Addressing a Yellow Fever Vaccine Shortage - United States, 2016-2017.

PubMed

Gershman, Mark D; Angelo, Kristina M; Ritchey, Julian; Greenberg, David P; Muhammad, Riyadh D; Brunette, Gary; Cetron, Martin S; Sotir, Mark J

2017-05-05

Recent manufacturing problems resulted in a shortage of the only U.S.-licensed yellow fever vaccine. This shortage is expected to lead to a complete depletion of yellow fever vaccine available for the immunization of U.S. travelers by mid-2017. CDC, the Food and Drug Administration (FDA), and Sanofi Pasteur are collaborating to ensure a continuous yellow fever vaccine supply in the United States. As part of this collaboration, Sanofi Pasteur submitted an expanded access investigational new drug (eIND) application to FDA in September 2016 to allow for the importation and use of an alternative yellow fever vaccine manufactured by Sanofi Pasteur France, with safety and efficacy comparable to the U.S.-licensed vaccine; the eIND was accepted by FDA in October 2016. The implementation of this eIND protocol included developing a systematic process for selecting a limited number of clinic sites to provide the vaccine. CDC and Sanofi Pasteur will continue to communicate with the public and other stakeholders, and CDC will provide a list of locations that will be administering the replacement vaccine at a later date.

Mechanisms of CDC-42 activation during contact-induced cell polarization.

PubMed

Chan, Emily; Nance, Jeremy

2013-04-01

Polarization of early embryos provides a foundation to execute essential patterning and morphogenetic events. In Caenorhabditis elegans, cell contacts polarize early embryos along their radial axis by excluding the cortical polarity protein PAR-6 from sites of cell contact, thereby restricting PAR-6 to contact-free cell surfaces. Radial polarization requires the cortically enriched Rho GTPase CDC-42, which in its active form recruits PAR-6 through direct binding. The Rho GTPase activating protein (RhoGAP) PAC-1, which localizes specifically to cell contacts, triggers radial polarization by inactivating CDC-42 at these sites. The mechanisms responsible for activating CDC-42 at contact-free surfaces are unknown. Here, in an overexpression screen of Rho guanine nucleotide exchange factors (RhoGEFs), which can activate Rho GTPases, we identify CGEF-1 and ECT-2 as RhoGEFs that act through CDC-42 to recruit PAR-6 to the cortex. We show that ECT-2 and CGEF-1 localize to the cell surface and that removing their activity causes a reduction in levels of cortical PAR-6. Through a structure-function analysis, we show that the tandem DH-PH domains of CGEF-1 and ECT-2 are sufficient for GEF activity, but that regions outside of these domains target each protein to the cell surface. Finally, we provide evidence suggesting that the N-terminal region of ECT-2 may direct its in vivo preference for CDC-42 over another known target, the Rho GTPase RHO-1. We propose that radial polarization results from a competition between RhoGEFs, which activate CDC-42 throughout the cortex, and the RhoGAP PAC-1, which inactivates CDC-42 at cell contacts.

Mechanisms of CDC-42 activation during contact-induced cell polarization

PubMed Central

Chan, Emily; Nance, Jeremy

2013-01-01

Summary Polarization of early embryos provides a foundation to execute essential patterning and morphogenetic events. In Caenorhabditis elegans, cell contacts polarize early embryos along their radial axis by excluding the cortical polarity protein PAR-6 from sites of cell contact, thereby restricting PAR-6 to contact-free cell surfaces. Radial polarization requires the cortically enriched Rho GTPase CDC-42, which in its active form recruits PAR-6 through direct binding. The Rho GTPase activating protein (RhoGAP) PAC-1, which localizes specifically to cell contacts, triggers radial polarization by inactivating CDC-42 at these sites. The mechanisms responsible for activating CDC-42 at contact-free surfaces are unknown. Here, in an overexpression screen of Rho guanine nucleotide exchange factors (RhoGEFs), which can activate Rho GTPases, we identify CGEF-1 and ECT-2 as RhoGEFs that act through CDC-42 to recruit PAR-6 to the cortex. We show that ECT-2 and CGEF-1 localize to the cell surface and that removing their activity causes a reduction in levels of cortical PAR-6. Through a structure–function analysis, we show that the tandem DH-PH domains of CGEF-1 and ECT-2 are sufficient for GEF activity, but that regions outside of these domains target each protein to the cell surface. Finally, we provide evidence suggesting that the N-terminal region of ECT-2 may direct its in vivo preference for CDC-42 over another known target, the Rho GTPase RHO-1. We propose that radial polarization results from a competition between RhoGEFs, which activate CDC-42 throughout the cortex, and the RhoGAP PAC-1, which inactivates CDC-42 at cell contacts. PMID:23424200

Conformational control and DNA-binding mechanism of the metazoan origin recognition complex.

PubMed

Bleichert, Franziska; Leitner, Alexander; Aebersold, Ruedi; Botchan, Michael R; Berger, James M

2018-06-26

In eukaryotes, the heterohexameric origin recognition complex (ORC) coordinates replication onset by facilitating the recruitment and loading of the minichromosome maintenance 2-7 (Mcm2-7) replicative helicase onto DNA to license origins. Drosophila ORC can adopt an autoinhibited configuration that is predicted to prevent Mcm2-7 loading; how the complex is activated and whether other ORC homologs can assume this state are not known. Using chemical cross-linking and mass spectrometry, biochemical assays, and electron microscopy (EM), we show that the autoinhibited state of Drosophila ORC is populated in solution, and that human ORC can also adopt this form. ATP binding to ORC supports a transition from the autoinhibited state to an active configuration, enabling the nucleotide-dependent association of ORC with both DNA and Cdc6. An unstructured N-terminal region adjacent to the conserved ATPase domain of Orc1 is shown to be required for high-affinity ORC-DNA interactions, but not for activation. ORC optimally binds DNA duplexes longer than the predicted footprint of the ORC ATPases associated with a variety of cellular activities (AAA + ) and winged-helix (WH) folds; cryo-EM analysis of Drosophila ORC bound to DNA and Cdc6 indicates that ORC contacts DNA outside of its central core region, bending the DNA away from its central DNA-binding channel. Our findings indicate that ORC autoinhibition may be common to metazoans and that ORC-Cdc6 remodels origin DNA before Mcm2-7 recruitment and loading.

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

CDC Vital Signs: Teen Drinking and Driving

MedlinePlus

... involvement, minimum legal drinking age and zero tolerance laws, and graduated driver licensing systems. These proven steps ... Driving: What Works Minimum legal drinking age (MLDA) laws in every state make it illegal to sell ...

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

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.

Regulation and Function of Cdt1; A Key Factor in Cell Proliferation and Genome Stability

PubMed Central

Pozo, Pedro N.; Cook, Jeanette Gowen

2016-01-01

Successful cell proliferation requires efficient and precise genome duplication followed by accurate chromosome segregation. The Cdc10-dependent transcript 1 protein (Cdt1) is required for the first step in DNA replication, and in human cells Cdt1 is also required during mitosis. Tight cell cycle controls over Cdt1 abundance and activity are critical to normal development and genome stability. We review here recent advances in elucidating Cdt1 molecular functions in both origin licensing and kinetochore–microtubule attachment, and we describe the current understanding of human Cdt1 regulation. PMID:28025526

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/

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

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 (cell division cycle protein 45) guards the gate of the Eukaryote Replisome helicase stabilizing leading strand engagement

PubMed Central

Petojevic, Tatjana; Pesavento, James J.; Costa, Alessandro; Liang, Jingdan; Wang, Zhijun; Berger, James M.; Botchan, Michael R.

2015-01-01

DNA replication licensing is now understood to be the pathway that leads to the assembly of double hexamers of minichromosome maintenance (Mcm2–7) at origin sites. Cell division control protein 45 (Cdc45) and GINS proteins activate the latent Mcm2–7 helicase by inducing allosteric changes through binding, forming a Cdc45/Mcm2-7/GINS (CMG) complex that is competent to unwind duplex DNA. The CMG has an active gate between subunits Mcm2 and Mcm5 that opens and closes in response to nucleotide binding. The consequences of inappropriate Mcm2/5 gate actuation and the role of a side channel formed between GINS/Cdc45 and the outer edge of the Mcm2–7 ring for unwinding have remained unexplored. Here we uncover a novel function for Cdc45. Cross-linking studies trace the path of the DNA with the CMG complex at a fork junction between duplex and single strands with the bound CMG in an open or closed gate conformation. In the closed state, the lagging strand does not pass through the side channel, but in the open state, the leading strand surprisingly interacts with Cdc45. Mutations in the recombination protein J fold of Cdc45 that ablate this interaction diminish helicase activity. These data indicate that Cdc45 serves as a shield to guard against occasional slippage of the leading strand from the core channel. PMID:25561522

Toward a More Sensitive Endpoint for Assessing Postoperative Complications in Patients with Inflammatory Bowel Disease: a Comparison Between Comprehensive Complication Index (CCI) and Clavien-Dindo Classification (CDC).

PubMed

Zhu, Feng; Feng, Dengyu; Zhang, Tenghui; Gu, Lili; Zhu, Weiming; Guo, Zhen; Li, Yi; Gong, Jianfeng; Li, Ning; Li, Jieshou

2018-05-15

The comprehensive complication index (CCI) is a novel approach to evaluate complications. However, application of the CCI in inflammatory bowel disease (IBD) population is scarce and the difference between the CCI and the Clavien-Dindo classification (CDC) remains unknown. The aim of this study was to compare the CCI to the conventional CDC by applying the CCI among the IBD patients. The data of 426 IBD patients who underwent surgery between September 1, 2015 and August 31, 2017 were collected. Univariate and multivariate analyses were conducted to identify risk factors for postoperative complications. The efficacy of CCI and CDC was compared using correlation analysis and logistic regression. Cumulative sum control (CUSUM) models were applied to monitor the CCI continuously. Totally, 297 complications occurred in 144 (33.8%) patients. The rate of severe complications (CDC grade ≥ III) was 12.9% and the mean CCI was 9.8 ± 15.5. Preoperative glucocorticoids usage and previous abdominal surgery were related to higher CCI value (p = 0.002, p = 0.006, respectively) but not related to higher incidence of severe complications (CDC grade ≥ III) (p = 0.117, p = 0.177, respectively). In patients with multiple complications, the CCI demonstrated a stronger correlation with hospital stay (ρ = 0.604, p < 0.001) than CDC (ρ = 0.508, p < 0.001). Higher CCI value (p < 0.001, OR 1.161, 95% CI 1.093-1.234) and the CDC grade (p < 0.001, OR 3.811, 95% CI 2.283-6.362) were risk factors for prolonged LOS. In the CUSUM-CCI model of IBD surgery, a gradual decrease was observed over time. The CCI and the CDC are both risk factors for prolonged postoperative LOS after surgery for IBD patients. The CCI is more strongly correlated with postoperative LOS than is the conventional CDC. The CUSUM-CCI model is effective in monitoring surgical quality.

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

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.

Dbl3 drives Cdc42 signaling at the apical margin to regulate junction position and apical differentiation

PubMed Central

Zihni, Ceniz; Munro, Peter M.G.; Elbediwy, Ahmed; Keep, Nicholas H.; Terry, Stephen J.; Harris, John

2014-01-01

Epithelial cells develop morphologically characteristic apical domains that are bordered by tight junctions, the apical–lateral border. Cdc42 and its effector complex Par6–atypical protein kinase c (aPKC) regulate multiple steps during epithelial differentiation, but the mechanisms that mediate process-specific activation of Cdc42 to drive apical morphogenesis and activate the transition from junction formation to apical differentiation are poorly understood. Using a small interfering RNA screen, we identify Dbl3 as a guanine nucleotide exchange factor that is recruited by ezrin to the apical membrane, that is enriched at a marginal zone apical to tight junctions, and that drives spatially restricted Cdc42 activation, promoting apical differentiation. Dbl3 depletion did not affect junction formation but did affect epithelial morphogenesis and brush border formation. Conversely, expression of active Dbl3 drove process-specific activation of the Par6–aPKC pathway, stimulating the transition from junction formation to apical differentiation and domain expansion, as well as the positioning of tight junctions. Thus, Dbl3 drives Cdc42 signaling at the apical margin to regulate morphogenesis, apical–lateral border positioning, and apical differentiation. PMID:24379416

Increased Cdc7 expression is a marker of oral squamous cell carcinoma and overexpression of Cdc7 contributes to the resistance to DNA-damaging agents.

PubMed

Cheng, An Ning; Jiang, Shih Sheng; Fan, Chi-Chen; Lo, Yu-Kang; Kuo, Chan-Yen; Chen, Chung-Hsing; Liu, Ying-Lan; Lee, Chun-Chung; Chen, Wei-Shone; Huang, Tze-Sing; Wang, Tao-Yeuan; Lee, Alan Yueh-Luen

2013-09-01

Cdc7-Dbf4 kinase (Dbf4-dependent kinase, DDK) is an essential factor of DNA replication and DNA damage response (DDR), which is associated with tumorigenesis. However, Cdc7 expression has never been associated to the outcome of oral squamous cell carcinoma (OSCC) patients, and the mechanism underlying cancer cell survival mediated by Cdc7 remains unclear. The Cdc7 protein expression of 105 OSCC tumor and 30 benign tissues was examined by immunohistochemistry assay. Overall survival rates of 80 OSCC patients were measured using Kaplan-Meier estimates and the log-rank tests. Cdc7 overexpression by adenovirus system was used to scrutinize the underlying mechanism contributed to cancer cell survival upon DDR. In silico analysis showed that increased Cdc7 is a common feature of cancer. Cdc7 overexpression was found in 96 of 105 (91.4%) studied cases of OSCC patients. Patients with higher Cdc7 expression, either categorized into two groups: Cdc7 high expression (2+ to 3+) versus Cdc7 low expression (0 to 1+) [hazard ratios (HR)=2.6; 95% confidence interval (CI)=1.28-5.43; P=0.0087] or four groups (0 to 3+) [HR=1.71; 95% CI=1.20-2.44; P=0.0032], exhibited a poorer outcome. Multivariate analysis showed that Cdc7 is an independent marker for survival prediction. Overexpressed Cdc7 inhibits genotoxin-induced apoptosis to increase the survival of cancer cells. In summary, Cdc7 expression, which is universally upregulated in cancer, is an independent prognostic marker of OSCC. Cdc7 inhibits genotoxin-induced apoptosis and increases survival in cancer cells upon DDR, suggesting that high expression of Cdc7 enhances the resistance to chemotherapy. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP).

PubMed

Cohn, Amanda C; MacNeil, Jessica R; Clark, Thomas A; Ortega-Sanchez, Ismael R; Briere, Elizabeth Z; Meissner, H Cody; Baker, Carol J; Messonnier, Nancy E

2013-03-22

Meningococcal disease describes the spectrum of infections caused by Neisseria meningiditis, including meningitdis, bacteremia, and bacteremic pneumonia. Two quadrivalent meningococcal polysaccharide-protein conjugate vaccines that provide protection against meningococcal serogroups A, C, W, and Y (MenACWY-D [Menactra, manufactured by Sanofi Pasteur, Inc., Swiftwater, Pennsylvania] and MenACWY-CRM [Menveo, manufactured by Novartis Vaccines, Cambridge, Massachusetts]) are licensed in the United States for use among persons aged 2 through 55 years. MenACWY-D also is licensed for use among infants and toddlers aged 9 through 23 months. Quadrivalent meningococcal polysaccharide vaccine (MPSV4 [Menommune, manufactured by sanofi pasteur, Inc., Swiftwater, Pennsylvania]) is the only vaccine licensed for use among persons aged ≥56 years. A bivalent meningococcal polysaccharide protein conjugate vaccine that provides protection against meningococcal serogroups C and Y along with Haemophilus influenzae type b (Hib) (Hib-MenCY-TT [MenHibrix, manufactured by GlaxoSmithKline Biologicals, Rixensart, Belgium]) is licensed for use in children aged 6 weeks through 18 months. This report compiles and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) regarding prevention and control of meningococcal disease in the United States, specifically the changes in the recommendations published since 2005 (CDC. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2005;54 [No. RR-7]). As a comprehensive summary of previously published recommendations, this report does not contain any new recommendations; it is intended for use by clinicians as a resource. ACIP recommends routine vaccination with a quadrivalent meningococcal conjugate vaccine (MenACWY) for adolescents aged 11 or 12 years, with a booster dose at age 16 years. ACIP also recommends routine vaccination for persons at increased risk for meningococcal disease (i.e., persons who have persistent complement component deficiencies, persons who have anatomic or functional asplenia, microbiologists who routinely are exposed to isolates of N. meningitidis, military recruits, and persons who travel to or reside in areas in which meningococcal disease is hyperendemic or epidemic). Guidelines for antimicrobial chemoprophylaxis and for evaluation and management of suspected outbreaks of meningococcal disease also are provided.

A network of conserved formins, regulated by the guanine exchange factor EXC-5 and the GTPase CDC-42, modulates tubulogenesis in vivo.

PubMed

Shaye, Daniel D; Greenwald, Iva

2016-11-15

The C. elegans excretory cell (EC) is a powerful model for tubulogenesis, a conserved process that requires precise cytoskeletal regulation. EXC-6, an ortholog of the disease-associated formin INF2, coordinates cell outgrowth and lumen formation during EC tubulogenesis by regulating F-actin at the tip of the growing canal and the dynamics of basolateral microtubules. EXC-6 functions in parallel with EXC-5/FGD, a predicted activator of the Rho GTPase Cdc42. Here, we identify the parallel pathway: EXC-5 functions through CDC-42 to regulate two other formins: INFT-2, another INF2 ortholog, and CYK-1, the sole ortholog of the mammalian diaphanous (mDia) family of formins. We show that INFT-2 promotes F-actin accumulation in the EC, and that CYK-1 inhibits INFT-2 to regulate F-actin levels and EXC-6-promoted outgrowth. As INF2 and mDia physically interact and cross-regulate in cultured cells, our work indicates that a conserved EXC-5-CDC-42 pathway modulates this regulatory interaction and that it is functionally important in vivo during tubulogenesis. © 2016. Published by The Company of Biologists Ltd.

Dbf4-dependent kinase and the Rtt107 scaffold promote Mus81-Mms4 resolvase activation during mitosis.

PubMed

Princz, Lissa N; Wild, Philipp; Bittmann, Julia; Aguado, F Javier; Blanco, Miguel G; Matos, Joao; Pfander, Boris

2017-03-01

DNA repair by homologous recombination is under stringent cell cycle control. This includes the last step of the reaction, disentanglement of DNA joint molecules (JMs). Previous work has established that JM resolving nucleases are activated specifically at the onset of mitosis. In case of budding yeast Mus81-Mms4, this cell cycle stage-specific activation is known to depend on phosphorylation by CDK and Cdc5 kinases. Here, we show that a third cell cycle kinase, Cdc7-Dbf4 (DDK), targets Mus81-Mms4 in conjunction with Cdc5-both kinases bind to as well as phosphorylate Mus81-Mms4 in an interdependent manner. Moreover, DDK-mediated phosphorylation of Mms4 is strictly required for Mus81 activation in mitosis, establishing DDK as a novel regulator of homologous recombination. The scaffold protein Rtt107, which binds the Mus81-Mms4 complex, interacts with Cdc7 and thereby targets DDK and Cdc5 to the complex enabling full Mus81 activation. Therefore, Mus81 activation in mitosis involves at least three cell cycle kinases, CDK, Cdc5 and DDK Furthermore, tethering of the kinases in a stable complex with Mus81 is critical for efficient JM resolution. © 2017 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

Current State of and Needs for Hepatitis B Screening: Results of a Large Screening Study in a Low-Prevalent, Metropolitan Region

PubMed Central

Bottero, Julie; Boyd, Anders; Lemoine, Maud; Carrat, Fabrice; Gozlan, Joel; Collignon, Anne; Boo, Nicolas; Dhotte, Philippe; Varsat, Brigitte; Muller, Gerard; Cha, Olivier; Valin, Nadia; Nau, Jean; Campa, Pauline; Silbermann, Benjamin; Bary, Marc; Girard, Pierre-Marie; Lacombe, Karine

2014-01-01

Background In low hepatitis B virus (HBV)-prevalent countries, most HBV-infected persons are unaware of their status. We aimed to evaluate whether (i) previous HBV-testing, (ii) physicians decision to screen, and (iii) CDC's recommendations identified infected individuals and which risk-factor groups needing testing. Methods During a mass, multi-center HBV-screening study from September 2010-August 2011, 3929 participants were screened for hepatitis B surface antigen (HBsAg), anti-HBs and anti-Hepatitis B core antibodies (anti-HBcAb). Questions on HBV risk-factors and testing practices were asked to participants, while participants' eligibility for HBV-testing was asked to study medical professionals. Results 85 (2.2%) participants were HBsAg-positive, while 659 (16.8%) had either resolved HBV infection or isolated anti-HBcAb. When comparing practices, HBV-testing was more likely to occur in HBV-infected participants if Centers for Disease Control and Prevention (CDC) recommendations were used (Sensitivity = 100%, 95%CI: 95.8–100) than physicians' discretion (Sensitivity = 87.1%, 95%CI: 78.0–93.4) or previous HBV-test (Sensitivity = 36.5%, 95%CI: 26.3–47.6) (p<0.0001). Nevertheless, many non-infected individuals would still have been screened using CDC-recommendations (Specificity = 31.1%, 95%CI: 29.6–32.6). Using multivariable logistic regression, HBsAg-positive status was significantly associated with the following: males, originating from high HBV-endemic region, contact with HBV-infected individual, without national healthcare, and intravenous-drug user (IDU). Of these risk-factors, physician's discretion for testing HBV was not significantly associated with participants' geographical origin or IDU. Conclusions Missed opportunities of HBV-screening are largely due to underestimating country of origin as a risk-factor. Applying CDC-recommendations could improve HBV-screening, but with the disadvantage of many tests. Further development of HBV-testing strategies is necessary, especially before severe disease occurs. PMID:24663387

Current state of and needs for hepatitis B screening: results of a large screening study in a low-prevalent, metropolitan region.

PubMed

Bottero, Julie; Boyd, Anders; Lemoine, Maud; Carrat, Fabrice; Gozlan, Joel; Collignon, Anne; Boo, Nicolas; Dhotte, Philippe; Varsat, Brigitte; Muller, Gerard; Cha, Olivier; Valin, Nadia; Nau, Jean; Campa, Pauline; Silbermann, Benjamin; Bary, Marc; Girard, Pierre-Marie; Lacombe, Karine

2014-01-01

In low hepatitis B virus (HBV)-prevalent countries, most HBV-infected persons are unaware of their status. We aimed to evaluate whether (i) previous HBV-testing, (ii) physicians decision to screen, and (iii) CDC's recommendations identified infected individuals and which risk-factor groups needing testing. During a mass, multi-center HBV-screening study from September 2010-August 2011, 3929 participants were screened for hepatitis B surface antigen (HBsAg), anti-HBs and anti-Hepatitis B core antibodies (anti-HBcAb). Questions on HBV risk-factors and testing practices were asked to participants, while participants' eligibility for HBV-testing was asked to study medical professionals. 85 (2.2%) participants were HBsAg-positive, while 659 (16.8%) had either resolved HBV infection or isolated anti-HBcAb. When comparing practices, HBV-testing was more likely to occur in HBV-infected participants if Centers for Disease Control and Prevention (CDC) recommendations were used (Sensitivity = 100%, 95%CI: 95.8-100) than physicians' discretion (Sensitivity = 87.1%, 95%CI: 78.0-93.4) or previous HBV-test (Sensitivity = 36.5%, 95%CI: 26.3-47.6) (p<0.0001). Nevertheless, many non-infected individuals would still have been screened using CDC-recommendations (Specificity = 31.1%, 95%CI: 29.6-32.6). Using multivariable logistic regression, HBsAg-positive status was significantly associated with the following: males, originating from high HBV-endemic region, contact with HBV-infected individual, without national healthcare, and intravenous-drug user (IDU). Of these risk-factors, physician's discretion for testing HBV was not significantly associated with participants' geographical origin or IDU. Missed opportunities of HBV-screening are largely due to underestimating country of origin as a risk-factor. Applying CDC-recommendations could improve HBV-screening, but with the disadvantage of many tests. Further development of HBV-testing strategies is necessary, especially before severe disease occurs.

Cognitive Function in Young Persons With and Without Perinatal HIV in the AALPHI Cohort in England: Role of Non-HIV-Related Factors.

PubMed

Judd, Ali; Le Prevost, Marthe; Melvin, Diane; Arenas-Pinto, Alejandro; Parrott, Francesca; Winston, Alan; Foster, Caroline; Sturgeon, Kate; Rowson, Katie; Gibb, Di M

2016-11-15

 There is limited evidence about the cognitive performance of older adolescents with perinatally acquired human immunodeficiency virus (HIV) compared with HIV-negative (HIV-) adolescents.  A total of 296 perinatally HIV-infected (PHIV+) and 97 HIV- adolescents (aged 12-21 and 13-23 years, respectively) completed 12 tests covering 6 cognitive domains. The HIV- participants had PHIV+ siblings and/or an HIV-infected mother. Domain-specific and overall (NPZ-6) z scores were calculated for PHIV+ participants, with or without Centers for Disease Control and Prevention (CDC) stage C disease, and HIV- participants. Linear regression was performed to explore predictors of NPZ-6.  One hundred twenty-five (42%) of the PHIV+ and 31 (32%) of the HIV- participants were male; 251 (85%) and 69 (71%), respectively, were black African; and their median ages (interquartile range) were 16 (15-18) and 16 (14-18) years, respectively. In PHIV+ participants, 247 (86%) were receiving antiretroviral therapy, and 76 (26%) had a previous CDC C diagnosis. The mean (standard deviation) NPZ-6 score was -0.81 (0.99) in PHIV+ participants with a CDC C diagnosis (PHIV+/C), -0.45 (0.80) in those without a CDC C diagnosis (PHIV+/no C), and -0.32 (0.76) in HIV- participants (P < .001). After adjustment, there was no difference in NPZ-6 scores between PHIV+/no C and HIV- participants (adjusted coefficient, -0.01; 95% confidence interval, -.22 to .20). PHIV+/C participants scored below the HIV- group (adjusted coefficient, -0.44; -.70 to -.19). Older age predicted higher NPZ-6 scores, and black African ethnicity and worse depression predicted lower NPZ-6 scores. In a sensitivity analysis including PHIV+ participants only, no HIV-related factors apart from a CDC C diagnosis were associated with NPZ-6 scores.  Cognitive performance was similar between PHIV+/no C and HIV- participants and indicated relatively mild impairment compared with normative data. The true impact on day-to-day functioning needs further investigation. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Intrinsic dielectric properties of magnetodielectric La2CoMnO6

NASA Astrophysics Data System (ADS)

Silva, R. X.; Moreira, R. L.; Almeida, R. M.; Paniago, R.; Paschoal, C. W. A.

2015-06-01

Manganite with a double perovskite structure is an attractive material because of its interesting magnetoelectric and dielectric responses. In particular, colossal dielectric constant (CDC) behavior has been observed in La2CoMnO6 (LCMO) at radio frequencies and at room temperature. In this paper, we used infrared-reflectivity spectroscopy to study a LCMO ceramic obtained through a modified Pechini's method to determine the phonon contribution to the intrinsic dielectric response of the system and to investigate the CDC origin. The analysis of the main polar modes and of the obtained phonon parameters indicate that the CDC effect of LCMO is of pure extrinsic origin. In addition, we estimated the dielectric constant and the quality factor of the material in the microwave region to be ɛ's ˜ 16 and Qu × f ˜ 124 THz, which verifies that LCMO is appropriate for application in microwave devices and circuitry.

HSPA6 augments garlic extract-induced inhibition of proliferation, migration, and invasion of bladder cancer EJ cells; Implication for cell cycle dysregulation, signaling pathway alteration, and transcription factor-associated MMP-9 regulation

PubMed Central

Hwang, Byungdoo; Noh, Dae-Hwa; Park, Sung Lyea; Kim, Won Tae; Park, Sung-Soo; Kim, Wun-Jae; Moon, Sung-Kwon

2017-01-01

Although recent studies have demonstrated the anti-tumor effects of garlic extract (GE), the exact molecular mechanism is still unclear. In this study, we investigated the molecular mechanism associated with the inhibitory action of GE against bladder cancer EJ cell responses. Treatment with GE significantly inhibited proliferation of EJ cells dose-dependently through G2/M-phase cell cycle arrest. This G2/M-phase cell cycle arrest by GE was due to the activation of ATM and CHK2, which appears to inhibit phosphorylation of Cdc25C (Ser216) and Cdc2 (Thr14/Tyr15), this in turn was accompanied by down-regulation of cyclin B1 and up-regulation of p21WAF1. Furthermore, GE treatment was also found to induce phosphorylation of MAPK (ERK1/2, p38MAPK, and JNK) and AKT. In addition, GE impeded the migration and invasion of EJ cells via inhibition of MMP-9 expression followed by decreased binding activities of AP-1, Sp-1, and NF-κB motifs. Based on microarray datasets, we selected Heat shock protein A6 (HSPA6) as the most up-regulated gene responsible for the inhibitory effects of GE. Interestingly, overexpression of HSPA6 gene resulted in an augmentation effect with GE inhibiting proliferation, migration, and invasion of EJ cells. The augmentation effect of HSPA6 was verified by enhancing the induction of G2/M-phase-mediated ATM-CHK2-Cdc25C-p21WAF1-Cdc2 cascade, phosphorylation of MAPK and AKT signaling, and suppression of transcription factor-associated MMP-9 regulation in response to GE in EJ cells. Overall, our novel results indicate that HSPA6 reinforces the GE-mediated inhibitory effects of proliferation, migration, and invasion of EJ cells and may provide a new approach for therapeutic treatment of malignancies. PMID:28187175

Arecoline decreases interleukin-6 production and induces apoptosis and cell cycle arrest in human basal cell carcinoma cells

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

Huang, Li-Wen; Hsieh, Bau-Shan; Cheng, Hsiao-Ling

2012-01-15

Arecoline, the most abundant areca alkaloid, has been reported to decrease interleukin-6 (IL-6) levels in epithelial cancer cells. Since IL-6 overexpression contributes to the tumorigenic potency of basal cell carcinoma (BCC), this study was designed to investigate whether arecoline altered IL-6 expression and its downstream regulation of apoptosis and the cell cycle in cultured BCC-1/KMC cells. BCC-1/KMC cells and a human keratinocyte cell line, HaCaT, were treated with arecoline at concentrations ranging from 10 to 100 μg/ml, then IL-6 production and expression of apoptosis- and cell cycle progress-related factors were examined. After 24 h exposure, arecoline inhibited BCC-1/KMC cell growthmore » and decreased IL-6 production in terms of mRNA expression and protein secretion, but had no effect on HaCaT cells. Analysis of DNA fragmentation and chromatin condensation showed that arecoline induced apoptosis of BCC-1/KMC cells in a dose-dependent manner, activated caspase-3, and decreased expression of the anti-apoptotic protein Bcl-2. In addition, arecoline induced progressive and sustained accumulation of BCC-1/KMC cells in G2/M phase as a result of reducing checkpoint Cdc2 activity by decreasing Cdc25C phosphatase levels and increasing p53 levels. Furthermore, subcutaneous injection of arecoline led to decreased BCC-1/KMC tumor growth in BALB/c mice by inducing apoptosis. This study demonstrates that arecoline has potential for preventing BCC tumorigenesis by reducing levels of the tumor cell survival factor IL-6, increasing levels of the tumor suppressor factor p53, and eliciting cell cycle arrest, followed by apoptosis. Highlights: ► Arecoline has potential to prevent against basal cell carcinoma tumorigenesis. ► It has more effectiveness on BCC as compared with a human keratinocyte cell line. ► Mechanisms involved including reducing tumor cells’ survival factor IL-6, ► Decreasing Cdc25C phosphatase, enhancing tumor suppressor factor p53, ► Eliciting G2/M phase arrest, followed by apoptosis.« less

Federal Public Health Workforce Development: An Evidence-Based Approach for Defining Competencies.

PubMed

Mumford, Karen; Young, Andrea C; Nawaz, Saira

2016-01-01

This study reports the use of exploratory factor analysis to describe essential skills and knowledge for an important segment of the domestic public health workforce-Centers for Disease Control and Prevention (CDC) project officers-using an evidence-based approach to competency development and validation. A multicomponent survey was conducted. Exploratory factor analysis was used to examine the underlying domains and relationships between competency domains and key behaviors. The Cronbach α coefficient determined the reliability of the overall scale and identified factors. All domestic (US state, tribe, local, and territorial) grantees who received funding from the CDC during fiscal year 2011 to implement nonresearch prevention or intervention programs were invited to participate in a Web-based questionnaire. A total of 34 key behaviors representing knowledge, skills, and abilities, grouped in 7 domains-communication, grant administration and management, public health applied science and knowledge, program planning and development, program management, program monitoring and improvement, and organizational consultation-were examined. There were 795 responses (58% response rate). A total of 6 factors were identified with loadings of 0.40 or more for all 34 behavioral items. The Cronbach α coefficient was 0.95 overall and ranged between 0.73 and 0.91 for the factors. This study provides empirical evidence for the construct validity of 6 competencies and 34 key behaviors important for CDC project officers and serves as an important first step to evidence-driven workforce development efforts in public health.

13 CFR 120.826 - Basic requirements for operating a CDC.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Board of the American Institute of Certified Public Accountants (AICPA). The auditor must be independent.... The audit or review must be conducted by an independent certified public accountant who: (1) Is registered or licensed to practice as a public accountant, and is in good standing, under the laws of the...

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.

Functional analyses of interacting factors involved in both pre-mRNA splicing and cell cycle progression in Saccharomyces cerevisiae.

PubMed Central

Russell, C S; Ben-Yehuda, S; Dix, I; Kupiec, M; Beggs, J D

2000-01-01

Through a genetic screen to search for factors that interact with Prp17/Cdc40p, a protein involved in both cell cycle progression and pre-mRNA splicing, we identify three novel factors, which we call Syf1p, Syf2p, and Syf3 (SYnthetic lethal with cdc Forty). Here we present evidence that all three proteins are spliceosome associated, that they associate weakly or transiently with U6 and U5 snRNAs, and that Syf1p and Syf3p (also known as Clf1p) are required for pre-mRNA splicing. In addition we show that depletion of Syf1p or Syf3p results in cell cycle arrest at the G2/M transition. Thus, like Prp17/Cdc40p, Syf1p and Syf3p are involved in two distinct cellular processes. We discuss the likelihood that Syf1p, Syf2p, and Syf3p are components of a protein complex that assembles into spliceosomes and also regulates cell cycle progression. PMID:11105756

Functional analyses of interacting factors involved in both pre-mRNA splicing and cell cycle progression in Saccharomyces cerevisiae.

PubMed

Russell, C S; Ben-Yehuda, S; Dix, I; Kupiec, M; Beggs, J D

2000-11-01

Through a genetic screen to search for factors that interact with Prp17/Cdc40p, a protein involved in both cell cycle progression and pre-mRNA splicing, we identify three novel factors, which we call Syf1p, Syf2p, and Syf3 (SYnthetic lethal with cdc Forty). Here we present evidence that all three proteins are spliceosome associated, that they associate weakly or transiently with U6 and U5 snRNAs, and that Syf1p and Syf3p (also known as Clf1p) are required for pre-mRNA splicing. In addition we show that depletion of Syf1p or Syf3p results in cell cycle arrest at the G2/M transition. Thus, like Prp17/Cdc40p, Syf1p and Syf3p are involved in two distinct cellular processes. We discuss the likelihood that Syf1p, Syf2p, and Syf3p are components of a protein complex that assembles into spliceosomes and also regulates cell cycle progression.

PTT Advisor: A CDC-supported initiative to develop a mobile clinical laboratory decision support application for the iOS platform

PubMed Central

Savel, Thomas G.; Lee, Brian A.; Ledbetter, Greg; Brown, Sara; LaValley, Dale; Taylor, Julie; Thompson, Pam

2013-01-01

Objectives: This manuscript describes the development of PTT (Partial Thromboplastin Time) Advisor, one of the first of a handful of iOS-based mobile applications to be released by the US Centers for Disease Control and Prevention (CDC). PTT Advisor has been a collaboration between two groups at CDC (Informatics R&D and Laboratory Science), and one partner team (Clinical Laboratory Integration into Healthcare Collaborative - CLIHC). The application offers clinicians a resource to quickly select the appropriate follow-up tests to evaluate patients with a prolonged PTT and a normal Prothrombin Time (PT) laboratory result. Methods: The application was designed leveraging an agile methodology, and best practices in user experience (UX) design and mobile application development. Results: As it is an open-source project, the code to PTT Advisor was made available to the public under the Apache Software License. On July 6, 2012, the free app was approved by Apple, and was published to their App Store. Conclusions: Regardless of the complexity of the mobile application, the level of effort required in the development process should not be underestimated. There are several issues that make designing the UI for a mobile phone challenging (not just small screen size): the touchscreen, users' mobile mindset (tasks need to be quick and focused), and the fact that mobile UI conventions/expectations are still being defined and refined (due to the maturity level of the field of mobile application development). PMID:23923100

PTT Advisor: A CDC-supported initiative to develop a mobile clinical laboratory decision support application for the iOS platform.

PubMed

Savel, Thomas G; Lee, Brian A; Ledbetter, Greg; Brown, Sara; Lavalley, Dale; Taylor, Julie; Thompson, Pam

2013-01-01

This manuscript describes the development of PTT (Partial Thromboplastin Time) Advisor, one of the first of a handful of iOS-based mobile applications to be released by the US Centers for Disease Control and Prevention (CDC). PTT Advisor has been a collaboration between two groups at CDC (Informatics R&D and Laboratory Science), and one partner team (Clinical Laboratory Integration into Healthcare Collaborative - CLIHC). The application offers clinicians a resource to quickly select the appropriate follow-up tests to evaluate patients with a prolonged PTT and a normal Prothrombin Time (PT) laboratory result. The application was designed leveraging an agile methodology, and best practices in user experience (UX) design and mobile application development. As it is an open-source project, the code to PTT Advisor was made available to the public under the Apache Software License. On July 6, 2012, the free app was approved by Apple, and was published to their App Store. Regardless of the complexity of the mobile application, the level of effort required in the development process should not be underestimated. There are several issues that make designing the UI for a mobile phone challenging (not just small screen size): the touchscreen, users' mobile mindset (tasks need to be quick and focused), and the fact that mobile UI conventions/expectations are still being defined and refined (due to the maturity level of the field of mobile application development).

Heat shock protein 70 promotes coxsackievirus B3 translation initiation and elongation via Akt-mTORC1 pathway depending on activation of p70S6K and Cdc2.

PubMed

Wang, Fengping; Qiu, Ye; Zhang, Huifang M; Hanson, Paul; Ye, Xin; Zhao, Guangze; Xie, Ronald; Tong, Lei; Yang, Decheng

2017-07-01

We previously demonstrated that coxsackievirus B3 (CVB3) infection upregulated heat shock protein 70 (Hsp70) and promoted CVB3 multiplication. Here, we report the underlying mechanism by which Hsp70 enhances viral RNA translation. By using an Hsp70-overexpressing cell line infected with CVB3, we found that Hsp70 enhanced CVB3 VP1 translation at two stages. First, Hsp70 induced upregulation of VP1 translation at the initiation stage via upregulation of internal ribosome entry site trans-acting factor lupus autoantigen protein and activation of eIF4E binding protein 1, a cap-dependent translation suppressor. Second, we found that Hsp70 increased CVB3 VP1 translation by enhancing translation elongation. This was mediated by the Akt-mammalian target of rapamycin complex 1 signal cascade, which led to the activation of eukaryotic elongation factor 2 via p70S6K- and cell division cycle protein 2 homolog (Cdc2)-mediated phosphorylation and inactivation of eukaryotic elongation factor 2 kinase. We also determined the position of Cdc2 in this signal pathway, indicating that Cdc2 is regulated by mammalian target of rapamycin complex 1. This signal transduction pathway was validated using a number of specific pharmacological inhibitors, short interfering RNAs (siRNAs) and a dominant negative Akt plasmid. Because Hsp70 is a central component of the cellular network of molecular chaperones enhancing viral replication, these data may provide new strategies to limit this viral infection. © 2017 John Wiley & Sons Ltd.

Stability, chromatin association and functional activity of mammalian pre-replication complex proteins during the cell cycle

PubMed Central

Okuno, Yukiko; McNairn, Adrian J.; den Elzen, Nicole; Pines, Jonathon; Gilbert, David M.

2001-01-01

We have examined the behavior of pre-replication complex (pre-RC) proteins in relation to key cell cycle transitions in Chinese Hamster Ovary (CHO) cells. ORC1, ORC4 and Cdc6 were stable (T1/2 >2 h) and associated with a chromatin-containing fraction throughout the cell cycle. Green fluorescent protein-tagged ORC1 associated with chromatin throughout mitosis in living cells and co-localized with ORC4 in metaphase spreads. Association of Mcm proteins with chromatin took place during telophase, ∼30 min after the destruction of geminin and cyclins A and B, and was coincident with the licensing of chromatin to replicate in geminin-supplemented Xenopus egg extracts. Neither Mcm recruitment nor licensing required protein synthesis throughout mitosis. Moreover, licensing could be uncoupled from origin specification in geminin-supplemented extracts; site-specific initiation within the dihydrofolate reductase locus required nuclei from cells that had passed through the origin decision point (ODP). These results demonstrate that mammalian pre-RC assembly takes place during telophase, mediated by post-translational modifications of pre-existing proteins, and is not sufficient to select specific origin sites. A subsequent, as yet undefined, step selects which pre-RCs will function as replication origins. PMID:11483529

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.

Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2017–18 Influenza Season

PubMed Central

Sokolow, Leslie Z.; Broder, Karen R.; Walter, Emmanuel B.; Bresee, Joseph S.; Fry, Alicia M.; Jernigan, Daniel B.

2017-01-01

Summary This report updates the 2016–17 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines (MMWR Recomm Rep 2016;65[No. RR-5]). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. A licensed, recommended, and age-appropriate vaccine should be used. For the 2017–18 season, quadrivalent and trivalent influenza vaccines will be available. Inactivated influenza vaccines (IIVs) will be available in trivalent (IIV3) and quadrivalent (IIV4) formulations. Recombinant influenza vaccine (RIV) will be available in trivalent (RIV3) and quadrivalent (RIV4) formulations. Live attenuated influenza vaccine (LAIV4) is not recommended for use during the 2017–18 season due to concerns about its effectiveness against (H1N1)pdm09 viruses during the 2013–14 and 2015–16 seasons. Recommendations for different vaccine types and specific populations are discussed. No preferential recommendation is made for one influenza vaccine product over another for persons for whom more than one licensed, recommended product is available. Updates to the recommendations described in this report reflect discussions during public meetings of ACIP held on October 20, 2016; February 22, 2017; and June 21, 2017. New and updated information in this report includes the following: •Vaccine viruses included in the 2017–18 U.S. trivalent influenza vaccines will be an A/Michigan/45/2015 (H1N1)pdm09–like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008–like virus (Victoria lineage). Quadrivalent influenza vaccines will contain these three viruses and an additional influenza B vaccine virus, a B/Phuket/3073/2013–like virus (Yamagata lineage). • Information on recent licensures and labelling changes is discussed, including licensure of Afluria Quadrivalent (IIV4; Seqirus, Parkville, Victoria, Australia); Flublok Quadrivalent (RIV4; Protein Sciences, Meriden, Connecticut); and expansion of the age indication for FluLaval Quadrivalent (IIV4; ID Biomedical Corporation of Quebec, Quebec City, Quebec, Canada), previously licensed for ≥3 years, to ≥6 months. • Pregnant women may receive any licensed, recommended, age-appropriate influenza vaccine. • Afluria (IIV3; Seqirus, Parkville, Victoria, Australia) may be used for persons aged ≥5 years, consistent with Food and Drug Administration–approved labeling. • FluMist Quadrivalent (LAIV4; MedImmune, Gaithersburg, Maryland) should not be used during the 2017–18 season due to concerns about its effectiveness against influenza A(H1N1)pdm09 viruses in the United States during the 2013–14 and 2015–16 influenza seasons. This report focuses on the recommendations for use of vaccines for the prevention and control of influenza during the 2017–18 season in the United States. A Background Document containing further information and a summary of these recommendations are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to licensed influenza vaccines used within Food and Drug Administration–licensed indications, including those licensed after the publication date of this report. Updates and other information are available at CDC’s influenza website (https://www.cdc.gov/flu). Vaccination and health care providers should check CDC’s influenza website periodically for additional information. PMID:28841201

Profiling MHC II immunopeptidome of blood-stage malaria reveals that cDC1 control the functionality of parasite-specific CD4 T cells.

PubMed

Draheim, Marion; Wlodarczyk, Myriam F; Crozat, Karine; Saliou, Jean-Michel; Alayi, Tchilabalo Dilezitoko; Tomavo, Stanislas; Hassan, Ali; Salvioni, Anna; Demarta-Gatsi, Claudia; Sidney, John; Sette, Alessandro; Dalod, Marc; Berry, Antoine; Silvie, Olivier; Blanchard, Nicolas

2017-11-01

In malaria, CD4 Th1 and T follicular helper (T FH ) cells are important for controlling parasite growth, but Th1 cells also contribute to immunopathology. Moreover, various regulatory CD4 T-cell subsets are critical to hamper pathology. Yet the antigen-presenting cells controlling Th functionality, as well as the antigens recognized by CD4 T cells, are largely unknown. Here, we characterize the MHC II immunopeptidome presented by DC during blood-stage malaria in mice. We establish the immunodominance hierarchy of 14 MHC II ligands derived from conserved parasite proteins. Immunodominance is shaped differently whether blood stage is preceded or not by liver stage, but the same ETRAMP-specific dominant response develops in both contexts. In naïve mice and at the onset of cerebral malaria, CD8α + dendritic cells (cDC1) are superior to other DC subsets for MHC II presentation of the ETRAMP epitope. Using in vivo depletion of cDC1, we show that cDC1 promote parasite-specific Th1 cells and inhibit the development of IL-10 + CD4 T cells. This work profiles the P. berghei blood-stage MHC II immunopeptidome, highlights the potency of cDC1 to present malaria antigens on MHC II, and reveals a major role for cDC1 in regulating malaria-specific CD4 T-cell responses. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Caenorhabditis elegans UBX cofactors for CDC-48/p97 control spermatogenesis.

PubMed

Sasagawa, Yohei; Yamanaka, Kunitoshi; Saito-Sasagawa, Yuko; Ogura, Teru

2010-12-01

UBX (ubiquitin regulatory X) domain-containing proteins act as cofactors for CDC-48/p97. CDC-48/p97 is essential for various cellular processes including retro-translocation in endoplasmic reticulum-associated degradation, homotypic membrane fusion, nuclear envelope assembly, degradation of ubiquitylated proteins, and cell cycle progression. CDC-48/p97-dependent processes are determined by differential binding of cofactors including UBX proteins, but the cellular functions of UBX proteins have not yet been elucidated, especially in multicellular organisms. Therefore, we investigated the functions of UBX family members using Caenorhabditis elegans, which expresses six UBX proteins, UBXN-1 to UBXN-6. All six UBXN proteins directly interacted with CDC-48.1 and CDC-48.2, and simultaneous knockdown of the expression of three genes, ubxn-1, ubxn-2 and ubxn-3, induced embryonic lethal and sterile phenotypes, but knockdown of either one or two did not. The sterile worms had a feminized germ-line phenotype, producing oocytes but no sperm. UBXN-1, UBXN-2 and UBXN-3 colocalized with CDC-48 in spermatocytes but not mature sperm. TRA-1A, which is a key factor in the sex determination pathway and inhibits spermatogenesis, accumulated in worms in which UBXN-1, UBXN-2 and UBXN-3 had been simultaneously knocked down. Taken together, these results suggest that UBXN-1, UBXN-2 and UBXN-3 are redundant cofactors for CDC-48/p97 and control spermatogenesis via the degradation of TRA-1A. © 2010 The Authors. Journal compilation © 2010 by the Molecular Biology Society of Japan/Blackwell Publishing Ltd.

MTBP, the partner of Treslin, contains a novel DNA-binding domain that is essential for proper initiation of DNA replication.

PubMed

Kumagai, Akiko; Dunphy, William G

2017-11-01

Treslin, which is essential for incorporation of Cdc45 into the replicative helicase, possesses a partner called MTBP (Mdm2-binding protein). We have analyzed Xenopus and human MTBP to assess its role in DNA replication. Depletion of MTBP from Xenopus egg extracts, which also removes Treslin, abolishes DNA replication. These extracts be can rescued with recombinant Treslin-MTBP but not Treslin or MTBP alone. Thus, Treslin-MTBP is collectively necessary for replication. We have identified a C-terminal region of MTBP (the CTM domain) that binds efficiently to both double-stranded DNA and G-quadruplex (G4) DNA. This domain also exhibits homology with budding yeast Sld7. Mutants of MTBP without a functional CTM domain are defective for DNA replication in Xenopus egg extracts. These mutants display an impaired localization to chromatin and the inability to support loading of Cdc45. Human cells harboring such a mutant also display severe S-phase defects. Thus, the CTM domain of MTBP plays a critical role in localizing Treslin-MTBP to the replication apparatus for initiation. © 2017 Kumagai and Dunphy. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Rapid HIV antibody testing among men who have sex with men who visited a gay bathhouse in Hangzhou, China: a cross-sectional study.

PubMed

Ma, Qiaoqin; Xia, Shichang; Pan, Xiaohong; Cai, Gaofeng; Zhou, Xin; Wang, Hui; Peng, Zhihang

2015-09-07

To understand the prevalence and correlates of rapid HIV antibody testing (RHT) among men who have sex with men (MSM) clients of gay bathhouses. Cross-sectional questionnaire survey. This study was conducted in a gay bathhouse in Hangzhou, China. 354 MSM were validly recruited from October to December 2012. Inclusion criteria were (1) men who visited the gay bathhouse, (2) men who had engaged in sex with men during the previous 6 months, (3) first-time participants in this survey and (4) men who were HIV-negative if already tested. Sociodemographic measures included factors related to sexual behaviour and HIV risk perception, and the scales of HIV-related knowledge and behavioural intervention that each participant received. Of the 354 participants, 222 (62.7%) were rapid tested during the previous 6 months; of them, 66.2% were tested at the Centers for Disease Prevention and Control (CDC), and 46.8% at gay venues. The following factors were independently associated with rapid testing within the previous 6 months: sexual initiation at 20-29 years of age, ever having undergone standard testing, ever having seen a sexually transmitted disease doctor, consistent use of condom during the past 6 months, familiarity with RHT and perception of possible HIV infection. Publicity of RHT and risk education for HIV infection are necessary to promote RHT among MSM who visit gay bathhouses. The characteristics of sexual behaviours among those who do and do not undergo RHT should be taken into consideration while promoting the service in this group. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Weight, height and body mass index of children and adolescents living at moderate altitude in Colombia.

PubMed

Díaz Bonilla, Edilberto; Torres Galvis, Claudia L; Gómez Campos, Rossana; de Arruda, Miguel; Pacheco Carrillo, Jaime; Cossio Bolaños, Marco

2018-04-01

There is increasing concern over the study of physical growth in different regions of the world, although altitude is not considered an adjustment factor. Compare physical growth variables and body mass index (BMI) patterns with the Centers for Disease Control and Prevention (CDC) 2012 reference data and develop percentiles for children and adolescents. School children living at moderate altitude in Bogotá (Colombia) were studied. Their weight and height were evaluated and their BMI was calculated. Anthropometric variables were compared against reference data of the CDC-2012, Brazil, Peru and Argentina. Curves were constructed using the least mean square (LMS) method. A total of 2241 school children (1159 girls) aged 6.0 to 17.9 years were included. There were no significant differences in weight and BMI in 6 to 8 year-olds relative to CDC-2012 reference data; in 9 to 17 year-old children, however, this sample evidenced lower values in terms of weight and BMI as compared to those of the CDC-2012. As far as height is concerned, in both sexes, values were lower than those of the CDC-2012. Comparisons against the regional curves of Argentina, Peru and Brazil yielded relatively similar results, with the exception of girls' BMI, as 13 to 17 year-old girls exhibited lower values. Growth variables of school children were lower relative to the CDC-2012 reference data. There were slight discrepancies in physical growth and BMI in relation to the curves of Argentina, Peru and Brazil. Curves were constructed to evaluate growth in school children living at moderate altitude in Colombia. Sociedad Argentina de Pediatría.

Enhanced CDC of B cell chronic lymphocytic leukemia cells mediated by rituximab combined with a novel anti-complement factor H antibody.

PubMed

Winkler, Mark T; Bushey, Ryan T; Gottlin, Elizabeth B; Campa, Michael J; Guadalupe, Eross S; Volkheimer, Alicia D; Weinberg, J Brice; Patz, Edward F

2017-01-01

Rituximab therapy for B cell chronic lymphocytic leukemia (B-CLL) has met with mixed success. Among several factors to which resistance can be attributed is failure to activate complement dependent cytotoxicity (CDC) due to protective complement regulatory proteins, including the soluble regulator complement factor H (CFH). We hypothesized that rituximab killing of non-responsive B-CLL cells could be augmented by a novel human monoclonal antibody against CFH. The B cells from 11 patients with B-CLL were tested ex vivo in CDC assays with combinations of CFH monoclonal antibody, rituximab, and a negative control antibody. CDC of rituximab non-responsive malignant B cells from CLL patients could in some cases be augmented by the CFH monoclonal antibody. Antibody-mediated cytotoxicity of cells was dependent upon functional complement. In one case where B-CLL cells were refractory to CDC by the combination of rituximab plus CFH monoclonal antibody, additionally neutralizing the membrane complement regulatory protein CD59 allowed CDC to occur. Inhibiting CDC regulatory proteins such as CFH holds promise for overcoming resistance to rituximab therapy in B-CLL.

SIRT6 inhibits colorectal cancer stem cell proliferation by targeting CDC25A

PubMed Central

Liu, Wenguang; Wu, Manwu; Du, Hechun; Shi, Xiaoliang; Zhang, Tao; Li, Jie

2018-01-01

Silent information regulator 6 (SIRT6) is broadly considered as a tumor suppressor due to its function in the suppression of oncogene expression. However, the role of SIRT6 in colorectal cancer stem cells (CSCs) remains uncharacterized. In the present study, it was demonstrated that SIRT6 expression was reduced in colorectal CSCs. Overexpression of SIRT6 in colorectal CSCs did not induce cell apoptosis. However, SIRT6 significantly inhibited cell proliferation, colony formation and induced G0/G1 phase arrest in colorectal CSCs. In addition, SIRT6 repressed the expression of cell division cycle 25A (CDC25A), an oncogenic phosphatase. Chromatin immunoprecipitation experiments indicated that SIRT6 directly bound to the CDC25A promoter and decreased the acetylation level of histone H3 lysine 9. Altogether, these data indicated that SIRT6 inhibits colorectal cancer stem cell proliferation by targeting CDC25A. PMID:29552180

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.

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

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.

The design and evaluation of a system for improved surveillance and prevention programmes in resource-limited settings using a hospital-based burn injury questionnaire.

PubMed

Peck, Michael; Falk, Henry; Meddings, David; Sugerman, David; Mehta, Sumi; Sage, Michael

2016-04-01

Limited and fragmented data collection systems exist for burn injury. A global registry may lead to better injury estimates and identify risk factors. A collaborative effort involving the WHO, the Global Alliance for Clean Cookstoves, the CDC and the International Society for Burn Injuries was undertaken to simplify and standardise inpatient burn data collection. An expert panel of epidemiologists and burn care practitioners advised on the development of a new Global Burn Registry (GBR) form and online data entry system that can be expected to be used in resource-abundant or resource-limited settings. International burn organisations, the CDC and the WHO solicited burn centre participation to pilot test the GBR system. The WHO and the CDC led a webinar tutorial for system implementation. During an 8-month period, 52 hospitals in 30 countries enrolled in the pilot and were provided the GBR instrument, guidance and a data visualisation tool. Evaluations were received from 29 hospitals (56%). Median time to upload completed forms was <10 min; physicians most commonly entered data (64%), followed by nurses (25%); layout, clarity, accuracy and relevance were all rated high; and a vast majority (85%) considered the GBR 'highly valuable' for prioritising, developing and monitoring burn prevention programmes. The GBR was shown to be simple, flexible and acceptable to users. Enhanced regional and global understanding of burn epidemiology may help prioritise the selection, development and testing of primary prevention interventions for burns in resource-limited settings. 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/

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

Redefining Myeloid Cell Subsets in Murine Spleen

PubMed Central

Hey, Ying-Ying; Tan, Jonathan K. H.; O’Neill, Helen C.

2016-01-01

Spleen is known to contain multiple dendritic and myeloid cell subsets, distinguishable on the basis of phenotype, function and anatomical location. As a result of recent intensive flow cytometric analyses, splenic dendritic cell (DC) subsets are now better characterized than other myeloid subsets. In order to identify and fully characterize a novel splenic subset termed “L-DC” in relation to other myeloid cells, it was necessary to investigate myeloid subsets in more detail. In terms of cell surface phenotype, L-DC were initially characterized as a CD11bhiCD11cloMHCII−Ly6C−Ly6G− subset in murine spleen. Their expression of CD43, lack of MHCII, and a low level of CD11c was shown to best differentiate L-DC by phenotype from conventional DC subsets. A complete analysis of all subsets in spleen led to the classification of CD11bhiCD11cloMHCII−Ly6CloLy6G− cells as monocytes expressing CX3CR1, CD43 and CD115. Siglec-F expression was used to identify a specific eosinophil population, distinguishable from both Ly6Clo and Ly6Chi monocytes, and other DC subsets. L-DC were characterized as a clear subset of CD11bhiCD11cloMHCII−Ly6C−Ly6G− cells, which are CD43+, Siglec-F− and CD115−. Changes in the prevalence of L-DC compared to other subsets in spleens of mutant mice confirmed the phenotypic distinction between L-DC, cDC and monocyte subsets. L-DC development in vivo was shown to occur independently of the BATF3 transcription factor that regulates cDC development, and also independently of the FLT3L and GM-CSF growth factors which drive cDC and monocyte development, so distinguishing L-DC from these commonly defined cell types. PMID:26793192

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

The signaling pathway of Campylobacter jejuni-induced Cdc42 activation: Role of fibronectin, integrin beta1, tyrosine kinases and guanine exchange factor Vav2

PubMed Central

2011-01-01

Background Host cell invasion by the foodborne pathogen Campylobacter jejuni is considered as one of the primary reasons of gut tissue damage, however, mechanisms and key factors involved in this process are widely unclear. It was reported that small Rho GTPases, including Cdc42, are activated and play a role during invasion, but the involved signaling cascades remained unknown. Here we utilised knockout cell lines derived from fibronectin-/-, integrin-beta1-/-, focal adhesion kinase (FAK)-/- and Src/Yes/Fyn-/- deficient mice, and wild-type control cells, to investigate C. jejuni-induced mechanisms leading to Cdc42 activation and bacterial uptake. Results Using high-resolution scanning electron microscopy, GTPase pulldowns, G-Lisa and gentamicin protection assays we found that each studied host factor is necessary for induction of Cdc42-GTP and efficient invasion. Interestingly, filopodia formation and associated membrane dynamics linked to invasion were only seen during infection of wild-type but not in knockout cells. Infection of cells stably expressing integrin-beta1 variants with well-known defects in fibronectin fibril formation or FAK signaling also exhibited severe deficiencies in Cdc42 activation and bacterial invasion. We further demonstrated that infection of wild-type cells induces increasing amounts of phosphorylated FAK and growth factor receptors (EGFR and PDGFR) during the course of infection, correlating with accumulating Cdc42-GTP levels and C. jejuni invasion over time. In studies using pharmacological inhibitors, silencing RNA (siRNA) and dominant-negative expression constructs, EGFR, PDGFR and PI3-kinase appeared to represent other crucial components upstream of Cdc42 and invasion. siRNA and the use of Vav1/2-/- knockout cells further showed that the guanine exchange factor Vav2 is required for Cdc42 activation and maximal bacterial invasion. Overexpression of certain mutant constructs indicated that Vav2 is a linker molecule between Cdc42 and activated EGFR/PDGFR/PI3-kinase. Using C. jejuni mutant strains we further demonstrated that the fibronectin-binding protein CadF and intact flagella are involved in Cdc42-GTP induction, indicating that the bacteria may directly target the fibronectin/integrin complex for inducing signaling leading to its host cell entry. Conclusion Collectively, our findings led us propose that C. jejuni infection triggers a novel fibronectin→integrin-beta1→FAK/Src→EGFR/PDGFR→PI3-kinase→Vav2 signaling cascade, which plays a crucial role for Cdc42 GTPase activity associated with filopodia formation and enhances bacterial invasion. PMID:22204307

Prevention and control of haemophilus influenzae type b disease: recommendations of the advisory committee on immunization practices (ACIP).

PubMed

Briere, Elizabeth C; Rubin, Lorry; Moro, Pedro L; Cohn, Amanda; Clark, Thomas; Messonnier, Nancy

2014-02-28

This report compiles and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) regarding prevention and control of Haemophilus influenzae type b (Hib) disease in the United States. As a comprehensive summary of previously published recommendations, this report does not contain any new recommendations; it is intended for use by clinicians, public health officials, vaccination providers, and immunization program personnel as a resource. ACIP recommends routine vaccination with a licensed conjugate Hib vaccine for infants aged 2 through 6 months (2 or 3 doses, depending on vaccine product) with a booster dose at age 12 through 15 months. ACIP also recommends vaccination for certain persons at increased risk for Hib disease (i.e., persons who have early component complement deficiencies, immunoglobulin deficiency, anatomic or functional asplenia, or HIV infection; recipients of hematopoietic stem cell transplant; and recipients of chemotherapy or radiation therapy for malignant neoplasms). This report summarizes current information on Hib epidemiology in the United States and describes Hib vaccines licensed for use in the United States. Guidelines for antimicrobial chemoprophylaxis of contacts of persons with Hib disease also are provided.

MCM Paradox: Abundance of Eukaryotic Replicative Helicases and Genomic Integrity.

PubMed

Das, Mitali; Singh, Sunita; Pradhan, Satyajit; Narayan, Gopeshwar

2014-01-01

As a crucial component of DNA replication licensing system, minichromosome maintenance (MCM) 2-7 complex acts as the eukaryotic DNA replicative helicase. The six related MCM proteins form a heterohexamer and bind with ORC, CDC6, and Cdt1 to form the prereplication complex. Although the MCMs are well known as replicative helicases, their overabundance and distribution patterns on chromatin present a paradox called the "MCM paradox." Several approaches had been taken to solve the MCM paradox and describe the purpose of excess MCMs distributed beyond the replication origins. Alternative functions of these MCMs rather than a helicase had also been proposed. This review focuses on several models and concepts generated to solve the MCM paradox coinciding with their helicase function and provides insight into the concept that excess MCMs are meant for licensing dormant origins as a backup during replication stress. Finally, we extend our view towards the effect of alteration of MCM level. Though an excess MCM constituent is needed for normal cells to withstand stress, there must be a delineation of the threshold level in normal and malignant cells. This review also outlooks the future prospects to better understand the MCM biology.

MCM Paradox: Abundance of Eukaryotic Replicative Helicases and Genomic Integrity

PubMed Central

Das, Mitali; Singh, Sunita; Pradhan, Satyajit

2014-01-01

As a crucial component of DNA replication licensing system, minichromosome maintenance (MCM) 2–7 complex acts as the eukaryotic DNA replicative helicase. The six related MCM proteins form a heterohexamer and bind with ORC, CDC6, and Cdt1 to form the prereplication complex. Although the MCMs are well known as replicative helicases, their overabundance and distribution patterns on chromatin present a paradox called the “MCM paradox.” Several approaches had been taken to solve the MCM paradox and describe the purpose of excess MCMs distributed beyond the replication origins. Alternative functions of these MCMs rather than a helicase had also been proposed. This review focuses on several models and concepts generated to solve the MCM paradox coinciding with their helicase function and provides insight into the concept that excess MCMs are meant for licensing dormant origins as a backup during replication stress. Finally, we extend our view towards the effect of alteration of MCM level. Though an excess MCM constituent is needed for normal cells to withstand stress, there must be a delineation of the threshold level in normal and malignant cells. This review also outlooks the future prospects to better understand the MCM biology. PMID:25386362

Novel Carbon Films for Next Generation Rotating Equipment Applications

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

Michael McNallan; Ali Erdemir; Yury Gogotsi

2006-02-20

This report describes the results of research performed on a new generation of low friction, wear resistant carbon coatings for seals and bearings in high speed rotating equipment. The low friction coatings, Near Frictionless Carbon (NFC), a high hydrogen content diamondlike carbon, and Carbide Derived Carbon (CDC), a conversion coating produced on the surfaces of metal carbides by halogenation, can be applied together or separately to improve the performance of seals and bearings, with benefits to energy efficiency and environmental protection. Because hard carbide ceramics, such as silicon carbide, are widely used in the seals industry, this coating is particularlymore » attractive as a low cost method to improve performance. The technology of CDC has been licensed to an Illinois company, Carbide Derivative Technologies, Inc. (CDTI) to implement the commercialization of this material.« less

Comparison of NCHS, CDC, and WHO curves in children with cardiovascular risk.

PubMed

Oliveira, Grasiela Junges de; Barbiero, Sandra Mari; Cesa, Claudia Ciceri; Pellanda, Lucia Campos

2013-01-01

The study aimed to compare the prevalence of overweight and obesity according to three growth curves, created by the World Health Organization (WHO/2006), by the National Center for Health Statistics (NCHS/1977), and by the Centers for Disease Control and Prevention (CDC/2000) in children with cardiovascular risk factors. Data from 118 children and adolescents, aged between 2 and 19 years, treated between the years 2001 to 2009 at the Pediatric Preventive Cardiology Outpatient Clinic of the Instituto de Cardiologia de Porto Alegre were evaluated. The variables analyzed were: weight, height, age, and gender. Variables were classified according to the following criteria: weight/age, height/age, and body mass index (BMI). The cutoff points used were obtained from the three growth curves: WHO/2006, NCHS/1977, and CDC/2000. Regarding the criterion weight/age by the NCHS curve, 18% of the children were classified as having normal weight, and 82% had excess weight; by the CDC curve, 28% had normal and 72% had excess weight; by the WHO curve, 16.0% had normal weight and 84% had excess weight. According to the BMI, 0.8% of the population was underweight. According to the CDC and WHO curves, 7.6% and 6.8% had normal weight; 26.3% and 11.9% were overweight; and 65.3% and 80.5% were obese, respectively. Regarding the height/age criterion, there was no significant difference between the references and, on average, 98.3% of the population showed adequate height for age. The new WHO curves are more sensitive to identify obesity in a population at risk, which has important implications for preventive and therapeutic management. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

Small GTPase CDC-42 promotes apoptotic cell corpse clearance in response to PAT-2 and CED-1 in C. elegans

PubMed Central

Neukomm, L J; Zeng, S; Frei, A P; Huegli, P A; Hengartner, M O

2014-01-01

The rapid clearance of dying cells is important for the well-being of multicellular organisms. In C. elegans, cell corpse removal is mainly mediated by three parallel engulfment signaling cascades. These pathways include two small GTPases, MIG-2/RhoG and CED-10/Rac1. Here we present the identification and characterization of CDC-42 as a third GTPase involved in the regulation of cell corpse clearance. Genetic analyses performed by both loss of cdc-42 function and cdc-42 overexpression place cdc-42 in parallel to the ced-2/5/12 signaling module, in parallel to or upstream of the ced-10 module, and downstream of the ced-1/6/7 module. CDC-42 accumulates in engulfing cells at membranes surrounding apoptotic corpses. The formation of such halos depends on the integrins PAT-2/PAT-3, UNC-112 and the GEF protein UIG-1, but not on the canonical ced-1/6/7 or ced-2/5/12 signaling modules. Together, our results suggest that the small GTPase CDC-42 regulates apoptotic cell engulfment possibly upstream of the canonical Rac GTPase CED-10, by polarizing the engulfing cell toward the apoptotic corpse in response to integrin signaling and ced-1/6/7 signaling in C. elegans. PMID:24632947

Small GTPase CDC-42 promotes apoptotic cell corpse clearance in response to PAT-2 and CED-1 in C. elegans.

PubMed

Neukomm, L J; Zeng, S; Frei, A P; Huegli, P A; Hengartner, M O

2014-06-01

The rapid clearance of dying cells is important for the well-being of multicellular organisms. In C. elegans, cell corpse removal is mainly mediated by three parallel engulfment signaling cascades. These pathways include two small GTPases, MIG-2/RhoG and CED-10/Rac1. Here we present the identification and characterization of CDC-42 as a third GTPase involved in the regulation of cell corpse clearance. Genetic analyses performed by both loss of cdc-42 function and cdc-42 overexpression place cdc-42 in parallel to the ced-2/5/12 signaling module, in parallel to or upstream of the ced-10 module, and downstream of the ced-1/6/7 module. CDC-42 accumulates in engulfing cells at membranes surrounding apoptotic corpses. The formation of such halos depends on the integrins PAT-2/PAT-3, UNC-112 and the GEF protein UIG-1, but not on the canonical ced-1/6/7 or ced-2/5/12 signaling modules. Together, our results suggest that the small GTPase CDC-42 regulates apoptotic cell engulfment possibly upstream of the canonical Rac GTPase CED-10, by polarizing the engulfing cell toward the apoptotic corpse in response to integrin signaling and ced-1/6/7 signaling in C. elegans.

PAR-2, LGL-1 and the CDC-42 GAP CHIN-1 act in distinct pathways to maintain polarity in the C. elegans embryo

PubMed Central

Beatty, Alexander; Morton, Diane G.; Kemphues, Kenneth

2013-01-01

In the one-cell C. elegans embryo, polarity is maintained by mutual antagonism between the anterior cortical proteins PAR-3, PKC-3, PAR-6 and CDC-42, and the posterior cortical proteins PAR-2 and LGL-1 on the posterior cortex. The mechanisms by which these proteins interact to maintain polarity are incompletely understood. In this study, we investigate the interplay among PAR-2, LGL-1, myosin, the anterior PAR proteins and CDC-42. We find that PAR-2 and LGL-1 affect cortical myosin accumulation by different mechanisms. LGL-1 does not directly antagonize the accumulation of cortical myosin and instead plays a role in regulating PAR-6 levels. By contrast, PAR-2 likely has separate roles in regulating cortical myosin accumulation and preventing the expansion of the anterior cortical domain. We also provide evidence that asymmetry of active CDC-42 can be maintained independently of LGL-1 and PAR-2 by a redundant pathway that includes the CDC-42 GAP CHIN-1. Finally, we show that, in addition to its primary role in regulating the size of the anterior cortical domain via its binding to PAR-6, CDC-42 has a secondary role in regulating cortical myosin that is not dependent on PAR-6. PMID:23536568

PAR-2, LGL-1 and the CDC-42 GAP CHIN-1 act in distinct pathways to maintain polarity in the C. elegans embryo.

PubMed

Beatty, Alexander; Morton, Diane G; Kemphues, Kenneth

2013-05-01

In the one-cell C. elegans embryo, polarity is maintained by mutual antagonism between the anterior cortical proteins PAR-3, PKC-3, PAR-6 and CDC-42, and the posterior cortical proteins PAR-2 and LGL-1 on the posterior cortex. The mechanisms by which these proteins interact to maintain polarity are incompletely understood. In this study, we investigate the interplay among PAR-2, LGL-1, myosin, the anterior PAR proteins and CDC-42. We find that PAR-2 and LGL-1 affect cortical myosin accumulation by different mechanisms. LGL-1 does not directly antagonize the accumulation of cortical myosin and instead plays a role in regulating PAR-6 levels. By contrast, PAR-2 likely has separate roles in regulating cortical myosin accumulation and preventing the expansion of the anterior cortical domain. We also provide evidence that asymmetry of active CDC-42 can be maintained independently of LGL-1 and PAR-2 by a redundant pathway that includes the CDC-42 GAP CHIN-1. Finally, we show that, in addition to its primary role in regulating the size of the anterior cortical domain via its binding to PAR-6, CDC-42 has a secondary role in regulating cortical myosin that is not dependent on PAR-6.

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.

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.

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

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.

ORC1/CDC6 and MCM7 distinct associate with chromatin through Trypanosoma cruzi life cycle.

PubMed

Calderano, Simone; Godoy, Patricia; Soares, Daiane; Sant'Anna, Osvaldo Augusto; Schenkman, Sergio; Elias, M Carolina

2014-02-01

Trypanosoma cruzi alternates between replicative and non-replicative stages. We analyzed the expression of components of the pre-replication machinery TcORC1/CDC6 and TcMCM7 and their interaction with DNA in all T. cruzi stages. TcORC1/CDC6 remains in the nuclear space during all stages of the life cycle and interacts with DNA in the replicative stages; however, it does not bind to DNA in the non-replicative forms. Moreover, TcMCM7 is not present in the non-replicative stages. These data suggest that the lacking of DNA replication during the T. cruzi life cycle may be a consequence of the blocking of TcORC1/CDC6-DNA interaction and of the down regulation of the TcMCM7 expression. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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.

Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009.

PubMed

Wright, Jennifer Gordon; Quinn, Conrad P; Shadomy, Sean; Messonnier, Nancy

2010-07-23

These recommendations from the Advisory Committee on Immunization Practices (ACIP) update the previous recommendations for anthrax vaccine adsorbed (AVA) (CDC. Use of anthrax vaccine in the United States: Recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2000;49:1-20; CDC. Use of anthrax vaccine in response to terrorism: supplemental recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2002;51:1024-6) and reflect the status of anthrax vaccine supplies in the United States. This statement 1) provides updated information on anthrax epidemiology; 2) summarizes the evidence regarding the effectiveness and efficacy, immunogenicity, and safety of AVA; 3) provides recommendations for pre-event and preexposure use of AVA; and 4) provides recommendations for postexposure use of AVA. In certain instances, recommendations that did not change were clarified. No new licensed anthrax vaccines are presented. Substantial changes to these recommendations include the following: 1) reducing the number of doses required to complete the pre-event and preexposure primary series from 6 doses to 5 doses, 2) recommending intramuscular rather than subcutaneous AVA administration for preexposure use, 3) recommending AVA as a component of postexposure prophylaxis in pregnant women exposed to aerosolized Bacillus anthracis spores, 4) providing guidance regarding preexposure vaccination of emergency and other responder organizations under the direction of an occupational health program, and 5) recommending 60 days of antimicrobial prophylaxis in conjunction with 3 doses of AVA for optimal protection of previously unvaccinated persons after exposure to aerosolized B. anthracis spores.

miR-133 is a key negative regulator of CDC42-PAK pathway in gastric cancer.

PubMed

Cheng, Zhenguo; Liu, Funan; Wang, Guanqiao; Li, Yanshu; Zhang, Hongyan; Li, Feng

2014-12-01

Cell division cycle 42 (CDC42), an important member of the Ras homolog (Rho) family, plays a key role in regulating multiple cellular processes such as cell cycle progression, migration, cell cytoskeleton organization, cell fate determination and differentiation. Among the downstream effectors of CDC42, P21-activated kinases (PAKs) obtain the most attention. Although a large body of evidence indicates that CDC42/PAKs pathway plays important role in tumor growth, invasion and metastasis, the mechanism of their negative regulation remains unclear. Here, we identified CDC42, a PAKs activating factor, was a target of miR-133. Ectopic overexpression of miRNAs not only downregulated CDC42 expression and PAKs activation, but also inhibited cancer cell proliferation and migration. We also found that miR-133 was down-regulated in 180 pairs gastric cancer tissues. miR-133 expression was negatively associated with tumor size, invasion depth and peripheral organ metastasis. Besides, dysfunction of miR-133 was an independent prognosis factor for overall survival. Our findings could provide new insights into the molecular mechanisms of gastric carcinogenesis, and may help facilitating development of CDC42/PAK-based therapies for human cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

13 CFR 120.812 - Probationary period for newly certified CDCs.

Code of Federal Regulations, 2010 CFR

2010-01-01

... its recommendation to the D/FA, who will make the final decision. SBA will determine permanent CDC... discretion. The CDC's Risk Rating, among other factors, will be considered in determining satisfactory SBA performance. Other factors may include, but are not limited to, on-site review/examination assessments...

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.

Molecular determinants of origin discrimination by Orc1 initiators in archaea.

PubMed

Dueber, Erin C; Costa, Alessandro; Corn, Jacob E; Bell, Stephen D; Berger, James M

2011-05-01

Unlike bacteria, many eukaryotes initiate DNA replication from genomic sites that lack apparent sequence conservation. These loci are identified and bound by the origin recognition complex (ORC), and subsequently activated by a cascade of events that includes recruitment of an additional factor, Cdc6. Archaeal organisms generally possess one or more Orc1/Cdc6 homologs, belonging to the Initiator clade of ATPases associated with various cellular activities (AAA(+)) superfamily; however, these proteins recognize specific sequences within replication origins. Atomic resolution studies have shown that archaeal Orc1 proteins contact double-stranded DNA through an N-terminal AAA(+) domain and a C-terminal winged-helix domain (WHD), but use remarkably few base-specific contacts. To investigate the biochemical effects of these associations, we mutated the DNA-interacting elements of the Orc1-1 and Orc1-3 paralogs from the archaeon Sulfolobus solfataricus, and tested their effect on origin binding and deformation. We find that the AAA(+) domain has an unpredicted role in controlling the sequence selectivity of DNA binding, despite an absence of base-specific contacts to this region. Our results show that both the WHD and ATPase region influence origin recognition by Orc1/Cdc6, and suggest that not only DNA sequence, but also local DNA structure help define archaeal initiator binding sites. © The Author(s) 2011. Published by Oxford University Press.

Insights into the Initiation of Eukaryotic DNA Replication.

PubMed

Bruck, Irina; Perez-Arnaiz, Patricia; Colbert, Max K; Kaplan, Daniel L

2015-01-01

The initiation of DNA replication is a highly regulated event in eukaryotic cells to ensure that the entire genome is copied once and only once during S phase. The primary target of cellular regulation of eukaryotic DNA replication initiation is the assembly and activation of the replication fork helicase, the 11-subunit assembly that unwinds DNA at a replication fork. The replication fork helicase, called CMG for Cdc45-Mcm2-7, and GINS, assembles in S phase from the constituent Cdc45, Mcm2-7, and GINS proteins. The assembly and activation of the CMG replication fork helicase during S phase is governed by 2 S-phase specific kinases, CDK and DDK. CDK stimulates the interaction between Sld2, Sld3, and Dpb11, 3 initiation factors that are each required for the initiation of DNA replication. DDK, on the other hand, phosphorylates the Mcm2, Mcm4, and Mcm6 subunits of the Mcm2-7 complex. Sld3 recruits Cdc45 to Mcm2-7 in a manner that depends on DDK, and recent work suggests that Sld3 binds directly to Mcm2-7 and also to single-stranded DNA. Furthermore, recent work demonstrates that Sld3 and its human homolog Treslin substantially stimulate DDK phosphorylation of Mcm2. These data suggest that the initiation factor Sld3/Treslin coordinates the assembly and activation of the eukaryotic replication fork helicase by recruiting Cdc45 to Mcm2-7, stimulating DDK phosphorylation of Mcm2, and binding directly to single-stranded DNA as the origin is melted.

CDC/1000: a Control Data Corporation remote batch terminal emulator for Hewlett-Packard minicomputers

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

Berg, D.E.

1981-02-01

The Control Data Corporation Type 200 User Terminal utilizes a unique communications protocol to provide users with batch mode remote terminal access to Control Data computers. CDC/1000 is a software subsystem that implements this protocol on Hewlett-Packard minicomputers running the Real Time Executive III, IV, or IVB operating systems. This report provides brief descriptions of the various software modules comprising CDC/1000, and contains detailed instructions for integrating CDC/1000 into the Hewlett Packard operating system and for operating UTERM, the user interface program for CDC/1000. 6 figures.

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.

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

Healthy Exercise Habits Are Associated With Lower Risk of Burnout and Higher Quality of Life Among U.S. Medical Students.

PubMed

Dyrbye, Liselotte N; Satele, Daniel; Shanafelt, Tait D

2017-07-01

Although burnout and low quality of life (QOL) are common among medical students, little remains known about personal fitness habits of medical students that may promote well-being. In 2012 the authors conducted a cross-sectional study of U.S. medical students to explore relationships between burnout, QOL, and compliance with Centers for Disease Control and Prevention (CDC) exercise recommendations. Wilcoxon-Mann-Whitney tests, Fisher exact tests, and multivariate logistic regression were performed. Among approximately 12,500 medical students invited to participate, 4,402 (35.2%) completed surveys. Most (2,738/4,367; 62.7%) engaged in aerobic exercise in accordance with CDC recommendations, while fewer (1,685/4,376; 38.5%) adhered to muscle strengthening recommendations. Burnout prevalence was lower among students who exercised aerobically consistent with CDC recommendations compared with those who exercised less (53.1% vs. 60.8%, P < .0001). Similarly, rates of burnout were also lower among students who strength trained consistent with CDC recommendations (51.8% vs. 58.6%, P < .0001). Overall QOL scores were higher for medical students adhering to CDC recommendations for aerobic exercise (7.2 vs. 6.6, P < .0001), strength training (7.2 vs. 6.8, P < .0001), or both aerobic and strength training (8.0 vs. 7.0, P < .0001). Compliance with CDC exercise guidelines remained independently associated with lower risk of burnout and higher QOL on multivariate analysis controlling for age, sex, relationship status, children, and year in school. Students whose aerobic exercise and/or strength training habits are consistent with CDC guidelines appear less likely to experience burnout and to have higher QOL.

Heart Disease Risk Factors

MedlinePlus

... commit" type="submit" value="Submit" /> Related CDC Web Sites Division for Heart Disease and Stroke Prevention ... commit" type="submit" value="Submit" /> Related CDC Web Sites Division for Heart Disease and Stroke Prevention ...

42 CFR 73.6 - Exemptions for overlap select agents and toxins.

Code of Federal Regulations, 2011 CFR

2011-10-01

... reported to CDC or APHIS and to other appropriate authorities when required by Federal, State, or local law... submission of APHIS/CDC Form 4 within seven calendar days after identification. (ii) For all other overlap select agents or toxins, APHIS/CDC Form 4 must be submitted within seven calendar days after...

