Although the CDC-AHG method is "old," its performance to detect anti-HLA antibodies in the samples analyzed was comparable to the SPI in the evaluation of percent class I PRA. © 2014 Wiley Periodicals, Inc.

cdc25 cell cycle-activating phosphatases and c-myc expression in human non-Hodgkin's lymphomas.

PubMed

Hernández, S; Hernández, L; Beà, S; Cazorla, M; Fernández, P L; Nadal, A; Muntané, J; Mallofré, C; Montserrat, E; Cardesa, A; Campo, E

1998-04-15

cdc25A, cdc25B, and cdc25C are a family of human phosphatases that activate the cyclin-dependent kinases at different points of the cell cycle. cdc25A and cdc25B have been shown to have oncogenic potential, and they have been identified as transcriptional targets of c-myc. To determine the role of cdc25 genes in the pathogenesis of human lymphomas and their possible correlation with c-myc deregulation, we have analyzed the expression of cdc25A, cdc25B, and cdc25C and c-myc genes in a series of 63 non-Hodgkin's lymphomas and 8 nonneoplastic lymphoid tissues. The mRNA levels of the three phosphatases in the nonneoplastic tissues were negative or negligible. cdc25B overexpression was detected in 35 tumors (56%). This overexpression was more frequently found in aggressive (81%) than in indolent lymphomas (36%; P < 0.01). cdc25B overexpression was also significantly associated with a higher proliferative activity of the tumors. No cdc25B gene amplification or rearrangements were detected by Southern blot analysis. A biallelic EcoRI polymorphism of cdc25B gene was identified with a similar distribution in patients with lymphoma and in a normal population. cdc25A was overexpressed in three aggressive lymphomas. No detectable cdc25C mRNA levels were seen in any of the tumors. c-myc was overexpressed in 43% of tumors, and it correlated significantly with the presence of cdc25B up-regulation. Twenty-six of 35 (74%) lymphomas with high levels of cdc25B mRNA also showed c-myc overexpression, whereas 27 of 28 (96%) tumors without detectable or with very low cdc25B expression also had undetectable c-myc levels (P < 0.0001). In addition, a significant linear correlation was found between the cdc25B and c-myc mRNA levels (r = 0.575, P < 0.001). These findings suggest that cdc25B overexpression in non-Hodkin's lymphoma may participate in the pathogenesis of aggressive variants, and it may cooperate with c-myc oncogene in the development of these tumors.

Differential transmission of the molecular signature of RBSP3, LIMD1 and CDC25A in basal/ parabasal versus spinous of normal epithelium during head and neck tumorigenesis: A mechanistic study.

PubMed

Sarkar, Shreya; Alam, Neyaz; Mandal, Syam Sundar; Chatterjee, Kabita; Ghosh, Supratim; Roychoudhury, Susanta; Panda, Chinmay Kumar

2018-01-01

Head and neck squamous cell carcinoma (HNSCC) is a global disease and mortality burden, necessitating the elucidation of its molecular progression for effective disease management. The study aims to understand the molecular profile of three candidate cell cycle regulatory genes, RBSP3, LIMD1 and CDC25A in the basal/ parabasal versus spinous layer of normal oral epithelium and during head and neck tumorigenesis. Immunohistochemical expression and promoter methylation was used to determine the molecular signature in normal oral epithelium. The mechanism of alteration transmission of this profile during tumorigenesis was then explored through additional deletion and mutation in HPV/ tobacco etiological groups, followed byclinico-pathological correlation. In basal/parabasal layer, the molecular signature of the genes was low protein expression/ high promoter methylation of RBSP3, high expression/ low methylation of LIMD1 and high expression of CDC25A. Dysplastic epithelium maintained the signature of RBSP3 through high methylation/ additional deletion with loss of the signatures of LIMD1 and CDC25A via deletion/ additional methylation. Similarly, maintenance and / or loss of signature in invasive tumors was by recurrent deletion/ methylation. Thus, differential patterns of alteration of the genes might be pre-requisite for the development of dysplastic and invasive lesions. Etiological factors played a key role in promoting genetic alterations and determining prognosis. Tobacco negative HNSCC patients had significantly lower alterations of LIMD1 and CDC25A, along with better survival among tobacco negative/ HPV positive patients. Our data suggests the necessity for perturbation of normal molecular profile of RBSP3, LIMD1 and CDC25A in conjunction with etiological factors for head and neck tumorigenesis, implying their diagnostic and prognostic significance.

A TOCA/CDC-42/PAR/WAVE functional module required for retrograde endocytic recycling.

PubMed

Bai, Zhiyong; Grant, Barth D

2015-03-24

Endosome-to-Golgi transport is required for the function of many key membrane proteins and lipids, including signaling receptors, small-molecule transporters, and adhesion proteins. The retromer complex is well-known for its role in cargo sorting and vesicle budding from early endosomes, in most cases leading to cargo fusion with the trans-Golgi network (TGN). Transport from recycling endosomes to the TGN has also been reported, but much less is understood about the molecules that mediate this transport step. Here we provide evidence that the F-BAR domain proteins TOCA-1 and TOCA-2 (Transducer of Cdc42 dependent actin assembly), the small GTPase CDC-42 (Cell division control protein 42), associated polarity proteins PAR-6 (Partitioning defective 6) and PKC-3/atypical protein kinase C, and the WAVE actin nucleation complex mediate the transport of MIG-14/Wls and TGN-38/TGN38 cargo proteins from the recycling endosome to the TGN in Caenorhabditis elegans. Our results indicate that CDC-42, the TOCA proteins, and the WAVE component WVE-1 are enriched on RME-1-positive recycling endosomes in the intestine, unlike retromer components that act on early endosomes. Furthermore, we find that retrograde cargo TGN-38 is trapped in early endosomes after depletion of SNX-3 (a retromer component) but is mainly trapped in recycling endosomes after depletion of CDC-42, indicating that the CDC-42-associated complex functions after retromer in a distinct organelle. Thus, we identify a group of interacting proteins that mediate retrograde recycling, and link these proteins to a poorly understood trafficking step, recycling endosome-to-Golgi transport. We also provide evidence for the physiological importance of this pathway in WNT signaling.

A TOCA/CDC-42/PAR/WAVE functional module required for retrograde endocytic recycling

PubMed Central

Bai, Zhiyong; Grant, Barth D.

2015-01-01

Endosome-to-Golgi transport is required for the function of many key membrane proteins and lipids, including signaling receptors, small-molecule transporters, and adhesion proteins. The retromer complex is well-known for its role in cargo sorting and vesicle budding from early endosomes, in most cases leading to cargo fusion with the trans-Golgi network (TGN). Transport from recycling endosomes to the TGN has also been reported, but much less is understood about the molecules that mediate this transport step. Here we provide evidence that the F-BAR domain proteins TOCA-1 and TOCA-2 (Transducer of Cdc42 dependent actin assembly), the small GTPase CDC-42 (Cell division control protein 42), associated polarity proteins PAR-6 (Partitioning defective 6) and PKC-3/atypical protein kinase C, and the WAVE actin nucleation complex mediate the transport of MIG-14/Wls and TGN-38/TGN38 cargo proteins from the recycling endosome to the TGN in Caenorhabditis elegans. Our results indicate that CDC-42, the TOCA proteins, and the WAVE component WVE-1 are enriched on RME-1–positive recycling endosomes in the intestine, unlike retromer components that act on early endosomes. Furthermore, we find that retrograde cargo TGN-38 is trapped in early endosomes after depletion of SNX-3 (a retromer component) but is mainly trapped in recycling endosomes after depletion of CDC-42, indicating that the CDC-42–associated complex functions after retromer in a distinct organelle. Thus, we identify a group of interacting proteins that mediate retrograde recycling, and link these proteins to a poorly understood trafficking step, recycling endosome-to-Golgi transport. We also provide evidence for the physiological importance of this pathway in WNT signaling. PMID:25775511

A structured approach to recording AIDS-defining illnesses in Kenya: A SNOMED CT based solution

PubMed Central

Oluoch, Tom; de Keizer, Nicolette; Langat, Patrick; Alaska, Irene; Ochieng, Kenneth; Okeyo, Nicky; Kwaro, Daniel; Cornet, Ronald

2016-01-01

Introduction Several studies conducted in sub-Saharan Africa (SSA) have shown that routine clinical data in HIV clinics often have errors. Lack of structured and coded documentation of diagnosis of AIDS defining illnesses (ADIs) can compromise data quality and decisions made on clinical care. Methods We used a structured framework to derive a reference set of concepts and terms used to describe ADIs. The four sources used were: (i) CDC/Accenture list of opportunistic infections, (ii) SNOMED Clinical Terms (SNOMED CT), (iii) Focus Group Discussion (FGD) among clinicians and nurses attending to patients at a referral provincial hospital in western Kenya, and (iv) chart abstraction from the Maternal Child Health (MCH) and HIV clinics at the same hospital. Using the January 2014 release of SNOMED CT, concepts were retrieved that matched terms abstracted from approach iii & iv, and the content coverage assessed. Post-coordination matching was applied when needed. Results The final reference set had 1054 unique ADI concepts which were described by 1860 unique terms. Content coverage of SNOMED CT was high (99.9% with pre-coordinated concepts; 100% with post-coordination). The resulting reference set for ADIs was implemented as the interface terminology on OpenMRS data entry forms. Conclusion Different sources demonstrate complementarity in the collection of concepts and terms for an interface terminology. SNOMED CT provides a high coverage in the domain of ADIs. Further work is needed to evaluate the effect of the interface terminology on data quality and quality of care. PMID:26184057

cdc-25.4, a Caenorhabditis elegans Ortholog of cdc25, Is Required for Male Mating Behavior

PubMed Central

Oh, Sangmi; Kawasaki, Ichiro; Park, Jae-Hyung; Shim, Yhong-Hee

2016-01-01

Cell division cycle 25 (cdc25) is an evolutionarily conserved phosphatase that promotes cell cycle progression. Among the four cdc25 orthologs in Caenorhabditis elegans, we found that cdc-25.4 mutant males failed to produce outcrossed progeny. This was not caused by defects in sperm development, but by defects in male mating behavior. The cdc-25.4 mutant males showed various defects during male mating, including contact response, backing, turning, and vulva location. Aberrant turning behavior was the most prominent defect in the cdc-25.4 mutant males. We also found that cdc-25.4 is expressed in many neuronal cells throughout development. The turning defect in cdc-25.4 mutant males was recovered by cdc-25.4 transgenic expression in neuronal cells, suggesting that cdc-25.4 functions in neurons for male mating. However, the neuronal morphology of cdc-25.4 mutant males appeared to be normal, as examined with several neuronal markers. Also, RNAi depletion of wee-1.3, a C. elegans ortholog of Wee1/Myt1 kinase, failed to suppress the mating defects of cdc-25.4 mutant males. These findings suggest that, for successful male mating, cdc-25.4 does not target cell cycles that are required for neuronal differentiation and development. Rather, cdc-25.4 likely regulates noncanonical substrates in neuronal cells. PMID:27770028

cdc-25.4, a Caenorhabditis elegans Ortholog of cdc25, Is Required for Male Mating Behavior.

PubMed

Oh, Sangmi; Kawasaki, Ichiro; Park, Jae-Hyung; Shim, Yhong-Hee

2016-12-07

Cell division cycle 25 (cdc25) is an evolutionarily conserved phosphatase that promotes cell cycle progression. Among the four cdc25 orthologs in Caenorhabditis elegans, we found that cdc-25.4 mutant males failed to produce outcrossed progeny. This was not caused by defects in sperm development, but by defects in male mating behavior. The cdc-25.4 mutant males showed various defects during male mating, including contact response, backing, turning, and vulva location. Aberrant turning behavior was the most prominent defect in the cdc-25.4 mutant males. We also found that cdc-25.4 is expressed in many neuronal cells throughout development. The turning defect in cdc-25.4 mutant males was recovered by cdc-25.4 transgenic expression in neuronal cells, suggesting that cdc-25.4 functions in neurons for male mating. However, the neuronal morphology of cdc-25.4 mutant males appeared to be normal, as examined with several neuronal markers. Also, RNAi depletion of wee-1.3, a C. elegans ortholog of Wee1/Myt1 kinase, failed to suppress the mating defects of cdc-25.4 mutant males. These findings suggest that, for successful male mating, cdc-25.4 does not target cell cycles that are required for neuronal differentiation and development. Rather, cdc-25.4 likely regulates noncanonical substrates in neuronal cells. Copyright © 2016 Oh et al.

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

PubMed

Araujo-Palomares, Cynthia L; Richthammer, Corinna; Seiler, Stephan; Castro-Longoria, Ernestina

2011-01-01

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.

A Review of the Centers for Disease Control and Prevention's Response to the HIV/AIDS Crisis Among Blacks in the United States, 1981–2009

PubMed Central

Jones, Rhondette L.; Wolitski, Richard J.; Cleveland, Janet C.; Dean, Hazel D.; Fenton, Kevin A.

2009-01-01

Among US racial/ethnic groups, Blacks are at the highest risk of acquiring HIV/AIDS. In response, the Centers for Disease Control and Prevention (CDC) has launched the Heightened National Response to Address the HIV/AIDS Crisis Among African Americans, which seeks to engage public and nonpublic partners in a synergistic effort to prevent HIV among Blacks. The CDC also recently launched Act Against AIDS, a campaign to refocus attention on the domestic HIV/AIDS crisis. Although the CDC's efforts to combat HIV/AIDS among Blacks have achieved some success, more must be done to address this crisis. New initiatives include President Obama's goal of developing a National HIV/AIDS Strategy to reduce HIV incidence, decrease HIV-related health disparities, and increase access to care, especially among Blacks and other disproportionately affected populations. PMID:19797748

13 CFR 120.822 - CDC membership.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false CDC membership. 120.822 Section... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.822 CDC membership. (a) CDC Membership. A CDC must have at least 25 members (or stockholders for for-profit CDCs approved...

13 CFR 120.822 - CDC membership.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false CDC membership. 120.822 Section... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.822 CDC membership. (a) CDC Membership. A CDC must have at least 25 members (or stockholders for for-profit CDCs approved...

13 CFR 120.822 - CDC membership.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false CDC membership. 120.822 Section... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.822 CDC membership. (a) CDC Membership. A CDC must have at least 25 members (or stockholders for for-profit CDCs approved...

13 CFR 120.822 - CDC membership.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false CDC membership. 120.822 Section... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.822 CDC membership. (a) CDC Membership. A CDC must have at least 25 members (or stockholders for for-profit CDCs approved...

13 CFR 120.822 - CDC membership.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false CDC membership. 120.822 Section... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.822 CDC membership. (a) CDC Membership. A CDC must have at least 25 members (or stockholders for for-profit CDCs approved...

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

Code of Federal Regulations, 2013 CFR

2013-01-01

... new CDC or for an existing CDC to expand Area of Operations. 120.837 Section 120.837 Business Credit...) Extending A Cdc's Area of Operations § 120.837 SBA decision on application for a new CDC or for an existing CDC to expand Area of Operations. The processing District Office must solicit the comments of any...

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

Code of Federal Regulations, 2014 CFR

2014-01-01

... new CDC or for an existing CDC to expand Area of Operations. 120.837 Section 120.837 Business Credit...) Extending A Cdc's Area of Operations § 120.837 SBA decision on application for a new CDC or for an existing CDC to expand Area of Operations. The processing District Office must solicit the comments of any...

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

Code of Federal Regulations, 2011 CFR

2011-01-01

... new CDC or for an existing CDC to expand Area of Operations. 120.837 Section 120.837 Business Credit...) Extending A Cdc's Area of Operations § 120.837 SBA decision on application for a new CDC or for an existing CDC to expand Area of Operations. The processing District Office must solicit the comments of any...

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

Code of Federal Regulations, 2012 CFR

2012-01-01

... new CDC or for an existing CDC to expand Area of Operations. 120.837 Section 120.837 Business Credit...) Extending A Cdc's Area of Operations § 120.837 SBA decision on application for a new CDC or for an existing CDC to expand Area of Operations. The processing District Office must solicit the comments of any...

Development and use of the generic WHO/CDC logic model for vitamin and mineral interventions in public health programmes

PubMed Central

De-Regil, Luz Maria; Peña-Rosas, Juan Pablo; Flores-Ayala, Rafael; del Socorro Jefferds, Maria Elena

2015-01-01

Objective Nutrition interventions are critical to achieve the Millennium Development Goals; among them, micronutrient interventions are considered cost-effective and programmatically feasible to scale up, but there are limited tools to communicate the programme components and their relationships. The WHO/CDC (Centers for Disease Control and Prevention) logic model for micronutrient interventions in public health programmes is a useful resource for planning, implementation, monitoring and evaluation of these interventions, which depicts the programme theory and expected relationships between inputs and expected Millennium Development Goals. Design The model was developed by applying principles of programme evaluation, public health nutrition theory and programmatic expertise. The multifaceted and iterative structure validation included feedback from potential users and adaptation by national stakeholders involved in public health programmes' design and implementation. Results In addition to the inputs, main activity domains identified as essential for programme development, implementation and performance include: (i) policy; (ii) products and supply; (iii) delivery systems; (iv) quality control; and (v) behaviour change communication. Outputs encompass the access to and coverage of interventions. Outcomes include knowledge and appropriate use of the intervention, as well as effects on micronutrient intake, nutritional status and health of target populations, for ultimate achievement of the Millennium Development Goals. Conclusions The WHO/CDC logic model simplifies the process of developing a logic model by providing a tool that has identified high-priority areas and concepts that apply to virtually all public health micronutrient interventions. Countries can adapt it to their context in order to support programme design, implementation, monitoring and evaluation for the successful scale-up of nutrition interventions in public health. PMID:23507463

Group B Strep Infection in Adults

MedlinePlus

... Y Z # Start of Search Controls Search Form Controls Cancel Submit Search The CDC Group B Strep (GBS) Note: Javascript is disabled or ... R, Farley MM, et al. Risk factors for group B streptococcal disease in adults . Ann Intern Med. 1995;123(6):415–20. Top of Page Related ... HHS/Open USA.gov TOP

Facts about Botulism

MedlinePlus

... Search Controls Search Form Controls Search The CDC Cancel Submit Search The CDC CDC A-Z Index ... Search Controls Search Form Controls Search The CDC Cancel Submit Search The CDC Page Not Found Note: ...

Injuries and Mass Casualty Events

MedlinePlus

... Search Controls Search Form Controls Search The CDC Cancel Submit Search The CDC CDC A-Z Index ... Search Controls Search Form Controls Search The CDC Cancel Submit Search The CDC Page Not Found Note: ...

Introducing routine HIV screening for patients on an internal medicine residency inpatient service: a quality improvement project.

PubMed

Padrnos, Leslie J; Barr, Patrick J; Klassen, Christine L; Fields, Heather E; Azadeh, Natalya; Mendoza, Neil; Saadiq, Rayya A; Pauwels, Emanuel M; King, Christopher S; Chung, Andrew A; Sakata, Kenneth K; Blair, Janis E

2016-01-01

The US Centers for Disease Control and Prevention (CDC) recommend human immunodeficiency virus (HIV) screening for all persons aged 13 to 64 years who present to a health care provider. We sought to improve adherence to the CDC guidelines on the Internal Medicine Resident Hospital Service. We surveyed residents about the CDC guidelines, sent email reminders, provided education, and engaged them in friendly competition. Credit for guideline adherence was awarded if an offer of HIV screening was documented at admission, if a screening test was performed, or if a notation in the resident sign out sheet indicated why screening was not performed. We examined HIV screening of a postintervention group of patients admitted between August 8, 2012, and June 30, 2013, and compared them to a preintervention group admitted between August 1, 2011, and June 30, 2012. Postintervention offers of HIV screening increased significantly (7.9% [44/559] vs 55.5% [300/541]; P<.001), as did documentation of residents' contemplation of screening (8.9% [50/559] vs 67.5% [365/541]; P<.001). A significantly higher proportion of HIV screening tests was ordered postintervention (7.7% [43/559] vs 44.4% [240/541]; P<.001). Monthly HIV screening documentation ranged from 0% (0/53) to 17% (9/53) preintervention, whereas it ranged from 30.6% (11/36) to 100% (62/62) postintervention. HIV screening adherence can be improved through resident education, friendly competition, and system reminders. Barriers to achieving sustained adherence to the CDC guidelines include a heterogeneous patient population and provider discomfort with the subject.

[Analysis on 2011 quality control results on aerobic plate count of microbiology laboratories in China].

PubMed

Han, Haihong; Li, Ning; Li, Yepeng; Fu, Ping; Yu, Dongmin; Li Zhigang; Du, Chunming; Guo, Yunchang

2015-01-01

To test the aerobic plate count examining capability of microbiology laboratories, to ensure the accuracy and comparability of quantitative bacteria examination results, and to improve the quality of monitoring. The 4 different concentration aerobic plate count piece samples were prepared and noted as I, II, III and IV. After homogeneity and stability tests, the samples were delivered to monitoring institutions. The results of I, II, III samples were logarithmic transformed, and evaluated with Z-score method using the robust average and standard deviation. The results of IV samples were evaluated as "satisfactory" when reported as < 10 CFU/piece or as "not satisfactory" otherwise. Pearson χ2 test was used to analyze the ratio results. 309 monitoring institutions, which was 99.04% of the total number, reported their results. 271 institutions reported a satisfactory result, and the satisfactory rate was 87.70%. There was no statistical difference in satisfactory rates of I, II and III samples which were 81.52%, 88.30% and 91.40% respectively. The satisfactory rate of IV samples was 93.33%. There was no statistical difference in satisfactory rates between provincial and municipal CDC. The quality control program has provided scientific data that the aerobic plate count capability of the laboratories meets the requirements of monitoring tasks.

[Expression levels of Cdc2 and Cdc25A mRNA in cattle, yak, and cattle-yak testis].

PubMed

Dong, Li-Yan; Li, Qi-Fa; Qu, Xu-Guang; Li, Yin-Xia; Li, Xin-Fu; Hu, Hong-Tao; Xie, Zhuang

2009-05-01

The infertility of cattle-yak, which is the hybrid offspring of cattle and yak, is a difficult problem in crossbreeding and improvement of yak. Cdc2 and Cdc25A are the key genes of meiosis. The decline of their expression levels will cause the spermatogenesis failure and lead to infertility. Therefore, this study was conducted to study the relationship between the infertility of cattle-yak and the expression levels of Cdc2/Cdc25A genes. The expression profiles were obtained by RT-PCR. Cdc2 and Cdc25A genes were widely expressed in many tissues, which confirmed their important role in cell division and the progression of cell cycle. Real-time quantitative PCR analysis indicated that the expression levels of Cdc2 and Cdc25A in cattle and yak testis were higher than those in cattle-yak (P<0.05). Therefore, low expression levels of Cdc2 and Cdc25A genes may have a relationship with the infertility of cattle-yak.

The Cdc48 Protein and Its Cofactor Vms1 Are Involved in Cdc13 Protein Degradation*

PubMed Central

Baek, Guem Hee; Cheng, Haili; Kim, Ikjin; Rao, Hai

2012-01-01

Vms1 is a newly identified Cdc48-binding protein. The biological function of Vms1 remains obscure. Here, we show that both Cdc48 and Vms1, but not Cdc48 cofactors Ufd1 and Ufd2, are crucial for the degradation of Cdc13, a telomere regulator. Interestingly, both autophagy and the proteasome are involved in Cdc13 turnover. Toxicity associated with accumulation of large amounts of Cdc13 in vms1Δ or autophagy mutants underscores the significance of the proteolytic regulation of Cdc13. Because few ubiquitylated yeast proteins are known to be degraded by autophagy under non-stress conditions, the identification of Cdc13 as a target of autophagy provides a valuable tool to unravel the mechanism of autophagy-mediated selective protein degradation. PMID:22718752

Split Renilla Luciferase Protein Fragment-assisted Complementation (SRL-PFAC) to Characterize Hsp90-Cdc37 Complex and Identify Critical Residues in Protein/Protein Interactions*

PubMed Central

Jiang, Yiqun; Bernard, Denzil; Yu, Yanke; Xie, Yehua; Zhang, Tao; Li, Yanyan; Burnett, Joseph P.; Fu, Xueqi; Wang, Shaomeng; Sun, Duxin

2010-01-01

Hsp90 requires cochaperone Cdc37 to load its clients to the Hsp90 superchaperone complex. The purpose of this study was to utilize split Renilla luciferase protein fragment-assisted complementation (SRL-PFAC) bioluminescence to study the full-length human Hsp90-Cdc37 complex and to identity critical residues and their contributions for Hsp90/Cdc37 interaction in living cells. SRL-PFAC showed that full-length human Hsp90/Cdc37 interaction restored dramatically high luciferase activity through Hsp90-Cdc37-assisted complementation of the N and C termini of luciferase (compared with the set of controls). Immunoprecipitation confirmed that the expressed fusion proteins (NRL-Hsp90 and Cdc37-CRL) preserved their ability to interact with each other and also with native Hsp90 or Cdc37. Molecular dynamic simulation revealed several critical residues in the two interaction patches (hydrophobic and polar) at the interface of Hsp90/Cdc37. Mutagenesis confirmed the critical residues for Hsp90-Cdc37 complex formation. SRL-PFAC bioluminescence evaluated the contributions of these critical residues in Hsp90/Cdc37 interaction. The results showed that mutations in Hsp90 (Q133A, F134A, and A121N) and mutations in Cdc37 (M164A, R167A, L205A, and Q208A) reduced the Hsp90/Cdc37 interaction by 70–95% as measured by the resorted luciferase activity through Hsp90-Cdc37-assisted complementation. In comparison, mutations in Hsp90 (E47A and S113A) and a mutation in Cdc37 (A204E) decreased the Hsp90/Cdc37 interaction by 50%. In contrast, mutations of Hsp90 (R46A, S50A, C481A, and C598A) and mutations in Cdc37 (C54S, C57S, and C64S) did not change Hsp90/Cdc37 interactions. The data suggest that single amino acid mutation in the interface of Hsp90/Cdc37 is sufficient to disrupt its interaction, although Hsp90/Cdc37 interactions are through large regions of hydrophobic and polar interactions. These findings provides a rationale to develop inhibitors for disruption of the Hsp90/Cdc37 interaction. PMID:20413594

Split Renilla luciferase protein fragment-assisted complementation (SRL-PFAC) to characterize Hsp90-Cdc37 complex and identify critical residues in protein/protein interactions.

PubMed

Jiang, Yiqun; Bernard, Denzil; Yu, Yanke; Xie, Yehua; Zhang, Tao; Li, Yanyan; Burnett, Joseph P; Fu, Xueqi; Wang, Shaomeng; Sun, Duxin

2010-07-02

Hsp90 requires cochaperone Cdc37 to load its clients to the Hsp90 superchaperone complex. The purpose of this study was to utilize split Renilla luciferase protein fragment-assisted complementation (SRL-PFAC) bioluminescence to study the full-length human Hsp90-Cdc37 complex and to identity critical residues and their contributions for Hsp90/Cdc37 interaction in living cells. SRL-PFAC showed that full-length human Hsp90/Cdc37 interaction restored dramatically high luciferase activity through Hsp90-Cdc37-assisted complementation of the N and C termini of luciferase (compared with the set of controls). Immunoprecipitation confirmed that the expressed fusion proteins (NRL-Hsp90 and Cdc37-CRL) preserved their ability to interact with each other and also with native Hsp90 or Cdc37. Molecular dynamic simulation revealed several critical residues in the two interaction patches (hydrophobic and polar) at the interface of Hsp90/Cdc37. Mutagenesis confirmed the critical residues for Hsp90-Cdc37 complex formation. SRL-PFAC bioluminescence evaluated the contributions of these critical residues in Hsp90/Cdc37 interaction. The results showed that mutations in Hsp90 (Q133A, F134A, and A121N) and mutations in Cdc37 (M164A, R167A, L205A, and Q208A) reduced the Hsp90/Cdc37 interaction by 70-95% as measured by the resorted luciferase activity through Hsp90-Cdc37-assisted complementation. In comparison, mutations in Hsp90 (E47A and S113A) and a mutation in Cdc37 (A204E) decreased the Hsp90/Cdc37 interaction by 50%. In contrast, mutations of Hsp90 (R46A, S50A, C481A, and C598A) and mutations in Cdc37 (C54S, C57S, and C64S) did not change Hsp90/Cdc37 interactions. The data suggest that single amino acid mutation in the interface of Hsp90/Cdc37 is sufficient to disrupt its interaction, although Hsp90/Cdc37 interactions are through large regions of hydrophobic and polar interactions. These findings provides a rationale to develop inhibitors for disruption of the Hsp90/Cdc37 interaction.

Single-layer group IV-V and group V-IV-III-VI semiconductors: Structural stability, electronic structures, optical properties, and photocatalysis

NASA Astrophysics Data System (ADS)

Lin, Jia-He; Zhang, Hong; Cheng, Xin-Lu; Miyamoto, Yoshiyuki

2017-07-01

Recently, single-layer group III monochalcogenides have attracted both theoretical and experimental interest at their potential applications in photonic devices, electronic devices, and solar energy conversion. Excited by this, we theoretically design two kinds of highly stable single-layer group IV-V (IV =Si ,Ge , and Sn; V =N and P) and group V-IV-III-VI (IV =Si ,Ge , and Sn; V =N and P; III =Al ,Ga , and In; VI =O and S) compounds with the same structures with single-layer group III monochalcogenides via first-principles simulations. By using accurate hybrid functional and quasiparticle methods, we show the single-layer group IV-V and group V-IV-III-VI are indirect bandgap semiconductors with their bandgaps and band edge positions conforming to the criteria of photocatalysts for water splitting. By applying a biaxial strain on single-layer group IV-V, single-layer group IV nitrides show a potential on mechanical sensors due to their bandgaps showing an almost linear response for strain. Furthermore, our calculations show that both single-layer group IV-V and group V-IV-III-VI have absorption from the visible light region to far-ultraviolet region, especially for single-layer SiN-AlO and SnN-InO, which have strong absorption in the visible light region, resulting in excellent potential for solar energy conversion and visible light photocatalytic water splitting. Our research provides valuable insight for finding more potential functional two-dimensional semiconductors applied in optoelectronics, solar energy conversion, and photocatalytic water splitting.

Zebrafish cdc6 hypomorphic mutation causes Meier-Gorlin syndrome-like phenotype.

PubMed

Yao, Likun; Chen, Jing; Wu, Xiaotong; Jia, Shunji; Meng, Anming

2017-11-01

Cell Division Cycle 6 (Cdc6) is a component of pre-replicative complex (preRC) forming on DNA replication origins in eukaryotes. Recessive mutations in ORC1, ORC4, ORC6, CDT1 or CDC6 of the preRC in human cause Meier-Gorlin syndrome (MGS) that is characterized by impaired post-natal growth, short stature and microcephaly. However, vertebrate models of MGS have not been reported. Through N-ethyl-N-nitrosourea mutagenesis and Cas9 knockout, we generate several cdc6 mutant lines in zebrafish. Loss-of-function mutations of cdc6, as manifested by cdc6tsu4305 and cdc6tsu7cd mutants, lead to embryonic lethality due to cell cycle arrest at the S phase and extensive apoptosis. Embryos homozygous for a cdc6 hypomorphic mutation, cdc6tsu21cd, develop normally during embryogenesis. Later on, compared with their wild-type (WT) siblings, cdc6tsu21cd mutant fish show growth retardation, and their body weight and length in adulthood are greatly reduced, which resemble human MGS. Surprisingly, cdc6tsu21cd mutant fish become males with a short life and fail to mate with WT females, suggesting defective reproduction. Overexpression of Cdc6 mutant forms, which mimic human CDC6(T323R) mutation found in a MGS patient, in zebrafish cdc6tsu4305 mutant embryos partially represses cell death phenotype, suggesting that the human CDC6(T323R) mutation is a hypomorph. cdc6tsu21cd mutant fish will be useful to detect more tissue defects and develop medical treatment strategies for MGS patients. © The Author 2017. Published by Oxford University Press.

Zebrafish cdc6 hypomorphic mutation causes Meier-Gorlin syndrome-like phenotype

PubMed Central

Yao, Likun; Chen, Jing; Wu, Xiaotong; Jia, Shunji; Meng, Anming

2017-01-01

Abstract Cell Division Cycle 6 (Cdc6) is a component of pre-replicative complex (preRC) forming on DNA replication origins in eukaryotes. Recessive mutations in ORC1, ORC4, ORC6, CDT1 or CDC6 of the preRC in human cause Meier-Gorlin syndrome (MGS) that is characterized by impaired post-natal growth, short stature and microcephaly. However, vertebrate models of MGS have not been reported. Through N-ethyl-N-nitrosourea mutagenesis and Cas9 knockout, we generate several cdc6 mutant lines in zebrafish. Loss-of-function mutations of cdc6, as manifested by cdc6tsu4305 and cdc6tsu7cd mutants, lead to embryonic lethality due to cell cycle arrest at the S phase and extensive apoptosis. Embryos homozygous for a cdc6 hypomorphic mutation, cdc6tsu21cd, develop normally during embryogenesis. Later on, compared with their wild-type (WT) siblings, cdc6tsu21cd mutant fish show growth retardation, and their body weight and length in adulthood are greatly reduced, which resemble human MGS. Surprisingly, cdc6tsu21cd mutant fish become males with a short life and fail to mate with WT females, suggesting defective reproduction. Overexpression of Cdc6 mutant forms, which mimic human CDC6(T323R) mutation found in a MGS patient, in zebrafish cdc6tsu4305 mutant embryos partially represses cell death phenotype, suggesting that the human CDC6(T323R) mutation is a hypomorph. cdc6tsu21cd mutant fish will be useful to detect more tissue defects and develop medical treatment strategies for MGS patients. PMID:28985365

The Analysis Phase of MITHRAS.

DTIC Science & Technology

1986-06-23

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Carbide-derived carbon (CDC) linear actuator properties in combination with conducting polymers

NASA Astrophysics Data System (ADS)

Kiefer, Rudolf; Aydemir, Nihan; Torop, Janno; Kilmartin, Paul A.; Tamm, Tarmo; Kaasik, Friedrich; Kesküla, Arko; Travas-Sejdic, Jadranka; Aabloo, Alvo

2014-03-01

Carbide-derived Carbon (CDC) material is applied for super capacitors due to their nanoporous structure and their high charging/discharging capability. In this work we report for the first time CDC linear actuators and CDC combined with polypyrrole (CDC-PPy) in ECMD (Electrochemomechanical deformation) under isotonic (constant force) and isometric (constant length) measurements in aqueous electrolyte. CDC-PPy actuators showing nearly double strain under cyclic voltammetric and square wave potential measurements in comparison to CDC linear actuators. The new material is investigated by SEM (scanning electron microscopy) and EDX (energy dispersive X-ray analysis) to reveal how the conducting polymer layer and the CDC layer interfere together.

Fission yeast cdc24(+) encodes a novel replication factor required for chromosome integrity.

PubMed

Gould, K L; Burns, C G; Feoktistova, A; Hu, C P; Pasion, S G; Forsburg, S L

1998-07-01

A mutation within the Schizosaccharomyces pombe cdc24(+) gene was identified previously in a screen for cell division cycle mutants and the cdc24(+) gene was determined to be essential for S phase in this yeast. We have isolated the cdc24(+) gene by complementation of a new temperature-sensitive allele of the gene, cdc24-G1. The DNA sequence predicts the presence of an open reading frame punctuated by six introns which encodes a pioneer protein of 58 kD. A cdc24 null mutant was generated by homologous recombination. Haploid cells lacking cdc24(+) are inviable, indicating that cdc24(+) is an essential gene. The transcript of cdc24(+) is present at constant levels throughout the cell cycle. Cells lacking cdc24(+) function show a checkpoint-dependent arrest with a 2N DNA content, indicating a block late in S phase. Arrest is accompanied by a rapid loss of viability and chromosome breakage. An S. pombe homolog of the replicative DNA helicase DNA2 of S. cerevisiae suppresses cdc24. These results suggest that Cdc24p plays a role in the progression of normal DNA replication and is required to maintain genomic integrity.

Fission yeast cdc24(+) encodes a novel replication factor required for chromosome integrity.

PubMed Central

Gould, K L; Burns, C G; Feoktistova, A; Hu, C P; Pasion, S G; Forsburg, S L

1998-01-01

A mutation within the Schizosaccharomyces pombe cdc24(+) gene was identified previously in a screen for cell division cycle mutants and the cdc24(+) gene was determined to be essential for S phase in this yeast. We have isolated the cdc24(+) gene by complementation of a new temperature-sensitive allele of the gene, cdc24-G1. The DNA sequence predicts the presence of an open reading frame punctuated by six introns which encodes a pioneer protein of 58 kD. A cdc24 null mutant was generated by homologous recombination. Haploid cells lacking cdc24(+) are inviable, indicating that cdc24(+) is an essential gene. The transcript of cdc24(+) is present at constant levels throughout the cell cycle. Cells lacking cdc24(+) function show a checkpoint-dependent arrest with a 2N DNA content, indicating a block late in S phase. Arrest is accompanied by a rapid loss of viability and chromosome breakage. An S. pombe homolog of the replicative DNA helicase DNA2 of S. cerevisiae suppresses cdc24. These results suggest that Cdc24p plays a role in the progression of normal DNA replication and is required to maintain genomic integrity. PMID:9649516

cdc-25.2, a C. elegans ortholog of cdc25, is required to promote oocyte maturation.

PubMed

Kim, Jiyoung; Kawasaki, Ichiro; Shim, Yhong-Hee

2010-03-15

Cdc25 is an evolutionarily conserved protein phosphatase that promotes progression through the cell cycle. Some metazoans have multiple isoforms of Cdc25, which have distinct functions and different expression patterns during development. C. elegans has four cdc-25 genes. cdc-25.1 is required for germline mitotic proliferation. To determine if the other members of the cdc-25 family also contribute to regulation of cell division in the germ line, we examined phenotypes of loss-of-function mutants of the other cdc-25 family genes. We found that cdc-25.2 is also essential for germline development. cdc-25.2 homozygous mutant hermaphrodites exhibited sterility as a result of defects in oogenesis: mutant oocytes were arrested as endomitotic oocytes that were not fertilized successfully. Spermatogenesis and male germline development were not affected. Through genetic interaction studies, we found that CDC-25.2 functions upstream of maturation-promoting factor containing CDK-1 and CYB-3 to promote oocyte maturation by counteracting function of WEE-1.3. We propose that cdc-25 family members function as distinct but related cell cycle regulators to control diverse cell cycles in C. elegans germline development.

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

PubMed

Liu, Huiquan; Zhang, Shijie; Ma, Jiwen; Dai, Yafeng; Li, Chaohui; Lyu, Xueliang; Wang, Chenfang; Xu, Jin-Rong

2015-06-01

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 indicate that cell cycle regulation is different between vegetative and infectious hyphae in F. graminearum and Cdc2A, possibly by interacting with a stage-specific cyclin, plays a more important role than Cdc2B during ascosporogenesis and plant infection.

CDC25AQ110del: A Novel Cell Division Cycle 25A Isoform Aberrantly Expressed in Non-Small Cell Lung Cancer

PubMed Central

Younis, Rania H.; Cao, Wei; Lin, Ruxian; Xia, Ronghui; Liu, Zhenqiu; Edelman, Martin J.; Mei, Yuping; Mao, Li; Ren, Hening

2012-01-01

Objective Lung cancer remains number one cause of cancer related deaths worldwide. Cell cycle deregulation plays a major role in the pathogenesis of Non-Small Cell Lung Cancer (NSCLC). CDC25A represents a critical cell cycle regulator that enhances cell cycle progression. In this study we aimed to investigate the role of a novel CDC25A transcriptional variant, CDC25AQ110del, on the regulation of the CDC25A protein, and its impact on prognosis of NSCLC patients. Methodology/Principal Findings Here we report a novel CDC25A transcript variant with codon 110 (Glutamine) deletion, that we termed CDC25AQ110del in NSCLC cells. In 9 (75%) of the 12 NSCLC cell lines, CDC25AQ110del expression accounted for more than 20% of the CDC25A transcripts. Biological effects of CDC25AQ110del were investigated in H1299 and HEK-293F cells using UV radiation, flowcytometry, cyclohexamide treatment, and confocal microscopy. Compared to CDC25Awt, CDC25AQ110del protein had longer half-life; cells expressing CDC25AQ110del were more resistant to UV irradiation and showed more mitotic activity. Taqman-PCR was used to quantify CDC25AQ110del expression levels in 88 primary NSCLC tumor/normal tissue pairs. In patients with NSCLC, Kaplan Meier curves showed tumors expressing higher levels of CDC25AQ110del relative to the adjacent lung tissues to have significantly inferior overall survival (P = .0018). Significance Here we identified CDC25AQ110del as a novel transcriptional variant of CDC25A in NSCLC. The sequence-specific nature of the abnormality could be a prognostic indicator in NSCLC patients as well as a candidate target for future therapeutic strategies. PMID:23071577

Relating calls to US poison centers for potential exposures to medications to Centers for Disease Control and Prevention reporting of influenza-like illness.

PubMed

Beauchamp, Gillian A; McKeown, Nathanael J; Rodriguez, Sergio; Spyker, Daniel A

2016-03-01

The Centers for Disease Control (CDC) monitors influenza like illness (ILI) and the National Poison Data System (NPDS) warehouses call data uploaded by US poison centers regarding reported exposures to medication. We examined the relationship between calls to poison centers regarding reported exposures to medications commonly used to treat ILI and weekly reports of ILI. The CDC reports ILI, by age group, for each of 10 Health and Human Services (HHS) regions. We examined NPDS summary data from calls reported to poison centers regarding reported exposures to acetaminophen, cough/cold medications, and promethazine, for the same weeks, age groups, and HHS regions for influenza seasons 2000-2013. ILI and NPDS exposures were examined using graphical plots, descriptive statistics, stepwise regression analysis, and Geographic Information Systems (GIS). About 5,101,841 influenza-like illness cases were reported to the CDC, and 2,122,940 calls regarding reported exposures to medications commonly used to treat ILI, were reported by poison centers to the NPDS over the 13 flu seasons. Analysis of stepwise models of the linear untransformed data involving 24 NPDS data groups and for 60 ILI measures, over the 13 influenza seasons, demonstrated that reported exposures to medications used to treat ILI correlated with reported cases of ILI with a median R(2 )=( )0.489 (min R(2 )=( )0.248, max R(2 )=( )0.717), with mean ± SD of R(2 )=( )0.494 ± 0.121. Median number of parameters used (degrees of freedom - 1) was 7. NPDS data regarding poison center calls for selected ILI medication exposures were highly correlated with CDC ILI data. Since NPDS data are available in real time, it provides complimentary ILI monitoring. This approach may provide public health value in predicting other illnesses which are not currently as thoroughly monitored.

Fast Facts about Group B Strep and Pregnancy

MedlinePlus

... Y Z # Start of Search Controls Search Form Controls Cancel Submit Search The CDC Group B Strep (GBS) Note: Javascript is disabled or ... people’s bodies without symptoms. The rate of serious group B strep disease increases with age. The average age of cases in non-pregnant adults is about 60 years old. ... HHS/Open USA.gov TOP

Roseomonas, a new genus associated with bacteremia and other human infections.

PubMed Central

Rihs, J D; Brenner, D J; Weaver, R E; Steigerwalt, A G; Hollis, D G; Yu, V L

1993-01-01

In the 1980s, a pink bacterium different from species of the genus Methylobacterium was implicated in human infection. Using biochemical tests and DNA hybridization, we examined 42 strains of pink-pigmented, gram-negative bacteria that were not members of the genus Methylobacterium. The isolates included 6 strains each of CDC "pink coccoid" groups I, II, III, and IV; 10 isolates from Gilardi's "unnamed taxon"; and 8 blood isolates from ill, debilitated, or immunosuppressed patients. The DNA hybridization studies supported the creation of six genomospecies encompassing the 42 strains. Reactions for esculin hydrolysis, glycerol oxidation, and D-mannose oxidation enabled separation of genomospecies 1 through 4. These tests, as well as motility, nitrate reduction, citrate utilization, and oxidation of L-arabinose, D-galactose, and D-xylose, differentiated genomospecies 5 and 6 from each other and from genomospecies 1 through 4. These organisms were susceptible in vitro to the aminoglycosides, tetracycline, and imipenem and generally susceptible to the quinolones. We propose the new genus, Roseomonas, for these bacteria to include three named species, Roseomonas gilardii sp. nov., Roseomonas cervicalis sp. nov., and Roseomonas fauriae sp. nov., and three unnamed genomospecies. Images PMID:8308122

Cell cycle entry triggers a switch between two modes of Cdc42 activation during yeast polarization

PubMed Central

Witte, Kristen; Strickland, Devin; Glotzer, Michael

2017-01-01

Cell polarization underlies many cellular and organismal functions. The GTPase Cdc42 orchestrates polarization in many contexts. In budding yeast, polarization is associated with a focus of Cdc42•GTP which is thought to self sustain by recruiting a complex containing Cla4, a Cdc42-binding effector, Bem1, a scaffold, and Cdc24, a Cdc42 GEF. Using optogenetics, we probe yeast polarization and find that local recruitment of Cdc24 or Bem1 is sufficient to induce polarization by triggering self-sustaining Cdc42 activity. However, the response to these perturbations depends on the recruited molecule, the cell cycle stage, and existing polarization sites. Before cell cycle entry, recruitment of Cdc24, but not Bem1, induces a metastable pool of Cdc42 that is sustained by positive feedback. Upon Cdk1 activation, recruitment of either Cdc24 or Bem1 creates a stable site of polarization that induces budding and inhibits formation of competing sites. Local perturbations have therefore revealed unexpected features of polarity establishment. DOI: http://dx.doi.org/10.7554/eLife.26722.001 PMID:28682236

Caffeine stabilizes Cdc25 independently of Rad3 in S chizosaccharomyces pombe contributing to checkpoint override

PubMed Central

Alao, John P; Sjölander, Johanna J; Baar, Juliane; Özbaki-Yagan, Nejla; Kakoschky, Bianca; Sunnerhagen, Per

2014-01-01

Cdc25 is required for Cdc2 dephosphorylation and is thus essential for cell cycle progression. Checkpoint activation requires dual inhibition of Cdc25 and Cdc2 in a Rad3-dependent manner. Caffeine is believed to override activation of the replication and DNA damage checkpoints by inhibiting Rad3-related proteins in both S chizosaccharomyces pombe and mammalian cells. In this study, we have investigated the impact of caffeine on Cdc25 stability, cell cycle progression and checkpoint override. Caffeine induced Cdc25 accumulation in S . pombe independently of Rad3. Caffeine delayed cell cycle progression under normal conditions but advanced mitosis in cells treated with replication inhibitors and DNA-damaging agents. In the absence of Cdc25, caffeine inhibited cell cycle progression even in the presence of hydroxyurea or phleomycin. Caffeine induces Cdc25 accumulation in S . pombe by suppressing its degradation independently of Rad3. The induction of Cdc25 accumulation was not associated with accelerated progression through mitosis, but rather with delayed progression through cytokinesis. Caffeine-induced Cdc25 accumulation appears to underlie its ability to override cell cycle checkpoints. The impact of Cdc25 accumulation on cell cycle progression is attenuated by Srk1 and Mad2. Together our findings suggest that caffeine overrides checkpoint enforcement by inducing the inappropriate nuclear localization of Cdc25. PMID:24666325

Estimating global, regional and national rotavirus deaths in children aged <5 years: Current approaches, new analyses and proposed improvements.

PubMed

Clark, Andrew; Black, Robert; Tate, Jacqueline; Roose, Anna; Kotloff, Karen; Lam, Diana; Blackwelder, William; Parashar, Umesh; Lanata, Claudio; Kang, Gagandeep; Troeger, Christopher; Platts-Mills, James; Mokdad, Ali; Sanderson, Colin; Lamberti, Laura; Levine, Myron; Santosham, Mathuram; Steele, Duncan

2017-01-01

Rotavirus is a leading cause of diarrhoeal mortality in children but there is considerable disagreement about how many deaths occur each year. We compared CHERG, GBD and WHO/CDC estimates of age under 5 years (U5) rotavirus deaths at the global, regional and national level using a standard year (2013) and standard list of 186 countries. The global estimates were 157,398 (CHERG), 122,322 (GBD) and 215,757 (WHO/CDC). The three groups used different methods: (i) to select data points for rotavirus-positive proportions; (ii) to extrapolate data points to individual countries; (iii) to account for rotavirus vaccine coverage; (iv) to convert rotavirus-positive proportions to rotavirus attributable fractions; and (v) to calculate uncertainty ranges. We conducted new analyses to inform future estimates. We found that acute watery diarrhoea was associated with 87% (95% CI 83-90%) of U5 diarrhoea hospitalisations based on data from 84 hospital sites in 9 countries, and 65% (95% CI 57-74%) of U5 diarrhoea deaths based on verbal autopsy reports from 9 country sites. We reanalysed data from the Global Enteric Multicenter Study (GEMS) and found 44% (55% in Asia, and 32% in Africa) rotavirus-positivity among U5 acute watery diarrhoea hospitalisations, and 28% rotavirus-positivity among U5 acute watery diarrhoea deaths. 97% (95% CI 95-98%) of the U5 diarrhoea hospitalisations that tested positive for rotavirus were entirely attributable to rotavirus. For all clinical syndromes combined the rotavirus attributable fraction was 34% (95% CI 31-36%). This increased by a factor of 1.08 (95% CI 1.02-1.14) when the GEMS results were reanalysed using a more sensitive molecular test. We developed consensus on seven proposals for improving the quality and transparency of future rotavirus mortality estimates.

Estimating global, regional and national rotavirus deaths in children aged <5 years: Current approaches, new analyses and proposed improvements

PubMed Central

Black, Robert; Tate, Jacqueline; Roose, Anna; Kotloff, Karen; Parashar, Umesh; Lanata, Claudio; Kang, Gagandeep; Troeger, Christopher; Platts-Mills, James; Mokdad, Ali; Sanderson, Colin; Lamberti, Laura; Santosham, Mathuram; Steele, Duncan

2017-01-01

Background Rotavirus is a leading cause of diarrhoeal mortality in children but there is considerable disagreement about how many deaths occur each year. Methods and findings We compared CHERG, GBD and WHO/CDC estimates of age under 5 years (U5) rotavirus deaths at the global, regional and national level using a standard year (2013) and standard list of 186 countries. The global estimates were 157,398 (CHERG), 122,322 (GBD) and 215,757 (WHO/CDC). The three groups used different methods: (i) to select data points for rotavirus-positive proportions; (ii) to extrapolate data points to individual countries; (iii) to account for rotavirus vaccine coverage; (iv) to convert rotavirus-positive proportions to rotavirus attributable fractions; and (v) to calculate uncertainty ranges. We conducted new analyses to inform future estimates. We found that acute watery diarrhoea was associated with 87% (95% CI 83–90%) of U5 diarrhoea hospitalisations based on data from 84 hospital sites in 9 countries, and 65% (95% CI 57–74%) of U5 diarrhoea deaths based on verbal autopsy reports from 9 country sites. We reanalysed data from the Global Enteric Multicenter Study (GEMS) and found 44% (55% in Asia, and 32% in Africa) rotavirus-positivity among U5 acute watery diarrhoea hospitalisations, and 28% rotavirus-positivity among U5 acute watery diarrhoea deaths. 97% (95% CI 95–98%) of the U5 diarrhoea hospitalisations that tested positive for rotavirus were entirely attributable to rotavirus. For all clinical syndromes combined the rotavirus attributable fraction was 34% (95% CI 31–36%). This increased by a factor of 1.08 (95% CI 1.02–1.14) when the GEMS results were reanalysed using a more sensitive molecular test. Conclusions We developed consensus on seven proposals for improving the quality and transparency of future rotavirus mortality estimates. PMID:28892480

76 FR 73647 - National Healthy Worksite Program; Information Webinar Series

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-29

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Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-17

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Federal Register 2010, 2011, 2012, 2013, 2014

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Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-12

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75 FR 34459 - National Center for Injury Prevention and Control/Initial Review Group, (NCIPC/IRG)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Center for Injury Prevention and Control/Initial Review Group, (NCIPC/IRG) Correction: This notice was... Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control and Prevention (CDC), announces...

Cdc6 is regulated by E2F and is essential for DNA replication in mammalian cells.

PubMed

Yan, Z; DeGregori, J; Shohet, R; Leone, G; Stillman, B; Nevins, J R; Williams, R S

1998-03-31

Cdc6 has a critical regulatory role in the initiation of DNA replication in yeasts, but its function in mammalian cells has not been characterized. We show here that Cdc6 is expressed selectively in proliferating but not quiescent mammalian cells, both in culture and within tissues of intact animals. During the transition from a growth-arrested to a proliferative state, transcription of mammalian Cdc6 is regulated by E2F proteins, as revealed by a functional analysis of the human Cdc6 promoter and by the ability of exogenously expressed E2F proteins to stimulate the endogenous Cdc6 gene. Immunodepletion of Cdc6 by microinjection of anti-Cdc6 antibody blocks initiation of DNA replication in a human tumor cell line. We conclude that expression of human Cdc6 is regulated in response to mitogenic signals though transcriptional control mechanisms involving E2F proteins, and that Cdc6 is required for initiation of DNA replication in mammalian cells.

Identification of cdc25 gene in pinewood nematode, Bursaphelenchus xylophilus, and its function in reproduction.

PubMed

Choi, Ye-Na; Oh, Bong-Kyeong; Kawasaki, Ichiro; Oh, Wan-Suk; Lee, Yi; Paik, Young-Ki; Shim, Yhong-Hee

2010-02-28

The cdc25 gene, which is highly conserved in many eukaryotes, encodes a phosphatase that plays essential roles in cell cycle regulation. We identified a cdc25 ortholog in the pinewood nematode, Bursaphelenchus xylophilus. The B. xylophilus ortholog (Bx-cdc25) was found to be highly similar to Caenorhabditis elegans cdc-25.2 in sequence as well as in gene structure, both having long intron 1. The Bx-cdc25 gene was determined to be composed of seven exons and six introns in a 2,580 bp region, and was shown to encode 360 amino acids of a protein containing a highly-conserved phosphatase domain. Bx-cdc25 mRNA was hardly detectable throughout the juvenile stages but was highly expressed in eggs and in both female and male adults. Functional conservation during germline development between C. elegans cdc25 and Bx-cdc25 was revealed by Bx-cdc25 RNA interference in C. elegans.

Recurrent Kawasaki disease: USA and Japan.

PubMed

Maddox, Ryan A; Holman, Robert C; Uehara, Ritei; Callinan, Laura S; Guest, Jodie L; Schonberger, Lawrence B; Nakamura, Yosikazu; Yashiro, Mayumi; Belay, Ermias D

2015-12-01

Descriptive epidemiologic studies of recurrent and non-recurrent Kawasaki disease (KD) may identify other potentially important differences between these illnesses. Data from the USA and Japan, the Centers for Disease Control and Prevention (CDC) national KD surveillance(1984-2008) and the 17th Japanese nationwide survey (2001-2002), respectively, were analyzed to examine recurrent KD patients <18 years of age meeting the CDC KD case or atypical KD case definition. These patients were compared with non-recurrent KD patients. Of the 5557 US KD patients <18 years of age during 1984-2008, 97 (1.7%) were identified as having had recurrent KD. Among the US Asian/Pacific Islander KD patients, 3.5% had recurrent KD, which was similar to the percentage identified among KD patients (3.5%) in the Japanese survey. Compared with non-recurrent KD patients, KD patients [with recurrent KD] were more likely to be older, fulfill the atypical KD case definition, and have coronary artery abnormalities (CAA) despite i.v. immunoglobulin (IVIG) treatment. Differences in the age, race, and frequency of CAA exist between recurrent and non-recurrent KD patients. The increased association of CAA with recurrent KD suggests that more aggressive treatment strategies in conjunction with IVIG may be indicated for the second episode of KD. © 2015 Japan Pediatric Society.

A novel functional domain of Cdc15 kinase is required for its interaction with Tem1 GTPase in Saccharomyces cerevisiae.

PubMed Central

Asakawa, K; Yoshida, S; Otake, F; Toh-e, A

2001-01-01

Exit from mitosis requires the inactivation of cyclin-dependent kinase (CDK) activity. In the budding yeast Saccharomyces cerevisiae, a number of gene products have been identified as components of the signal transduction network regulating inactivation of CDK (called the MEN, for the mitotic exit network). Cdc15, one of such components of the MEN, is an essential protein kinase. By the two-hybrid screening, we identified Cdc15 as a binding protein of Tem1 GTPase, another essential regulator of the MEN. Coprecipitation experiments revealed that Tem1 binds to Cdc15 in vivo. By deletion analysis, we found that the Tem1-binding domain resides near the conserved kinase domain of Cdc15. The cdc15-LF mutation, which was introduced into the Tem1-binding domain, reduced the interaction with Cdc15 and Tem1 and caused temperature-sensitive growth.The kinase activity of Cdc15 was not so much affected by the cdc15-LF mutation. However, Cdc15-LF failed to localize to the SPB at the restrictive temperature. Our data show that the interaction with Tem1 is important for the function of Cdc15 and that Cdc15 and Tem1 function in a complex to direct the exit from mitosis. PMID:11290702

Signaling Cascades Governing Cdc42-Mediated Chondrogenic Differentiation and Mensenchymal Condensation.

PubMed

Wang, Jirong R; Wang, Chaojun J; Xu, Chengyun Y; Wu, Xiaokai K; Hong, Dun; Shi, Wei; Gong, Ying; Chen, Haixiao X; Long, Fanxin; Wu, Ximei M

2016-03-01

Endochondral ossification consists of successive steps of chondrocyte differentiation, including mesenchymal condensation, differentiation of chondrocytes, and hypertrophy followed by mineralization and ossification. Loss-of-function studies have revealed that abnormal growth plate cartilage of the Cdc42 mutant contributes to the defects in endochondral bone formation. Here, we have investigated the roles of Cdc42 in osteogenesis and signaling cascades governing Cdc42-mediated chondrogenic differentiation. Though deletion of Cdc42 in limb mesenchymal progenitors led to severe defects in endochondral ossification, either ablation of Cdc42 in limb preosteoblasts or knockdown of Cdc42 in vitro had no obvious effects on bone formation and osteoblast differentiation. However, in Cdc42 mutant limb buds, loss of Cdc42 in mesenchymal progenitors led to marked inactivation of p38 and Smad1/5, and in micromass cultures, Cdc42 lay on the upstream of p38 to activate Smad1/5 in bone morphogenetic protein-2-induced mesenchymal condensation. Finally, Cdc42 also lay on the upstream of protein kinase B to transactivate Sox9 and subsequently induced the expression of chondrocyte differential marker in transforming growth factor-β1-induced chondrogenesis. Taken together, by using biochemical and genetic approaches, we have demonstrated that Cdc42 is involved not in osteogenesis but in chondrogenesis in which the BMP2/Cdc42/Pak/p38/Smad signaling module promotes mesenchymal condensation and the TGF-β/Cdc42/Pak/Akt/Sox9 signaling module facilitates chondrogenic differentiation. Copyright © 2016 by the Genetics Society of America.

Evaluation and improvement of real-time PCR assays targeting lytA, ply, and psaA genes for detection of pneumococcal DNA.

PubMed

Carvalho, Maria da Gloria S; Tondella, Maria Lucia; McCaustland, Karen; Weidlich, Luciana; McGee, Lesley; Mayer, Leonard W; Steigerwalt, Arnold; Whaley, Melissa; Facklam, Richard R; Fields, Barry; Carlone, George; Ades, Edwin W; Dagan, Ron; Sampson, Jacquelyn S

2007-08-01

The accurate diagnosis of pneumococcal disease has frequently been hampered not only by the difficulties in obtaining isolates of the organism from patient specimens but also by the misidentification of pneumococcus-like viridans group streptococci (P-LVS) as Streptococcus pneumoniae. This is especially critical when the specimen comes from the respiratory tract. In this study, three novel real-time PCR assays designed for the detection of specific sequence regions of the lytA, ply, and psaA genes were developed (lytA-CDC, ply-CDC, and psaA, respectively). These assays showed high sensitivity (<10 copies for lytA-CDC and ply-CDC and an approximately twofold less sensitivity for psaA). Two additional real-time PCR assays for lytA and ply described previously for pneumococcal DNA detection were also evaluated. A panel of isolates consisting of 67 S. pneumoniae isolates (44 different serotypes and 3 nonencapsulated S. pneumoniae isolates from conjunctivitis outbreaks) and 104 nonpneumococcal isolates was used. The 67 S. pneumoniae isolates were reactive in all five assays. The new real-time detection assays targeting the lytA and psaA genes were the most specific for the detection of isolates confirmed to be S. pneumoniae, with lytA-CDC showing the greatest specificity. Both ply PCRs were positive for all isolates of S. pseudopneumoniae, along with 13 other isolates of other P-LVS isolates confirmed to be non-S. pneumoniae by DNA-DNA reassociation. Thus, the use of the ply gene for the detection of pneumococci can lead to false-positive reactions in the presence of P-LVS. The five assays were applied to 15 culture-positive cerebrospinal fluid specimens with 100% sensitivity; and serum and ear fluid specimens were also evaluated. Both the lytA-CDC and psaA assays, particularly the lytA-CDC assay, have improved specificities compared with those of currently available assays and should therefore be considered the assays of choice for the detection of pneumococcal DNA, particularly when upper respiratory P-LVS might be present in the clinical specimen.

77 FR 16508 - National Emission Standards for Hazardous Air Pollutant Emissions: Group IV Polymers and Resins...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-21

... National Emission Standards for Hazardous Air Pollutant Emissions: Group IV Polymers and Resins; Pesticide... Hazardous Air Pollutant Emissions: Group IV Polymers and Resins; National Emission Standards for Hazardous... proposed rule titled, National Emission Standards for Hazardous Air Pollutant Emissions: Group IV Polymers...

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

Code of Federal Regulations, 2014 CFR

2014-01-01

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

13 CFR 120.810 - Applications for certification as a CDC.

Code of Federal Regulations, 2011 CFR

2011-01-01

... a CDC. 120.810 Section 120.810 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Certification Procedures to Become A Cdc § 120.810 Applications for certification as a CDC. (a) An applicant for certification as a CDC must apply to the SBA...

13 CFR 120.810 - Applications for certification as a CDC.

Code of Federal Regulations, 2012 CFR

2012-01-01

... a CDC. 120.810 Section 120.810 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Certification Procedures to Become A Cdc § 120.810 Applications for certification as a CDC. (a) An applicant for certification as a CDC must apply to the SBA...

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

Code of Federal Regulations, 2010 CFR

2010-01-01

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

13 CFR 120.810 - Applications for certification as a CDC.

Code of Federal Regulations, 2014 CFR

2014-01-01

... a CDC. 120.810 Section 120.810 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Certification Procedures to Become A Cdc § 120.810 Applications for certification as a CDC. (a) An applicant for certification as a CDC must apply to the SBA...

13 CFR 120.810 - Applications for certification as a CDC.

Code of Federal Regulations, 2013 CFR

2013-01-01

... a CDC. 120.810 Section 120.810 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Certification Procedures to Become A Cdc § 120.810 Applications for certification as a CDC. (a) An applicant for certification as a CDC must apply to the SBA...

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

Code of Federal Regulations, 2011 CFR

2011-01-01

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

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

Code of Federal Regulations, 2013 CFR

2013-01-01

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

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

Code of Federal Regulations, 2012 CFR

2012-01-01

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

Comparative Field Evaluation of Different Traps for Collecting Adult Phlebotomine Sand Flies (Diptera: Psychodidae) in an Endemic Area of Cutaneous Leishmaniasis in Quintana Roo, Mexico.

PubMed

Rodríguez-Rojas, Jorge J; Arque-Chunga, Wilfredo; Fernández-Salas, Ildefonso; Rebollar-Téllez, Eduardo A

2016-06-01

Phlebotominae are the vectors of Leishmania parasites. It is important to have available surveillance and collection methods for the sand fly vectors. The objectives of the present study were to evaluate and compare traps for the collection of sand fly species and to analyze trap catches along months and transects. Field evaluations over a year were conducted in an endemic area of leishmaniasis in the state of Quintana Roo, Mexico. A randomized-block design was implemented in study area with tropical rainforest vegetation. The study design utilized 4 transects with 11 trap types: 1) Centers for Disease Control and Prevention (CDC) light trap with incandescent bulb (CDC-I), 2) CDC light trap with blue light-emitting diodes (LEDs) (CDC-B), 3) CDC light trap with white LEDs (CDC-W), 4) CDC light trap with red LEDs (CDC-R), 5) CDC light trap with green LEDs (CDC-G), 6) Disney trap, 7) Disney trap with white LEDs, 8) sticky panels, 9) sticky panels with white LEDs, 10) delta-like trap, and 11) delta-like trap with white LEDs. A total of 1,014 specimens of 13 species and 2 genera (Lutzomyia and Brumptomyia) were collected. There were significant differences in the mean number of sand flies caught with the 11 traps; CDC-I was (P  =  0.0000) more effective than the other traps. Other traps exhibited the following results: CDC-W (17.46%), CDC-B (15.68%), CDC-G (14.89%), and CDC-R (14.30%). The relative abundance of different species varied according to trap types used, and the CDC-I trap attracted more specimens of the known vectors of Leishmania spp., such as like Lutzomyia cruciata, Lu. shannoni, and Lu. ovallesi. Disney trap captured more specimens of Lu. olmeca olmeca. Based on abundance and number of species, CDC light traps and Disney traps appeared to be good candidates for use in vector surveillance programs in this endemic area of Mexico.

Consumer Directed Care in Australia: early perceptions and experiences of staff, clients and carers.

PubMed

Gill, Liz; McCaffrey, Nikki; Cameron, Ian D; Ratcliffe, Julie; Kaambwa, Billingsley; Corlis, Megan; Fiebig, Jeff; Gresham, Meredith

2017-03-01

The study aimed to identify the shared issues and challenges being experienced by staff, their clients and informal carers, with the introduction of Consumer Directed Care (CDC). Secondary analysis was undertaken of data that had been initially collected, via semi-structured in-depth interviews, to inform the development of a discrete choice experiment. The raw staff and client/carer data were re-examined using an iterative inductive process. The analysis focused on locating the shared themes and differences between the participant groups based on their CDC experience. The data were also assessed for difficulties or barriers that impacted on the service. Four broad shared themes were derived: culture, role change, operational systems and resourcing, but with a range of diverse and sometimes conflicting sub-themes between the different participant groups. Differences can be linked to participant role in the service chain, with discordance emerging between what has been traditionally offered and what might be possible. This investigation occurred during the period in which services were transitioning from a traditional aged care service model to a new model of service provision requiring considerable industry change. We conclude that existing industry regulation, culture and practice supports an established service model in Australia that arguably makes translation of the objectives of CDC difficult. © 2016 John Wiley & Sons Ltd.

Group B Streptococcus prophylaxis in patients who report a penicillin allergy: a follow-up study.

PubMed

Critchfield, Agatha S; Lievense, Stacey P; Raker, Christina A; Matteson, Kristen A

2011-02-01

The purpose of this study was to compare adherence to the 2002 Centers for Disease Control (CDC) guidelines for the prevention of perinatal group B Streptococcus (GBS) disease in patients who are allergic to penicillin during the years 2004-2006 and 2008. Previous data from our institution revealed suboptimal adherence to the 2002 CDC guidelines for GBS prophylaxis among women who are allergic to penicillin. These data caused the hospital to implement a series of interventions. The original cohort (2004-2006) was compared with a cohort of women who delivered between April 2008 and January 2009 (n = 74) to determine whether the proportion of women who had antimicrobial sensitivity testing and who had received an appropriate antibiotic had improved. In 2008, 76% (95% confidence interval, 66-84%) of GBS-positive women who are allergic to penicillin received an appropriate antibiotic (compared with 16.2% in 2004-2006; P < .001). Antimicrobial sensitivity testing was performed in 79.4% of cases (95% confidence interval, 68-87%), compared with 11.4% in 2004-2006 (P < .001). With directed intervention, adherence to the 2002 CDC guidelines for GBS prophylaxis in women who are allergic to penicillin improved dramatically. Copyright © 2011 Mosby, Inc. All rights reserved.

Hospitalization Costs for Patients Undergoing Orthopedic Surgery Treated With Intravenous Acetaminophen (IV-APAP) Plus Other IV Analgesics or IV Opioid Monotherapy for Postoperative Pain.

PubMed

Maiese, Brett A; Pham, An T; Shah, Manasee V; Eaddy, Michael T; Lunacsek, Orsolya E; Wan, George J

2017-02-01

To assess the impact on hospitalization costs of multimodal analgesia (MMA), including intravenous acetaminophen (IV-APAP), versus IV opioid monotherapy for postoperative pain management in patients undergoing orthopedic surgery. Utilizing the Truven Health MarketScan ® Hospital Drug Database (HDD), patients undergoing total knee arthroplasty (TKA), total hip arthroplasty (THA), or surgical repair of hip fracture between 1/1/2011 and 8/31/2014 were separated into postoperative pain management groups: MMA with IV-APAP plus other IV analgesics (IV-APAP group) or an IV opioid monotherapy group. All patients could have received oral analgesics. Baseline characteristics and total hospitalization costs were compared. Additionally, an inverse probability treatment weighting [IPTW] with propensity scores analysis further assessed hospitalization cost differences. The IV-APAP group (n = 33,954) and IV opioid monotherapy group (n = 110,300) differed significantly (P < 0.0001) across baseline characteristics, though the differences may not have been clinically meaningful. Total hospitalization costs (mean ± standard deviation) were significantly lower for the IV-APAP group than the IV opioid monotherapy group (US$12,540 ± $9564 vs. $13,242 ± $35,825; P < 0.0001). Medical costs accounted for $701 of the $702 between-group difference. Pharmacy costs were similar between groups. Results of the IPTW-adjusted analysis further supported the statistically significant cost difference. Patients undergoing orthopedic surgery who received MMA for postoperative pain management, including IV-APAP, had significantly lower total costs than patients who received IV opioid monotherapy. This difference was driven by medical costs; importantly, there was no difference in pharmacy costs. Generalizability of the results may be limited to patients admitted to hospitals similar to those included in HDD. Dosing could not be determined, so it was not possible to quantify utilization of IV-APAP or ascertain differences in opioid consumption between the 2 groups. This study did not account for healthcare utilization post-discharge.

Traumatic Brain Injury (TBI) Data and Statistics

MedlinePlus

... data.cdc.gov . Emergency Department Visits, Hospitalizations, and Deaths Rates of TBI-related Emergency Department Visits, Hospitalizations, ... related Hospitalizations by Age Group and Injury Mechanism Deaths Rates of TBI-related Deaths by Sex Rates ...

Species identities and antimicrobial susceptibilities of corynebacteria isolated from various clinical sources.

PubMed

Riegel, P; Ruimy, R; Christen, R; Monteil, H

1996-08-01

Over a 14-month period, 415 clinical isolates of coryneform gram-positive rods were recovered from various sources and identified to the species level according to recent identification schemes. Corynebacterium urealyticum, Corynebacterium striatum, Corynebacterium amycolatum, and Corynebacterium jeikeium predominated, accounting for 63% of all isolates. Corynebacterium accolens, Corynebacterium striatum, Corynebacterium argentoratense, Corynebacterium propinquum and Corynebacterium pseudodiphtheriticum were mostly recovered from the respiratory tract, whereas Corynebacterium afermentans, CDC group G, and Corynebacterium jeikeium were mainly isolated from blood. None of the isolates was identified as Corynebacterium diphtheriae or Corynebacterium xerosis. Ampicillin resistance was detected in Corynebacterium jeikeium (96%) and Corynebacterium urealyticum (99%) and varied among Corynebacterium amycolatum (56%) and CDC group G (26%). These data emphasize the need for an accurate identification of coryneform organisms at the species level and for antimicrobial susceptibility testing of these organisms.

A conserved mechanism for replication origin recognition and binding in archaea.

PubMed

Majerník, Alan I; Chong, James P J

2008-01-15

To date, methanogens are the only group within the archaea where firing DNA replication origins have not been demonstrated in vivo. In the present study we show that a previously identified cluster of ORB (origin recognition box) sequences do indeed function as an origin of replication in vivo in the archaeon Methanothermobacter thermautotrophicus. Although the consensus sequence of ORBs in M. thermautotrophicus is somewhat conserved when compared with ORB sequences in other archaea, the Cdc6-1 protein from M. thermautotrophicus (termed MthCdc6-1) displays sequence-specific binding that is selective for the MthORB sequence and does not recognize ORBs from other archaeal species. Stabilization of in vitro MthORB DNA binding by MthCdc6-1 requires additional conserved sequences 3' to those originally described for M. thermautotrophicus. By testing synthetic sequences bearing mutations in the MthORB consensus sequence, we show that Cdc6/ORB binding is critically dependent on the presence of an invariant guanine found in all archaeal ORB sequences. Mutation of a universally conserved arginine residue in the recognition helix of the winged helix domain of archaeal Cdc6-1 shows that specific origin sequence recognition is dependent on the interaction of this arginine residue with the invariant guanine. Recognition of a mutated origin sequence can be achieved by mutation of the conserved arginine residue to a lysine or glutamine residue. Thus despite a number of differences in protein and DNA sequences between species, the mechanism of origin recognition and binding appears to be conserved throughout the archaea.

p53 mediates bcl-2 phosphorylation and apoptosis via activation of the Cdc42/JNK1 pathway.

PubMed

Thomas, A; Giesler, T; White, E

2000-11-02

A member of the small G protein family, cdc42, was isolated from a screen undertaken to identify p53-inducible genes during apoptosis in primary baby rat kidney (BRK) cells transformed with E1A and a temperature-sensitive mutant p53 using a PCR-based subtractive hybridization method. Cdc42 is a GTPase that belongs to the Rho/Rac subfamily of Ras-like GTPases. In response to external stimuli, Cdc42 is known to transduce signals to regulate the organization of the actin cytoskeleton, induce DNA synthesis in quiescent fibroblasts, and promote apoptosis in neuronal and immune cells. In this study, we have demonstrated that cdc42 mRNA and protein were up-regulated in the presence of wild-type p53 in BRK cells, followed by cytoplasmic to plasma membrane translocation of Cdc42. Overexpression of Cdc42 in the presence of a dominant-negative mutant p53 induced apoptosis rapidly, indicating that Cdc42 functions downstream of p53. Furthermore, stable expression of a dominant-negative mutant of Cdc42 partially inhibited p53-mediated apoptosis. The Bcl-2 family members Bcl-xL, and the adenovirus protein E1B 19K, inhibited Cdc42-mediated apoptosis, whereas Bcl-2 did not. We provide evidence that PAK1 and JNK1 may play a role downstream of Cdc42 to transduce its apoptotic signal. Cdc42/PAK1 activates JNK1-induced phosphorylation of Bcl-2, thereby inactivating its function, and that a phosphorylation resistant mutant (Bcl-2S70,87A,T56,74A) gains the ability to inhibit Cdc42- and p53-mediated apoptosis. Thus, one mechanism by which p53 promotes apoptosis is through activation of Cdc42 and inactivation of Bcl-2.

Assembly, molecular organization, and membrane-binding properties of development-specific septins

PubMed Central

Garcia, Galo; Finnigan, Gregory C.; Heasley, Lydia R.; Sterling, Sarah M.; Aggarwal, Adeeti; Pearson, Chad G.

2016-01-01

Septin complexes display remarkable plasticity in subunit composition, yet how a new subunit assembled into higher-order structures confers different functions is not fully understood. Here, this question is addressed in budding yeast, where during meiosis Spr3 and Spr28 replace the mitotic septin subunits Cdc12 and Cdc11 (and Shs1), respectively. In vitro, the sole stable complex that contains both meiosis-specific septins is a linear Spr28–Spr3–Cdc3–Cdc10–Cdc10–Cdc3–Spr3–Spr28 hetero-octamer. Only coexpressed Spr3 and Spr28 colocalize with Cdc3 and Cdc10 in mitotic cells, indicating that incorporation requires a Spr28-Spr3 protomer. Unlike their mitotic counterparts, Spr28-Spr3–capped rods are unable to form higher-order structures in solution but assemble to form long paired filaments on lipid monolayers containing phosphatidylinositol-4,5-bisphosphate, mimicking presence of this phosphoinositide in the prospore membrane. Spr28 and Spr3 fail to rescue the lethality of a cdc11Δ cdc12Δ mutant, and Cdc11 and Cdc12 fail to restore sporulation proficiency to spr3Δ/spr3Δ spr28Δ/spr28Δ diploids. Thus, specific meiotic and mitotic subunits endow septin complexes with functionally distinct properties. PMID:26929450

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

PubMed

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

2016-07-26

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.

13 CFR 120.823 - CDC Board of Directors.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false CDC Board of Directors. 120.823... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.823 CDC Board of Directors. The CDC must have a Board of Directors chosen from the membership by the members, and...

13 CFR 120.851 - CDC ethical requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false CDC ethical requirements. 120.851... Company Loan Program (504) Other Cdc Requirements § 120.851 CDC ethical requirements. CDCs and their... § 120.140. In addition, they are subject to the following: (a) Any benefit flowing to a CDC's Associate...

13 CFR 120.823 - CDC Board of Directors.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false CDC Board of Directors. 120.823... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.823 CDC Board of Directors. The CDC must have a Board of Directors chosen from the membership by the members, and...

13 CFR 120.829 - Job Opportunity average a CDC must maintain.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Job Opportunity average a CDC must... LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.829 Job Opportunity average a CDC must maintain. (a) A CDC's portfolio must maintain a minimum average of...

13 CFR 120.851 - CDC ethical requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false CDC ethical requirements. 120.851... Company Loan Program (504) Other Cdc Requirements § 120.851 CDC ethical requirements. CDCs and their... § 120.140. In addition, they are subject to the following: (a) Any benefit flowing to a CDC's Associate...

13 CFR 120.851 - CDC ethical requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false CDC ethical requirements. 120.851... Company Loan Program (504) Other Cdc Requirements § 120.851 CDC ethical requirements. CDCs and their... § 120.140. In addition, they are subject to the following: (a) Any benefit flowing to a CDC's Associate...

13 CFR 120.829 - Job Opportunity average a CDC must maintain.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Job Opportunity average a CDC must... LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.829 Job Opportunity average a CDC must maintain. (a) A CDC's portfolio must maintain a minimum average of...

13 CFR 120.823 - CDC Board of Directors.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false CDC Board of Directors. 120.823... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.823 CDC Board of Directors. The CDC must have a Board of Directors chosen from the membership by the members, and...

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

Code of Federal Regulations, 2011 CFR

2011-01-01

... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false CDC non-profit status and good... LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.820 CDC non-profit status and good standing. A CDC must be a non-profit corporation, except that for...

13 CFR 120.821 - CDC Area of Operations.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false CDC Area of Operations. 120.821... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.821 CDC Area of Operations. A CDC must operate only within its designated Area of Operations approved by SBA except as...

13 CFR 120.823 - CDC Board of Directors.

Code of Federal Regulations, 2010 CFR

2010-01-01

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

13 CFR 120.821 - CDC Area of Operations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false CDC Area of Operations. 120.821... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.821 CDC Area of Operations. A CDC must operate only within its designated Area of Operations approved by SBA except as...

13 CFR 120.823 - CDC Board of Directors.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false CDC Board of Directors. 120.823... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.823 CDC Board of Directors. The CDC must have a Board of Directors chosen from the membership by the members, and...

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

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false CDC non-profit status and good... LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.820 CDC non-profit status and good standing. A CDC must be a non-profit corporation, except that for...

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

Code of Federal Regulations, 2014 CFR

2014-01-01

... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false CDC non-profit status and good... LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.820 CDC non-profit status and good standing. A CDC must be a non-profit corporation, except that for...

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

Code of Federal Regulations, 2013 CFR

2013-01-01

... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false CDC non-profit status and good... LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.820 CDC non-profit status and good standing. A CDC must be a non-profit corporation, except that for...

13 CFR 120.821 - CDC Area of Operations.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false CDC Area of Operations. 120.821... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.821 CDC Area of Operations. A CDC must operate only within its designated Area of Operations approved by SBA except as...

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

Code of Federal Regulations, 2012 CFR

2012-01-01

... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false CDC non-profit status and good... LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.820 CDC non-profit status and good standing. A CDC must be a non-profit corporation, except that for...

13 CFR 120.821 - CDC Area of Operations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false CDC Area of Operations. 120.821... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.821 CDC Area of Operations. A CDC must operate only within its designated Area of Operations approved by SBA except as...

13 CFR 120.821 - CDC Area of Operations.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false CDC Area of Operations. 120.821... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.821 CDC Area of Operations. A CDC must operate only within its designated Area of Operations approved by SBA except as...

13 CFR 120.829 - Job Opportunity average a CDC must maintain.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Job Opportunity average a CDC must... LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.829 Job Opportunity average a CDC must maintain. (a) A CDC's portfolio must maintain a minimum average of...

75 FR 61505 - Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)-Health...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-05

... Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)--Health Disparities... provide recommendations for consideration to the ACD on strategic and other broad issues facing CDC... collaboration with the CDC Health Equity Workgroup; CDC Director's Annual Health Disparity Report; and briefing...

cdc-25.2, a Caenorhabditis elegans ortholog of cdc25, is required for male tail morphogenesis.

PubMed

Oh, Sangmi; Yoon, Sunghee; Youn, Esther; Kawasaki, Ichiro; Shim, Yhong-Hee

2017-01-22

Cell division cycle 25 (Cdc25) is an evolutionarily conserved phosphatase that promotes cell cycle progression by activating cyclin-dependent kinases (Cdks) which are inactivated by Wee1/Myt1 kinases. It was previously reported that cdc-25.2 promotes oocyte maturation and intestinal cell divisions in Caenorhabditis elegans hermaphrodites. Here, we report a novel function of cdc-25.2 in male tail development which was significantly deformed by cdc-25.2 RNAi depletion and in cdc-25.2 mutant males. The deformation was also observed after RNAi depletion of other cell cycle regulators, cdk-1, cyb-3, cyd-1, and cyl-1. Furthermore, wee-1.3 counteracted cdc-25.2 in male tail development as observed in oocyte maturation and intestine development. The number of cells in ray precursor cell lineages was significantly reduced in cdc-25.2 depleted males. These results indicate that CDC-25.2 is essential for cell divisions in ray precursor cell lineages for proper male tail development. Copyright © 2016 Elsevier Inc. All rights reserved.

Cdc13 N-Terminal Dimerization DNA Binding and Telomere Length Regulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

M Mitchell; J Smith; M Mason

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 ismore » 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.« less

Underage Drinking

MedlinePlus

... and Prevention (CDC). Fact Sheets: Underage Drinking . Atlanta, GA: CDC, 2016. Available at: http://www.cdc.gov/ ... Public Health: Alcohol-Related Disease Impact (ARDI) . Atlanta, GA: CDC, 2016. Available at: http://go.usa.gov/ ...

Instrumental variables vs. grouping approach for reducing bias due to measurement error.

PubMed

Batistatou, Evridiki; McNamee, Roseanne

2008-01-01

Attenuation of the exposure-response relationship due to exposure measurement error is often encountered in epidemiology. Given that error cannot be totally eliminated, bias correction methods of analysis are needed. Many methods require more than one exposure measurement per person to be made, but the `group mean OLS method,' in which subjects are grouped into several a priori defined groups followed by ordinary least squares (OLS) regression on the group means, can be applied with one measurement. An alternative approach is to use an instrumental variable (IV) method in which both the single error-prone measure and an IV are used in IV analysis. In this paper we show that the `group mean OLS' estimator is equal to an IV estimator with the group mean used as IV, but that the variance estimators for the two methods are different. We derive a simple expression for the bias in the common estimator which is a simple function of group size, reliability and contrast of exposure between groups, and show that the bias can be very small when group size is large. We compare this method with a new proposal (group mean ranking method), also applicable with a single exposure measurement, in which the IV is the rank of the group means. When there are two independent exposure measurements per subject, we propose a new IV method (EVROS IV) and compare it with Carroll and Stefanski's (CS IV) proposal in which the second measure is used as an IV; the new IV estimator combines aspects of the `group mean' and `CS' strategies. All methods are evaluated in terms of bias, precision and root mean square error via simulations and a dataset from occupational epidemiology. The `group mean ranking method' does not offer much improvement over the `group mean method.' Compared with the `CS' method, the `EVROS' method is less affected by low reliability of exposure. We conclude that the group IV methods we propose may provide a useful way to handle mismeasured exposures in epidemiology with or without replicate measurements. Our finding may also have implications for the use of aggregate variables in epidemiology to control for unmeasured confounding.

Interaction of the Small GTPase Cdc42 with Arginine Kinase Restricts White Spot Syndrome Virus in Shrimp

PubMed Central

Xu, Ji-Dong; Jiang, Hai-Shan; Wei, Tian-Di; Zhang, Ke-Yi; Wang, Xian-Wei; Zhao, Xiao-Fan

2016-01-01

ABSTRACT Many types of small GTPases are widely expressed in eukaryotes and have different functions. As a crucial member of the Rho GTPase family, Cdc42 serves a number of functions, such as regulating cell growth, migration, and cell movement. Several RNA viruses employ Cdc42-hijacking tactics in their target cell entry processes. However, the function of Cdc42 in shrimp antiviral immunity is not clear. In this study, we identified a Cdc42 protein in the kuruma shrimp (Marsupenaeus japonicus) and named it MjCdc42. MjCdc42 was upregulated in shrimp challenged by white spot syndrome virus (WSSV). The knockdown of MjCdc42 and injection of Cdc42 inhibitors increased the proliferation of WSSV. Further experiments determined that MjCdc42 interacted with an arginine kinase (MjAK). By analyzing the binding activity and enzyme activity of MjAK and its mutant, ΔMjAK, we found that MjAK could enhance the replication of WSSV in shrimp. MjAK interacted with the envelope protein VP26 of WSSV. An inhibitor of AK activity, quercetin, could impair the function of MjAK in WSSV replication. Further study demonstrated that the binding of MjCdc42 and MjAK depends on Cys271 of MjAK and suppresses the WSSV replication-promoting effect of MjAK. By interacting with the active site of MjAK and suppressing its enzyme activity, MjCdc42 inhibits WSSV replication in shrimp. Our results demonstrate a new function of Cdc42 in the cellular defense against viral infection in addition to the regulation of actin and phagocytosis, which has been reported in previous studies. IMPORTANCE The interaction of Cdc42 with arginine kinase plays a crucial role in the host defense against WSSV infection. This study identifies a new mechanism of Cdc42 in innate immunity and enriches the knowledge of the antiviral innate immunity of invertebrates. PMID:28031362

Interaction of the Small GTPase Cdc42 with Arginine Kinase Restricts White Spot Syndrome Virus in Shrimp.

PubMed

Xu, Ji-Dong; Jiang, Hai-Shan; Wei, Tian-Di; Zhang, Ke-Yi; Wang, Xian-Wei; Zhao, Xiao-Fan; Wang, Jin-Xing

2017-03-01

Many types of small GTPases are widely expressed in eukaryotes and have different functions. As a crucial member of the Rho GTPase family, Cdc42 serves a number of functions, such as regulating cell growth, migration, and cell movement. Several RNA viruses employ Cdc42-hijacking tactics in their target cell entry processes. However, the function of Cdc42 in shrimp antiviral immunity is not clear. In this study, we identified a Cdc42 protein in the kuruma shrimp ( Marsupenaeus japonicus ) and named it Mj Cdc42. Mj Cdc42 was upregulated in shrimp challenged by white spot syndrome virus (WSSV). The knockdown of Mj Cdc42 and injection of Cdc42 inhibitors increased the proliferation of WSSV. Further experiments determined that Mj Cdc42 interacted with an arginine kinase ( Mj AK). By analyzing the binding activity and enzyme activity of Mj AK and its mutant, Δ Mj AK, we found that Mj AK could enhance the replication of WSSV in shrimp. Mj AK interacted with the envelope protein VP26 of WSSV. An inhibitor of AK activity, quercetin, could impair the function of Mj AK in WSSV replication. Further study demonstrated that the binding of Mj Cdc42 and Mj AK depends on Cys 271 of Mj AK and suppresses the WSSV replication-promoting effect of Mj AK. By interacting with the active site of Mj AK and suppressing its enzyme activity, Mj Cdc42 inhibits WSSV replication in shrimp. Our results demonstrate a new function of Cdc42 in the cellular defense against viral infection in addition to the regulation of actin and phagocytosis, which has been reported in previous studies. IMPORTANCE The interaction of Cdc42 with arginine kinase plays a crucial role in the host defense against WSSV infection. This study identifies a new mechanism of Cdc42 in innate immunity and enriches the knowledge of the antiviral innate immunity of invertebrates. Copyright © 2017 American Society for Microbiology.

Outcome based state budget allocation for diabetes prevention programs using multi-criteria optimization with robust weights.

PubMed

Mehrotra, Sanjay; Kim, Kibaek

2011-12-01

We consider the problem of outcomes based budget allocations to chronic disease prevention programs across the United States (US) to achieve greater geographical healthcare equity. We use Diabetes Prevention and Control Programs (DPCP) by the Center for Disease Control and Prevention (CDC) as an example. We present a multi-criteria robust weighted sum model for such multi-criteria decision making in a group decision setting. The principal component analysis and an inverse linear programming techniques are presented and used to study the actual 2009 budget allocation by CDC. Our results show that the CDC budget allocation process for the DPCPs is not likely model based. In our empirical study, the relative weights for different prevalence and comorbidity factors and the corresponding budgets obtained under different weight regions are discussed. Parametric analysis suggests that money should be allocated to states to promote diabetes education and to increase patient-healthcare provider interactions to reduce disparity across the US.

Health communication takes on new dimensions at CDC.

PubMed

Roper, W L

1993-01-01

Actions by the Centers for Disease Control and Prevention (CDC) to integrate health communication into overall prevention programs as a means of influencing individual behavior to reduce risks to health are described. These actions include a set of 5-year goals for the Agency; a proposal to establish an Office of Health Communication to provide leadership and support for accomplishing the goals; and establishment of a working group to create the proposed Office of Health Communication and to develop a framework for accomplishing the goals. Fundamental to the policy was development of a definition of health communication as the Agency would practice it. Steps taken to reach this definition are outlined as well as the 10 steps adopted as a framework for health communication. The article concludes with a statement describing communication as a part of CDC's overall mission. The hope is that the ultimate accomplishment will be increased awareness among Americans of the importance of good health and their ability to achieve it.

Health communication takes on new dimensions at CDC.

PubMed Central

Roper, W L

1993-01-01

Actions by the Centers for Disease Control and Prevention (CDC) to integrate health communication into overall prevention programs as a means of influencing individual behavior to reduce risks to health are described. These actions include a set of 5-year goals for the Agency; a proposal to establish an Office of Health Communication to provide leadership and support for accomplishing the goals; and establishment of a working group to create the proposed Office of Health Communication and to develop a framework for accomplishing the goals. Fundamental to the policy was development of a definition of health communication as the Agency would practice it. Steps taken to reach this definition are outlined as well as the 10 steps adopted as a framework for health communication. The article concludes with a statement describing communication as a part of CDC's overall mission. The hope is that the ultimate accomplishment will be increased awareness among Americans of the importance of good health and their ability to achieve it. PMID:8385358

Circumcision of male infants and children as a public health measure in developed countries: A critical assessment of recent evidence.

PubMed

Frisch, Morten; Earp, Brian D

2018-05-01

In December of 2014, an anonymous working group under the United States' Centers for Disease Control and Prevention (CDC) issued a draft of the first-ever federal recommendations regarding male circumcision. In accordance with the American Academy of Pediatrics' circumcision policy from 2012 - but in contrast to the more recent 2015 policy from the Canadian Paediatric Society as well as prior policies (still in force) from medical associations in Europe and Australasia - the CDC suggested that the benefits of the surgery outweigh the risks. In this article, we provide a brief scientific and conceptual analysis of the CDC's assessment of benefit versus risk, and argue that it deserves a closer look. Although we set aside the burgeoning bioethical debate surrounding the moral permissibility of performing non-therapeutic circumcisions on healthy minors, we argue that, from a scientific and medical perspective, current evidence suggests that such circumcision is not an appropriate public health measure for developed countries such as the United States.

Comparison of WHO and CDC growth charts in predicting pulmonary outcomes in cystic fibrosis.