42 CFR 73.6 - Exemptions for overlap select agents and toxins.

Code of Federal Regulations, 2010 CFR

2010-10-01

... reported to CDC or APHIS and to other appropriate authorities when required by Federal, State, or local law... submission of APHIS/CDC Form 4 within seven calendar days after identification. (ii) For all other overlap select agents or toxins, APHIS/CDC Form 4 must be submitted within seven calendar days after...

42 CFR 73.6 - Exemptions for overlap select agents and toxins.

Code of Federal Regulations, 2012 CFR

2012-10-01

... reported to CDC or APHIS and to other appropriate authorities when required by Federal, State, or local law... submission of APHIS/CDC Form 4 within seven calendar days after identification. (ii) For all other overlap select agents or toxins, APHIS/CDC Form 4 must be submitted within seven calendar days after...

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.

Rescue of p53 function by small-molecule RITA in cervical carcinoma by blocking E6-mediated degradation.

PubMed

Zhao, Carolyn Ying; Szekely, Laszlo; Bao, Wenjie; Selivanova, Galina

2010-04-15

Proteasomal degradation of p53 by human papilloma virus (HPV) E6 oncoprotein plays a pivotal role in the survival of cervical carcinoma cells. Abrogation of HPV-E6-dependent p53 destruction can therefore be a good strategy to combat cervical carcinomas. Here, we show that a small-molecule reactivation of p53 and induction of tumor cell apoptosis (RITA) is able to induce the accumulation of p53 and rescue its tumor suppressor function in cells containing high-risk HPV16 and HPV18 by inhibiting HPV-E6-mediated proteasomal degradation. RITA blocks p53 ubiquitination by preventing p53 interaction with E6-associated protein, required for HPV-E6-mediated degradation. RITA activates the transcription of proapoptotic p53 targets Noxa, PUMA, and BAX, and repressed the expression of pro-proliferative factors CyclinB1, CDC2, and CDC25C, resulting in p53-dependent apoptosis and cell cycle arrest. Importantly, RITA showed substantial suppression of cervical carcinoma xenografts in vivo. These results provide a proof of principle for the treatment of cervical cancer in a p53-dependent manner by using small molecules that target p53. (c)2010 AACR.

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.

Overweight and Underweight Prevalence Trends in Children from Romania - Pooled Analysis of Cross-Sectional Studies between 2006 and 2015

PubMed Central

Chirita-Emandi, Adela; Barbu, Carmen Gabriela; Cinteza, Elena Eliza; Chesaru, Bianca Ioana; Gafencu, Mihai; Mocanu, Veronica; Pascanu, Ionela M.; Tatar, Simona Alexandra; Balgradean, Mihaela; Dobre, Michaela; Fica, Simona Vasilica; Ichim, Gabriela Edita; Pop, Raluca; Puiu, Maria

2016-01-01

Aim High-quality national representative data on obesity in Romanian children are needed to shape public health policies. To provide a unified data landscape on national prevalence, trends and other factors associated with underweight, overweight, and obesity in Romanian children aged 6-19 years, across the last decade (2006-2015). Methods Using a common protocol, we selected published and unpublished studies that measured Romanian children in schools between 2006 and 2015. Children's BMI was classified using the current WHO, IOTF, and CDC references. Results 25,060 children from 8 Romanian counties were included in the analysis. The prevalence of underweight children was 5%/4.5%/8.5% (WHO/IOTF/CDC), while the prevalence of overweight (including obese) children was 28.3%/23%/23.2% (WHO/IOTF/CDC). The prevalence of overweight children did not change significantly over the last decade (chi-square test p = 0.6). Male gender (odds ratio (OR) 1.37; 95% CI 1.29-1.45, compared to female); prepubertal age (OR = 3.86; 95% CI 3.41-4.36,compared to postpubertal age), and urban environment (OR 1.12; 95% CI 1.01-1.26, compared to rural environment) had higher risk for overweight. Conclusion While the prevalence of underweight children was low, almost one in four children in Romania was overweight or obese (according to WHO criteria) between 2006 and 2015. This prevalence remained relatively stable over the last decade. Male gender, prepubertal age, and urban environment, were the most relevant risk factors associated with overweight status in Romanian children. PMID:27319017

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.

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

Cdc42 and the Guanine Nucleotide Exchange Factors Ect2 and Trio Mediate Fn14-Induced Migration and Invasion of Glioblastoma Cells

PubMed Central

Fortin, Shannon P.; Ennis, Matthew J.; Schumacher, Cassie A.; Zylstra-Diegel, Cassandra R.; Williams, Bart O.; Ross, Julianna T.D.; Winkles, Jeffrey A.; Loftus, Joseph C.; Symons, Marc H.; Tran, Nhan L.

2012-01-01

Malignant glioblastomas are characterized by their ability to infiltrate into normal brain. We previously reported that binding of the multifunctional cytokine TNF-like weak inducer of apoptosis (TWEAK) to its receptor fibroblast growth factor–inducible 14 (Fn14) induces glioblastoma cell invasion via Rac1 activation. Here, we show that Cdc42 plays an essential role in Fn14-mediated activation of Rac1. TWEAK-treated glioma cells display an increased activation of Cdc42, and depletion of Cdc42 using siRNA abolishes TWEAK-induced Rac1 activation and abrogates glioma cell migration and invasion. In contrast, Rac1 depletion does not affect Cdc42 activation by Fn14, showing that Cdc42 mediates TWEAK-stimulated Rac1 activation. Furthermore, we identified two guanine nucleotide exchange factors (GEF), Ect2 and Trio, involved in TWEAK-induced activation of Cdc42 and Rac1, respectively. Depletion of Ect2 abrogates both TWEAK-induced Cdc42 and Rac1 activation, as well as subsequent TWEAK-Fn14–directed glioma cell migration and invasion. In contrast, Trio depletion inhibits TWEAK-induced Rac1 activation but not TWEAK-induced Cdc42 activation. Finally, inappropriate expression of Fn14 or Ect2 in mouse astrocytes in vivo using an RCAS vector system for glial-specific gene transfer in G-tva transgenic mice induces astrocyte migration within the brain, corroborating the in vitro importance of the TWEAK-Fn14 signaling cascade in glioblastoma invasion. Our results suggest that the TWEAK-Fn14 signaling axis stimulates glioma cell migration and invasion through two GEF-GTPase signaling units, Ect2-Cdc42 and Trio-Rac1. Components of the Fn14-Rho GEF-Rho GTPase signaling pathway present innovative drug targets for glioma therapy. PMID:22571869

42 CFR 73.6 - Exemptions for overlap select agents and toxins.

Code of Federal Regulations, 2013 CFR

2013-10-01

... reported to CDC or APHIS and to other appropriate authorities when required by Federal, State, or local law... pseudomallei. This report must be followed by submission of APHIS/CDC Form 4 within seven calendar days after identification. (ii) For all other overlap select agents or toxins, APHIS/CDC Form 4 must be submitted within...

42 CFR 73.6 - Exemptions for overlap select agents and toxins.

Code of Federal Regulations, 2014 CFR

2014-10-01

... reported to CDC or APHIS and to other appropriate authorities when required by Federal, State, or local law... pseudomallei. This report must be followed by submission of APHIS/CDC Form 4 within seven calendar days after identification. (ii) For all other overlap select agents or toxins, APHIS/CDC Form 4 must be submitted within...

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.

Overweight and obesity prevalence among Cree youth of Eeyou Istchee according to three body mass index classification systems.

PubMed

St-Jean, Audray; Meziou, Salma; Ayotte, Pierre; Lucas, Michel

2017-11-22

Little is known about the suitability of three commonly used body mass index (BMI) classification systems for Indigenous youth. We estimated overweight and obesity prevalence among Cree youth of Eeyou Istchee according to three BMI classification systems, assessed the level of agreement between them, and evaluated their accuracy through body fat and cardiometabolic risk factors. Data on 288 youth (aged 8-17 years) were collected. Overweight and obesity prevalence were estimated with Centers for Disease Control and Prevention (CDC), International Obesity Task Force (IOTF) and World Health Organization (WHO) criteria. Agreement was measured with weighted kappa (κw). Associations with body fat and cardiometabolic risk factors were evaluated by analysis of variance. Obesity prevalence was 42.7% with IOTF, 47.2% with CDC, and 49.3% with WHO criteria. Agreement was almost perfect between IOTF and CDC (κw = 0.93), IOTF and WHO (κw = 0.91), and WHO and CDC (κw = 0.94). Means of body fat and cardiometabolic risk factors were significantly higher (P trend  < 0.001) from normal weight to obesity, regardless of the system used. Youth considered overweight by IOTF but obese by CDC or WHO exhibited less severe clinical obesity. IOTF seems to be more accurate in identifying obesity in Cree youth.

HIV Testing Among Transgender Women and Men - 27 States and Guam, 2014-2015.

PubMed

Pitasi, Marc A; Oraka, Emeka; Clark, Hollie; Town, Machell; DiNenno, Elizabeth A

2017-08-25

Transgender persons are at high risk for human immunodeficiency virus (HIV) infection; in a recent analysis of the results of over nine million CDC funded HIV tests, transgender women* had the highest percentage of confirmed positive results (2.7%) of any gender category (1). Transgender men, † particularly those who have sex with cisgender § men, are also at high risk for infection (2). HIV testing is critical for detecting and treating persons who are infected and delivering preventive services to those who are uninfected. CDC recommends that persons at high risk for HIV infection be screened for HIV at least annually, although transgender persons are not specified in the current recommendations. CDC analyzed data from the Behavioral Risk Factor Surveillance System (BRFSS) to describe HIV testing among transgender women and men and two cisgender comparison groups in 27 states and Guam. After adjusting for demographic characteristics, transgender women and men had a lower prevalence of ever testing and past year testing for HIV (35.6% and 31.6% ever, and 10.0% and 10.2% past year, respectively) compared with cisgender gay and bisexual men (61.8% ever and 21.6% past year) and instead reported testing at levels comparable to cisgender heterosexual men and women (35.2% ever, and 8.6% past year). This finding suggests that transgender women and men might not be sufficiently reached by current HIV testing measures. Tailoring HIV testing activities to overcome the unique barriers faced by transgender women and men might increase rates of testing among these populations.

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.

Protein Phosphatase 2A Antagonizes ATM and ATR in a Cdk2- and Cdc7-Independent DNA Damage Checkpoint

PubMed Central

Petersen, Paris; Chou, Danny M.; You, Zhongsheng; Hunter, Tony; Walter, Johannes C.; Walter, Gernot

2006-01-01

We previously used a soluble cell-free system derived from Xenopus eggs to investigate the role of protein phosphatase 2A (PP2A) in chromosomal DNA replication. We found that immunodepletion of PP2A or inhibition of PP2A by okadaic acid (OA) inhibits initiation of DNA replication by preventing loading of the initiation factor Cdc45 onto prereplication complexes. Evidence was provided that PP2A counteracts an inhibitory protein kinase that phosphorylates and inactivates a crucial Cdc45 loading factor. Here, we report that the inhibitory effect of OA is abolished by caffeine, an inhibitor of the checkpoint kinases ataxia-telangiectasia mutated protein (ATM) and ataxia-telangiectasia related protein (ATR) but not by depletion of ATM or ATR from the extract. Furthermore, we demonstrate that double-strand DNA breaks (DSBs) cause inhibition of Cdc45 loading and initiation of DNA replication and that caffeine, as well as immunodepletion of either ATM or ATR, abolishes this inhibition. Importantly, the DSB-induced inhibition of Cdc45 loading is prevented by addition of the catalytic subunit of PP2A to the extract. These data suggest that DSBs and OA prevent Cdc45 loading through different pathways, both of which involve PP2A, but only the DSB-induced checkpoint implicates ATM and ATR. The inhibitory effect of DSBs on Cdc45 loading does not result from downregulation of cyclin-dependent kinase 2 (Cdk2) or Cdc7 activity and is independent of Chk2. However, it is partially dependent on Chk1, which becomes phosphorylated in response to DSBs. These data suggest that PP2A counteracts ATM and ATR in a DNA damage checkpoint in Xenopus egg extracts. PMID:16479016

CDC Vital Signs: Drinking and Driving

MedlinePlus

... driving episodes SOURCE: CDC Behavioral Risk Factor Surveillance System, US 2006, 2008 and 2010 Top of Page What Can Be Done States can Enforce 0.08% blood alcohol concentration and minimum legal drinking age laws. Expand the use of sobriety ...

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

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.

Molecular structures of cdc2-like kinases in complex with a new inhibitor chemotype

PubMed Central

Helmer, Renate; Loaëc, Nadège; Preu, Lutz; Ott, Ingo; Knapp, Stefan; Meijer, Laurent

2018-01-01

Cdc2-like kinases (CLKs) represent a family of serine-threonine kinases involved in the regulation of splicing by phosphorylation of SR-proteins and other splicing factors. Although compounds acting against CLKs have been described, only a few show selectivity against dual-specificity tyrosine phosphorylation regulated-kinases (DYRKs). We here report a novel CLK inhibitor family based on a 6,7-dihydropyrrolo[3,4-g]indol-8(1H)-one core scaffold. Within the series, 3-(3-chlorophenyl)-6,7-dihydropyrrolo[3,4-g]indol-8(1H)-one (KuWal151) was identified as inhibitor of CLK1, CLK2 and CLK4 with a high selectivity margin towards DYRK kinases. The compound displayed a potent antiproliferative activity in an array of cultured cancer cell lines. The X-ray structure analyses of three members of the new compound class co-crystallized with CLK proteins corroborated a molecular binding mode predicted by docking studies. PMID:29723265

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.

78 FR 78363 - Notice of Request for Comments on Chapters 6 and 8 of the NIOSH document titled: “Criteria for a...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-26

... formatted as Microsoft Word. Please make reference to CDC-2013-0021 and Docket Number NIOSH 245-A. To access... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention [CDC-2013-0021... materials, visit http://www.regulations.gov and enter CDC-2013- 0021 in the search field and click ``Search...

CDC25B and p53 are independently implicated in radiation sensitivity for human esophageal cancers.

PubMed

Miyata, H; Doki, Y; Shiozaki, H; Inoue, M; Yano, M; Fujiwara, Y; Yamamoto, H; Nishioka, K; Kishi, K; Monden, M

2000-12-01

Ionized radiation leads to G1 arrest and apoptosis by a p53-dependent pathway and G2-M arrest through a p53-independent pathway. In this study, we evaluated the role of cell cycle-regulating molecules in the sensitivity of cancer cells for radiation therapy. Forty-seven patients with squamous cell carcinomas of the esophagus had undergone radiation therapy, followed by surgical resection. They were classified as sensitive to radiation (SR, 14 cases) with no residual tumor in the surgical specimen or as resistant to radiation (RR, 33 cases) with viable residual tumors. Their preradiation biopsy samples were immunohistochemically investigated for the expressions of cell cycle-related molecules, including p53, CDC25A, CDC25B, cyclin D1, cyclin B1, and Ki-67. p53 expression was negative in 71% (10 of 14) of SR and positive in 91% (30 of 33) of RR. The association was strong between high radiation sensitivity and negative p53 expression (P < 0.0001). CDC25B, which is not expressed in normal epithelium but is in the cytoplasm of esophageal cancers, was strongly expressed (2+) in 46% (6 of 14) of SR and in 6% (2 of 23) of RR. Thus, the sensitivity for radiation therapy was significantly correlated with CDC25B overexpression. With respect to CDC25A, cyclin D1, cyclin B1, and Ki-67, no statistically significant differences were found in their expressions between SR and RR tumors. p53 and CDC25B expressions showed no significant associations, and multivariate analysis revealed that both p53 and CDC25B are significant independent markers for predicting radiation sensitivity. CDC25B was revealed to be a novel predictor of radiation sensitivity in esophageal cancers. Because CDC25B is an oncogene, which affects G2-M progression, these results suggest the importance of a p53-independent G2-M checkpoint in radiation therapy.

Actin organization and endocytic trafficking are controlled by a network linking NIMA-related kinases to the CDC-42-SID-3/ACK1 pathway

PubMed Central

Bernazzani, Sarina M.

2018-01-01

Molting is an essential process in the nematode Caenorhabditis elegans during which the epidermal apical extracellular matrix, termed the cuticle, is detached and replaced at each larval stage. The conserved NIMA-related kinases NEKL-2/NEK8/NEK9 and NEKL-3/NEK6/NEK7, together with their ankyrin repeat partners, MLT-2/ANKS6, MLT-3/ANKS3, and MLT-4/INVS, are essential for normal molting. In nekl and mlt mutants, the old larval cuticle fails to be completely shed, leading to entrapment and growth arrest. To better understand the molecular and cellular functions of NEKLs during molting, we isolated genetic suppressors of nekl molting-defective mutants. Using two independent approaches, we identified CDC-42, a conserved Rho-family GTPase, and its effector protein kinase, SID-3/ACK1. Notably, CDC42 and ACK1 regulate actin dynamics in mammals, and actin reorganization within the worm epidermis has been proposed to be important for the molting process. Inhibition of NEKL–MLT activities led to strong defects in the distribution of actin and failure to form molting-specific apical actin bundles. Importantly, this phenotype was reverted following cdc-42 or sid-3 inhibition. In addition, repression of CDC-42 or SID-3 also suppressed nekl-associated defects in trafficking, a process that requires actin assembly and disassembly. Expression analyses indicated that components of the NEKL–MLT network colocalize with both actin and CDC-42 in specific regions of the epidermis. Moreover, NEKL–MLT components were required for the normal subcellular localization of CDC-42 in the epidermis as well as wild-type levels of CDC-42 activation. Taken together, our findings indicate that the NEKL–MLT network regulates actin through CDC-42 and its effector SID-3. Interestingly, we also observed that downregulation of CDC-42 in a wild-type background leads to molting defects, suggesting that there is a fine balance between NEKL–MLT and CDC-42–SID-3 activities in the epidermis. PMID:29608564

Actin organization and endocytic trafficking are controlled by a network linking NIMA-related kinases to the CDC-42-SID-3/ACK1 pathway.

PubMed

Lažetić, Vladimir; Joseph, Braveen B; Bernazzani, Sarina M; Fay, David S

2018-04-01

Molting is an essential process in the nematode Caenorhabditis elegans during which the epidermal apical extracellular matrix, termed the cuticle, is detached and replaced at each larval stage. The conserved NIMA-related kinases NEKL-2/NEK8/NEK9 and NEKL-3/NEK6/NEK7, together with their ankyrin repeat partners, MLT-2/ANKS6, MLT-3/ANKS3, and MLT-4/INVS, are essential for normal molting. In nekl and mlt mutants, the old larval cuticle fails to be completely shed, leading to entrapment and growth arrest. To better understand the molecular and cellular functions of NEKLs during molting, we isolated genetic suppressors of nekl molting-defective mutants. Using two independent approaches, we identified CDC-42, a conserved Rho-family GTPase, and its effector protein kinase, SID-3/ACK1. Notably, CDC42 and ACK1 regulate actin dynamics in mammals, and actin reorganization within the worm epidermis has been proposed to be important for the molting process. Inhibition of NEKL-MLT activities led to strong defects in the distribution of actin and failure to form molting-specific apical actin bundles. Importantly, this phenotype was reverted following cdc-42 or sid-3 inhibition. In addition, repression of CDC-42 or SID-3 also suppressed nekl-associated defects in trafficking, a process that requires actin assembly and disassembly. Expression analyses indicated that components of the NEKL-MLT network colocalize with both actin and CDC-42 in specific regions of the epidermis. Moreover, NEKL-MLT components were required for the normal subcellular localization of CDC-42 in the epidermis as well as wild-type levels of CDC-42 activation. Taken together, our findings indicate that the NEKL-MLT network regulates actin through CDC-42 and its effector SID-3. Interestingly, we also observed that downregulation of CDC-42 in a wild-type background leads to molting defects, suggesting that there is a fine balance between NEKL-MLT and CDC-42-SID-3 activities in the epidermis.

Implementation of a workplace intervention using financial rewards to promote adherence to physical activity guidelines: a feasibility study.

PubMed

Losina, Elena; Smith, Savannah R; Usiskin, Ilana M; Klara, Kristina M; Michl, Griffin L; Deshpande, Bhushan R; Yang, Heidi Y; Smith, Karen C; Collins, Jamie E; Katz, Jeffrey N

2017-12-01

We designed and implemented the Brigham and Women's Wellness Initiative (B-Well), a single-arm study to examine the feasibility of a workplace program that used individual and team-based financial incentives to increase physical activity among sedentary hospital employees. We enrolled sedentary, non-clinician employees of a tertiary medical center who self-reported low physical activity. Eligible participants formed or joined teams of three members and wore Fitbit Flex activity monitors for two pre-intervention weeks followed by 24 weeks during which they could earn monetary rewards. Participants were rewarded for increasing their moderate-to-vigorous physical activity (MVPA) by 10% from the previous week or for meeting the Centers for Disease Control and Prevention (CDC) physical activity guidelines (150 min of MVPA per week). Our primary outcome was the proportion of participants meeting weekly MVPA goals and CDC physical activity guidelines. Secondary outcomes included Fitbit-wear adherence and factors associated with meeting CDC guidelines more consistently. B-Well included 292 hospital employees. Participants had a mean age of 38 years (SD 11), 83% were female, 38% were obese, and 62% were non-Hispanic White. Sixty-three percent of participants wore the Fitbit ≥4 days per week for ≥20 weeks. Two-thirds were satisfied with the B-Well program, with 79% indicating that they would participate again. Eighty-six percent met either their personal weekly goal or CDC physical activity guidelines for at least 6 out of 24 weeks, and 52% met their goals or CDC physical activity guidelines for at least 12 weeks. African Americans, non-obese subjects, and those with lower impulsivity scores reached CDC guidelines more consistently. Our data suggest that a financial incentives-based workplace wellness program can increase MVPA among sedentary employees. These results should be reproduced in a randomized controlled trial. Clinicaltrials.gov, NCT02850094 . Registered July 27, 2016 [retrospectively registered].

Novel Activities of Select NSAID R-Enantiomers against Rac1 and Cdc42 GTPases

PubMed Central

Oprea, Tudor I.; Sklar, Larry A.; Agola, Jacob O.; Guo, Yuna; Silberberg, Melina; Roxby, Joshua; Vestling, Anna; Romero, Elsa; Surviladze, Zurab; Murray-Krezan, Cristina; Waller, Anna; Ursu, Oleg; Hudson, Laurie G.; Wandinger-Ness, Angela

2015-01-01

Rho family GTPases (including Rac, Rho and Cdc42) collectively control cell proliferation, adhesion and migration and are of interest as functional therapeutic targets in numerous epithelial cancers. Based on high throughput screening of the Prestwick Chemical Library® and cheminformatics we identified the R-enantiomers of two approved drugs (naproxen and ketorolac) as inhibitors of Rac1 and Cdc42. The corresponding S-enantiomers are considered the active component in racemic drug formulations, acting as non-steroidal anti-inflammatory drugs (NSAIDs) with selective activity against cyclooxygenases. Here, we show that the S-enantiomers of naproxen and ketorolac are inactive against the GTPases. Additionally, more than twenty other NSAIDs lacked inhibitory action against the GTPases, establishing the selectivity of the two identified NSAIDs. R-naproxen was first identified as a lead compound and tested in parallel with its S-enantiomer and the non-chiral 6-methoxy-naphthalene acetic acid (active metabolite of nabumetone, another NSAID) as a structural series. Cheminformatics-based substructure analyses—using the rotationally constrained carboxylate in R-naproxen—led to identification of racemic [R/S] ketorolac as a suitable FDA-approved candidate. Cell based measurement of GTPase activity (in animal and human cell lines) demonstrated that the R-enantiomers specifically inhibit epidermal growth factor stimulated Rac1 and Cdc42 activation. The GTPase inhibitory effects of the R-enantiomers in cells largely mimic those of established Rac1 (NSC23766) and Cdc42 (CID2950007/ML141) specific inhibitors. Docking predicts that rotational constraints position the carboxylate moieties of the R-enantiomers to preferentially coordinate the magnesium ion, thereby destabilizing nucleotide binding to Rac1 and Cdc42. The S-enantiomers can be docked but are less favorably positioned in proximity to the magnesium. R-naproxen and R-ketorolac have potential for rapid translation and efficacy in the treatment of several epithelial cancer types on account of established human toxicity profiles and novel activities against Rho-family GTPases. PMID:26558612

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.

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.

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.

The structure of FMNL2-Cdc42 yields insights into the mechanism of lamellipodia and filopodia formation

NASA Astrophysics Data System (ADS)

Kühn, Sonja; Erdmann, Constanze; Kage, Frieda; Block, Jennifer; Schwenkmezger, Lisa; Steffen, Anika; Rottner, Klemens; Geyer, Matthias

2015-05-01

Formins are actin polymerization factors that elongate unbranched actin filaments at the barbed end. Rho family GTPases activate Diaphanous-related formins through the relief of an autoregulatory interaction. The crystal structures of the N-terminal domains of human FMNL1 and FMNL2 in complex with active Cdc42 show that Cdc42 mediates contacts with all five armadillo repeats of the formin with specific interactions formed by the Rho-GTPase insert helix. Mutation of three residues within Rac1 results in a gain-of-function mutation for FMNL2 binding and reconstitution of the Cdc42 phenotype in vivo. Dimerization of FMNL1 through a parallel coiled coil segment leads to formation of an umbrella-shaped structure that--together with Cdc42--spans more than 15 nm in diameter. The two interacting FMNL-Cdc42 heterodimers expose six membrane interaction motifs on a convex protein surface, the assembly of which may facilitate actin filament elongation at the leading edge of lamellipodia and filopodia.

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.

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

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.

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.

Anti-Colon Cancer Effects of 6-Shogaol Through G2/M Cell Cycle Arrest by p53/p21-cdc2/cdc25A Crosstalk.

PubMed

Qi, Lian-Wen; Zhang, Zhiyu; Zhang, Chun-Feng; Anderson, Samantha; Liu, Qun; Yuan, Chun-Su; Wang, Chong-Zhi

2015-01-01

Chemopreventive agents can be identified from botanicals. Recently, there has been strong support for the potential of 6-shogaol, a natural compound from dietary ginger (Zingiber officinale), in cancer chemoprevention. However, whether 6-shogaol inhibits the growth of colorectal tumors in vivo remains unknown, and the underlying anticancer mechanisms have not been well characterized. In this work, we observed that 6-shogaol (15 mg/kg) significantly inhibited colorectal tumor growth in a xenograft mouse model. We show that 6-shogaol inhibited HCT-116 and SW-480 cell proliferation with IC50 of 7.5 and 10 μM, respectively. Growth of HCT-116 cells was arrested at the G2/M phase of the cell cycle, primarily mediated by the up-regulation of p53, the CDK inhibitor p21(waf1/cip1) and GADD45α, and by the down-regulation of cdc2 and cdc25A. Using p53(-/-) and p53(+/+) HCT-116 cells, we confirmed that p53/p21 was the main pathway that contributed to the G2/M cell cycle arrest by 6-shogaol. 6-Shogaol induced apoptosis, mainly through the mitochondrial pathway, and the bcl-2 family might act as a key regulator. Our results demonstrated that 6-shogaol induces cancer cell death by inducing G2/M cell cycle arrest and apoptosis. 6-Shogaol could be an active natural product in colon cancer chemoprevention.

Structure and dimerization of the catalytic domain of the protein phosphatase Cdc14p, a key regulator of mitotic exit in Saccharomyces cerevisiae.

PubMed

Kobayashi, Junya; Matsuura, Yoshiyuki

2017-10-01

In the budding yeast Saccharomyces cerevisiae, the protein phosphatase Cdc14p orchestrates various events essential for mitotic exit. We have determined the X-ray crystal structures at 1.85 Å resolution of the catalytic domain of Cdc14p in both the apo state, and as a complex with S160-phosphorylated Swi6p peptide. Each asymmetric unit contains two Cdc14p chains arranged in an intimately associated homodimer, consistent with its oligomeric state in solution. The dimerization interface is located on the backside of the substrate-binding cleft. Structure-based mutational analyses indicate that the dimerization of Cdc14p is required for normal growth of yeast cells. © 2017 The Protein Society.

The Aarskog-Scott Syndrome Protein Fgd1 Regulates Podosome Formation and Extracellular Matrix Remodeling in Transforming Growth Factor β-Stimulated Aortic Endothelial Cells ▿

PubMed Central

Daubon, Thomas; Buccione, Roberto; Génot, Elisabeth

2011-01-01

Podosomes are dynamic actin-rich adhesion plasma membrane microdomains endowed with extracellular matrix-degrading activities. In aortic endothelial cells, podosomes are induced by transforming growth factor β (TGF-β), but how this occurs is largely unknown. It is thought that, in endothelial cells, podosomes play a role in vessel remodeling and/or in breaching anatomical barriers. We demonstrate here that, in bovine aortic endothelial cells, that the Cdc42-specific guanine exchange factor (GEF) Fgd1 is expressed and regulated by TGF-β to induce Cdc42-dependent podosome assembly. Within 15 min of TGF-β stimulation, Fgd1, but none of the other tested Cdc42 GEFs, undergoes tyrosine phosphorylation, associates with Cdc42, and translocates to the subcortical cytoskeleton via a cortactin-dependent mechanism. Small interfering RNA-mediated Fgd1 knockdown inhibits TGF-β-induced Cdc42 activation. Fgd1 depletion also reduces podosome formation and associated matrix degradation and these defects are rescued by reexpression of Fgd1. Although overexpression of Fgd1 does not promote podosome formation per se, it enhances TGF-β-induced matrix degradation. Our results identify Fgd1 as a TGF-β-regulated GEF and, as such, the first GEF to be involved in the process of cytokine-induced podosome formation. Our findings reveal the involvement of Fgd1 in endothelial cell biology and open up new avenues to study its role in vascular pathophysiology. PMID:21911474

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

How Health Department Contextual Factors Affect Public Health Preparedness (PHP) and Perceptions of the 15 PHP Capabilities.

PubMed

Horney, Jennifer A; Carbone, Eric G; Lynch, Molly; Wang, Z Joan; Jones, Terrance; Rose, Dale A

2017-09-01

To assess how health department contextual factors influence perceptions of the 15 Public Health Preparedness Capabilities, developed by the Centers for Disease Control and Prevention (CDC) to provide guidance on organizing preparedness activities. We conducted an online survey and focus group between September 2015 and May 2016 with directors of preparedness programs in state, metropolitan, and territorial jurisdictions funded by CDC's Public Health Emergency Preparedness (PHEP) cooperative agreement. The survey collected demographic information and data on contextual factors including leadership, partnerships, organizational structure, resources and structural capacity, and data and evaluation. Seventy-seven percent (48 of 62) of PHEP directors completed the survey and 8 participated in the focus group. Respondents were experienced directors (mean = 10.6 years), and 58% led 7 or more emergency responses. Leadership, partnerships, and access to fiscal and human resources were associated with perception and use of the capabilities. Despite some deficiencies, PHEP awardees believe the capabilities provide useful guidance and a flexible framework for organizing their work. Contextual factors affect perceptions of the capabilities and possibly the effectiveness of their use. Public Health Implications. The capabilities can be used to address challenges in preparedness, including identifying evidence-based practices, developing performance measures, and improving responses.

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

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

Wan, Qiaoqiao; Cho, Eunhye; Yokota, Hiroki

2013-04-19

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

CDC-reported assisted reproductive technology live-birth rates may mislead the public.

PubMed

Kushnir, Vitaly A; Choi, Jennifer; Darmon, Sarah K; Albertini, David F; Barad, David H; Gleicher, Norbert

2017-08-01

The Centre for Disease Control and Prevention (CDC) publicly reports assisted reproductive technology live-birth rates (LBR) for each US fertility clinic under legal mandate. The 2014 CDC report excluded 35,406 of 184,527 (19.2%) autologous assisted reproductive technology cycles that involved embryo or oocyte banking from LBR calculations. This study calculated 2014 total clinic LBR for all patients utilizing autologous oocytes two ways: including all initiated assisted reproductive technology cycles or excluding banking cycles, as done by the CDC. The main limitation of this analysis is the CDC report did not differentiate between cycles involving long-term banking of embryos or oocytes for fertility preservation from cycles involving short-term embryo banking. Twenty-seven of 458 (6%) clinics reported over 40% of autologous cycles involved banking, collectively performing 12% of all US assisted reproductive technology cycles. LBR in these outlier clinics calculated by the CDC method, was higher than the other 94% of clinics (33.1% versus 31.1%). However, recalculated LBR including banking cycles in the outlier clinics was lower than the other 94% of clinics (15.5% versus 26.6%). LBR calculated by the two methods increasingly diverged based on proportion of banking cycles performed by each clinic reaching 4.5-fold, thereby, potentially misleading the public. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Measles: Information for Parents

MedlinePlus

... 6 months to 11 months old should have 1 dose of MMR shot before traveling to another country. CS HCVG15 -CHD - ... my child? To learn more about the MMR shot, talk to your child’s doctor, call 1- 800- CDC- INFO, or visit www. cdc. gov/ ...

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.

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.

Head-circumference distribution in a large primary care network differs from CDC and WHO curves.

PubMed

Daymont, Carrie; Hwang, Wei-Ting; Feudtner, Chris; Rubin, David

2010-10-01

To compare currently available head-circumference growth curves to curves constructed from clinical measurements from patients in a large US primary care network (PCN). We performed a retrospective cohort study of 75 412 patients in an urban-suburban PCN. Patients with a birth weight of <1500 g or gestational age of <33 weeks at birth were excluded. We compared percentile values and the proportion of head-circumference observations above the 95th percentile and below the 5th percentile for the existing and PCN curves. The PCN curves were most similar to the National Center for Health Statistics (NCHS) curves and were substantially different from the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) curves. The overall proportion of observations above the 95th percentile was 4.9% (PCN), 6.2% (NCHS), 8.6% (CDC), and 14.0% (WHO). The proportion below the 5th percentile was 4.4% (PCN), 5.1% (NCHS), 2.9% (CDC), and 2.3% (WHO). When using the CDC curves, the proportion above the 95th percentile increased from 0.2% for children younger than 2 weeks to 11.8% for children 12 months old. When using the WHO curves, the proportion above the 95th percentile was >5% at all ages, with a maximum of 18.0% for children older than 24 months. The CDC and WHO head-circumference curves describe different distributions than the clinical measurements in our PCN population, especially for children with larger heads. The resulting percentile misclassification may delay diagnosis in children with intracranial pathology in very young infants and spur unnecessary evaluation of healthy children older than 6 months.

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.

Disruption of Fibroblast Growth Factor Receptor (FGFR) Signaling as an Approach to Prostate Cancer Therapy

DTIC Science & Technology

2005-04-01

presented in tenth Annual Meeting of Association of Molecular Pathology and the abstract was published in the Journal of Molecular Diagnostics . The full...CDC25C Phosphatase Activity in Prostate Cancer: Correlation to Biochemical Recurrence. Journal of Molecular Diagnostics 2004, (6)4: 431. A manuscript in...receptor signaling. Clinical Cancer Research (in press). Acceptance letter for the above manuscript An abstract published in the Journal of Molecular

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.

Vectorization of transport and diffusion computations on the CDC Cyber 205

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

Abu-Shumays, I.K.

1986-01-01

The development and testing of alternative numerical methods and computational algorithms specifically designed for the vectorization of transport and diffusion computations on a Control Data Corporation (CDC) Cyber 205 vector computer are described. Two solution methods for the discrete ordinates approximation to the transport equation are summarized and compared. Factors of 4 to 7 reduction in run times for certain large transport problems were achieved on a Cyber 205 as compared with run times on a CDC-7600. The solution of tridiagonal systems of linear equations, central to several efficient numerical methods for multidimensional diffusion computations and essential for fluid flowmore » and other physics and engineering problems, is also dealt with. Among the methods tested, a combined odd-even cyclic reduction and modified Cholesky factorization algorithm for solving linear symmetric positive definite tridiagonal systems is found to be the most effective for these systems on a Cyber 205. For large tridiagonal systems, computation with this algorithm is an order of magnitude faster on a Cyber 205 than computation with the best algorithm for tridiagonal systems on a CDC-7600.« less

Bone-Derived Stem Cells Repair the Heart after Myocardial Infarction Through Transdifferentiation and Paracrine Signaling Mechanisms

PubMed Central

Duran, Jason M.; Makarewich, Catherine A.; Sharp, Thomas E.; Starosta, Timothy; Fang, Zhu; Hoffman, Nicholas E.; Chiba, Yumi; Madesh, Muniswamy; Berretta, Remus M.; Kubo, Hajime; Houser, Steven R.

2013-01-01

Rationale Autologous bone marrow- or cardiac-derived stem cell therapy for heart disease has demonstrated safety and efficacy in clinical trials but functional improvements have been limited. Finding the optimal stem cell type best suited for cardiac regeneration is key toward improving clinical outcomes. Objective To determine the mechanism by which novel bone-derived stem cells support the injured heart. Methods and Results Cortical bone stem cells (CBSCs) and cardiac-derived stem cells (CDCs) were isolated from EGFP+ transgenic mice and were shown to express c-kit and Sca-1 as well as 8 paracrine factors involved in cardioprotection, angiogenesis and stem cell function. Wild-type C57BL/6 mice underwent sham operation (n=21) or myocardial infarction (MI) with injection of CBSCs (n=67), CDCs (n=36) or saline (n=60). Cardiac function was monitored using echocardiography. Only 2/8 paracrine factors were detected in EGFP+ CBSCs in vivo (basic fibroblast growth factor and vascular endothelial growth factor) and this expression was associated with increased neovascularization of the infarct border zone. CBSC therapy improved survival, cardiac function, regional strain, attenuated remodeling, and decreased infarct size relative to CDC- or saline-treated MI controls. By 6 weeks, EGFP+ cardiomyocytes, vascular smooth muscle and endothelial cells could be identified in CBSC- but not in CDC-treated animals. EGFP+ CBSC-derived isolated myocytes were smaller and more frequently mononucleated, but were functionally indistinguishable from EGFP- myocytes. Conclusions CBSCs improve survival, cardiac function, and attenuate remodeling through two mechanisms:1) secretion of pro-angiogenic factors that stimulate endogenous neovascularization, and 2) differentiation into functional adult myocytes and vascular cells. PMID:23801066

[PKA-regulated phosphorylation status of S149 and S321 sites of CDC25B inhibits mitosis of fertilized mouse eggs].

PubMed

Xiao, Jian-Ying; Liu, Chao; Sun, Xiao-Han; Yu, Bing-Zhi

2012-02-25

To further test whether protein kinase A (PKA) can affect the mitotic cell cycle, one-cell stage mouse embryos at S phase (22 h after hCG injection) were incubated in M16 medium containing various concentrations of H-89, a PKA inhibitor. With increasing concentrations of H-89 (0-50 μmol/L), the G(2) phase of eggs was decreased and the cleavage rate was accelerated. A concentration of 40 μmol/L H-89 led to all of the mouse eggs entering the M phase of mitosis. Furthermore, to study the role of PKA in regulating the phosphorylation status of S149 and S321 sites of cell division cycle 25B (CDC25B) on one-cell stage fertilized mouse eggs, pBSK-CDC25B-WT, pBSK-CDC25B-S149A, pBSK-CDC25B-S321A and pBSK-CDC25B-S149A/S321A were transcribed into mRNAs in vitro, then mRNAs were microinjected into S phase of mouse fertilized eggs and cultured in M16 medium pretreated with H-89. Then, the cleavage of fertilized eggs, maturation promoting factor (MPF) activity and phosphorylation status of CDC2-Tyr15 were observed. In the presence of 40 μmol/L H-89, the cleavage rate of fertilized eggs in CDC25B-S/A-mRNAs and CDC25B-WT-mRNA injected groups was significantly higher than that in the control groups, and the peak of MPF activity appeared in the CDC25B-S/A-mRNAs and CDC25B-WT-mRNA injected groups earlier than that in the control groups. CDC2-Tyr15 phosphorylation state was consistent with MPF activity. In conclusion, the present study suggests that PKA regulates the early development of mouse embryos by phosphorylation of S149 and S321 of CDC25B, which plays an important role in the regulation of G(2)/M transition in the mitotic cell cycle of fertilized mouse eggs.

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.

Motor vehicle injury, mortality, and hospital charges by strength of graduated driver licensing laws in 36 States.

PubMed

Pressley, Joyce C; Benedicto, Camilla B; Trieu, Lisa; Kendig, Tiffany; Barlow, Barbara

2009-07-01

To assess the relation between strength of graduated driver licensing (GDL) laws and motor vehicle (MV) injury burden, this study examined injury mortality, hospitalizations and related charges for 15 year to 17 year olds in 36 states by strength of GDL legislation. Data sources include the CDC's Web-Based Injury Statistics Query and Reporting System (WISQARS) and the 2003 Healthcare Cost and Utilization Kids' Inpatient database (KID). Hospital admissions for injuries in 15 year to 17 year olds (n = 49,520) are unweighted. Injury severity was assessed using ICDMAP-90 and International Classification of Injury Severity Scores. The Insurance Institute for Highway Safety rating system was used to categorize legislative strength: good, fair, marginal/poor, and none. Logistic regression was used to assess independent predictors of MV injury. MV injury accounted for 14.6% of all-cause injury-related hospital admissions with 47.7% classified as drivers. Total MV occupant mortality was 14.6% lower after enactment of GDL with greater improvement observed in the good law category (26.0%). In multivariate models for hospitalized injury, all GDL law categories were protective for MV driver injury in 16 year olds. Compared with whites, black and Hispanic teens were more frequently injured as passengers than drivers. The contribution of MV occupant to all-cause injury-related hospital charges was 16.0% lower in good versus no-GDL categories and 39.5% lower for MV drivers. These findings suggest that the presence of any GDL legislation is associated with a lower burden of MV-related injury and expenditures with the largest differences observed for 16-year-old drivers.