PubMed

Machogu, Evans; Cao, Yumei; Miller, Tami; Simpson, Pippa; Levy, Hara; Quintero, Diana; Goday, Praveen S

2015-03-01

The relation of weight-for-length (WFL) and weight-for-age (WFA) measurements with pulmonary function in patients with cystic fibrosis (CF) using the World Health Organization (WHO) growth standards has not been evaluated. The objective of the present study was to show that the relation of WFL and WFA measurements at 2 years with forced expiratory volume in 1 second (FEV1) at 6 to 8 years differs when using the WHO versus the Centers for Disease Control and Prevention (CDC) growth charts. We assessed 1155 patients in the CF Foundation Patient Registry born between 2001 and 2004. Comparisons were made between the CDC and WHO growth charts. The WFL percentiles are significantly higher for the WHO growth standards compared with those for the CDC growth charts (median and interquartile range [IQR] WHO--64.8 [41.7-84.9], CDC--48.1 [23.7-75.7], P < 0.0001). WFL and WFA percentiles at 2 years on both charts are strongly associated with FEV1 at 6 to 8 years of age. The FEV1 at 6 to 8 years was statistically significantly lower for children who were classified as reaching a WFL ≥ 50 th percentile at 2 years by WHO standards alone versus those who qualified by both growth charts (median and IQR 103 [94-115] vs 107 [96-117], P < 0.05). Continued weight gain between 2 and 6 years was associated with a higher lung function at age 6 to 8 years. Although children attaining the 50th WFL percentile on the WHO growth chart by age 2 years have a lower FEV1 at 6 years than children attaining the same percentile on the CDC chart, both groups of children attain clinically normal FEV1. Further studies are needed to determine whether this difference is clinically meaningful.

Binding and inhibition of Cdc25 phosphatases by vitamin K analogues.

PubMed

Kar, Siddhartha; Lefterov, Iliya M; Wang, Meifang; Lazo, John S; Scott, Colleen N; Wilcox, Craig S; Carr, Brian I

2003-09-09

A synthetic K vitamin analogue, 2-(2-mercaptothenol)-3-methyl-1,4-naphthoquinone or Cpd 5, was previously found to be a potent inhibitor of cell growth [Nishikawa et al., (1995) J. Biol. Chem. 270, 28304-28310]. The mechanisms of cell growth were hypothesized to include the inactivation of cellular protein tyrosine phosphatases, especially the Cdc25 family [Tamura et al. (2000) Cancer Res. 60, 1317-1325]. In this study, we synthesized PD 49, a new biotin containing Cpd 5 derivative, to search for evidence of direct interaction of these arylating analogues with Cdc25A, Cdc25B, and Cdc25C phosphatases. PD 49 was shown to directly bind to GST-Cdc25A, GST-Cdc25B, their catalytic fragments, and GST-Cdc25C. The binding could be competed with excess glutathione or Cpd 5, and a cysteine-to-serine mutation of the catalytic cysteine abolished binding. This was consistent with an involvement in binding of cysteine in the catalytic domain. This interaction between PD 49 and Cdc25 also occurred in lysates of treated cells. PD 49 also bound to protein phosphatases other than Cdc25. We found that the new analogue also inhibited Hep3B human hepatoma cell growth. This growth inhibition involved ERK1/2 phosphorylation and was inhibited by a MEK antagonist. The results demonstrate a direct interaction and binding between this growth-inhibiting K vitamin derivative with both purified as well as with cellular Cdc25A, Cdc25B, and Cdc25C.

Activation of Rho GTPase Cdc42 promotes adhesion and invasion in colorectal cancer cells.

PubMed

Gao, Lei; Bai, Lan; Nan, Qing zhen

2013-07-25

The purpose of this study was to investigate the role of activated Rho GTPase cell division control protein 42 homolog (Cdc42) in colorectal cancer cell adhesion, migration, and invasion. The constitutively active form of Cdc42 (GFP-Cdc42L61) or control vector was overexpressed in the colorectal cancer cell line SW480. The localization of active Cdc42 was monitored by immunofluorescence staining, and the effects of active Cdc42 on cell migration and invasion were examined using an attachment assay, a wound healing assay, and a Matrigel migration assay in vitro. Immunofluorescence staining revealed that constitutively active Cdc42 predominately localized to the plasma membrane. Compared to SW480 cells transfected with the control vector, overexpression of constitutively active Cdc42 in SW480 cells promoted filopodia formation and cell stretch and dramatically enhanced cell adhesion to the coated plates. The wound healing assay revealed a significant increase of migration capability in SW480 cells expressing active Cdc42 compared to the control cells. Additionally, the Matrigel invasion assay demonstrated that active Cdc42 significantly promoted SW480 cell migration through the chamber. Our results suggest that active Rho GTPase Cdc42 can greatly enhance colorectal cancer cell SW480 to spread, migrate, and invade, which may contribute to colorectal cancer metastasis.

Articles Published and Downloaded by Public Health Scientists: Analysis of Data From the CDC Public Health Library, 2011-2013.

PubMed

Iskander, John; Bang, Gail; Stupp, Emma; Connick, Kathy; Gomez, Onnalee; Gidudu, Jane

2016-01-01

To describe scientific information usage and publication patterns of the Centers for Disease Control and Prevention (CDC) Public Health Library and Information Center patrons. Administratively collected patron usage data and aggregate data on CDC-authored publications from the CDC Library for 3 consecutive years were analyzed. The CDC Public Health Library and Information Center, which serves CDC employees nationally and internationally. Internal patrons and external users of the CDC Library. Three-year trends in full-text article publication and downloads including most common journals used for each purpose, systematic literature searches requested and completed, and subscriptions to a weekly public health current literature awareness service. From 2011 to 2013, CDC scientists published a total of 7718 articles in the peer-reviewed literature. During the same period, article downloads from the CDC Library increased 25% to more than 1.1 million, completed requests for reviews of the scientific literature increased by 34%, and electronic subscriptions to literature compilation services increased by 23%. CDC's scientific output and information use via the CDC Library are both increasing. Researchers and field staff are making greater use of literature review services and other customized information content delivery. Virtual public health library access is an increasingly important resource for the scientific practice of public health.

Rapid Cdc13 turnover and telomere length homeostasis are controlled by Cdk1-mediated phosphorylation of Cdc13.

PubMed

Tseng, Shun-Fu; Shen, Zih-Jie; Tsai, Hung-Ji; Lin, Yi-Hsuan; Teng, Shu-Chun

2009-06-01

Budding yeast telomerase is mainly activated by Tel1/Mec1 (yeast ATM/ATR) on Cdc13 from late S to G2 phase of the cell cycle. Here, we demonstrated that the telomerase-recruitment domain of Cdc13 is also phosphorylated by Cdk1 at the same cell cycle stage as the Tel1/Mec1-dependent regulation. Phosphor-specific gel analysis demonstrated that Cdk1 phosphorylates residues 308 and 336 of Cdc13. The residue T308 of Cdc13 is critical for efficient Mec1-mediated S306 phosphorylation in vitro. Phenotypic analysis in vivo revealed that the mutations in the Cdc13 S/TP motifs phosphorylated by Cdk1 caused cell cycle delay and telomere shortening and these phenotypes could be partially restored by the replacement with a negative charge residue. In the absence of Ku or Tel1, Cdk1-mediated phosphorylation of Cdc13 showed no effect on telomere length maintenance. Moreover, this Cdk1-mediated phosphorylation was required to promote the regular turnover of Cdc13. Together these results demonstrate that Cdk1 phosphorylates the telomerase recruitment domain of Cdc13, thereby preserves optimal function and expression level of Cdc13 for precise telomere replication and cell cycle progression.

13 CFR 120.827 - Other services a CDC may provide to small businesses.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Other services a CDC may provide... ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.827 Other services a CDC may provide to small businesses. A CDC may provide a small business...

33 CFR 165.503 - Security Zone; Captain of the Port Hampton Roads Zone.

Code of Federal Regulations, 2012 CFR

2012-07-01

... section— Certain dangerous cargo or CDC means a material defined as CDC in 33 CFR 160.204. Designated... a passenger vessel or vessel carrying a CDC, while the passenger vessel or vessel carrying CDC is... vessel or vessel carrying a CDC within the Captain of the Port Hampton Roads zone, unless traveling at...

13 CFR 120.935 - Deposit from the Borrower that a CDC may require.

Code of Federal Regulations, 2012 CFR

2012-01-01

... CDC may require. 120.935 Section 120.935 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION... Borrower that a CDC may require. At the time of application for a 504 loan, the CDC may require a deposit... application is denied. If the small business withdraws its application, the CDC may deduct from the deposit...

33 CFR 165.503 - Security Zone; Captain of the Port Hampton Roads Zone.

Code of Federal Regulations, 2014 CFR

2014-07-01

... section— Certain dangerous cargo or CDC means a material defined as CDC in 33 CFR 160.204. Designated... a passenger vessel or vessel carrying a CDC, while the passenger vessel or vessel carrying CDC is... vessel or vessel carrying a CDC within the Captain of the Port Hampton Roads zone, unless traveling at...

42 CFR 73.7 - Registration and related security risk assessments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... requested in the registration application package (APHIS/CDC Form 1) to CDC. To apply for a certificate of... application package (APHIS/CDC Form 1) to CDC or APHIS, but not both. (e) Prior to the issuance of a... entity must immediately notify CDC or APHIS if it loses the services of its Responsible Official. In the...

75 FR 48699 - Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-11

... Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)--National Biosurveillance.... L. 92-463), the CDC announces the following meeting of aforementioned subcommittee: Time and Date: 8.... Purpose: As a subcommittee to the CDC's ACD, the NBAS will provide counsel to the CDC and the Federal...

13 CFR 120.827 - Other services a CDC may provide to small businesses.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Other services a CDC may provide... ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.827 Other services a CDC may provide to small businesses. A CDC may provide a small business...

13 CFR 120.827 - Other services a CDC may provide to small businesses.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Other services a CDC may provide... ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.827 Other services a CDC may provide to small businesses. A CDC may provide a small business...

13 CFR 120.830 - Reports a CDC must submit.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Reports a CDC must submit. 120.830... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.830 Reports a CDC must submit. A CDC must submit the following reports to SBA: (a) An annual report within one hundred-eighty...

13 CFR 120.827 - Other services a CDC may provide to small businesses.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Other services a CDC may provide... ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.827 Other services a CDC may provide to small businesses. A CDC may provide a small business...

42 CFR 73.7 - Registration and related security risk assessments.

Code of Federal Regulations, 2011 CFR

2011-10-01

... requested in the registration application package (APHIS/CDC Form 1) to CDC. To apply for a certificate of... application package (APHIS/CDC Form 1) to CDC or APHIS, but not both. (e) Prior to the issuance of a... entity must immediately notify CDC or APHIS if it loses the services of its Responsible Official. In the...

13 CFR 120.852 - Restrictions regarding CDC participation in the Small Business Investment Company (SBIC) program...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Restrictions regarding CDC... Company Loan Program (504) Other Cdc Requirements § 120.852 Restrictions regarding CDC participation in.... A CDC must not invest in or be an Affiliate of a Lender participating in the 7(a) loan program...

13 CFR 120.935 - Deposit from the Borrower that a CDC may require.

Code of Federal Regulations, 2014 CFR

2014-01-01

... CDC may require. 120.935 Section 120.935 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION... Borrower that a CDC may require. At the time of application for a 504 loan, the CDC may require a deposit... application is denied. If the small business withdraws its application, the CDC may deduct from the deposit...

13 CFR 120.827 - Other services a CDC may provide to small businesses.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Other services a CDC may provide... ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.827 Other services a CDC may provide to small businesses. A CDC may provide a small business...

13 CFR 120.935 - Deposit from the Borrower that a CDC may require.

Code of Federal Regulations, 2013 CFR

2013-01-01

... CDC may require. 120.935 Section 120.935 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION... Borrower that a CDC may require. At the time of application for a 504 loan, the CDC may require a deposit... application is denied. If the small business withdraws its application, the CDC may deduct from the deposit...

13 CFR 120.935 - Deposit from the Borrower that a CDC may require.

Code of Federal Regulations, 2010 CFR

2010-01-01

... CDC may require. 120.935 Section 120.935 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION... Borrower that a CDC may require. At the time of application for a 504 loan, the CDC may require a deposit... application is denied. If the small business withdraws its application, the CDC may deduct from the deposit...

13 CFR 120.830 - Reports a CDC must submit.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Reports a CDC must submit. 120.830... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.830 Reports a CDC must submit. A CDC must submit the following reports to SBA: (a) An annual report within one hundred-eighty...

13 CFR 120.830 - Reports a CDC must submit.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Reports a CDC must submit. 120.830... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.830 Reports a CDC must submit. A CDC must submit the following reports to SBA: (a) An annual report within one hundred-eighty...

13 CFR 120.852 - Restrictions regarding CDC participation in the Small Business Investment Company (SBIC) program...

Code of Federal Regulations, 2012 CFR

2012-01-01

... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Restrictions regarding CDC... Company Loan Program (504) Other Cdc Requirements § 120.852 Restrictions regarding CDC participation in.... A CDC must not invest in or be an Affiliate of a Lender participating in the 7(a) loan program...

13 CFR 120.830 - Reports a CDC must submit.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Reports a CDC must submit. 120.830... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.830 Reports a CDC must submit. A CDC must submit the following reports to SBA: (a) An annual report within one hundred-eighty...

33 CFR 165.503 - Security Zone; Captain of the Port Hampton Roads Zone.

Code of Federal Regulations, 2013 CFR

2013-07-01

... section— Certain dangerous cargo or CDC means a material defined as CDC in 33 CFR 160.204. Designated... a passenger vessel or vessel carrying a CDC, while the passenger vessel or vessel carrying CDC is... vessel or vessel carrying a CDC within the Captain of the Port Hampton Roads zone, unless traveling at...

13 CFR 120.852 - Restrictions regarding CDC participation in the Small Business Investment Company (SBIC) program...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Restrictions regarding CDC... Company Loan Program (504) Other Cdc Requirements § 120.852 Restrictions regarding CDC participation in.... A CDC must not invest in or be an Affiliate of a Lender participating in the 7(a) loan program...

13 CFR 120.852 - Restrictions regarding CDC participation in the Small Business Investment Company (SBIC) program...

Code of Federal Regulations, 2013 CFR

2013-01-01

... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Restrictions regarding CDC... Company Loan Program (504) Other Cdc Requirements § 120.852 Restrictions regarding CDC participation in.... A CDC must not invest in or be an Affiliate of a Lender participating in the 7(a) loan program...

13 CFR 120.852 - Restrictions regarding CDC participation in the Small Business Investment Company (SBIC) program...

Code of Federal Regulations, 2014 CFR

2014-01-01

... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Restrictions regarding CDC... Company Loan Program (504) Other Cdc Requirements § 120.852 Restrictions regarding CDC participation in.... A CDC must not invest in or be an Affiliate of a Lender participating in the 7(a) loan program...

13 CFR 120.935 - Deposit from the Borrower that a CDC may require.

Code of Federal Regulations, 2011 CFR

2011-01-01

... CDC may require. 120.935 Section 120.935 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION... Borrower that a CDC may require. At the time of application for a 504 loan, the CDC may require a deposit... application is denied. If the small business withdraws its application, the CDC may deduct from the deposit...

42 CFR 73.7 - Registration and related security risk assessments.

Code of Federal Regulations, 2012 CFR

2012-10-01

... requested in the registration application package (APHIS/CDC Form 1) to CDC. To apply for a certificate of... application package (APHIS/CDC Form 1) to CDC or APHIS, but not both. (e) Prior to the issuance of a... entity must immediately notify CDC or APHIS if it loses the services of its Responsible Official. In the...

75 FR 19983 - National Center for Injury Prevention and Control Initial Review Group

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Center for Injury Prevention and Control Initial Review Group In accordance with section 10(a)(2) of the Federal Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control and Prevention (CDC...

77 FR 68122 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Public...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-15

... prevention program or a control group. Surveys will be distributed and collected by trained professional... part of a control group. Burden Statement: Burden in this context means the time expended by persons to... Control and Prevention (CDC), and the Administration for Children and Families (ACF) on adolescent...

Norovirus

MedlinePlus

... Safety Website CDC Vital Signs — Preventing Norovirus Outbreaks, Food Service has a Key Role CDC Vital Signs: Making ... Safety Website CDC Vital Signs — Preventing Norovirus Outbreaks, Food Service has a Key Role CDC Vital Signs: Making ...

Tribology of carbide derived carbon films synthesized on tungsten carbide

NASA Astrophysics Data System (ADS)

Tlustochowicz, Marcin

Tribologically advantageous films of carbide derived carbon (CDC) have been successfully synthesized on binderless tungsten carbide manufactured using the plasma pressure compaction (P2CRTM) technology. In order to produce the CDC films, tungsten carbide samples were reacted with chlorine containing gas mixtures at temperatures ranging from 800°C to 1000°C in a sealed tube furnace. Some of the treated samples were later dechlorinated by an 800°C hydrogenation treatment. Detailed mechanical and structural characterizations of the CDC films and sliding contact surfaces were done using a series of analytical techniques and their results were correlated with the friction and wear behavior of the CDC films in various tribosystems, including CDC-steel, CDC-WC, CDC-Si3N4 and CDC-CDC. Optimum synthesis and treatment conditions were determined for use in two specific environments: moderately humid air and dry nitrogen. It was found that CDC films first synthesized at 1000°C and then hydrogen post-treated at 800°C performed best in air with friction coefficient values as low as 0.11. However, for dry nitrogen applications, no dechlorination was necessary and both hydrogenated and as-synthesized CDC films exhibited friction coefficients of approximately 0.03. A model of tribological behavior of CDC has been proposed that takes into consideration the tribo-oxidation of counterface material, the capillary forces from adsorbed water vapor, the carbon-based tribofilm formation, and the lubrication effect of both chlorine and hydrogen.

Biological and biochemical characterization of two new PLA2 isoforms Cdc-9 and Cdc-10 from Crotalus durissus cumanensis snake venom.

PubMed

Romero-Vargas, Frey Francisco; Ponce-Soto, Luis Alberto; Martins-de-Souza, Daniel; Marangoni, Sergio

2010-01-01

This work reports the purification, biological characterization and amino acid sequence of two new basic PLA(2) isoforms, Cdc-9 and Cdc-10, purified from the Crotalus durissus cumanensis venom by one step analytical chromatography reverse phase HPLC. The molecular masses of the PLA(2) were 14,175+/-2.7 Da for Cdc-9 and 14,228+/-3.5 Da for Cdc-10 both deduced by primary structure and confirmed by MALDI-TOF. The isoforms presented an amino acid sequence of 122 amino acid residues, being Cdc-9: SLVQFNKMIK FETRKSGLPF YAAYGCYCGW GGQRPKDATD RCCFVHDCCY GKVAKCNTKW DIYSYSLKSG YITCGKGTWC KEQICECDRV AAECLRRSLS TYKNEYMFYP DSRCREPPEY TC with pI value of 8.25 and Cdc-10: SLLQFNKMIK FETRKSGVPF YAAYGCYCGW GGRRPKDPTD RCCFVHDCCY GKLTKCNTKW DIYSYSLKSG YITCGKGTWC KEQICECDRV AAECLRRSLN TYKNEYMFYP DSRCRGPPEY TC with a pI value of 8.46, showing highly conserved Ca(2+)-binding and catalytic sites. The PLA(2) activity decreased when the isoforms Cdc-9 and Cdc-10 were incubated with 4-bromophenacyl bromide (p-BPB), anhydrous acetic acid and p-nitrobenzene sulfonyl fluoride (NBSF) when compared with the activity of both native isoforms. In mice, the PLA(2) isoforms Cdc-9 and Cdc-10 induced myonecrosis and edema. Myotoxic and edema activities were reduced after treatment of the isoforms with p-BPB; acetylation of the lysine residues and the treatment of PLA(2) with NBSF have also induced edema reduction. However, p-BPB strongly diminishes the local and systemic myotoxic effects.

Structural bases of dimerization of yeast telomere protein Cdc13 and its interaction with the catalytic subunit of DNA polymerase [alpha

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Jia; Yang, Yuting; Wan, Ke

Budding yeast Cdc13-Stn1-Ten1 (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, ourmore » 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 {alpha} (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.« less

CDC-48/p97 coordinates CDT-1 degradation with GINS chromatin dissociation to ensure faithful DNA replication.

PubMed

Franz, André; Orth, Michael; Pirson, Paul A; Sonneville, Remi; Blow, J Julian; Gartner, Anton; Stemmann, Olaf; Hoppe, Thorsten

2011-10-07

Faithful transmission of genomic information requires tight spatiotemporal regulation of DNA replication factors. In the licensing step of DNA replication, CDT-1 is loaded onto chromatin to subsequently promote the recruitment of additional replication factors, including CDC-45 and GINS. During the elongation step, the CDC-45/GINS complex moves with the replication fork; however, it is largely unknown how its chromatin association is regulated. Here, we show that the chaperone-like ATPase CDC-48/p97 coordinates degradation of CDT-1 with release of the CDC-45/GINS complex. C. elegans embryos lacking CDC-48 or its cofactors UFD-1/NPL-4 accumulate CDT-1 on mitotic chromatin, indicating a critical role of CDC-48 in CDT-1 turnover. Strikingly, CDC-48(UFD-1/NPL-4)-deficient embryos show persistent chromatin association of CDC-45/GINS, which is a consequence of CDT-1 stabilization. Moreover, our data confirmed a similar regulation in Xenopus egg extracts, emphasizing a conserved coordination of licensing and elongation events during eukaryotic DNA replication by CDC-48/p97. Copyright © 2011 Elsevier Inc. All rights reserved.

Crystallographic analysis of the conserved C-terminal domain of transcription factor Cdc73 from Saccharomyces cerevisiae reveals a GTPase-like fold.

PubMed

Chen, Hongkai; Shi, Nuo; Gao, Yongxiang; Li, Xu; Teng, Maikun; Niu, Liwen

2012-08-01

The yeast Paf1 complex (Paf1C), which is composed of the proteins Paf1, Cdc73, Ctr9, Leo1 and Rtf1, accompanies RNA polymerase II from the promoter to the 3'-end formation site of mRNA- and snoRNA-encoding genes. As one of the first identified subunits of Paf1C, yeast Cdc73 (yCdc73) takes part in many transcription-related processes, including binding to RNA polymerase II, recruitment and activation of histone-modification factors and communication with other transcriptional activators. The human homologue of yCdc73, parafibromin, has been identified as a tumour suppressor linked to breast, renal and gastric cancers. However, the functional mechanism of yCdc73 has until recently been unclear. Here, a 2.2 Å resolution crystal structure of the highly conserved C-terminal region of yCdc73 is reported. It revealed that yCdc73 appears to have a GTPase-like fold. However, no GTPase activity was observed. The crystal structure of yCdc73 will shed new light on the modes of function of Cdc73 and Paf1C.

Item response theory analysis of Centers for Disease Control and Prevention Health-Related Quality of Life (CDC HRQOL) items in adults with arthritis.

PubMed

Mielenz, Thelma J; Callahan, Leigh F; Edwards, Michael C

2016-03-12

Examine the feasibility of performing an item response theory (IRT) analysis on two of the Centers for Disease Control and Prevention health-related quality of life (CDC HRQOL) modules - the 4-item Healthy Days Core Module (HDCM) and the 5-item Healthy days Symptoms Module (HDSM). Previous principal components analyses confirm that the two scales both assess a mix of mental (CDC-MH) and physical health (CDC-PH). The purpose is to conduct item response theory (IRT) analysis on the CDC-MH and CDC-PH scales separately. 2182 patients with self-reported or physician-diagnosed arthritis completed a cross-sectional survey including HDCM and HDSM items. Besides global health, the other 8 items ask the number of days that some statement was true; we chose to recode the data into 8 categories based on observed clustering. The IRT assumptions were assessed using confirmatory factor analysis and the data could be modeled using an unidimensional IRT model. The graded response model was used for IRT analyses and CDC-MH and CDC-PH scales were analyzed separately in flexMIRT. The IRT parameter estimates for the five-item CDC-PH all appeared reasonable. The three-item CDC-MH did not have reasonable parameter estimates. The CDC-PH scale is amenable to IRT analysis but the existing The CDC-MH scale is not. We suggest either using the 4-item Healthy Days Core Module (HDCM) and the 5-item Healthy days Symptoms Module (HDSM) as they currently stand or the CDC-PH scale alone if the primary goal is to measure physical health related HRQOL.

Using Repellent Products to Protect against Mosquito-Borne Illnesses

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The effects of intravenous, enteral and combined administration of glutamine on malnutrition in sepsis: a randomized clinical trial.

PubMed

Koksal, Guniz Meyancı; Erbabacan, Emre; Tunali, Yusuf; Karaoren, Gulsah; Vehid, Suphi; Oz, Huseyin

2014-01-01

Our aim was to compare the effects of intravenous, enteral, and enteral plus intravenous supplemented glutamine on plasma transferrin, nitrogen balance, and creatinine/height index in septic patients with malnutrition. Blood and urine samples were collected for transferrin, urea and creatinine measurements. Samples, SOFA score and protein-calorie intake values were repeated on days 7 and 15. Patients (n:120) were randomly divided into 4 groups. Group I received 30 g/day IV glutamine, group II received 30 g/day enteral glutamine, group III received 15 g/day IV and 15 g/day enteral glutamine. Group IV received only enteral feeding as a control group. Transferrin levels decreased in group IV (p<0.01 0-7 days, p<0.01 7-15 days, p<0.01 0-15 days). Nitrogen balance levels were highest in group IV when compared with group I (p<0.05, p<0.001), group II (p<0.001), and group III (p<0.05, p<0.001) on days 7-15. Creatinine/height indexes increased in group I (p<0.001), group II (p<0.001), group III (p<0.001), and group IV (p<0.05) on day 15. In group III the creatinine/height index was higher than in groups I and II (p<0.05). In group IV, creatinine/height index was lower than in group I (p<0.01) and group II (p<0.001). Protein-calorie intake in group IV was higher than others on day 7 (p<0.05). SOFA scores of group IV were higher than the other groups on day 15 (p<0.05). This study demonstrated, that combined route of gln supplementation resulted in the most positive outcome to transferrin, creatine/height index and nitrogen balance (on days 7 and 15) during the catabolic phase of septic patients with malnutrition.

Cdc42 Promotes Schwann Cell Proliferation and Migration Through Wnt/β-Catenin and p38 MAPK Signaling Pathway After Sciatic Nerve Injury.

PubMed

Han, Bin; Zhao, Jun-Ying; Wang, Wu-Tao; Li, Zheng-Wei; He, Ai-Ping; Song, Xiao-Yang

2017-05-01

Schwann cells (SCs) are unique glial cells in the peripheral nerve and may secrete multiple neurotrophic factors, adhesion molecules, extracellular matrix molecules to form the microenvironment of peripheral nerve regeneration, guiding and supporting nerve proliferation and migration. Cdc42 plays an important regulatory role in dynamic changes of the cytoskeleton. However, there is a little study referred to regulation and mechanism of Cdc42 on glial cells after peripheral nerve injury. The present study investigated the role of Cdc42 in the proliferation and migration of SCs after sciatic nerve injury. Cdc42 expression was tested, showing that the mRNA and protein expression levels of Cdc42 were significantly up-regulated after sciatic nerve injury. Then, we isolated and purified SCs from injuried sciatic nerve at day 7. The purified SCs were transfected with Cdc42 siRNA and pcDNA3.1-Cdc42, and the cell proliferation, cell cycle and migration were assessed. The results implied that Cdc42 siRNA remarkably inhibited Schwann cell proliferation and migration, and resulted in S phase arrest. While pcDNA3.1-Cdc42 showed a contrary effect. Besides, we also observed that Cdc42 siRNA down-regulated the protein expression of β-catenin, Cyclin D1, c-myc and p-p38, which were up-regulated by pcDNA3.1-Cdc42. Meanwhile, the inhibitor of Wnt/β-catenin and p38 MAPK signaling pathway IWP-2 and SB203580 significantly inhibited the effect of pcDNA3.1-Cdc42 on cell proliferation and migration. Overall, our data indicate that Cdc42 regulates Schwann cell proliferation and migration through Wnt/β-catenin and p38 MAPK signaling pathway after sciatic nerve injury, which provides further insights into the therapy of the sciatic nerve injury.

Characterization of the PcCdc42 small G protein from Pneumocystis carinii, which interacts with the PcSte20 life cycle regulatory kinase

PubMed Central

Krajicek, Bryan J.; Kottom, Theodore J.; Villegas, Leah

2010-01-01

Pneumocystis carinii (Pc) causes severe pneumonia in immunocompromised hosts. The binding of Pc trophic forms to alveolar epithelial cells is a central feature of infection, inducing the expression and activation of PcSte20, a gene participating in mating, proliferation, and pseudohyphal growth. In related fungi, Ste20 proteins are generally activated by immediate upstream small G proteins of the Cdc42-like family. PcCdc42 has not been previously described in Pneumocystis. To address the potential role of such a G protein in Pneumocystis, PcCdc42 was cloned from a Pc cDNA library. Using the full-length 576-bp PcCdc42 cDNA sequence, a CHEF blot of genomic DNA yielded a single band, providing evidence that this gene is present as a single copy within the genome. The total length of PcCdc42 cDNA was 576 bp with an estimated molecular mass of ∼38 kDa. BLASTP analysis demonstrated greater than 80% homology with other fungal Cdc42p proteins. Northern analysis indicated equal mRNA expression in both cystic and trophic life forms. Heterologous expression of PcCdc42 in Saccharomyces cerevisiae (Sc) demonstrated that PcCdc42p was able to restore growth in an ScCdc42Δ yeast strain. Additional assays with purified PcCdc42 protein demonstrated GTP binding and intrinsic GTPase activity, which was partially but significantly suppressed by Clostridium difficile toxin B, characteristic of Cdc42 GTPases. Furthermore, PcCdc42 protein was also shown to bind to the downstream PCSte20 kinase partner in the presence (but not the absence) of GTP. These data indicate that Pc possesses a Cdc42 gene expressing an active G protein, which binds the downstream regulatory kinase PcSte20, important in Pc life cycle regulation. PMID:19915161

Cyclin B Proteolysis and the Cyclin-dependent Kinase Inhibitor rum1p Are Required for Pheromone-induced G1 Arrest in Fission Yeast

PubMed Central

Stern, Bodo; Nurse, Paul

1998-01-01

The blocking of G1 progression by fission yeast pheromones requires inhibition of the cyclin-dependent kinase cdc2p associated with the B-cyclins cdc13p and cig2p. We show that cyclosome-mediated degradation of cdc13p and cig2p is necessary for down-regulation of B-cyclin–associated cdc2p kinase activity and for phermone-induced G1 arrest. The cyclin-dependent kinase inhibitor rum1p is also required to maintain this G1 arrest; it binds both cdc13p and cig2p and is specifically required for cdc13p proteolysis. We propose that rum1p acts as an adaptor targeting cdc13p for degradation by the cyclosome. In contrast, the cig2p–cdc2p kinase can be down-regulated, and the cyclin cig2p can be proteolyzed independently of rum1p. We suggest that pheromone signaling inhibits the cig2p–cdc2p kinase, bringing about a transient G1 arrest. As a consequence, rum1p levels increase, thus inhibiting and inducing proteolysis of the cdc13p–cdc2p kinase; this is necessary to maintain G1 arrest. We have also shown that pheromone-induced transcription occurs only in G1 and is independent of rum1p. PMID:9614176

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Gwang Su; Kang, Jeeheon; Bang, Sung Woong

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 centrosomesmore » 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.« less

Loss of Cdc42 leads to defects in synaptic plasticity and remote memory recall.

PubMed

Kim, Il Hwan; Wang, Hong; Soderling, Scott H; Yasuda, Ryohei

2014-07-08

Cdc42 is a signaling protein important for reorganization of actin cytoskeleton and morphogenesis of cells. However, the functional role of Cdc42 in synaptic plasticity and in behaviors such as learning and memory are not well understood. Here we report that postnatal forebrain deletion of Cdc42 leads to deficits in synaptic plasticity and in remote memory recall using conditional knockout of Cdc42. We found that deletion of Cdc42 impaired LTP in the Schaffer collateral synapses and postsynaptic structural plasticity of dendritic spines in CA1 pyramidal neurons in the hippocampus. Additionally, loss of Cdc42 did not affect memory acquisition, but instead significantly impaired remote memory recall. Together these results indicate that the postnatal functions of Cdc42 may be crucial for the synaptic plasticity in hippocampal neurons, which contribute to the capacity for remote memory recall.

Cdc20/p55 mediates the resistance to docetaxel in castration-resistant prostate cancer in a Bim-dependent manner.

PubMed

Wu, Fei; Lin, Yun; Cui, Peng; Li, Hongyun; Zhang, Lechao; Sun, Zeqiang; Huang, Shengliang; Li, Shun; Huang, Shiming; Zhao, Qingli; Liu, Qingyong

2018-06-01

At least to date, no effective treatment for advanced castration-resistant prostate cancer (CRPC) has been established. Recent studies indicated that cell division cycle 20 homolog (Cdc20) overexpression is associated with poor prognosis in patients with castration-resistant prostate cancer. However, the mechanism of Cdc20 in the development of docetaxel resistance in CRPC remains elusive. In this study, the transcription of Cdc20 was confirmed in three independent CRPC cell lines derived from different tissues, including LNCaP, PC3, and DU145. Docetaxel resistant (DR) cell lines were generated within the background of DU145 and PC3. The protein levels of Cdc20 and the biological phenotype were detected in both wild-type and DR cell lines. To further explore the mechanism of Cdc20 overexpression, stable cell lines with Cdc20 or Bcl-2 interacting mediator of cell death (Bim) deprivation were generated and examined for biological parameters. In addition, a specific Cdc20 inhibitor was used in DR cell lines to explore the potential solution for docetaxel resistant CRPC. Here, we identified Cdc20 is overexpressed in docetaxel resistant CRPC cell lines, including LNCaP, PC3, and DU145. We also reported that DR cell lines, which mimic the recurrent prostate cancer cells after docetaxel treatment, have higher levels of Cdc20 protein compared with the CRPC cell lines. Interestingly, the protein levels of Bim, an E3 ligase substrate of Cdc20, were decreased in DR cell lines compared with the wild-type, while the mRNA levels were similar. More importantly, in DR cell lines, the biological phenotype induced by Cdc20 deletion could be significantly reversed by the additional knockdown of Bim. As a result, docetaxel resistant prostate cancer cells treated with the pharmacological Cdc20 inhibitor became sensitive to docetaxel treatment. In conclusion, our data collectively demonstrated that Cdc20 overexpression facilitates the docetaxel resistant of the CRPC cell lines in a Bim-dependent manner. Furthermore, additionally targeting Cdc20 might be a promising solution for the treatment of the CRPC with docetaxel resistance.

76 FR 12118 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-04

... that come to CDC for Select Agents. The term select agents is used to describe a limited group of... bioterrorism, inflicting significant morbidity and mortality on susceptible populations. In light of current...

MRSA

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Developing a new national approach to surveillance for ventilator-associated events: executive summary.

PubMed

Magill, Shelley S; Klompas, Michael; Balk, Robert; Burns, Suzanne M; Deutschman, Clifford S; Diekema, Daniel; Fridkin, Scott; Greene, Linda; Guh, Alice; Gutterman, David; Hammer, Beth; Henderson, David; Hess, Dean R; Hill, Nicholas S; Horan, Teresa; Kollef, Marin; Levy, Mitchell; Septimus, Edward; VanAntwerpen, Carole; Wright, Don; Lipsett, Pamela

2013-11-01

In September 2011, the Centers for Disease Control and Prevention (CDC) convened a Ventilator-Associated Pneumonia (VAP) Surveillance Definition Working Group to organize a formal process for leaders and experts of key stakeholder organizations to discuss the challenges of VAP surveillance definitions and to propose new approaches to VAP surveillance in adult patients (Table 1). The charges to the Working Group were to (1) critically review a draft, streamlined VAP surveillance definition developed for use in adult patients; (2) suggest modifications to enhance the reliability and credibility of the surveillance definition within the critical care and infection prevention communities; and (3) propose a final adult surveillance definition algorithm to be implemented in the CDC's National Healthcare Safety Network (NHSN), taking into consideration the potential future use of the definition algorithm in public reporting, interfacility comparisons, and pay-for-reporting and pay-for-performance programs. Published by Mosby, Inc.

What's the appeal? Testing public service advertisements to raise awareness about gynecologic cancer.

PubMed

Cooper, Crystale Purvis; Gelb, Cynthia A; Chu, Jennifer

2014-06-01

In 2013, the Centers for Disease Control and Prevention's (CDC) Inside Knowledge: Get the Facts About Gynecologic Cancer campaign tested creative concepts for English- and Spanish-language video advertisements (for use on television and the Internet) with women aged 35-64 years. Sixteen English and nine Spanish focus groups were conducted in four U.S. cities. CDC used animatics (a series of photographs edited together with a sound track) to simulate produced advertisements, without having to incur the high cost of filming and production. Advertisement concepts consistently resonating with participants featured cancer survivors, were straightforward, included information about cancer symptoms, displayed Inside Knowledge educational materials, and featured diverse women. In the general population focus groups, a primacy testing order effect was observed in which the concept tested first tended to be the most favorably received. Varying the order in which concepts were tested and considering testing order when interpreting results was critical.

Opioid use in knee arthroplasty after receiving intravenous acetaminophen.

PubMed

Kelly, Jennifer S; Opsha, Yekaterina; Costello, Jennifer; Schiller, Daryl; Hola, Eric T

2014-12-01

Intravenous (IV) acetaminophen may be an effective component of multimodal postoperative pain management. The primary objective of this study was to evaluate the impact of IV acetaminophen on total opioid use in postoperative patients. The secondary objective was to evaluate the effect of IV acetaminophen on hospital length of stay. This retrospective, case-control study evaluated the impact of IV acetaminophen on total opioid use in surgical patients. Patients were included if they received at least one perioperative dose of IV acetaminophen and underwent a surgical knee procedure. Controls were matched and randomly selected based on procedure type, age, and severity of illness. Postoperative opioids were converted into oral morphine equivalents, and overall use was compared between groups. One hundred patients were enrolled, with 25 patients receiving IV acetaminophen and 75 matched controls. A total of 135 mg versus 112.5 mg oral morphine equivalents were used in the IV acetaminophen group and control group, respectively (p=0.987). There were 45 mg/day oral morphine equivalents used in the IV acetaminophen group versus 37.5 mg in the control group (p=0.845). The median hospital length of stay in both groups was 3 days (p=0.799). IV acetaminophen did not significantly decrease postoperative opioid use in patients who underwent surgical knee procedures. In addition, there was a nonsignificant trend toward increased opioid use in the IV acetaminophen group. There was no significant difference in hospital length of stay between the IV acetaminophen group and the control group. These findings require further study in larger patient populations and in other orthopedic procedures that typically require longer hospital stays. © 2014 Pharmacotherapy Publications, Inc.

Rho GTPase protein Cdc42 is critical for postnatal cartilage development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagahama, Ryo; Department of Orthodontics, School of Dentistry, Showa University, Tokyo; Yamada, Atsushi, E-mail: yamadaa@dent.showa-u.ac.jp

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 {sup fl/fl}; Col2-CreERT) mice, which were generated by crossing Cdc42 flox mice (Cdc42 {sup fl/fl}) with tamoxifen-induced type II collagen (Col2) Cre transgenic mice using a Cre/loxP system.more » 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. - Highlights: • Tamoxifen-induced cartilage specific inactivated Cdc42 mutant mice were generated. • Cdc42 mutant mice were shorter limbs and body. • Severe defects were found in growth plate chondrocytes.« less

Ran1 functions to control the Cdc10/Sct1 complex through Puc1.

PubMed Central

Caligiuri, M; Connolly, T; Beach, D

1997-01-01

We have undertaken a biochemical analysis of the regulation of the G1/S-phase transition and commitment to the cell cycle in the fission yeast Schizosaccharomyces pombe. The execution of Start requires the activity of the Cdc2 protein kinase and the Sct1/Cdc10 transcription complex. Progression through G1 also requires the Ran1 protein kinase whose inactivation leads to activation of the meiotic pathway under conditions normally inhibitory to this process. We have found that in addition to Cdc2, Sct1/Cdc10 complex formation requires Ran1. We demonstrate that the Puc1 cyclin associates with Ran1 and Cdc10 in vivo and that the Ran1 protein kinase functions to control the association between Puc1 and Cdc10. In addition, we present evidence that the phosphorylation state of Cdc10 is altered upon inactivation of Ran1. These results provide biochemical evidence that demonstrate one mechanism by which the Ran1 protein kinase serves to control cell fate through Cdc10 and Puc1. Images PMID:9201720

Multiple domains of fission yeast Cdc19p (MCM2) are required for its association with the core MCM complex.

PubMed

Sherman, D A; Pasion, S G; Forsburg, S L

1998-07-01

The members of the MCM protein family are essential eukaryotic DNA replication factors that form a six-member protein complex. In this study, we use antibodies to four MCM proteins to investigate the structure of and requirements for the formation of fission yeast MCM complexes in vivo, with particular regard to Cdc19p (MCM2). Gel filtration analysis shows that the MCM protein complexes are unstable and can be broken down to subcomplexes. Using coimmunoprecipitation, we find that Mis5p (MCM6) and Cdc21p (MCM4) are tightly associated with one another in a core complex with which Cdc19p loosely associates. Assembly of Cdc19p with the core depends upon Cdc21p. Interestingly, there is no obvious change in Cdc19p-containing MCM complexes through the cell cycle. Using a panel of Cdc19p mutants, we find that multiple domains of Cdc19p are required for MCM binding. These studies indicate that MCM complexes in fission yeast have distinct substructures, which may be relevant for function.

Multiple Domains of Fission Yeast Cdc19p (MCM2) Are Required for Its Association with the Core MCM Complex

PubMed Central

Sherman, Daniel A.; Pasion, Sally G.; Forsburg, Susan L.

1998-01-01

The members of the MCM protein family are essential eukaryotic DNA replication factors that form a six-member protein complex. In this study, we use antibodies to four MCM proteins to investigate the structure of and requirements for the formation of fission yeast MCM complexes in vivo, with particular regard to Cdc19p (MCM2). Gel filtration analysis shows that the MCM protein complexes are unstable and can be broken down to subcomplexes. Using coimmunoprecipitation, we find that Mis5p (MCM6) and Cdc21p (MCM4) are tightly associated with one another in a core complex with which Cdc19p loosely associates. Assembly of Cdc19p with the core depends upon Cdc21p. Interestingly, there is no obvious change in Cdc19p-containing MCM complexes through the cell cycle. Using a panel of Cdc19p mutants, we find that multiple domains of Cdc19p are required for MCM binding. These studies indicate that MCM complexes in fission yeast have distinct substructures, which may be relevant for function. PMID:9658174

Cdc13 prevents telomere uncapping and Rad50-dependent homologous recombination

PubMed Central

Grandin, Nathalie; Damon, Christelle; Charbonneau, Michel

2001-01-01

Cdc13 performs an essential function in telomere end protection in budding yeast. Here, we analyze the consequences on telomere dynamics of cdc13-induced telomeric DNA damage in proliferating cells. Checkpoint-deficient cdc13-1 cells accumulated DNA damage and eventually senesced. However, these telomerase-proficient cells could survive by using homologous recombination but, contrary to telomerase-deficient cells, did so without prior telomere shortening. Strikingly, homologous recombination in cdc13-1 mec3, as well as in telomerase-deficient cdc13-1 cells, which were Rad52- and Rad50-dependent but Rad51-independent, exclusively amplified the TG1–3 repeats. This argues that not only short telomeres are substrates for type II recombination. The Cdc13-1 mutant protein harbored a defect in its association with Stn1 and Ten1 but also an additional, unknown, defect that could not be cured by expressing a Cdc13-1– Ten1–Stn1 fusion. We propose that Cdc13 prevents telomere uncapping and inhibits recombination between telomeric sequences through a pathway distinct from and complementary to that used by telomerase. PMID:11689452

Alteronol induces cell cycle arrest and apoptosis via increased reactive oxygen species production in human breast cancer T47D cells.

PubMed

Ren, Boxue; Li, Defang; Si, Lingling; Ding, Yangfang; Han, Jichun; Chen, Xiaoyu; Zheng, Qiusheng

2018-04-01

Emerging evidence showed that alteronol has a potential antitumour effect in several tumour cells. However, the antitumour effect of alteronol on breast cancer has not been reported. This study investigated the mechanisms of alteronol-induced cell proliferation inhibition in human breast cancer T47D cells. After treatment with alteronol, T47D cell proliferation was examined by MTT assay. The cell cycle distribution, cell apoptosis, reactive oxygen species level and mitochondrial membrane potential were evaluated via flow cytometry. Next, the protein levels of cyclin B1, cdc2, p21, p-cyclin B1, p-cdc2, p53, Bax, Bcl-2 and cytochrome c were analysed using Western blot analysis. Meanwhile, the mRNA levels of cyclin B1, cdc2, p21 and p53 were examined by qRT-PCR. Our data showed that alteronol inhibited the proliferation of T47D cells via inducing G2-phase arrest and cell apoptosis. Compared with control group, alteronol significantly increased ROS level and triggered mitochondrial dysfunction in alteronol-treated T47D cells. Further studies showed that the mRNA and protein levels of cdc2 and cyclin B1 were downregulated, while the mRNA and protein levels of p21, p53, p-cyclin B1, p-cdc2 and cytochrome c were upregulated. In addition, the expression level of Bax was increased, and the expression level of Bcl-2 was decreased. Alteronol induced T47D cell cycle arrest and cell apoptosis through increasing ROS production and triggering mitochondrial dysfunction, and subsequently inhibiting T47D cell proliferation. © 2018 Royal Pharmaceutical Society.

Antioxidant and antimicrobial proprieties of chitin and chitosan extracted from Parapenaeus Longirostris shrimp shell waste.

PubMed

Hafsa, J; Smach, M A; Charfeddine, B; Limem, K; Majdoub, H; Rouatbi, S

2016-01-01

Chitosan, the linear polymer, is produced by alkali deacetylation of chitin (CHI). Recently chitin and chitosan were attracted marked interest due to their biocompatibility, biodegradability and non-toxicity. In this study, chitin was extracted from shrimp shell (Parapenaeus longirostris) and chitosan was deacetylated by classical and ultrasound-assisted method. The identification of functional groups and the determination of degree of deacetylation of chitin (CHI), classical deacetylated chitosan (CDC) and ultrasound-assisted deacetylated chitosan (UDC) were carried through Fourier Transform-Infrared Spectroscopy. Their antimicrobial and antioxidant activity were also investigated. The degree of deacetylation of CHI, CDC and UDC is 33.64%, 73.68% and 83.55%, respectively. Results showed that CHI, CDC and UDC exhibited a good antimicrobial activity against (S. aureus, E. coli, P. aeruginosa, K. pneumonia) and (C. albicans and C. parapsilosis). The scavenging ability of CHI, CDC and UDC on 1,1-diphenyl-2-picrylhydrazyl radicals is ranging from 4.71% to 21.25%, 11.45% to 32.78% and 18.27% to 44.17%, respectively, at the concentrations of 0.25 to 1mg/mL. The inhibition of lipid peroxidation with thiobarbituric acid-reacting substances is ranging from 11.7% to 51.63%, 17.24% to 63.52% and 29.31% to 77.39%, respectively, at varying concentrations of 0.25 to 1mg/mL. The effectiveness of CHI, CDC and UDC is correlated with their degree of deacetylation. The results indicate the possibility of exploiting chitin and chitosan as antimicrobial agent. Copyright © 2015 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

Field performance of clinical case definitions for influenza screening during the 2009 pandemic.

PubMed

Chen, Shey-Ying; Chen, Yee-Chun; Chiang, Wen-Chu; Kung, Hsiang-Chi; King, Chwan-Chuen; Lai, Mei-Shu; Chie, Wei-Chu; Chen, Shyr-Chyr; Chen, Wen-Jone; Chang, Shan-Chwen

2012-11-01

The aim of this study was to assess the performance of 3 different influenza-like illness (ILI) case definitions, adopted by the European (European-CDC), USA (USA-CDC), and Taiwan Centers for Disease Prevention and Control (Taiwan-CDC), as screening tools for influenza during the 2009 H1N1 pandemic. From August 15 to 30, 2009, all emergency department patients with clinical symptoms or at epidemiologic risk for influenza were enrolled in an observational cohort study. Influenza diagnosis was established by positive rapid influenza diagnostic test or virus isolation. Sensitivity, specificity, positive predictive value, and negative predictive value of the European-, USA, and Taiwan-CDC ILI case definitions for screening were determined. A total of 870 patients were screened during the study period. Rapid influenza diagnostic test was positive in 315 patients, 273 (85.6%) of whom had fever duration less than 72 hours. Virus isolation identified 4 more patients with influenza A initially negative by rapid influenza diagnostic test. The mean (SD) age of these 319 patients was 24.3 (18.1) years. Of the 870 screened patients, 670 (77.0%), 476 (54.7%), and 325 (37.4%) met the European-, USA-, and Taiwan-CDC ILI case definition, respectively. Screening sensitivity was 95%, 77.7%, and 57.7% and specificity was 33.4%, 58.6%, and 74.4%, respectively. Differences in sensitivity and specificity between any 2 of the 3 groups were statistically significant (P < .05). First-line physicians should recognize the advantage and limitation of different ILI case definitions in influenza screening, especially confronted by pandemic or highly pathogenic avian influenza in the future. Copyright © 2012 Elsevier Inc. All rights reserved.

Using the Six Sigma Process to Implement the Centers for Disease Control and Prevention Guideline for Hand Hygiene in 4 Intensive Care Units

PubMed Central

Eldridge, Noel E; Woods, Susan S; Bonello, Robert S; Clutter, Kay; Ellingson, LeAnn; Harris, Mary Ann; Livingston, Barbara K; Bagian, James P; Danko, Linda H; Dunn, Edward J; Parlier, Renee L; Pederson, Cheryl; Reichling, Kim J; Roselle, Gary A; Wright, Steven M

2006-01-01

BACKGROUND The Centers for Disease Control and Prevention (CDC) Guideline for Hand Hygiene in Health Care Settings was issued in 2002. In 2003, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) established complying with the CDC Guideline as a National Patient Safety Goal for 2004. This goal has been maintained through 2006. The CDC's emphasis on the use of alcohol-based hand rubs (ABHRs) rather than soap and water was an opportunity to improve compliance, but the Guideline contained over 40 specific recommendations to implement. OBJECTIVE To use the Six Sigma process to examine hand hygiene practices and increase compliance with the CDC hand hygiene recommendations required by JCAHO. DESIGN Six Sigma Project with pre-post design. PARTICIPANTS Physicians, nurses, and other staff working in 4 intensive care units at 3 hospitals. MEASUREMENTS Observed compliance with 10 required hand hygiene practices, mass of ABHR used per month per 100 patient-days, and staff attitudes and perceptions regarding hand hygiene reported by questionnaire. RESULTS Observed compliance increased from 47% to 80%, based on over 4,000 total observations. The mass of ABHR used per 100 patient-days in 3 intensive care units (ICUs) increased by 97%, 94%, and 70%; increases were sustained for 9 months. Self-reported compliance using the questionnaire did not change. Staff reported increased use of ABHR and increased satisfaction with hand hygiene practices and products. CONCLUSIONS The Six Sigma process was effective for organizing the knowledge, opinions, and actions of a group of professionals to implement the CDC's evidence-based hand hygiene practices in 4 ICUs. Several tools were developed for widespread use. PMID:16637959

Using the six sigma process to implement the Centers for Disease Control and Prevention Guideline for Hand Hygiene in 4 intensive care units.

PubMed

Eldridge, Noel E; Woods, Susan S; Bonello, Robert S; Clutter, Kay; Ellingson, Leann; Harris, Mary Ann; Livingston, Barbara K; Bagian, James P; Danko, Linda H; Dunn, Edward J; Parlier, Renee L; Pederson, Cheryl; Reichling, Kim J; Roselle, Gary A; Wright, Steven M

2006-02-01

The Centers for Disease Control and Prevention (CDC) Guideline for Hand Hygiene in Health Care Settings was issued in 2002. In 2003, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) established complying with the CDC Guideline as a National Patient Safety Goal for 2004. This goal has been maintained through 2006. The CDC's emphasis on the use of alcohol-based hand rubs (ABHRs) rather than soap and water was an opportunity to improve compliance, but the Guideline contained over 40 specific recommendations to implement. To use the Six Sigma process to examine hand hygiene practices and increase compliance with the CDC hand hygiene recommendations required by JCAHO. Six Sigma Project with pre-post design. Physicians, nurses, and other staff working in 4 intensive care units at 3 hospitals. Observed compliance with 10 required hand hygiene practices, mass of ABHR used per month per 100 patient-days, and staff attitudes and perceptions regarding hand hygiene reported by questionnaire. Observed compliance increased from 47% to 80%, based on over 4,000 total observations. The mass of ABHR used per 100 patient-days in 3 intensive care units (ICUs) increased by 97%, 94%, and 70%; increases were sustained for 9 months. Self-reported compliance using the questionnaire did not change. Staff reported increased use of ABHR and increased satisfaction with hand hygiene practices and products. The Six Sigma process was effective for organizing the knowledge, opinions, and actions of a group of professionals to implement the CDC's evidence-based hand hygiene practices in 4 ICUs. Several tools were developed for widespread use.

Role of cdc25 Phosphatases in Human Breast Cancer

DTIC Science & Technology

2008-05-01

Cdc25C in these assays, their cat - alytically inactive mutants Cdc25B (C488S) and Cdc25C (C377S) (referred to as mt25B and mt25C) were generated and...chimeras. B and C, N25B and N25C (B) and their corresponding cat - alytically inactive mutants N25B/C and N25C/B (C). Cdc25B Inhibits Cell...HCT116 cells because similar results were obtained using U2OS (osteosarcoma) andHT1080 ( fibrosarcoma ) cells (data not shown). The level of Cdc25B

Phosphorylation of Rga2, a Cdc42 GAP, by CDK/Hgc1 is crucial for Candida albicans hyphal growth

PubMed Central

Zheng, Xin-De; Lee, Raymond Teck Ho; Wang, Yan-Ming; Lin, Qi-Shan; Wang, Yue

2007-01-01

Cyclin-dependent kinases (CDKs) control yeast morphogenesis, although how they regulate the polarity machinery remains unclear. The dimorphic fungus Candida albicans uses Cdc28/Hgc1, a CDK/cyclin complex, to promote persistent actin polarization for hyphal growth. Here, we report that Rga2, a GTPase-activating protein (GAP) of the central polarity regulator Cdc42, undergoes Hgc1-dependent hyperphosphorylation. Using the analog-sensitive Cdc28as mutant, we confirmed that Cdc28 controls Rga2 phosphorylation in vitro and in vivo. Deleting RGA2 produced elongated yeast cells without apparent effect on hyphal morphogenesis. However, deleting it or inactivating its GAP activity restored hyphal growth in hgc1Δ mutants, suggesting that Rga2 represses hyphal development and Cdc28/Hgc1 inactivates it upon hyphal induction. We provide evidence that Cdc28/Hgc1 may act to prevent Rga2 from localizing to hyphal tips, leading to localized Cdc42 activation for hyphal extension. Rga2 also undergoes transient Cdc28-dependent hyperphosphorylation at bud emergence, suggesting that regulating a GAP(s) of Cdc42 by CDKs may play an important role in governing different forms of polarized morphogenesis in yeast. This study reveals a direct molecular link between CDKs and the polarity machinery. PMID:17673907

Identification of a new class of potent Cdc7 inhibitors designed by putative pharmacophore model: Synthesis and biological evaluation of 2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-ones.

PubMed

Kurasawa, Osamu; Oguro, Yuya; Miyazaki, Tohru; Homma, Misaki; Mori, Kouji; Iwai, Kenichi; Hara, Hideto; Skene, Robert; Hoffman, Isaac; Ohashi, Akihiro; Yoshida, Sei; Ishikawa, Tomoyasu; Cho, Nobuo

2017-04-01

Cell division cycle 7 (Cdc7) is a serine/threonine kinase that plays important roles in the regulation of DNA replication process. A genetic study indicates that Cdc7 inhibition can induce selective tumor-cell death in a p53-dependent manner, suggesting that Cdc7 is an attractive target for the treatment of cancers. In order to identify a new class of potent Cdc7 inhibitors, we generated a putative pharmacophore model based on in silico docking analysis of a known inhibitor with Cdc7 homology model. The pharmacophore model provided a minimum structural motif of Cdc7 inhibitor, by which preliminary medicinal chemistry efforts identified a dihydrothieno[3,2-d]-pyrimidin-4(1H)-one scaffold having a heteroaromatic hinge-binding moiety. The structure-activity relationship (SAR) studies resulted in the discovery of new, potent, and selective Cdc7 inhibitors 14a, c, e. Furthermore, the high selectivity of 14c, e for Cdc7 over Rho-associated protein kinase 1 (ROCK1) is discussed by utilizing a docking study with Cdc7 and ROCK2 crystal structures. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Green Acres Effect: The Need for a New Colorectal Cancer Screening Campaign Tailored to Rural Audiences

ERIC Educational Resources Information Center

Campo, Shelly; Askelson, Natoshia M.; Routsong, Tracy; Graaf, Lorrie J.; Losch, Mary; Smith, Holly

2008-01-01

National health communication campaign developers have ignored rural audiences in campaign development and testing, despite the health disparities that exist for this group. Researchers in a rural Midwestern state tested the appropriateness of CDC's national colorectal cancer screening campaign, Screen for Life. Based on focus groups and a…

76 FR 19952 - Not Applying the Mark of Inspection Pending Certain Test Results

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-11

... analysis. Human Health Benefits Introduction The Centers for Disease Control and Prevention (CDC) has... groups: (1) E. coli O157:H7 in raw, non-intact beef produced by domestic official establishments,\\17\\ (2... size for the first 8 months of year 2006 for the five test groups described above. Table 3--Percent of...

CDC Kerala 1: Organization of clinical child development services (1987-2013).

PubMed

Nair, M K C; George, Babu; Nair, G S Harikumaran; Bhaskaran, Deepa; Leena, M L; Russell, Paul Swamidhas Sudhakar

2014-12-01

The main objective of establishing the Child Development Centre (CDC), Kerala for piloting comprehensive child adolescent development program in India, has been to understand the conceptualization, design and scaling up of a pro-active positive child development initiative, easily replicable all over India. The process of establishing the Child Development Centre (CDC) Kerala for research, clinical services, training and community extension services over the last 25 y, has been as follows; Step 1: Conceptualization--The life cycle approach to child development; Step 2: Research basis--CDC model early stimulation is effective; Step 3: Development and validation of seven simple developmental screening tools; Step 4: CDC Diagnostic services--Ultrasonology and genetic, and metabolic laboratory; Step 5: Developing seven intervention packages; Step 6: Training--Post graduate diploma in clinical child development; Step 7: CDC Clinic Services--seven major ones; Step 8: CDC Community Services--Child development referral units; Step 9: Community service delivery models--Childhood disability and for adolescent care counselling projects; Step 10: National capacity building--Four child development related courses. CDC Kerala follow-up and clinic services are offered till 18 y of age and premarital counselling till 24 y of age as shown in "CDC Kerala Clinic Services Flow Chart" and 74,291 children have availed CDC clinic services in the last 10 y. CDC Kerala is the first model for comprehensive child adolescent development services using a lifecycle approach in the Government sector and hence declared as the collaborative centre for Rashtriya Bal Swasthya Karyakram (RBSK), in Kerala.

Impact of Cardiac Progenitor Cells on Heart Failure and Survival in Single Ventricle Congenital Heart Disease.

PubMed

Sano, Toshikazu; Ousaka, Daiki; Goto, Takuya; Ishigami, Shuta; Hirai, Kenta; Kasahara, Shingo; Ohtsuki, Shinichi; Sano, Shunji; Oh, Hidemasa

2018-03-30

Intracoronary administration of cardiosphere-derived cells (CDCs) in patients with single ventricles resulted in a short-term improvement in cardiac function. To test the hypothesis that CDC infusion is associated with improved cardiac function and reduced mortality in patients with heart failure. We evaluated the effectiveness of CDCs using an integrated cohort study in 101 patients with single ventricles, including 41 patients who received CDC infusion and 60 controls treated with staged palliation alone. Heart failure with preserved ejection fraction (EF) or reduced EF was stratified by the cardiac function after surgical reconstruction. The main outcome measure was to evaluate the magnitude of improvement in cardiac function and all-cause mortality at 2 years. Animal studies were conducted to clarify the underlying mechanisms of heart failure with preserved EF and heart failure with reduced EF phenotypes. At 2 years, CDC infusion increased ventricular function (stage 2: +8.4±10.0% versus +1.6±6.4%, P =0.03; stage 3: +7.9±7.5% versus -1.1±5.5%, P <0.001) compared with controls. In all available follow-up data, survival did not differ between the 2 groups (log-rank P =0.225), whereas overall patients treated by CDCs had lower incidences of late failure ( P =0.022), adverse events ( P =0.013), and catheter intervention ( P =0.005) compared with controls. CDC infusion was associated with a lower risk of adverse events (hazard ratio, 0.411; 95% CI, 0.179-0.942; P =0.036). Notably, CDC infusion reduced mortality ( P =0.038) and late complications ( P <0.05) in patients with heart failure with reduced EF but not with heart failure with preserved EF. CDC-treated rats significantly reversed myocardial fibrosis with differential collagen deposition and inflammatory responses between the heart failure phenotypes. CDC administration in patients with single ventricles showed favorable effects on ventricular function and was associated with reduced late complications except for all-cause mortality after staged procedures. Patients with heart failure with reduced EF but not heart failure with preserved EF treated by CDCs resulted in significant improvement in clinical outcome. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01273857 and NCT01829750. © 2018 American Heart Association, Inc.

Cdc42 deficiency induces podocyte apoptosis by inhibiting the Nwasp/stress fibers/YAP pathway

PubMed Central

Huang, Z; Zhang, L; Chen, Y; Zhang, H; Zhang, Q; Li, R; Ma, J; Li, Z; Yu, C; Lai, Y; Lin, T; Zhao, X; Zhang, B; Ye, Z; Liu, S; Wang, W; Liang, X; Liao, R; Shi, W

2016-01-01

Podocyte apoptosis is a major mechanism that leads to proteinuria in many chronic kidney diseases. However, the concert mechanisms that cause podocyte apoptosis in these kidney diseases are not fully understood. The Rho family of small GTPases has been shown to be required in maintaining podocyte structure and function. Recent studies have indicated that podocyte-specific deletion of Cdc42 in vivo, but not of RhoA or Rac1, leads to congenital nephrotic syndrome and glomerulosclerosis. However, the underlying cellular events in podocyte controlled by Cdc42 remain unclear. Here, we assessed the cellular mechanisms by which Cdc42 regulates podocyte apoptosis. We found that the expression of Cdc42 and its activity were significantly decreased in high glucose-, lipopolysaccharide- or adriamycin-injured podocytes. Reduced Cdc42 expression in vitro and in vivo by small interfering RNA and selective Cdc42 inhibitor ML-141, respectively, caused podocyte apoptosis and proteinuria. Our results further demonstrated that insufficient Cdc42 or Nwasp, its downstream effector, could decrease the mRNA and protein expression of YAP, which had been regarded as an anti-apoptosis protein in podocyte. Moreover, our data indicated that the loss of stress fibers caused by Cdc42/Nwasp deficiency also decreased Yes-associated protein (YAP) mRNA and protein expression, and induced podocyte apoptosis. Podocyte apoptosis induced by Cdc42/Nwasp/stress fiber deficiency was significantly inhibited by overexpressing-active YAP. Thus, the Cdc42/Nwasp/stress fibers/YAP signal pathway may potentially play an important role in regulating podocyte apoptosis. Maintaining necessary Cdc42 would be one potent way to prevent proteinuria kidney diseases. PMID:26986510

Characterization of Synthetic-Lethal Mutants Reveals a Role for the Saccharomyces Cerevisiae Guanine-Nucleotide Exchange Factor Cdc24p in Vacuole Function and Na(+) Tolerance

PubMed Central

White, W. H.; Johnson, D. I.

1997-01-01

Cdc24p is the guanine-nucleotide exchange factor for the Cdc42p GTPase, which controls cell polarity in Saccharomyces cerevisiae. To identify new genes that may affect cell polarity, we characterized six UV-induced csl (CDC24 synthetic-lethal) mutants that exhibited synthetic-lethality with cdc24-4(ts) at 23°. Five mutants were not complemented by plasmid-borne CDC42, RSR1, BUD5, BEM1, BEM2, BEM3 or CLA4 genes, which are known to play a role in cell polarity. The csl3 mutant displayed phenotypes similar to those observed with calcium-sensitive, Pet(-) vma mutants defective in vacuole function. CSL5 was allelic to VMA5, the vacuolar H(+)-ATPase subunit C, and one third of csl5 cdc24-4(ts) cells were elongated or had misshapen buds. A cdc24-4(ts) Δvma5::LEU2 double mutant did not exhibit synthetic lethality, suggesting that the csl5/vma5 cdc24-4(ts) synthetic-lethality was not simply due to altered vacuole function. The cdc24-4(ts) mutant, like Δvma5::LEU2 and csl3 mutants, was sensitive to high levels of Ca(2+) as well as Na(+) in the growth media, which did not appear to be a result of a fragile cell wall because the phenotypes were not remedied by 1 M sorbitol. Our results indicated that Cdc24p was required in one V-ATPase mutant and another mutant affecting vacuole morphology, and also implicated Cdc24p in Na(+) tolerance. PMID:9286667

CDC14A phosphatase is essential for hearing and male fertility in mouse and human.

PubMed

Imtiaz, Ayesha; Belyantseva, Inna A; Beirl, Alisha J; Fenollar-Ferrer, Cristina; Bashir, Rasheeda; Bukhari, Ihtisham; Bouzid, Amal; Shaukat, Uzma; Azaiez, Hela; Booth, Kevin T; Kahrizi, Kimia; Najmabadi, Hossein; Maqsood, Azra; Wilson, Elizabeth A; Fitzgerald, Tracy S; Tlili, Abdelaziz; Olszewski, Rafal; Lund, Merete; Chaudhry, Taimur; Rehman, Atteeq U; Starost, Matthew F; Waryah, Ali M; Hoa, Michael; Dong, Lijin; Morell, Robert J; Smith, Richard J H; Riazuddin, Sheikh; Masmoudi, Saber; Kindt, Katie S; Naz, Sadaf; Friedman, Thomas B

2018-03-01

The Cell Division-Cycle-14 gene encodes a dual-specificity phosphatase necessary in yeast for exit from mitosis. Numerous disparate roles of vertebrate Cell Division-Cycle-14 (CDC14A) have been proposed largely based on studies of cultured cancer cells in vitro. The in vivo functions of vertebrate CDC14A are largely unknown. We generated and analyzed mutations of zebrafish and mouse CDC14A, developed a computational structural model of human CDC14A protein and report four novel truncating and three missense alleles of CDC14A in human families segregating progressive, moderate-to-profound deafness. In five of these families segregating pathogenic variants of CDC14A, deaf males are infertile, while deaf females are fertile. Several recessive mutations of mouse Cdc14a, including a CRISPR/Cas9-edited phosphatase-dead p.C278S substitution, result in substantial perinatal lethality, but survivors recapitulate the human phenotype of deafness and male infertility. CDC14A protein localizes to inner ear hair cell kinocilia, basal bodies and sound-transducing stereocilia. Auditory hair cells of postnatal Cdc14a mutants develop normally, but subsequently degenerate causing deafness. Kinocilia of germ-line mutants of mouse and zebrafish have normal lengths, which does not recapitulate the published cdc14aa knockdown morphant phenotype of short kinocilia. In mutant male mice, degeneration of seminiferous tubules and spermiation defects result in low sperm count, and abnormal sperm motility and morphology. These findings for the first time define a new monogenic syndrome of deafness and male infertility revealing an absolute requirement in vivo of vertebrate CDC14A phosphatase activity for hearing and male fertility.

Osler-Weber-Rendu syndrome

MedlinePlus

... your provider what other precautions you should take. Support Groups These resources can provide more information on HHT: Centers for Disease Control and Prevention -- www.cdc.gov/ncbddd/hht Cure HHT -- curehht.org National Organization for Rare Disorders -- rarediseases.org/rare-diseases/hereditary- ...

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yuefeng; Zhu, Xiaolan; Xu, Wenlin

2013-02-15

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

Loss of Cdc42 leads to defects in synaptic plasticity and remote memory recall

PubMed Central

Kim, Il Hwan; Wang, Hong; Soderling, Scott H; Yasuda, Ryohei

2014-01-01

Cdc42 is a signaling protein important for reorganization of actin cytoskeleton and morphogenesis of cells. However, the functional role of Cdc42 in synaptic plasticity and in behaviors such as learning and memory are not well understood. Here we report that postnatal forebrain deletion of Cdc42 leads to deficits in synaptic plasticity and in remote memory recall using conditional knockout of Cdc42. We found that deletion of Cdc42 impaired LTP in the Schaffer collateral synapses and postsynaptic structural plasticity of dendritic spines in CA1 pyramidal neurons in the hippocampus. Additionally, loss of Cdc42 did not affect memory acquisition, but instead significantly impaired remote memory recall. Together these results indicate that the postnatal functions of Cdc42 may be crucial for the synaptic plasticity in hippocampal neurons, which contribute to the capacity for remote memory recall. DOI: http://dx.doi.org/10.7554/eLife.02839.001 PMID:25006034

Human replication protein Cdc6 is selectively cleaved by caspase 3 during apoptosis

PubMed Central

Pelizon, Cristina; d’Adda di Fagagna, Fabrizio; Farrace, Lorena; Laskey, Ronald A.

2002-01-01

In eukaryotes, the initiation of DNA replication involves the ordered assembly on chromatin of pre-replicative complexes (pre-RCs), including the origin recognition complex (ORC), Cdc6, Cdt1 and the minichromosome maintenance proteins (MCMs). In light of its indispensable role in the formation of pre-RCs, Cdc6 binding to chromatin represents a key step in the regulation of DNA replication and cell proliferation. Here, we study the human Cdc6 (HuCdc6) protein during programmed cell death (apoptosis). We find that HuCdc6, but not HuOrc2 (a member of the ORC) or HuMcm5 (one of the MCMs), is specifically cleaved in several human cell lines induced to undergo apoptosis by a variety of stimuli. Expression of caspase-uncleavable mutant HuCdc6 attenuates apoptosis, delaying cell death. Therefore, an important function for cleavage of HuCdc6 is to prevent a wounded cell from replicating and to facilitate death. PMID:12151338

Cdc45-induced loading of human RPA onto single-stranded DNA

PubMed Central

Tessmer, Ingrid; Prus, Piotr; Schlott, Bernhard; Pospiech, Helmut

2017-01-01

Abstract Cell division cycle protein 45 (Cdc45) is an essential component of the eukaryotic replicative DNA helicase. We found that human Cdc45 forms a complex with the single-stranded DNA (ssDNA) binding protein RPA. Moreover, it actively loads RPA onto nascent ssDNA. Pull-down assays and surface plasmon resonance studies revealed that Cdc45-bound RPA complexed with ssDNA in the 8–10 nucleotide binding mode, but dissociated when RPA covered a 30-mer. Real-time analysis of RPA-ssDNA binding demonstrated that Cdc45 catalytically loaded RPA onto ssDNA. This placement reaction required physical contacts of Cdc45 with the RPA70A subdomain. Our results imply that Cdc45 controlled stabilization of the 8-nt RPA binding mode, the subsequent RPA transition into 30-mer mode and facilitated an ordered binding to ssDNA. We propose that a Cdc45-mediated loading guarantees a seamless deposition of RPA on newly emerging ssDNA at the nascent replication fork. PMID:28100698

A putative homologue of CDC20/CDH1 in the malaria parasite is essential for male gamete development.

PubMed

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

2012-02-01

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 with male gametogenesis. Cell-cycle regulation and DNA replication in Plasmodium was recently shown to be dependent on the activity of a number of protein kinases. However, the function of cell division cycle proteins that are also involved in this process, such as CDC20 and CDH1 is totally unknown. Here we examine the role of a putative CDC20/CDH1 in the rodent malaria Plasmodium berghei (Pb) using reverse genetics. Phylogenetic analysis identified a single putative Plasmodium CDC20/CDH1 homologue (termed CDC20 for simplicity) suggesting that Plasmodium APC/C has only one regulator. In our genetic approach to delete the endogenous cdc20 gene of P. berghei, we demonstrate that PbCDC20 plays a vital role in male gametogenesis, but is not essential for mitosis in the asexual blood stage. Furthermore, qRT-PCR analysis in parasite lines with deletions of two kinase genes involved in male sexual development (map2 and cdpk4), showed a significant increase in cdc20 transcription in activated gametocytes. DNA replication and ultra structural analyses of cdc20 and map2 mutants showed similar blockage of nuclear division at the nuclear spindle/kinetochore stage. CDC20 was phosphorylated in asexual and sexual stages, but the level of modification was higher in activated gametocytes and ookinetes. Changes in global protein phosphorylation patterns in the Δcdc20 mutant parasites were largely different from those observed in the Δmap2 mutant. This suggests that CDC20 and MAP2 are both likely to play independent but vital roles in male gametogenesis.

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

PubMed Central

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

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 with male gametogenesis. Cell-cycle regulation and DNA replication in Plasmodium was recently shown to be dependent on the activity of a number of protein kinases. However, the function of cell division cycle proteins that are also involved in this process, such as CDC20 and CDH1 is totally unknown. Here we examine the role of a putative CDC20/CDH1 in the rodent malaria Plasmodium berghei (Pb) using reverse genetics. Phylogenetic analysis identified a single putative Plasmodium CDC20/CDH1 homologue (termed CDC20 for simplicity) suggesting that Plasmodium APC/C has only one regulator. In our genetic approach to delete the endogenous cdc20 gene of P. berghei, we demonstrate that PbCDC20 plays a vital role in male gametogenesis, but is not essential for mitosis in the asexual blood stage. Furthermore, qRT-PCR analysis in parasite lines with deletions of two kinase genes involved in male sexual development (map2 and cdpk4), showed a significant increase in cdc20 transcription in activated gametocytes. DNA replication and ultra structural analyses of cdc20 and map2 mutants showed similar blockage of nuclear division at the nuclear spindle/kinetochore stage. CDC20 was phosphorylated in asexual and sexual stages, but the level of modification was higher in activated gametocytes and ookinetes. Changes in global protein phosphorylation patterns in the Δcdc20 mutant parasites were largely different from those observed in the Δmap2 mutant. This suggests that CDC20 and MAP2 are both likely to play independent but vital roles in male gametogenesis. PMID:22383885

Meiotic inheritance of a fungal supernumerary chromosome and its effect on sexual fertility in Nectria haematococca.

PubMed

Garmaroodi, Hamid S; Taga, Masatoki

2015-10-01

PDA1-conditionally dispensable chromosome (CDC) of Nectria haematococca MP VI has long served as a model of supernumerary chromosomes in plant pathogenic fungi because of pathogenicity-related genes located on it. In our previous study, we showed the dosage effects of PDA1-CDC on pathogenicity and homoserine utilization by exploiting tagged PDA1-CDC with a marker gene. CDC content of mating partners and progenies analyzed by PCR, PFGE combined with Southern analysis and chromosome painting via FISH. In this study, we analyzed mode of meiotic inheritance of PDA1-CDC in several mating patterns with regard to CDC content and found a correlation between CDC content of parental strains with fertility of crosses. The results showed non-Mendelian inheritance of this chromosome followed by duplication or loss of the CDC in haploid genome through meiosis that probably were due to premature centromere division, not by nondisjunction as reported for the supernumerary chromosomes in other species. Correlation of CDC with fertility is the first time to be examined in fungi in this study. Copyright © 2015 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Comparative analysis of expression of two p97 homologues in Caenorhabditis elegans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamauchi, Seiji; Yamanaka, Kunitoshi; Ogura, Teru

2006-06-30

Caenorhabditis elegans possesses two p97/VCP/Cdc48p homologues, named CDC-48.1 (C06A1.1) and CDC-48.2 (C41C4.8), although their expression regulation and functional diversity have not yet been studied. We therefore investigated spatial and temporal expression patterns of two p97 homologues in this study. RT-PCR and Western blot analysis showed that the amount of cdc-48.1 was about twofold of that of cdc-48.2 in adults and that two p97 homologues were induced by ER stress. The amount of cdc-48.1 mRNA did not increase in the cdc-48.2 deletion mutant and vice versa. In situ hybridization showed that two p97 homologues are mainly expressed in germ cells. Inmore » vivo expression analysis by using GFP translational fusion constructs revealed that CDC-48.1::GFP was expressed from embryos through to adult worms, while CDC-48.2::GFP was expressed mainly in embryos. These results suggest that the expression of two p97 homologues of C. elegans is differently regulated and independent of each other.« less

GO-Cu7S4 catalyzed ortho-aminomethylation of phenol derivatives with N,N-dimethylbenzylamines: site-selective oxidative CDC.

PubMed

Gupta, Sonu; Chandna, Nisha; Dubey, Pooja; Singh, Ajai K; Jain, Nidhi

2018-06-21

Copper chalcogenide nanoparticles (Cu7S4) supported on graphene oxide (GO) have been synthesized for the first time from Cu2S, and used as highly efficient heterogeneous catalysts for oxidative ortho-selective C-H aminomethylation of phenols with N,N-dimethylbenzylamines. The NPs (30-80 nm) have been characterized by HRTEM, SEM-EDX, PXRD, FTIR, Raman, ICP-AES and XPS analyses. The NP catalyzed sp2-sp3 cross dehydrogenative coupling (CDC) features a broad substrate scope, excellent functional group tolerance, high yields, use of an inexpensive and reusable copper catalyst, mild conditions, and no need for pre-functionalization of substrates.

78 FR 27396 - Statement of Organization, Functions, and Delegations of Authority

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-10

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76 FR 38655 - Office for State, Tribal, Local, and Territorial Support

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-01

... collaborative approaches to these issues and needs. Within the CDC Consultation Policy, it is stated that CDC... the Director (OD), other CDC Centers, Institutes, and Offices, leadership shall actively participate... and presentations from various CDC senior leaderships on activities and areas identified by TAC...

LASL benchmark performance 1978. [CDC STAR-100, 6600, 7600, Cyber 73, and CRAY-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

McKnight, A.L.

1979-08-01

This report presents the results of running several benchmark programs on a CDC STAR-100, a Cray Research CRAY-1, a CDC 6600, a CDC 7600, and a CDC Cyber 73. The benchmark effort included CRAY-1's at several installations running different operating systems and compilers. This benchmark is part of an ongoing program at Los Alamos Scientific Laboratory to collect performance data and monitor the development trend of supercomputers. 3 tables.

Cell cycle regulation in Schizosaccharomyces pombe.

PubMed

Moser, B A; Russell, P

2000-12-01

Cdc2, a cyclin-dependent kinase, controls cell cycle progression in fission yeast. New details of Cdc2 regulation and function have been uncovered in recent studies. These studies involve cyclins that associate with Cdc2 in G1-phase and the proteins that regulate inhibitory phosphorylation of Cdc2 during S-phase and G2-phase. Recent investigations have also provided a better understanding of proteins that regulate DNA replication and that are directly or indirectly controlled by Cdc2.

CDC20 maintains tumor initiating cells

PubMed Central

Xie, Qi; Wu, Qiulian; Mack, Stephen C.; Yang, Kailin; Kim, Leo; Hubert, Christopher G.; Flavahan, William A.; Chu, Chengwei; Bao, Shideng; Rich, Jeremy N.

2015-01-01

Glioblastoma is the most prevalent and lethal primary intrinsic brain tumor. Glioblastoma displays hierarchical arrangement with a population of self-renewing and tumorigenic glioma tumor initiating cells (TICs), or cancer stem cells. While non-neoplastic neural stem cells are generally quiescent, glioblastoma TICs are often proliferative with mitotic control offering a potential point of fragility. Here, we interrogate the role of cell-division cycle protein 20 (CDC20), an essential activator of anaphase-promoting complex (APC) E3 ubiquitination ligase, in the maintenance of TICs. By chromatin analysis and immunoblotting, CDC20 was preferentially expressed in TICs relative to matched non-TICs. Targeting CDC20 expression by RNA interference attenuated TIC proliferation, self-renewal and in vivo tumor growth. CDC20 disruption mediated its effects through induction of apoptosis and inhibition of cell cycle progression. CDC20 maintains TICs through degradation of p21CIP1/WAF1, a critical negative regulator of TICs. Inhibiting CDC20 stabilized p21CIP1/WAF1, resulting in repression of several genes critical to tumor growth and survival, including CDC25C, c-Myc and Survivin. Transcriptional control of CDC20 is mediated by FOXM1, a central transcription factor in TICs. These results suggest CDC20 is a critical regulator of TIC proliferation and survival, linking two key TIC nodes – FOXM1 and p21CIP1/WAF1 — elucidating a potential point for therapeutic intervention. PMID:25938542

Rga6 is a fission yeast Rho GAP involved in Cdc42 regulation of polarized growth

PubMed Central

Revilla-Guarinos, M. T.; Martín-García, Rebeca; Villar-Tajadura, M. Antonia; Estravís, Miguel; Coll, Pedro M.; Pérez, Pilar

2016-01-01

Active Cdc42 is essential for the establishment of polarized growth. This GTPase is negatively regulated by the GTPase-activating proteins (GAPs), which are important for the spatial specificity of Cdc42 function. Rga4 is the only GAP described as negative regulator of fission yeast Cdc42. We report here that Rga6, another fission yeast Cdc42 GAP, shares some functions with Rga4. Cells lacking Rga6 are viable but slightly shorter and broader than wild type, and cells lacking Rga6 and Rga4 simultaneously are rounded. In these cells, active Cdc42 is observed all around the membrane. These additive effects indicate that both GAPs collaborate in the spatial regulation of active Cdc42. Rga6 localizes to the plasma membrane, forming clusters different from those formed by Rga4. A polybasic region at the Rga6 C-terminus is responsible for its membrane localization. Rga6-GFP fluorescence decreases considerably at the growing tips, and this decrease is dependent on the actin cables. Of note, in the absence of Rga6, the amplitude of active Cdc42 oscillations at the tips decreases, and less GTP-Cdc42 accumulates at the new end of the cells. We propose that Rga6 collaborates with Rga4 to spatially restrict active Cdc42 at the cell tips and maintain cell dimensions. PMID:26960792

Deviation of the typical AAA substrate-threading pore prevents fatal protein degradation in yeast Cdc48.

PubMed

Esaki, Masatoshi; Islam, Md Tanvir; Tani, Naoki; Ogura, Teru

2017-07-14

Yeast Cdc48 is a well-conserved, essential chaperone of ATPases associated with diverse cellular activity (AAA) proteins, which recognizes substrate proteins and modulates their conformations to carry out many cellular processes. However, the fundamental mechanisms underlying the diverse pivotal roles of Cdc48 remain unknown. Almost all AAA proteins form a ring-shaped structure with a conserved aromatic amino acid residue that is essential for proper function. The threading mechanism hypothesis suggests that this residue guides the intrusion of substrate proteins into a narrow pore of the AAA ring, thereby becoming unfolded. By contrast, the aromatic residue in one of the two AAA rings of Cdc48 has been eliminated through evolution. Here, we show that artificial retrieval of this aromatic residue in Cdc48 is lethal, and essential features to support the threading mechanism are required to exhibit the lethal phenotype. In particular, genetic and biochemical analyses of the Cdc48 lethal mutant strongly suggested that when in complex with the 20S proteasome, essential proteins are abnormally forced to thread through the Cdc48 pore to become degraded, which was not detected in wild-type Cdc48. Thus, the widely applicable threading model is less effective for wild-type Cdc48; rather, Cdc48 might function predominantly through an as-yet-undetermined mechanism.

CDC-48/p97 is required for proper meiotic chromosome segregation via controlling AIR-2/Aurora B kinase localization in Caenorhabditis elegans.

PubMed

Sasagawa, Yohei; Higashitani, Atsushi; Urano, Takeshi; Ogura, Teru; Yamanaka, Kunitoshi

2012-08-01

CDC-48/p97 is a AAA (ATPases associated with diverse cellular activities) chaperone involved in protein conformational changes such as the disassembly of protein complexes. We previously reported that Caenorhabditis elegans CDC-48.1 and CDC-48.2 (CDC-48s) are essential for the progression of meiosis I metaphase. Here, we report that CDC-48s are required for proper chromosome segregation during meiosis in C. elegans. In wild-type worms, at the diakinesis phase, phosphorylation of histone H3, one of the known substrates of aurora B kinase (AIR-2), on meiosis I chromatids correlated with AIR-2 localization at the cohesion sites of homologous chromatids. Conversely, depletion of CDC-48s resulted in a significant expansion of signals for AIR-2 and phosphorylated histone H3 over the entire length of meiotic chromosomes, leading to defective chromosome segregation, while the total amount of AIR-2 in lysates was not changed by the depletion of CDC-48s. The defective segregation of meiotic chromosomes caused by the depletion of CDC-48s was suppressed by the simultaneous depletion of AIR-2 and is similar to that observed following the depletion of protein phosphatase 1 (PP1) phosphatases. However, the amount and localization of PP1 were not changed by the depletion of CDC-48s. These results suggest that CDC-48s control the restricted localization of AIR-2 to the cohesion sites of homologous chromatids in meiosis I. Copyright © 2012 Elsevier Inc. All rights reserved.

Inducible recruitment of Cdc42 or WASP to a cell-surface receptor triggers actin polymerization and filopodium formation.

PubMed

Castellano, F; Montcourrier, P; Guillemot, J C; Gouin, E; Machesky, L; Cossart, P; Chavrier, P

1999-04-08

Cdc42, a GTP-binding protein of the Rho family, controls actin cytoskeletal organization and helps to generate actin-based protruding structures, such as filopodia. In vitro, Cdc42 regulates actin polymerization by facilitating the creation of free barbed ends - the more rapidly growing ends of actin filaments - and subsequent elongation at these ends. The Wiskott- Aldrich syndrome protein, WASP, which has a pleckstrin-homology domain and a Cdc42/Rac-binding motif, has been implicated in cell signaling and cytoskeleton reorganization. We have investigated the consequences of local recruitment of activated Cdc42 or WASP to the plasma membrane. We used an activated Cdc42 protein that could be recruited to an engineered membrane receptor by adding rapamycin as a bridge, and added antibody-coupled beads to aggregate these receptors. Inducible recruitment of Cdc42 to clusters of receptors stimulated actin polymerization, resulting in the formation of membrane protrusions. Cdc42-induced protrusions were enriched in the vasodilator-stimulated phosphoprotein VASP and the focal-adhesion-associated proteins zyxin and ezrin. The Cdc42 effector WASP could also induce the formation of protrusions, albeit of different morphology. This is the first demonstration that the local recruitment of activated Cdc42 or its downstream effector, WASP, to a membrane receptor in whole cells is sufficient to trigger actin polymerization that results in the formation of membrane protrusions. Our data suggest that Cdc42-induced actin-based protrusions result from the local and serial recruitment of cytoskeletal proteins including zyxin, VASP, and ezrin.

13 CFR 120.851 - CDC ethical requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false CDC ethical requirements. 120.851... Company Loan Program (504) Other Cdc Requirements § 120.851 CDC ethical requirements. CDCs and their Associates must act ethically and exhibit good character. They must meet all of the ethical requirements of...

13 CFR 120.851 - CDC ethical requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false CDC ethical requirements. 120.851... Company Loan Program (504) Other Cdc Requirements § 120.851 CDC ethical requirements. CDCs and their Associates must act ethically and exhibit good character. They must meet all of the ethical requirements of...

33 CFR 105.295 - Additional requirements-Certain Dangerous Cargo (CDC) facilities.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Dangerous Cargo (CDC) facilities. 105.295 Section 105.295 Navigation and Navigable Waters COAST GUARD... Requirements § 105.295 Additional requirements-Certain Dangerous Cargo (CDC) facilities. (a) At all MARSEC Levels, owners or operators of CDC facilities must ensure the implementation of the following security...

33 CFR 105.295 - Additional requirements-Certain Dangerous Cargo (CDC) facilities.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Dangerous Cargo (CDC) facilities. 105.295 Section 105.295 Navigation and Navigable Waters COAST GUARD... Requirements § 105.295 Additional requirements-Certain Dangerous Cargo (CDC) facilities. (a) At all MARSEC Levels, owners or operators of CDC facilities must ensure the implementation of the following security...

33 CFR 105.295 - Additional requirements-Certain Dangerous Cargo (CDC) facilities.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Dangerous Cargo (CDC) facilities. 105.295 Section 105.295 Navigation and Navigable Waters COAST GUARD... Requirements § 105.295 Additional requirements-Certain Dangerous Cargo (CDC) facilities. (a) At all MARSEC Levels, owners or operators of CDC facilities must ensure the implementation of the following security...

33 CFR 105.295 - Additional requirements-Certain Dangerous Cargo (CDC) facilities.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Dangerous Cargo (CDC) facilities. 105.295 Section 105.295 Navigation and Navigable Waters COAST GUARD... Requirements § 105.295 Additional requirements-Certain Dangerous Cargo (CDC) facilities. (a) At all MARSEC Levels, owners or operators of CDC facilities must ensure the implementation of the following security...

33 CFR 105.295 - Additional requirements-Certain Dangerous Cargo (CDC) facilities.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Dangerous Cargo (CDC) facilities. 105.295 Section 105.295 Navigation and Navigable Waters COAST GUARD... Requirements § 105.295 Additional requirements-Certain Dangerous Cargo (CDC) facilities. (a) At all MARSEC Levels, owners or operators of CDC facilities must ensure the implementation of the following security...

Diagnosis and Management of Uncomplicated Chlamydia trachomatis Infections in Adolescents and Adults: Summary of Evidence Reviewed for the 2015 Centers for Disease Control and Prevention Sexually Transmitted Diseases Treatment Guidelines.

PubMed

Geisler, William M

2015-12-15

In preparation for the 2015 Centers for Disease Control and Prevention (CDC) Sexually Transmitted Diseases (STD) Treatment Guidelines, the CDC convened an advisory group in 2013 to examine recent abstracts and published literature addressing the epidemiology, diagnosis, and management of STDs. This article summarizes the key questions, evidence, and recommendations for the diagnosis and management of uncomplicated Chlamydia trachomatis (CT) infection in adolescents and adults that were considered in development of the 2015 CDC STD Treatment Guidelines. The evidence reviewed primarily focused on CT infection risk factors in women, clinical significance of oropharyngeal CT detection, acceptability and performance of CT testing on self-collected specimens in men, performance of CT point-of-care tests, efficacy of recommended and investigational CT infection treatments, and timing of test of cure following CT infection treatment in pregnant women. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Effects of Lignocaine Administered Intravenously or Intratracheally on Airway and Hemodynamic Responses during Emergence and Extubation in Patients Undergoing Elective Craniotomies in Supine Position.

PubMed

Shabnum, Tabasum; Ali, Zulfiqar; Naqash, Imtiaz Ahmad; Mir, Aabid Hussain; Azhar, Khan; Zahoor, Syed Amer; Mir, Abdul Waheed

2017-01-01

Sympathoadrenergic responses during emergence and extubation can lead to an increase in heart rate (HR) and blood pressure whereas increased airway responses may lead to coughing and laryngospasm. The aim of our study was to compare the effects of lignocaine administered intravenously (IV) or intratracheally on airway and hemodynamic responses during emergence and extubation in patients undergoing elective craniotomies. Sixty patients with physical status American Society of Anaesthesiologists Classes I and II aged 18-70 years, scheduled to undergo elective craniotomies were included. The patients were randomly divided into three groups of twenty patients; Group 1 receiving IV lignocaine and intratracheal placebo (IV group), Group 2 receiving intratracheal lignocaine and IV placebo (I/T group), and Group 3 receiving IV and intratracheal placebo (placebo group). The tolerance to the endotracheal tube was monitored, and number of episodes of cough was recorded during emergence and at the time of extubation. Hemodynamic parameters such as HR and blood pressure (systolic, diastolic, mean arterial pressure) were also recorded. There was a decrease of HR in both IV and intratracheal groups in comparison with placebo group ( P < 0.005). Rise in blood pressure (systolic blood pressure, diastolic blood pressure and mean arterial pressure) was comparable in both Groups 1 and 2 but was lower in comparison with placebo group ( P < 0.005). Cough suppression was comparable in all the three groups. Grade III cough (15%) was documented only in placebo group. Both IV and intratracheal lignocaine are effective in attenuation of hemodynamic response if given within 20 min from skull pin removal to extubation. There was comparable cough suppression through intratracheal route and IV routes than the placebo group.

Archaeal orthologs of Cdc45 and GINS form a stable complex that stimulates the helicase activity of MCM

PubMed Central

Xu, Yuli; Gristwood, Tamzin; Hodgson, Ben; Trinidad, Jonathan C.; Albers, Sonja-Verena; Bell, Stephen D.

2016-01-01

The regulated recruitment of Cdc45 and GINS is key to activating the eukaryotic MCM(2-7) replicative helicase. We demonstrate that the homohexameric archaeal MCM helicase associates with orthologs of GINS and Cdc45 in vivo and in vitro. Association of these factors with MCM robustly stimulates the MCM helicase activity. In contrast to the situation in eukaryotes, archaeal Cdc45 and GINS form an extremely stable complex before binding MCM. Further, the archaeal GINS•Cdc45 complex contains two copies of Cdc45. Our analyses give insight into the function and evolution of the conserved core of the archaeal/eukaryotic replisome. PMID:27821767

Archaeal orthologs of Cdc45 and GINS form a stable complex that stimulates the helicase activity of MCM.