Mumps and the Vaccine (Shot) to Prevent It

MedlinePlus

... 6 months to 11 months old should have 1 dose of MMR shot before traveling abroad. Fact Sheet for Parents Color [ ... my child? To learn more about the MMR shot, talk to your child’s doctor, call 1-800-CDC-INFO, or visit www.cdc.gov/ ...

Key Ethical Issues Discussed at CDC-Sponsored International, Regional Meetings to Explore Cultural Perspectives and Contexts on Pandemic Influenza Preparedness and Response.

PubMed

Lor, Aun; Thomas, James C; Barrett, Drue H; Ortmann, Leonard W; Herrera Guibert, Dionisio J

2016-05-17

Recognizing the importance of having a broad exploration of how cultural perspectives may shape thinking about ethical considerations, the Centers for Disease Control and Prevention (CDC) funded four regional meetings in Africa, Asia, Latin America, and the Eastern Mediterranean to explore these perspectives relevant to pandemic influenza preparedness and response. The meetings were attended by 168 health professionals, scientists, academics, ethicists, religious leaders, and other community members representing 40 countries in these regions. We reviewed the meeting reports, notes and stories and mapped outcomes to the key ethical challenges for pandemic influenza response described in the World Health Organization's (WHO's) guidance, Ethical Considerations in Developing a Public Health Response to Pandemic Influenza: transparency and public engagement, allocation of resources, social distancing, obligations to and of healthcare workers, and international collaboration. The important role of transparency and public engagement were widely accepted among participants. However, there was general agreement that no "one size fits all" approach to allocating resources can address the variety of economic, cultural and other contextual factors that must be taken into account. The importance of social distancing as a tool to limit disease transmission was also recognized, but the difficulties associated with this measure were acknowledged. There was agreement that healthcare workers often have competing obligations and that government has a responsibility to assist healthcare workers in doing their job by providing appropriate training and equipment. Finally, there was agreement about the importance of international collaboration for combating global health threats. Although some cultural differences in the values that frame pandemic preparedness and response efforts were observed, participants generally agreed on the key ethical principles discussed in the WHO's guidance. Most significantly the input gathered from these regional meetings pointed to the important role that procedural ethics can play in bringing people and countries together to respond to the shared health threat posed by a pandemic influenza despite the existence of cultural differences. © 2016 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Two subunits of human ORC are dispensable for DNA replication and proliferation.

PubMed

Shibata, Etsuko; Kiran, Manjari; Shibata, Yoshiyuki; Singh, Samarendra; Kiran, Shashi; Dutta, Anindya

2016-12-01

The six-subunit Origin Recognition Complex (ORC) is believed to be an essential eukaryotic ATPase that binds to origins of replication as a ring-shaped heterohexamer to load MCM2-7 and initiate DNA replication. We have discovered that human cell lines in culture proliferate with intact chromosomal origins of replication after disruption of both alleles of ORC2 or of the ATPase subunit, ORC1 . The ORC1 or ORC2 -depleted cells replicate with decreased chromatin loading of MCM2-7 and become critically dependent on another ATPase, CDC6, for survival and DNA replication. Thus, either the ORC ring lacking a subunit, even its ATPase subunit, can load enough MCM2-7 in partnership with CDC6 to initiate DNA replication, or cells have an ORC-independent, CDC6-dependent mechanism to load MCM2-7 on origins of replication.

Society of Behavioral Medicine (SBM) position statement: restore CDC funding for firearms and gun violence prevention research.

PubMed

Behrman, Pamela; Redding, Colleen A; Raja, Sheela; Newton, Tamara; Beharie, Nisha; Printz, Destiny

2018-02-21

The Society for Behavioral Medicine (SBM) urges restoration of Centers for Disease Control and Prevention (CDC) funding for firearms and gun violence prevention research. Gun violence in the United States is an important and costly public health issue in need of research attention. Unfortunately, there have been no concerted CDC-funded research efforts in this area since 1996, due to the passage of the Dickey Amendment. To remedy the information-gathering restrictions caused by the Dickey Amendment bans, it is recommended that Congress remove 'policy riders' on federal appropriations bills that limit firearms research at the CDC; expand NVDRS firearms-related data collection efforts to include all fifty states; fund CDC research on the risk and protective factors of gun use and gun violence prevention; fund research on evidence-based primary, secondary, and tertiary prevention and treatment initiatives for communities that are seriously impacted by the effects of gun violence; and support the development of evidence-based policy and prevention recommendations for gun use and ownership.

Mechanism of IRSp53 inhibition and combinatorial activation by Cdc42 and downstream effectors.

PubMed

Kast, David J; Yang, Changsong; Disanza, Andrea; Boczkowska, Malgorzata; Madasu, Yadaiah; Scita, Giorgio; Svitkina, Tatyana; Dominguez, Roberto

2014-04-01

The Rho family GTPase effector IRSp53 has essential roles in filopodia formation and neuronal development, but its regulatory mechanism is poorly understood. IRSp53 contains a membrane-binding BAR domain followed by an unconventional CRIB motif that overlaps with a proline-rich region (CRIB-PR) and an SH3 domain that recruits actin cytoskeleton effectors. Using a fluorescence reporter assay, we show that human IRSp53 adopts a closed inactive conformation that opens synergistically with the binding of human Cdc42 to the CRIB-PR and effector proteins, such as the tumor-promoting factor Eps8, to the SH3 domain. The crystal structure of Cdc42 bound to the CRIB-PR reveals a new mode of effector binding to Rho family GTPases. Structure-inspired mutations disrupt autoinhibition and Cdc42 binding in vitro and decouple Cdc42- and IRSp53-dependent filopodia formation in cells. The data support a combinatorial mechanism of IRSp53 activation.

Small-GTPase-associated signaling by the guanine nucleotide exchange factors CpDock180 and CpCdc24, the GTPase effector CpSte20, and the scaffold protein CpBem1 in Claviceps purpurea.

PubMed

Herrmann, Andrea; Tillmann, Britta A M; Schürmann, Janine; Bölker, Michael; Tudzynski, Paul

2014-04-01

Monomeric GTPases of the Rho subfamily are important mediators of polar growth and NADPH (Nox) signaling in a variety of organisms. These pathways influence the ability of Claviceps purpurea to infect host plants. GTPase regulators contribute to the nucleotide loading cycle that is essential for proper functionality of the GTPases. Scaffold proteins gather GTPase complexes to facilitate proper function. The guanine nucleotide exchange factors (GEFs) CpCdc24 and CpDock180 activate GTPase signaling by triggering nucleotide exchange of the GTPases. Here we show that CpCdc24 harbors nucleotide exchange activity for both Rac and Cdc42 homologues. The GEFs partly share the cellular distribution of the GTPases and interact with the putative upstream GTPase CpRas1. Interaction studies show the formation of higher-order protein complexes, mediated by the scaffold protein CpBem1. Besides the GTPases and GEFs, these complexes also contain the GTPase effectors CpSte20 and CpCla4, as well as the regulatory protein CpNoxR. Functional characterizations suggest a role of CpCdc24 mainly in polarity, whereas CpDock180 is involved in stress tolerance mechanisms. These findings indicate the dynamic formation of small GTPase complexes and improve the model for GTPase-associated signaling in C. purpurea.

Deficiency of transcription factor RelB perturbs myeloid and DC development by hematopoietic-extrinsic mechanisms

PubMed Central

Briseño, Carlos G.; Gargaro, Marco; Durai, Vivek; Davidson, Jesse T.; Theisen, Derek J.; Anderson, David A.; Novack, Deborah V.; Murphy, Theresa L.; Murphy, Kenneth M.

2017-01-01

RelB is an NF-κB family transcription factor activated in the noncanonical pathway downstream of NF-κB–inducing kinase (NIK) and TNF receptor family members including lymphotoxin-β receptor (LTβR) and CD40. Early analysis suggested that RelB is required for classical dendritic cell (cDC) development based on a severe reduction of cDCs in Relb−/− mice associated with profound myeloid expansion and perturbations in B and T cells. Subsequent analysis of radiation chimeras generated from wild-type and Relb−/− bone marrow showed that RelB exerts cell-extrinsic actions on some lineages, but it has remained unclear whether the impact of RelB on cDC development is cell-intrinsic or -extrinsic. Here, we reevaluated the role of RelB in cDC and myeloid development using a series of radiation chimeras. We found that there was no cell-intrinsic requirement for RelB for development of most cDC subsets, except for the Notch2- and LTβR-dependent subset of splenic CD4+ cDC2s. These results identify a relatively restricted role of RelB in DC development. Moreover, the myeloid expansion in Relb−/− mice resulted from hematopoietic-extrinsic actions of RelB. This result suggests that there is an unrecognized but critical role for RelB within the nonhematopoietic niche that controls normal myelopoiesis. PMID:28348230

TCF4-Targeting miR-124 is Differentially Expressed amongst Dendritic Cell Subsets

PubMed Central

Han, Sun Murray; Na, Hye Young; Ham, Onju; Choi, Wanho; Sohn, Moah; Ryu, Seul Hye; In, Hyunju; Hwang, Ki-Chul

2016-01-01

Dendritic cells (DCs) are professional antigen-presenting cells that sample their environment and present antigens to naïve T lymphocytes for the subsequent antigen-specific immune responses. DCs exist in a range of distinct subpopulations including plasmacytoid DCs (pDCs) and classical DCs (cDCs), with the latter consisting of the cDC1 and cDC2 lineages. Although the roles of DC-specific transcription factors across the DC subsets have become understood, the posttranscriptional mechanisms that regulate DC development are yet to be elucidated. MicroRNAs (miRNAs) are pivotal posttranscriptional regulators of gene expression in a myriad of biological processes, but their contribution to the immune system is just beginning to surface. In this study, our in-house probe collection was screened to identify miRNAs possibly involved in DC development and function by targeting the transcripts of relevant mouse transcription factors. Examination of DC subsets from the culture of mouse bone marrow with Flt3 ligand identified high expression of miR-124 which was able to target the transcript of TCF4, a transcription factor critical for the development and homeostasis of pDCs. Further expression profiling of mouse DC subsets isolated from in vitro culture as well as via ex vivo purification demonstrated that miR-124 was outstandingly expressed in CD24+ cDC1 cells compared to in pDCs and CD172α+ cDC2 cells. These results imply that miR-124 is likely involved in the processes of DC subset development by posttranscriptional regulation of a transcription factor(s). PMID:26937233

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

Identification of key transcription factors in caerulein-induced pancreatitis through expression profiling data

PubMed Central

QI, DACHUAN; WU, BO; TONG, DANIAN; PAN, YE; CHEN, WEI

2015-01-01

The current study aimed to isolate key transcription factors (TFs) in caerulein-induced pancreatitis, and to identify the difference between wild type and Mist1 knockout (KO) mice, in order to elucidate the contribution of Mist1 to pancreatitis. The gene profile of GSE3644 was downloaded from the Gene Expression Omnibus database then analyzed using the t-test. The isolated differentially expressed genes (DEGs) were mapped into a transcriptional regulatory network derived from the Integrated Transcription Factor Platform database and in the network, the interaction pairs involving at least one DEG were screened. Fisher’s exact test was used to analyze the functional enrichment of the target genes. A total of 1,555 and 3,057 DEGs were identified in the wild type and Mist1KO mice treated with caerulein, respectively. DEGs screened in Mist1KO mice were predominantly enriched in apoptosis, mitogen-activated protein kinase signaling and other cancer-associated pathways. A total of 188 and 51 TFs associated with pathopoiesis were isolated in Mist1KO and wild type mice, respectively. Out of the top 10 TFs (ranked by P-value), 7 TFs, including S-phase kinase-associated protein 2 (Skp2); minichromosome maintenance complex component 3 (Mcm3); cell division cycle 6 (Cdc6); cyclin B1 (Ccnb1); mutS homolog 6 (Msh6); cyclin A2 (Ccna2); and cyclin B2 (Ccnb2), were expressed in the two types of mouse. These TFs were predominantly involved in phosphorylation, DNA replication, cell division and DNA mismatch repair. In addition, specific TFs, including minichromosome maintenance complex component 7 (Mcm7); lymphoid-specific helicase (Hells); and minichromosome maintenance complex component 6 (Mcm6), that function in the unwinding of DNA were identified to participate in Mist1KO pancreatitis. The DEGs, including Cdc6, Mcm6, Msh6 and Wdr1 are closely associated with the regulation of caerulein-induced pancreatitis. Furthermore, other identified TFs were also involved in this type of regulation. PMID:25975747

A Scan of CDC-Authored Articles on Legal Epidemiology, 2011-2015

PubMed Central

Martini, Leila; Presley, David; Klieger, Sarah

2016-01-01

Objective: 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. Methods: 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. Results: 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. Conclusion: 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. PMID:28123227

The RNA-binding protein Spo5 promotes meiosis II by regulating cyclin Cdc13 in fission yeast.

PubMed

Arata, Mayumi; Sato, Masamitsu; Yamashita, Akira; Yamamoto, Masayuki

2014-03-01

Meiosis comprises two consecutive nuclear divisions, meiosis I and II. Despite this unique progression through the cell cycle, little is known about the mechanisms controlling the sequential divisions. In this study, we carried out a genetic screen to identify factors that regulate the initiation of meiosis II in the fission yeast Schizosaccharomyces pombe. We identified mutants deficient in meiosis II progression and repeatedly isolated mutants defective in spo5, which encodes an RNA-binding protein. Using fluorescence microscopy to visualize YFP-tagged protein, we found that spo5 mutant cells precociously lost Cdc13, the major B-type cyclin in fission yeast, before meiosis II. Importantly, the defect in meiosis II was rescued by increasing CDK activity. In wild-type cells, cdc13 transcripts increased during meiosis II, but this increase in cdc13 expression was weaker in spo5 mutants. Thus, Spo5 is a novel regulator of meiosis II that controls the level of cdc13 expression and promotes de novo synthesis of Cdc13. We previously reported that inhibition of Cdc13 degradation is necessary to initiate meiosis II; together with the previous information, the current findings indicate that the dual control of Cdc13 by de novo synthesis and suppression of proteolysis ensures the progression of meiosis II. © 2014 The Authors Genes to Cells © 2014 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

Maritime illness and death reporting and public health response, United States, 2010-2014.

PubMed

Stamatakis, Caroline E; Rice, Marion E; Washburn, Faith M; Krohn, Kristopher J; Bannerman, Millicent; Regan, Joanna J

2017-09-01

Deaths and certain illnesses onboard ships arriving at US ports are required to be reported to the US Centers for Disease Control and Prevention (CDC), and notifications of certain illnesses are requested. We performed a descriptive analysis of required maritime illness and death reports of presumptive diagnoses and requested notifications to CDC's Division of Global Migration and Quarantine, which manages CDC's Quarantine Stations, from January 2010 to December 2014. CDC Quarantine Stations received 2891 individual maritime case reports: 76.8% (2221/2891) illness reports, and 23.2% (670/2891) death reports. The most frequent individual illness reported was varicella (35.9%, 797/2221) and the most frequently reported causes of death were cardiovascular- or pulmonary-related conditions (79.6%, 533/670). There were 7695 cases of influenza-like illness received within aggregate notifications. CDC coordinated 63 contact investigations with partners to identify 972 contacts; 88.0% (855/972) were notified. There was documentation of 6.5% (19/293) receiving post-exposure prophylaxis. Three pertussis contacts were identified as secondary cases; and one tuberculosis contact was diagnosed with active tuberculosis. These data provide a picture of US maritime illness and death reporting and response. Varicella reports are the most frequent individual disease reports received. Contact investigations identified few cases of disease transmission. Copyright © 2017. Published by Elsevier Ltd.

Foodborne (1973-2013) and Waterborne (1971-2013) Disease Outbreaks - United States.

PubMed

Dewey-Mattia, Daniel; Roberts, Virginia A; Vieira, Antonio; Fullerton, Kathleen E

2016-10-14

CDC collects data on foodborne and waterborne disease outbreaks reported by all U.S. states and territories through the Foodborne Disease Outbreak Surveillance System (FDOSS) (http://www.cdc.gov/foodsafety/fdoss/surveillance/index.html) and the Waterborne Disease and Outbreak Surveillance System (WBDOSS) http://www.cdc.gov/healthywater/surveillance), respectively. These two systems are the primary source of national data describing the number of reported outbreaks; outbreak-associated illnesses, hospitalizations, and deaths; etiologic agents; water source or implicated foods; settings of exposure; and other factors associated with recognized foodborne and waterborne disease outbreaks in the United States.

Examining Demographic, Economic, and Educational Factors: Overweight Children in Pennsylvania

ERIC Educational Resources Information Center

Center for Rural Pennsylvania, 2005

2005-01-01

The number of overweight children and adolescents in the U.S. has reached epidemic proportions, according to the Centers for Disease Control and Prevention (CDC). In 2000, the CDC estimated that 15 percent of the nation's youth were overweight. Overweight children and adolescents are exposed to many health risks, most notably the increased risk…

76 FR 13191 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-10

.... Proposed Project FoodNet Non-O157 Shiga toxin-Producing E. coli Study: Assessment of Risk Factors for... (CDC). Background and Brief Description Each year many Shiga toxin-producing E. coli (STEC) infections... these requests, call the CDC Reports Clearance Officer at (404) 639-5960 or send an e-mail to om[email protected

Different roles of the small GTPases Rac1, Cdc42, and RhoG in CALEB/NGC-induced dendritic tree complexity.

PubMed

Schulz, Jana; Franke, Kristin; Frick, Manfred; Schumacher, Stefan

2016-10-01

Rho GTPases play prominent roles in the regulation of cytoskeletal reorganization. Many aspects have been elaborated concerning the individual functions of Rho GTPases in distinct signaling pathways leading to cytoskeletal rearrangements. However, major questions have yet to be answered regarding the integration and the signaling hierarchy of different Rho GTPases in regulating the cytoskeleton in fundamental physiological events like neuronal process differentiation. Here, we investigate the roles of the small GTPases Rac1, Cdc42, and RhoG in defining dendritic tree complexity stimulated by the transmembrane epidermal growth factor family member CALEB/NGC. Combining gain-of-function and loss-of-function analysis in primary hippocampal neurons, we find that Rac1 is essential for CALEB/NGC-mediated dendritic branching. Cdc42 reduces the complexity of dendritic trees. Interestingly, we identify the palmitoylated isoform of Cdc42 to adversely affect dendritic outgrowth and dendritic branching, whereas the prenylated Cdc42 isoform does not. In contrast to Rac1, CALEB/NGC and Cdc42 are not directly interconnected in regulating dendritic tree complexity. Unlike Rac1, the Rac1-related GTPase RhoG reduces the complexity of dendritic trees by acting upstream of CALEB/NGC. Mechanistically, CALEB/NGC activates Rac1, and RhoG reduces the amount of CALEB/NGC that is located at the right site for Rac1 activation at the cell membrane. Thus, Rac1, Cdc42, and RhoG perform very specific and non-redundant functions at different levels of hierarchy in regulating dendritic tree complexity induced by CALEB/NGC. Rho GTPases play a prominent role in dendritic branching. CALEB/NGC is a transmembrane member of the epidermal growth factor (EGF) family that mediates dendritic branching, dependent on Rac1. CALEB/NGC stimulates Rac1 activity. RhoG inhibits CALEB/NGC-mediated dendritic branching by decreasing the amount of CALEB/NGC at the plasma membrane. Palmitoylated, but not prenylated form of the GTPase Cdc42 decreases dendritic branching. CALEB/NGC and Cdc42 are not directly interconnected in regulating dendritic branching. Thus, CALEB/NGC organizes a Rho GTPase signaling module at the plasma membrane for shaping dendritic trees. © 2016 International Society for Neurochemistry.

Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R.

PubMed

Li, Ge; Park, Hyeon U; Liang, Dong; Zhao, Richard Y

2010-07-07

Cell cycle G2 arrest induced by HIV-1 Vpr is thought to benefit viral proliferation by providing an optimized cellular environment for viral replication and by skipping host immune responses. Even though Vpr-induced G2 arrest has been studied extensively, how Vpr triggers G2 arrest remains elusive. To examine this initiation event, we measured the Vpr effect over a single cell cycle. We found that even though Vpr stops the cell cycle at the G2/M phase, but the initiation event actually occurs in the S phase of the cell cycle. Specifically, Vpr triggers activation of Chk1 through Ser345 phosphorylation in an S phase-dependent manner. The S phase-dependent requirement of Chk1-Ser345 phosphorylation by Vpr was confirmed by siRNA gene silencing and site-directed mutagenesis. Moreover, downregulation of DNA replication licensing factors Cdt1 by siRNA significantly reduced Vpr-induced Chk1-Ser345 phosphorylation and G2 arrest. Even though hydroxyurea (HU) and ultraviolet light (UV) also induce Chk1-Ser345 phosphorylation in S phase under the same conditions, neither HU nor UV-treated cells were able to pass through S phase, whereas vpr-expressing cells completed S phase and stopped at the G2/M boundary. Furthermore, unlike HU/UV, Vpr promotes Chk1- and proteasome-mediated protein degradations of Cdc25B/C for G2 induction; in contrast, Vpr had little or no effect on Cdc25A protein degradation normally mediated by HU/UV. These data suggest that Vpr induces cell cycle G2 arrest through a unique molecular mechanism that regulates host cell cycle regulation in an S-phase dependent fashion.

Mapping of binding epitopes of a human decay-accelerating factor monoclonal antibody capable of enhancing rituximab-mediated complement-dependent cytotoxicity.

PubMed

Guo, Bo; Ma, Zheng-wei; Li, Hua; Xu, Gui-lian; Zheng, Ping; Zhu, Bo; Wu, Yu-Zhang; Zou, Qiang

2008-08-01

Complement-dependent cytotoxicity (CDC) is thought to be one of the most important mechanisms of action of therapeutic monoclonal antibodies (mAbs). The decay-accelerating factor (DAF) overexpressed in certain tumors limits the CDC effect of the therapeutic anticancer antibodies. The use of DAF blocking antibodies targeted specifically at cancer cells in combination with immunotherapeutic mAbs of cancer may improve the therapeutic effect in cancer patients. In this study, the lysis of Raji cells mediated by CDC was determined after blocking DAF function by anti-DAF polyclonal antibody and 3 mAbs (DG3, DG9, DA11) prepared in our laboratory, respectively, in the presence of the anti-CD20 chimeric mAb rituximab. The binding domains of the three anti-DAF mAbs were identified using yeast surface display technique, and the mimic epitopes of mAb DG3 were screened from a random phage-display nonapeptide library. The results showed that blocking DAF function by anti-DAF polyclonal antibody enhanced complement-mediated killing of Raji cells. Among the 3 mAbs against DAF, only DG3 was found to be able to remarkably enhance the CDC effect of the therapeutic mAb rituximab. DG3 bound to the third short consensus repeat (SCR) of DAF. Binding of DG3 to immobilized DAF was inhibited by mimic epitope peptides screened from the peptide library. Our results suggest that a higher level of DAF expressed by certain tumor cells is significant to abolish the CDC effect of therapeutic anticancer antibodies, and mAbs binding to SCR3 can enhance the complement-mediated killing of Raji cells. It is of significance to identify the DAF epitopes required in inhibiting CDC not only for better understanding of the relationship between the structure and function of DAF, but also for designing and developing anti-DAF mAbs capable of enhancing CDC.

Identifying Factors Associated with Risk Assessment Competencies of Public Health Emergency Responders.

PubMed

Hao, Jiejing; Ren, Jiaojiao; Wu, Qunhong; Hao, Yanhua; Sun, Hong; Ning, Ning; Ding, Ding

2017-06-04

This study aimed to better understand the current situation of risk assessment and identify the factors associated with competence of emergency responders in public health risk assessment. The participants were selected by a multi-stage, stratified cluster sampling method in Heilongjiang Centers for Disease Control and Prevention (CDC). The questionnaires that measured their perceptions on risk assessment competences were administered through the face-to-face survey. A final sample of 1889 staff was obtained. Of this sample, 78.6% of respondents rated their own risk assessment competences as "relatively low", contrasting with 21.4% rated as "relatively high". Most of the respondents (62.7%) did not participate in any risk assessment work. Only 13.7% and 42.7% of respondents reported participating in risk assessment training and were familiar with risk assessment tools. There existed statistical significance between risk assessment-related characteristics of respondents and their self-rated competences scores. Financial support from the government and administrative attention were regarded as the important factors contributing to risk assessment competences of CDC responders. Higher attention should be given to risk assessment training and enhancing the availability of surveillance data. Continuous efforts should be made to remove the financial and technical obstacles to improve the competences of risk assessment for public health emergency responders.

Identifying Factors Associated with Risk Assessment Competencies of Public Health Emergency Responders

PubMed Central

Hao, Jiejing; Ren, Jiaojiao; Wu, Qunhong; Hao, Yanhua; Sun, Hong; Ning, Ning; Ding, Ding

2017-01-01

This study aimed to better understand the current situation of risk assessment and identify the factors associated with competence of emergency responders in public health risk assessment. The participants were selected by a multi-stage, stratified cluster sampling method in Heilongjiang Centers for Disease Control and Prevention (CDC). The questionnaires that measured their perceptions on risk assessment competences were administered through the face-to-face survey. A final sample of 1889 staff was obtained. Of this sample, 78.6% of respondents rated their own risk assessment competences as “relatively low”, contrasting with 21.4% rated as “relatively high”. Most of the respondents (62.7%) did not participate in any risk assessment work. Only 13.7% and 42.7% of respondents reported participating in risk assessment training and were familiar with risk assessment tools. There existed statistical significance between risk assessment-related characteristics of respondents and their self-rated competences scores. Financial support from the government and administrative attention were regarded as the important factors contributing to risk assessment competences of CDC responders. Higher attention should be given to risk assessment training and enhancing the availability of surveillance data. Continuous efforts should be made to remove the financial and technical obstacles to improve the competences of risk assessment for public health emergency responders. PMID:28587226

Preparation and properties of plate-like titanate (PLT)/calcia-doped ceria (CDC) composites by sol-gel coating method.

PubMed

Liu, Xiangwen; Liu, Jingxiao; Dong, Xiaoli; Yin, Shu; Sato, Tsugio

2009-08-01

In order to obtain UV-shielding materials with good comfort, higher safety and effective UV-shielding ability, lepidocrocite type plate-like titanate (K(0.8)Li(0.27)Ti(1.73)O(4), donated as: PLT)/calcia-doped ceria (donated as: CDC) composites were synthesized by a sol-gel method. After dissolving Ce(NO(3))(3).6H(2)O and Ca(NO(3))(2).4H(2)O into absolute ethanol at 40 degrees C, glacial acetic acid (HAc) and PLT particles dispersed into absolute ethanol were added. Then, the solution was heated at 60 degrees C to get gel-like substance. This gel was dried in a vacuum oven at 333 K for 5 h, and then, the product was collected and ground in an agate mortar followed by calcination at 1073 K for 2 h to form PLT/CDC composites. By optimization, 20 mass% of CDC was coated by one operation. PLT/CDC composites with higher CDC content were obtained by repeating the coating process. The morphology, catalytic activity for the oxidation of organic material, UV-shielding ability and dynamic friction coefficient of as-obtained PLT/CDC composites were characterized. As a result, broad-spectrum UV-shielding composite materials with good comfort and low oxidation catalytic activity were successfully synthesized.

Dynamic and thermodynamic response of the Ras protein Cdc42Hs upon association with the effector domain of PAK3

PubMed Central

Moorman, Veronica R.; Valentine, Kathleen G.; Bédard, Sabrina; Kasinath, Vignesh; Dogan, Jakob; Love, Fiona M.; Wand, A. Joshua

2014-01-01

Human cell division cycle protein 42 (Cdc42Hs) is a small, Rho-type GTPase involved in multiple cellular processes through its interactions with downstream effectors. The binding domain of one such effector, the actin cytoskeleton-regulating p21 activated kinase 3 (PAK3) is known as PBD46. Nitrogen-15 backbone and carbon-13 methyl NMR relaxation were measured to investigate the dynamical changes in activated GMPPCP•Cdc42Hs upon PBD46 binding. Changes in internal motion of the Cdc42Hs, as revealed by methyl axis order parameters, were observed not only near the Cdc42Hs–PBD46 interface but also in remote sites on the Cdc42Hs molecule. The binding-induced changes in side chain dynamics propagate along the long axis of Cdc42Hs away from the site of PBD46 binding with a sharp distance dependence. Overall, the binding of the PBD46 effector domain on the dynamics of methyl bearing side chains of Cdc42Hs results in a modest rigidification, which is estimated to correspond to an unfavorable change in conformational entropy of approximately −10 kcal mol−1 at 298 K. A cluster of methyl probes closest to the nucleotide-binding pocket of Cdc42Hs become more rigid upon binding of PBD46 and is proposed to slow the catalytic hydrolysis of the γ phosphate moiety. An additional cluster of methyl probes surrounding the guanine ring become more flexible on binding of PBD46, presumably facilitating nucleotide exchange mediated by a guanosine exchange factor. In addition, the Rho insert helix, which is located at a site remote from the PBD46 binding interface, shows a significant dynamic response to PBD46 binding. PMID:25109462

Predictors of physician confidence to diagnose pneumonia and determine illness severity in ventilated patients. Australian and New Zealand practice in intensive care (ANZPIC II).

PubMed

Boots, R J; Lipman, J; Bellomo, R; Stephens, D; Heller, R E

2005-02-01

The manner in which elements of clinical history, physical examination and investigations influence subjectively assessed illness severity and outcome prediction is poorly understood. This study investigates the relationship between clinician and objectively assessed illness severity and the factors influencing clinician's diagnostic confidence and illness severity rating for ventilated patients with suspected pneumonia in the intensive care unit (ICU). A prospective study of fourteen ICUs included all ventilated admissions with a clinical diagnosis of pneumonia. Data collection included pneumonia type - community-acquired (CAP), hospital-acquired (HAP) and ventilator-associated (VAP), clinician determined illness severity (CDIS), diagnostic methods, clinical diagnostic confidence (CDC), microbiological isolates and antibiotic use. For 476 episodes of pneumonia (48% CAP, 24% HAP, 28% VAP), CDC was greatest for CAP (64% CAP, 50% HAP and 49% VAP, P<0.01) or when pneumonia was considered "life-threatening" (84% high CDC, 13% medium CDC and 3% low CDC, P<0. 001). "Life-threatening" pneumonia was predicted by worsening gas exchange (OR 4.8, CI 95% 2.3-10.2, P<0.001), clinical signs of consolidation (OR 2.0, CI 95% 1.2-3.2, P<0.01) and the Sepsis-Related Organ Failure Assessment (SOFA) Score (OR 1.1, CI 95% 1.1-1.2, P<0.001). Diagnostic confidence increased with CDIS (OR 16.3, CI 95% 8.4-31.4, P<0.001), definite pathogen isolation (OR 3.3, CI 95% 2.0-5.6) and clinical signs of consolidation (OR 2.1, CI 95% 1.3-3.3, P=0.001). Although the CDIS, SOFA Score and the Simplified Acute Physiologic Score (SAPS II) were all associated with mortality, the SAPS II Score was the best predictor of mortality (P = 0. 02). Diagnostic confidence for pneumonia is moderate but increases with more classical presentations. A small set of clinical parameters influence subjective assessment. Objective assessment using SAPS II Scoring is a better predictor of mortality.

7 CFR 6.32 - Globalization of licenses.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false Globalization of licenses. 6.32 Section 6.32 Agriculture Office of the Secretary of Agriculture IMPORT QUOTAS AND FEES Dairy Tariff-Rate Import Quota Licensing § 6.32 Globalization of licenses. If the Licensing Authority determines that entries of an article...

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.

7 CFR 6.33 - License fee.

Code of Federal Regulations, 2010 CFR

2010-01-01

... utilizing the electronic software designated for the purpose by the Licensing Authority. (c) If the license... 7 Agriculture 1 2010-01-01 2010-01-01 false License fee. 6.33 Section 6.33 Agriculture Office of... License fee. (a) A fee will be assessed each quota year for each license to defray the Department's costs...

R-ketorolac Targets Cdc42 and Rac1 and Alters Ovarian Cancer Cell Behaviors Critical for Invasion and Metastasis

PubMed Central

Guo, Yuna; Kenney, Shelby Ray; Muller, Carolyn Y.; Adams, Sarah; Rutledge, Teresa; Romero, Elsa; Murray-Krezan, Cristina; Prekeris, Rytis; Sklar, Larry A.; Hudson, Laurie G.; Wandinger-Ness, Angela

2015-01-01

Cdc42 (cell division control protein 42) and Rac1 (Ras-related C3 botulinum toxin substrate 1) are attractive therapeutic targets in ovarian cancer based on established importance in tumor cell migration, adhesion and invasion. Despite a predicted benefit, targeting GTPases has not yet been translated to clinical practice. We previously established that Cdc42 and constitutively active Rac1b are overexpressed in primary ovarian tumor tissues. Through high throughput screening and computational shape homology approaches we identified R-ketorolac as a Cdc42 and Rac1 inhibitor; distinct from the anti-inflammatory, cyclooxygenase inhibitory activity of S-ketorolac. In the present study, we establish R-ketorolac as an allosteric inhibitor of Cdc42 and Rac1. Cell-based assays validate R-ketorolac activity against Cdc42 and Rac1. Studies on immortalized human ovarian adenocarcinoma cells (SKOV3ip), and primary, patient-derived ovarian cancer cells show R-ketorolac is a robust inhibitor of growth factor or serum dependent Cdc42 and Rac1 activation with a potency and cellular efficacy similar to small molecule inhibitors of Cdc42 (CID2950007/ML141) and Rac1 (NSC23766). Furthermore, GTPase inhibition by R-ketorolac reduces downstream p21-activated kinases (PAK1/PAK2) effector activation by >80%. Multiple assays of cell behavior using SKOV3ip and primary patient-derived ovarian cancer cells show that R-ketorolac significantly inhibits cell adhesion, migration and invasion. In sum, we provide evidence for R-ketorolac as direct inhibitor of Cdc42 and Rac1 that is capable of modulating downstream GTPase-dependent, physiological responses, which are critical to tumor metastasis. Our findings demonstrate the selective inhibition of Cdc42 and Rac1 GTPases by an FDA approved drug-racemic ketorolac that can be used in humans. PMID:26206334

R-Ketorolac Targets Cdc42 and Rac1 and Alters Ovarian Cancer Cell Behaviors Critical for Invasion and Metastasis.

PubMed

Guo, Yuna; Kenney, S Ray; Muller, Carolyn Y; Adams, Sarah; Rutledge, Teresa; Romero, Elsa; Murray-Krezan, Cristina; Prekeris, Rytis; Sklar, Larry A; Hudson, Laurie G; Wandinger-Ness, Angela

2015-10-01

Cdc42 (cell division control protein 42) and Rac1 (Ras-related C3 botulinum toxin substrate 1) are attractive therapeutic targets in ovarian cancer based on established importance in tumor cell migration, adhesion, and invasion. Despite a predicted benefit, targeting GTPases has not yet been translated to clinical practice. We previously established that Cdc42 and constitutively active Rac1b are overexpressed in primary ovarian tumor tissues. Through high-throughput screening and computational shape homology approaches, we identified R-ketorolac as a Cdc42 and Rac1 inhibitor, distinct from the anti-inflammatory, cyclooxygenase inhibitory activity of S-ketorolac. In the present study, we establish R-ketorolac as an allosteric inhibitor of Cdc42 and Rac1. Cell-based assays validate R-ketorolac activity against Cdc42 and Rac1. Studies on immortalized human ovarian adenocarcinoma cells (SKOV3ip) and primary patient-derived ovarian cancer cells show that R-ketorolac is a robust inhibitor of growth factor or serum-dependent Cdc42 and Rac1 activation with a potency and cellular efficacy similar to small-molecule inhibitors of Cdc42 (CID2950007/ML141) and Rac1 (NSC23766). Furthermore, GTPase inhibition by R-ketorolac reduces downstream p21-activated kinases (PAK1/PAK2) effector activation by >80%. Multiple assays of cell behavior using SKOV3ip and primary patient-derived ovarian cancer cells show that R-ketorolac significantly inhibits cell adhesion, migration, and invasion. In summary, we provide evidence for R-ketorolac as a direct inhibitor of Cdc42 and Rac1 that is capable of modulating downstream GTPase-dependent, physiologic responses, which are critical to tumor metastasis. Our findings demonstrate the selective inhibition of Cdc42 and Rac1 GTPases by an FDA-approved drug, racemic ketorolac, that can be used in humans. ©2015 American Association for Cancer Research.

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

PubMed

Baldwin, Grant; Breiding, Matt; Sleet, David

2016-06-30

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

Suicidal Ideation and Attempts Among Students in Grades 8, 10, and 12 - Utah, 2015.

PubMed

Zwald, Marissa L; Annor, Francis B; Wilkinson, Amanda; Friedrichs, Mike; Fondario, Anna; Dunn, Angela C; Nakashima, Allyn; Gilbert, Leah K; Ivey-Stephenson, Asha

2018-04-20

Suicidal thoughts and behaviors among youths are important public health concerns in Utah, where the suicide rate among youths consistently exceeds the national rate and has been increasing for nearly a decade (1). In March 2017, CDC was invited to assist the Utah Department of Health (UDOH) with an investigation to characterize the epidemiology of fatal and nonfatal suicidal behaviors and identify risk and protective factors associated with these behaviors, among youths aged 10-17 years. This report presents findings related to nonfatal suicidal behaviors among Utah youths. To examine the prevalence of suicidal ideation and attempts among Utah youths and evaluate risk and protective factors, data from the 2015 Utah Prevention Needs Assessment survey were analyzed. Among 27,329 respondents in grades 8, 10, and 12, 19.6% reported suicidal ideation and 8.2% reported suicide attempts in the preceding 12 months. Significant risk factors for suicidal ideation and attempts included being bullied, illegal substance or tobacco use in the previous month, and psychological distress. A significant protective factor for suicidal ideation and attempts was a supportive family environment. UDOH, local health departments, and other stakeholders are using these findings to develop tailored suicide prevention strategies that address multiple risk and protective factors for suicidal ideation and attempts. Resources such as CDC's Preventing Suicide: A Technical Package of Policy, Programs, and Practices (2) can help states and communities identify strategies and approaches using the best available evidence to prevent suicide, which include tailored strategies for youths.

Risk and direct protective factors for youth violence: results from the Centers for Disease Control and Prevention's Multisite Violence Prevention Project.

PubMed

Henry, David B; Tolan, Patrick H; Gorman-Smith, Deborah; Schoeny, Michael E

2012-08-01

This study was conducted as part of a multisite effort to examine risk and direct protective factors for youth violence. The goal was to identify those factors in the lives of young people that increase or decrease the risk of violence. These analyses fill an important gap in the literature, as few studies have examined risk and direct protective factors for youth violence across multiple studies. Data on 4432 middle-school youth, from the CDC Multisite Violence Prevention Project were used. Evaluations were made of effects of variables coded as risk and direct protective factors in the fall of 6th grade on violence measured in spring of 7th and 8th grades. Factors tested included depression, delinquency, alcohol and drug involvement, involvement in family activities, academic achievement, attitudes toward school, truancy, and peer deviance. Most variables were coded with two sets of dummy variables indicating risk and protective directions of effects. Results showed that higher teacher-rated study skills were associated with lower subsequent violence across genders and ethnic groups. Affiliation with deviant peers was significantly associated with increased subsequent violence among youth reporting their race/ethnicity as white or other, marginally associated with increased violence among African-American youth, and unrelated among Latino youth. This study identified some factors than should be areas of interest for effective prevention programs. Some ethnic differences also should be considered in planning of prevention. The CDC Multisite Violence Prevention Project completed enrollment prior to July 2005. Copyright © 2012. Published by Elsevier Inc.

Influence of environmental pH on G2-phase arrest caused by ionizing radiation.

PubMed

Park, Heon Joo; Lee, Sang Hwa; Chung, HyunSook; Rhee, Yun Hee; Lim, Byung Uk; Ha, Sung Whan; Griffin, Robert J; Lee, Hyung Sik; Song, Chang Won; Choi, Eun Kyung

2003-01-01

We investigated the effects of an acidic environment on the G2/M-phase arrest, apoptosis, clonogenic death, and changes in cyclin B1-CDC2 kinase activity caused by a 4-Gy irradiation in RKO.C human colorectal cancer cells in vitro. The time to reach peak G2/M-phase arrest after irradiation was delayed in pH 6.6 medium compared to that in pH 7.5 medium. Furthermore, the radiation-induced G2/M-phase arrest decayed more slowly in pH 6.6 medium than in pH 7.5 medium. Finally, there was less radiation-induced apoptosis and clonogenic cell death in pH 6.6 medium than in pH 7.5 medium. It appeared that the prolongation of G2-phase arrest after irradiation in the acidic environment allowed for greater repair of radiation-induced DNA damage, thereby decreasing the radiation-induced cell death. The prolongation of G2-phase arrest after irradiation in the acidic pH environment appeared to be related at least in part to a prolongation of the phosphorylation of CDC2, which inhibited cyclin B1-CDC2 kinase activity.