PubMed

Xu, Yuli; Gristwood, Tamzin; Hodgson, Ben; Trinidad, Jonathan C; Albers, Sonja-Verena; Bell, Stephen D

2016-11-22

The regulated recruitment of Cdc45 and GINS is key to activating the eukaryotic MCM(2-7) replicative helicase. We demonstrate that the homohexameric archaeal MCM helicase associates with orthologs of GINS and Cdc45 in vivo and in vitro. Association of these factors with MCM robustly stimulates the MCM helicase activity. In contrast to the situation in eukaryotes, archaeal Cdc45 and GINS form an extremely stable complex before binding MCM. Further, the archaeal GINS•Cdc45 complex contains two copies of Cdc45. Our analyses give insight into the function and evolution of the conserved core of the archaeal/eukaryotic replisome.

Cdc48 regulates a deubiquitylase cascade critical for mitochondrial fusion

PubMed Central

den Brave, Fabian

2018-01-01

Cdc48/p97, a ubiquitin-selective chaperone, orchestrates the function of E3 ligases and deubiquitylases (DUBs). Here, we identify a new function of Cdc48 in ubiquitin-dependent regulation of mitochondrial dynamics. The DUBs Ubp12 and Ubp2 exert opposing effects on mitochondrial fusion and cleave different ubiquitin chains on the mitofusin Fzo1. We demonstrate that Cdc48 integrates the activities of these two DUBs, which are themselves ubiquitylated. First, Cdc48 promotes proteolysis of Ubp12, stabilizing pro-fusion ubiquitylation on Fzo1. Second, loss of Ubp12 stabilizes Ubp2 and thereby facilitates removal of ubiquitin chains on Fzo1 inhibiting fusion. Thus, Cdc48 synergistically regulates the ubiquitylation status of Fzo1, allowing to control the balance between activation or repression of mitochondrial fusion. In conclusion, we unravel a new cascade of ubiquitylation events, comprising Cdc48 and two DUBs, fine-tuning the fusogenic activity of Fzo1. PMID:29309037

Comparative Efficiency of Biogents Gravid Aedes Trap, Cdc Autocidal Gravid Ovitrap, and CDC Gravid Trap in Northeastern Florida.

PubMed

Cilek, James E; Knapp, Jennifer A; Richardson, Alec G

2017-06-01

We conducted a study to compare the effectiveness of the Biogents Gravid Aedes Trap (BG-GAT) and Centers for Disease Control and Prevention (CDC) Autocidal Gravid Ovitrap (AGO) with that of the CDC Gravid Trap (CDC-GT) (as a standard) for their proficiency to collect mosquitoes in an urban residential neighborhood in northeastern Florida. Aedes aegypti , Ae. albopictus, and Culex quinquefasciatus were collected from each trap, with the latter species being predominant. Significantly more Cx. quinquefasciatus were collected from CDC-GT traps compared with the other 2 traps. Pairwise comparison of the efficiency of the CDC-GT revealed that this trap collected 6.7- to 21.5-fold more mosquitoes than the BG-GAT, depending on species. The BG-GAT collected overall more mosquitoes (3- to 6-fold) than the AGO, with the exception of Ae. aegypti, where both traps were nearly equal in effectiveness.

Validation of the prognostic grouping of the seventh edition of the tumor-nodes-metastasis classification using a large-scale prospective cohort study database of prostate cancer treated with primary androgen deprivation therapy.

PubMed

Kimura, Tomokazu; Onozawa, Mizuki; Miyazaki, Jun; Kawai, Koji; Nishiyama, Hiroyuki; Hinotsu, Shiro; Akaza, Hideyuki

2013-09-01

In the TNM seventh edition, a prognostic grouping for prostate cancer incorporating prostate-specific antigen and Gleason score was advocated. The present study was carried out to evaluate and validate prognostic grouping in prostate cancer patients. The 15 259 study patients treated with primary androgen deprivation therapy were enrolled in the Japan Study Group of Prostate Cancer. Overall survival was stratified by tumor-nodes-metastasis, Gleason score and prostate-specific antigen, and extensively analyzed. The accuracy of grouping systems was evaluated by the concordance index. The 5-year overall survival in prognostic grouping-I, IIA, IIB, III and IV was 90.0%, 88.3%, 84.8%, 80.6% and 57.1%, respectively. When considering subgroup stratification, the 5-year overall survival of subgroups prognostic grouping-IIA, IIB, III and IV was 80.9∼90.5%, 75.4∼91.8%, 75.7∼89.0% and 46.9∼86.2%, respectively. When prognostic grouping-IIB was subclassified into IIB1 (except IIB2) and IIB2 (T1-2b, prostate-specific antigen >20, Gleason score ≥8, and T2c, Gleason score ≥8), the 5-year overall survival of IIB2 was significantly lower than that of IIB1 (79.4% and 87.3%, P < 0.0001). Also, when prognostic grouping-IV was subclassified into IV1 (except IV2) and IV2 (M1, prostate-specific antigen >100 or Gleason score ≥8), the 5-year overall survival of prognostic grouping-IV1 was superior to that of IV2 (72.9% and 49.5%, P < 0.0001). Prognostic groupings were reclassified into modified prognostic groupings, divided into modified prognostic grouping-A (prognostic grouping-I, IIA, and IIB1), modified prognostic grouping-B (prognostic grouping-IIB2 and III), modified prognostic grouping-C (prognostic grouping-IV1) and modified prognostic grouping-D (prognostic grouping-IV2). The concordance index of prognostic grouping and modified prognostic grouping for overall survival was 0.670 and 0.685, respectively. Prognostic grouping could stratify the prognosis of prostate cancer patients. However, there is considerable variation among the prognostic grouping subgroups. Thus, the use of a modified prognostic grouping for patients treated with primary androgen deprivation therapy is advisable. © 2013 The Japanese Urological Association.

77 FR 2550 - Office for State, Tribal, Local and Territorial Support (OSTLTS)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-18

... in October of 2005 with the primary purpose of providing guidance across the agency to work.../AN access to CDC resources and programs. In November of 2006, an Agency Advisory Committee (the CDC... government-to-government consultation activities rests within the CDC Office of the Director (OD), other CDC...

13 CFR 120.926 - Referral fee.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Loan Program (504) Third Party Loans § 120.926 Referral fee. The CDC can receive a reasonable referral fee from the Third Party Lender if the CDC secured the Third Party Lender for the Borrower under a written contract between the CDC and the Third Party Lender. Both the CDC and the Third Party Lender are...

76 FR 54774 - Notice of Intent To Award Affordable Care Act Funding, Funding Opportunity Announcement CDC-RFA...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-02

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13 CFR 120.926 - Referral fee.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Loan Program (504) Third Party Loans § 120.926 Referral fee. The CDC can receive a reasonable referral fee from the Third Party Lender if the CDC secured the Third Party Lender for the Borrower under a written contract between the CDC and the Third Party Lender. Both the CDC and the Third Party Lender are...

13 CFR 120.926 - Referral fee.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Loan Program (504) Third Party Loans § 120.926 Referral fee. The CDC can receive a reasonable referral fee from the Third Party Lender if the CDC secured the Third Party Lender for the Borrower under a written contract between the CDC and the Third Party Lender. Both the CDC and the Third Party Lender are...

13 CFR 120.926 - Referral fee.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Loan Program (504) Third Party Loans § 120.926 Referral fee. The CDC can receive a reasonable referral fee from the Third Party Lender if the CDC secured the Third Party Lender for the Borrower under a written contract between the CDC and the Third Party Lender. Both the CDC and the Third Party Lender are...

13 CFR 120.926 - Referral fee.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Loan Program (504) Third Party Loans § 120.926 Referral fee. The CDC can receive a reasonable referral fee from the Third Party Lender if the CDC secured the Third Party Lender for the Borrower under a written contract between the CDC and the Third Party Lender. Both the CDC and the Third Party Lender are...

Cdc20 hypomorphic mice fail to counteract de novo synthesis of cyclin B1 in mitosis

PubMed Central

Malureanu, Liviu; Jeganathan, Karthik B.; Jin, Fang; Baker, Darren J.; van Ree, Janine H.; Gullon, Oliver; Chen, Zheyan; Henley, John R.

2010-01-01

Cdc20 is an activator of the anaphase-promoting complex/cyclosome that initiates anaphase onset by ordering the destruction of cyclin B1 and securin in metaphase. To study the physiological significance of Cdc20 in higher eukaryotes, we generated hypomorphic mice that express small amounts of this essential cell cycle regulator. In this study, we show that these mice are healthy and not prone to cancer despite substantial aneuploidy. Cdc20 hypomorphism causes chromatin bridging and chromosome misalignment, revealing a requirement for Cdc20 in efficient sister chromosome separation and chromosome–microtubule attachment. We find that cyclin B1 is newly synthesized during mitosis via cytoplasmic polyadenylation element–binding protein-dependent translation, causing its rapid accumulation between prometaphase and metaphase of Cdc20 hypomorphic cells. Anaphase onset is significantly delayed in Cdc20 hypomorphic cells but not when translation is inhibited during mitosis. These data reveal that Cdc20 is particularly rate limiting for cyclin B1 destruction because of regulated de novo synthesis of this cyclin after prometaphase onset. PMID:20956380

Cdc7 kinase - a new target for drug development.

PubMed

Swords, Ronan; Mahalingam, Devalingam; O'Dwyer, Michael; Santocanale, Corrado; Kelly, Kevin; Carew, Jennifer; Giles, Francis

2010-01-01

The cell division cycle 7 (Cdc7) is a serine threonine kinase that is of critical importance in the regulation of normal cell cycle progression. Cdc7 kinase is highly conserved during evolution and much has been learned about its biological roles in humans through the study of lower eukaryotes, particularly yeasts. Two important regulator proteins, Dbf4 and Drf1, bind to and modulate the kinase activity of human Cdc7 which phosphorylates several sites on Mcm2 (minichromosome maintenance protein 2), one of the six subunits of the replicative DNA helicase needed for duplication of the genome. Through regulation of both DNA synthesis and DNA damage response, both key functions in the survival of tumour cells, Cdc7 becomes an attractive target for pharmacological inhibition. There are much data available on the pre-clinical anti-cancer effects of Cdc7 depletion and although there are no available Cdc7 inhibitors in clinical trials as yet, several lead compounds are being optimised for this purpose. In this review, we will address the current status of Cdc7 as an important target for new drug development.

Comparison of automatic traps to capture mosquitoes (Diptera: Culicidae) in rural areas in the tropical Atlantic rainforest

PubMed Central

de Sá, Ivy Luizi Rodrigues; Sallum, Maria Anice Mureb

2013-01-01

In several countries, surveillance of insect vectors is accomplished with automatic traps. This study addressed the performance of Mosquito Magnet® Independence (MMI) in comparison with those of CDC with CO2 and lactic acid (CDC-A) and CDC light trap (CDC-LT). The collection sites were in a rural region located in a fragment of secondary tropical Atlantic rainforest, southeastern Brazil. Limatus durhami and Limatus flavisetosus were the dominant species in the MMI, whereas Ochlerotatus scapularis was most abundant in CDC-A. Culex ribeirensis and Culex sacchettae were dominant species in the CDC-LT. Comparisons among traps were based on diversity indices. Results from the diversity analyses showed that the MMI captured a higher abundance of mosquitoes and that the species richness estimated with it was higher than with CDC-LT. Contrasting, difference between MMI and CDC-A was not statistically significant. Consequently, the latter trap seems to be both an alternative for the MMI and complementary to it for ecological studies and entomological surveillance. PMID:24402154

Cdc45-induced loading of human RPA onto single-stranded DNA.

PubMed

Szambowska, Anna; Tessmer, Ingrid; Prus, Piotr; Schlott, Bernhard; Pospiech, Helmut; Grosse, Frank

2017-04-07

Cell division cycle protein 45 (Cdc45) is an essential component of the eukaryotic replicative DNA helicase. We found that human Cdc45 forms a complex with the single-stranded DNA (ssDNA) binding protein RPA. Moreover, it actively loads RPA onto nascent ssDNA. Pull-down assays and surface plasmon resonance studies revealed that Cdc45-bound RPA complexed with ssDNA in the 8-10 nucleotide binding mode, but dissociated when RPA covered a 30-mer. Real-time analysis of RPA-ssDNA binding demonstrated that Cdc45 catalytically loaded RPA onto ssDNA. This placement reaction required physical contacts of Cdc45 with the RPA70A subdomain. Our results imply that Cdc45 controlled stabilization of the 8-nt RPA binding mode, the subsequent RPA transition into 30-mer mode and facilitated an ordered binding to ssDNA. We propose that a Cdc45-mediated loading guarantees a seamless deposition of RPA on newly emerging ssDNA at the nascent replication fork. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

The Zds proteins control entry into mitosis and target protein phosphatase 2A to the Cdc25 phosphatase.

PubMed

Wicky, Sidonie; Tjandra, Hendri; Schieltz, David; Yates, John; Kellogg, Douglas R

2011-01-01

The Wee1 kinase restrains entry into mitosis by phosphorylating and inhibiting cyclin-dependent kinase 1 (Cdk1). The Cdc25 phosphatase promotes entry into mitosis by removing Cdk1 inhibitory phosphorylation. Experiments in diverse systems have established that Wee1 and Cdc25 are regulated by protein phosphatase 2A (PP2A), but a full understanding of the function and regulation of PP2A in entry into mitosis has remained elusive. In budding yeast, entry into mitosis is controlled by a specific form of PP2A that is associated with the Cdc55 regulatory subunit (PP2A(Cdc55)). We show here that related proteins called Zds1 and Zds2 form a tight stoichiometric complex with PP2A(Cdc55) and target its activity to Cdc25 but not to Wee1. Conditional inactivation of the Zds proteins revealed that their function is required primarily at entry into mitosis. In addition, Zds1 undergoes cell cycle-dependent changes in phosphorylation. Together, these observations define a role for the Zds proteins in controlling specific functions of PP2A(Cdc55) and suggest that upstream signals that regulate PP2A(Cdc55) may play an important role in controlling entry into mitosis.

Dendritic spine geometry can localize GTPase signaling in neurons

PubMed Central

Ramirez, Samuel A.; Raghavachari, Sridhar; Lew, Daniel J.

2015-01-01

Dendritic spines are the postsynaptic terminals of most excitatory synapses in the mammalian brain. Learning and memory are associated with long-lasting structural remodeling of dendritic spines through an actin-mediated process regulated by the Rho-family GTPases RhoA, Rac, and Cdc42. These GTPases undergo sustained activation after synaptic stimulation, but whereas Rho activity can spread from the stimulated spine, Cdc42 activity remains localized to the stimulated spine. Because Cdc42 itself diffuses rapidly in and out of the spine, the basis for the retention of Cdc42 activity in the stimulated spine long after synaptic stimulation has ceased is unclear. Here we model the spread of Cdc42 activation at dendritic spines by means of reaction-diffusion equations solved on spine-like geometries. Excitable behavior arising from positive feedback in Cdc42 activation leads to spreading waves of Cdc42 activity. However, because of the very narrow neck of the dendritic spine, wave propagation is halted through a phenomenon we term geometrical wave-pinning. We show that this can account for the localization of Cdc42 activity in the stimulated spine, and, of interest, retention is enhanced by high diffusivity of Cdc42. Our findings are broadly applicable to other instances of signaling in extreme geometries, including filopodia and primary cilia. PMID:26337387

Phosphorylation of Bem2p and Bem3p may contribute to local activation of Cdc42p at bud emergence

PubMed Central

Knaus, Michèle; Pelli-Gulli, Marie-Pierre; van Drogen, Frank; Springer, Sander; Jaquenoud, Malika; Peter, Matthias

2007-01-01

Site-specific activation of the Rho-type GTPase Cdc42p is critical for the establishment of cell polarity. Here we investigated the role and regulation of the GTPase-activating enzymes (GAPs) Bem2p and Bem3p for Cdc42p activation and actin polarization at bud emergence in Saccharomyces cerevisiae. Bem2p and Bem3p are localized throughout the cytoplasm and the cell cortex in unbudded G1 cells, but accumulate at sites of polarization after bud emergence. Inactivation of Bem2p results in hyperactivation of Cdc42p and polarization toward multiple sites. Bem2p and Bem3p are hyperphosphorylated at bud emergence most likely by the Cdc28p-Cln2p kinase. This phosphorylation appears to inhibit their GAP activity in vivo, as non-phosphorylatable Bem3p mutants are hyperactive and interfere with Cdc42p activation. Taken together, our results indicate that Bem2p and Bem3p may function as global inhibitors of Cdc42p activation during G1, and their inactivation by the Cdc28p/Cln kinase contributes to site-specific activation of Cdc42p at bud emergence. PMID:17914457

Promoting influenza vaccination: insights from a qualitative meta-analysis of 14 years of influenza-related communications research by U.S. Centers for Disease Control and Prevention (CDC).

PubMed

Nowak, Glen J; Sheedy, Kristine; Bursey, Kelli; Smith, Teresa M; Basket, Michelle

2015-06-04

A primary mission of the U.S. Centers for Disease Control and Prevention's (CDC) is promoting immunization against seasonal influenza. As with most education efforts, CDC's influenza-related communications are often informed by formative research. A qualitative meta-analysis of 29 unpublished, primarily qualitative CDC-sponsored studies related to flu and flu vaccination knowledge, attitudes and beliefs (KABs). The studies, undertaken between 2000 and 2013, involved focus groups, in-depth interviews, message testing and surveys. Some involved health care professionals, while others involved members of the public, including sub-populations at risk for severe illness. The themes that emerged suggested progress in terms of KABs related to influenza and influenza vaccination, but also the persistence of many barriers to vaccine acceptance. With respect to the public, recurring themes included limited understanding of influenza and immunization recommendations, indications of greater sub-group recognition of the value of flu vaccination, continued resistance to vaccination among many, and overestimation of the effectiveness of non-vaccine measures. Seven cognitive facilitators of vaccination were identified in the studies along with six cognitive barriers. For health care providers, the analysis suggests greater knowledge and more favorable beliefs, but many misperceptions persist and are similar to those held by the public. KABs often differed by type or category of health care provider. The themes identified in this qualitative analysis illustrate the difficulty in changing KABs related to influenza and influenza vaccine, particularly on the scope and scale needed to greatly improve uptake. Even with an influenza pandemic and more vaccine options available, public and some health care provider perceptions and beliefs are difficult and slow to change. This meta-analysis does, however, provide important insights from previously unpublished information that can help those who are promoting influenza vaccination to health care providers, the general public and specific populations within the general population. Copyright © 2015 Elsevier Ltd. All rights reserved.

The yeast SUMO isopeptidase Smt4/Ulp2 and the polo kinase Cdc5 act in an opposing fashion to regulate sumoylation in mitosis and cohesion at centromeres.

PubMed

Baldwin, Melissa L; Julius, Jeffrey A; Tang, Xianying; Wang, Yanchang; Bachant, Jeff

2009-10-15

Post-translation modification through the SUMO pathway is cell cycle regulated, with specific SUMO conjugates accumulating in mitotic cells. The basis for this regulation, however, and its functional significance remain poorly understood. We present evidence that in budding yeast sumoylation during mitosis may be controlled through the SUMO deconjugating enzyme Smt4/Ulp2. We isolated the polo kinase Cdc5 as an Ulp2-interacting protein, and find a C-terminal region of Ulp2 is phosphorylated during mitosis in a Cdc5-dependent manner. cdc5 mutants display reduced levels of mitotic SUMO conjugates, suggesting Cdc5 may negatively regulate Ulp2 to promote sumoylation. Previously, we found one phenotype associated with ulp2 mutants is an inability to maintain chromatid cohesion at centromere-proximal chromosomal regions. We now show this defect is rescued by inactivating Cdc5, indicating Ulp2 maintains cohesion by counter-acting Cdc5 activity. The cohesinregulator Pds5 is a likely target of this pathway, as Cdc5 overproduction forces Pds5 dissociation from chromosomes and Pds5 overproduction restores cohesion in ulp2 mutants. Overall, these observations reveal Cdc5 is a novel regulator of the SUMO pathway and suggest the outlines of a broader circuitry in which Ulp2 and Cdc5 act in a mutually antagonistic fashion to modulate maintenance and dissolution of cohesion at centromeres.

Large deletion at the CDC73 gene locus and search for predictive markers of the presence of a CDC73 genetic lesion.

PubMed

Muscarella, Lucia Anna; Turchetti, Daniela; Fontana, Andrea; Baorda, Filomena; Palumbo, Orazio; la Torre, Annamaria; de Martino, Danilo; Franco, Renato; Losito, Nunzia Simona; Repaci, Andrea; Pagotto, Uberto; Cinque, Luigia; Copetti, Massimiliano; Chiofalo, Maria Grazia; Pezzullo, Luciano; Graziano, Paolo; Scillitani, Alfredo; Guarnieri, Vito

2018-04-17

The Hyperparathyroidism with Jaw-Tumours syndrome is caused by mutations of the CDC73 gene: it has been suggested that early onset of the disease and high Ca 2+ levels may predict the presence of a CDC73 mutation. We searched for large deletions at the CDC73 locus in patients with: HPT-JT (nr 2), atypical adenoma (nr 7) or sporadic parathyroid carcinoma (nr 11) with a specific MLPA and qRT-PCR assays applied on DNA extracted from whole blood. A Medline search in database for all the papers reporting a CDC73 gene mutation, clinical/histological diagnosis, age at onset, Ca 2+ , PTH levels for familial/sporadic cases was conducted with the aim to possibly identify biochemical/clinical markers predictive, in first diagnosis, of the presence of a CDC73 gene mutation. A novel genomic deletion of the first 10 exons of the CDC73 gene was found in a 3-generation HPT-JT family, confirmed by SNP array analysis. A classification tree built on the published data, showed the highest probability of having a CDC73 mutation in subjects with age at the onset < 41.5 years (44/47 subjects, 93.6%, had the mutation). Whereas the lowest probability was found in subjects with age at the onset ≥ 41.5 years and Ca 2+ levels <13.96 mg/dL (7/20 subjects, 35.0%, had the mutation, odds ratio = 27.1, p < 0.001). We report a novel large genomic CDC73 gene deletion identified in an Italian HPT-JT family. Age at onset < 41.5 ys and Ca 2+ > 13.96 mg/dL are predictive for the presence of a CDC73 genetic lesion.

Measurement characteristics for two health-related quality of life measures in older adults: The SF-36 and the CDC Healthy Days items.

PubMed

Barile, John P; Horner-Johnson, Willi; Krahn, Gloria; Zack, Matthew; Miranda, David; DeMichele, Kimberly; Ford, Derek; Thompson, William W

2016-10-01

The Short Form Health Survey (SF-36) and the Centers for Disease Control and Prevention (CDC) Healthy Days items are well known measures of health-related quality of life. The validity of the SF-36 for older adults and those with disabilities has been questioned. Assess the extent to which the SF-36 and the Centers for Disease Control and Prevention (CDC) Healthy Days items measure the same aspects of health; whether the SF-36 and the CDC unhealthy days items are invariant across gender, functional status, or the presence of chronic health conditions of older adults; and whether each of the SF-36's eight subscales is independently associated with the CDC Healthy Days items. We analyzed data from 66,269 adult Medicare advantage members age 65 and older. We used confirmatory factor analyses and regression modeling to test associations between the CDC Healthy Days items and subscales of the SF-36. The CDC Healthy Days items were associated with the SF-36 global measures of physical and mental health. The CDC physically unhealthy days item was associated with the SF-36 subscales for bodily pain, physical role limitations, and general health, while the CDC mentally unhealthy days item was associated with the SF-36 subscales for mental health, emotional role limitations, vitality and social functioning. The SF-36 physical functioning subscale was not independently associated with either of the CDC Healthy Days items. The CDC Healthy Days items measure similar domains as the SF-36 but appear to assess HRQOL without regard to limitations in functioning. Copyright © 2016 Elsevier Inc. All rights reserved.

Measurement characteristics for two health-related quality of life measures in older adults: The SF-36 and the CDC Healthy Days items

PubMed Central

Barile, John P.; Horner-Johnson, Willi; Krahn, Gloria; Zack, Matthew; Miranda, David; DeMichele, Kimberly; Ford, Derek; Thompson, William W.

2017-01-01

Background The Short Form Health Survey (SF-36) and the Centers for Disease Control and Prevention (CDC) Healthy Days items are well known measures of health-related quality of life. The validity of the SF-36 for older adults and those with disabilities has been questioned. Objective Assess the extent to which the SF-36 and the Centers for Disease Control and Prevention (CDC) Healthy Days items measure the same aspects of health; whether the SF-36 and the CDC unhealthy days items are invariant across gender, functional status, or the presence of chronic health conditions of older adults; and whether each of the SF-36’s eight subscales is independently associated with the CDC Healthy Days items. Methods We analyzed data from 66,269 adult Medicare advantage members age 65 and older. We used confirmatory factor analyses and regression modeling to test associations between the CDC Healthy Days items and subscales of the SF-36. Results The CDC Healthy Days items were associated with the SF-36 global measures of physical and mental health. The CDC physically unhealthy days item was associated with the SF-36 subscales for bodily pain, physical role limitations, and general health, while the CDC mentally unhealthy days item was associated with the SF-36 subscales for mental health, emotional role limitations, vitality and social functioning. The SF-36 physical functioning subscale was not independently associated with either of the CDC Healthy Days items. Conclusions The CDC Healthy Days items measure similar domains as the SF-36 but appear to assess HRQOL without regard to limitations in functioning. PMID:27259343

Cognitive and Adaptive Skills in Toddlers Who Meet Criteria for Autism in DSM-IV but not DSM-5

PubMed Central

Brennan, Laura A.; Barton, Marianne L.; Fein, Deborah

2017-01-01

The current study compared adaptive and cognitive skills, and autism severity of toddlers with an autism spectrum disorder (ASD) diagnosis under DSM-IV but not DSM-5 criteria (DSM-IV only group) to those who met autism criteria under both diagnostic systems (DSM-5 group) and to those without ASD (non-ASD group). The toddlers in the DSM-IV only group were less delayed on various domains of adaptive (Communication, Socialization) and cognitive (Expressive and Receptive language, Fine Motor, Visual Reception) skills, and had less severe symptoms of ASD than the DSM-5 group. Thus, they might have the best potential for successful intervention. The DSM-IV only group did not differ from the non-ASD group in any adaptive or cognitive skills except for socialization skills, the hallmark of ASD. PMID:27628939

Cognitive and Adaptive Skills in Toddlers Who Meet Criteria for Autism in DSM-IV but not DSM-5.

PubMed

Jashar, Dasal Tenzin; Brennan, Laura A; Barton, Marianne L; Fein, Deborah

2016-12-01

The current study compared adaptive and cognitive skills, and autism severity of toddlers with an autism spectrum disorder (ASD) diagnosis under DSM-IV but not DSM-5 criteria (DSM-IV only group) to those who met autism criteria under both diagnostic systems (DSM-5 group) and to those without ASD (non-ASD group). The toddlers in the DSM-IV only group were less delayed on various domains of adaptive (Communication, Socialization) and cognitive (Expressive and Receptive language, Fine Motor, Visual Reception) skills, and had less severe symptoms of ASD than the DSM-5 group. Thus, they might have the best potential for successful intervention. The DSM-IV only group did not differ from the non-ASD group in any adaptive or cognitive skills except for socialization skills, the hallmark of ASD.

Prophylactic use of intravenous ondansetron versus ketamine - midazolam combination for prevention of shivering during spinal anesthesia: A randomized double-blind placebo-controlled trial

PubMed Central

Safavi, Mohammadreza; Honarmand, Azim; Mohammadsadeqie, Sara

2015-01-01

Background: The aim of this study was to compare the efficacy intravenous (IV) ondansetron with ketamine plus midazolam for the prevention of shivering during spinal anesthesia (SA). Materials and Methods: Ninety patients, aged 18–65 years, undergoing lower extremity orthopedic surgery were included in the present study. SA was performed in all patients with hyperbaric bupivacaine 15 mg. The patients were randomly allocated to receive normal saline (Group C), ondansetron 8 mg IV (Group O) or ketamine 0.25 mg/kg IV plus midazolam 37.5 μg/kg IV (Group KM) immediately after SA. During surgery, shivering scores were recorded at 5 min intervals. The operating room temperature was maintained at 24°C. Results: The incidences of shivering were 18 (60%) in Group C, 6 (20%) in Group KM and 8 (26.6%) in Group O. The difference between Groups O and Group KM with Group C was statistically significant (P < 0.05). No significant difference was noted between Groups KM with Group O in this regard (P > 0.05). Peripheral and core temperature changes throughout surgery were not significantly different among three groups (P > 0.05). Incidence (%) of hallucination was not significantly different between the three groups (0, 3.3, 0 in Group O, Group KM, Group C respectively, P > 0.05). Conclusion: Prophylactic use of ondansetron 8 mg IV was comparable to ketamine 0.25 mg/kg IV plus midazolam 37.5 μg/kg IV in preventing shivering during SA. PMID:26605236

HCdc14A is involved in cell cycle regulation of human brain vascular endothelial cells following injury induced by high glucose, free fatty acids and hypoxia.

PubMed

Su, Jingjing; Zhou, Houguang; Tao, Yinghong; Guo, Zhuangli; Zhang, Shuo; Zhang, Yu; Huang, Yanyan; Tang, Yuping; Hu, Renming; Dong, Qiang

2015-01-01

Cell cycle processes play a vital role in vascular endothelial proliferation and dysfunction. Cell division cycle protein 14 (Cdc14) is an important cell cycle regulatory phosphatase. Previous studies in budding yeast demonstrated that Cdc14 could trigger the inactivation of mitotic cyclin-dependent kinases (Cdks), which are required for mitotic exit and cytokinesis. However, the exact function of human Cdc14 (hCdc14) in cell cycle regulation during vascular diseases is yet to be elucidated. There are two HCdc14 homologs: hCdc14A and hCdc14B. In the current study, we investigated the potential role of hCdc14A in high glucose-, free fatty acids (FFAs)-, and hypoxia-induced injury in cultured human brain vascular endothelial cells (HBVECs). Data revealed that high glucose, FFA, and hypoxia down-regulated hCdc14A expression remarkably, and also affected the expression of other cell cycle-related proteins such as cyclin B, cyclin D, cyclin E, and p53. Furthermore, the combined addition of the three stimuli largely blocked cell cycle progression, decreased cell proliferation, and increased apoptosis. We also determined that hCdc14A was localized mainly to centrosomes during interphase and spindles during mitosis using confocal microscopy, and that it could affect the expression of other cycle-related proteins. More importantly, the overexpression of hCdc14A accelerated cell cycle progression, enhanced cell proliferation, and promoted neoplastic transformation, whereas the knockdown of hCdc14A using small interfering RNA produced the opposite effects. Therefore, these findings provide novel evidence that hCdc14A might be involved in cell cycle regulation in cultured HBVECs during high glucose-, FFA-, and hypoxia-induced injury. Copyright © 2014 Elsevier Inc. All rights reserved.

Preliminary user's manuals for DYNA3D and DYNAP. [In FORTRAN IV for CDC 7600 and Cray-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hallquist, J. O.

1979-10-01

This report provides a user's manual for DYNA3D, an explicit three-dimensional finite-element code for analyzing the large deformation dynamic response of inelastic solids. A contact-impact algorithm permits gaps and sliding along material interfaces. By a specialization of this algorithm, such interfaces can be rigidly tied to admit variable zoning without the need of transition regions. Spatial discretization is achieved by the use of 8-node solid elements, and the equations of motion are integrated by the central difference method. Post-processors for DYNA3D include GRAPE for plotting deformed shapes and stress contours and DYNAP for plotting time histories. A user's manual formore » DYNAP is also provided. 23 figures.« less

Systematic Investigation of Expression of G2/M Transition Genes Reveals CDC25 Alteration in Nonfunctioning Pituitary Adenomas.

PubMed

Butz, Henriett; Németh, Kinga; Czenke, Dóra; Likó, István; Czirják, Sándor; Zivkovic, Vladimir; Baghy, Kornélia; Korbonits, Márta; Kovalszky, Ilona; Igaz, Péter; Rácz, Károly; Patócs, Attila

2017-07-01

Dysregulation of G1/S checkpoint of cell cycle has been reported in pituitary adenomas. In addition, our previous finding showing that deregulation of Wee1 kinase by microRNAs together with other studies demonstrating alteration of G2/M transition in nonfunctioning pituitary adenomas (NFPAs) suggest that G2/M transition may also be important in pituitary tumorigenesis. To systematically study the expression of members of the G2/M transition in NFPAs and to investigate potential microRNA (miRNA) involvement. Totally, 80 NFPA and 14 normal pituitary (NP) tissues were examined. Expression of 46 genes encoding members of the G2/M transition was profiled on 34 NFPA and 10 NP samples on TaqMan Low Density Array. Expression of CDC25A and two miRNAs targeting CDC25A were validated by individual quantitative real time PCR using TaqMan assays. Protein expression of CDC25A, CDC25C, CDK1 and phospho-CDK1 (Tyr-15) was investigated on tissue microarray and immunohistochemistry. Several genes' expression alteration were observed in NFPA compared to normal tissues by transcription profiling. On protein level CDC25A and both the total and the phospho-CDK1 were overexpressed in adenoma tissues. CDC25A correlated with nuclear localized CDK1 (nCDK1) and with tumor size and nCDK1 with Ki-67 index. Comparing primary vs. recurrent adenomas we found that Ki-67 proliferation index was higher and phospho-CDK1 (inactive form) was downregulated in recurrent tumors compared to primary adenomas. Investigating the potential causes behind CDC25A overexpression we could not find copy number variation at the coding region nor expression alteration of CDC25A regulating transcription factors however CDC25A targeting miRNAs were downregulated in NFPA and negatively correlated with CDC25A expression. Our results suggest that among alterations of G2/M transition of the cell cycle, overexpression of the CDK1 and CDC25A may have a role in the pathogenesis of the NFPA and that CDC25A is potentially regulated by miRNAs.

Carbide derived carbon from MAX-phases and their separation applications

NASA Astrophysics Data System (ADS)

Hoffman, Elizabeth N.

Improved sorbents with increased selectivity and permeability are needed to meet growing energy and environmental needs. New forms of carbon based sorbents have been discovered recently, including carbons produced by etching metals from metal carbides, known as carbide derived carbons (CDCs). A common method for the synthesis of CDC is by chlorination at elevated temperatures. The goal of this work is to synthesize CDC from ternary carbides and to explore the links between the initial carbide chemistry and structure with the resulting CDCs properties, including porosity. CDC was produced from MAX-phase carbides, in particular Ti3SiC 2, Ti3AlC2, Ti2AlC, and Ta2AlC. Additionally, CDC was produced from Ta-based binary carbides, TaC and Ta 2C, and one carbo-nitride Ti2AlC0.5N0.5. The CDC structure was characterized using XRD, Raman microspectroscopy, and HRTEM. Porosity characterization was performed using sorption analysis with both Ar and N2 as adsorbates. It was determined the microporosity of CDC is related to the density of the initial carbide. The layered structure of the MAX-phase carbides lent toward the formation of larger mesopores within the resulting CDCs, while the amount of mesopores was dependent on the chemistry of the carbide. Furthermore, CDC produced from carbides with extremely high theoretical porosity resulted in small specific surface areas due to a collapse of the carbon structure. To expand the potential applications for CDC beyond powder and bulk forms, CDC membranes were produced from a thin film of TiC deposited by magnetron sputtering onto porous ceramic substrates. The TiC thin film was subsequently chlorinated to produce a bilayer membrane with CDC as the active layer. Both gases and liquids are capable of passing the membrane. The membrane separates based on selective adsorption, rather than a size separation molecular sieving effect. Two applications for CDC produced from MAX-phases were investigated: protein adsorption and gas separation. Sorbents capable of adsorbing large protein molecules efficiently are desirable for many medical applications, including the treatment of sepsis. Primarily mesoporous Ti2AlC-CDC and Ti3AlC2-CDC were proven to adsorb a significant amount of proteins compared to two current carbon adsorbents. When tested for gas separation, CDC was capable of selectively adsorbing gases including SF6, CO2, CH4, and H2. However, the gases were not separated based on their size, but rather on their interaction with the CDC surface.

Human immunodeficiency virus type 1 Vpr induces cell cycle G2 arrest through Srk1/MK2-mediated phosphorylation of Cdc25.

PubMed

Huard, Sylvain; Elder, Robert T; Liang, Dong; Li, Ge; Zhao, Richard Y

2008-03-01

Human immunodeficiency virus type 1 (HIV-1) Vpr induces cell cycle G(2) arrest in fission yeast (Schizosaccharomyces pombe) and mammalian cells, suggesting the cellular pathway(s) targeted by Vpr is conserved among eukaryotes. Our previous studies in fission yeast demonstrated that Vpr induces G(2) arrest in part through inhibition of Cdc25, a Cdc2-specific phosphatase that promotes G(2)/M transition. The goal of this study was to further elucidate molecular mechanism underlying the inhibitory effect of Vpr on Cdc25. We show here that, similar to the DNA checkpoint controls, expression of vpr promotes subcellular relocalization of Cdc25 from nuclear to cytoplasm and thereby prevents activation of Cdc2 by Cdc25. Vpr-induced nuclear exclusion of Cdc25 appears to depend on the serine/threonine phosphorylation of Cdc25 and the presence of Rad24/14-3-3 protein, since amino acid substitutions of the nine possible phosphorylation sites of Cdc25 with Ala (9A) or deletion of the rad24 gene abolished nuclear exclusion induced by Vpr. Interestingly, Vpr is still able to promote Cdc25 nuclear export in mutants defective in the checkpoints (rad3 and chk1/cds1), the kinases that are normally required for Cdc25 phosphorylation and nuclear exclusion of Cdc25, suggesting that others kinase(s) might modulate phosphorylation of Cdc25 for the Vpr-induced G(2) arrest. We report here that this kinase is Srk1. Deletion of the srk1 gene blocks the nuclear exclusion of Cdc25 caused by Vpr. Overexpression of srk1 induces cell elongation, an indication of cell cycle G(2) delay, in a similar fashion to Vpr; however, no additive effect of cell elongation was observed when srk1 and vpr were coexpressed, indicating Srk1 and Vpr are likely affecting the cell cycle G(2)/M transition through the same cellular pathway. Immunoprecipitation further shows that Vpr and Srk1 are part of the same protein complex. Consistent with our findings in fission yeast, depletion of the MK2 gene, a human homologue of Srk1, either by small interfering RNA or an MK2 inhibitor suppresses Vpr-induced cell cycle G(2) arrest in mammalian cells. Collectively, our data suggest that Vpr induces cell cycle G(2) arrest at least in part through a Srk1/MK2-mediated mechanism.

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

PubMed Central

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

2009-01-01

Abstract The University of Pittsburgh Molecular Library Screening Center (Pittsburgh, PA) conducted a screen with the National Institutes of Health compound library for inhibitors of in vitro cell division cycle 25 protein (Cdc25) B activity during the pilot phase of the Molecular Library Screening Center Network. Seventy-nine (0.12%) of the 65,239 compounds screened at 10 μM met the active criterion of ≥50% inhibition of Cdc25B activity, and 25 (31.6%) of these were confirmed as Cdc25B inhibitors with 50% inhibitory concentration (IC50) values <50 μM. Thirteen of the Cdc25B inhibitors were represented by singleton chemical structures, and 12 were divided among four clusters of related structures. Thirteen (52%) of the Cdc25B inhibitor hits were quinone-based structures. The Cdc25B inhibitors were further characterized in a series of in vitro secondary assays to confirm their activity, to determine their phosphatase selectivity against two other dual-specificity phosphatases, mitogen-activated protein kinase phosphatase (MKP)-1 and MKP-3, and to examine if the mechanism of Cdc25B inhibition involved oxidation and inactivation. Nine Cdc25B inhibitors did not appear to affect Cdc25B through a mechanism involving oxidation because they did not generate detectable amounts of H2O2 in the presence of dithiothreitol, and their Cdc25B IC50 values were not significantly affected by exchanging the dithiothreitol for β-mercaptoethanol or reduced glutathione or by adding catalase to the assay. Six of the nonoxidative hits were selective for Cdc25B inhibition versus MKP-1 and MKP-3, but only the two bisfuran-containing hits, PubChem substance identifiers 4258795 and 4260465, significantly inhibited the growth of human MBA-MD-435 breast and PC-3 prostate cancer cell lines. To confirm the structure and biological activity of 4260465, the compound was resynthesized along with two analogs. Neither of the substitutions to the two analogs was tolerated, and only the resynthesized hit 26683752 inhibited Cdc25B activity in vitro (IC50 = 13.83 ± 1.0 μM) and significantly inhibited the growth of the MBA-MD-435 breast and PC-3 prostate cancer cell lines (IC50 = 20.16 ± 2.0 μM and 24.87 ± 2.25 μM, respectively). The two bis-furan-containing hits identified in the screen represent novel nonoxidative Cdc25B inhibitor chemotypes that block tumor cell proliferation. The availability of non-redox active Cdc25B inhibitors should provide valuable tools to explore the inhibition of the Cdc25 phosphatases as potential mono- or combination therapies for cancer. PMID:19530895

Surgical wound management made easier and more cost-effective.

PubMed

Akagi, Ichiro; Furukawa, Kiyonori; Miyashita, Masao; Kiyama, Teruo; Matsuda, Akihisa; Nomura, Tsutomu; Makino, Hiroshi; Hagiwara, Nobutoshi; Takahashi, Ken; Uchida, Eiji

2012-07-01

Evidence-based guidelines for the prevention of surgical site infection (SSI) have been published by the U.S. Centers for Disease Control and Prevention (CDC). According to these guidelines, a wound should usually be covered with a sterile dressing for 24 to 48 h when a surgical incision is closed primarily. However, it is not recommended that an incision be covered by a dressing beyond 48 h. In this study, patients were stratified into two groups for analysis: patients whose surgical wound was sterilized and whose gauze was changed once daily until postoperative day 7 (7POD; group A); and patients whose surgical wound was sterilized and whose gauze was changed once daily until 2POD (group B). We evaluated the incidence of SSI, nursing hours and cost implications. The results showed that there was no significant difference in SSI occurrence between the two groups (group A, 10% vs. group B, 7.3%). By contrast, the average nursing time differed by 2.8 min (group A, 3.8 min vs. group B, 0.9 min). The material costs per patient were also reduced by $14.70 (group A, $61.80 vs. group B, $47.10). In conclusion, we applied our knowledge of the evidence-based CDC guidelines to determine whether 48-h wound management can be made easier, more uniform and more cost-effective compared to conventional wound management. The results of the present study showed that surgical wound management methods can be more convenient and inexpensive.

Comparison of the effects of sternal and tibial intraosseous administered resuscitative drugs on return of spontaneous circulation in a swine model of cardiac arrest.

PubMed

O'Sullivan, Mara; Martinez, Andre; Long, Audrey; Johnson, Michelle; Blouin, Dawn; Johnson, Arthur D; Burgert, James M

2016-01-01

Compare vasopressin, amiodarone, and epinephrine administration by sternal intraosseous (SIO), tibial intraosseous (TIO), and intravenous (IV) routes in a swine model of cardiac arrest. Prospective, randomized, between subjects, experimental design. Laboratory. Male Yorkshire-cross swine (N = 35), seven per group. Swine were randomized to SIO, TIO, IV, cardiopulmonary resuscitation (CPR) with defibrillation, or CPR-only groups. Ventricular fibrillation (VF) was induced under general anesthesia. Mechanical CPR began 2 minutes postarrest. Vasopressin (40 U) was administered to the SIO, TIO, and IV groups 4 minutes postarrest. Defibrillation was performed and amiodarone (300 mg) was administered 6 minutes postarrest. Defibrillation was repeated, and epinephrine (1 mg) was administered 10 minutes postarrest. Defibrillation was repeated every 2 minutes and epinephrine repeated every 4 minutes until return of spontaneous circulation (ROSC) or 26 postarrest minutes elapsed. Rate of ROSC, time to ROSC, and odds of ROSC. There were no significant differences in rate of ROSC between the SIO and TIO (p = 0.22) or IV groups (p = 1.0). Time to ROSC was five times less in the SIO group than the TIO group (p = 0.003) but not compared to IV (p = 0.125). Time to ROSC in the IV group was significantly less than the TIO group (p = 0.04). Odds of ROSC for the SIO group were five times higher compared to the TIO group but same as IV. Odds of ROSC in the IV group were higher than the TIO group. There was a statistically significant delay in the time to ROSC and a clinically significant difference in odds of ROSC when resuscitative drugs, including lipophilic amiodarone, were administered by the TIO route compared to the SIO and IV routes in a swine model of sudden cardiac arrest. Further investigations are warranted to isolate the mechanism behind these findings.

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

PubMed

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

2014-10-23

The Enterobacteriaceae are environmental and enteric microbes. We sequenced the genomes of two Enterobacter reference strains, E. aerogenes CDC 6003-71 and E. cloacae CDC 442-68, as well as one near neighbor used as an exclusionary reference for diagnostics, Pantoea agglomerans CDC UA0804-01. The genome sizes range from 4.72 to 5.55 Mbp and have G+C contents from 54.6 to 55.1%. Copyright © 2014 Minogue et al.

Physical activity measurements affected participants' behavior in a randomized controlled trial.

PubMed

van Sluijs, Esther M F; van Poppel, Mireille N M; Twisk, Jos W R; van Mechelen, Willem

2006-04-01

Assessing levels and determinants of physical activity as outcome measurements might have an independent effect on participant's physical activity behavior. The objective is to study this effect in a randomized controlled trial (RCT) promoting regular physical activity in Dutch general practice. Using a Solomon four-group design, participants were randomized twice. After randomization to a control or intervention-condition at general practice level (N = 29), participants were randomized to a group participating in measurements at baseline, 2 and 6 months (3M-group, N = 361), or a group only participating in measurements at 6 months (1M-group, N = 356). Outcome measures assessed at 6 months included: level of physical activity (self-reported and objectively measured with accelerometry), meeting ACSM/CDC guideline for regular physical activity, stage of change, and determinants of physical activity. Follow-up data on 635 participants (89%) was collected. Statistically significant measurement effects were found for meeting the ACSM/CDC guideline (self-reported), self-efficacy for resisting relapse, knowledge, and on awareness. Other outcome measures showed positive trends, except stages of change. Measurements of physical activity affect participant's physical activity behavior, possibly triggered by a raised awareness about their own physical activity level. Implications for future research are discussed, as well as methodologic limitations of the study design.

Exporting simulation technology to the Philippines: a comparative study of traditional versus simulation methods for teaching intravenous cannulation.