Experiences of disability consumer-directed care users in Australia: results from a longitudinal qualitative study.

PubMed

Ottmann, Goetz; Laragy, Carmel; Haddon, Michelle

2009-09-01

The rapidly growing body of literature suggests that Consumer-directed Care (CDC) has the potential to empower consumers and improve the flexibility and quality of care. However, reports highlighting quality and risk concerns associated with CDC focusing on a longer time frame have been few. This paper presents the findings from a qualitative longitudinal evaluation of an Australian CDC programme. Focusing on the period between 2003 and 2008, it reports on the experiences of 12 families caring for a dependent family member. It is based on two external evaluations completed 6 and 36 months after enrollment, and one internal evaluation completed 48 months after enrollment. The findings were triangulated with internal memos, reports and minutes of meetings, as well as with the theoretical literature. The study demonstrates that CDC harbours considerable benefits for people with disabilities and their carers. However, the study also suggests that, over time, carers may experience an increased sense of isolation and lack of support as a result of their involvement in the CDC programme. The paper argues that the development of safeguards addressing these weaknesses is crucial for the sustainability of CDC programmes in contexts where risk cannot be simply transferred onto consumers.

Age-related guanine nucleotide exchange factor, mouse Zizimin2, induces filopodia in bone marrow-derived dendritic cells

PubMed Central

2012-01-01

Background We recently isolated and identified Zizimin2 as a functional factor that is highly expressed in murine splenic germinal center B cells after immunization with T-cell-dependent antigen. Zizimin2 was revealed to be a new family member of Dock (dedicator of cytokinesis), Dock11, which is the guanine nucleotide exchange factor for Cdc42, a low-molecular-weight GTPase. However, the molecular function of Zizimin2 in acquired immunity has not been elucidated. Results In this study, we show that the protein expression of Zizimin2, which is also restricted to lymphoid tissues and lymphocytes, is reduced in aged mice. Over-expression of full-length Zizimin2 induced filopodial formation in 293T cells, whereas expression of CZH2 domain inhibited it. Stimulation of Fcγ receptor and Toll-like receptor 4 triggered Zizimin2 up-regulation and Cdc42 activation in bone marrow-derived dendritic cells. Conclusions These data suggest that Zizimin2 is an immune-related and age-regulated guanine nucleotide exchange factor, which facilitates filopodial formation through activation of Cdc42, which results in activation of cell migration. PMID:22494997

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.

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.

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.

Al Qaeda’s Seapower Strategy

DTIC Science & Technology

2011-08-08

variety of factors have driven AQ to look towards the sea to spread and support their movement. The network’s combat power has depended upon on the...Islam will be established from the ocean to the ocean.” 6 Regardless, given the innovation and independence demonstrated by AQ’s “ franchises ” in...commercial use is licensed via a Creative Commons BY-NC-SA 3.0 license per our Terms of Use. No FACTUAL STATEMENT should be relied upon without further

Cdc42 controls primary mesenchyme cell morphogenesis in the sea urchin embryo.

PubMed

Sepúlveda-Ramírez, Silvia P; Toledo-Jacobo, Leslie; Henson, John H; Shuster, Charles B

2018-05-15

In the sea urchin embryo, gastrulation is characterized by the ingression and directed cell migration of primary mesenchyme cells (PMCs), as well as the primary invagination and convergent extension of the endomesoderm. Like all cell shape changes, individual and collective cell motility is orchestrated by Rho family GTPases and their modulation of the actomyosin cytoskeleton. And while endomesoderm specification has been intensively studied in echinoids, much less is known about the proximate regulators driving cell motility. Toward these ends, we employed anti-sense morpholinos, mutant alleles and pharmacological inhibitors to assess the role of Cdc42 during sea urchin gastrulation. While inhibition of Cdc42 expression or activity had only mild effects on PMC ingression, PMC migration, alignment and skeletogenesis were disrupted in the absence of Cdc42, as well as elongation of the archenteron. PMC migration and patterning of the larval skeleton relies on the extension of filopodia, and Cdc42 was required for filopodia in vivo as well as in cultured PMCs. Lastly, filopodial extension required both Arp2/3 and formin actin-nucleating factors, supporting models of filopodial nucleation observed in other systems. Together, these results suggest that Cdc42 plays essential roles during PMC cell motility and organogenesis. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Bruton's tyrosine kinase and protein kinase C µ are required for TLR7/9-induced IKKα and IRF-1 activation and interferon-β production in conventional dendritic cells.

PubMed

Li, Yan-Feng; Lee, Koon-Guan; Ou, Xijun; Lam, Kong-Peng

2014-01-01

Stimulation of TLR7/9 by their respective ligands leads to the activation of IκB kinase α (IKKα) and Interferon Regulatory Factor 1 (IRF-1) and results in interferon (IFN)-β production in conventional dendritic cells (cDC). However, which other signaling molecules are involved in IKKα and IRF-1 activation during TLR7/9 signaling pathway are not known. We and others have shown that Bruton's Tyrosine Kinase (BTK) played a part in TLR9-mediated cytokine production in B cells and macrophages. However, it is unclear if BTK participates in TLR7/9-induced IFN-β production in cDC. In this study, we show that BTK is required for IFN-β synthesis in cDC upon TLR7/9 stimulation and that stimulated BTK-deficient cDC are defective in the induction of IKKα/β phosphorylation and IRF-1 activation. In addition, we demonstrate that Protein Kinase C µ (PKCµ) is also required for TLR7/9-induced IRF-1 activation and IFN-β upregulation in cDC and acts downstream of BTK. Taken together, we have uncovered two new molecules, BTK and PKCµ, that are involved in TLR7/9-triggered IFN-β production in cDC.

Genome-wide Analysis Reveals Extensive Functional Interaction between DNA Replication Initiation and Transcription in the Genome of Trypanosoma brucei

PubMed Central

Tiengwe, Calvin; Marcello, Lucio; Farr, Helen; Dickens, Nicholas; Kelly, Steven; Swiderski, Michal; Vaughan, Diane; Gull, Keith; Barry, J. David; Bell, Stephen D.; McCulloch, Richard

2012-01-01

Summary Identification of replication initiation sites, termed origins, is a crucial step in understanding genome transmission in any organism. Transcription of the Trypanosoma brucei genome is highly unusual, with each chromosome comprising a few discrete transcription units. To understand how DNA replication occurs in the context of such organization, we have performed genome-wide mapping of the binding sites of the replication initiator ORC1/CDC6 and have identified replication origins, revealing that both localize to the boundaries of the transcription units. A remarkably small number of active origins is seen, whose spacing is greater than in any other eukaryote. We show that replication and transcription in T. brucei have a profound functional overlap, as reducing ORC1/CDC6 levels leads to genome-wide increases in mRNA levels arising from the boundaries of the transcription units. In addition, ORC1/CDC6 loss causes derepression of silent Variant Surface Glycoprotein genes, which are critical for host immune evasion. PMID:22840408

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

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.

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

Use of Ancillary Carbapenemase Tests To Improve Specificity of Phenotypic Definitions for Carbapenemase-Producing Enterobacteriaceae.

PubMed

Miller, Shelley A; Hindler, Janet A; Chengcuenca, Angelo; Humphries, Romney M

2017-06-01

Carbapenemase-producing Enterobacteriaceae (CPE) are a significant threat to public health. In 2015, CDC revised the surveillance definition for CPE to include all Enterobacteriaceae resistant to any carbapenem tested. However, this definition is associated with poor specificity. We evaluated the performance of this definition, compared to carbapenemase PCR, for a collection of 125 Enterobacteriaceae We also investigated the impact of ancillary testing for carbapenemase of isolates that met the CDC CPE surveillance definition. The two ancillary tests evaluated were the Xpert Carba-R assay, a molecular test, and the carbapenem inactivation method (CIM). Two variables were evaluated for the CIM: suspension of organisms in double-distilled water (ddH 2 O) versus tryptic soy broth (TSB) to incubate disks, and incubation of plates for 6 h versus 18 to 20 h. The sensitivity and specificity of the Carba-R assay were 100% compared to the results of in-house PCR. The sensitivities of the CIM performed with TSB were 94.6% when read at 6 h and 97.7% when read at 18 to 20 h; the sensitivities with ddH 2 O were 88.0% when read at 6 h and 93.0% when incubated for 18 to 20 h. The specificity was 100% for all variables tested. Without ancillary testing, the sensitivity of the CDC definition was 98.9% for CPE, and the specificity was 6.1%. Testing isolates that screened positive by the CDC definition with the Xpert Carba-R did not change the sensitivity, and it improved the specificity to 100%. Similarly, the use of the CIM (TSB and 18 to 20 h of incubation) to confirm screen-positive isolates resulted in a sensitivity of 95.6% and specificity of 100%. Copyright © 2017 American Society for Microbiology.

46 CFR 11.705 - Route familiarization requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... such as bridges, narrow channels, or sharp turns; and, (6) Any other factors unique to the route that... paragraph (c) of this section. (c) An applicant who currently holds a deck officer license or MMC...

Redrawing the US Obesity Landscape: Bias-Corrected Estimates of State-Specific Adult Obesity Prevalence

PubMed Central

Ward, Zachary J.; Long, Michael W.; Resch, Stephen C.; Gortmaker, Steven L.; Cradock, Angie L.; Giles, Catherine; Hsiao, Amber; Wang, Y. Claire

2016-01-01

Background State-level estimates from the Centers for Disease Control and Prevention (CDC) underestimate the obesity epidemic because they use self-reported height and weight. We describe a novel bias-correction method and produce corrected state-level estimates of obesity and severe obesity. Methods Using non-parametric statistical matching, we adjusted self-reported data from the Behavioral Risk Factor Surveillance System (BRFSS) 2013 (n = 386,795) using measured data from the National Health and Nutrition Examination Survey (NHANES) (n = 16,924). We validated our national estimates against NHANES and estimated bias-corrected state-specific prevalence of obesity (BMI≥30) and severe obesity (BMI≥35). We compared these results with previous adjustment methods. Results Compared to NHANES, self-reported BRFSS data underestimated national prevalence of obesity by 16% (28.67% vs 34.01%), and severe obesity by 23% (11.03% vs 14.26%). Our method was not significantly different from NHANES for obesity or severe obesity, while previous methods underestimated both. Only four states had a corrected obesity prevalence below 30%, with four exceeding 40%–in contrast, most states were below 30% in CDC maps. Conclusions Twelve million adults with obesity (including 6.7 million with severe obesity) were misclassified by CDC state-level estimates. Previous bias-correction methods also resulted in underestimates. Accurate state-level estimates are necessary to plan for resources to address the obesity epidemic. PMID:26954566

Characteristics of and Precipitating Circumstances Surrounding Suicide Among Persons Aged 10-17 Years - Utah, 2011-2015.

PubMed

Annor, Francis B; Zwald, Marissa L; Wilkinson, Amanda; Friedrichs, Mike; Fondario, Anna; Dunn, Angela; Nakashima, Allyn; Gilbert, Leah K; Ivey-Stephenson, Asha Z

2018-03-23

In 2015, suicide was the third leading cause of death among persons aged 10-17 years (1), and in Utah, the age-adjusted suicide rate was consistently higher than the national rate during the past decade (2). In January 2017, the Utah Department of Health (UDOH) invited CDC to assist with an epidemiologic investigation of suicides among youths aged 10-17 years during 2011-2015 to identify precipitating factors. CDC analyzed data from the Utah Violent Death Reporting System (UTVDRS), National Vital Statistics System, and additional information collected in the field. During 2011-2015 in Utah, 150 youths died by suicide. Approximately three fourths of decedents were male (77.4%) and aged 15-17 years (75.4%). During this period, the unadjusted suicide rate per 100,000 youths in Utah increased 136.2%, from 4.7 per 100,000 population (2011) to 11.1 (2015), whereas among youths nationwide, the rate increased 23.5%, from 3.4 to 4.1. Among suicide decedents with circumstances data available, more than two thirds (68.3%) had multiple precipitating circumstances, including mental health diagnosis (35.2%), depressed mood (31.0%), recent crisis (55.3%), and history of suicidal ideation or attempt (29.6%). CDC's technical package of policies, programs, and practices to prevent suicide supported by the best available evidence can be used as a suicide prevention resource (3).

34 CFR 6.3 - Licensing of Government-owned patents.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 1 2011-07-01 2011-07-01 false Licensing of Government-owned patents. 6.3 Section 6.3 Education Office of the Secretary, Department of Education INVENTIONS AND PATENTS (GENERAL) § 6.3 Licensing of Government-owned patents. (a) Licenses to practice inventions covered by patents and pending...

34 CFR 6.3 - Licensing of Government-owned patents.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 34 Education 1 2012-07-01 2012-07-01 false Licensing of Government-owned patents. 6.3 Section 6.3 Education Office of the Secretary, Department of Education INVENTIONS AND PATENTS (GENERAL) § 6.3 Licensing of Government-owned patents. (a) Licenses to practice inventions covered by patents and pending...

34 CFR 6.3 - Licensing of Government-owned patents.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 34 Education 1 2013-07-01 2013-07-01 false Licensing of Government-owned patents. 6.3 Section 6.3 Education Office of the Secretary, Department of Education INVENTIONS AND PATENTS (GENERAL) § 6.3 Licensing of Government-owned patents. (a) Licenses to practice inventions covered by patents and pending...

34 CFR 6.3 - Licensing of Government-owned patents.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 34 Education 1 2014-07-01 2014-07-01 false Licensing of Government-owned patents. 6.3 Section 6.3 Education Office of the Secretary, Department of Education INVENTIONS AND PATENTS (GENERAL) § 6.3 Licensing of Government-owned patents. (a) Licenses to practice inventions covered by patents and pending...

34 CFR 6.3 - Licensing of Government-owned patents.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Licensing of Government-owned patents. 6.3 Section 6.3 Education Office of the Secretary, Department of Education INVENTIONS AND PATENTS (GENERAL) § 6.3 Licensing of Government-owned patents. (a) Licenses to practice inventions covered by patents and pending...

An Evaluation of the Conservative Dual-Criterion Method for Teaching University Students to Visually Inspect AB-Design Graphs

ERIC Educational Resources Information Center

Stewart, Kelise K.; Carr, James E.; Brandt, Charles W.; McHenry, Meade M.

2007-01-01

The present study evaluated the effects of both a traditional lecture and the conservative dual-criterion (CDC) judgment aid on the ability of 6 university students to visually inspect AB-design line graphs. The traditional lecture reliably failed to improve visual inspection accuracy, whereas the CDC method substantially improved the performance…

Testing the Adequacy of a Semi-Markov Process

DTIC Science & Technology

2015-09-17

emphasis on covariate detection. 49 VI. BMI Model Analysis According to the Centers of Disease Control and Prevention (CDC) website [24], childhood obesity ...identified an increasing trend over a span of merely four years. Previous studies have drawn correlations between childhood obesity and various childhood and...started in recent years targeting poor dieting and lack of exercise, two of the primary causal factors in childhood obesity according to the CDC

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.

Delivering risk information in a dynamic information environment: Framing and authoritative voice in Centers for Disease Control (CDC) and primetime broadcast news media communications during the 2014 Ebola outbreak.

PubMed

Kott, Anne; Limaye, Rupali J

2016-11-01

During a disease outbreak, media serve as primary transmitters of information from public health agencies to the public, and have been shown to influence both behavior and perception of risk. Differences in news frequency, framing and information source can impact the public's interpretation of risk messages and subsequent attitudes and behaviors about a particular threat. The media's framing of an outbreak is important, as it may affect both perception of risk and the ability to process important health information. To understand how risk communication by the Centers for Disease Control and Prevention (CDC) during the 2014 Ebola outbreak was framed and delivered and to what extent primetime broadcast news media mirrored CDC's framing and authoritative voice, 209 CDC communications and primetime broadcast transcripts issued between July 24 and December 29, 2014 were analyzed and coded by thematic frame and authoritative voice. Dominant frame and voice were determined for each month and for overall period of analysis. Medical frame was dominant in CDC (60%), Anderson Cooper 360 (49%), The Rachel Maddow Show (47%) and All In with Chris Hayes (47%). The human interest frame was dominant in The Kelly File (45%), while The O'Reilly Factor coverage was equally split between sociopolitical and medical frames (28%, respectively). Primetime news media also changed dominant frames over time. Dominant authoritative voice in CDC communications was that of CDC officials, while primetime news dominantly featured local and federal (non-CDC) government officials and academic/medical experts. Differences in framing and delivery could have led the public to interpret risk in a different way than intended by CDC. Overall, public health agencies should consider adapting risk communication strategies to account for a dynamic news environment and the media's agenda. Options include adapting communications to short-form styles and embracing the concept of storytelling. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of emergency drug releases from the Centers for Disease Control and Prevention Quarantine Stations

PubMed Central

Roohi, Shahrokh; Grinnell, Margaret; Sandoval, Michelle; Cohen, Nicole J.; Crocker, Kimberly; Allen, Christopher; Dougherty, Cindy; Jolly, Julian; Pesik, Nicki

2018-01-01

The Centers for Disease Control and Prevention (CDC) Quarantine Stations distribute select lifesaving drug products that are not commercially available or are in limited supply in the United States for emergency treatment of certain health conditions. Following a retrospective analysis of shipment records, the authors estimated an average of 6.66 hours saved per shipment when drug products were distributed from quarantine stations compared to a hypothetical centralized site from CDC headquarters in Atlanta, GA. This evaluation supports the continued use of a decentralized model which leverages CDC's regional presence and maximizes efficiency in the distribution of lifesaving drugs. PMID:25779896

Evaluation of emergency drug releases from the Centers for Disease Control and Prevention Quarantine Stations.

PubMed

Roohi, Shahrokh; Grinnell, Margaret; Sandoval, Michelle; Cohen, Nicole J; Crocker, Kimberly; Allen, Christopher; Dougherty, Cindy; Jolly, Julian; Pesik, Nicki

2015-01-01

The Centers for Disease Control and Prevention (CDC) Quarantine Stations distribute select lifesaving drug products that are not commercially available or are in limited supply in the United States for emergency treatment of certain health conditions. Following a retrospective analysis of shipment records, the authors estimated an average of 6.66 hours saved per shipment when drug products were distributed from quarantine stations compared to a hypothetical centralized site from CDC headquarters in Atlanta, GA. This evaluation supports the continued use of a decentralized model which leverages CDC's regional presence and maximizes efficiency in the distribution of lifesaving drugs.

Accumulation of Phosphorus-Containing Compounds in Developing Seeds of Low-Phytate Pea (Pisum sativum L.) Mutants

PubMed Central

Shunmugam, Arun S.K.; Bock, Cheryl; Arganosa, Gene C.; Georges, Fawzy; Gray, Gordon R.; Warkentin, Thomas D.

2014-01-01

Low phytic acid (lpa) crops are low in phytic acid and high in inorganic phosphorus (Pi). In this study, two lpa pea genotypes, 1-150-81, 1-2347-144, and their progenitor CDC Bronco were grown in field trials for two years. The lpa genotypes were lower in IP6 and higher in Pi when compared to CDC Bronco. The total P concentration was similar in lpa genotypes and CDC Bronco throughout the seed development. The action of myo-inositol phosphate synthase (MIPS) (EC 5.5.1.4) is the first and rate-limiting step in the phytic acid biosynthesis pathway. Aiming at understanding the genetic basis of the lpa mutation in the pea, a 1530 bp open reading frame of MIPS was amplified from CDC Bronco and the lpa genotypes. Sequencing results showed no difference in coding sequence in MIPS between CDC Bronco and lpa genotypes. Transcription levels of MIPS were relatively lower at 49 days after flowering (DAF) than at 14 DAF for CDC Bronco and lpa lines. This study elucidated the rate and accumulation of phosphorus compounds in lpa genotypes. The data also demonstrated that mutation in MIPS was not responsible for the lpa trait in these pea lines. PMID:27135314

Yeast heterochromatin regulators Sir2 and Sir3 act directly at euchromatic DNA replication origins.

PubMed

Hoggard, Timothy A; Chang, FuJung; Perry, Kelsey Rae; Subramanian, Sandya; Kenworthy, Jessica; Chueng, Julie; Shor, Erika; Hyland, Edel M; Boeke, Jef D; Weinreich, Michael; Fox, Catherine A

2018-05-01

Most active DNA replication origins are found within euchromatin, while origins within heterochromatin are often inactive or inhibited. In yeast, origin activity within heterochromatin is negatively controlled by the histone H4K16 deacetylase, Sir2, and at some heterochromatic loci also by the nucleosome binding protein, Sir3. The prevailing view has been that direct functions of Sir2 and Sir3 are confined to heterochromatin. However, growth defects in yeast mutants compromised for loading the MCM helicase, such as cdc6-4, are suppressed by deletion of either SIR2 or SIR3. While these and other observations indicate that SIR2,3 can have a negative impact on at least some euchromatic origins, the genomic scale of this effect was unknown. It was also unknown whether this suppression resulted from direct functions of Sir2,3 within euchromatin, or was an indirect effect of their previously established roles within heterochromatin. Using MCM ChIP-Seq, we show that a SIR2 deletion rescued MCM complex loading at ~80% of euchromatic origins in cdc6-4 cells. Therefore, Sir2 exhibited a pervasive effect at the majority of euchromatic origins. Using MNase-H4K16ac ChIP-Seq, we show that origin-adjacent nucleosomes were depleted for H4K16 acetylation in a SIR2-dependent manner in wild type (i.e. CDC6) cells. In addition, we present evidence that both Sir2 and Sir3 bound to nucleosomes adjacent to euchromatic origins. The relative levels of each of these molecular hallmarks of yeast heterochromatin-SIR2-dependent H4K16 hypoacetylation, Sir2, and Sir3 -correlated with how strongly a SIR2 deletion suppressed the MCM loading defect in cdc6-4 cells. Finally, a screen for histone H3 and H4 mutants that could suppress the cdc6-4 growth defect identified amino acids that map to a surface of the nucleosome important for Sir3 binding. We conclude that heterochromatin proteins directly modify the local chromatin environment of euchromatic DNA replication origins.

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.

INM Integrated Noise Model Version 2. Programmer’s Guide

DTIC Science & Technology

1979-09-01

cost, turnaround time, and system-dependent limitations. 3.2 CONVERSION PROBLEMS Item Item Item No. Desciption Category 1 BLOCK DATA Initialization IBM ...Restricted 2 Boolean Operations Differences Call Statement Parameters Extensions 4 Data Initialization IBM Restricted 5 ENTRY Differences 6 EQUIVALENCE...Machine Dependent 7 Format: A CDC Extension 8 Hollerith Strings IBM Restricted 9 Hollerith Variables IBM Restricted 10 Identifier Names CDC Extension

78 FR 69683 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-20

... public in accordance with provisions set forth in Section 552b(c) (4) and (6), Title 5 U.S.C., and the...: Gregory Anderson, M.S., M.P.H., Scientific Review Officer, CDC, 1600 Clifton Road NE., Mailstop E60... Disease Control and Prevention (CDC) announces the aforementioned meeting: Time And Date: 1:00 p.m.-3:00 p...

Steady-State Acceptor Fluorescence Anisotropy Imaging under Evanescent Excitation for Visualisation of FRET at the Plasma Membrane

PubMed Central

Devauges, Viviane; Matthews, Daniel R.; Aluko, Justin; Nedbal, Jakub; Levitt, James A.; Poland, Simon P.; Coban, Oana; Weitsman, Gregory; Monypenny, James; Ng, Tony; Ameer-Beg, Simon M.

2014-01-01

We present a novel imaging system combining total internal reflection fluorescence (TIRF) microscopy with measurement of steady-state acceptor fluorescence anisotropy in order to perform live cell Förster Resonance Energy Transfer (FRET) imaging at the plasma membrane. We compare directly the imaging performance of fluorescence anisotropy resolved TIRF with epifluorescence illumination. The use of high numerical aperture objective for TIRF required correction for induced depolarization factors. This arrangement enabled visualisation of conformational changes of a Raichu-Cdc42 FRET biosensor by measurement of intramolecular FRET between eGFP and mRFP1. Higher activity of the probe was found at the cell plasma membrane compared to intracellularly. Imaging fluorescence anisotropy in TIRF allowed clear differentiation of the Raichu-Cdc42 biosensor from negative control mutants. Finally, inhibition of Cdc42 was imaged dynamically in live cells, where we show temporal changes of the activity of the Raichu-Cdc42 biosensor. PMID:25360776

Competing targets of microRNA-608 affect anxiety and hypertension

PubMed Central

Hanin, Geula; Shenhar-Tsarfaty, Shani; Yayon, Nadav; Hoe, Yau Yin; Bennett, Estelle R.; Sklan, Ella H.; Rao, Dabeeru. C.; Rankinen, Tuomo; Bouchard, Claude; Geifman-Shochat, Susana; Shifman, Sagiv; Greenberg, David S.; Soreq, Hermona

2014-01-01

MicroRNAs (miRNAs) can repress multiple targets, but how a single de-balanced interaction affects others remained unclear. We found that changing a single miRNA–target interaction can simultaneously affect multiple other miRNA–target interactions and modify physiological phenotype. We show that miR-608 targets acetylcholinesterase (AChE) and demonstrate weakened miR-608 interaction with the rs17228616 AChE allele having a single-nucleotide polymorphism (SNP) in the 3′-untranslated region (3′UTR). In cultured cells, this weakened interaction potentiated miR-608-mediated suppression of other targets, including CDC42 and interleukin-6 (IL6). Postmortem human cortices homozygote for the minor rs17228616 allele showed AChE elevation and CDC42/IL6 decreases compared with major allele homozygotes. Additionally, minor allele heterozygote and homozygote subjects showed reduced cortisol and elevated blood pressure, predicting risk of anxiety and hypertension. Parallel suppression of the conserved brain CDC42 activity by intracerebroventricular ML141 injection caused acute anxiety in mice. We demonstrate that SNPs in miRNA-binding regions could cause expanded downstream effects changing important biological pathways. PMID:24722204

Polarizing the Neuron through Sustained Co-expression of Alternatively Spliced Isoforms.

PubMed

Yap, Karen; Xiao, Yixin; Friedman, Brad A; Je, H Shawn; Makeyev, Eugene V

2016-05-10

Alternative splicing (AS) is an important source of proteome diversity in eukaryotes. However, how this affects protein repertoires at a single-cell level remains an open question. Here, we show that many 3'-terminal exons are persistently co-expressed with their alternatives in mammalian neurons. In an important example of this scenario, cell polarity gene Cdc42, a combination of polypyrimidine tract-binding, protein-dependent, and constitutive splicing mechanisms ensures a halfway switch from the general (E7) to the neuron-specific (E6) alternative 3'-terminal exon during neuronal differentiation. Perturbing the nearly equimolar E6/E7 ratio in neurons results in defects in both axonal and dendritic compartments and suggests that Cdc42E7 is involved in axonogenesis, whereas Cdc42E6 is required for normal development of dendritic spines. Thus, co-expression of a precise blend of functionally distinct splice isoforms rather than a complete switch from one isoform to another underlies proper structural and functional polarization of neurons. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

MicroRNA let-7c Inhibits Cell Proliferation and Induces Cell Cycle Arrest by Targeting CDC25A in Human Hepatocellular Carcinoma

PubMed Central

Zhu, Xiuming; Wu, Lingjiao; Yao, Jian; Jiang, Han; Wang, Qiangfeng; Yang, Zhijian; Wu, Fusheng

2015-01-01

Down-regulation of the microRNA let-7c plays an important role in the pathogenesis of human hepatocellular carcinoma (HCC). The aim of the present study was to determine whether the cell cycle regulator CDC25A is involved in the antitumor effect of let-7c in HCC. The expression levels of let-7c in HCC cell lines were examined by quantitative real-time PCR, and a let-7c agomir was transfected into HCC cells to overexpress let-7c. The effects of let-7c on HCC proliferation, apoptosis and cell cycle were analyzed. The in vivo tumor-inhibitory efficacy of let-7c was evaluated in a xenograft mouse model of HCC. Luciferase reporter assays and western blotting were conducted to identify the targets of let-7c and to determine the effects of let-7c on CDC25A, CyclinD1, CDK6, pRb and E2F2 expression. The results showed that the expression levels of let-7c were significantly decreased in HCC cell lines. Overexpression of let-7c repressed cell growth, induced cell apoptosis, led to G1 cell cycle arrest in vitro, and suppressed tumor growth in a HepG2 xenograft model in vivo. The luciferase reporter assay showed that CDC25A was a direct target of let-7c, and that let-7c inhibited the expression of CDC25A protein by directly targeting its 3ʹ UTR. Restoration of CDC25A induced a let-7c-mediated G1-to-S phase transition. Western blot analysis demonstrated that overexpression of let-7c decreased CyclinD1, CDK6, pRb and E2F2 protein levels. In conclusion, this study indicates that let-7c suppresses HCC progression, possibly by directly targeting the cell cycle regulator CDC25A and indirectly affecting its downstream target molecules. Let-7c may therefore be an effective therapeutic target for HCC. PMID:25909324

Centers for Disease Control and Prevention Funding for HIV Testing Associated With Higher State Percentage of Persons Tested.

PubMed

Hayek, Samah; Dietz, Patricia M; Van Handel, Michelle; Zhang, Jun; Shrestha, Ram K; Huang, Ya-Lin A; Wan, Choi; Mermin, Jonathan

2015-01-01

To assess the association between state per capita allocations of Centers for Disease Control and Prevention (CDC) funding for HIV testing and the percentage of persons tested for HIV. We examined data from 2 sources: 2011 Behavioral Risk Factor Surveillance System and 2010-2011 State HIV Budget Allocations Reports. Behavioral Risk Factor Surveillance System data were used to estimate the percentage of persons aged 18 to 64 years who had reported testing for HIV in the last 2 years in the United States by state. State HIV Budget Allocations Reports were used to calculate the state mean annual per capita allocations for CDC-funded HIV testing reported by state and local health departments in the United States. The association between the state fixed-effect per capita allocations for CDC-funded HIV testing and self-reported HIV testing in the last 2 years among persons aged 18 to 64 years was assessed with a hierarchical logistic regression model adjusting for individual-level characteristics. The percentage of persons tested for HIV in the last 2 years. In 2011, 18.7% (95% confidence interval = 18.4-19.0) of persons reported being tested for HIV in last 2 years (state range, 9.7%-28.2%). During 2010-2011, the state mean annual per capita allocation for CDC-funded HIV testing was $0.34 (state range, $0.04-$1.04). A $0.30 increase in per capita allocation for CDC-funded HIV testing was associated with an increase of 2.4 percentage points (14.0% vs 16.4%) in the percentage of persons tested for HIV per state. Providing HIV testing resources to health departments was associated with an increased percentage of state residents tested for HIV.

Yeast G-proteins mediate directional sensing and polarization behaviors in response to changes in pheromone gradient direction

PubMed Central

Moore, Travis I.; Tanaka, Hiromasa; Kim, Hyung Joon; Jeon, Noo Li; Yi, Tau-Mu

2013-01-01

Yeast cells polarize by projecting up mating pheromone gradients, a classic cell polarity behavior. However, these chemical gradients may shift direction. We examine how yeast cells sense and respond to a 180o switch in the direction of microfluidically generated pheromone gradients. We identify two behaviors: at low concentrations of α-factor, the initial projection grows by bending, whereas at high concentrations, cells form a second projection toward the new source. Mutations that increase heterotrimeric G-protein activity expand the bending-growth morphology to high concentrations; mutations that increase Cdc42 activity result in second projections at low concentrations. Gradient-sensing projection bending requires interaction between Gβγ and Cdc24, whereas gradient-nonsensing projection extension is stimulated by Bem1 and hyperactivated Cdc42. Of interest, a mutation in Gα affects both bending and extension. Finally, we find a genetic perturbation that exhibits both behaviors. Overexpression of the formin Bni1, a component of the polarisome, makes both bending-growth projections and second projections at low and high α-factor concentrations, suggesting a role for Bni1 downstream of the heterotrimeric G-protein and Cdc42 during gradient sensing and response. Thus we demonstrate that G-proteins modulate in a ligand-dependent manner two fundamental cell-polarity behaviors in response to gradient directional change. PMID:23242998

Formocresol versus calcium hydroxide direct pulp capping of human primary molars: two year follow-up.

PubMed

Aminabadi, Naser Asl; Farahani, Ramin Mostofi Zadeh; Oskouei, Sina Ghertasi

2010-01-01

Clinical and radiographic evaluation of the premedicated direct pulp capping using formocresol (PDC) versus conventional direct pulp capping using calcium hydroxide (CDC) in human carious primary molars. A total of 120 vital primary molars with pinpoint exposure during caries removal in 84 patients aged 4-5 years were selected. In the PDC group (n = 60), 20% Buckley's formocresol solution, and in the CDC group (n = 60), calcium hydroxide powder were applied to the exposure sites followed by placement of zinc oxide-eugenol base. Teeth were restored with preformed stainless steel crowns. Clinical and radiographic evaluations of the treatment outcomes were performed at regular intervals of 6 and 12 months, respectively, for two years post-operatively. The prevalence of spontaneous pain, sensitivity on percussion, and fistula were significantly higher in the CDC group compared to the PDC group (P < 0.05). The number of teeth exhibiting periapical/furcal radiolucency or external/internal root resorption was also higher in the CDC group (P < 0.05). The clinical success rate of the PDC was 90% compared to the 61.7% of the CDC (P < 0.05). The radiographic success rates of the PDC and CDC groups were 85% and 53.3%, respectively (P < 0.05). It seems formocresol premedicated direct pulp capping could safely be used as a substitute for conventional direct pulp capping.

Identification of the quinolinedione inhibitor binding site in Cdc25 phosphatase B through docking and molecular dynamics simulations.

PubMed

Ge, Yushu; van der Kamp, Marc; Malaisree, Maturos; Liu, Dan; Liu, Yi; Mulholland, Adrian J

2017-11-01

Cdc25 phosphatase B, a potential target for cancer therapy, is inhibited by a series of quinones. The binding site and mode of quinone inhibitors to Cdc25B remains unclear, whereas this information is important for structure-based drug design. We investigated the potential binding site of NSC663284 [DA3003-1 or 6-chloro-7-(2-morpholin-4-yl-ethylamino)-quinoline-5, 8-dione] through docking and molecular dynamics simulations. Of the two main binding sites suggested by docking, the molecular dynamics simulations only support one site for stable binding of the inhibitor. Binding sites in and near the Cdc25B catalytic site that have been suggested previously do not lead to stable binding in 50 ns molecular dynamics (MD) simulations. In contrast, a shallow pocket between the C-terminal helix and the catalytic site provides a favourable binding site that shows high stability. Two similar binding modes featuring protein-inhibitor interactions involving Tyr428, Arg482, Thr547 and Ser549 are identified by clustering analysis of all stable MD trajectories. The relatively flexible C-terminal region of Cdc25B contributes to inhibitor binding. The binding mode of NSC663284, identified through MD simulation, likely prevents the binding of protein substrates to Cdc25B. The present results provide useful information for the design of quinone inhibitors and their mechanism of inhibition.

Identification of the quinolinedione inhibitor binding site in Cdc25 phosphatase B through docking and molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Ge, Yushu; van der Kamp, Marc; Malaisree, Maturos; Liu, Dan; Liu, Yi; Mulholland, Adrian J.

2017-11-01

Cdc25 phosphatase B, a potential target for cancer therapy, is inhibited by a series of quinones. The binding site and mode of quinone inhibitors to Cdc25B remains unclear, whereas this information is important for structure-based drug design. We investigated the potential binding site of NSC663284 [DA3003-1 or 6-chloro-7-(2-morpholin-4-yl-ethylamino)-quinoline-5, 8-dione] through docking and molecular dynamics simulations. Of the two main binding sites suggested by docking, the molecular dynamics simulations only support one site for stable binding of the inhibitor. Binding sites in and near the Cdc25B catalytic site that have been suggested previously do not lead to stable binding in 50 ns molecular dynamics (MD) simulations. In contrast, a shallow pocket between the C-terminal helix and the catalytic site provides a favourable binding site that shows high stability. Two similar binding modes featuring protein-inhibitor interactions involving Tyr428, Arg482, Thr547 and Ser549 are identified by clustering analysis of all stable MD trajectories. The relatively flexible C-terminal region of Cdc25B contributes to inhibitor binding. The binding mode of NSC663284, identified through MD simulation, likely prevents the binding of protein substrates to Cdc25B. The present results provide useful information for the design of quinone inhibitors and their mechanism of inhibition.

CEF1/CDC5 alleles modulate transitions between catalytic conformations of the spliceosome

PubMed Central

Query, Charles C.; Konarska, Maria M.

2012-01-01

Conformational change within the spliceosome is required between the first and second catalytic steps of pre-mRNA splicing. A prior genetic screen for suppressors of an intron mutant that stalls between the two steps yielded both prp8 and non-prp8 alleles that suppressed second-step splicing defects. We have now identified the strongest non-prp8 suppressors as alleles of the NTC (Prp19 complex) component, CEF1. These cef1 alleles generally suppress second-step defects caused by a variety of intron mutations, mutations in U6 snRNA, or deletion of the second-step protein factor Prp17, and they can activate alternative 3′ splice sites. Genetic and functional interactions between cef1 and prp8 alleles suggest that they modulate the same event(s) in the first-to-second-step transition, most likely by stabilization of the second-step spliceosome; in contrast, alleles of U6 snRNA that also alter this transition modulate a distinct event, most likely by stabilization of the first-step spliceosome. These results implicate a myb-like domain of Cef1/CDC5 in interactions that modulate conformational states of the spliceosome and suggest that alteration of these events affects splice site use, resulting in alternative splicing-like patterns in yeast. PMID:22408182

Direct, Operational Field Test Evaluation, Human Factors

DOT National Transportation Integrated Search

1998-08-01

IN THIS EXPERIMENT, 32 LICENSED DRIVERS (16 YOUNG, 16 OLD) DROVE ON AN EXPRESSWAY. ON EACH TRIAL (96 PER SUBJECT), 1 TO 3 TRAFFIC MESSAGES CONTAINING 6 TO 14 ITEMS WERE PRESENTED. (L-94 EASTBOUND AT SOUTHFIELD FREEWAY, CONTINUING CONSTRUCTION, RIGHT ...

Perceptions, intentions and behavioral norms that affect pre-license driving among Arab youth in Israel.

PubMed

Gesser-Edelsburg, Anat; Zemach, Mina; Lotan, Tsippy; Elias, Wafa; Grimberg, Einat

2018-02-01

The present study examines reported pre-license driving among youth from the population of Arab citizens of Israel. The purpose of the present study is to examine which sociodemographic variables, attitudes and perceptions about safe driving and individual and societal behavioral norms are associated with pre-license driving. The research distinguished between the factors that actually contribute to pre-license driving (reported behavior, peer norms, gender and parents' messages) and the factors that explain the intention (parental authority, social norms, parents' messages and fear of road crashes). Even though there was a significant partial overlap (84%) between those who intend to drive without a license and those who reported driving without a license, the main factors that distinguish pre-license driving groups are different from the factors that distinguish the intention to drive before receiving a license. What is unique about the findings is the identification of the context in which social norms are influential and that in which parental authority is influential. The study indicated that in the case of pre-license driving, the main motivating factor is subjective norms, whereas in the case of expecting to drive without a license, the main motivating factor is the interaction between parental authority and the messages that parents convey. While actual behavior pertains to the behavioral level, we argue that intended behavior pertains to the cognitive level. At this level, rational considerations arise, such as fear of parental punishment and fear of accidents. These considerations compete with the influence of friends and their norms, and may outweigh them. The findings suggest that it is important to safeguard youth against the influence of peer pressure as early as the stage of behavioral intentions. Follow-up studies can simulate situations of pre-license driving due to social pressure and identify the factors that might affect young people's decision-making. Moreover, providing parents with training before the accompaniment period is highly recommended. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prevalence and sociodemographic correlates of stunting, underweight, and overweight among Palestinian school adolescents (13-15 years) in two major governorates in the West Bank

PubMed Central

2009-01-01

Background There is little information about height and weight status of Palestinian adolescents. The objective of this paper was to assess the prevalence of stunting, underweight, and overweight/obesity among Palestinian school adolescents (13-15 years) and associated sociodemographic factors in 2 major governorates in the West Bank. Methods A Cross-sectional survey was conducted in 2005 comprising 1942 students in 65 schools in Ramallah and Hebron governorates. Data was collected through self-administered questionnaires from students and parents. Weights and heights were measured. Overweight and obesity were assessed using the 2000 Centers for Disease Control and Prevention (CDC) reference and the International Obesity Task Force (IOTF) criteria. Stunting and underweight were assessed using the 2000 CDC reference. Results Overweight/obesity was more prevalent in Ramallah than in Hebron and affected more girls than boys. Using the 2000 CDC reference, the prevalence of overweight and obesity in Ramallah among boys was 9.6% and 8.2%, respectively versus 15.6% and 6.0% among girls (P < 0.01). In Hebron, the corresponding figures were 8.5% and 4.9% for boys and 13.5% and 3.4% for girls (P < 0.01). Using the IOTF criteria, the prevalence of overweight and obesity among boys in Ramallah was 13.3% and 5.2%, respectively versus 18.9% and 3.3% for girls. The prevalence of overweight and obesity among boys in Hebron was 10.9% and 2.2%, respectively versus 14.9% and 2.0% for girls. Overweight/obesity was associated with high standard of living (STL) among boys and with the onset of puberty among girls. More boys were underweight than girls, and the prevalence was higher in Hebron (12.9% and 6.0% in boys and girls, respectively (P < 0.01)) than in Ramallah (9.7% and 3.1% in boys and girls, respectively (p < 0.01)). The prevalence of stunting was similar in both governorates, and was higher among boys (9.2% and 9.4% in Ramallah and Hebron, respectively) than among girls (5.9% and 4.2% in Ramallah and Hebron, respectively). Stunting was negatively associated with father's education among boys and with urban residence, medium STL and onset of puberty among girls. Conclusion Under- and overnutrition co-exist among Palestinian adolescents, with differences between sexes. Region, residence, STL, and onset of puberty were associated factors. PMID:20030822

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.

Phosphatidylinositol 3-kinase, Cdc42, and Rac1 act downstream of Ras in integrin-dependent neurite outgrowth in N1E-115 neuroblastoma cells.

PubMed

Sarner, S; Kozma, R; Ahmed, S; Lim, L

2000-01-01

Ras and Rho family GTPases have been ascribed important roles in signalling pathways determining cellular morphology and growth. Here we investigated the roles of the GTPases Ras, Cdc42, Rac1, and Rho and that of phosphatidylinositol 3-kinase (PI 3-kinase) in the pathway leading from serum starvation to neurite outgrowth in N1E-115 neuroblastoma cells. Serum-starved cells grown on a laminin matrix exhibited integrin-dependent neurite outgrowth. Expression of dominant negative mutants of Ras, PI 3-kinase, Cdc42, or Rac1 all blocked this neurite outgrowth, while constitutively activated mutants of Ras, PI 3-kinase, or Cdc42 were each sufficient to promote outgrowth even in the presence of serum. A Ras(H40C;G12V) double mutant which binds preferentially to PI 3-kinase also promoted neurite formation. Activated Ras(G12V)-induced outgrowth required PI 3-kinase activity, but activated PI 3-kinase-induced outgrowth did not require Ras activity. Although activated Rac1 by itself did not induce neurites, neurite outgrowth induced by activated Cdc42(G12V) was Rac1 dependent. Cdc42(G12V)-induced neurites appeared to lose their normal polarization, almost doubling the average number of neurites produced by a single cell. Outgrowth induced by activated Ras or PI 3-kinase required both Cdc42 and Rac1 activity, but Cdc42(G12V)-induced outgrowth did not need Ras or PI 3-kinase activity. Active Rho(G14V) reduced outgrowth promoted by Ras(G12V). Finally, expression of dominant negative Jun N-terminal kinase or extracellular signal-regulated kinase did not inhibit outgrowth, suggesting these pathways are not essential for this process. Our results suggest a hierarchy of signalling where Ras signals through PI 3-kinase to Cdc42 and Rac1 activation (and Rho inactivation), culminating in neurite outgrowth. Thus, in the absence of serum factors, Ras may initiate cell cycle arrest and terminal differentiation in N1E-115 neuroblastoma cells.

Phosphatidylinositol 3-Kinase, Cdc42, and Rac1 Act Downstream of Ras in Integrin-Dependent Neurite Outgrowth in N1E-115 Neuroblastoma Cells

PubMed Central

Sarner, Shula; Kozma, Robert; Ahmed, Sohail; Lim, Louis

2000-01-01

Ras and Rho family GTPases have been ascribed important roles in signalling pathways determining cellular morphology and growth. Here we investigated the roles of the GTPases Ras, Cdc42, Rac1, and Rho and that of phosphatidylinositol 3-kinase (PI 3-kinase) in the pathway leading from serum starvation to neurite outgrowth in N1E-115 neuroblastoma cells. Serum-starved cells grown on a laminin matrix exhibited integrin-dependent neurite outgrowth. Expression of dominant negative mutants of Ras, PI 3-kinase, Cdc42, or Rac1 all blocked this neurite outgrowth, while constitutively activated mutants of Ras, PI 3-kinase, or Cdc42 were each sufficient to promote outgrowth even in the presence of serum. A RasH40C;G12V double mutant which binds preferentially to PI 3-kinase also promoted neurite formation. Activated RasG12V-induced outgrowth required PI 3-kinase activity, but activated PI 3-kinase-induced outgrowth did not require Ras activity. Although activated Rac1 by itself did not induce neurites, neurite outgrowth induced by activated Cdc42G12V was Rac1 dependent. Cdc42G12V-induced neurites appeared to lose their normal polarization, almost doubling the average number of neurites produced by a single cell. Outgrowth induced by activated Ras or PI 3-kinase required both Cdc42 and Rac1 activity, but Cdc42G12V-induced outgrowth did not need Ras or PI 3-kinase activity. Active RhoG14V reduced outgrowth promoted by RasG12V. Finally, expression of dominant negative Jun N-terminal kinase or extracellular signal-regulated kinase did not inhibit outgrowth, suggesting these pathways are not essential for this process. Our results suggest a hierarchy of signalling where Ras signals through PI 3-kinase to Cdc42 and Rac1 activation (and Rho inactivation), culminating in neurite outgrowth. Thus, in the absence of serum factors, Ras may initiate cell cycle arrest and terminal differentiation in N1E-115 neuroblastoma cells. PMID:10594018

Alterations of 3p21.31 tumor suppressor genes in head and neck squamous cell carcinoma: Correlation with progression and prognosis.

PubMed

Ghosh, Susmita; Ghosh, Amlan; Maiti, Guru Prasad; Alam, Neyaz; Roy, Anup; Roy, Bidyut; Roychoudhury, Susanta; Panda, Chinmay Kumar

2008-12-01

The aim of our study was to analyze the alterations of some candidate tumor suppressor genes (TSGs) viz. LIMD1, LTF, CDC25A, SCOTIN, RASSF1A and CACNA2D2 located in the chromosomal region 3p21.31 associated with the development of early dysplastic lesions of head and neck. In analysis of 72 dysplastic lesions and 116 squamous cell carcinoma of head and neck, both deletion and promoter methylation have been seen in these genes except for CDC25A and SCOTIN where no methylation has been detected. The alteration of LIMD1 was highest (50%) in the mild dysplastic lesions and did not change significantly during progression of tumor indicating its association with this stage of the disease. It was evident that alterations of LTF, CDC25A and CACNA2D2 were associated with development of moderate dysplastic lesions, while alterations in RASSF1A and CACNA2D2 were needed for progression. Novel somatic mutations were seen in exon 1 of LIMD1 (7%), intron 3/exon4 splice junction of LTF (2%) and exon 7 of cdc25A (10%). Quantitative RT-PCR analysis revealed mean reduced expression of the genes in the following order: LTF (67.6 +/- 16.8) > LIMD1 (53.2 +/- 20.1) > CACNA2D2 (23.7 +/- 7.1) > RASSF1A (15.1 +/- 5.6) > CDC25A (5.3 +/- 2.3) > SCOTIN (0.58 +/- 0.54). Immunohistochemical analysis of CDC25A showed its localization both in cytoplasm and nucleus in primary lesions and oral cancer cell lines. In absence of HPV infection, LTF and RASSF1A alterations jointly have adverse impact on survival of tobacco addicted patients. Thus, our data suggested that multiple candidate TSGs in the chromosomal 3p21.31 region were differentially associated with the early dysplastic lesions of head and neck. (c) 2008 Wiley-Liss, Inc.

In Vivo Ubiquitin Linkage-type Analysis Reveals that the Cdc48-Rad23/Dsk2 Axis Contributes to K48-Linked Chain Specificity of the Proteasome.

PubMed

Tsuchiya, Hikaru; Ohtake, Fumiaki; Arai, Naoko; Kaiho, Ai; Yasuda, Sayaka; Tanaka, Keiji; Saeki, Yasushi

2017-05-18

Ubiquitin-binding domain (UBD) proteins regulate numerous cellular processes, but their specificities toward ubiquitin chain types in cells remain obscure. Here, we perform a quantitative proteomic analysis of ubiquitin linkage-type selectivity of 14 UBD proteins and the proteasome in yeast. We find that K48-linked chains are directed to proteasomal degradation through selectivity of the Cdc48 cofactor Npl4. Mutating Cdc48 results in decreased selectivity, and lacking Rad23/Dsk2 abolishes interactions between ubiquitylated substrates and the proteasome. Among them, only Npl4 has K48 chain specificity in vitro. Thus, the Cdc48 complex functions as a K48 linkage-specifying factor upstream of Rad23/Dsk2 for proteasomal degradation. On the other hand, K63 chains are utilized in endocytic pathways, whereas both K48 and K63 chains are found in the MVB and autophagic pathways. Collectively, our results provide an overall picture of the ubiquitin network via UBD proteins and identify the Cdc48-Rad23/Dsk2 axis as a major route to the proteasome. Copyright © 2017 Elsevier Inc. All rights reserved.

High performance bonded neo magnets using high density compaction

NASA Astrophysics Data System (ADS)

Herchenroeder, J.; Miller, D.; Sheth, N. K.; Foo, M. C.; Nagarathnam, K.

2011-04-01

This paper presents a manufacturing method called Combustion Driven Compaction (CDC) for the manufacture of isotropic bonded NdFeB magnets (bonded Neo). Magnets produced by the CDC method have density up to 6.5 g/cm3 which is 7-10% higher compared to commercially available bonded Neo magnets of the same shape. The performance of an actual seat motor with a representative CDC ring magnet is presented and compared with the seat motor performance with both commercial isotropic bonded Neo and anisotropic NdFeB rings of the same geometry. The comparisons are made at both room and elevated temperatures. The airgap flux for the magnet produced by the proposed method is 6% more compared to the commercial isotropic bonded Neo magnet. After exposure to high temperature due to the superior thermal aging stability of isotropic NdFeB powders the motor performance with this material is comparable to the motor performance with an anisotropic NdFeB magnet.

Incidence of surgical site infection after spine surgery: what is the impact of the definition of infection?

PubMed

Nota, Sjoerd P F T; Braun, Yvonne; Ring, David; Schwab, Joseph H

2015-05-01

Orthopaedic surgical site infections (SSIs) can delay recovery, add impairments, and decrease quality of life, particularly in patients undergoing spine surgery, in whom SSIs may also be more common. Efforts to prevent and treat SSIs of the spine rely on the identification and registration of these adverse events in large databases. The effective use of these databases to answer clinical questions depends on how the conditions in question, such as infection, are defined in the databases queried, but the degree to which different definitions of infection might cause different risk factors to be identified by those databases has not been evaluated. The purpose of this study was to determine whether different definitions of SSI identify different risk factors for SSI. Specifically, we compared the International Classification of Diseases, 9th Revision (ICD-9) coding, Centers for Disease Control and Prevention (CDC) criteria for deep infection, and incision and débridement for infection to determine if each is associated with distinct risk factors for SSI. In this single-center retrospective study, a sample of 5761 adult patients who had an orthopaedic spine surgery between January 2003 and August 2013 were identified from our institutional database. The mean age of the patients was 56 years (± 16 SD), and slightly more than half were men. We applied three different definitions of infection: ICD-9 code for SSI, the CDC criteria for deep infection, and incision and débridement for infection. Three hundred sixty-one (6%) of the 5761 surgeries received an ICD-9 code for SSI within 90 days of surgery. After review of the medical records of these 361 patients, 216 (4%) met the CDC criteria for deep SSI, and 189 (3%) were taken to the operating room for irrigation and débridement within 180 days of the day of surgery. We found the Charlson Comorbidity Index, the duration of the operation, obesity, and posterior surgical approach were independently associated with a higher risk of infection for each of the three definitions of SSI. The influence of malnutrition, smoking, specific procedures, and specific surgeons varied by definition of infection. These elements accounted for approximately 6% of the variability in the risk of developing an infection. The frequency of SSI after spine surgery varied according to the definition of an infection, but the most important risk factors did not. We conclude that large database studies may be better suited for identifying risk factors than for determining absolute numbers of infections. Level III, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Low sustainability, poor governance, and other challenges encountered by grassroots non-governmental organizations targeting HIV prevention for men who have sex with men in China - a nation-wide study.

PubMed

Lau, Joseph T F; Wang, Zixin; Kim, Yoona; Li, Jinghua; Gu, Jing; Mo, Phoenix K H; Wang, Xiaodong

2017-12-01

Grassroots non-governmental organizations (NGOs) played pivotal roles in HIV prevention among men who have sex with men (MSM) in China. Their governance and sustainability issues were under-studied. This nation-wide study surveyed leaders of 202 of the HIV related NGOs in China.58.4% of the leaders believed that their NGO would last for ≤5 years; which was negatively associated with perceived good relationship with CDC. 65.3% mentioned ≥3 non-sustainability issues; associated factors included perceived inadequacies in prevention skills, management skills, policy support, technical support, operational support, and CDC's support; a reverse association was found for frequent collaboration with organizations in China. 30.6% of the leaders mentioned ≥7 governance issues; a stepwise model found a positive association with having no office and negative associations with number of full-time staff and core volunteers. These problems would severely limit the effectiveness of HIV prevention among MSM. Related improvements and support are warranted.

Fungal neuroinfections and fungaemia: unexpected increase of mortality from invasive fungal infections in 2005-2011 in comparison to 1989-1998: analysis of 210 cases.

PubMed

Demitrovicova, Andrea; Liskova, Anna; Valach, Michal; Izakovic, Martin; Noge, Adriana; Baranova, Jana; Kalatova, Dagmar; Syrovatkova, Ludmila; Velicova, Jana; Bugykova, Beata; Gulasova, Ivica; Seinova, Dagmar; Mikolasova, Gertruda; Mutalova, Martina; Pilkova, Martina; Szabo, Ivan; Findova, Lubica; Madarasz, Istvan; Stanzyk, Martin; Mikulickova, Dagmar; Blazekova, Maria; Jankechova, Monika; Slezakova, Zuzana; Kuriplachova, Gabriela; Visnovsky, Jozef; Obrocnikova, Andrea; Blumm, Mathias; Blumm, Bernard; Wolfram, Simon; Zeleny, Peter; Otrubova, Jana; Rudinsky, Bruno; Nagyova, Zuzana; Vravcova, Martina; Kajaba, Jozef; Jexova, Sona; Oravec, Svetoslav; Toth, Slavomir; Klobucka, Stanislava; Gerigh, Jana; Schumann, Frank; Ambra, Robert; Bandura, Peter; Bonnack, Christian; Kubisova, Zuzana; Palo, Marek; Kalavsky, Erich; Drgona, Lubos; Mahesvaari, Rajoo; Riedl, Jan

2013-09-01

In this short communication we compared the data of fungaemia cases in Slovak hospitals from 1989-1998 published in 1999-2000 with data from 2005-2011. Risk factors, etiology and outcome of fungaemia between two periods (1989-1998 vs. 2005-2011) were compared and risk factors for death assessed by univariate analysis (CDC 2006 Statistical Package). In comparison to 1989-1998 when only amphotericin B and fluconazole has been used (55%), in 2005-2011 only 35.2% patients received FLU, but 26.4% received voriconazole, 22% caspofungin and anidulafungin and about 6.6% lipid formulations of Amphotericin B. In etiology, while in 1989-1998 only 37.1% (115/310) represented non-albicans Candida (NAC) and non-Candida yeasts in 2005-2011 already reached 63.7%. The significant increase of breakthrough fungaemia may be a sign of inappropriate empiric therapy.

Modelling IRF8 Deficient Human Hematopoiesis and Dendritic Cell Development with Engineered iPS Cells.

PubMed

Sontag, Stephanie; Förster, Malrun; Qin, Jie; Wanek, Paul; Mitzka, Saskia; Schüler, Herdit M; Koschmieder, Steffen; Rose-John, Stefan; Seré, Kristin; Zenke, Martin

2017-04-01

Human induced pluripotent stem (iPS) cells can differentiate into cells of all three germ layers, including hematopoietic stem cells and their progeny. Interferon regulatory factor 8 (IRF8) is a transcription factor, which acts in hematopoiesis as lineage determining factor for myeloid cells, including dendritic cells (DC). Autosomal recessive or dominant IRF8 mutations occurring in patients cause severe monocytic and DC immunodeficiency. To study IRF8 in human hematopoiesis we generated human IRF8-/- iPS cells and IRF8-/- embryonic stem (ES) cells using RNA guided CRISPR/Cas9n genome editing. Upon induction of hematopoietic differentiation, we demonstrate that IRF8 is dispensable for iPS cell and ES cell differentiation into hemogenic endothelium and for endothelial-to-hematopoietic transition, and thus development of hematopoietic progenitors. We differentiated iPS cell and ES cell derived progenitors into CD141+ cross-presenting cDC1 and CD1c+ classical cDC2 and CD303+ plasmacytoid DC (pDC). We found that IRF8 deficiency compromised cDC1 and pDC development, while cDC2 development was largely unaffected. Additionally, in an unrestricted differentiation regimen, IRF8-/- iPS cells and ES cells exhibited a clear bias toward granulocytes at the expense of monocytes. IRF8-/- DC showed reduced MHC class II expression and were impaired in cytokine responses, migration, and antigen presentation. Taken together, we engineered a human IRF8 knockout model that allows studying molecular mechanisms of human immunodeficiencies in vitro, including the pathophysiology of IRF8 deficient DC. Stem Cells 2017;35:898-908. © 2017 The Authors Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

6-Mercaptopurine (6-MP) induces cell cycle arrest and apoptosis of neural progenitor cells in the developing fetal rat brain.

PubMed

Kanemitsu, H; Yamauchi, H; Komatsu, M; Yamamoto, S; Okazaki, S; Uchida, K; Nakayama, H

2009-01-01

6-Mercaptopurine (6-MP), an analogue of hypoxanthine, is used in the therapy of acute lymphoblastic leukemia and causes fetal neurotoxicity. To clarify the mechanisms of 6-MP-induced fetal neurotoxicity leading to the cell cycle arrest and apoptosis of neural progenitor cells, pregnant rats were treated with 50 mg/kg 6-MP on embryonic day (E) 13, and the fetal telencephalons were examined at 12 to 72 h (h) after treatment. Flow-cytometric analysis confirmed an accumulation of cells at G2/M, S, and sub-G1 (apoptotic cells) phases from 24 to 72 h. The number of phosphorylated histone H3-positive cells (mitotic cells) decreased from 36 to 72 h, and the phosphorylated (active) form of p53 protein, which is a mediator of apoptosis and cell cycle arrest, increased from 24 to 48 h. An executor of p53-mediated cell cycle arrest, p21, showed intense overexpression at both the mRNA and protein levels from 24 to 72 h. Cdc25A protein, which is needed for the progression of S phase, decreased at 36 and 48 h. In addition, phosphorylated cdc2 protein, which is an inactive form of cdc2 necessary for G2/M progression, increased from 24 to 48 h. These results suggest that 6-MP induced G2/M arrest, delayed S-phase progression, and finally induced apoptosis of neural progenitor cells mediated by p53 in the fetal rat telencephalon.

The plant cell cycle: Pre-Replication complex formation and controls

PubMed Central

Brasil, Juliana Nogueira; Costa, Carinne N. Monteiro; Cabral, Luiz Mors; Ferreira, Paulo C. G.; Hemerly, Adriana S.

2017-01-01

Abstract The multiplication of cells in all living organisms requires a tight regulation of DNA replication. Several mechanisms take place to ensure that the DNA is replicated faithfully and just once per cell cycle in order to originate through mitoses two new daughter cells that contain exactly the same information from the previous one. A key control mechanism that occurs before cells enter S phase is the formation of a pre-replication complex (pre-RC) that is assembled at replication origins by the sequential association of the origin recognition complex, followed by Cdt1, Cdc6 and finally MCMs, licensing DNA to start replication. The identification of pre-RC members in all animal and plant species shows that this complex is conserved in eukaryotes and, more importantly, the differences between kingdoms might reflect their divergence in strategies on cell cycle regulation, as it must be integrated and adapted to the niche, ecosystem, and the organism peculiarities. Here, we provide an overview of the knowledge generated so far on the formation and the developmental controls of the pre-RC mechanism in plants, analyzing some particular aspects in comparison to other eukaryotes. PMID:28304073

Gender Differences in CDC Guideline Compliance for STIs in Emergency Departments.

PubMed

Kane, Bryan G; Guillaume, Alexander W D; Evans, Elizabeth M; Goyke, Terrence E; Eygnor, Jessica K; Semler, Lauren; Dusza, Stephen W; Greenberg, Marna Rayl

2017-04-01

Sexually transmitted infections (STIs) are a common reason for emergency department (ED) visits. The objective of this study was to determine if there were gender differences in adherence to Centers for Disease Control and Prevention (CDC) STI diagnosis and treatment guidelines, as documented by emergency providers. We performed a retrospective chart review to identify patients treated for urethritis, cervicitis, and pelvic inflammatory disease (PID) in the EDs of three hospitals in a Pennsylvania network during a calendar year. Cases were reviewed to assess for compliance with CDC guidelines. We used descriptive statistics to assess the distributions of study variables by patient sex. In the analysis we used Student's t-tests, chi-square tests, and logistic regression. Statistical significance was set at p ≤ 0.05. We identified 286 patient records. Of these, we excluded 39 for the following reasons: incorrect disease coding; the patient was admitted and treated as an inpatient for his/her disease; or the patient left the ED after refusing care. Of the 247 participants, 159 (64.4%) were female. Females were significantly younger (26.6 years, SD=8.0) than males (31.2, SD=11.5%), (95% confidence interval [CI] [2.0- 7.0], p=0.0003). All of the males (n=88) in the cohort presented with urethritis; 25.8% of females presented with cervicitis, and 74.2% with PID. Physician compliance for the five CDC criteria ranged from 68.8% for patient history to 93.5% for patient diagnostic testing, including urine pregnancy and gonorrhea/chlamydia cultures. We observed significant differences by patient sex. Fifty-four percent of the charts had symptoms recorded for female patients that were consistent with CDC characteristics for diagnostic criteria compared to over 95% for males, OR=16.9; 95% CI [5.9-48.4], p<0.001. Similar results were observed for patient discharge instructions, with physicians completely documenting delivery of discharge instructions to 51.6% of females compared to 97.7% of complete documentation in males, OR=42.3; 95% CI [10.0-178.6] p<0.001). We observed no significant sex differences in physician documentation for physical exam or for therapeutic antibiotic treatment. This retrospective study found patient gender differences in how emergency providers complied with documenting with regard to the 2010 CDC guidelines for the diagnosis and treatment of urethritis, cervicitis, and PID. Specifically medical records of men were more likely to have complete documentation of symptoms recorded (95% CI 5.9-48.4) and to have discharge instruction documentation (95% CI 10.0-178.6) than records of women.

9 CFR 102.6 - Conditional licenses.

Code of Federal Regulations, 2011 CFR

2011-01-01

... PRODUCTS § 102.6 Conditional licenses. In order to meet an emergency condition, limited market, local...) of this part, issue a conditional U.S. Veterinary Biological Product License to an establishment... available, the Administrator shall either reissue the U.S. Veterinary Biological Product License or allow it...

18 CFR 16.13 - Standards and factors for issuing a new license.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Standards and factors for issuing a new license. 16.13 Section 16.13 Conservation of Power and Water Resources FEDERAL... and 15 of the Federal Power Act § 16.13 Standards and factors for issuing a new license. (a) In...

Hierarchical micro- and mesoporous carbide-derived carbon as a high-performance electrode material in supercapacitors.

PubMed

Rose, Marcus; Korenblit, Yair; Kockrick, Emanuel; Borchardt, Lars; Oschatz, Martin; Kaskel, Stefan; Yushin, Gleb

2011-04-18

Ordered mesoporous carbide-derived carbon (OM-CDC) materials produced by nanocasting of ordered mesoporous silica templates are characterized by a bimodal pore size distribution with a high ratio of micropores. The micropores result in outstanding adsorption capacities and the well-defined mesopores facilitate enhanced kinetics in adsorption processes. Here, for the first time, a systematic study is presented, in which the effects of synthesis temperature on the electrochemical performance of these materials in supercapacitors based on a 1 M aqueous solution of sulfuric acid and 1-ethyl-3-methylimidazolium tetrafluoroborate ionic liquid are reported. Cyclic voltammetry shows the specific capacitance of the OM-CDC materials exceeds 200 F g(-1) in the aqueous electrolyte and 185 F g(-1) in the ionic liquid, when measured in a symmetric configuration in voltage ranges of up to 0.6 and 2 V, respectively. The ordered mesoporous channels in the produced OM-CDC materials serve as ion-highways and allow for very fast ionic transport into the bulk of the OM-CDC particles. At room temperature the enhanced ion transport leads to 75% and 90% of the capacitance retention at current densities in excess of ∼10 A g(-1) in ionic liquid and aqueous electrolytes, respectively. The supercapacitors based on 250-300 μm OM-CDC electrodes demonstrate an operating frequency of up to 7 Hz in aqueous electrolyte. The combination of high specific capacitance and outstanding rate capabilities of the OM-CDC materials is unmatched by state-of-the art activated carbons and strictly microporous CDC materials. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Health of children classified as underweight by CDC reference but normal by WHO standard.

PubMed

Meyers, Alan; Joyce, Katherine; Coleman, Sharon M; Cook, John T; Cutts, Diana; Ettinger de Cuba, Stephanie; Heeren, Timothy C; Rose-Jacobs, Ruth; Black, Maureen M; Casey, Patrick H; Chilton, Mariana; Sandel, Megan; Frank, Deborah A

2013-06-01

To ascertain measures of health status among 6- to 24-month-old children classified as below normal weight-for-age (underweight) by the Centers for Disease Control and Prevention (CDC) 2000 growth reference but as normal weight-for-age by the World Health Organization (WHO) 2006 standard. Data were gathered from children and primary caregivers at emergency departments and primary care clinics in 7 US cities. Outcome measures included caregiver rating of child health, parental evaluation of developmental status, history of hospitalizations, and admission to hospital at the time of visit. Children were classified as (1) not underweight by either CDC 2000 or WHO 2006 criteria, (2) underweight by CDC 2000 but not by WHO 2006 criteria, or (3) underweight by both criteria. Associations between these categories and health outcome measures were assessed by using multiple logistic regression analysis. Data were available for 18 420 children. For each health outcome measure, children classified as underweight by CDC 2000 but normal by WHO 2006 had higher adjusted odds ratios (aORs) of adverse health outcomes than children not classified as underweight by either; children classified as underweight by both had the highest aORs of adverse outcomes. For example, compared with children not underweight by either criteria, the aORs for fair/poor health rating were 2.54 (95% confidence interval: 2.20-2.93) among children underweight by CDC but not WHO and 3.76 (3.13-4.51) among children underweight by both. Children who are reclassified from underweight to normal weight in changing from CDC 2000 to WHO 2006 growth charts may still be affected by morbidities associated with underweight.

How do we understand the disagreement in the frequency of surgical site infection between the CDC and Clavien-Dindo classifications?

PubMed

Yamamoto, Takanobu; Takahashi, Satoshi; Ichihara, Koji; Hiyama, Yoshiki; Uehara, Teruhisa; Hashimoto, Jiro; Hirobe, Megumi; Masumori, Naoya

2015-02-01

To clarify the discrepancy in the incidence and severity of surgical site infections (SSI) for radical cystectomy between reports based on the CDC guideline and those using the Clavien-Dindo classification we evaluated 449 consecutive patients who underwent radical cystectomy for bladder cancer between 1990 and 2012. Of the 115 (25.6%) patients with SSI defined by the CDC guideline, 89 could be analyzed. We compared the SSI rates and severity defined by the CDC guideline and Clavien-Dindo classifications. There were 58 patients with superficial SSI, 16 with deep SSI, and 15 with organ/space SSI according to the CDC guideline. All patients with organ/space SSI were judged as "not having SSI" by the Clavien-Dindo classification. They were classified as having "intestinal prolapse", "intestinal fistula", "abdominal abscess" and "pelvic abscess." There was a significant association between the treatment duration and depth of SSI based on the CDC guideline by Spearman's rank-correlation coefficient (p < 0.001, r = 0.614) and with the grade of complications (p < 0.001, r = 0.632) in the Clavien-Dindo classification. Multivariate analysis showed that patients with grade III SSI in the Clavien-Dindo classification needed a significantly longer treatment duration. It is necessary to be aware that a discrepancy can occur automatically due to the different natures of the definitions. Using the CDC guideline, we can effectively estimate the future treatment period when SSI occurs. With the Clavien-Dindo classification, grade III SSI requires a longer treatment duration. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

MicroRNA-137 Negatively Regulates H2O2-Induced Cardiomyocyte Apoptosis Through CDC42

PubMed Central

Wang, Junnan; Xu, Rihao; Wu, Junduo; Li, Zhibo

2015-01-01

Background Oxidative stress, inducing cardiomyocyte apoptosis or myocardial ischemia, is the major denominator of many cardiac diseases. In this study, we intended to explore the regulatory function of microRNA-137 (miR-137) in oxidative stress-induced cardiomyocyte apoptosis. Material/Methods Cardiomyocytes were extracted from newborn C57BL/6 mice and cultured in vitro. Apoptosis was induced by H2O2, and evaluated by TUNEL assay. The effect of cardiomyocyte apoptosis on gene expression of miR-137 was evaluated by qRT-PCR. Lentivirus was used to stably down-regulate miR-137, and the subsequent effects of miR-137 down-regulation on cardiomyocyte apoptosis, its targeted gene CDC42, and caspase pathway were evaluated by TUNEL assay, dual-luciferase reporter assay, and Western blot assay, respectively. Finally, CDC42 was down-regulated by siRNA and its effect on miR-137-mediated cardiomyocyte apoptosis protection was examined. Results H2O2 induced significant apoptosis and up-regulated miR-137 in cardiomyocytes, whereas lentivirus-mediated miR-137 down-regulation protected against apoptosis. CDC42 was the direct target gene of miR-137 and proteins of CDC42, caspase-3, and caspase-9 were all regulated by miR-137 down-regulation in cardiomyocyte apoptosis. SiRNA-mediated CDC42 down-regulation reversed the protection of miR-137 down-regulation against cardiomyocyte apoptosis. Conclusions Our work demonstrated miR-137 and CDC42 are critical regulators in cardiomyocyte apoptosis. It may help to identify the molecular targets to prevent myocardial injury in human patients. PMID:26566162

Evaluation of CDC light traps for mosquito surveillance in a malaria endemic area on the Thai-Myanmar border.

PubMed

Sriwichai, Patchara; Karl, Stephan; Samung, Yudthana; Sumruayphol, Suchada; Kiattibutr, Kirakorn; Payakkapol, Anon; Mueller, Ivo; Yan, Guiyun; Cui, Liwang; Sattabongkot, Jetsumon

2015-12-15

Centers for Disease Control and Prevention miniature light traps (CDC-LT) baited with CO2 are a routine tool for adult mosquito sampling used in entomological surveys, and for monitoring and surveillance of disease vectors. The present study was aimed at evaluating the performance of baited and unbaited CDC-LT for indoor and outdoor trapping of endemic mosquito species in northwestern Thailand. CDC-LT (n = 112) with and without dry ice baits were set both indoors and outdoors in 88 selected houses for stretches of 5 consecutive nights per month in 7 villages in Tha Song Yang district, Tak province between January 2011 and March 2013. Individual traps were repeatedly placed in the same location for a median of 6 (range 1-10) times. Mosquitoes were identified by morphological characteristics and classified into blood-fed, empty, male/female and gravid. Absolute mosquito numbers were converted to capture rates (i.e., mosquitoes per trap and year). Capture rates were compared using multilevel negative binomial regression to account for multiple trap placements and adjust for regional and seasonal differences. A total of 6,668 mosquitoes from 9 genera were collected from 576 individual CDC-LT placements. Culex was the predominant captured genus (46%), followed by anopheline mosquitoes (45%). Overall, CO2 baited traps captured significantly more Culex (especially Culex vishnui Theobald) and Anopheles mosquitoes per unit time (adjusted capture rate ratio (aCRR) 1.64 and 1.38, respectively). Armigeres spp. mosquitoes were trapped in outdoor traps with significantly higher frequency (aCRR: 1.50), whereas Aedes albopictus (Skuse) had a tendency to be trapped more frequently indoors (aCRR: 1.89, p = 0.07). Furthermore, capture rate ratios between CO2 baited and non-baited CDC-LT were significantly influenced by seasonality and indoor vs. outdoor trap placement. The present study shows that CDC-LT with CO2 baiting capture significantly more Culex and Anopheles mosquitoes, some of which (e.g., Cx. vishnui, Cx. quinquefasciatus Say, An. minimus s.l. Theobald, An. maculatus s.l. Theobald) represent important disease vectors in Thailand. This study also shows significant differences in the capture efficiency of CDC-LT when placed indoors or outdoors and in different seasons. Our study thus provides important guidelines for more targeted future vector trapping studies on the Thai-Myanmar border, which is an important cross-border malaria transmission region in Thailand.

A Role of hIPI3 in DNA Replication Licensing in Human Cells.

PubMed

Huang, Yining; Amin, Aftab; Qin, Yan; Wang, Ziyi; Jiang, Huadong; Liang, Lu; Shi, Linjing; Liang, Chun

2016-01-01

The yeast Ipi3p is required for DNA replication and cell viability in Sacharomyces cerevisiae. It is an essential component of the Rix1 complex (Rix1p/Ipi2p-Ipi1p-Ipi3p) that is required for the processing of 35S pre-rRNA in pre-60S ribosomal particles and for the initiation of DNA replication. The human IPI3 homolog is WDR18 (WD repeat domain 18), which shares significant homology with yIpi3p. Here we report that knockdown of hIPI3 resulted in substantial defects in the chromatin association of the MCM complex, DNA replication, cell cycle progression and cell proliferation. Importantly, hIPI3 silencing did not result in a reduction of the protein level of hCDC6, hMCM7, or the ectopically expressed GFP protein, indicating that protein synthesis was not defective in the same time frame of the DNA replication and cell cycle defects. Furthermore, the mRNA and protein levels of hIPI3 fluctuate in the cell cycle, with the highest levels from M phase to early G1 phase, similar to other pre-replicative (pre-RC) proteins. Moreover, hIPI3 interacts with other replication-initiation proteins, co-localizes with hMCM7 in the nucleus, and is important for the nuclear localization of hMCM7. We also found that hIPI3 preferentially binds to the origins of DNA replication including those at the c-Myc, Lamin-B2 and β-Globin loci. These results indicate that hIPI3 is involved in human DNA replication licensing independent of its role in ribosome biogenesis.

Clinical inquiries regarding Ebola virus disease received by CDC--United States, July 9-November 15, 2014.

PubMed

Karwowski, Mateusz P; Meites, Elissa; Fullerton, Kathleen E; Ströher, Ute; Lowe, Luis; Rayfield, Mark; Blau, Dianna M; Knust, Barbara; Gindler, Jacqueline; Van Beneden, Chris; Bialek, Stephanie R; Mead, Paul; Oster, Alexandra M

2014-12-12

Since early 2014, there have been more than 6,000 reported deaths from Ebola virus disease (Ebola), mostly in Guinea, Liberia, and Sierra Leone. On July 9, 2014, CDC activated its Emergency Operations Center for the Ebola outbreak response and formalized the consultation service it had been providing to assist state and local public health officials and health care providers evaluate persons in the United States thought to be at risk for Ebola. During July 9-November 15, CDC responded to clinical inquiries from public health officials and health care providers from 49 states and the District of Columbia regarding 650 persons thought to be at risk. Among these, 118 (18%) had initial signs or symptoms consistent with Ebola and epidemiologic risk factors placing them at risk for infection, thereby meeting the definition of persons under investigation (PUIs). Testing was not always performed for PUIs because alternative diagnoses were made or symptoms resolved. In total, 61 (9%) persons were tested for Ebola virus, and four, all of whom met PUI criteria, had laboratory-confirmed Ebola. Overall, 490 (75%) inquiries concerned persons who had neither traveled to an Ebola-affected country nor had contact with an Ebola patient. Appropriate medical evaluation and treatment for other conditions were noted in some instances to have been delayed while a person was undergoing evaluation for Ebola. Evaluating and managing persons who might have Ebola is one component of the overall approach to domestic surveillance, the goal of which is to rapidly identify and isolate Ebola patients so that they receive appropriate medical care and secondary transmission is prevented. Health care providers should remain vigilant and consult their local and state health departments and CDC when assessing ill travelers from Ebola-affected countries. Most of these persons do not have Ebola; prompt diagnostic assessments, laboratory testing, and provision of appropriate care for other conditions are essential for appropriate patient care and reflect hospital preparedness.

A new structurally atypical bradykinin-potentiating peptide isolated from Crotalus durissus cascavella venom (South American rattlesnake).

PubMed

Lopes, Denise M; Junior, Norberto E G; Costa, Paula P C; Martins, Patrícia L; Santos, Cláudia F; Carvalho, Ellaine D F; Carvalho, Maria D F; Pimenta, Daniel C; Cardi, Bruno A; Fonteles, Manassés C; Nascimento, Nilberto R F; Carvalho, Krishnamurti M

2014-11-01

Venom glands of some snakes synthesize bradykinin-potentiating peptides (BPP's) which increase bradykinin-induced hypotensive effect and decrease angiotensin I vasopressor effect by angiotensin-converting enzyme (ACE) inhibition. The present study shows a new BPP (BPP-Cdc) isolated from Crotalus durissus cascavella venom: Pro-Asn-Leu-Pro-Asn-Tyr-Leu-Gly-Ile-Pro-Pro. Although BPP-Cdc presents the classical sequence IPP in the C-terminus, it has a completely atypical N-terminal sequence, which shows very low homology with all other BPPs isolated to date. The pharmacological effects of BPP-Cdc were compared to BBP9a from Bothrops jararaca and captopril. BPP-Cdc (1 μM) significantly increased BK-induced contractions (BK; 1 μM) on the guinea pig ileum by 267.8% and decreased angiotensin I-induced contractions (AngI; 10 nM) by 62.4% and these effects were not significantly different from those of BPP9a (1 μM) or captopril (200 nM). Experiments with 4-week hypertensive 2K-1C rats show that the vasopressor effect of AngI (10 ng) was decreased by 50 μg BPP-Cdc (69.7%), and this result was similar to that obtained with 50 μg BPP9a (69.8%). However, the action duration of BPP-Cdc (60 min) was 2 times greater than that of BPP-9a (30 min). On the other hand, the hypotensive effect of BK (250 ng) was significantly increased by 176.6% after BPP-Cdc (50 μg) administration, value 2.5 times greater than that obtained with BPP9a administered at the same doses (71.4%). In addition, the duration of the action of BPP-Cdc (120 min) was also at least 4 times greater than that of BPP-9a (30 min). Taken together, these results suggest that BPP-Cdc presents more selective action on arterial blood system than BPP9a. Besides the inhibition of ACE, it may present other mechanisms of action yet to be elucidated. Copyright © 2014 Elsevier Ltd. All rights reserved.

PAR proteins regulate maintenance-phase myosin dynamics during Caenorhabditis elegans zygote polarization

PubMed Central

Small, Lawrence E.; Dawes, Adriana T.

2017-01-01

Establishment of anterior–posterior polarity in the Caenorhabditis elegans zygote requires two different processes: mechanical activity of the actin–myosin cortex and biochemical activity of partitioning-defective (PAR) proteins. Here we analyze how PARs regulate the behavior of the cortical motor protein nonmuscle myosin (NMY-2) to complement recent efforts that investigate how PARs regulate the Rho GTPase CDC-42, which in turn regulates the actin-myosin cortex. We find that PAR-3 and PAR-6 concentrate CDC-42–dependent NMY-2 in the anterior cortex, whereas PAR-2 inhibits CDC-42–dependent NMY-2 in the posterior domain by inhibiting PAR-3 and PAR-6. In addition, we find that PAR-1 and PAR-3 are necessary for inhibiting movement of NMY-2 across the cortex. PAR-1 protects NMY-2 from being moved across the cortex by forces likely originating in the cytoplasm. Meanwhile, PAR-3 stabilizes NMY-2 against PAR-2 and PAR-6 dynamics on the cortex. We find that PAR signaling fulfills two roles: localizing NMY-2 to the anterior cortex and preventing displacement of the polarized cortical actin–myosin network. PMID:28615321

USP37 deubiquitinates Cdt1 and contributes to regulate DNA replication.

PubMed

Hernández-Pérez, Santiago; Cabrera, Elisa; Amoedo, Hugo; Rodríguez-Acebes, Sara; Koundrioukoff, Stephane; Debatisse, Michelle; Méndez, Juan; Freire, Raimundo

2016-10-01

DNA replication control is a key process in maintaining genomic integrity. Monitoring DNA replication initiation is particularly important as it needs to be coordinated with other cellular events and should occur only once per cell cycle. Crucial players in the initiation of DNA replication are the ORC protein complex, marking the origin of replication, and the Cdt1 and Cdc6 proteins, that license these origins to replicate by recruiting the MCM2-7 helicase. To accurately achieve its functions, Cdt1 is tightly regulated. Cdt1 levels are high from metaphase and during G1 and low in S/G2 phases of the cell cycle. This control is achieved, among other processes, by ubiquitination and proteasomal degradation. In an overexpression screen for Cdt1 deubiquitinating enzymes, we isolated USP37, to date the first ubiquitin hydrolase controlling Cdt1. USP37 overexpression stabilizes Cdt1, most likely a phosphorylated form of the protein. In contrast, USP37 knock down destabilizes Cdt1, predominantly during G1 and G1/S phases of the cell cycle. USP37 interacts with Cdt1 and is able to de-ubiquitinate Cdt1 in vivo and, USP37 is able to regulate the loading of MCM complexes onto the chromatin. In addition, downregulation of USP37 reduces DNA replication fork speed. Taken together, here we show that the deubiquitinase USP37 plays an important role in the regulation of DNA replication. Whether this is achieved via Cdt1, a central protein in this process, which we have shown to be stabilized by USP37, or via additional factors, remains to be tested. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

CDC Kerala 7: Effect of early language intervention among children 0-3 y with speech and language delay.