PubMed

Sotto, Juan Alejandro R; Ayuste, Eduardo C; Bowyer, Mark W; Almonte, Josefina R; Dofitas, Rodney B; Lapitan, Marie C M; Pimentel, Elisabeth A; Ritter, E Matthew; Wherry, David C

2009-01-01

This study examines effectiveness of a donated Laerdal Virtual I.V. simulator when compared with traditional methods of teaching intravenous (IV) cannulation to third year medical students in the Philippines. Forty novice Filipino medical students viewed an instructional video on how to start intravenous lines and were then randomly divided into two groups of twenty. The "Traditional" group observed an IV insertion on an actual patient performed by an experienced practitioner, and then subsequently performed an IV on an actual patient which was videotaped. The "Simulation" group practiced the Virtual I.V. simulator until they successfully completed level three using the "doctor" setting. These students then performed an IV on an actual patient which was videotaped. The videotapes for both groups were reviewed by two pre-trained (Inter-rater reliability of > or =0.84) observers who were blinded to the group using a previously validated checklist for IV insertion. Students trained on the Virtual I.V. showed significantly greater success in successfully starting an IV on an actual patient (40% VS. 15%, p<0.05), decreased constrictive band time (p<.05), increased raw score on the check list (p<.03), and decreased overall time to start an IV (p<.05). The technology was well received but wider application in the non western world is limited by lack of in country company support and the relative expense.

Cognitive and Adaptive Skills in Toddlers Who Meet Criteria for Autism in DSM-IV but Not DSM-5

ERIC Educational Resources Information Center

Jashar, Dasal Tenzin; Brennan, Laura A.; Barton, Marianne L.; Fein, Deborah

2016-01-01

The current study compared adaptive and cognitive skills, and autism severity of toddlers with an autism spectrum disorder (ASD) diagnosis under DSM-IV but not DSM-5 criteria (DSM-IV only group) to those who met autism criteria under both diagnostic systems (DSM-5 group) and to those without ASD (non-ASD group). The toddlers in the DSM-IV only…

Effects of Intraosseous Tibial vs. Intravenous Vasopressin in a Hypovolemic Cardiac Arrest Model

PubMed Central

Fulkerson, Justin; Lowe, Robert; Anderson, Tristan; Moore, Heather; Craig, William; Johnson, Don

2016-01-01

Introduction This study compared the effects of vasopressin via tibial intraosseous (IO) and intravenous (IV) routes on maximum plasma concentration (Cmax), the time to maximum concentration (Tmax), return of spontaneous circulation (ROSC), and time to ROSC in a hypovolemic cardiac arrest model. Methods This study was a randomized prospective, between-subjects experimental design. A computer program randomly assigned 28 Yorkshire swine to one of four groups: IV (n=7), IO tibia (n=7), cardiopulmonary resuscitation (CPR) + defibrillation (n=7), and a control group that received just CPR (n=7). Ventricular fibrillation was induced, and subjects remained in arrest for two minutes. CPR was initiated and 40 units of vasopressin were administered via IO or IV routes. Blood samples were collected at 0.5, 1, 1.5, 2, 2.5, 3, and 4 minutes. CPR and defibrillation were initiated for 20 minutes or until ROSC was achieved. We measured vasopressin concentrations using high-performance liquid chromatography. Results There was no significant difference between the IO and IV groups relative to achieving ROSC (p=1.0) but a significant difference between the IV compared to the CPR+ defibrillation group (p=0.031) and IV compared to the CPR-only group (p=0.001). There was a significant difference between the IO group compared to the CPR+ defibrillation group (p=0.031) and IO compared to the CPR-only group (p=0.001). There was no significant difference between the CPR + defibrillation group and the CPR group (p=0.127). There was no significant difference in Cmax between the IO and IV groups (p=0.079). The mean ± standard deviation of Cmax of the IO group was 58,709±25, 463pg/mL compared to the IV group, which was 106,198±62, 135pg/mL. There was no significant difference in mean Tmax between the groups (p=0.084). There were no significant differences in odds of ROSC between the tibial IO and IV groups. Conclusion Prompt access to the vascular system using the IO route can circumvent the interruption in treatment observed with attempting conventional IV access. The IO route is an effective modality for the treatment of hypovolemic cardiac arrest and may be considered first line for rapid vascular access. PMID:26973756

Effects of Intraosseous Tibial vs. Intravenous Vasopressin in a Hypovolemic Cardiac Arrest Model.

PubMed

Fulkerson, Justin; Lowe, Robert; Anderson, Tristan; Moore, Heather; Craig, William; Johnson, Don

2016-03-01

This study compared the effects of vasopressin via tibial intraosseous (IO) and intravenous (IV) routes on maximum plasma concentration (Cmax), the time to maximum concentration (Tmax), return of spontaneous circulation (ROSC), and time to ROSC in a hypovolemic cardiac arrest model. This study was a randomized prospective, between-subjects experimental design. A computer program randomly assigned 28 Yorkshire swine to one of four groups: IV (n=7), IO tibia (n=7), cardiopulmonary resuscitation (CPR) + defibrillation (n=7), and a control group that received just CPR (n=7). Ventricular fibrillation was induced, and subjects remained in arrest for two minutes. CPR was initiated and 40 units of vasopressin were administered via IO or IV routes. Blood samples were collected at 0.5, 1, 1.5, 2, 2.5, 3, and 4 minutes. CPR and defibrillation were initiated for 20 minutes or until ROSC was achieved. We measured vasopressin concentrations using high-performance liquid chromatography. There was no significant difference between the IO and IV groups relative to achieving ROSC (p=1.0) but a significant difference between the IV compared to the CPR+ defibrillation group (p=0.031) and IV compared to the CPR-only group (p=0.001). There was a significant difference between the IO group compared to the CPR+ defibrillation group (p=0.031) and IO compared to the CPR-only group (p=0.001). There was no significant difference between the CPR + defibrillation group and the CPR group (p=0.127). There was no significant difference in Cmax between the IO and IV groups (p=0.079). The mean ± standard deviation of Cmax of the IO group was 58,709±25, 463 pg/mL compared to the IV group, which was 106,198±62, 135 pg/mL. There was no significant difference in mean Tmax between the groups (p=0.084). There were no significant differences in odds of ROSC between the tibial IO and IV groups. Prompt access to the vascular system using the IO route can circumvent the interruption in treatment observed with attempting conventional IV access. The IO route is an effective modality for the treatment of hypovolemic cardiac arrest and may be considered first line for rapid vascular access.

Native cysteine residues are dispensable for the structure and function of all five yeast mitotic septins

PubMed Central

de Val, Natalia; McMurray, Michael A.; Lam, Lisa H.; Hsiung, Chris C.-S.; Bertin, Aurélie; Nogales, Eva; Thorner, Jeremy

2013-01-01

Budding yeast septins assemble into hetero-octamers and filaments required for cytokinesis. Solvent-exposed cysteine (Cys) residues provide sites for attaching substituents useful in assessing assembly kinetics and protein interactions. To introduce Cys at defined locations, site-directed mutagenesis was used, first, to replace the native Cys residues in Cdc3 (C124 C253 C279), Cdc10 (C266), Cdc11 (C43 C137 C138), Cdc12 (C40 C278), and Shs1 (C29 C148) with Ala, Ser, Val, or Phe. When plasmid-expressed, each Cys-less septin mutant rescued the cytokinesis defects caused by absence of the corresponding chromosomal gene. When integrated and expressed from its endogenous promoter, the same mutants were fully functional, except Cys-less Cdc12 mutants (which were viable, but exhibited slow growth and aberrant morphology) and Cdc3(C124V C253V C279V) (which was inviable). No adverse phenotypes were observed when certain pairs of Cys-less septins were co-expressed as the sole source of these proteins. Cells grew less well when three Cys-less septins were co-expressed, suggesting some reduction in fitness. Nonetheless, cells chromosomally expressing Cys-less Cdc10, Cdc11, and Cdc12, and expressing Cys-less Cdc3 from a plasmid, grew well at 30ºC. Moreover, recombinant Cys-less septins—or where one of the Cys-less septins contained a single Cys introduced at a new site—displayed assembly properties in vitro indistinguishable from wild-type. PMID:23775754

Engineering and public health at CDC.

PubMed

Earnest, G Scott; Reed, Laurence D; Conover, D; Estill, C; Gjessing, C; Gressel, M; Hall, R; Hudock, S; Hudson, H; Kardous, C; Sheehy, J; Topmiller, J; Trout, D; Woebkenberg, M; Amendola, A; Hsiao, H; Keane, P; Weissman, D; Finfinger, G; Tadolini, S; Thimons, E; Cullen, E; Jenkins, M; McKibbin, R; Conway, G; Husberg, B; Lincoln, J; Rodenbeck, S; Lantagne, D; Cardarelli, J

2006-12-22

Engineering is the application of scientific and technical knowledge to solve human problems. Using imagination, judgment, and reasoning to apply science, technology, mathematics, and practical experience, engineers develop the design, production, and operation of useful objects or processes. During the 1940s, engineers dominated the ranks of CDC scientists. In fact, the first CDC director, Assistant Surgeon General Mark Hollis, was an engineer. CDC engineers were involved in malaria control through the elimination of standing water. Eventually the CDC mission expanded to include prevention and control of dengue, typhus, and other communicable diseases. The development of chlorination, water filtration, and sewage treatment were crucial to preventing waterborne illness. Beginning in the 1950s, CDC engineers began their work to improve public health while developing the fields of environmental health, industrial hygiene, and control of air pollution. Engineering disciplines represented at CDC today include biomedical, civil, chemical, electrical, industrial, mechanical, mining, and safety engineering. Most CDC engineers are located in the National Institute for Occupational Safety and Health (NIOSH) and the Agency for Toxic Substances and Disease Registry (ATSDR). Engineering research at CDC has a broad stakeholder base. With the cooperation of industry, labor, trade associations, and other stakeholders and partners, current work includes studies of air contaminants, mining, safety, physical agents, ergonomics, and environmental hazards. Engineering solutions remain a cornerstone of the traditional "hierarchy of controls" approach to reducing public health hazards.

Tinman/Nkx2-5 acts via miR-1 and upstream of Cdc42 to regulate heart function across species

PubMed Central

Wythe, Joshua D.; Liu, Jiandong; Cartry, Jerome; Vogler, Georg; Mohapatra, Bhagyalaxmi; Otway, Robyn T.; Huang, Yu; King, Isabelle N.; Maillet, Marjorie; Zheng, Yi; Crawley, Timothy; Taghli-Lamallem, Ouarda; Semsarian, Christopher; Dunwoodie, Sally; Winlaw, David; Harvey, Richard P.; Fatkin, Diane; Towbin, Jeffrey A.; Molkentin, Jeffery D.; Srivastava, Deepak; Ocorr, Karen; Bruneau, Benoit G.

2011-01-01

Unraveling the gene regulatory networks that govern development and function of the mammalian heart is critical for the rational design of therapeutic interventions in human heart disease. Using the Drosophila heart as a platform for identifying novel gene interactions leading to heart disease, we found that the Rho-GTPase Cdc42 cooperates with the cardiac transcription factor Tinman/Nkx2-5. Compound Cdc42, tinman heterozygous mutant flies exhibited impaired cardiac output and altered myofibrillar architecture, and adult heart–specific interference with Cdc42 function is sufficient to cause these same defects. We also identified K+ channels, encoded by dSUR and slowpoke, as potential effectors of the Cdc42–Tinman interaction. To determine whether a Cdc42–Nkx2-5 interaction is conserved in the mammalian heart, we examined compound heterozygous mutant mice and found conduction system and cardiac output defects. In exploring the mechanism of Nkx2-5 interaction with Cdc42, we demonstrated that mouse Cdc42 was a target of, and negatively regulated by miR-1, which itself was negatively regulated by Nkx2-5 in the mouse heart and by Tinman in the fly heart. We conclude that Cdc42 plays a conserved role in regulating heart function and is an indirect target of Tinman/Nkx2-5 via miR-1. PMID:21690310

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

PubMed

Kokkoris, Kyriakos; Gallo Castro, Daniela; Martin, Sophie G

2014-05-01

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) catalytic subunit Dis2 or Sds21, and ectopic targeting of either catalytic subunit is similarly instructive for growth. The Cdc42 guanine-nucleotide-exchange factor Gef1 and the GTPase-activating protein Rga4 are required for Tea4-PP1-dependent ectopic growth. Gef1 is recruited to ectopic Tea4 and Dis2 locations to promote Cdc42 activation. By contrast, Rga4 is locally excluded by Tea4, and its forced colocalization with Tea4 blocks ectopic growth, indicating that Rga4 must be present, but at sites distinct from Tea4. Thus, a Tea4-PP1 landmark promotes local Cdc42 activation and growth both through Cdc42 GEF recruitment and by creating a local trough in a Cdc42 GAP.

Site-specific regulation of the GEF Cdc24p by the scaffold protein Far1p during yeast mating

PubMed Central

Wiget, Philippe; Shimada, Yukiko; Butty, Anne-Christine; Bi, Efrei; Peter, Matthias

2004-01-01

Receptor-mediated cell polarization via heterotrimeric G-proteins induces cytoskeletal rearrangements in a variety of organisms. In yeast, Far1p is required for orienting cell growth towards the mating partner by linking activated Gβγ to the guanine-nucleotide exchange factor (GEF) Cdc24p, which activates the Rho-type GTPase Cdc42p. Here we investigated the role of Far1p in the regulation of Cdc24p in vivo. Using time-lapse microscopy of mating cells and artificial membrane targeting of Far1p, we show that Far1p is necessary and sufficient to recruit Cdc24p to the plasma membrane. Wild-type Far1p contains a PH-like domain, which is required for its membrane localization in vivo. Interestingly, expression of membrane-targeted Far1p causes toxicity, most likely by activating Cdc42p uniformly at the cell cortex. The ability of full-length Far1p to function as an activator of Cdc24p in vivo requires its interaction with Cdc24p and Gβγ. Our results imply that Gβγ not only targets Far1p to the correct site but may also trigger a conformational change in Far1p that is required for its ability to activate Cdc24p in vivo. PMID:14988725

Update on Multistate Outbreak of Fungal Infections Associated with Contaminated Methylprednisolone Injections, 2012-2014.

PubMed

McCotter, Orion Z; Smith, Rachel M; Westercamp, Mathew; Kerkering, Thomas M; Malani, Anurag N; Latham, Robert; Peglow, Sheree L; Mody, Rajal K; Pappas, Peter G; Chiller, Tom M

2015-10-30

During September 2012, CDC, in collaboration with state and local health departments and the Food and Drug Administration (FDA), investigated a multistate outbreak of fungal meningitis and other infections caused by injections of contaminated methylprednisolone acetate solution (MPA). After this unprecedented outbreak, scientists in the CDC Mycotic Diseases Branch, along with infectious diseases specialists who cared for patients from the outbreak, clinical experts, and public health officials from affected states, have continued to monitor the recovery of affected patients. A long-term follow-up study involving these patients was initiated and is being conducted by the Mycoses Study Group Education and Research Consortium (MSGERC). This update summarizes subsequent information about the current state of the outbreak.

A septin from the filamentous fungus A. nidulans induces atypical pseudohyphae in the budding yeast S. cerevisiae

USDA-ARS?s Scientific Manuscript database

Septins were first discovered in Saccharomyces cerevisiae where they form a scaffold that organizes the bud site and are a component of the morphogenesis checkpoint that coordinates budding with mitosis. Five of the seven S. cerevisiae septins (Cdc3, Cdc10, Cdc11, Cdc12 and Shs1) colocalize as a rin...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-06

... Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC) In accordance with section 10(a)(2) of the Federal Advisory Committee Act (Pub. L. 92-463), CDC announces the following meeting of the aforementioned committee. Time and date: 8:30 a.m.-2:30 p.m., October 27, 2011. Place: CDC...

78 FR 18602 - Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-27

... Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC) In accordance with section... Prevention (CDC) announces the following meeting of the aforementioned committee. Time and Date: 8:30 a.m.-3:00 p.m. (EDT), April 25, 2013. Place: CDC, Building 21, Rooms 1204 A/B, 1600 Clifton Road, NE...

IVS Working Group 4: VLBI Data Structures

NASA Technical Reports Server (NTRS)

Gipson, John

2010-01-01

In 2007 the IVS Directing Board established IVS Working Group 4 on VLBI Data Structures. This note discusses the current VLBI data format, goals for a new format, the history and formation of the Working Group, and a timeline for the development of a new VLBI data format.

Transcriptional and post-transcriptional regulation of Cdc20 during the spindle assembly checkpoint in S. cerevisiae

PubMed Central

Wang, Ruiwen; Burton, Janet L.; Solomon, Mark J.

2017-01-01

The anaphase-promoting complex (APC) is a ubiquitin ligase responsible for promoting the degradation of many cell cycle regulators. One of the activators and substrate-binding proteins for the APC is Cdc20. It has been shown previously that Cdc20 can promote its own degradation by the APC in normal cycling cells mainly through a cis-degradation mode (i.e. via an intramolecular mechanism). However, how Cdc20 is degraded during the spindle assembly checkpoint (SAC) is still not fully clear. In this study, we used a dual-Cdc20 system to investigate this issue and found that the cis-degradation mode is also the major pathway responsible for Cdc20 degradation during the SAC. In addition, we found that there is an inverse relationship between APCCdc20 activity and the transcriptional activity of the CDC20 promoter, which likely occurs through feedback regulation by APCCdc20 substrates, such as the cyclins Clb2 and Clb5. These findings contribute to our understanding of how the inhibition of APCCdc20 activity and enhanced Cdc20 degradation are required for proper spindle checkpoint arrest. PMID:28189585

Cdc15 integrates Tem1 GTPase-mediated spatial signals with Polo kinase-mediated temporal cues to activate mitotic exit.

PubMed

Rock, Jeremy M; Amon, Angelika

2011-09-15

In budding yeast, a Ras-like GTPase signaling cascade known as the mitotic exit network (MEN) promotes exit from mitosis. To ensure the accurate execution of mitosis, MEN activity is coordinated with other cellular events and restricted to anaphase. The MEN GTPase Tem1 has been assumed to be the central switch in MEN regulation. We show here that during an unperturbed cell cycle, restricting MEN activity to anaphase can occur in a Tem1 GTPase-independent manner. We found that the anaphase-specific activation of the MEN in the absence of Tem1 is controlled by the Polo kinase Cdc5. We further show that both Tem1 and Cdc5 are required to recruit the MEN kinase Cdc15 to spindle pole bodies, which is both necessary and sufficient to induce MEN signaling. Thus, Cdc15 functions as a coincidence detector of two essential cell cycle oscillators: the Polo kinase Cdc5 synthesis/degradation cycle and the Tem1 G-protein cycle. The Cdc15-dependent integration of these temporal (Cdc5 and Tem1 activity) and spatial (Tem1 activity) signals ensures that exit from mitosis occurs only after proper genome partitioning.

Glycated Apolipoprotein A-IV Induces Atherogenesis in Patients With CAD in Type 2 Diabetes.

PubMed

Dai, Yang; Shen, Ying; Li, Qing Run; Ding, Feng Hua; Wang, Xiao Qun; Liu, Hong Juan; Yan, Xiao Xiang; Wang, Ling Jie; Yang, Ke; Wang, Hai Bo; Chen, Qiu Jing; Shen, Wei Feng; Zhang, Rui Yan; Lu, Lin

2017-10-17

Nonenzymatic glycation of apolipoproteins plays a role in the pathogenesis of the vascular complications of diabetes. This study investigated whether apolipoprotein (apo) A-IV was glycated in patients with type 2 diabetes mellitus (T2DM) and whether apoA-IV glycation was related to coronary artery disease (CAD). The study also determined the biological effects of glycated apoA-IV. The authors consecutively enrolled 204 patients with T2DM without CAD (Group I), 515 patients with T2DM with CAD (Group II), and 176 healthy subjects (control group) in this study. ApoA-IV was precipitated from ultracentrifugally isolated high-density lipoprotein, and its glycation level was determined based on Western blotting densitometry (relative intensity of apoA-IV glycation). ApoA-IV NƐ-(carboxylmethyl) lysine (CML) modification sites were identified by mass spectrometry in 37 control subjects, 63 patients in Group I, and 138 patients in Group II. Saline or glycated apoA-IV (g-apoA-IV) generated by glyoxal culture was injected into apoE -/- mice to evaluate atherogenesis, and was also used for the cell experiments. The relative intensity and the abundance of apoA-IV glycation were associated with the presence and severity of CAD in patients with T2DM (all p < 0.05). The experiments showed that g-apoA-IV induced proinflammatory reactions in vitro and promoted atherogenesis in apoE -/- mice through the nuclear receptor NR4A3. G-apoA-IV with mutations (K-A) at high-frequency glycation sites exhibited more weakened proinflammatory and atherogenic effects than did g-apoA-IV both in vitro and in vivo. ApoA-IV glycation is associated with CAD severity in patients with T2DM, and g-apoA-IV induces atherogenesis through NR4A3 in apoE -/- mice. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The yeast DNA ligase gene CDC9 is controlled by six orientation specific upstream activating sequences that respond to cellular proliferation but which alone cannot mediate cell cycle regulation.

PubMed Central

White, J H; Johnson, A L; Lowndes, N F; Johnston, L H

1991-01-01

By fusing the CDC9 structural gene to the PGK upstream sequences and the CDC9 upstream to lacZ, we showed that the cell cycle expression of CDC9 is largely due to transcriptional regulation. To investigate the role of six ATGATT upstream repeats in CDC9 regulation, synthetic copies of the sequence were attached to a heterologous gene. The repeats stimulated transcription strongly and additively, but, unlike conventional yeast UAS elements, only when present in one orientation. Transcription driven by the repeats declines in cells held at START of the cell cycle or in stationary phase, as occurs with CDC9. However, the repeats by themselves cannot impart cell cycle regulation to a heterologous gene. CDC9 may therefore be controlled by an activating system operating through the repeats that is sensitive to cellular proliferation and a separate mechanism that governs the periodic expression in the cell cycle. Images PMID:1901644

Polo kinase Cdc5 is a central regulator of meiosis I

PubMed Central

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 segregation. CDC5 also establishes conditions for centromeric cohesin removal during meiosis II by promoting the degradation of Spo13, a protein that protects centromeric cohesin during meiosis I. Despite CDC5’s central role in meiosis I, the protein kinase is dispensable during meiosis II and does not even phosphorylate its meiosis I targets during the second meiotic division. We conclude that Cdc5 has evolved into a master regulator of the unique meiosis I chromosome segregation pattern. PMID:23918381

CDC-25.2, a C. elegans ortholog of cdc25, is essential for the progression of intestinal divisions.

PubMed

Lee, Yong-Uk; Son, Miseol; Kim, Jiyoung; Shim, Yhong-Hee; Kawasaki, Ichiro

2016-01-01

Intestinal divisions in Caenorhabditis elegans take place in 3 stages: (1) cell divisions during embryogenesis, (2) binucleations at the L1 stage, and (3) endoreduplications at the end of each larval stage. Here, we report that CDC-25.2, a C. elegans ortholog of Cdc25, is required for these specialized division cycles between the 16E cell stage and the onset of endoreduplication. Results of our genetic analyses suggest that CDC-25.2 regulates intestinal cell divisions and binucleations by counteracting WEE-1.3 and by activating the CDK-1/CYB-1 complex. CDC-25.2 activity is then repressed by LIN-23 E3 ubiquitin ligase before the onset of intestinal endoreduplication, and this repression is maintained by LIN-35, the C. elegans ortholog of Retinoblastoma (Rb). These findings indicate that timely regulation of CDC-25.2 activity is essential for the progression of specialized division cycles and development of the C. elegans intestine.

CDC-25.2, a C. elegans ortholog of cdc25, is essential for the progression of intestinal divisions

PubMed Central

Lee, Yong-Uk; Son, Miseol; Kim, Jiyoung; Shim, Yhong-Hee; Kawasaki, Ichiro

2016-01-01

ABSTRACT Intestinal divisions in Caenorhabditis elegans take place in 3 stages: (1) cell divisions during embryogenesis, (2) binucleations at the L1 stage, and (3) endoreduplications at the end of each larval stage. Here, we report that CDC-25.2, a C. elegans ortholog of Cdc25, is required for these specialized division cycles between the 16E cell stage and the onset of endoreduplication. Results of our genetic analyses suggest that CDC-25.2 regulates intestinal cell divisions and binucleations by counteracting WEE-1.3 and by activating the CDK-1/CYB-1 complex. CDC-25.2 activity is then repressed by LIN-23 E3 ubiquitin ligase before the onset of intestinal endoreduplication, and this repression is maintained by LIN-35, the C. elegans ortholog of Retinoblastoma (Rb). These findings indicate that timely regulation of CDC-25.2 activity is essential for the progression of specialized division cycles and development of the C. elegans intestine. PMID:27104746

Embedded Carbide-derived Carbon (CDC) particles in polypyrrole (PPy) for linear actuator

NASA Astrophysics Data System (ADS)

Zondaka, Zane; Valner, Robert; Aabloo, Alvo; Tamm, Tarmo; Kiefer, Rudolf

2016-04-01

Conducting polymer linear actuators, for example sodium dodecylbenzenesulfonate (NaDBS) doped polypyrrole (PPy/DBS), have shown moderate strain and stress. The goal of this work was to increase the obtainable strain and stress by adding additional active material to PPy/DBS. In recent year's carbide-derived carbon (CDC)-based materials have been applied in actuators; however, the obtained displacement and actuation speed has been low comparing to conducting polymer based actuators. In the present work, a CDC-PPy hybrid was synthesized electrochemically and polyoxometalate (POM) - phosphotungstic acid - was used to attach charge to CDC particles. The CDC-POM served in the presence of NaDBS as an additional electrolyte. Cyclic voltammetry and chronopotentiometric electrochemomechanical deformation (ECMD) measurements were performed in Lithium bis(trifluoromethanesulfonyl)- imide (LiTFSI) aqueous electrolyte. The ECMD measurements revealed that the hybrid CDC-PPy material exhibited higher force and strain in comparison to PPy/DBS films. The new material was investigated by scanning electron microscopy (SEM) to evaluate CDC particle embedding in the polymer network.

Exploring the Knowledge, Attitudes, Beliefs, and Communication Preferences of the General Public regarding HPV: Findings from CDC Focus Group Research and Implications for Practice

ERIC Educational Resources Information Center

Friedman, Allison L.; Shepeard, Hilda

2007-01-01

Genital human papillomavirus (HPV) infection is the most common sexually transmitted virus in the United States, causing genital warts, cervical cell abnormalities, and cervical cancer in women. To inform HPV education efforts, 35 focus groups were conducted with members of the general public, stratified by gender, race/ethnicity, and urban/rural…

Disparities in universal prenatal screening for group B streptococcus--North Carolina, 2002-2003.

PubMed

2005-07-22

Group B streptococcus (GBS) is a leading cause of neonatal morbidity and mortality in the United States. Intrapartum antibiotics administered to women at risk for transmitting GBS to their newborns are effective in preventing perinatal GBS infection. In 2002, CDC, the American Academy of Pediatrics, and the American College of Obstetricians and Gynecologists recommended universal prenatal screening for vaginal and rectal GBS colonization at 35-37 weeks' gestation. To examine prenatal GBS screening among pregnant women in North Carolina, CDC analyzed 2002 and 2003 data from the North Carolina Pregnancy Risk Assessment Monitoring System (PRAMS). The proportions of women reporting prenatal screening for GBS were similar in 2002 and 2003 (70% and 74%, respectively); however, for both years, women of Hispanic ethnicity and women who received prenatal care at a hospital or health department clinic were less likely to report prenatal screening for GBS. These findings underscore the need to increase GBS-related education and prevention activities targeted to these populations.

Mumps Photos

MedlinePlus

... content Start of Search Controls Search Form Controls Cancel Submit Search The CDC CDC A-Z Index ... Z # Start of Search Controls Search Form Controls Cancel Submit Search The CDC Mumps Note: Javascript is ...

Family History

MedlinePlus

... CDC Cancel Submit Search The CDC Family Health History Note: Javascript is disabled or is not supported ... visit this page: About CDC.gov . Family Health History The Basics Family Health History & Chronic Disease Planning ...

Underage Drinking

MedlinePlus

... Prevention (CDC). Alcohol-Related Disease Impact (ARDI) . Atlanta, GA: CDC. Sacks JJ, Gonzales KR, Bouchery EE, Tomedi ... No Fear Act OIG 1600 Clifton Road Atlanta , GA 30329-4027 USA 800-CDC-INFO (800-232- ...

Cyclin A-mediated inhibition of intra-Golgi transport requires p34cdc2.

PubMed

Mackay, D; Kieckbusch, R; Adamczewski, J; Warren, G

1993-12-28

An in vitro assay was used to study the role of p34cdc2 in cyclin A-mediated vesicular transport inhibition. It was shown that the S-phase kinase p33cdk2 reduced the effect of cyclin A on transport assays performed with sHeLa cytosol, even though histone kinase was strongly activated. Also, transport with FT210 cytosol (which is temperature-sensitive for p34cdc2) was inhibited by cyclin A only at the permissive temperature. However, the phosphatase inhibitor microcystin inhibited transport without any requirement for p34cdc2 activity. These results show that transport is inhibited by cyclin A via p34cdc2, and also by another kinase, possibly downstream of p34cdc2.

Photos of Shingles

MedlinePlus

... content Start of Search Controls Search Form Controls Cancel Submit Search The CDC CDC A-Z Index ... Z # Start of Search Controls Search Form Controls Cancel Submit Search The CDC Shingles (Herpes Zoster) Note: ...

Unintentional Drowning

MedlinePlus

... area unsupervised. If you are in and around natural water settings: Use U.S. Coast Guard approved life ... Swimming Pools CDC Feature Article: Drowning Risks in Natural Water Settings CDC: Recreational Water Illnesses (RWIs) CDC ...

Chickenpox (Varicella) Complications

MedlinePlus

... Search The CDC Cancel Submit Search The CDC Chickenpox (Varicella) Note: Javascript is disabled or is not ... message, please visit this page: About CDC.gov . Chickenpox Home About Chickenpox Signs & Symptoms Complications Transmission Prevention & ...

PAX8 (+)/p63 (-) immunostaining pattern in renal collecting duct carcinoma (CDC): a useful immunoprofile in the differential diagnosis of CDC versus urothelial carcinoma of upper urinary tract.

PubMed

Albadine, Roula; Schultz, Luciana; Illei, Peter; Ertoy, Dilek; Hicks, Jessica; Sharma, Rajni; Epstein, Jonathan I; Netto, George J

2010-07-01

Collecting duct carcinoma (CDC) is a relatively rare but aggressive type of renal malignancy with variable morphologic features. One of the World Health Organization diagnostic criteria for CDC is the exclusion of urothelial carcinoma of renal pelvis from the differential diagnosis. PAX8 is a novel lineage restricted transcription factor expressed in renal tubules. We investigated the expression pattern of PAX8 in CDC and its utility, in combination with p63, in resolving the differential diagnosis of CDC versus upper tract urothelial carcinoma (UUC). Archival tissues from 21 CDC and 34 UUC were retrieved from our institutional files. Immunohistochemistry for PAX8 and p63 were performed on routine and tissue microarray sections using standard immunohistochemistry protocol. Intensity of nuclear staining was evaluated for each marker and assigned an incremental 0, 1+, 2+, and 3+ score. Extent of staining was categorized as focal (<25%), nonfocal (25% to 75%), or diffuse (>75%). CDC: All 21 (100%) CDC were positive for PAX8. Intensity of expression was moderate to strong (2+/3+) in 19 cases (90%). Extent of staining was diffuse in 13 of 21 tumors. The p63 was positive in 3 of 21 (14%) CDC cases (PAX8+/p63+). UUC: The 34 UUC included 5 pT1, 4 pT2, and 25 pT3/pT4 tumors. Thirty-one of 34 (91.2%) UUC were negative for PAX8, whereas 33 of 34 (97%) were p63 positive. Staining intensity was moderate in 15 cases (44%), of which 12 were nonfocal or diffuse. The unique p63-negative UUC was a pT1 tumor that was also negative for PAX8 (PAX8-/p63-). We propose the use of the combination of PAX8 and p63 in the diagnosis of poorly differentiated renal sinus epithelial neoplasms where the differential diagnosis includes CDC versus UUC. The immunoprofile of PAX8+/p63- supports the diagnosis of CDC with a sensitivity of 85.7% and a specificity of 100%. In contrast, a (PAX8-/p63+) profile supports the diagnosis of UUC with a sensitivity of 88.2% and a specificity of 100%. The inverse PAX8/p63 expression seen in CDC and UUC supports a renal tubular rather than an urothelial differentiation in CDC given the nephric lineage restriction of PAX8.

Cultural and chemical characterization of CDC groups EO-2, M-5, and M-6, Moraxella (Moraxella) species, Oligella urethralis, Acinetobacter species, and Psychrobacter immobilis.

PubMed

Moss, C W; Wallace, P L; Hollis, D G; Weaver, R E

1988-03-01

We determined phenotypic characteristics, cellular fatty acid composition, and isoprenoid quinone content of representative strains of CDC groups EO-2, M-5, and M-6, Moraxella (Moraxella) species, Oligella urethralis, Acinetobacter species, and Psychrobacter immobilis. All organisms contained ubiquinone with eight isoprene units as the major isoprenolog, but distinct differences were observed in fatty acid composition. Twenty-eight of the original collection of CDC group EO-2 strains were further identified as P. immobilis, EO-2, or EO-3 by distinctive cellular fatty acid profiles, cellular morphology, and pigment production. The cellular fatty acid compositions of M-5 and M-6 were similar but were clearly different from those of other organisms. The genus Acinetobacter was differentiated from other organisms in the study by small amounts of 2-hydroxydodecanoic acid (2-OH-12:0), and P. immobilis was differentiated by small amounts of decanoic acid (10:0) and a branched-chain 17-carbon acid (i-17:0). All Moraxella species were distinguished by small amounts of decanoic acid (10:0) and the absence of i-17:0. M. bovis, M. nonliquefaciens, and some strains of M. lacunata formed a single fatty acid group, while M. osloensis, M. phenylpyruvica, M. atlantae, and other strains of M. lacunata (M. lacunata II) had species-specific fatty acid profiles. O. urethralis differed from Moraxella species by the presence of large amounts (49%) of cis-vaccenic acid (18:1 omega 7c), small amounts (1%) of 3-hydroxyhexadecanoate (3-OH-16:0), and the absence of 10:0 and 3-hydroxydodecanoate (3-OH-12:0). The combined use of chemical data and a small number of conventional tests permitted rapid identification and differentiation of these organisms from each other and from related organisms.

Cultural and chemical characterization of CDC groups EO-2, M-5, and M-6, Moraxella (Moraxella) species, Oligella urethralis, Acinetobacter species, and Psychrobacter immobilis.

PubMed Central

Moss, C W; Wallace, P L; Hollis, D G; Weaver, R E

1988-01-01

We determined phenotypic characteristics, cellular fatty acid composition, and isoprenoid quinone content of representative strains of CDC groups EO-2, M-5, and M-6, Moraxella (Moraxella) species, Oligella urethralis, Acinetobacter species, and Psychrobacter immobilis. All organisms contained ubiquinone with eight isoprene units as the major isoprenolog, but distinct differences were observed in fatty acid composition. Twenty-eight of the original collection of CDC group EO-2 strains were further identified as P. immobilis, EO-2, or EO-3 by distinctive cellular fatty acid profiles, cellular morphology, and pigment production. The cellular fatty acid compositions of M-5 and M-6 were similar but were clearly different from those of other organisms. The genus Acinetobacter was differentiated from other organisms in the study by small amounts of 2-hydroxydodecanoic acid (2-OH-12:0), and P. immobilis was differentiated by small amounts of decanoic acid (10:0) and a branched-chain 17-carbon acid (i-17:0). All Moraxella species were distinguished by small amounts of decanoic acid (10:0) and the absence of i-17:0. M. bovis, M. nonliquefaciens, and some strains of M. lacunata formed a single fatty acid group, while M. osloensis, M. phenylpyruvica, M. atlantae, and other strains of M. lacunata (M. lacunata II) had species-specific fatty acid profiles. O. urethralis differed from Moraxella species by the presence of large amounts (49%) of cis-vaccenic acid (18:1 omega 7c), small amounts (1%) of 3-hydroxyhexadecanoate (3-OH-16:0), and the absence of 10:0 and 3-hydroxydodecanoate (3-OH-12:0). The combined use of chemical data and a small number of conventional tests permitted rapid identification and differentiation of these organisms from each other and from related organisms. Images PMID:3356788

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

Code of Federal Regulations, 2011 CFR

2011-01-01

... 504 loan outside of a CDC's Area of Operations. 120.839 Section 120.839 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Extending A Cdc's Area of Operations § 120.839 Case-by-case application to make a 504 loan outside of a CDC's Area of...

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

Code of Federal Regulations, 2010 CFR

2010-01-01

... 504 loan outside of a CDC's Area of Operations. 120.839 Section 120.839 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Extending A Cdc's Area of Operations § 120.839 Case-by-case application to make a 504 loan outside of a CDC's Area of...

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

Code of Federal Regulations, 2014 CFR

2014-01-01

... 504 loan outside of a CDC's Area of Operations. 120.839 Section 120.839 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Extending A Cdc's Area of Operations § 120.839 Case-by-case application to make a 504 loan outside of a CDC's Area of...

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

Code of Federal Regulations, 2012 CFR

2012-01-01

... 504 loan outside of a CDC's Area of Operations. 120.839 Section 120.839 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Extending A Cdc's Area of Operations § 120.839 Case-by-case application to make a 504 loan outside of a CDC's Area of...

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

Code of Federal Regulations, 2013 CFR

2013-01-01

... 504 loan outside of a CDC's Area of Operations. 120.839 Section 120.839 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Extending A Cdc's Area of Operations § 120.839 Case-by-case application to make a 504 loan outside of a CDC's Area of...

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

Code of Federal Regulations, 2010 CFR

2010-01-01

... 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 Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504...

Contents, Followers, and Retweets of the Centers for Disease Control and Prevention’s Office of Advanced Molecular Detection (@CDC_AMD) Twitter Profile: Cross-Sectional Study

PubMed Central

Blankenship, Elizabeth B; Goff, Mary Elizabeth; Guinn, Amy J; Saroha, Nitin; Tse, Zion Tsz Ho

2018-01-01

Background The Office of Advanced Molecular Detection (OAMD), Centers for Disease Control and Prevention (CDC), manages a Twitter profile (@CDC_AMD). To our knowledge, no prior study has analyzed a CDC Twitter handle’s entire contents and all followers. Objective This study aimed to describe the contents and followers of the Twitter profile @CDC_AMD and to assess if attaching photos or videos to tweets posted by @CDC_AMD would increase retweet frequency. Methods Data of @CDC_AMD were retrieved on November 21, 2016. All followers (N=809) were manually categorized. All tweets (N=768) were manually coded for contents and whether photos or videos were attached. Retweet count for each tweet was recorded. Negative binomial regression models were applied to both the original and the retweet corpora. Results Among the 809 followers, 26.0% (210/809) were individual health professionals, 11.6% (94/809) nongovernmental organizations, 3.3% (27/809) government agencies’ accounts, 3.3% (27/809) accounts of media organizations and journalists, and 0.9% (7/809) academic journals, with 54.9% (444/809) categorized as miscellaneous. A total of 46.9% (360/768) of @CDC_AMD’s tweets referred to the Office’s website and their current research; 17.6% (135/768) referred to their scientists’ publications. Moreover, 80% (69/86) of tweets retweeted by @CDC_AMD fell into the miscellaneous category. In addition, 43.4% (333/768) of the tweets contained photos or videos, whereas the remaining 56.6% (435/768) did not. Attaching photos or videos to original @CDC_AMD tweets increases the number of retweets by 37% (probability ratio=1.37, 95% CI 1.13-1.67, P=.002). Content topics did not explain or modify this association. Conclusions This study confirms CDC health communicators’ experience that original tweets created by @CDC_AMD Twitter profile sharing images or videos (or their links) received more retweets. The current policy of attaching images to tweets should be encouraged. PMID:29610112

Comparison of Effectiveness of Betamethasone gel Applied to the Tracheal Tube and IV Dexamethasone on Postoperative Sore Throat: A Randomized Controlled Trial.

PubMed

Tabari, Masumeh; Soltani, Ghasem; Zirak, Nahid; Alipour, Moammad; Khazaeni, Kamran

2013-09-01

Postoperative sore throat is a common complaint in patients with endotracheal intubation and has potentially dangerous complications. This randomized controlled trial study investigated the incidence of postoperative sore throat after general anesthesia when betamethasone gel is applied to a tracheal tube compared with when IV dexamethasone is prescribed. Two hundred and twenty five American Society of Anesthesiologist (ASA)-class I and II patients undergoing elective abdominal surgery with tracheal intubation were randomly divided into three groups: betamethasone gel, intravenous (IV) dexamethasone, and control groups. In the post-anesthesia care unit, a blinded anesthesiologist interviewed all patients regarding postoperative sore throat at 1,6, and 24 hours after surgery. The incidence of sore throat was significantly lower in the betamethasone gel group compared with the IV dexamethasone and control groups, 1, 6, and 24 hours after surgery. In the first day after surgery 10.7% of the betamethasone group had sore throat whereas 26.7% of the IV dexamethasone group and 30.7% of the control group had sore throat. Bucking before extubation was observed in 14(18.4%), 8(10.4%), and 9(12.2%) patients, in the IV dexamethasone, betamethasone gel, and control group, respectively. We concluded that wide spread application of betamethasone gel over tracheal tubes effectively mitigates postoperative sore throat, compared with IV dexamethasone application.

Articular cartilage-derived cells hold a strong osteogenic differentiation potential in comparison to mesenchymal stem cells in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salamon, Achim, E-mail: achim.salamon@med.uni-rostock.de; Jonitz-Heincke, Anika, E-mail: anika.jonitz@med.uni-rostock.de; Adam, Stefanie, E-mail: stefanie.adam@med.uni-rostock.de

Cartilaginous matrix-degenerative diseases like osteoarthritis (OA) are characterized by gradual cartilage erosion, and also by increased presence of cells with mesenchymal stem cell (MSC) character within the affected tissues. Moreover, primary chondrocytes long since are known to de-differentiate in vitro and to be chondrogenically re-differentiable. Since both findings appear to conflict with each other, we quantitatively assessed the mesenchymal differentiation potential of OA patient cartilage-derived cells (CDC) towards the osteogenic and adipogenic lineage in vitro and compared it to that of MSC isolated from adipose tissue (adMSC) of healthy donors. We analyzed expression of MSC markers CD29, CD44, CD105, andmore » CD166, and, following osteogenic and adipogenic induction in vitro, quantified their expression of osteogenic and adipogenic differentiation markers. Furthermore, CDC phenotype and proliferation were monitored. We found that CDC exhibit an MSC CD marker expression pattern similar to adMSC and a similar increase in proliferation rate during osteogenic differentiation. In contrast, the marked reduction of proliferation observed during adipogenic differentiation of adMSC was absent in CDC. Quantification of differentiation markers revealed a strong osteogenic differentiation potential for CDC, however almost no capacity for adipogenic differentiation. Since in the pathogenesis of OA, cartilage degeneration coincides with high bone turnover rates, the high osteogenic differentiation potential of OA patient-derived CDC may affect clinical therapeutic regimens aiming at autologous cartilage regeneration in these patients. - Highlights: • We analyze the mesenchymal differentiation capacity of cartilage-derived cells (CDC). • CDC express mesenchymal stem cell (MSC) markers CD29, CD44, CD105, and CD166. • CDC and MSC proliferation is reduced in adipogenesis and increased in osteogenesis. • Adipogenic differentiation is virtually absent in CDC, but strong in MSC. • Osteogenic differentiation is significantly stronger for CDC than for MSC.« less

Comparative study of topical vs. intravenous tranexamic acid regarding blood loss in total knee arthroplasty.

PubMed

Zekcer, Ari; Priori, Ricardo Del; Tieppo, Clauber; Silva, Ricardo Soares da; Severino, Nilson Roberto

2017-01-01

To compare topical vs. intravenous tranexamic acid (TA) in total knee arthroplasty regarding blood loss and transfusion. Ninety patients were randomized to receive TA intravenously (20 mg/kg in 100 mL of saline; group IV), topically (1.5 g in 50 mL of saline, sprayed over the operated site, before release of the tourniquet; topical group), or intravenous saline (100 mL with anesthesia; control group). The volume of drained blood in 48 h, the amount of transfused blood, and the serum levels of hemoglobin and hematocrit before and after surgery were evaluated. The groups were similar for gender, age, weight, laterality, and preoperative hemoglobin and hematocrit levels ( p  > 0.2). The hemoglobin level dropped in all groups when comparing the preoperative and the 48-h evaluations: the control group decreased 3.8 mg/dL on average, while the IV group had a decrease of 3.0, and the topical group, of 3.2 ( p  = 0.019). The difference between the control and IV groups was confirmed by Bonferroni test ( p  = 0.020). The difference between the control group and the topical group was not significant ( p  = 0.130), although there was less reduction in hemoglobin in the topical group; the comparison between the IV group and the topical group was also not significant ( p  = 1.000). Using topic and IV tranexamic acid decreased blood loss and the need for transfusion in total knee arthroplasty. Topical application showed results similar to IV use regarding the need for blood transfusion, but without the possible side effects of IV administration.

A Two-Year Randomized Trial of Interventions to Decrease Stress Hormone Vasopressin Production in Patients with Meniere's Disease-A Pilot Study.

PubMed

Kitahara, Tadashi; Okamoto, Hidehiko; Fukushima, Munehisa; Sakagami, Masaharu; Ito, Taeko; Yamashita, Akinori; Ota, Ichiro; Yamanaka, Toshiaki

2016-01-01

Meniere's disease, a common inner ear condition, has an incidence of 15-50 per 100,000. Because mental/physical stress and subsequent increase in the stress hormone vasopressin supposedly trigger Meniere's disease, we set a pilot study to seek new therapeutic interventions, namely management of vasopressin secretion, to treat this disease. We enrolled 297 definite Meniere's patients from 2010 to 2012 in a randomized-controlled and open-label trial, assigning Group-I (control) traditional oral medication, Group-II abundant water intake, Group-III tympanic ventilation tubes and Group-IV sleeping in darkness. Two hundred sixty-three patients completed the planned 2-year-follow-up, which included assessment of vertigo, hearing, plasma vasopressin concentrations and changes in stress/psychological factors. At 2 years, vertigo was completely controlled in 54.3% of patients in Group-I, 81.4% in Group-II, 84.1% in Group-III, and 80.0% in Group-IV (statistically I < II = III = IV). Hearing was improved in 7.1% of patients in Group-I, 35.7% in Group-II, 34.9% in Group-III, and 31.7% in Group-IV (statistically I < II = III = IV). Plasma vasopressin concentrations decreased more in Groups-II, -III, and -IV than in Groups-I (statistically I < II = III = IV), although patients' stress/psychological factors had not changed. Physicians have focused on stress management for Meniere's disease. However, avoidance of stress is unrealistic for patients who live in demanding social environments. Our findings in this pilot study suggest that interventions to decrease vasopressin secretion by abundant water intake, tympanic ventilation tubes and sleeping in darkness is feasible in treating Meniere's disease, even though these therapies did not alter reported mental/physical stress levels. ClinicalTrials.gov NCT01099046.

Intravenous vs Oral Acetaminophen as an Adjunct to Multimodal Analgesia After Total Knee Arthroplasty: A Prospective, Randomized, Double-Blind Clinical Trial.

PubMed

O'Neal, Jason B; Freiberg, Andrew A; Yelle, Marc D; Jiang, Yandong; Zhang, Chengwei; Gu, Yin; Kong, Xiangyi; Jian, Wenling; O'Neal, Wesley T; Wang, Jingping

2017-10-01

The efficacy of intravenous (IV) acetaminophen compared with its oral formulation for postoperative analgesia is unknown. We hypothesized that the addition of acetaminophen to a multimodal analgesia regimen would provide improved pain management in patients after total knee arthroplasty (TKA) and that the effect of acetaminophen would be variable based on the route of delivery. The study was a single-center, randomized, double-blinded, placebo-controlled clinical trial on the efficacy of IV vs oral acetaminophen in patients undergoing unilateral TKA. One hundred seventy-four subjects were randomized to one of the 3 groups: IV acetaminophen group (IV group, n = 57) received 1 g IV acetaminophen and oral placebo before postanesthesia care unit (PACU) admission; oral acetaminophen group (PO group, n = 58) received 1 g oral acetaminophen and volume-matched IV normal saline; placebo group (Placebo group, n = 59) received oral placebo and volume-matched IV normal saline. Pain scores were obtained every 15 minutes during PACU stay. Average pain scores, maximum pain score, and pain scores before physical therapy were compared among the 3 groups. Secondary outcomes included total opiate consumption, time to PACU discharge, time to rescue analgesia, and time to breakthrough pain. The average PACU pain score was similar in the IV group (0.56 ± 0.99 [mean ± standard deviation]) compared with the PO group (0.67 ± 1.20; P = .84) and Placebo group (0.58 ± 0.99; P = .71). Total opiate consumption at 6 hours (0.47 mg hydromorphone equivalents ± 0.56 vs 0.54 ± 0.53 vs 0.54 ± 0.61; P = .69) and at 24 hours (1.25 ± 1.30 vs 1.49 ± 1.34 vs 1.36 ± 1.31; P = .46) were also similar between the IV, PO, and Placebo groups. No significant differences were found between all groups for any other outcome. Neither IV nor oral acetaminophen provides additional analgesia in the immediate postoperative period when administered as an adjunct to multimodal analgesia in patients undergoing TKA in the setting of a spinal anesthetic. Copyright © 2017 Elsevier Inc. All rights reserved.

WISEWOMAN: Frequently Asked Questions

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Osteoblast-specific deletion of Hrpt2/Cdc73 results in high bone mass and increased bone turnover.

PubMed

Droscha, Casey J; Diegel, Cassandra R; Ethen, Nicole J; Burgers, Travis A; McDonald, Mitchell J; Maupin, Kevin A; Naidu, Agni S; Wang, PengFei; Teh, Bin T; Williams, Bart O

2017-05-01

Inactivating mutations that lead to loss of heterozygosity within the HRPT2/Cdc73 gene are directly linked to the development of primary hyperparathyroidism, parathyroid adenomas, and ossifying fibromas of the jaw (HPT-JT). The protein product of the Cdc73 gene, parafibromin, is a core member of the polymerase-associated factors (PAF) complex, which coordinates epigenetic modifiers and transcriptional machinery to control gene expression. We conditionally deleted Cdc73 within mesenchymal progenitors or within mature osteoblasts and osteocytes to determine the consequences of parafibromin loss within the mesenchymal lineage. Homozygous deletion of Cdc73 via the Dermo1-Cre driver resulted in embryos which lacked mesenchymal organ development of internal organs, including the heart and fetal liver. Immunohistochemical detection of cleaved caspase-3 revealed extensive apoptosis within the progenitor pools of developing organs. Unexpectedly, when Cdc73 was homozygously deleted within mature osteoblasts and osteocytes (via the Ocn-Cre driver), the mice had a normal life span but increased cortical and trabecular bone. OCN-Cre;Cdc73 flox/flox bones displayed large cortical pores actively undergoing bone remodeling. Additionally the cortical bone of OCN-Cre;Cdc73 flox/flox femurs contained osteocytes with marked amounts of cytoplasmic RNA and a high rate of apoptosis. Transcriptional analysis via RNA-seq within OCN-Cre;Cdc73 flox/flox osteoblasts showed that loss of Cdc73 led to a derepression of osteoblast-specific genes, specifically those for collagen and other bone matrix proteins. These results aid in our understanding of the role parafibromin plays within transcriptional regulation, terminal differentiation, and bone homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

Mechanism of APC/CCDC20 activation by mitotic phosphorylation.

PubMed

Qiao, Renping; Weissmann, Florian; Yamaguchi, Masaya; Brown, Nicholas G; VanderLinden, Ryan; Imre, Richard; Jarvis, Marc A; Brunner, Michael R; Davidson, Iain F; Litos, Gabriele; Haselbach, David; Mechtler, Karl; Stark, Holger; Schulman, Brenda A; Peters, Jan-Michael

2016-05-10

Chromosome segregation and mitotic exit are initiated by the 1.2-MDa ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome) and its coactivator CDC20 (cell division cycle 20). To avoid chromosome missegregation, APC/C(CDC20) activation is tightly controlled. CDC20 only associates with APC/C in mitosis when APC/C has become phosphorylated and is further inhibited by a mitotic checkpoint complex until all chromosomes are bioriented on the spindle. APC/C contains 14 different types of subunits, most of which are phosphorylated in mitosis on multiple sites. However, it is unknown which of these phospho-sites enable APC/C(CDC20) activation and by which mechanism. Here we have identified 68 evolutionarily conserved mitotic phospho-sites on human APC/C bound to CDC20 and have used the biGBac technique to generate 47 APC/C mutants in which either all 68 sites or subsets of them were replaced by nonphosphorylatable or phospho-mimicking residues. The characterization of these complexes in substrate ubiquitination and degradation assays indicates that phosphorylation of an N-terminal loop region in APC1 is sufficient for binding and activation of APC/C by CDC20. Deletion of the N-terminal APC1 loop enables APC/C(CDC20) activation in the absence of mitotic phosphorylation or phospho-mimicking mutations. These results indicate that binding of CDC20 to APC/C is normally prevented by an autoinhibitory loop in APC1 and that its mitotic phosphorylation relieves this inhibition. The predicted location of the N-terminal APC1 loop implies that this loop controls interactions between the N-terminal domain of CDC20 and APC1 and APC8. These results reveal how APC/C phosphorylation enables CDC20 to bind and activate the APC/C in mitosis.

Sternal wound infection after cardiac surgery: incidence and risk factors according to clinical presentation.

PubMed

Lemaignen, A; Birgand, G; Ghodhbane, W; Alkhoder, S; Lolom, I; Belorgey, S; Lescure, F-X; Armand-Lefevre, L; Raffoul, R; Dilly, M-P; Nataf, P; Lucet, J C

2015-07-01

The incidence of surgical site infection (SSI) after cardiac surgery depends on the definition used. A distinction is generally made between mediastinitis, as defined by the US Centers for Disease Control and Prevention (CDC), and superficial SSI. Our objective was to decipher these entities in terms of presentation and risk factors. We performed a 7-year single centre analysis of prospective surveillance of patients with cardiac surgery via median sternotomy. SSI was defined as the need for reoperation due to infection. Among 7170 patients, 292 (4.1%) developed SSI, including 145 CDC-defined mediastinitis (CDC-positive SSI, 2.0%) and 147 superficial SSI without associated bloodstream infection (CDC-negative SSI, 2.1%). Median time to reoperation for CDC-negative SSI was 18 days (interquartile range, 14-26) and 16 (interquartile range, 11-24) for CDC-positive SSI (p 0.02). Microorganisms associated with CDC-negative SSI were mainly skin commensals (62/147, 41%) or originated in the digestive tract (62/147, 42%); only six were due to Staphylococcus aureus (4%), while CDC-positive SSI were mostly due to S. aureus (52/145, 36%) and germs from the digestive tract (52/145, 36%). Risk factors for SSI were older age, obesity, chronic obstructive bronchopneumonia, diabetes mellitus, critical preoperative state, postoperative vasopressive support, transfusion or prolonged ventilation and coronary artery bypass grafting, especially if using both internal thoracic arteries in female patients. The number of internal thoracic arteries used and factors affecting wound healing were primarily associated with CDC-negative SSI, whereas comorbidities and perioperative complications were mainly associated with CDC-positive SSI. These 2 entities differed in time to revision surgery, bacteriology and risk factors, suggesting a differing pathophysiology. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Devor, E.J.; Dill-Devor, R.M.

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 PCRmore » 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.« less

To nearly come full circle: Nonoperative management of high-grade IV-V blunt splenic trauma is safe using a protocol with routine angioembolization.

PubMed

Bhullar, Indermeet S; Tepas, Joseph J; Siragusa, Daniel; Loper, Todd; Kerwin, Andrew; Frykberg, Eric R

2017-04-01

Nonoperative management (NOM) of hemodynamically stable high-grade (IV-V) blunt splenic trauma remains controversial given the high failure rates (19%) that persist despite angioembolization (AE) protocols. The NOM protocol was modified in 2011 to include mandatory AE of all grade (IV-V) injuries without contrast blush (CB) along with selective AE of grade (I-V) with CB. The purpose of this study was to determine if this new AE (NAE) protocol significantly lowered the failure rates for grade (IV-V) injuries allowing for safe observation without surgery and if the exclusion of grade III injuries allowed for the prevention of unnecessary angiograms without affecting the overall failure rates. The records of patients with blunt splenic trauma from January 2000 to October 2014 at a Level I trauma center were retrospectively reviewed. Patients were divided into two groups and failure of NOM (FNOM) rates compared: NAE protocol (2011-2014) with mandatory AE for all grade (IV-V) injuries without CB and selective AE for grade (I-V) with CB versus old AE (OAE) protocol (2000-2010) with selective AE for grade (I-V) with CB. Seven hundred twelve patients underwent NOM with 522 (73%) in the OAE group and 190 (27%) in the NAE group. Evolving from the OAE to the NAE strategy resulted in a significantly lower FNOM rate for the overall group (grade I-V) (OAE vs. NAE, 4% to 1%, p = 0.04) and the grade (IV-V) group (OAE vs. NAE, 19% vs. 3%, p = 0.01). Angiograms were avoided in 113 grade (I-III) injuries with no CB; these patients had NOM with observation alone and none failed. A protocol using mandatory AE of all high-grade (IV-V) injuries without CB and selective AE of grade (I-V) with CB may provide for optimum salvage with safe NOM of the high-grade injuries (IV-V) and limited unnecessary angiograms. Therapeutic study, level IV.

How would case managers' practice change in a consumer-directed care environment in Australia?

PubMed

You, Emily Chuanmei; Dunt, David; Doyle, Colleen

2017-01-01

The aim of this study was to explore case managers' perceived changes in their practice in the future when consumer-directed care (CDC) is widely implemented in Australia's community aged care system. Purposeful sampling was used and semi-structured individual and group interviews were conducted between September 2012 and March 2013. Participants were drawn from a list of all case managers who administered publicly funded community aged care packages in Victoria, Australia. Empowerment theory was used to guide the analysis and interpretation of the data. The thematic analysis revealed that case managers had mixed views about CDC. They also perceived changes in case managers' practice in the future when CDC is widely implemented. These might specifically include: first, case managers would not directly manage clients' budgets. While some case managers were concerned about losing power for this change, others believed that they would still have important financial roles to perform, such as setting rules, providing financial support and monitoring clients' use of budgets. Second, case managers would focus on performing roles in providing information, and empowering, facilitating and educating clients. These would help to strengthen clients' capacities and assist them to self-manage their care. Third, case managers would work in partnership with clients through frequent or skilful communication, mutual goal setting and goal facilitation. Fourth, case managers would manage more clients. In addition, they would provide less support to each individual client and perform less care co-ordination role. The findings suggest case managers paying attention to power balance regarding budget management in a CDC environment. Furthermore, they might frequently or skilfully communicate with, empower, facilitate and educate clients; work together with them to set up goals; and facilitate them to achieve goals. New research using empowerment theory to examine the actual practice of case managers in a well-established CDC system is warranted. © 2015 John Wiley & Sons Ltd.

A novel strategy of integrated microarray analysis identifies CENPA, CDK1 and CDC20 as a cluster of diagnostic biomarkers in lung adenocarcinoma.

PubMed

Liu, Wan-Ting; Wang, Yang; Zhang, Jing; Ye, Fei; Huang, Xiao-Hui; Li, Bin; He, Qing-Yu

2018-07-01

Lung adenocarcinoma (LAC) is the most lethal cancer and the leading cause of cancer-related death worldwide. The identification of meaningful clusters of co-expressed genes or representative biomarkers may help improve the accuracy of LAC diagnoses. Public databases, such as the Gene Expression Omnibus (GEO), provide rich resources of valuable information for clinics, however, the integration of multiple microarray datasets from various platforms and institutes remained a challenge. To determine potential indicators of LAC, we performed genome-wide relative significance (GWRS), genome-wide global significance (GWGS) and support vector machine (SVM) analyses progressively to identify robust gene biomarker signatures from 5 different microarray datasets that included 330 samples. The top 200 genes with robust signatures were selected for integrative analysis according to "guilt-by-association" methods, including protein-protein interaction (PPI) analysis and gene co-expression analysis. Of these 200 genes, only 10 genes showed both intensive PPI network and high gene co-expression correlation (r > 0.8). IPA analysis of this regulatory networks suggested that the cell cycle process is a crucial determinant of LAC. CENPA, as well as two linked hub genes CDK1 and CDC20, are determined to be potential indicators of LAC. Immunohistochemical staining showed that CENPA, CDK1 and CDC20 were highly expressed in LAC cancer tissue with co-expression patterns. A Cox regression model indicated that LAC patients with CENPA + /CDK1 + and CENPA + /CDC20 + were high-risk groups in terms of overall survival. In conclusion, our integrated microarray analysis demonstrated that CENPA, CDK1 and CDC20 might serve as novel cluster of prognostic biomarkers for LAC, and the cooperative unit of three genes provides a technically simple approach for identification of LAC patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Influenza (flu) vaccine (Inactivated or Recombinant): What you need to know

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78 FR 949 - Office for State, Tribal, Local and Territorial Support (OSTLTS)

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Surgical site infection after breast surgery: impact of 2010 CDC reporting guidelines.

PubMed

Degnim, Amy C; Throckmorton, Alyssa D; Boostrom, Sarah Y; Boughey, Judy C; Holifield, Andrea; Baddour, Larry M; Hoskin, Tanya L

2012-12-01

Reported surgical site infection (SSI) rates after breast operations ranges 0.8-26 % in the literature. The aims of the present study were to characterize SSI after breast/axillary operations and determine the impact on the SSI rate of the 2010 Centers for Disease Control and Prevention (CDC) reporting guidelines that now specifically exclude cellulitis. Retrospective chart review identified 368 patients with 449 operated sides between July 2004 and June 2006. SSI was defined by CDC criteria: purulent drainage (category 1), positive aseptically collected culture (category 2), signs of inflammation with opening of incision and absence of negative culture (category 3), and physician diagnosis of infection (category 4). The impact of excluding cellulitis was assessed. Prior CDC reporting guidelines revealed that among 368 patients, 32 (8.7 %) experienced SSI in 33 (7.3 %) of 449 operated sides. Of these, 11 (33 %) met CDC criteria 1-3, while 22 (67 %) met CDC criterion 4. Excluding cellulitis cases per 2010 CDC SSI reporting guidelines eliminates 21 of the 22 infections previously meeting CDC criterion 4. Under the new reporting guidelines, the SSI rate is 12 (2.7 %) of 449 operated sides. SSI rates varied by procedure, but these differences were not statistically significant. Cellulitis after breast and axillary surgery is much more common than other criteria for SSI, and SSI rates are reduced almost threefold if cellulitis cases are excluded. Recently revised CDC reporting guidelines may result in underestimates of the clinical burden of SSI after breast/axillary surgery.

Phosphatidylserine and GTPase activation control Cdc42 nanoclustering to counter dissipative diffusion.

PubMed

Sartorel, Elodie; Ünlü, Caner; Jose, Mini; Massoni-Laporte, Aurélie; Meca, Julien; Sibarita, Jean-Baptiste; McCusker, Derek

2018-04-18

The anisotropic organization of plasma membrane constituents is indicative of mechanisms that drive the membrane away from equilibrium. However, defining these mechanisms is challenging due to the short spatio-temporal scales at which diffusion operates. Here, we use high-density single protein tracking combined with photoactivation localization microscopy (sptPALM) to monitor Cdc42 in budding yeast, a system in which Cdc42 exhibits anisotropic organization. Cdc42 exhibited reduced mobility at the cell pole, where it was organized in nanoclusters. The Cdc42 nanoclusters were larger at the cell pole than those observed elsewhere in the cell. These features were exacerbated in cells expressing Cdc42-GTP, and were dependent on the scaffold Bem1, which contributed to the range of mobility and nanocluster size exhibited by Cdc42. The lipid environment, in particular phosphatidylserine levels, also played a role in regulating Cdc42 nanoclustering. These studies reveal how the mobility of a Rho GTPase is controlled to counter the depletive effects of diffusion, thus stabilizing Cdc42 on the plasma membrane and sustaining cell polarity. Movie S1 Movie S1 sptPALM imaging of live yeast expressing Pil1-mEOS expressed at the genomic locus. Pil1-mEOS was simultaneously photo-converted with a 405 nm laser and imaged with a 561 nm laser using HiLo illumination. Images were acquired at 20 ms intervals, of which 300 frames are shown at 7 frames per second.

The Cytokinin Requirement for Cell Division in Cultured Nicotiana plumbaginifolia Cells Can Be Satisfied by Yeast Cdc25 Protein Tyrosine Phosphatase. Implications for Mechanisms of Cytokinin Response and Plant Development

PubMed Central

Zhang, Kerong; Diederich, Ludger; John, Peter C.L.

2005-01-01

Cultured cells of Nicotiana plumbaginifolia, when deprived of exogenous cytokinin, arrest in G2 phase prior to mitosis and then contain cyclin-dependent protein kinase (CDK) that is inactive because phosphorylated on tyrosine (Tyr). The action of cytokinin in stimulating the activation of CDK by removal of inhibitory phosphorylation from Tyr is not a secondary downstream consequence of other hormone actions but is the key primary effect of the hormone in its stimulation of cell proliferation, since cytokinin could be replaced by expression of cdc25, which encodes the main Cdc2 (CDK)-Tyr dephosphorylating enzyme of yeast (Saccharomyces cerevisiae). The cdc25 gene, under control of a steroid-inducible promoter, induced a rise in cdc25 mRNA, accumulation of p67Cdc25 protein, and increase in Cdc25 phosphatase activity that was measured in vitro with Tyr-phosphorylated Cdc2 as substrate. Cdc25 phosphatase activity peaked during mitotic prophase at the time CDK activation was most rapid. Mitosis that was induced by cytokinin also involved increase in endogenous plant CDK Tyr phosphatase activity during prophase, therefore indicating that this is a normal part of plant mitosis. These results suggest a biochemical mechanism for several previously described transgene phenotypes in whole plants and suggest that a primary signal from cytokinin leading to progression through mitosis is the activation of CDK by dephosphorylation of Tyr. PMID:15618425

The cytokinin requirement for cell division in cultured Nicotiana plumbaginifolia cells can be satisfied by yeast Cdc25 protein tyrosine phosphatase: implications for mechanisms of cytokinin response and plant development.

PubMed

Zhang, Kerong; Diederich, Ludger; John, Peter C L

2005-01-01

Cultured cells of Nicotiana plumbaginifolia, when deprived of exogenous cytokinin, arrest in G2 phase prior to mitosis and then contain cyclin-dependent protein kinase (CDK) that is inactive because phosphorylated on tyrosine (Tyr). The action of cytokinin in stimulating the activation of CDK by removal of inhibitory phosphorylation from Tyr is not a secondary downstream consequence of other hormone actions but is the key primary effect of the hormone in its stimulation of cell proliferation, since cytokinin could be replaced by expression of cdc25, which encodes the main Cdc2 (CDK)-Tyr dephosphorylating enzyme of yeast (Saccharomyces cerevisiae). The cdc25 gene, under control of a steroid-inducible promoter, induced a rise in cdc25 mRNA, accumulation of p67(Cdc25) protein, and increase in Cdc25 phosphatase activity that was measured in vitro with Tyr-phosphorylated Cdc2 as substrate. Cdc25 phosphatase activity peaked during mitotic prophase at the time CDK activation was most rapid. Mitosis that was induced by cytokinin also involved increase in endogenous plant CDK Tyr phosphatase activity during prophase, therefore indicating that this is a normal part of plant mitosis. These results suggest a biochemical mechanism for several previously described transgene phenotypes in whole plants and suggest that a primary signal from cytokinin leading to progression through mitosis is the activation of CDK by dephosphorylation of Tyr.

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MSE55, a Cdc42 effector protein, induces long cellular extensions in fibroblasts

PubMed Central

Burbelo, Peter D.; Snow, Dianne M.; Bahou, Wadie; Spiegel, Sarah

1999-01-01

Cdc42 is a member of the Rho GTPase family that regulates multiple cellular activities, including actin polymerization, kinase-signaling activation, and cell polarization. MSE55 is a nonkinase CRIB (Cdc42/Rac interactive-binding) domain-containing molecule of unknown function. Using glutathione S-transferase-capture experiments, we show that MSE55 binds to Cdc42 in a GTP-dependent manner. MSE55 binding to Cdc42 required an intact CRIB domain, because a MSE55 CRIB domain mutant no longer interacted with Cdc42. To study the function of MSE55 we transfected either wild-type MSE55 or a MSE55 CRIB mutant into mammalian cells. In Cos-7 cells, wild-type MSE55 localized at membrane ruffles and increased membrane actin polymerization, whereas expression of the MSE55 CRIB mutant showed fewer membrane ruffles. In contrast to these results, MSE55 induced the formation of long, actin-based protrusions in NIH 3T3 cells as detected by immunofluorescence and live-cell video microscopy. MSE55-induced protrusion formation was blocked by expression of dominant-negative N17Cdc42, but not by expression of dominant-negative N17Rac. These findings indicate that MSE55 is a Cdc42 effector protein that mediates actin cytoskeleton reorganization at the plasma membrane. PMID:10430899

Human Cdc14A regulates Wee1 stability by counteracting CDK-mediated phosphorylation

PubMed Central

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 such as Plk1, triggering Wee1 degradation at the onset of mitosis. Here we report that Cdc14A plays an important role in the regulation of Wee1 stability. Depletion of Cdc14A results in a significant reduction in Wee1 protein levels. Cdc14A binds to Wee1 at its amino-terminal domain and reverses CDK-mediated Wee1 phosphorylation. In particular, we found that Cdc14A inhibits Wee1 degradation through the dephosphorylation of Ser-123 and Ser-139 residues. Thus the lack of phosphorylation of these two residues prevents the interaction with Plk1 and the consequent efficient Wee1 degradation at the onset of mitosis. These data support the hypothesis that Cdc14A counteracts Cdk1–cyclin B1 activity through Wee1 dephosphorylation. PMID:23051732

Clostridium difficile colitis in patients after kidney and pancreas–kidney transplantation

PubMed Central

Keven, K.; Basu, A.; Re, L.; Tan, H.; Marcos, A.; Fung, J.J.; Starzl, T.E.; Simmons, R.L.; Shapiro, R.

2010-01-01

Limited data exist about Clostridium difficile colitis (CDC) in solid organ transplant patients. Between 1/1/99 and 12/31/02, 600 kidney and 102 pancreas–kidney allograft recipients were transplanted. Thirty-nine (5.5%) of these patients had CDC on the basis of clinical and laboratory findings. Of these 39 patients, 35 have information available for review. CDC developed at a median of 30 days after transplantation, and the patients undergoing pancreas–kidney transplantation had a slightly higher incidence of CDC than recipients of kidney alone (7.8% vs. 4.5%, P> 0.05). All but one patient presented with diarrhea. Twenty-four patients (64.9%) were diagnosed in the hospital, and CDC occurred during first hospitalization in 14 patients (40%). Treatment was with oral metronidazole (M) in 33 patients (94%)and M + oral vancomycin (M + V) in 2 patients. Eight patients had recurrent CDC, which occurred at a median of 30 days (range 15–314) after the first episode. Two patients (5.7%) developed fulminant CDC, presented with toxic megacolon, and underwent colectomy. One of them died; the other patient survived after colectomy. CDC should be considered as a diagnosis in transplant patients with history of diarrhea after antibiotic use, and should be treated aggressively before the infection becomes complicated. PMID:15225221

Cloning, sequencing and phylogenetic analysis of the small GTPase gene cdc-42 from Ancylostoma caninum.

PubMed

Yang, Yurong; Zheng, Jing; Chen, Jiaxin

2012-12-01

CDC-42 is a member of the Rho GTPase subfamily that is involved in many signaling pathways, including mitosis, cell polarity, cell migration and cytoskeleton remodeling. Here, we present the first characterization of a full-length cDNA encoding the small GTPase cdc-42, designated as Accdc-42, isolated from the parasitic nematode Ancylostoma caninum. The encoded protein contains 191 amino acid residues with a predicted molecular weight of 21 kDa and displays a high level of identity with the Rho-family GTPase protein CDC-42. Phylogenetic analysis revealed that Accdc-42 was most closely related to Caenorhabditis briggsae cdc-42. Comparison with selected sequences from the free-living nematode Caenorhabditis elegans, Drosophila melanogaster, Xenopus laevis, Danio rerio, Mus musculus and human genomes showed that Accdc-42 is highly conserved. AcCDC-42 demonstrates the highest identity to CDC-42 from C. briggsae (94.2%), and it also exhibits 91.6% identity to CDC-42 from C. elegans and 91.1% from Brugia malayi. Additionally, the transcript of Accdc-42 was analyzed during the different developmental stages of the worm. Accdc-42 was expressed in the L1/L2 larvae, L3 larvae and female and male adults of A. caninum. Copyright © 2012 Elsevier Inc. All rights reserved.

LIN-23, an E3 Ubiquitin Ligase Component, Is Required for the Repression of CDC-25.2 Activity during Intestinal Development in Caenorhabditis elegans.

PubMed

Son, Miseol; Kawasaki, Ichiro; Oh, Bong-Kyeong; Shim, Yhong-Hee

2016-11-30

Caenorhabditis elegans ( C. elegans ) utilizes two different cell-cycle modes, binucleations during the L1 larval stage and endoreduplications at four larval moltings, for its postembryonic intestinal development. Previous genetic studies indicated that CDC-25.2 is specifically required for binucleations at the L1 larval stage and is repressed before endoreduplications. Furthermore, LIN-23, the C. elegans β-TrCP ortholog, appears to function as a repressor of CDC-25.2 to prevent excess intestinal divisions. We previously reported that intestinal hyperplasia in lin-23(e1883) mutants was effectively suppressed by the RNAi depletion of cdc-25.2 . Nevertheless, LIN-23 targeting CDC-25.2 for ubiquitination as a component of E3 ubiquitin ligase has not yet been tested. In this study, LIN-23 is shown to be the major E3 ubiquitin ligase component, recognizing CDC-25.2 to repress their activities for proper transition of cell-cycle modes during the C. elegans postembryonic intestinal development. In addition, for the first time that LIN-23 physically interacts with both CDC-25.1 and CDC-25.2 and facilitates ubiquitination for timely regulation of their activities during the intestinal development.

Intrathecal versus IV fentanyl in pediatric cardiac anesthesia.

PubMed

Pirat, Arash; Akpek, Elif; Arslan, Gülnaz

2002-11-01

Systemic large-dose opioids are widely used in pediatric cardiac anesthesia, but there are no randomized, prospective studies regarding the use of intrathecal (IT) opioids for these procedures. In this randomized, prospective study, we compared cardiovascular and neurohumoral responses during IT or IV fentanyl anesthesia for pediatric cardiac surgery. Thirty children aged 6 mo to 6 yr were anesthetized with an IV fentanyl bolus of 10 micro g/kg. This was followed by a fentanyl infusion of 10 micro g. kg(-1). h(-1) (Group IV; n = 10), 2 micro g/kg of IT fentanyl (Group IT; n = 10), or combined IV and IT protocols (Group IV + IT; n = 10). Heart rate, mean arterial blood pressure, additional fentanyl doses, time to first analgesic requirement, COMFORT and Children's Hospital of Eastern Ontario Pain Scale scores, and extubation time were recorded. Blood cortisol, insulin, glucose, and lactate levels were measured presurgery, poststernotomy, during the rewarming phase of cardiopulmonary bypass (CPB), and 6 and 24 h after surgery. The patients' urinary cortisol excretion rates were also measured during the first postoperative day. The findings in all three groups were statistically similar, except for higher blood glucose levels during CPB in Group IT compared with Group IV (P < 0.004). Group IV + IT was the only group in which the increases in heart rate and mean arterial blood pressure from presurgery to poststernotomy were not significant. The 24-h urinary cortisol excretion rates ( micro g. kg(-1). d(-1)) were 61.51 +/- 39, 92.54 +/- 67.55, and 40.15 +/- 29.69 for Groups IV, IT, and IV + IT, respectively (P > 0.05). A single IT injection of fentanyl 2 micro g/kg offers no advantage over systemic fentanyl (10 micro g/kg bolus and 10 micro g. kg(-1). h(-1)) with regard to hemodynamic stability or suppression of stress response. The combination of these two regimens may provide better hemodynamic stability during the pre-CPB period and may be associated with a decreased 24-h urinary cortisol excretion rate. In this prospective, randomized study, we investigated the adequacy of a single intrathecal injection of fentanyl for intraoperative analgesia, compared the effects of IT and IV fentanyl on stress response, and assessed for an additive effect of IT and IV fentanyl administration in pediatric cardiac anesthesia. The results with these three different anesthetic regimens were similar regarding anesthesia depth and level of stress response. However, the combination of IT and IV routes may provide better hemodynamic stability and a less pronounced stress response, as reflected by 24-h urinary cortisol excretion.

Pneumococcal polysaccharide vaccine - what you need to know

MedlinePlus

... taken in its entirety from the CDC Pneumococcal Polysaccharide Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... statements/ppv.html CDC review information for Pneumococcal Polysaccharide VIS: Page last reviewed: April 24, 2015 Page ...

HPV (Human Papillomavirus) vaccine - what you need to know

MedlinePlus

... taken in its entirety from the CDC HPV (Human Papillomavirus) Vaccine Information Statement (VIS): www.cdc.gov/ ... statements/hpv.html . CDC review information for HPV (Human Papillomavirus) VIS: Page last reviewed: December 2, 2016 ...

Varicella (chickenpox) vaccine - what you need to know

MedlinePlus

... is taken in its entirety from the CDC Chickenpox Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... statements/varicella.html CDC review information for the Chickenpox VIS: Page last reviewed: February 12, 2018 Page ...

78 FR 75923 - Office for State, Tribal, Local and Territorial Support (OSTLTS)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-13

... among parties that leads to mutual understanding and comprehension. CDC believes that consultation is..., tribes and CDC leaders will engage in a listening session with CDC's director and roundtable discussions...

Rac1/WAVE2 and Cdc42/N-WASP Participation in Actin-Dependent Host Cell Invasion by Extracellular Amastigotes of Trypanosoma cruzi.

PubMed

Bonfim-Melo, Alexis; Ferreira, Éden R; Mortara, Renato A

2018-01-01

This study evaluated the participation of host cell Rho-family GTPases and their effector proteins in the actin-dependent invasion by Trypanosoma cruzi extracellular amastigotes (EAs). We observed that all proteins were recruited and colocalized with actin at EA invasion sites in live or fixed cells. EA internalization was inhibited in cells depleted in Rac1, N-WASP, and WAVE2. Time-lapse experiments with Rac1, N-WASP and WAVE2 depleted cells revealed that EA internalization kinetics is delayed even though no differences were observed in the proportion of EA-induced actin recruitment in these groups. Overexpression of constitutively active constructs of Rac1 and RhoA altered the morphology of actin recruitments to EA invasion sites. Additionally, EA internalization was increased in cells overexpressing CA-Rac1 but inhibited in cells overexpressing CA-RhoA. WT-Cdc42 expression increased EA internalization, but curiously, CA-Cdc42 inhibited it. Altogether, these results corroborate the hypothesis of EA internalization in non-phagocytic cells by a phagocytosis-like mechanism and present Rac1 as the key Rho-family GTPase in this process.

Rac1/WAVE2 and Cdc42/N-WASP Participation in Actin-Dependent Host Cell Invasion by Extracellular Amastigotes of Trypanosoma cruzi

PubMed Central

Bonfim-Melo, Alexis; Ferreira, Éden R.; Mortara, Renato A.

2018-01-01

This study evaluated the participation of host cell Rho-family GTPases and their effector proteins in the actin-dependent invasion by Trypanosoma cruzi extracellular amastigotes (EAs). We observed that all proteins were recruited and colocalized with actin at EA invasion sites in live or fixed cells. EA internalization was inhibited in cells depleted in Rac1, N-WASP, and WAVE2. Time-lapse experiments with Rac1, N-WASP and WAVE2 depleted cells revealed that EA internalization kinetics is delayed even though no differences were observed in the proportion of EA-induced actin recruitment in these groups. Overexpression of constitutively active constructs of Rac1 and RhoA altered the morphology of actin recruitments to EA invasion sites. Additionally, EA internalization was increased in cells overexpressing CA-Rac1 but inhibited in cells overexpressing CA-RhoA. WT-Cdc42 expression increased EA internalization, but curiously, CA-Cdc42 inhibited it. Altogether, these results corroborate the hypothesis of EA internalization in non-phagocytic cells by a phagocytosis-like mechanism and present Rac1 as the key Rho-family GTPase in this process. PMID:29541069

A human monoclonal autoantibody to a nucleolar structure.

PubMed Central

Gonzalez, M F; Wichmann, I; Yelamos, J; Melero, J; Magariño, R; Sanchez-Roman, J; Nuñez-Roldan, A; Sanchez, B

1992-01-01

Peripheral blood lymphocytes from a scleroderma patient (CDC) were isolated, transformed with Epstein-Barr virus and fused to the heteromyeloma SHM-D33. Supernatants from cultures were screened for autoantibody production against nucleoprotamine by ELISA. Positive wells were cloned by limiting dilution. After cloning, supernatants from two wells were positive for the nucleoprotamine assay. One named CDC-1 has been studied in our laboratory. CDC-1 recognized a nucleolar antigen by indirect immunofluorescence. By using an ELISA with purified recombinant antigens, CDC-1 reacted against Ro/SS-A, U1 (RNP) and Sm. By immunoblotting using a lysate of MOLT-4 cell line, CDC-1 was able to react against a structure of 60 kD. When the antigen recognized by CDC-1 was purified, SDS-PAGE under reducing conditions with purified antigen and subsequent silver staining of the gel allowed us to detect three bands at 60, 55 and 39 kD, respectively. A screening by ELISA with previously characterized antisera against our purified antigen demonstrated reactivity of the CDC-1 antigen with those antisera able to recognize Ro/SS-A. Images Fig. 1 Fig. 2 Fig. 3 PMID:1572098

A New Genetically Encoded Single-Chain Biosensor for Cdc42 Based on FRET, Useful for Live-Cell Imaging

PubMed Central

Cox, Dianne; Hodgson, Louis

2014-01-01

Cdc42 is critical in a myriad of cellular morphogenic processes, requiring precisely regulated activation dynamics to affect specific cellular events. To facilitate direct observations of Cdc42 activation in live cells, we developed and validated a new biosensor of Cdc42 activation. The biosensor is genetically encoded, of single-chain design and capable of correctly localizing to membrane compartments as well as interacting with its upstream regulators including the guanine nucleotide dissociation inhibitor. We characterized this new biosensor in motile mouse embryonic fibroblasts and observed robust activation dynamics at leading edge protrusions, similar to those previously observed for endogenous Cdc42 using the organic dye-based biosensor system. We then extended our validations and observations of Cdc42 activity to macrophages, and show that this new biosensor is able to detect differential activation patterns during phagocytosis and cytokine stimulation. Furthermore, we observe for the first time, a highly transient and localized activation of Cdc42 during podosome formation in macrophages, which was previously hypothesized but never directly visualized. PMID:24798463

Cdc42 and formin activity control non-muscle myosin dynamics during Drosophila heart morphogenesis

PubMed Central

Vogler, Georg; Liu, Jiandong; Iafe, Timothy W.; Migh, Ede; Mihály, József

2014-01-01

During heart formation, a network of transcription factors and signaling pathways guide cardiac cell fate and differentiation, but the genetic mechanisms orchestrating heart assembly and lumen formation remain unclear. Here, we show that the small GTPase Cdc42 is essential for Drosophila melanogaster heart morphogenesis and lumen formation. Cdc42 genetically interacts with the cardiogenic transcription factor tinman; with dDAAM which belongs to the family of actin organizing formins; and with zipper, which encodes nonmuscle myosin II. Zipper is required for heart lumen formation, and its spatiotemporal activity at the prospective luminal surface is controlled by Cdc42. Heart-specific expression of activated Cdc42, or the regulatory formins dDAAM and Diaphanous caused mislocalization of Zipper and induced ectopic heart lumina, as characterized by luminal markers such as the extracellular matrix protein Slit. Placement of Slit at the lumen surface depends on Cdc42 and formin function. Thus, Cdc42 and formins play pivotal roles in heart lumen formation through the spatiotemporal regulation of the actomyosin network. PMID:25267295

A new genetically encoded single-chain biosensor for Cdc42 based on FRET, useful for live-cell imaging.

PubMed

Hanna, Samer; Miskolci, Veronika; Cox, Dianne; Hodgson, Louis

2014-01-01

Cdc42 is critical in a myriad of cellular morphogenic processes, requiring precisely regulated activation dynamics to affect specific cellular events. To facilitate direct observations of Cdc42 activation in live cells, we developed and validated a new biosensor of Cdc42 activation. The biosensor is genetically encoded, of single-chain design and capable of correctly localizing to membrane compartments as well as interacting with its upstream regulators including the guanine nucleotide dissociation inhibitor. We characterized this new biosensor in motile mouse embryonic fibroblasts and observed robust activation dynamics at leading edge protrusions, similar to those previously observed for endogenous Cdc42 using the organic dye-based biosensor system. We then extended our validations and observations of Cdc42 activity to macrophages, and show that this new biosensor is able to detect differential activation patterns during phagocytosis and cytokine stimulation. Furthermore, we observe for the first time, a highly transient and localized activation of Cdc42 during podosome formation in macrophages, which was previously hypothesized but never directly visualized.

Apo AI/ABCA1-dependent and HDL3-mediated lipid efflux from compositionally distinct cholesterol-based microdomains.

PubMed

Drobnik, Wolfgang; Borsukova, Hana; Böttcher, Alfred; Pfeiffer, Alexandra; Liebisch, Gerhard; Schütz, Gerhard J; Schindler, Hansgeorg; Schmitz, Gerd

2002-04-01

We have investigated whether a raft heterogeneity exists in human monocyte-derived macrophages and fibroblasts and whether these microdomains are modulated by lipid efflux. Triton X-100 (Triton) or Lubrol WX (Lubrol) detergent-resistant membranes from cholesterol-loaded monocytes were associated with the following findings: (i) Lubrol-DRM contained most of the cellular cholesterol and at least 75% of Triton-detergent-resistant membranes. (ii) 'Lubrol rafts', defined by their solubility in Triton but insolubility in Lubrol, were enriched in unsaturated phosphatidylcholine and showed a lower cholesterol to choline-phospholipid ratio compared to Triton rafts. (iii) CD14 and CD55 were recovered in Triton- and Lubrol-detergent-resistant membranes, whereas CD11b was found exclusively in Triton DRM. ABCA1 implicated in apo AI-mediated lipid efflux and CDC42 were partially localized in Lubrol- but not in Triton-detergent-resistant membranes. (iv) Apo AI preferentially depleted cholesterol and choline-phospholipids from Lubrol rafts, whereas HDL3 additionally decreased the cholesterol content of Triton rafts. In fibroblasts, neither ABCA1 nor CDC42 was found in Lubrol rafts, and both apo AI and HDL3 reduced the lipid content in Lubrol- as well as in Triton-detergent-resistant membranes. In summary, we provide evidence for the existence of compositionally distinct membrane microdomains in human cells and their modulation by apo AI/ABCA1-dependent and HDL3-mediated lipid efflux.

Biosafety Recommendations for Work with Influenza Viruses Containing a Hemagglutinin from the A/goose/Guangdong/1/96 Lineage.

PubMed

Gangadharan, Denise; Smith, Jacinta; Weyant, Robbin

2013-06-28

The CDC and National Institutes of Health (NIH) Biosafety in Microbiological and Biomedical Laboratories (BMBL) manual describes biosafety recommendations for work involving highly pathogenic avian influenza (HPAI) (US Department of Health and Human Services [HHS], CDC. Biosafety in microbiological and biomedical laboratories, 5th ed. Atlanta, GA: CDC; 2009. HHS publication no. [CDC] 21-1112. Available at http://www.cdc.gov/biosafety/publications/bmbl5). The U.S. Department of Agriculture Guidelines for Avian Influenza Viruses builds on the BMBL manual and provides additional biosafety and biocontainment guidelines for laboratories working with HPAI (US Department of Agriculture, Animal and Plant Health Inspection Service, Agricultural Select Agent Program. Guidelines for avian influenza viruses. Washington, DC: US Department of Agriculture; 2011. Available at http://www.selectagents.gov/Guidelines_for_Avian_Influenza_Viruses.html). The recommendations in this report, which are intended for laboratories in the United States, outline the essential baseline biosafety measures for working with the subset of influenza viruses that contain a hemagglutinin (HA) from the HPAI influenza A/goose/Guangdong/1/96 lineage, including reassortant influenza viruses created in a laboratory setting. All H5N1 influenza virus clades known to infect humans to date have been derived from this lineage (WHO/OIE/FAO H5N1 Evolution Working Group. Continued evolution of highly pathogenic avian influenza A [H5N1]: updated nomenclature. Influenza Other Respir Viruses 2012;6:1-5). In 2009, the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules were amended to include specific biosafety and biocontainment recommendations for laboratories working with Recombinant Risk Group 3 influenza viruses, including HPAI H5N1 influenza viruses within the Goose/Guangdong/1/96-like H5 lineage. In February 2013, the NIH guidelines were further revised to provide additional biosafety containment enhancements and practices for research with HPAI H5N1 viruses that are transmissible among mammals by respiratory droplets (i.e., mammalian-transmissible HPAI H5N1) (National Institutes of Health, Office of Biotechnology Activities. NIH guidelines for research involving recombinant or synthetic nucleic acid molecules. Appendix G-II-C-5: biosafety level 3 enhanced for research involving risk group 3 influenza viruses. Bethesda, MD: National Institutes of Health; 2013. Available at http://oba.od.nih.gov/rdna/nih_guidelines_oba.html). The recent revisions to the NIH guidelines focus on a smaller subset of viruses but are applicable and consistent with the recommendations in this report. The biosafety recommendations in this report were developed by CDC with advice from the Intragovernmental Select Agents and Toxins Technical Advisory Committee, which is a panel composed of federal government subject-matter experts, and from public input received in response to the request for information that was published in the Federal Register on October 17, 2012 (US Department of Health and Human Services, CDC. Influenza viruses containing the hemagglutinin from the Goose/ Guangdong/1/96 lineage; proposed rule; request for information and comment. 42 CFR, Part 73. Federal Register 2012;77:63783-5). Work with HPAI H5N1 virus should be conducted, at a minimum, at biosafety level 3 (BSL-3), with specific enhancements to protect workers, the public, animal health, and animal products. Original clinical specimens suspected of containing viruses of this lineage can only be handled at BSL-2 if the procedures do not involve the propagation of the virus. An appropriate biosafety level should be determined in accordance with a biosafety risk assessment. Additional information on performing biosafety risk assessments and establishing effective biosafety containment is available in the BMBL manual.

Rodent Control: Seal Up! Trap Up! Clean Up!

MedlinePlus

... Skip directly to site content Start of Search Controls Search Form Controls Cancel Submit Search The CDC CDC A-Z ... V W X Y Z # Start of Search Controls Search Form Controls Cancel Submit Search The CDC ...

Infection Control: The Use and Handling of Toothbrushes

MedlinePlus

... Skip directly to site content Start of Search Controls Search Form Controls Cancel Submit Search the CDC CDC A-Z ... V W X Y Z # Start of Search Controls Search Form Controls Search The CDC Cancel Submit ...

Pneumococcal conjugate vaccine (PCV13) - What you need to know

MedlinePlus

... the CDC Information Statement (VIS): www.cdc.gov/vaccines/hcp/vis/vis-statements/pcv13.html CDC review ... at the highest risk. Before there was a vaccine, the United States saw: more than 700 cases ...

Hepatitis B vaccine - what you need to know

MedlinePlus

... is taken in its entirety from the CDC Hepatitis B Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... statements/hep-b.html CDC review information for Hepatitis B VIS: Page last reviewed: July 20, 2016 Page ...

Cdc7-Dbf4 Regulates NDT80 Transcription as Well as Reductional Segregation during Budding Yeast Meiosis

PubMed Central

Lo, Hsiao-Chi; Wan, Lihong; Rosebrock, Adam; Futcher, Bruce

2008-01-01

In budding yeast, as in other eukaryotes, the Cdc7 protein kinase is important for initiation of DNA synthesis in vegetative cells. In addition, Cdc7 has crucial meiotic functions: it facilitates premeiotic DNA replication, and it is essential for the initiation of recombination. This work uses a chemical genetic approach to demonstrate that Cdc7 kinase has additional roles in meiosis. First, Cdc7 allows expression of NDT80, a meiosis-specific transcriptional activator required for the induction of genes involved in exit from pachytene, meiotic progression, and spore formation. Second, Cdc7 is necessary for recruitment of monopolin to sister kinetochores, and it is necessary for the reductional segregation occurring at meiosis I. The use of the same kinase to regulate several distinct meiosis-specific processes may be important for the coordination of these processes during meiosis. PMID:18768747

Wee1 and Cdc25 are controlled by conserved PP2A-dependent mechanisms in fission yeast.