PubMed

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

2014-12-01

To assess the effect of systematic clinic and home based early language intervention program in children reporting to the early language intervention clinic with full partnership of specially trained developmental therapist and the parents. All babies between 0 and 3 y referred to Child Development Centre (CDC) Kerala for suspected speech/language delay were assessed and those without hearing impairment were screened first using Language Evaluation Scale Trivandrum (LEST) and assessed in detail using Receptive Expressive Emergent Language Scale (REELS). Those having language delay are enrolled into the early language intervention program for a period of 6 mo, 1 h at the CDC clinic once every month followed by home stimulation for rest of the month by the mother trained at CDC. Out of the total 455 children between 0 and 3 y, who successfully completed 6 mo intervention, the mean pre and post intervention language quotient (LQ) were 60.79 and 70.62 respectively and the observed 9.83 increase was statistically significant. The developmental diagnosis included developmental delay (62.4%), global developmental delay (18.5%), Trisomy and other chromosomal abnormalities (10.5%), microcephaly and other brain problems (9.9%), misarticulation (8.4%), autistic features (5.3%) and cleft palate and lip (3.3%) in the descending order. In the present study among 455 children between 0 and 3 y without hearing impairment, who successfully completed 6 mo early language intervention, the mean pre and post intervention LQ were 60.79 and 70.62 respectively and the observed 9.83 increase was statistically significant.

Menadione induces G2/M arrest in gastric cancer cells by down-regulation of CDC25C and proteasome mediated degradation of CDK1 and cyclin B1

PubMed Central

Lee, Min Ho; Cho, Yoonjung; Kim, Do Hyun; Woo, Hyun Jun; Yang, Ji Yeong; Kwon, Hye Jin; Yeon, Min Ji; Park, Min; Kim, Sa-Hyun; Moon, Cheol; Tharmalingam, Nagendran; Kim, Tae Ue; Kim, Jong-Bae

2016-01-01

Menadione (vitamin K3) has been reported to induce apoptotic cell death and growth inhibition in various types of cancer cells. However, involvement of menadione in cell cycle control has not been considered in gastric cancer cells yet. In the current study, we have investigated whether menadione is involved in the cell cycle regulation and suppression of growth in gastric cancer cells. In the cell cycle analysis, we found that menadione induced G2/M cell cycle arrest in AGS cells. To elucidate the underlying mechanism, we investigated the cell cycle regulatory molecules involved in the G2/M cell cycle transition. After 24 h of menadione treatment, the protein level of CDK1, CDC25C and cyclin B1 in AGS cells was decreased in a menadione dose-dependent manner. In the time course experiment, the protein level of CDC25C decreased in 6 h, and CDK1and cyclin B1 protein levels began to decrease after 18 h of menadione treatment. We found that mRNA level of CDC25C decreased by menadione treatment in 6 h. Menadione did not have an influence on mRNA level of CDK1 and cyclin B1 though the protein levels were decreased. However, the decreased protein levels of CDK1 and cyclin B1 were recovered by inhibition of proteasome. Collectively, these results suggest that menadione inhibits growth of gastric cancer cells by reducing expression of CDC25C and promoting proteasome mediated degradation of CDK1 and cyclin B1 thereby blocking transition of the cell cycle from G2 phase to M phase. PMID:28077999

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.

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.

CSL protein regulates transcription of genes required to prevent catastrophic mitosis in fission yeast.

PubMed

Převorovský, Martin; Oravcová, Martina; Zach, Róbert; Jordáková, Anna; Bähler, Jürg; Půta, František; Folk, Petr

2016-11-16

For every eukaryotic cell to grow and divide, intricately coordinated action of numerous proteins is required to ensure proper cell-cycle progression. The fission yeast Schizosaccharomyces pombe has been instrumental in elucidating the fundamental principles of cell-cycle control. Mutations in S. pombe 'cut' (cell untimely torn) genes cause failed coordination between cell and nuclear division, resulting in catastrophic mitosis. Deletion of cbf11, a fission yeast CSL transcription factor gene, triggers a 'cut' phenotype, but the precise role of Cbf11 in promoting mitotic fidelity is not known. We report that Cbf11 directly activates the transcription of the acetyl-coenzyme A carboxylase gene cut6, and the biotin uptake/biosynthesis genes vht1 and bio2, with the former 2 implicated in mitotic fidelity. Cbf11 binds to a canonical, metazoan-like CSL response element (GTGGGAA) in the cut6 promoter. Expression of Cbf11 target genes shows apparent oscillations during the cell cycle using temperature-sensitive cdc25-22 and cdc10-M17 block-release experiments, but not with other synchronization methods. The penetrance of catastrophic mitosis in cbf11 and cut6 mutants is nutrient-dependent. We also show that drastic decrease in biotin availability arrests cell proliferation but does not cause mitotic defects. Taken together, our results raise the possibility that CSL proteins play conserved roles in regulating cell-cycle progression, and they could guide experiments into mitotic CSL functions in mammals.

A model-based estimation of inter-prefectural migration of physicians within Japan and associated factors: A 20-year retrospective study.

PubMed

Okada, Naoki; Tanimoto, Tetsuya; Morita, Tomohiro; Higuchi, Asaka; Yoshida, Izumi; Kosugi, Kazuhiro; Maeda, Yuto; Nishikawa, Yoshitaka; Ozaki, Akihiko; Tsuda, Kenji; Mori, Jinichi; Ohnishi, Mutsuko; Ward, Larry Wesley; Narimatsu, Hiroto; Yuji, Koichiro; Kami, Masahiro

2018-06-01

Despite an increase in the number of physicians in Japan, misdistribution of physicians within the 47 prefectures remains a major issue. Migration of physicians among prefectures might partly explain the misdistribution. However, geographical differences and the magnitude of physicians' migration are unclear. The aim of this study was to estimate the extent of migration of physicians among prefectures and explore possible factors associated with physicians' migration patterns.Using a publicly available government database from 1995 to 2014, a quantitative estimation of physicians' migration after graduation from a medical school was performed. The inflow and outflow of physicians were ostensibly calculated in each prefecture based on the differences between the number of newly licensed physicians and the actual number of practicing physicians after an adjustment for the number of deceased or retired physicians. Simple and multiple linear regression analyses were conducted to examine socio-demographic background factors.During the 20-year study period, the mean annual numbers of newly licensed physicians, deceased or retired physicians, and increase in practicing physicians in the whole country were 7416, 3382, and 4034, respectively. Among the 47 prefectures, the median annual number of newly licensed physicians to 100,000 population ratio (PPR) was 6.4 (range 1.5-16.5), the median annual adjusted number of newly licensed physicians was 61 (range, -18 to 845; the negative and positive values denote outflow and inflow, respectively), whereas the median annual number of migrating physicians was 13 (range, -171 to 241). The minimum and maximum migration ratios observed were -68% and 245%, respectively. In the final regression model of the 8 variables examined, only "newly licensed PPR" remained significantly associated with physician's migration ratios.A significant inequality in the proportion of the migration of physicians among prefectures in Japan was observed. The multivariate analyses suggest that the newly licensed PPRs, and not from-rural-to-urban migration, might be one of the keys to explaining the migration ratios of physicians. The differences and magnitude of physicians' migration should be factored into mitigate misdistribution of physicians.

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

Defining Arthritis for Public Health Surveillance: Methods and Estimates in Four US Population Health Surveys.

PubMed

Murphy, Louise B; Cisternas, Miriam G; Greenlund, Kurt J; Giles, Wayne; Hannan, Casey; Helmick, Charles G

2017-03-01

To determine the variability of arthritis prevalence in 4 US population health surveys. We estimated annualized arthritis prevalence in 2011-2012, among adults age ≥20 years, using 2 definition methods, both based on self-report: 1) doctor-/health care provider-diagnosed arthritis in the Behavioral Risk Factor Surveillance Survey (BRFSS), National Health and Nutrition Examination Survey (NHANES), National Health Interview Survey (NHIS), and Medical Expenditure Panel Survey (MEPS); and 2) three arthritis definitions based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) criteria in MEPS (National Arthritis Data Workgroup on Arthritis and Other Rheumatic Conditions [NADW-AORC], Clinical Classifications Software [CCS], and Centers for Disease Control and Prevention [CDC]). Diagnosed arthritis prevalence percentages using the surveys were within 3 points of one another (BRFSS 26.2% [99% confidence interval (99% CI) 26.0-26.4], MEPS 26.1% [99% CI 25.0-27.2], NHIS 23.5% [99% CI 22.9-24.1], NHANES 23.0% [99% CI 19.2-26.8]), and those using ICD-9-CM were within 5 percentage points of one another (CCS 25.8% [99% CI 24.6-27.1]; CDC 28.3% [99% CI 27.0-29.6]; and NADW-AORC 30.7% [99% CI 29.4-32.1]). The variation in the estimated number (in millions) affected with diagnosed arthritis was 7.8 (BRFSS 58.5 [99% CI 58.1-59.1], MEPS 59.3 [99% CI 55.6-63.1], NHANES 51.5 [99% CI 37.2-65.5], and NHIS 52.6 [99% CI 50.9-54.4]), and using ICD-9-CM definitions it was 11.1 (CCS 58.7 [99% CI 54.5-62.9], CDC 64.3 [99% CI 59.9-68.6], and NADW 69.9 [99% CI 65.2-74.5]). Most (57-70%) reporting diagnosed arthritis also reported ICD-9-CM arthritis; respondents reporting diagnosed arthritis were older than those meeting ICD-9-CM definitions. Proxy response status affected arthritis prevalence differently across surveys. Public health practitioners and decision makers are frequently charged with choosing a single number to represent arthritis prevalence in the US population. We encourage them to consider the surveys' purpose, design, measurement methods, and statistical precision when choosing an estimate. © 2016, American College of Rheumatology.

Genetic and physical interactions between factors involved in both cell cycle progression and pre-mRNA splicing in Saccharomyces cerevisiae.

PubMed Central

Ben-Yehuda, S; Dix, I; Russell, C S; McGarvey, M; Beggs, J D; Kupiec, M

2000-01-01

The PRP17/CDC40 gene of Saccharomyces cerevisiae functions in two different cellular processes: pre-mRNA splicing and cell cycle progression. The Prp17/Cdc40 protein participates in the second step of the splicing reaction and, in addition, prp17/cdc40 mutant cells held at the restrictive temperature arrest in the G2 phase of the cell cycle. Here we describe the identification of nine genes that, when mutated, show synthetic lethality with the prp17/cdc40Delta allele. Six of these encode known splicing factors: Prp8p, Slu7p, Prp16p, Prp22p, Slt11p, and U2 snRNA. The other three, SYF1, SYF2, and SYF3, represent genes also involved in cell cycle progression and in pre-mRNA splicing. Syf1p and Syf3p are highly conserved proteins containing several copies of a repeated motif, which we term RTPR. This newly defined motif is shared by proteins involved in RNA processing and represents a subfamily of the known TPR (tetratricopeptide repeat) motif. Using two-hybrid interaction screens and biochemical analysis, we show that the SYF gene products interact with each other and with four other proteins: Isy1p, Cef1p, Prp22p, and Ntc20p. We discuss the role played by these proteins in splicing and cell cycle progression. PMID:11102353

Genetic and physical interactions between factors involved in both cell cycle progression and pre-mRNA splicing in Saccharomyces cerevisiae.

PubMed

Ben-Yehuda, S; Dix, I; Russell, C S; McGarvey, M; Beggs, J D; Kupiec, M

2000-12-01

The PRP17/CDC40 gene of Saccharomyces cerevisiae functions in two different cellular processes: pre-mRNA splicing and cell cycle progression. The Prp17/Cdc40 protein participates in the second step of the splicing reaction and, in addition, prp17/cdc40 mutant cells held at the restrictive temperature arrest in the G2 phase of the cell cycle. Here we describe the identification of nine genes that, when mutated, show synthetic lethality with the prp17/cdc40Delta allele. Six of these encode known splicing factors: Prp8p, Slu7p, Prp16p, Prp22p, Slt11p, and U2 snRNA. The other three, SYF1, SYF2, and SYF3, represent genes also involved in cell cycle progression and in pre-mRNA splicing. Syf1p and Syf3p are highly conserved proteins containing several copies of a repeated motif, which we term RTPR. This newly defined motif is shared by proteins involved in RNA processing and represents a subfamily of the known TPR (tetratricopeptide repeat) motif. Using two-hybrid interaction screens and biochemical analysis, we show that the SYF gene products interact with each other and with four other proteins: Isy1p, Cef1p, Prp22p, and Ntc20p. We discuss the role played by these proteins in splicing and cell cycle progression.

9 CFR 102.6 - Conditional licenses.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Conditional licenses. 102.6 Section 102.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS LICENSES FOR BIOLOGICAL...

9 CFR 102.6 - Conditional licenses.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Conditional licenses. 102.6 Section 102.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS LICENSES FOR BIOLOGICAL...

Enterobiasis (Pinworm Infection): Diagnosis

MedlinePlus

... About CDC.gov . Pinworm Infection General Information Pinworm Infection FAQs Epidemiology & Risk Factors Biology Disease Diagnosis Treatment Prevention & Control Resources for Health Professionals Publications Get Email Updates ...

Enterobiasis (Pinworm Infection): Treatment

MedlinePlus

... About CDC.gov . Pinworm Infection General Information Pinworm Infection FAQs Epidemiology & Risk Factors Biology Disease Diagnosis Treatment Prevention & Control Resources for Health Professionals Publications Get Email Updates ...

The A- and B-type cyclin associated cdc2 kinases in Xenopus turn on and off at different times in the cell cycle.

PubMed Central

Minshull, J; Golsteyn, R; Hill, C S; Hunt, T

1990-01-01

Cyclins play a key role in the induction of mitosis. In this paper we report the isolation of a cyclin A cDNA clone from Xenopus eggs. Its cognate mRNA encodes a protein that shows characteristic accumulation and destruction during mitotic cell cycles. The cyclin A polypeptide is associated with a protein that cross-reacts with an antibody against the conserved 'PSTAIR' epitope of p34cdc2, and the cyclin A-cdc2 complex exhibits protein kinase activity that oscillates with the cell cycle. This kinase activity rises more smoothly than that of the cyclin B-cdc2 complexes and reaches a peak earlier in the cell cycle; indeed, cyclin A is destroyed before nuclear envelope breakdown. None of the cyclin-cdc2 complexes show simple relationships between the concentration of the cyclin moiety and the kinase activity. All three cyclin associated kinases (A, B1 and B2) phosphorylate identical sites on histones with the consensus XSPXK/R, although they show significant differences in their substrate preferences. We discuss possible models for the different roles of the A- and B-type cyclins in the control of cell division. Images Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. PMID:2143983

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.

Systems for rapidly detecting and treating persons with ebola virus disease--United States.

PubMed

Koonin, Lisa M; Jamieson, Denise J; Jernigan, John A; Van Beneden, Chris A; Kosmos, Christine; Harvey, Melissa Cole; Pietz, Harald; Bertolli, Jeanne; Perz, Joseph F; Whitney, Cynthia G; Halpin, Alison Sheehan-Laufer; Daley, W Randolph; Pesik, Nicki; Margolis, Gregg S; Tumpey, Abbigail; Tappero, Jordan; Damon, Inger

2015-03-06

The U.S. Department of Health and Human Services (HHS), CDC, other U.S. government agencies, the World Health Organization (WHO), and international partners are taking multiple steps to respond to the current Ebola virus disease (Ebola) outbreak in West Africa to reduce its toll there and to reduce the chances of international spread. At the same time, CDC and HHS are working to ensure that persons who have a risk factor for exposure to Ebola and who develop symptoms while in the United States are rapidly identified and isolated, and safely receive treatment. HHS and CDC have actively worked with state and local public health authorities and other partners to accelerate health care preparedness to care for persons under investigation (PUI) for Ebola or with confirmed Ebola. This report describes some of these efforts and their impact.

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.

Saccharomyces cerevisiae Gle2/Rae1 is involved in septin organization, essential for cell cycle progression.

PubMed

Zander, Gesa; Kramer, Wilfried; Seel, Anika; Krebber, Heike

2017-11-01

Gle2/Rae1 is highly conserved from yeast to humans and has been described as an mRNA export factor. Additionally, it is implicated in the anaphase-promoting complex-mediated cell cycle regulation in higher eukaryotes. Here we identify an involvement for Saccharomyces cerevisiae Gle2 in septin organization, which is crucial for cell cycle progression and cell division. Gle2 genetically and physically interacts with components of the septin ring. Importantly, deletion of GLE2 leads to elongated buds, severe defects in septin-assembly and their cellular mislocalization. Septin-ring formation is triggered by the septin-regulating GTPase Cdc42, which establishes and maintains cell polarity. Additionally, activity of the master cell cycle regulator Cdc28 (Cdk1) is needed, which is, besides other functions, also required for G 2 /M-transition, and in yeast particularly responsible for initiating the apical-isotropic switch. We show genetic and physical interactions of Gle2 with both Cdc42 and Cdc28. Most importantly, we find that gle2∆ severely mislocalizes Cdc42, leading to defects in septin-complex formation and cell division. Thus, our findings suggest that Gle2 participates in the efficient organization of the septin assembly network, where it might act as a scaffold protein. © 2017 The Authors. Yeast published by John Wiley & Sons, Ltd. © 2017 The Authors. Yeast published by John Wiley & Sons, Ltd.

36 CFR 14.6 - In form of easement, license, or permit.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false In form of easement, license, or permit. 14.6 Section 14.6 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR RIGHTS-OF-WAY Nature of Interest § 14.6 In form of easement, license, or permit. No...

36 CFR 14.6 - In form of easement, license, or permit.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false In form of easement, license, or permit. 14.6 Section 14.6 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR RIGHTS-OF-WAY Nature of Interest § 14.6 In form of easement, license, or permit. No...

27 CFR 6.45 - Assistance in acquiring license.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Assistance in acquiring license. 6.45 Section 6.45 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS âTIED-HOUSEâ Unlawful Inducements Furnishing Things of Value § 6.45 Assistance in acquiring license. Any...

Toxic hypoglycemic syndrome--Jamaica, 1989-1991.

PubMed

1992-01-31

In January and February 1991, the health officer in the parish of St. Ann, Jamaica, received reports of eight persons with toxic hypoglycemic syndrome (THS), an illness associated with consumption of unripe ackee fruit and, possibly, renta yam; two cases were fatal. On July 25, the Jamaican Ministry of Health (JMH) contacted CDC for assistance in investigating the continued occurrence of THS; the collaborative JMH and CDC epidemiologic investigation focused on characterizing the epidemiology of THS in Jamaica and assessing the role of ackee fruit, renta yams, and other factors.

Experience with a vectorized general circulation weather model on Star-100

NASA Technical Reports Server (NTRS)

Soll, D. B.; Habra, N. R.; Russell, G. L.

1977-01-01

A version of an atmospheric general circulation model was vectorized to run on a CDC STAR 100. The numerical model was coded and run in two different vector languages, CDC and LRLTRAN. A factor of 10 speed improvement over an IBM 360/95 was realized. Efficient use of the STAR machine required some redesigning of algorithms and logic. This precludes the application of vectorizing compilers on the original scalar code to achieve the same results. Vector languages permit a more natural and efficient formulation for such numerical codes.

15 CFR 742.19 - Anti-terrorism: North Korea.

Code of Federal Regulations, 2010 CFR

2010-01-01

...-users or nuclear end-uses. Applications for non-nuclear end-users or for non-nuclear end-uses, excluding... Korea under section 6(a) of the EAA. License applications for items reviewed under section 6(a) controls... processing license applications for items controlled under EAA section 6(j).) (b) Licensing policy. (1...

15 CFR 742.19 - Anti-terrorism: North Korea.

Code of Federal Regulations, 2011 CFR

2011-01-01

... reexport is destined to nuclear end-users or nuclear end-uses. Applications for non-nuclear end-users or... Korea under section 6(a) of the EAA. License applications for items reviewed under section 6(a) controls... processing license applications for items controlled under EAA section 6(j).) (b) Licensing policy. (1...

22 CFR 124.6 - Termination of manufacturing license agreements and technical assistance agreements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... and technical assistance agreements. 124.6 Section 124.6 Foreign Relations DEPARTMENT OF STATE... Termination of manufacturing license agreements and technical assistance agreements. The U.S. party to a manufacturing license or a technical assistance agreement must inform the Directorate of Defense Trade Controls...

Diagnostic Doses of Insecticides for Adult Aedes aegypti to Assess Insecticide Resistance in Cuba.

PubMed

Rodríguez, María Magdalena; Crespo, Ariel; Hurtado, Daymi; Fuentes, Ilario; Rey, Jorge; Bisset, Juan Andrés

2017-06-01

The objective of this study was to determine diagnostic doses (DDs) of 5 insecticides for the Rockefeller susceptible strain of Aedes aegypti , using the Centers for Disease Control and Prevention (CDC) bottle bioassay as a tool for monitoring insecticide resistance in the Cuban vector control program. The 30-min DD values determined in this study were 13.5 μg/ml, 6.5 μg/ml, 6 μg/ml, 90.0 μg/ml, and 15.0 μg/ml for cypermethrin, deltamethrin, lambda-cyhalothrin, chlorpyrifos, and propoxur, respectively. To compare the reliability of CDC bottle bioassay with the World Health Organization susceptible test, 3 insecticide-resistant strains were evaluated for deltamethrin and lambda-cyhalothrin. Results showed that the bottles can be used effectively from 21 to 25 days after treatment and reused up to 4 times, depending on the storage time. The CDC bottle bioassay is an effective tool to assess insecticide resistance in field populations of Ae. aegypti in Cuba and can be incorporated into vector management programs using the diagnostic doses determined in this study.

Entomologic Inoculation Rates of Anopheles arabiensis in Southwestern Ethiopia

PubMed Central

Massebo, Fekadu; Balkew, Meshesha; Gebre-Michael, Teshome; Lindtjørn, Bernt

2013-01-01

We collected anophelines every second week for one year from randomly selected houses in southwestern Ethiopia by using Centers for Disease Control (CDC) light traps, pyrethrum spray catches, and artificial pit shelter constructions to detect circumsporozoite proteins and estimate entomologic inoculation rates (EIRs). Of 3,678 Anopheles arabiensis tested for circumsporozoite proteins, 11 were positive for Plasmodium falciparum and three for P. vivax. The estimated annual P. falciparum EIR of An. arabiensis was 17.1 infectious bites per person per year (95% confidence interval = 7.03–34.6) based on CDC light traps and 0.1 infectious bites per person per year based on pyrethrum spray catches. The P. falciparum EIRs from CDC light traps varied from 0 infectious bites per person per year (in 60% of houses) to 73.2 infectious bites per person per year in the house nearest the breeding sites. Risk of exposure to infectious bites was higher in wet months than dry months, with a peak in April (9.6 infectious bites per person per month), the period of highest mosquito density. PMID:23878184

Entomologic inoculation rates of Anopheles arabiensis in southwestern Ethiopia.

PubMed

Massebo, Fekadu; Balkew, Meshesha; Gebre-Michael, Teshome; Lindtjørn, Bernt

2013-09-01

We collected anophelines every second week for one year from randomly selected houses in southwestern Ethiopia by using Centers for Disease Control (CDC) light traps, pyrethrum spray catches, and artificial pit shelter constructions to detect circumsporozoite proteins and estimate entomologic inoculation rates (EIRs). Of 3,678 Anopheles arabiensis tested for circumsporozoite proteins, 11 were positive for Plasmodium falciparum and three for P. vivax. The estimated annual P. falciparum EIR of An. arabiensis was 17.1 infectious bites per person per year (95% confidence interval = 7.03-34.6) based on CDC light traps and 0.1 infectious bites per person per year based on pyrethrum spray catches. The P. falciparum EIRs from CDC light traps varied from 0 infectious bites per person per year (in 60% of houses) to 73.2 infectious bites per person per year in the house nearest the breeding sites. Risk of exposure to infectious bites was higher in wet months than dry months, with a peak in April (9.6 infectious bites per person per month), the period of highest mosquito density.

CDC2 Mediates Progestin Initiated Endometrial Stromal Cell Proliferation: A PR Signaling to Gene Expression Independently of Its Binding to Chromatin

PubMed Central

Vallejo, Griselda; Mestre-Citrinovitz, Ana C.; Ballaré, Cecilia; Beato, Miguel; Saragüeta, Patricia

2014-01-01

Although non-genomic steroid receptor pathways have been studied over the past decade, little is known about the direct gene expression changes that take place as a consequence of their activation. Progesterone controls proliferation of rat endometrial stromal cells during the peri-implantation phase of pregnancy. We showed that picomolar concentration of progestin R5020 mimics this control in UIII endometrial stromal cells via ERK1-2 and AKT activation mediated by interaction of Progesterone Receptor (PR) with Estrogen Receptor beta (ERb) and without transcriptional activity of endogenous PR and ER. Here we identify early downstream targets of cytoplasmic PR signaling and their possible role in endometrial stromal cell proliferation. Microarray analysis of global gene expression changes in UIII cells treated for 45 min with progestin identified 97 up- and 341 down-regulated genes. The most over-represented molecular functions were transcription factors and regulatory factors associated with cell proliferation and cell cycle, a large fraction of which were repressors down-regulated by hormone. Further analysis verified that progestins regulate Ccnd1, JunD, Usf1, Gfi1, Cyr61, and Cdkn1b through PR-mediated activation of ligand-free ER, ERK1-2 or AKT, in the absence of genomic PR binding. ChIP experiments show that progestin promoted the interaction of USF1 with the proximal promoter of the Cdc2 gene. Usf1 knockdown abolished Cdc2 progestin-dependent transcriptional regulation and cell proliferation, which also blocked Cdc2 knockdown. We conclude that progestin-induced proliferation of endometrial stromal cells is mediated by ERK1-2 and AKT dependent early regulation of USF1, which directly induces Cdc2. To our knowledge, this is the first description of early target genes of progestin-activated classical PR via crosstalk with protein kinases and independently of hormone receptor binding to the genomic targets. PMID:24859236

The architecture of the DNA replication origin recognition complex in Saccharomyces cerevisiae

PubMed Central

Chen, Zhiqiang; Speck, Christian; Wendel, Patricia; Tang, Chunyan; Stillman, Bruce; Li, Huilin

2008-01-01

The origin recognition complex (ORC) is conserved in all eukaryotes. The six proteins of the Saccharomyces cerevisiae ORC that form a stable complex bind to origins of DNA replication and recruit prereplicative complex (pre-RC) proteins, one of which is Cdc6. To further understand the function of ORC we recently determined by single-particle reconstruction of electron micrographs a low-resolution, 3D structure of S. cerevisiae ORC and the ORC–Cdc6 complex. In this article, the spatial arrangement of the ORC subunits within the ORC structure is described. In one approach, a maltose binding protein (MBP) was systematically fused to the N or the C termini of the five largest ORC subunits, one subunit at a time, generating 10 MBP-fused ORCs, and the MBP density was localized in the averaged, 2D EM images of the MBP-fused ORC particles. Determining the Orc1–5 structure and comparing it with the native ORC structure localized the Orc6 subunit near Orc2 and Orc3. Finally, subunit–subunit interactions were determined by immunoprecipitation of ORC subunits synthesized in vitro. Based on the derived ORC architecture and existing structures of archaeal Orc1–DNA structures, we propose a model for ORC and suggest how ORC interacts with origin DNA and Cdc6. The studies provide a basis for understanding the overall structure of the pre-RC. PMID:18647841

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.

Overview, Control Strategies, and Lessons Learned in the CDC Response to the 2014-2016 Ebola Epidemic.

PubMed

Bell, Beth P; Damon, Inger K; Jernigan, Daniel B; Kenyon, Thomas A; Nichol, Stuart T; O'Connor, John P; Tappero, Jordan W

2016-07-08

During 2014-2016, CDC, working with U.S. and international partners, mounted a concerted response to end the unprecedented epidemic of Ebola virus disease (Ebola) in West Africa. CDC's response, which was the largest in the agency's history, was directed simultaneously at controlling the epidemic in West Africa and strengthening preparedness for Ebola in the United States. Although experience in responding to approximately 20 Ebola outbreaks since 1976 had provided CDC and other international responders an understanding of the disease and how to stop its spread, the epidemic in West Africa presented new and formidable challenges. The initial response was slow and complicated for several reasons, including wide geographic spread of cases, poor public health and societal infrastructure, sociodemographic factors, local unfamiliarity with Ebola, and distrust of government and health care workers. In the United States, widespread public alarm erupted after Ebola cases were diagnosed in Dallas, Texas, and New York City, New York. CDC, in collaboration with its U.S. and international counterparts, applied proven public health strategies as well as innovative new approaches to help control the Ebola epidemic in West Africa and strengthen public health readiness in the United States. Lessons learned include the recognition that West African and other countries need effective systems to detect and stop infectious disease threats, the need for stronger international surge capacity for times when countries are overwhelmed by an outbreak, and the importance of improving infection prevention and control in health care settings. The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html).

Cdc42 is required in a genetically distinct subset of cardiac cells during Drosophila dorsal vessel closure

PubMed Central

Swope, David; Kramer, Joseph; King, Tiffany R.; Cheng, Yi-Shan; Kramer, Sunita G.

2017-01-01

The embryonic heart tube is formed by the migration and subsequent midline convergence of two bilateral heart fields. In Drosophila the heart fields are organized into two rows of cardioblasts (CBs). While morphogenesis of the dorsal ectoderm, which lies directly above the Drosophila dorsal vessel (DV), has been extensively characterized, the migration and concomitant fundamental factors facilitating DV formation remain poorly understood. Here we provide evidence that DV closure occurs at multiple independent points along the A-P axis of the embryo in a “buttoning” pattern, divergent from the zippering mechanism observed in the overlying epidermis during dorsal closure. Moreover, we demonstrate that a genetically distinct subset of CBs is programmed to make initial contact with the opposing row. To elucidate the cellular mechanisms underlying this process, we examined the role of Rho GTPases during cardiac migration using inhibitory and overexpression approaches. We found that Cdc42 shows striking cell-type specificity during DV formation. Disruption of Cdc42 function specifically prevents CBs that express the homeobox gene tinman from completing their dorsal migration, resulting in a failure to make connections with their partnering CBs. Conversely, neighboring CBs that express the orphan nuclear receptor, seven-up, are not sensitive to Cdc42 inhibition. Furthermore, this phenotype was specific to Cdc42 and was not observed upon perturbation of Rac or Rho function. Together with the observation that DV closure occurs through the initial contralateral pairing of tinman-expressing CBs, our studies suggest that the distinct buttoning mechanism we propose for DV closure is elaborated through signaling pathways regulating Cdc42 activity in this cell type. PMID:24949939

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

Occurrence of carbapenem-resistant Escherichia coli from ...

EPA Pesticide Factsheets

E. coli isolates from primary and secondary effluents collected from seven WWTPs between 2003 and 2004 were recovered and then screened using one of four antibiotics (trimethoprim-sulfamethoxazole, ampicillin, tetracycline, and trimethoprim). We now report on the testing of a subset of these isolates to determine whether they met the Centers for Disease Control and Prevention (CDC) 2012 CRE definition (intermediate or full resistance to one or more carbapenem antibiotics (imipenem) and resistant to at least two extended-spectrum cephalosporins (cefotaxime, ceftazidime)) or the updated CDC 2015 definition (resistant to a carbapenem antibiotic or producing a carbapenemase). Based on minimum inhibitory concentrations (MICs), isolates classified as nonsusceptible to imipenem or resistant to the two cephalosporin antibiotics or resistant to a fluoroquinolone (ciprofloxacin) were used for PCR assays targeting nine carbapenemase and extended-spectrum -lactamase (ESBL) genes. Of the 500 antibiotic-resistant E. coli isolates tested, the most prevalent resistance was to cefotaxime (3.6%), followed by ciprofloxacin (2.6%), ceftazidime (2.2%) and imipenem (1.8%). Six (1.2%) isolates were nonsusceptible to imipenem, and resistant to cefotaxime and ceftazidime, meeting the CDC 2012 CRE definition. According to the CDC’s updated definition, eight (1.6%) isolates were CRE with full resistance to imipenem; only two of these eight isolates were also determined to be CRE acco

Cyclin A recruits p33cdk2 to the cellular transcription factor DRTF1.

PubMed

Bandara, L R; Adamczewski, J P; Zamanian, M; Poon, R Y; Hunt, T; Thangue, N B

1992-01-01

Cyclins are regulatory molecules that undergo periodic accumulation and destruction during each cell cycle. By activating p34cdc2 and related kinase subunits they control important events required for normal cell cycle progression. Cyclin A, for example, regulates at least two distinct kinase subunits, the mitotic kinase subunit p34cdc2 and related subunit p33cdk2, and is widely believed to be necessary for progression through S phase. However, cyclin A also forms a stable complex with the cellular transcription factor DRTF1 and thus may perform other functions during S phase. DRTF1, in addition, associates with the tumour suppressor retinoblastoma (Rb) gene product and the Rb-related protein p107. We now show, using biologically active fusion proteins, that cyclin A can direct the binding of the cdc2-like kinase subunit, p33cdk2, to complexed DRTF1, containing either Rb or p107, as well as activate its histone H1 kinase activity. Cyclin A cannot, however, direct p34cdc2 to the DRTF1 complex and we present evidence suggesting that the stability of the cyclin A-p33cdk2 complex is influenced by DRTF1 or an associated protein. Cyclin A, therefore, serves as an activating and targeting subunit of p33cdk2. The ability of cyclin A to activate and recruit p33cdk2 to DRTF1 may play an important role in regulating cell cycle progression and moreover defines a mechanism for coupling cell-cycle events to transcriptional initiation.

Repression of TFIIH Transcriptional Activity and TFIIH-Associated cdk7 Kinase Activity at Mitosis

PubMed Central

Long, John J.; Leresche, Anne; Kriwacki, Richard W.; Gottesfeld, Joel M.

1998-01-01

Nuclear transcription is repressed when eukaryotic cells enter mitosis. Mitotic repression of transcription of various cellular and viral gene promoters by RNA polymerase II can be reproduced in vitro either with extracts prepared from cells arrested at mitosis with the microtubule polymerization inhibitor nocodazole or with nuclear extracts prepared from asynchronous cells and the mitotic protein kinase cdc2/cyclin B. Purified cdc2/cyclin B kinase is also sufficient to inhibit transcription in reconstituted transcription reactions with biochemically purified and recombinant basal transcription factors and RNA polymerase II. The cyclin-dependent kinase inhibitor p21Waf1/Cip1/Sdi1 can reverse the effect of cdc2/cyclin B kinase, indicating that repression of transcription is due to protein phosphorylation. Transcription rescue and inhibition experiments with each of the basal factors and the polymerase suggest that multiple components of the transcription machinery are inactivated by cdc2/cyclin B kinase. For an activated promoter, targets of repression are TFIID and TFIIH, while for a basal promoter, TFIIH is the major target for mitotic inactivation of transcription. Protein labeling experiments indicate that the p62 and p36 subunits of TFIIH are in vitro substrates for mitotic phosphorylation. Using the carboxy-terminal domain of the large subunit of RNA polymerase II as a test substrate for phosphorylation, the TFIIH-associated kinase, cdk7/cyclin H, is inhibited concomitant with inhibition of transcription activity. Our results suggest that there exist multiple phosphorylation targets for the global shutdown of transcription at mitosis. PMID:9488463

Mutant RBL mast cells defective in Fc epsilon RI signaling and lipid raft biosynthesis are reconstituted by activated Rho-family GTPases.

PubMed

Field, K A; Apgar, J R; Hong-Geller, E; Siraganian, R P; Baird, B; Holowka, D

2000-10-01

Characterization of defects in a variant subline of RBL mast cells has revealed a biochemical event proximal to IgE receptor (Fc epsilon RI)-stimulated tyrosine phosphorylation that is required for multiple functional responses. This cell line, designated B6A4C1, is deficient in both Fc epsilon RI-mediated degranulation and biosynthesis of several lipid raft components. Agents that bypass receptor-mediated Ca(2+) influx stimulate strong degranulation responses in these variant cells. Cross-linking of IgE-Fc epsilon RI on these cells stimulates robust tyrosine phosphorylation but fails to mobilize a sustained Ca(2+) response. Fc epsilon RI-mediated inositol phosphate production is not detectable in these cells, and failure of adenosine receptors to mobilize Ca(2+) suggests a general deficiency in stimulated phospholipase C activity. Antigen stimulation of phospholipases A(2) and D is also defective. Infection of B6A4C1 cells with vaccinia virus constructs expressing constitutively active Rho family members Cdc42 and Rac restores antigen-stimulated degranulation, and active Cdc42 (but not active Rac) restores ganglioside and GPI expression. The results support the hypothesis that activation of Cdc42 and/or Rac is critical for Fc epsilon RI-mediated signaling that leads to Ca(2+) mobilization and degranulation. Furthermore, they suggest that Cdc42 plays an important role in the biosynthesis and expression of certain components of lipid rafts.

[Prevalence of overweight and obesity in adolescents from an urban district of Lima, Peru 2012].

PubMed

Lozano-Rojas, Gaudi; Cabello-Morales, Emilio; Hernádez-Diaz, Herminio; Loza-Munarriz, Cesar

2014-01-01

To determine the prevalence of overweight and obesity according to the criteria of the WHO and CDC in adolescents from an urban district of Lima, Peru 2012. This cross-sectional study included 1,743 school children of 12 to 17 years of age selected from ten public and private educational institutions, using a randomized and stratified sample of "conglomerados" (neighborhoods). In the selected schools, weight and height were measured. For the diagnosis of overweight and obesity, criteria from the WHO and CDC were used. For data analysis, descriptive and inferential statistics were performed. According to the WHO criteria, the prevalence of overweight was 33.7% (95% CI 31.5-36.0) and obesity was 14.4% (95% CI 12.8-16.1). According to CDC criteria, the prevalence of overweight was 26.5% (95% CI 24.4-28.6) and obesity was 13.9% (95% CI 12.3-15.6). The prevalence of overweight and obesity was significantly higher in males aged 12 and 13 years old and private educational institutions (p<0.05). We found very good agreement between the WHO and CDC criteria for the diagnosis of overweight and obesity. A high prevalence of overweight and obesity was found, predominantly in male students between 12 and 13 years and private educational institutions. It is necessary to initiate intervention measures that can contribute to the prevention of chronic diseases in adulthood, secondary to obesity in adolescence.

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.

Compendium of animal rabies prevention and control, 2011.

PubMed

2011-11-04

Rabies has one of the highest case-fatality ratios of any infectious disease. This report provides recommendations for public health officials, veterinarians, animal control officials, and other parties engaged in rabies prevention and control activities and should serve as the basis for standardizing procedures among jurisdictions. The recommendations regarding domestic animal vaccination, management of animals exposed to rabies, and management of animals that bite humans are the core elements of animal rabies control and human rabies prevention. These updated 2011 guidelines include the national case definition for animal rabies and clarify the role of the CDC rabies laboratory in providing confirmatory testing of suspect animals. The table of rabies vaccines licensed and marketed in the United States has been updated, and additional references have been included to provide scientific support for information in this report.

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.

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.

CDC Kerala 3: At-risk baby clinic service using different screening tools--outcome at 12 months using Developmental Assessment Scale for Indian Infants.

PubMed

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

2014-12-01

To describe CDC Kerala experience of establishing an at-risk baby clinic and the comparison of different developmental screening tools at 12 mo against the gold standard Developmental Assessment Scale for Indian Infants (DASII). At risk baby clinic of CDC, Kerala was established as a facility for follow up of NICU graduates from Sree Avittam Thirunal Hospital at 2, 4, 6, 8 and 12 mo corrected age and during each visit the mother is taught the CDC model early stimulation by developmental therapists and encouraged to continue to do the same at home. At 12 mo, assessment results of four simple developmental tools were compared with the gold standard DASII administered by a senior developmental therapist. Out of a total of 800 babies, outcome measurements at 12 mo were available for 604 infants. The prevalence of developmental delay using the screening tools, CDC grading for standing, Amiel Tison angles and DDST II (Denver II) gross motor were 24.8, 24 and 24.3% respectively and using DASII, a diagnostic tool (13.3%). Also the combination of Amiel Tison angles, CDC standing grading and DDST gross motor against DASII motor DQ had high specificity (94.15%) and negative predictive value (NPV) (70.18%) but with a very low sensitivity of 14.58% and low positive predictive value (PPV) of 53.85%. It was observed that a significant odds ratio for DASII mental deviation quotient (DQ) was seen for neonatal seizures (2.34) and low birth weight (1.49). The prevalence of developmental delay using the screening tools, CDC grading for standing, Amiel Tison angles and DDST II (Denver II) gross motor were 24.8, 24 and 24.3% respectively and together they had a high specificity, NPV and accuracy against DASII motor DQ as gold standard at one year assessment.