PubMed

Lucena, Rafael; Alcaide-Gavilán, Maria; Anastasia, Steph D; Kellogg, Douglas R

2017-03-04

Wee1 and Cdc25 are conserved regulators of mitosis. Wee1 is a kinase that delays mitosis via inhibitory phosphorylation of Cdk1, while Cdc25 is a phosphatase that promotes mitosis by removing the inhibitory phosphorylation. Although Wee1 and Cdc25 are conserved proteins, it has remained unclear whether their functions and regulation are conserved across diverse species. Here, we analyzed regulation of Wee1 and Cdc25 in fission yeast. Both proteins undergo dramatic cell cycle-dependent changes in phosphorylation that are dependent upon PP2A associated with the regulatory subunit Pab1. The mechanisms that control Wee1 and Cdc25 in fission yeast appear to share similarities to those in budding yeast and vertebrates, which suggests that there may be common mechanisms that control mitotic entry in all eukaryotic cells.

Wee1 and Cdc25 are controlled by conserved PP2A-dependent mechanisms in fission yeast

PubMed Central

2017-01-01

ABSTRACT Wee1 and Cdc25 are conserved regulators of mitosis. Wee1 is a kinase that delays mitosis via inhibitory phosphorylation of Cdk1, while Cdc25 is a phosphatase that promotes mitosis by removing the inhibitory phosphorylation. Although Wee1 and Cdc25 are conserved proteins, it has remained unclear whether their functions and regulation are conserved across diverse species. Here, we analyzed regulation of Wee1 and Cdc25 in fission yeast. Both proteins undergo dramatic cell cycle-dependent changes in phosphorylation that are dependent upon PP2A associated with the regulatory subunit Pab1. The mechanisms that control Wee1 and Cdc25 in fission yeast appear to share similarities to those in budding yeast and vertebrates, which suggests that there may be common mechanisms that control mitotic entry in all eukaryotic cells. PMID:28103117

Depletion of cdc-25.3, a Caenorhabditis elegans orthologue of cdc25, increases physiological germline apoptosis.

PubMed

Sung, Minhee; Kawasaki, Ichiro; Shim, Yhong-Hee

2017-07-01

In Caenorhabditis elegans hermaphrodites, physiological germline apoptosis is higher in cdc-25.3 mutants than in wild-type. The elevated germline apoptosis in cdc-25.3 mutants seems to be induced by accumulation of double-stranded DNA breaks (DSBs). Both DNA damage and synapsis checkpoint genes are required to increase the germline apoptosis. Notably, the number of germ cells that lose P-granule components, PGL-1 and PGL-3, increase in cdc-25.3 mutants, and the increase in germline apoptosis requires the activity of SIR-2.1, a Sirtuin orthologue. These results suggest that elevation of germline apoptosis in cdc-25.3 mutants is induced by accumulation of DSBs, leading to a loss of PGL-1 and PGL-3 in germ cells, which promotes cytoplasmic translocation of SIR-2.1, and finally activates the core apoptotic machinery. © 2017 Federation of European Biochemical Societies.

75 FR 38531 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-02

.... Customers are defined as any individual or group seeking health or public health information from CDC. This... increasingly guided by a comprehensive evaluation that includes point-of-service and follow-up customer satisfaction surveys. These surveys provide the public with ongoing opportunity to express their level of...

76 FR 59132 - Agency Information Collection Request. 60-Day Public Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-23

... counterfactual, or the ``business as usual'' services received by youth in the control group. This information... Evaluation (ASPE), the Centers for Disease Control and Prevention (CDC), and the Administration for Children... Evaluation). The TPP Replication Evaluation will be an experimental evaluation which will determine the...

Intravenous Acetaminophen for Postoperative Pain Management in Patients Undergoing Living Laparoscopic Living-Donor Nephrectomy.

PubMed

Vu, Van; Baker, William L; Tencza, Elizabeth M; Rochon, Caroline; Sheiner, Patricia A; Martin, Spencer T

2017-01-01

Postoperative pain is a common complication of laparoscopic living-donor nephrectomies (LLDNs). To determine whether intravenous (IV) acetaminophen administration post-LLDN influenced length of stay (LOS) when used for pain management. This single-center, retrospective study compared patients undergoing LLDN who had received IV acetaminophen for pain control versus those who did not between June 1, 2011, and November 30, 2015. Patient LOS, 30-day readmissions, frequency of pain assessments, patient-reported pain scores, and opioid administration were assessed. A total of 90 patients were included in the analysis (IV acetaminophen, n = 48; non-IV acetaminophen, n = 42). Patients who did not receive IV acetaminophen were more often older (48.8 ± 12.1 vs 39.3 ± 12.1 years; P = 0.012) and female (71.4% vs 47.9%; P < 0.001). The average LOS was similar between the 2 groups (median = 3.0; interquartile range = [3, 4] vs 3.5 [3, 4]; P = 0.737). The 30-day readmissions were higher in the IV acetaminophen group (16.7%) compared with the group not receiving IV acetaminophen (2.4%; P = 0.033). After the first postoperative day, the frequencies of pain assessments performed were similar among the 2 groups. There was no difference in average pain scores between the groups at any time after LLDN. Patients receiving IV acetaminophen were found to have no improvements in hospital LOS, average pain score, or opioid requirements compared with patients not receiving IV acetaminophen. Patients who received IV acetaminophen were also found to have a higher 30-day readmission rate.

Comparison of Effectiveness of Betamethasone gel Applied to the Tracheal Tube and IV Dexamethasone on Postoperative Sore Throat: A Randomized Controlled Trial

PubMed Central

Tabari, Masoomeh; Soltani, Ghasem; Zirak, Nahid; Alipour, Mohammad; Khazaeni, Kamran

2013-01-01

Introduction: Postoperative sore throat is a common complaint in patients with endotracheal intubation and has potentially dangerous complications. This randomized controlled trial study investigated the incidence of postoperative sore throat after general anesthesia when betamethasone gel is applied to a tracheal tube compared with when IV dexamethasone is prescribed. Materials and Methods: Two hundred and twenty five American Society of Anesthesiologist (ASA)-class I and II patients undergoing elective abdominal surgery with tracheal intubation were randomly divided into three groups: betamethasone gel, intravenous (IV) dexamethasone, and control groups. In the post-anesthesia care unit, a blinded anesthesiologist interviewed all patients regarding postoperative sore throat at 1,6, and 24 hours after surgery. Results: The incidence of sore throat was significantly lower in the betamethasone gel group compared with the IV dexamethasone and control groups, 1, 6, and 24 hours after surgery. In the first day after surgery 10.7% of the betamethasone group had sore throat whereas 26.7% of the IV dexamethasone group and 30.7% of the control group had sore throat. Bucking before extubation was observed in 14(18.4%), 8(10.4%), and 9(12.2%) patients, in the IV dexamethasone, betamethasone gel, and control group, respectively. Conclusion: We concluded that wide spread application of betamethasone gel over tracheal tubes effectively mitigates postoperative sore throat, compared with IV dexamethasone application. PMID:24303443

2010 Perinatal GBS Prevention Guideline and Resource Utilization

PubMed Central

Mukhopadhyay, Sagori; Dukhovny, Dmitry; Mao, Wenyang; Eichenwald, Eric C.

2014-01-01

OBJECTIVES: To quantify differences in early-onset sepsis (EOS) evaluations, evaluation-associated resource utilization, and EOS cases detected, when comparing time periods before and after the implementation of an EOS algorithm based on the Centers for Disease Control and Prevention (CDC) 2010 guidelines for prevention of perinatal Group B Streptococcus (GBS) disease. METHODS: Retrospective cohort study of infants born at ≥36 weeks’ gestation from 2009 to 2012 in a single tertiary care center. One 12-month period during which EOS evaluations were based on the CDC 2002 guideline was compared with a second 12-month period during which EOS evaluations were based on the CDC 2010 guideline. A cost minimization analysis was performed to determine the EOS evaluation-associated costs and resources during each time period. RESULTS: During the study periods, among well-appearing infants ≥36 weeks’ gestation, EOS evaluations for inadequate GBS prophylaxis decreased from 32/1000 to <1/1000 live births; EOS evaluation-associated costs decreased by $6994 per 1000 live births; and EOS evaluation-associated work hours decreased by 29 per 1000 live births. We found no increase in EOS evaluations for other indications, total NICU admissions, frequency of infants evaluated for symptoms before hospital discharge, or incidence of EOS during the 2 study periods. CONCLUSIONS: Implementation of an EOS algorithm based on CDC 2010 GBS guidelines resulted in a 25% decrease in EOS evaluations performed among well-appearing infants ≥36 weeks’ gestation, attributable to decreased evaluation of infants born in the setting of inadequate indicated GBS prophylaxis. This resulted in significant changes in EOS evaluation-associated resource expenditures. PMID:24446442

Evidence-based HIV/STD prevention intervention for black men who have sex with men.

PubMed

Herbst, Jeffrey H; Painter, Thomas M; Tomlinson, Hank L; Alvarez, Maria E

2014-04-18

This report summarizes published findings of a community-based organization in New York City that evaluated and demonstrated the efficacy of the Many Men, Many Voices (3MV) human immunodeficiency virus (HIV)/sexually transmitted disease (STD) prevention intervention in reducing sexual risk behaviors and increasing protective behaviors among black men who have sex with men (MSM). The intervention addressed social determinants of health (e.g., stigma, discrimination, and homophobia) that can influence the health and well-being of black MSM at high risk for HIV infection. This report also highlights efforts by CDC to disseminate this evidence-based behavioral intervention throughout the United States. CDC's Office of Minority Health and Health Equity selected the intervention analysis and discussion to provide an example of a program that might be effective for reducing HIV infection- and STD-related disparities in the United States. 3MV uses small group education and interaction to increase knowledge and change attitudes and behaviors related to HIV/STD risk among black MSM. Since its dissemination by CDC in 2004, 3MV has been used in many settings, including health department- and community-based organization programs. The 3MV intervention is an important component of a comprehensive HIV and STD prevention portfolio for at-risk black MSM. As CDC continues to support HIV prevention programming consistent with the National HIV/AIDS Strategy and its high-impact HIV prevention approach, 3MV will remain an important tool for addressing the needs of black MSM at high risk for HIV infection and other STDs.

Evaluation of field triage decision scheme educational resources: audience research with emergency medical service personnel.

PubMed

Sarmiento, Kelly; Eckstein, Daniel; Zambon, Allison

2013-03-01

In an effort to encourage appropriate field triage procedures, the Centers for Disease Control and Prevention (CDC), in collaboration with the National Highway Traffic Safety Administration and the American College of Surgeons-Committee on Trauma, convened the National Expert Panel on Field Triage to update the Field Triage Decision Scheme: The National Trauma Triage Protocol (Decision Scheme). In support of the Decision Scheme, CDC developed educational resources for emergency medical service (EMS) professionals, one of CDC's first efforts to develop and broadly disseminate educational information for the EMS community. CDC wanted to systematically collect information from the EMS community on what worked and what did not with respect to these educational materials and which materials were of most use. An evaluation was conducted to obtain feedback from EMS professionals about the Decision Scheme and use of Decision Scheme educational materials. The evaluation included a survey and a series of focus groups. Findings indicate that a segment of the Decision Scheme's intended audience is using the materials and learning from them, and they have had a positive influence on their triage practices. However, many of the individuals who participated in this research are not using the Decision Scheme and indicated that the materials have not affected their triage practices. Findings presented in this article can be used to inform development and distribution of additional Decision Scheme educational resources to ensure they reach a greater proportion of EMS professionals and to inform other education and dissemination efforts with the EMS community.

Defining overweight and obesity among Greek children living in Thessaloniki: International versus local reference standards.

PubMed

Christoforidis, A; Dimitriadou, M; Papadopolou, E; Stilpnopoulou, D; Katzos, G; Athanassiou-Metaxa, M

2011-04-01

Body Mass Index (BMI) offers a simple and reasonable measure of obesity that, with the use of the appropriate reference, can help in the early detection of children with weight problems. Our aim was to compare the two most commonly used international BMI references and the national Greek BMI reference in identifying Greek children being overweight and obese. A group of 1557 children (820 girls and 737 boys, mean age: 11.42 ± 3.51 years) were studied. Weight and height was measured using standard methods, and BMI was calculated. Overweight and obesity were determined using the International Obesity Task Force (IOTF) standards, the Centers for Disease Control and Prevention (CDC) BMI-forage curves and the most recent Greek BMI-for-age curves. RESULTS showed that the IOTF's cut-off limits identifies a significantly higher prevalence of overweight (22.4%) compared with both the CDC's (11.8%, p=0.03) and the Greek's (7.4%, p=0.002) cut-off limits. However, the prevalence of obesity was generally increased when it was determined using the CDC's cut-off limits (13.9%) compared to the prevalence calculated with both the IOTF's (6.5%, p=0.05) and the Greek's (6.9%, n.s.) cut off limits. The use of the national Greek reference standards for BMI underestimates the true prevalence of overweight and obesity. On the contrary, both the IOTF and the CDC standards, although independently, detect an increased number of overweight and obese children and thus they should be adopted in the clinical practice for an earlier identification and a timelier intervention.

Transforming Growth Factor-Beta Inhibition Reduces Progression of Early Choroidal Neovascularization Lesions in Rats: P17 and P144 Peptides

PubMed Central

Zarranz-Ventura, Javier; Fernández-Robredo, Patricia; Recalde, Sergio; Salinas-Alamán, Angel; Borrás-Cuesta, Francisco; Dotor, Javier; García-Layana, Alfredo

2013-01-01

The purpose of this study was to assess the effects of transforming growth factor beta (TGF-β) inhibitor peptides (P17 & P144) on early laser-induced choroidal neovascularization (LI-CNV) lesions in rats, two weeks after laser CNV induction. Seventy-one Long Evans rats underwent diode laser application in an established LI-CNV model. Baseline fluorescein angiography (FA) was performed 14 days following laser procedure, and treatments were administered 16 days post-laser application via different administration routes. Intravenous groups included control (IV-Control), P17 (IV-17), and P144 (IV-144) groups, whereas intravitreal groups included P17 (IVT-17), P144 (IVT-144), and a mixture of both peptides (IVT-17+144) (with fellow eyes receiving vehicle alone). CNV evolution was assessed using FA performed weekly for four weeks after treatment. Following sacrifice, VEGF, TGF-β, COX-2, IGF-1, PAI-1, IL-6, MMP-2, MMP-9, and TNF-α gene expression was assessed using RT-PCR. VEGF and p-SMAD2 protein levels were also assessed by western-blot, while MMP-2 activity was assessed with gelatin zymography. Regarding the FA analysis, the mean CNV area was lower from the 3rd week in IVT-17 and IVT-144 groups, and also from the 2nd week in IVT-17+144. Biochemical analysis revealed that gene expression was lower for VEGF and COX-2 genes in IV-17 and IV-144 groups, VEGF gene in IVT-17+144 group and MMP-2 gene in IVT-17 and IVT-144 groups. VEGF protein expression was also decreased in IV-17, IV-144, IVT-17 and IVT-144, whereas pSMAD-2 levels were lower in IV-17, IV-144 and IVT-17+144 groups. Zymogram analysis revealed decreased MMP-2 activity in IV-17, IV-144, IVT-17 and IVT-144 groups. These data suggest that the use of TGF-β inhibitor peptides (P17 & P144) decrease the development of early CNV lesions by targeting different mediators than those typically affected using current anti-angiogenic therapies. Its potential role in the treatment of early CNV appears promising as a single therapy or adjuvant to anti-VEGF drugs. PMID:23741494

Evaluation of Commercially Available Chikungunya Virus Immunoglobulin M Detection Assays

PubMed Central

Johnson, Barbara W.; Goodman, Christin H.; Holloway, Kimberly; de Salazar, P. Martinez; Valadere, Anne M.; Drebot, Michael A.

2016-01-01

Commercial chikungunya virus (CHIKV)–specific IgM detection kits were evaluated at the Centers for Disease Control and Prevention (CDC), the Public Health Agency of Canada National Microbiology Laboratory, and the Caribbean Public Health Agency (CARPHA). The Euroimmun Anti-CHIKV IgM ELISA kit had ≥ 95% concordance with all three reference laboratory results. The limit of detection for low CHIK IgM+ samples, as measured by serial dilution of seven sera up to 1:12,800 ranged from 1:800 to 1:3,200. The Euroimmun IIFT kit evaluated at CDC and CARPHA performed well, but required more retesting of equivocal results. The InBios CHIKjj Detect MAC-ELISA had 100% and 98% concordance with CDC and CARPHA results, respectively, and had equal sensitivity to the CDC MAC-ELISA to 1:12,800 dilution in serially diluted samples. The Abcam Anti-CHIKV IgM ELISA had high performance at CARPHA, but at CDC, performance was inconsistent between lots. After replacement of the biotinylated IgM antibody controls with serum containing CHIKV-specific IgM and additional quality assurance/control measures, the Abcam kit was rereleased and reevaluated at CDC. The reformatted Abcam kit had 97% concordance with CDC results and limit of detection of 1:800 to 1:3,200. Two rapid tests and three other CHIKV MAC-ELISAs evaluated at CDC had low sensitivity, as the CDC CHIKV IgM in-house positive controls were below the level of detection. In conclusion, laboratories have options for CHIKV serological diagnosis using validated commercial kits. PMID:26976887

[Differences in magnitude of nutritional status in Chilean school children according to CDC and WHO 2005-2008 reference].

PubMed

Vásquez, Fabián; Cerda Rioseco, Ricardo; Andrade, Margarita; Morales, Gladys; Gálvez, Patricia; Orellana, Yasna; Leyton, Bárbara

2013-01-01

Further discussions are needed regarding the magnitude of nutritional problems diagnosed using CDC or WHO, against the existence of new biological or statistical definitions of obesity. To compare the evolution of the prevalence of nutritional status among schoolchildren in first grade, from 2005 to 2008, according to CDC and WHO. Retrospective cohort study, of 140.265 students of both sexes of first grade, evaluated from 2005- 2008, whose anthropometric data (weight and height), were obtained from annual registration system of school nutrition. To classify the nutritional status of children, CDC and WHO patterns were used. The mean BMI was slightly different and lower in girls than in boys, in 2005 and 2006. During 2007 and 2008 the average BMI in girls reached the observed in males. There was a higher prevalence of underweight according to WHO (p=0,03), with a tendency to decrease in the subsequent years. The prevalence of normality was greater according to the CDC criteria, with a reduction between 2005 and 2007 and an increase in 2008 (P < 0,001). There was a lower prevalence of overweight according to CDC criteria (P < 0,001), with an increase between 2005 and 2007, both CDC and WHO. The prevalence of obesity was lower according to the WHO criteria, and there were not statistically significant differences when comparing the CDC pattern. By comparing both patterns, CDC tends to overestimate the normal and underestimate the overweight, while obesity was not significant differences. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

Antigen Presenting Properties of a Myeloid Dendritic-Like Cell in Murine Spleen.

PubMed

Hey, Ying-Ying; O'Neill, Helen C

This paper distinguishes a rare subset of myeloid dendritic-like cells found in mouse spleen from conventional (c) dendritic cells (DC) in terms of phenotype, function and gene expression. These cells are tentatively named "L-DC" since they resemble dendritic-like cells produced in longterm cultures of spleen. L-DC can be distinguished on the basis of their unique phenotype as CD11bhiCD11cloMHCII-CD43+Ly6C-Ly6G-Siglec-F- cells. They demonstrate similar ability as cDC to uptake and retain complex antigens like mannan via mannose receptors, but much lower ability to endocytose and retain soluble antigen. While L-DC differ from cDC by their inability to activate CD4+ T cells, they are capable of antigen cross-presentation for activation of CD8+ T cells, although less effectively so than the cDC subsets. In terms of gene expression, CD8- cDC and CD8+ cDC are quite distinct from L-DC. CD8+ cDC are distinguishable from the other two subsets by expression of CD24a, Clec9a, Xcr1 and Tlr11, while CD8- cDC are distinguished by expression of Ccnd1 and H-2Eb2. L-DC are distinct from the two cDC subsets through upregulated expression of Clec4a3, Emr4, Itgam, Csf1r and CD300ld. The L-DC gene profile is quite distinct from that of cDC, confirming a myeloid cell type with distinct antigen presenting properties.

Nek2A destruction marks APC/C activation at the prophase-to-prometaphase transition by spindle-checkpoint-restricted Cdc20.

PubMed

Boekhout, Michiel; Wolthuis, Rob

2015-04-15

Nek2 isoform A (Nek2A) is a presumed substrate of the anaphase-promoting complex/cyclosome containing Cdc20 (APC/C(Cdc20)). Nek2A, like cyclin A, is degraded in mitosis while the spindle checkpoint is active. Cyclin A prevents spindle checkpoint proteins from binding to Cdc20 and is recruited to the APC/C in prometaphase. We found that Nek2A and cyclin A avoid being stabilized by the spindle checkpoint in different ways. First, enhancing mitotic checkpoint complex (MCC) formation by nocodazole treatment inhibited the degradation of geminin and cyclin A, whereas Nek2A disappeared at a normal rate. Second, depleting Cdc20 effectively stabilized cyclin A but not Nek2A. Nevertheless, Nek2A destruction crucially depended on Cdc20 binding to the APC/C. Third, in contrast to cyclin A, Nek2A was recruited to the APC/C before the start of mitosis. Interestingly, the spindle checkpoint very effectively stabilized an APC/C-binding mutant of Nek2A, which required the Nek2A KEN box. Apparently, in cells, the spindle checkpoint primarily prevents Cdc20 from binding destruction motifs. Nek2A disappearance marks the prophase-to-prometaphase transition, when Cdc20, regardless of the spindle checkpoint, activates the APC/C. However, Mad2 depletion accelerated Nek2A destruction, showing that spindle checkpoint release further increases APC/C(Cdc20) catalytic activity. © 2015. Published by The Company of Biologists Ltd.

NUP98 fusion oncoproteins interact with the APC/C(Cdc20) as a pseudosubstrate and prevent mitotic checkpoint complex binding.

PubMed

Salsi, Valentina; Fantini, Sebastian; Zappavigna, Vincenzo

2016-09-01

NUP98 is a recurrent partner gene in translocations causing acute myeloid leukemias and myelodisplastic syndrome. The expression of NUP98 fusion oncoproteins has been shown to induce mitotic spindle defects and chromosome missegregation, which correlate with the capability of NUP98 fusions to cause mitotic checkpoint attenuation. We show that NUP98 oncoproteins physically interact with the APC/C(Cdc20) in the absence of the NUP98 partner protein RAE1, and prevent the binding of the mitotic checkpoint complex to the APC/C(Cdc20). NUP98 oncoproteins require the GLEBS-like domain present in their NUP98 moiety to bind the APC/C(Cdc20). We found that NUP98 wild-type is a substrate of APC/C(Cdc20) prior to mitotic entry, and that its binding to APC/C(Cdc20) is controlled via phosphorylation of a PEST sequence located within its C-terminal portion. We identify S606, within the PEST sequence, as a key target site, whose phosphorylation modulates the capability of NUP98 to interact with APC/C(Cdc20). We finally provide evidence for an involvement of the peptidyl-prolyl isomerase PIN1 in modulating the possible conformational changes within NUP98 that lead to its dissociation from the APC/C(Cdc20) during mitosis. Our results provide novel insight into the mechanisms underlying the aberrant capability of NUP98 oncoproteins to interact with APC/C(Cdc20) and to interfere with its function.

Cdc1 removes the ethanolamine phosphate of the first mannose of GPI anchors and thereby facilitates the integration of GPI proteins into the yeast cell wall

PubMed Central

Vazquez, Hector M.; Vionnet, Christine; Roubaty, Carole; Conzelmann, Andreas

2014-01-01

Temperature-sensitive cdc1ts mutants are reported to stop the cell cycle upon a shift to 30°C in early G2, that is, as small budded cells having completed DNA replication but unable to duplicate the spindle pole body. A recent report showed that PGAP5, a human homologue of CDC1, acts as a phosphodiesterase removing an ethanolamine phosphate (EtN-P) from mannose 2 of the glycosylphosphatidylinositol (GPI) anchor, thus permitting efficient endoplasmic reticulum (ER)-to-Golgi transport of GPI proteins. We find that the essential CDC1 gene can be deleted in mcd4∆ cells, which do not attach EtN-P to mannose 1 of the GPI anchor, suggesting that Cdc1 removes the EtN-P added by Mcd4. Cdc1-314ts mutants do not accumulate GPI proteins in the ER but have a partial secretion block later in the secretory pathway. Growth tests and the genetic interaction profile of cdc1-314ts pinpoint a distinct cell wall defect. Osmotic support restores GPI protein secretion and actin polarization but not growth. Cell walls of cdc1-314ts mutants contain large amounts of GPI proteins that are easily released by β-glucanases and not attached to cell wall β1,6-glucans and that retain their original GPI anchor lipid. This suggests that the presumed transglycosidases Dfg5 and Dcw1 of cdc1-314ts transfer GPI proteins to cell wall β1,6-glucans inefficiently. PMID:25165136

Maternal intravenous treatment with either azithromycin or solithromycin clears Ureaplasma parvum from the amniotic fluid in an ovine model of intrauterine infection.

PubMed

Miura, Yuichiro; Payne, Matthew S; Keelan, Jeffrey A; Noe, Andres; Carter, Sean; Watts, Rory; Spiller, Owen B; Jobe, Alan H; Kallapur, Suhas G; Saito, Masatoshi; Stock, Sarah J; Newnham, John P; Kemp, Matthew W

2014-09-01

Intrauterine infection with Ureaplasma spp. is strongly associated with preterm birth and adverse neonatal outcomes. We assessed whether combined intraamniotic (IA) and maternal intravenous (IV) treatment with one of two candidate antibiotics, azithromycin (AZ) or solithromycin (SOLI), would eradicate intrauterine Ureaplasma parvum infection in a sheep model of pregnancy. Sheep with singleton pregnancies received an IA injection of U. parvum serovar 3 at 85 days of gestational age (GA). At 120 days of GA, animals (n=5 to 8/group) received one of the following treatments: (i) maternal IV SOLI with a single IA injection of vehicle (IV SOLI only); (ii) maternal IV SOLI with a single IA injection of SOLI (IV+IA SOLI); (iii) maternal IV AZ and a single IA injection of vehicle (IV AZ only); (iv) maternal IV AZ and a single IA injection of AZ (IV+IA AZ); or (v) maternal IV and single IA injection of vehicle (control). Lambs were surgically delivered at 125 days of GA. Treatment efficacies were assessed by U. parvum culture, quantitative PCR, enzyme-linked immunosorbent assay, and histopathology. Amniotic fluid (AF) from all control animals contained culturable U. parvum. AF, lung, and chorioamnion from all AZ- or SOLI-treated animals (IV only or IV plus IA) were negative for culturable U. parvum. Relative to the results for the control, the levels of expression of interleukin 1β (IL-1β), IL-6, IL-8, and monocyte chemoattractant protein 2 (MCP-2) in fetal skin were significantly decreased in the IV SOLI-only group, the MCP-1 protein concentration in the amniotic fluid was significantly increased in the IV+IA SOLI group, and there was no significant difference in the histological inflammation scoring of lung or chorioamnion among the five groups. In the present study, treatment with either AZ or SOLI (IV only or IV+IA) effectively eradicated macrolide-sensitive U. parvum from the AF. There was no discernible difference in antibiotic therapy efficacy between IV-only and IV+IA treatment regimens relative to the results for the control. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Contents, Followers, and Retweets of the Centers for Disease Control and Prevention's Office of Advanced Molecular Detection (@CDC_AMD) Twitter Profile: Cross-Sectional Study.

PubMed

Fung, Isaac Chun-Hai; Jackson, Ashley M; Mullican, Lindsay A; Blankenship, Elizabeth B; Goff, Mary Elizabeth; Guinn, Amy J; Saroha, Nitin; Tse, Zion Tsz Ho

2018-04-02

The Office of Advanced Molecular Detection (OAMD), Centers for Disease Control and Prevention (CDC), manages a Twitter profile (@CDC_AMD). To our knowledge, no prior study has analyzed a CDC Twitter handle's entire contents and all followers. This study aimed to describe the contents and followers of the Twitter profile @CDC_AMD and to assess if attaching photos or videos to tweets posted by @CDC_AMD would increase retweet frequency. Data of @CDC_AMD were retrieved on November 21, 2016. All followers (N=809) were manually categorized. All tweets (N=768) were manually coded for contents and whether photos or videos were attached. Retweet count for each tweet was recorded. Negative binomial regression models were applied to both the original and the retweet corpora. Among the 809 followers, 26.0% (210/809) were individual health professionals, 11.6% (94/809) nongovernmental organizations, 3.3% (27/809) government agencies' accounts, 3.3% (27/809) accounts of media organizations and journalists, and 0.9% (7/809) academic journals, with 54.9% (444/809) categorized as miscellaneous. A total of 46.9% (360/768) of @CDC_AMD's tweets referred to the Office's website and their current research; 17.6% (135/768) referred to their scientists' publications. Moreover, 80% (69/86) of tweets retweeted by @CDC_AMD fell into the miscellaneous category. In addition, 43.4% (333/768) of the tweets contained photos or videos, whereas the remaining 56.6% (435/768) did not. Attaching photos or videos to original @CDC_AMD tweets increases the number of retweets by 37% (probability ratio=1.37, 95% CI 1.13-1.67, P=.002). Content topics did not explain or modify this association. This study confirms CDC health communicators' experience that original tweets created by @CDC_AMD Twitter profile sharing images or videos (or their links) received more retweets. The current policy of attaching images to tweets should be encouraged. ©Isaac Chun-Hai Fung, Ashley M Jackson, Lindsay A Mullican, Elizabeth B Blankenship, Mary Elizabeth Goff, Amy J Guinn, Nitin Saroha, Zion Tsz Ho Tse. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 02.04.2018.

Emergency communication and information issues in terrorist events involving radioactive materials.

PubMed

Becker, Steven M

2004-01-01

With the threat posed by terrorism involving radioactive materials now high on the nation's agenda, local, state, and federal agencies are moving to enhance preparedness and response capabilities. Crucial to these efforts is the development of effective risk communication strategies. This article reports findings from an ongoing study of risk communication issues in nuclear/radiological terrorism situations. It is part of a larger CDC-funded effort that aims to better understand communication challenges associated with weapons of mass destruction terrorism incidents. Presented here are formative research findings from 16 focus groups (n = 163) in which a multi-part, hypothetical radioactive materials terrorism situation was discussed. Twelve of the focus groups were carried out with members of the general public (drawn from a variety of ethnic backgrounds and geographic locations), and four groups were composed of first responders, hospital emergency department personnel, and public health professionals. One aim of the focus groups was to elicit detailed information on people's knowledge, views, perceptions, reactions, and concerns related to a nuclear/radiological terrorism event, and to better understand people's specific information needs and preferred information sources. A second aim was to pretest draft informational materials prepared by CDC and NIOSH. Key findings for the public and professional groups are presented, and the implications of the research for developing messages in radiological/nuclear terrorism situations are explored.

P97/CDC-48: proteostasis control in tumor cell biology.

PubMed

Fessart, Delphine; Marza, Esther; Taouji, Saïd; Delom, Frédéric; Chevet, Eric

2013-08-28

P97/CDC-48 is a prominent member of a highly evolutionary conserved Walker cassette - containing AAA+ATPases. It has been involved in numerous cellular processes ranging from the control of protein homeostasis to membrane trafficking through the intervention of specific accessory proteins. Expression of p97/CDC-48 in cancers has been correlated with tumor aggressiveness and prognosis, however the precise underlying molecular mechanisms remain to be characterized. Moreover p97/CDC-48 inhibitors were developed and are currently under intense investigation as anticancer drugs. Herein, we discuss the role of p97/CDC-48 in cancer development and its therapeutic potential in tumor cell biology. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

What is the Ideal Route of Administration of Tranexamic Acid in TKA? A Randomized Controlled Trial.

PubMed

Lee, Sung Yup; Chong, Suri; Balasubramanian, Dhanasekaraprabu; Na, Young Gon; Kim, Tae Kyun

2017-08-01

TKA commonly involves substantial blood loss and tranexamic acid has been used to reduce blood loss after TKA. Numerous clinical trials have documented the efficacy and safety of intravenous (IV) or intraarticular (IA) use of tranexamic acid. Combined administration of tranexamic acid also has been suggested; however, there is no consensus regarding the ideal route of tranexamic acid administration. (1) To compare the efficacy of tranexamic acid in terms of total blood loss and the allogeneic transfusion rate among three routes of administration: IV alone, IA alone, and combined IV and IA. (2) To compare these regimens in terms of venous thromboembolism (VTE) and the frequency of wound complications. In total, 376 patients undergoing TKA between March 2014 and March 2015 were randomized to four groups by the route of tranexamic acid administration: IV only, IA only, low-dose combined (IV + IA injection of 1 g), and high-dose combined (IV + IA injection of 2 g). The calculated total blood loss, allogeneic transfusion rate, decrease in hemoglobin, the frequency of symptomatic deep vein thrombosis and pulmonary embolism, wound complications, and periprosthetic joint infection were compared among the groups. Total blood loss was calculated using estimated total body blood volume and hemoglobin loss. The decision regarding when to transfuse was determined based on preset criteria. The high- and low-dose combined groups and the IA-only group had lower total blood loss (564 ± 242 mL, 642 ± 242 mL, and 633 ± 205 mL, respectively) than the IV-only group (764 ± 217 mL; mean differences = 199 mL [95% CI, 116-283 mL], p < 0.001; 121 mL [95% CI, 38-205 mL], p = 0.001; 131 mL [95% CI, 47-214 mL], p < 0.001); no differences were found among the other three groups. No patients in any study group received an allogeneic transfusion. One patient in the IV-only group had a symptomatic pulmonary embolism develop, but no other symptomatic VTE events occurred in any group. In addition, no differences were observed in wound complications, such as superficial wound necrosis (one patient in the IV-only and the high-dose combined group, respectively) and oozing (IV-only, IA-only, low-dose combined, high-dose combined = 3%, 4%, 4%, and 7%; p = 0.572) between the groups. No patients had a periprosthetic joint infection. IA tranexamic acid administration further reduces blood loss after TKA in comparison to IV use alone; no additional effect in further reducing blood loss was found in combination with IV tranexamic acid. Appropriately powered studies are needed to confirm the safety of this route of administration as the preferred route of administration in TKA. Level I, therapeutic study.

UPEML: a machine-portable CDC Update emulator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mehlhorn, T.A.; Young, M.F.

1984-12-01

UPEML is a machine-portable CDC Update emulation program. UPEML is written in ANSI standard Fortran-77 and is relatively simple and compact. It is capable of emulating a significant subset of the standard CDC Update functions including program library creation and subsequent modification. Machine-portability is an essential attribute of UPEML. It was written primarily to facilitate the use of CDC-based scientific packages on alternate computer systems such as the VAX 11/780 and the IBM 3081.

A Scan of CDC-Authored Articles on Legal Epidemiology, 2011-2015.

PubMed

Martini, Leila; Presley, David; Klieger, Sarah; Burris, Scott

2016-11-01

The Centers for Disease Control and Prevention (CDC) conducts research on legal epidemiology, the scientific study of law as a factor in the cause, distribution, and prevention of disease. This study describes a scan of articles written by CDC staff members to characterize the frequency and key features of legal epidemiology articles and their distribution across CDC departments and divisions. CDC librarians searched an internal repository for journal articles by CDC staff published from January 1, 2011, to May 31, 2015. Researchers reviewed and coded the abstracts to produce data on key features of the articles. Researchers identified 158 CDC-authored legal epidemiology articles published in 83 journals, most frequently in Preventing Chronic Disease (14 publications), Journal of Public Health Management Practice (10 publications), and Morbidity and Mortality Weekly Report (9 publications). Most articles concerned the use and impact of law as a deliberate tool of intervention. Thirteen articles addressed the legal infrastructure of public health, and 3 assessed the incidental or unintended effects of nonhealth laws. CDC-authored articles encompassed policy making, implementation, and impact. Literature reviews and studies mapping laws across multiple jurisdictions constituted one-quarter of all publications. Studies addressed laws at the international, national, state, local, and organizational levels. Results of the scan can be used to identify opportunities for the agency to better support research, professional development, networking, publication, and tracking of publication in this emerging field.

Molecular Mapping of Flowering Time Major Genes and QTLs in Chickpea (Cicer arietinum L.)

PubMed Central

Mallikarjuna, Bingi P.; Samineni, Srinivasan; Thudi, Mahendar; Sajja, Sobhan B.; Khan, Aamir W.; Patil, Ayyanagowda; Viswanatha, Kannalli P.; Varshney, Rajeev K.; Gaur, Pooran M.

2017-01-01

Flowering time is an important trait for adaptation and productivity of chickpea in the arid and the semi-arid environments. This study was conducted for molecular mapping of genes/quantitative trait loci (QTLs) controlling flowering time in chickpea using F2 populations derived from four crosses (ICCV 96029 × CDC Frontier, ICC 5810 × CDC Frontier, BGD 132 × CDC Frontier and ICC 16641 × CDC Frontier). Genetic studies revealed monogenic control of flowering time in the crosses ICCV 96029 × CDC Frontier, BGD 132 × CDC Frontier and ICC 16641 × CDC Frontier, while digenic control with complementary gene action in ICC 5810 × CDC Frontier. The intraspecific genetic maps developed from these crosses consisted 75, 75, 68 and 67 markers spanning 248.8 cM, 331.4 cM, 311.1 cM and 385.1 cM, respectively. A consensus map spanning 363.8 cM with 109 loci was constructed by integrating four genetic maps. Major QTLs corresponding to flowering time genes efl-1 from ICCV 96029, efl-3 from BGD 132 and efl-4 from ICC 16641 were mapped on CaLG04, CaLG08 and CaLG06, respectively. The QTLs and linked markers identified in this study can be used in marker-assisted breeding for developing early maturing chickpea. PMID:28729871

Cross-species and tissue variations in cyanide detoxification rates in rodents and non-human primates on protein-restricted diet.

PubMed

Kimani, S; Moterroso, V; Morales, P; Wagner, J; Kipruto, S; Bukachi, F; Maitai, C; Tshala-Katumbay, D

2014-04-01

We sought to elucidate the impact of diet, cyanide or cyanate exposure on mammalian cyanide detoxification capabilities (CDC). Male rats (~8 weeks old) (N=52) on 75% sulfur amino acid (SAA)-deficient diet were treated with NaCN (2.5mg/kg bw) or NaOCN (50mg/kg bw) for 6 weeks. Macaca fascicularis monkeys (~12 years old) (N=12) were exclusively fed cassava for 5 weeks. CDC was assessed in plasma, or spinal cord, or brain. In rats, NaCN induced seizures under SAA-restricted diet whereas NaOCN induced motor deficits. No deficits were observed in non-human primates. Under normal diet, the CDC were up to ~80× faster in the nervous system (14 ms to produce one μmol of thiocyanate from the detoxification of cyanide) relative to plasma. Spinal cord CDC was impaired by NaCN, NaOCN, or SAA deficiency. In M. fascicularis, plasma CDC changed proportionally to total proteins (r=0.43; p<0.001). The plasma CDC was ~2× relative to that of rodents. The nervous system susceptibility to cyanide may result from a "multiple hit" by the toxicity of cyanide or its cyanate metabolite, the influences of dietary deficiencies, and the tissue variations in CDC. Chronic dietary reliance on cassava may cause metabolic derangement including poor CDC. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cross-species and tissue variations in cyanide detoxification rates in rodents and non-human primates on protein-restricted diet

PubMed Central

Kimani, S.; Moterroso, V.; Morales, P.; Wagner, J.; Kipruto, S.; Bukachi, F.; Maitai, C.; Tshala-Katumbay, D.

2014-01-01

We sought to elucidate the impact of diet, cyanide or cyanate exposure on mammalian cyanide detoxification capabilities (CDC). Male rats (~8 weeks old) (N=52) on 75% sulfur amino acid (SAA)-deficient diet were treated with NaCN (2.5 mg/kg bw) or NaOCN (50 mg/kg bw) for 6 weeks. Macaca fascicularis monkeys (~12 years old) (N=12) were exclusively fed cassava for 5 weeks. CDC was assessed in plasma, or spinal cord, or brain. In rats, NaCN induced seizures under SAA-restricted diet whereas NaOCN induced motor deficits. No deficits were observed in non-human primates. Under normal diet, the CDC were up to ~ 80X faster in the nervous system (14 milliseconds to produce one μmol of thiocyanate from the detoxification of cyanide) relative to plasma. Spinal cord CDC was impaired by NaCN, NaOCN, or SAA deficiency. In macaca fascicularis, plasma CDC changed proportionally to total proteins (r=0.43; p<0.001). The plasma CDC was ~ 2X relative to that of rodents. The nervous system susceptibility to cyanide may result from a “multiple hit” by the toxicity of cyanide or its cyanate metabolite, the influences of dietary deficiencies, and the tissue variations in CDC. Chronic dietary reliance on cassava may cause metabolic derangement including poor CDC. PMID:24500607

CDC-42 Orients Cell Migration during Epithelial Intercalation in the Caenorhabditis elegans Epidermis.

PubMed

Walck-Shannon, Elise; Lucas, Bethany; Chin-Sang, Ian; Reiner, David; Kumfer, Kraig; Cochran, Hunter; Bothfeld, William; Hardin, Jeff

2016-11-01

Cell intercalation is a highly directed cell rearrangement that is essential for animal morphogenesis. As such, intercalation requires orchestration of cell polarity across the plane of the tissue. CDC-42 is a Rho family GTPase with key functions in cell polarity, yet its role during epithelial intercalation has not been established because its roles early in embryogenesis have historically made it difficult to study. To circumvent these early requirements, in this paper we use tissue-specific and conditional loss-of-function approaches to identify a role for CDC-42 during intercalation of the Caenorhabditis elegans dorsal embryonic epidermis. CDC-42 activity is enriched in the medial tips of intercalating cells, which extend as cells migrate past one another. Moreover, CDC-42 is involved in both the efficient formation and orientation of cell tips during cell rearrangement. Using conditional loss-of-function we also show that the PAR complex functions in tip formation and orientation. Additionally, we find that the sole C. elegans Eph receptor, VAB-1, functions during this process in an Ephrin-independent manner. Using epistasis analysis, we find that vab-1 lies in the same genetic pathway as cdc-42 and is responsible for polarizing CDC-42 activity to the medial tip. Together, these data establish a previously uncharacterized role for polarized CDC-42, in conjunction with PAR-6, PAR-3 and an Eph receptor, during epithelial intercalation.

CDC-42 Orients Cell Migration during Epithelial Intercalation in the Caenorhabditis elegans Epidermis

PubMed Central

Lucas, Bethany; Chin-Sang, Ian; Reiner, David; Kumfer, Kraig

2016-01-01

Cell intercalation is a highly directed cell rearrangement that is essential for animal morphogenesis. As such, intercalation requires orchestration of cell polarity across the plane of the tissue. CDC-42 is a Rho family GTPase with key functions in cell polarity, yet its role during epithelial intercalation has not been established because its roles early in embryogenesis have historically made it difficult to study. To circumvent these early requirements, in this paper we use tissue-specific and conditional loss-of-function approaches to identify a role for CDC-42 during intercalation of the Caenorhabditis elegans dorsal embryonic epidermis. CDC-42 activity is enriched in the medial tips of intercalating cells, which extend as cells migrate past one another. Moreover, CDC-42 is involved in both the efficient formation and orientation of cell tips during cell rearrangement. Using conditional loss-of-function we also show that the PAR complex functions in tip formation and orientation. Additionally, we find that the sole C. elegans Eph receptor, VAB-1, functions during this process in an Ephrin-independent manner. Using epistasis analysis, we find that vab-1 lies in the same genetic pathway as cdc-42 and is responsible for polarizing CDC-42 activity to the medial tip. Together, these data establish a previously uncharacterized role for polarized CDC-42, in conjunction with PAR-6, PAR-3 and an Eph receptor, during epithelial intercalation. PMID:27861585

Cdc7 is required throughout the yeast S phase to activate replication origins.

PubMed

Donaldson, A D; Fangman, W L; Brewer, B J

1998-02-15

The long-standing conclusion that the Cdc7 kinase of Saccharomyces cerevisiae is required only to trigger S phase has been challenged by recent data that suggests it acts directly on individual replication origins. We tested the possibility that early- and late-activated origins have different requirements for Cdc7 activity. Cells carrying a cdc7(ts) allele were first arrested in G1 at the cdc7 block by incubation at 37 degrees C, and then were allowed to enter S phase by brief incubation at 23 degrees C. During the S phase, after return to 37 degrees C, early-firing replication origins were activated, but late origins failed to fire. Similarly, a plasmid with a late-activated origin was defective in replication. As a consequence of the origin activation defect, duplication of chromosomal sequences that are normally replicated from late origins was greatly delayed. Early-replicating regions of the genome duplicated at approximately their normal time. The requirements of early and late origins for Cdc7 appear to be temporally rather than quantitatively different, as reducing overall levels of Cdc7 by growth at semi-permissive temperature reduced activation at early and late origins approximately equally. Our results show that Cdc7 activates early and late origins separately, with late origins requiring the activity later in S phase to permit replication initiation.

Mechanism of Cdc42-induced Actin Polymerization in Neutrophil Extracts

PubMed Central

Zigmond, Sally H.; Joyce, Michael; Yang, Changsong; Brown, Kevin; Huang, Minzhou; Pring, Martin

1998-01-01

Cdc42, activated with GTPγS, induces actin polymerization in supernatants of lysed neutrophils. This polymerization, like that induced by agonists, requires elongation at filament barbed ends. To determine if creation of free barbed ends was sufficient to induce actin polymerization, free barbed ends in the form of spectrin-actin seeds or sheared F-actin filaments were added to cell supernatants. Neither induced polymerization. Furthermore, the presence of spectrin-actin seeds did not increase the rate of Cdc42-induced polymerization, suggesting that the presence of Cdc42 did not facilitate polymerization from spectrin-actin seeds such as might have been the case if Cdc42 inhibited capping or released G-actin from a sequestered pool. Electron microscopy revealed that Cdc42-induced filaments elongated rapidly, achieving a mean length greater than 1 μm in 15 s. The mean length of filaments formed from spectrin-actin seeds was <0.4 μm. Had spectrin-actin seeds elongated at comparable rates before they were capped, they would have induced longer filaments. There was little change in mean length of Cdc42-induced filaments between 15 s and 5 min, suggesting that the increase in F-actin over this time was due to an increase in filament number. These data suggest that Cdc42 induction of actin polymerization requires both creation of free barbed ends and facilitated elongation at these ends. PMID:9722612