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...

GM-CSF Inhibits c-Kit and SCF Expression by Bone Marrow-Derived Dendritic Cells

PubMed Central

Barroeta Seijas, Amairelys Belen; Simonetti, Sonia; Vitale, Sara; Runci, Daniele; Quinci, Angela Caterina; Soriani, Alessandra; Criscuoli, Mattia; Filippi, Irene; Naldini, Antonella; Sacchetti, Federico Maria; Tarantino, Umberto; Oliva, Francesco; Piccirilli, Eleonora; Santoni, Angela; Di Rosa, Francesca

2017-01-01

Stem cell factor (SCF), the ligand of c-kit, is a key cytokine for hematopoiesis. Hematopoietic precursors express c-kit, whereas differentiated cells of hematopoietic lineage are negative for this receptor, with the exception of NK cells, mast cells, and a few others. While it has long been recognized that dendritic cells (DCs) can express c-kit, several questions remain concerning the SCF/c-kit axis in DCs. This is particularly relevant for DCs found in those organs wherein SCF is highly expressed, including the bone marrow (BM). We characterized c-kit expression by conventional DCs (cDCs) from BM and demonstrated a higher proportion of c-kit+ cells among type 1 cDC subsets (cDC1s) than type 2 cDC subsets (cDC2s) in both humans and mice, whereas similar levels of c-kit expression were observed in cDC1s and cDC2s from mouse spleen. To further study c-kit regulation, DCs were generated with granulocyte-macrophage colony-stimulating factor (GM-CSF) from mouse BM, a widely used protocol. CD11c+ cells were purified from pooled non-adherent and slightly adherent cells collected after 7 days of culture, thus obtaining highly purified BM-derived DCs (BMdDCs). BMdDCs contained a small fraction of c-kit+ cells, and by replating them for 2 days with GM-CSF, we obtained a homogeneous population of c-kit+ CD40hi MHCIIhi cells. Not only did BMdDCs express c-kit but they also produced SCF, and both were striking upregulated if GM-CSF was omitted after replating. Furthermore, a small but significant reduction in BMdDC survival was observed upon SCF silencing. Incubation of BMdDCs with SCF did not modulate antigen presentation ability of these cells, nor it did regulate their membrane expression of the chemokine receptor CXCR4. We conclude that the SCF/c-kit-mediated prosurvival circuit may have been overlooked because of the prominent use of GM-CSF in DC cultures in vitro, including those human DC cultures destined for the clinics. We speculate that DCs more prominently rely on SCF in vivo in some microenvironments, with potential implications for graft-versus-host disease and antitumor immunity. PMID:28261209

On Channel-Discontinuity-Constraint Routing in Wireless Networks☆

PubMed Central

Sankararaman, Swaminathan; Efrat, Alon; Ramasubramanian, Srinivasan; Agarwal, Pankaj K.

2011-01-01

Multi-channel wireless networks are increasingly deployed as infrastructure networks, e.g. in metro areas. Network nodes frequently employ directional antennas to improve spatial throughput. In such networks, between two nodes, it is of interest to compute a path with a channel assignment for the links such that the path and link bandwidths are the same. This is achieved when any two consecutive links are assigned different channels, termed as “Channel-Discontinuity-Constraint” (CDC). CDC-paths are also useful in TDMA systems, where, preferably, consecutive links are assigned different time-slots. In the first part of this paper, we develop a t-spanner for CDC-paths using spatial properties; a sub-network containing O(n/θ) links, for any θ > 0, such that CDC-paths increase in cost by at most a factor t = (1−2 sin (θ/2))−2. We propose a novel distributed algorithm to compute the spanner using an expected number of O(n log n) fixed-size messages. In the second part, we present a distributed algorithm to find minimum-cost CDC-paths between two nodes using O(n2) fixed-size messages, by developing an extension of Edmonds’ algorithm for minimum-cost perfect matching. In a centralized implementation, our algorithm runs in O(n2) time improving the previous best algorithm which requires O(n3) running time. Moreover, this running time improves to O(n/θ) when used in conjunction with the spanner developed. PMID:24443646

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: ...

State laws on tobacco control--United States, 1998.

PubMed

Fishman, J A; Allison, H; Knowles, S B; Fishburn, B A; Woollery, T A; Marx, W T; Shelton, D M; Husten, C G; Eriksen, M P

1999-06-25

State laws addressing tobacco use, the leading preventable cause of death in the United States, are summarized. Laws address smoke-free indoor air, minors' access to tobacco products, advertising of tobacco products, and excise taxes on tobacco products. Legislation effective through December 31, 1998. CDC identified laws addressing tobacco control by using an on-line legal research database. CDC's findings were verified with the National Cancer Institute's State Cancer Legislative Database. Since a previous surveillance summary on state tobacco-control laws published in November 1995 (covering legislation effective through June 30, 1995), several states have enacted new restrictions or strengthened existing legislation that addresses smoke-free indoor air, minors' access to tobacco, tobacco advertising, and tobacco taxes. Five states strengthened their smoke-free indoor air legislation. All states and Washington, D.C., continued to prohibit the sale and distribution of tobacco products to minors; however, 21 states expanded minors' access laws by designating enforcement authorities, adding license suspension or revocation for sale to minors, or requiring signage. Since the 1995 report, eight additional states (a total of 19 states and Washington, D.C.) now ban vending machines from areas accessible to minors. Thirteen states restrict advertising of tobacco products, an increase of four states since the 1995 report. Although the number of states that tax cigarettes and smokeless tobacco did not change, 13 states increased excise taxes on cigarettes, and five states increased excise taxes on smokeless tobacco products. The average state excise tax on cigarettes is 38.9 cents per pack, an increase of 7.4 cents compared with the average tax in the 1995 report. State laws addressing tobacco control vary in relation to restrictiveness, enforcement and penalties, preemptions, and exceptions. The data summarizing state tobacco-control laws are available through CDC's State Tobacco Activities Tracking and Evaluation (STATE) System; the laws are collected and updated every quarter. The STATE System also contains state-specific data on the prevalence of tobacco use, tobacco-related deaths, and the costs of tobacco use. Information from the STATE System is available for use by policy makers at the state and local levels to plan and implement initiatives to prevent and reduce tobacco use. In addition, CDC is using this information to assess the ongoing impact of tobacco-control programs and policies on tobacco use.

47 CFR 25.136 - Licensing provisions for user transceivers in the 1.6/2.4 GHz, 1.5/1.6 GHz, and 2 GHz Mobile...

Code of Federal Regulations, 2011 CFR

2011-10-01

... Applications and Licenses Earth Stations § 25.136 Licensing provisions for user transceivers in the 1.6/2.4 GHz... specified in § 25.213, earth stations operating in the 1.6/2.4 GHz and 1.5/1.6 GHz Mobile Satellite Services... aircraft unless the earth station has a direct physical connection to the aircraft cabin or cockpit...

47 CFR 25.136 - Licensing provisions for user transceivers in the 1.6/2.4 GHz, 1.5/1.6 GHz, and 2 GHz Mobile...

Code of Federal Regulations, 2012 CFR

2012-10-01

... Applications and Licenses Earth Stations § 25.136 Licensing provisions for user transceivers in the 1.6/2.4 GHz... specified in § 25.213, earth stations operating in the 1.6/2.4 GHz and 1.5/1.6 GHz Mobile Satellite Services... aircraft unless the earth station has a direct physical connection to the aircraft cabin or cockpit...

47 CFR 25.136 - Licensing provisions for user transceivers in the 1.6/2.4 GHz, 1.5/1.6 GHz, and 2 GHz Mobile...

Code of Federal Regulations, 2013 CFR

2013-10-01

... Applications and Licenses Earth Stations § 25.136 Licensing provisions for user transceivers in the 1.6/2.4 GHz... specified in § 25.213, earth stations operating in the 1.6/2.4 GHz and 1.5/1.6 GHz Mobile-Satellite Services... aircraft unless the earth station has a direct physical connection to the aircraft cabin or cockpit...

Injuries and Mass Casualty Events

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[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

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.

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.

SUBSCAPULAR AND TRICEPS SKINFOLDS REFERENCE VALUES OF HISPANIC AMERICAN CHILDREN AND ADOLESCENTS AND THEIR COMPARISON WITH THE REFERENCE OF CENTERS FOR DISEASE CONTROL AND PREVENTION (CDC).

PubMed

Marrodán Serrano, María Dolores; González-Montero de Espinosa, Marisa; Herráez, Ángel; Alfaro, Emma Laura; Felipe Bejarano, Ignacio; Carmenate, María Margarita; Prado, Consuelo; Beatriz Lomaglio, Delia; López-Ejeda, Noemí; Martínez, Antonio; Mesa, María Soledad; Méndez Pérez, Betty; Meléndez, Juana María; Moreno Romero, Susana; Pacheco, Jose Luis; Vázquez, Vanessa; Dipierri, José E

2015-12-01

the assessment of the skinfold thickness is an objective measure of adiposity. Therefore, it is a useful tool for nutritional diagnosis and prevention of metabolic risk associated with excess fat in chilhood and adolescence. to provide percentiles of subscapular and triceps skinfolds for Hispanic American schoolchildren and compare them with those published by the Centers for Disease Control and Prevention (CDC) from United States, that it have been commonly used as a reference in most of these countries. subscapular and triceps skinfolds were measured in 9.973 schoolchildren 4-19 aged from Spain, Argentina, Cuba, Venezuela and Mexico with Holtain caliper with 0.2 mm accuracy. Percentiles were obtained with the LMS statistical method and were presented in tables divided in stages of 6 months and in curves graphics. The difference between Hispanic American and CDC mean values were provided for P3, P50 and P97 in mm and also were graphically represented. skinfolds measurements obviously increased with age in both sexes but, in boys, this increase is much more marked in highest percentiles between 8 and 13 years; this maximum is reached earlier than what occurs in CDC reference. In both sexes, all percentiles analized in Hispanic American schoolchildren were higher than the CDC reference except P97 up to 10 or 13 years that was notably smaller. the skinfolds percentiles of Hispanic American children and adolescents differ from CDC that are usually used as reference. The values of subscapular and triceps skinfolds provided in this study, could be applied to populations of a similar ethnic background, especially in comparative studies of body composition. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Isolation and biochemical characterization of a γ-type phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum.

PubMed

Gimenes, Sarah Natalie Cirilo; Ferreira, Francis Barbosa; Silveira, Ana Carolina Portella; Rodrigues, Renata Santos; Yoneyama, Kelly Aparecida Geraldo; Izabel Dos Santos, Juliana; Fontes, Marcos Roberto de Mattos; de Campos Brites, Vera Lúcia; Santos, André Luiz Quagliatto; Borges, Márcia Helena; Lopes, Daiana Silva; Rodrigues, Veridiana M

2014-04-01

In the present work, we describe the isolation and partial structural and biochemical characterization of the first phospholipase A2 inhibitor (γPLI) from Crotalus durissus collilineatus (Cdc) snake serum. Initially, the Cdc serum was subjected to a Q-Sepharose ion exchange column, producing six peaks at 280 nm absorbance (Q1-Q6). Subsequently, Q4 fraction was submitted to affinity chromatography with immobilized PLA2 BnSP-7, a step that resulted in two fractions (NHS-1 and NHS-2). The latter contained the inhibitor, denominated γCdcPLI. The molecular mass of γCdcPLI, determined by Matrix-Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF), was 22,340 Da. Partial sequences obtained by Edman degradation and by mass spectrometry (MALDI-TOF/TOF), showed similarity, as expected, to other related inhibitors. Circular dichroism (CD) analysis showed the presence of approximately 22% alpha helices and 29% beta sheets in the protein secondary structure. Additionally, CD studies also indicated no significant changes in the secondary structure of γCdcPLI when it is complexed to BpPLA2-TXI. On the other hand, dynamic light scattering (DLS) assays showed a temperature-dependent oligomerization behavior for this inhibitor. Biochemical analyses showed γCdcPLI was able to inhibit the enzymatic, cytotoxic and myotoxic activities of PLA2s. Structural and functional studies performed on this inhibitor may elucidate the action mechanisms of PLA2 inhibitors. In addition, we hope this study may contribute to investigating the potential use of these inhibitors for the treatment of snakebite or inflammatory diseases in which PLA2s may be involved. Copyright © 2014 Elsevier Ltd. All rights reserved.

Chlamydia - CDC Fact Sheet

MedlinePlus

... behaviors and biological factors common among young people. Gay, bisexual, and other men who have sex with ... should get a test for chlamydia every year. Gay, bisexual, and other men who have sex with ...

Bread: CDC 7600 program that processes Spent Fuel Test Climax data

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

Hage, G.L.

BREAD will process a family of files copied from a data tape made by Hewlett-Packard equipment employed for data acquisition on the Spent Fuel Test-Climax at NTS. Tapes are delivered to Livermore approximately monthly. The process at this stage consists of four steps: read the binary files and convert from H-P 16-bit words to CDC 7600 60-bit words; check identification and data ranges; write the data in 6-bit ASCII (BCD) format, one data point per line; then sort the file by identifier and time.

15 CFR 740.2 - Restrictions on all License Exceptions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... EXCEPTIONS § 740.2 Restrictions on all License Exceptions. (a) You may not use any License Exception if any...) “Space qualified” items. Commodities defined in ECCNs 3A001.b.8 (Traveling Wave Tube Amplifiers (TWTAs... (Traveling Wave Tube Amplifiers (TWTAs) exceeding 18 GHz), 6A002.e, 6A008.j.1, or 6A998.b and controlled...

A p21-activated kinase (PAK1) signaling cascade coordinately regulates F-actin remodeling and insulin granule exocytosis in pancreatic β cells

PubMed Central

Kalwat, Michael A.; Yoder, Stephanie M.; Wang, Zhanxiang; Thurmond, Debbie C.

2012-01-01

Human islet studies implicate an important signaling role for the Cdc42 effector protein p21-activated kinase (PAK1) in the sustained/second-phase of insulin secretion. Because human islets from type 2 diabetic donors lack ~80% of normal PAK1 protein levels, the mechanistic requirement for PAK1 signaling in islet function was interrogated. Similar to MIN6 β cells, human islets elicited glucose-stimulated PAK1 activation that was sensitive to the PAK1 inhibitor, IPA3. Given that sustained insulin secretion has been correlated with glucose-induced filamentous actin (F-actin) remodeling, we tested the hypothesis that a Cdc42-activated PAK1 signaling cascade is required to elicit F-actin remodeling to mobilize granules to the cell surface. Live-cell imaging captured the glucose-induced cortical F-actin remodeling in MIN6 β cells; IPA3-mediated inhibition of PAK1 abolished this remodeling. IPA3 also ablated glucose-stimulated insulin granule accumulation at the plasma membrane, consistent with its role in sustained/second-phase insulin release. Both IPA3 and a selective inhibitor of the Cdc42 GTPase, ML-141, blunted the glucose-stimulated activation of Raf-1, suggesting Raf-1 to be downstream of Cdc42→PAK1. IPA3 also inhibited MEK1/2 activation, implicating the MEK1/2→ERK1/2 cascade to occur downstream of PAK1. Importantly, PD0325901, a new selective inhibitor of MEK1/2→ERK1/2 activation, impaired F-actin remodeling and the sustained/amplification pathway of insulin release. Taken together, these data suggest that glucose-mediated activation of Cdc42 leads to activation of PAK1 and prompts activation of its downstream targets Raf-1, MEK1/2 and ERK1/2 to elicit F-actin remodeling and recruitment of insulin granules to the plasma membrane to support the sustained phase of insulin release. PMID:23246867

Other High-Risk Factors for Young Drivers--How Graduated Licensing Does, Doesn't, or Could Address Them.

ERIC Educational Resources Information Center

Ferguson, Susan A.

2003-01-01

Examines the risk factors underlying the high crash rates of newly licensed drivers and assesses the extent to which existing graduated driver-licensing programs address these risks. Discusses such risks as driver fatigue, not using seat belts, high speeds, high-powered vehicles, and in-vehicle distractions. (Contains 66 references.) (AUTHOR/WFA)

MATLAB Software Versions and Licenses for the Peregrine System |

Science.gov Websites

: Feature usage info: Users of MATLAB: (Total of 6 licenses issued; Total of ... licenses in use) Users of Compiler: (Total of 1 license issued; Total of ... licenses in use) Users of Distrib_Computing_Toolbox : (Total of 4 licenses issued; Total of ... licenses in use) Users of MATLAB_Distrib_Comp_Engine: (Total of

Evidence and the Politics of Deimplementation: The Rise and Decline of the “Counseling and Testing” Paradigm for HIV Prevention at the US Centers for Disease Control and Prevention

PubMed Central

BAYER, RONALD; FAIRCHILD, AMY L.

2016-01-01

Policy Points: In situations of scientific uncertainty, public health interventions, such as counseling for HIV infection, sometimes must be implemented before obtaining evidence of efficacy.The history of HIV counseling and testing, which served as the cornerstone of HIV prevention efforts at the US Centers for Disease Control and Prevention (CDC) for a quarter of a century, illustrates the influence of institutional resistance on public health decision making and the challenge of de‐implementing well‐established programs. Context In 1985, amid uncertainty about the accuracy of the new test for HIV, public health officials at the Centers for Disease Control and Prevention (CDC) and AIDS activists agreed that counseling should always be provided both before and after testing to ensure that patients were tested voluntarily and understood the meaning of their results. As the “exceptionalist” perspective that framed HIV in the early years began to recede, the purpose of HIV test counseling shifted over the next 30 years from emphasizing consent, to providing information, to encouraging behavioral change. With this increasing emphasis on prevention, HIV test counseling faced mounting doubts about whether it “worked.” The CDC finally discontinued its preferred test counseling approach in October 2014. Methods Drawing on key informant interviews with current and former CDC officials, behavioral scientists, AIDS activists, and others, along with archival material, news reports, and scientific and governmental publications, we examined the origins, development, and decline of the CDC's “counseling and testing” paradigm for HIV prevention. Findings Disagreements within the CDC emerged by the 1990s over whether test counseling could be justified on the basis of efficacy and cost. Resistance to the prospect of policy change by supporters of test counseling in the CDC, gay activists for whom counseling carried important ethical and symbolic meanings, and community organizations dependent on federal funding made it difficult for the CDC to de‐implement the practice. Conclusions Analyses of changes in public health policy that emphasize the impact of research evidence produced in experimental or epidemiological inquiries may overlook key social and political factors involving resistance to deimplementation that powerfully shape the relationship between science and policy. PMID:26994712

Evidence and the Politics of Deimplementation: The Rise and Decline of the "Counseling and Testing" Paradigm for HIV Prevention at the US Centers for Disease Control and Prevention.

PubMed

Johns, David Merritt; Bayer, Ronald; Fairchild, Amy L

2016-03-01

In situations of scientific uncertainty, public health interventions, such as counseling for HIV infection, sometimes must be implemented before obtaining evidence of efficacy. The history of HIV counseling and testing, which served as the cornerstone of HIV prevention efforts at the US Centers for Disease Control and Prevention (CDC) for a quarter of a century, illustrates the influence of institutional resistance on public health decision making and the challenge of de-implementing well-established programs. In 1985, amid uncertainty about the accuracy of the new test for HIV, public health officials at the Centers for Disease Control and Prevention (CDC) and AIDS activists agreed that counseling should always be provided both before and after testing to ensure that patients were tested voluntarily and understood the meaning of their results. As the "exceptionalist" perspective that framed HIV in the early years began to recede, the purpose of HIV test counseling shifted over the next 30 years from emphasizing consent, to providing information, to encouraging behavioral change. With this increasing emphasis on prevention, HIV test counseling faced mounting doubts about whether it "worked." The CDC finally discontinued its preferred test counseling approach in October 2014. Drawing on key informant interviews with current and former CDC officials, behavioral scientists, AIDS activists, and others, along with archival material, news reports, and scientific and governmental publications, we examined the origins, development, and decline of the CDC's "counseling and testing" paradigm for HIV prevention. Disagreements within the CDC emerged by the 1990s over whether test counseling could be justified on the basis of efficacy and cost. Resistance to the prospect of policy change by supporters of test counseling in the CDC, gay activists for whom counseling carried important ethical and symbolic meanings, and community organizations dependent on federal funding made it difficult for the CDC to de-implement the practice. Analyses of changes in public health policy that emphasize the impact of research evidence produced in experimental or epidemiological inquiries may overlook key social and political factors involving resistance to deimplementation that powerfully shape the relationship between science and policy. © 2016 Milbank Memorial Fund.

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.

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

75 FR 33851 - Florida Power & Light Company; Turkey Point, Units 6 and 7; Combined License Application, Notice...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-15

... Company; Turkey Point, Units 6 and 7; Combined License Application, Notice of Intent To Prepare an... application for a combined license (COL) to build Units 6 and 7 at its Turkey Point site, located in Miami... approximately 4.5 miles from the nearest boundary of the Turkey Point site; the site is approximately 25 miles...

Dissemination of the CDC's Hand Hygiene Guideline and impact on infection rates

PubMed Central

Larson, Elaine L.; Quiros, Dave; Lin, Susan X.

2007-01-01

Background The diffusion of national evidence-based practice guidelines and their impact on patient outcomes often go unmeasured. Methods Our objectives were to (1) evaluate implementation and compliance with clinical practices recommended in the new Centers for Disease Control and Prevention (CDC) Hand Hygiene Guideline, (2) compare rates of health care-associated infections (HAI) before and after implementation of the Guideline recommendations, and (3) examine the patterns and correlates of changes in rates of HAI. We used pre- and post-Guideline implementation site visits and surveys in the setting of 40 US hospitals—members of the National Nosocomial Infections Surveillance System—and measured HAI rates 1 year before and after publication of the CDC Guideline and used direct observation of hand hygiene compliance and Guideline implementation scores. Results All study hospitals had changed their policies and procedures and provided products in compliance with Guideline recommendations; 89.8% of 1359 staff members surveyed anonymously reported that they were familiar with the Guideline. However, in 44.2% of the hospitals (19/40), there was no evidence of a multidisciplinary program to improve compliance. Hand hygiene rates remained low (mean, 56.6%). Rates of central line-associated bloodstream infections were significantly lower in hospitals with higher rates of hand hygiene (P < .001). No impact of Guideline implementation or hand hygiene compliance on other HAI rates was identified. Other factors occurring over time could affect rates of HAI. Observed hand hygiene compliance rates were likely to overestimate rates in actual practice. The study may have been of too short duration to detect the impact of a practice guideline. Conclusion Wide dissemination of this Guideline was not sufficient to change practice. Only some hospitals had initiated multidisciplinary programs; practice change is unlikely without such multidisciplinary efforts and explicit administrative support. PMID:18063132

Dissemination of the CDC's Hand Hygiene Guideline and impact on infection rates.

PubMed

Larson, Elaine L; Quiros, Dave; Lin, Susan X

2007-12-01

The diffusion of national evidence-based practice guidelines and their impact on patient outcomes often go unmeasured. Our objectives were to (1) evaluate implementation and compliance with clinical practices recommended in the new Centers for Disease Control and Prevention (CDC) Hand Hygiene Guideline, (2) compare rates of health care-associated infections (HAI) before and after implementation of the Guideline recommendations, and (3) examine the patterns and correlates of changes in rates of HAI. We used pre- and post-Guideline implementation site visits and surveys in the setting of 40 US hospitals--members of the National Nosocomial Infections Surveillance System--and measured HAI rates 1 year before and after publication of the CDC Guideline and used direct observation of hand hygiene compliance and Guideline implementation scores. All study hospitals had changed their policies and procedures and provided products in compliance with Guideline recommendations; 89.8% of 1359 staff members surveyed anonymously reported that they were familiar with the Guideline. However, in 44.2% of the hospitals (19/40), there was no evidence of a multidisciplinary program to improve compliance. Hand hygiene rates remained low (mean, 56.6%). Rates of central line-associated bloodstream infections were significantly lower in hospitals with higher rates of hand hygiene (P < .001). No impact of Guideline implementation or hand hygiene compliance on other HAI rates was identified. Other factors occurring over time could affect rates of HAI. Observed hand hygiene compliance rates were likely to overestimate rates in actual practice. The study may have been of too short duration to detect the impact of a practice guideline. Wide dissemination of this Guideline was not sufficient to change practice. Only some hospitals had initiated multidisciplinary programs; practice change is unlikely without such multidisciplinary efforts and explicit administrative support.

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

Enhancing HIV Testing and Treatment among Men Who Have Sex with Men in China: A Pilot Model with Two-Rapid Tests, Single Blood Draw Session, and Intensified Case Management in Six Cities in 2013.

PubMed

Zhang, Dapeng; Lu, Hongyan; Zhuang, Minghua; Wu, Guohui; Yan, Hongjing; Xu, Jun; Wei, Xiaoli; Li, Chengmei; Meng, Sining; Fu, Xiaojing; Qi, Jinlei; Wang, Peng; Luo, Mei; Dai, Min; Yip, Ray; Sun, Jiangping; Wu, Zunyou

2016-01-01

To explore models to improve HIV testing, linkage to care and treatment among men who have sex with men (MSM) in cooperation with community-based organizations (CBOs) in China. We introduced a new model for HIV testing services targeting MSM in six cities in 2013.These models introduced provision of rapid HIV testing by CBO staff and streamlined processes for HIV screening, confirmation of initial reactive screening results, and linkage to care among diagnosed people. We monitored attrition along each step of the continuum of care from screening to treatment and compared program performance between 2012 and 2013. According to the providers of two rapid tests (HIV screening), four different services delivery models were examined in 2013: Model A = first screen at CDC, second at CDC (Model A = CDC+CDC), Model B = first and second screens at CBOs (Model B = CBO+CBO), Model C = first screen at CBO, second at Hospital (Model C = CBO+Hosp), and Model D = first screen at CBO, second at CDC (Model D = CBO+CDC). Logistic regressions were performed to assess advantages of different screening models of case finding and case management. Compared to 2012, the number of HIV screening tests performed for MSM increased 35.8% in 2013 (72,577 in 2013 vs. 53,455 in 2012). We observed a 5.6% increase in proportion of cases screened reactive receiving HIV confirmatory tests (93.9% in 2013 vs. 89.2% in 2012, χ2 = 48.52, p<0.001) and 65% reduction in loss to CD4 cell count tests (15% in 2013 vs. 43% in 2012, χ2 = 628.85, p<0.001). Regarding linkage to care and treatment, the 2013 pilot showed that the Model D had the highest rate of loss between screening reactive and confirmatory test among the four models, with 18.1% fewer receiving a second screening test and a further 5.9% loss among those receiving HIV confirmatory tests. The Model B and the Model C showed lower losses (0.8% and 1.3%) for newly diagnosed HIV positives receiving CD4 cell count tests, and higher rates of HIV positives referred to designated ART hospitals (88.0% and 93.3%) than the Model A and Model D (4.6% and 5.7% for CD4 cell count test, and 68.9% and 64.4% for referring to designated ART hospitals). The proportion of cases where the screening test was reactive that were commenced on ART was highest in Model C; 52.8% of cases commenced on ART compared to 38.9%, 34.2% and 21.1% in Models A, B and D respectively. Using Model A as a reference group, the multivariate logistic regression results also showed the advantages of Models B, C and D, which increased CD4 cell count test, referral to designated ART hospitals and initiation of ART, when controlling for program city and other factors. This study has demonstrated that involvement of CBOs in HIV rapid testing provision, streamlining testing and care procedures and early hospital case management can improve testing, linkage to, and retention in care and treatment among MSM in China.

Insufficient amount of Cdc2 and continuous activation of Wee1 B are the cause of meiotic failure in porcine growing oocytes.

PubMed

Nishimura, Takanori; Shimaoka, Takuma; Kano, Kiyoshi; Naito, Kunihiko

2009-10-01

In mammals, growing oocytes with a diameter less than 80% of that of full-grown oocytes cannot start meiotic maturation, and their maturation promoting factor (MPF) cannot be activated by hormonal stimulation or isolation from follicles. The aim of the present study was to identify the key molecules responsible for meiotic failure of these growing oocytes (referred to as "small oocytes" in the present study). To this end, we altered the expression of the molecules involved in MPF activation in the small oocytes of pigs by injecting them with mRNA or antisense RNA (asRNA) and examined the effects on the meiotic ability of the small oocytes. Immunoblotting analyses revealed three defects in small oocytes compared with full-grown oocytes, an inactive mitogen activated protein kinase (MAPK) cascade, a failure of cyclin B synthesis and an insufficient amount of Cdc2. Injection with mRNAs of Mos, the uppermost molecule of the MAPK cascade, cyclin B1, cyclin B2 or Cdc2 into small porcine oocytes indicated directly and for the first time that the cause of meiotic failure of porcine small oocytes is an insufficient amount of Cdc2 rather than MAPK inactivation or failure of cyclin B synthesis. Next, in order to suppress Myt1 and Wee1B, which phosphorylates at inhibitory phosphorylation sites of Cdc2 and inactive MPF, we injected their asRNAs into the porcine small oocytes and found that the Wee1B asRNA significantly increased meiotic ability, whereas the Myt1 asRNA had no effect. When Cdc2 overexpression and suppression of Wee1B expression were simultaneously induced in the small oocytes of pigs, about 70% of the small oocytes resumed meiosis, and this rate was nearly comparable with that of the full-grown oocytes. These results strongly suggest that an insufficient amount of Cdc2 and continuous activation of Wee1 B are the cause of meiotic failure of small oocytes in pigs.

Activation of maturation promoting factor in Bufo arenarum oocytes: injection of mature cytoplasm and germinal vesicle contents.

PubMed

Toranzo, G Sánchez; Bonilla, F; Zelarayán, L; Oterino, J; Bühler, M I

2006-11-01

Although progesterone is the established maturation inducer in amphibians, Bufo arenarum oocytes obtained during the reproductive period (spring-summer) resume meiosis with no need of an exogenous hormonal stimulus if deprived of their enveloping follicle cells, a phenomenon called spontaneous maturation. In this species it is possible to obtain oocytes competent and incompetent to undergo spontaneous maturation according to the seasonal period in which animals are captured. Reinitiation of meiosis is regulated by maturation promoting factor (MPF), a complex of the cyclin-dependent kinase p34cdc2 and cyclin B. Although the function and molecule of MPF are common among species, the formation and activation mechanisms of MPF differ according to species. This study was undertaken to evaluate the presence of pre-MPF in Bufo arenarum oocytes incompetent to mature spontaneously and the effect of the injection of mature cytoplasm or germinal vesicle contents on the resumption of meiosis. The results of our treatment of Bufo arenarum immature oocytes incompetent to mature spontaneously with sodium metavanadate (NaVO3) and dexamethasone (DEX) indicates that these oocytes have a pre-MPF, which activates and induces germinal vesicle breakdown (GVBD) by dephosphorylation on Thr-14/Tyr-15 by cdc25 phosphatase and without cyclin B synthesis. The injection of cytoplasm containing active MPF is sufficient to activate an amplification loop that requires the activation of cdc25 and protein kinase C, the decrease in cAMP levels, and is independent of protein synthesis. However, the injection of germinal vesicle content also induces GVBD in the immature receptor oocyte, a process dependent on protein synthesis but not on cdc25 phosphatase or PKC activity.

Comparison between CDC and WHO BMI z-score and their relation with metabolic risk markers in Northern Portuguese obese adolescents.

PubMed

Nascimento, Henrique; Catarino, Cristina; Mendonça, Denisa; Oliveira, Pedro; Alves, Ana Inês; Medeiros, Ana Filipa; Pereira, Petronila Rocha; Rêgo, Carla; Mansilha, Helena Ferreira; Aires, Luísa; Mota, Jorge; Quintanilha, Alexandre; Santos-Silva, Alice; Belo, Luís

2015-01-01

Growth-curves are an important tool for evaluating the anthropometric development in pediatrics. The different growth-curves available are based in different populations, what leads to different cut-offs. Pediatric obesity tracks into adulthood and is associated with increased cardiovascular risk. The accurate assessment of a child nutritional status using growth-curves can indicate individuals that are either obese or in risk of becoming obese, allowing an early intervention. Moreover, the association between the data obtained from growth-curves with specific metabolic risk factors further highlights the importance of these charts. This study aimed to evaluate the associations between body mass index z-score (BMIzsc), determined using the growth-curves from the Centre for Disease Control and Prevention (CDC) and from the World Health Organization (WHO), with cardiovascular risk factors, represented here by metabolic syndrome (MS) and insulin resistance (IR) related parameters. The study involved 246 obese adolescents (10-18 years, 122 females). MS was defined according to the International Diabetes Federation. IR was considered for HOMA-IR greater than 2.5. No difference between both BMIzsc in identifying MS was noticeable by a ROC analysis. For both indexes the area-under-the-curve increased for older groups, particularly for males. CDC-BMIzsc was the best predictor of MS by logistic regression when all population was considered, however MS was better predicted by WHO-BMIzsc for females and by CDC-BMIzsc for males. Younger girls and older boys were in increased risk for MS. Similar results were obtained for IR. A significant difference between the two BMIzsc regarding their association with MS and IR was not clear, being these associations weaker in younger individuals.

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

CDC Kerala 5: Developmental therapy clinic experience--use of Child Development Centre grading for motor milestones.

PubMed

Nair, M K C; Resmi, V R; Krishnan, Rajee; Harikumaran Nair, G S; Leena, M L; Bhaskaran, Deepa; George, Babu; Russell, Paul Swamidhas Sudhakar

2014-12-01

To document the experiences of the intervention given to children who attended the developmental therapy clinic of Child Development Centre (CDC) Kerala, a specialized clinic for providing developmental intervention/therapy for babies less than two years with developmental delay/disability. All the babies referred to this speciality clinic from developmental screening/evaluation clinics of CDC were registered in the clinic and re-evaluation was done using CDC grading for head holding, sitting, standing, Amiel Tison passive angles, and Trivandrum Developmental Screening Chart (TDSC) 0-2 y. Out of a total of 600 consecutive babies below 2 y with developmental delay/disability referred to developmental therapy clinic, on comparing the test results at enrollment and after 6 mo of intervention, a statistically significant reduction was observed (i) in the 2-4 mo age group with regard to abnormal TDSC (25.5%), (ii) in the 4-8 mo age group with regard to abnormal head holding grade (87.1%) and abnormal TDSC (19.4%), (iii) in the 8-12 mo age group, with regard to abnormal sitting grade (71.7%) and (iv) in the above 12 mo age group with regard to abnormal sitting grade (35.3%) and abnormal standing grade (78.8%). The experience of organizing the developmental intervention/therapy clinic at CDC Kerala has shown that therapy services by developmental therapists in a centre and supportive therapy by mother at home is useful in improving the developmental status of children with developmental delay.

21 CFR 515.10 - Medicated feed mill license applications.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Medicated feed mill license applications. 515.10... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS MEDICATED FEED MILL LICENSE Applications § 515.10 Medicated feed mill license applications. (a) Medicated feed mill license applications (Forms FDA 3448) may...

21 CFR 515.23 - Voluntary revocation of medicated feed mill license.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Voluntary revocation of medicated feed mill... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS MEDICATED FEED MILL LICENSE Administrative Actions on Licenses § 515.23 Voluntary revocation of medicated feed mill license. A license issued under...

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.

Multiple Rap1 effectors control Epac1-mediated tightening of endothelial junctions.

PubMed

Pannekoek, Willem-Jan; Vliem, Marjolein J; Bos, Johannes L

2018-02-17

Epac1 and Rap1 mediate cAMP-induced tightening of endothelial junctions. We have previously found that one of the mechanisms is the inhibition of Rho-mediated tension in radial stress fibers by recruiting the RhoGAP ArhGAP29 in a complex containing the Rap1 effectors Rasip1 and Radil. However, other mechanisms have been proposed as well, most notably the induction of tension in circumferential actin cables by Cdc42 and its GEF FGD5. Here, we have investigated how Rap1 controls FGD5/Cdc42 and how this interconnects with Radil/Rasip1/ArhGAP29. Using endothelial barrier measurements, we show that Rho inhibition is not sufficient to explain the barrier stimulating effect of Rap1. Indeed, Cdc42-mediated tension is induced at cell-cell contacts upon Rap1 activation and this is required for endothelial barrier function. Depletion of potential Rap1 effectors identifies AF6 to mediate Rap1 enhanced tension and concomitant Rho-independent barrier function. When overexpressed in HEK293T cells, AF6 is found in a complex with FGD5 and Radil. From these results we conclude that Rap1 utilizes multiple pathways to control tightening of endothelial junctions, possibly through a multiprotein effector complex, in which AF6 functions to induce tension in circumferential actin cables.

Estimation of the Percentage of Newly Diagnosed HIV-Positive Persons Linked to HIV Medical Care in CDC-Funded HIV Testing Programs.

PubMed

Wang, Guoshen; Pan, Yi; Seth, Puja; Song, Ruiguang; Belcher, Lisa

2017-01-01

Missing data create challenges for determining progress made in linking HIV-positive persons to HIV medical care. Statistical methods are not used to address missing program data on linkage. In 2014, 61 health department jurisdictions were funded by Centers for Disease Control and Prevention (CDC) and submitted data on HIV testing, newly diagnosed HIV-positive persons, and linkage to HIV medical care. Missing or unusable data existed in our data set. A new approach using multiple imputation to address missing linkage data was proposed, and results were compared to the current approach that uses data with complete information. There were 12,472 newly diagnosed HIV-positive persons from CDC-funded HIV testing events in 2014. Using multiple imputation, 94.1% (95% confidence interval (CI): [93.7%, 94.6%]) of newly diagnosed persons were referred to HIV medical care, 88.6% (95% CI: [88.0%, 89.1%]) were linked to care within any time frame, and 83.6% (95% CI: [83.0%, 84.3%]) were linked to care within 90 days. Multiple imputation is recommended for addressing missing linkage data in future analyses when the missing percentage is high. The use of multiple imputation for missing values can result in a better understanding of how programs are performing on key HIV testing and HIV service delivery indicators.

[Presentation of the "CDC de Canarias" cohort: objectives, design and preliminary results].

PubMed

Cabrera de León, Antonio; Rodríguez Pérez, Ma del Cristo; Almeida González, Delia; Domínguez Coello, Santiago; Aguirre Jaime, Armando; Brito Díaz, Buenaventura; González Hernández, Ana; Pérez Méndez, Lina I

2008-01-01

The Canary Islands rank first in Spain with respect to the ischaemic heart disease and diabetes mortality rates. The Islands female population leads the country in deaths from breast cancer. The "CDC de Canarias" is a general population cohort study in order to analyse the prevalence and incidence of these diseases and the exposure to their risk factors (RF) in the adult population of the archipelago. Prospective study with a random sampling of the general population, in which 6,729 individuals participated between 2000 and 2005 (aged 18-75). Anthropometric measurements were taken, and blood was drawn for the storage of serum and genetic samples. The following information was gathered through a questionnaire: eating habits, physical activity, personal and family medical history, exposure to occupational or environmental risk factors, smoking, etc. The prevalence of obesity is close to 30%, without differences between sexes, however, more male subjects were overweight than women (45 vs. 33%; p <0.001) and also presented a greater prevalence of diabetes (12 vs. 10%; p =0.005), high blood pressure (43 vs. 33%; p <0.001), excessive intake of alcohol (13 vs. 2%; p <0.001) and lack of sun protection (46 vs. 18%; p <0.001). Exposure to low levels of HDL cholesterol is more frequent in women (37 vs. 30%; p <0.001) as is also the case with a sedentary life style (71 vs. 55%; p <0.001). The exposure to the risk factors studied, including poverty, is greater in advanced age groups, except for smoking (26%) which is greater in the younger subjects. The estimate of relative risks of exposure to cardiovascular and cancer risk factors is higher in low-income social classes. The current adult population of the Canaries presents a high prevalence of exposure to risk factors for cardiovascular disease, diabetes and cancer, among which overweight, obesity and lack of exercise stand out particularly.

Success factors in technology development

NASA Astrophysics Data System (ADS)

Preston, John T.

1995-01-01

Universities in the U.S. have a significant impact on business through the transfer of technology. This paper describes goals and philosophy of the Technology Licensing Office at the Massachusetts Institute of Technology. This paper also relates the critical factors for susscessful technology transfer, particularly relating to new business formation. These critical factors include the quality of the technology, the quality of the management, the quality of the investor, the passion for success, and the image of the company. Descriptions of three different levels of investment are also given and the most successful level of investment for starting a new company is reviewed. Licensing to large companies is also briefly reviewed, as this type of licensing requires some different strategies than that of licensing to start-up companies. High quality critical factors and intelligent investment create rewards for the parties and successful ventures.

47 CFR 13.7 - Classification of operator licenses and endorsements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... are twelve types of commercial radio operator licenses, certificates and permits (licenses). The... Radiotelephone Operator License (radiotelephone operator's general certificate). (6) Marine Radio Operator Permit (radiotelephone operator's restricted certificate). (7) Restricted Radiotelephone Operator Permit (radiotelephone...

47 CFR 13.7 - Classification of operator licenses and endorsements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... are twelve types of commercial radio operator licenses, certificates and permits (licenses). The... Radiotelephone Operator License (radiotelephone operator's general certificate). (6) Marine Radio Operator Permit (radiotelephone operator's restricted certificate). (7) Restricted Radiotelephone Operator Permit (radiotelephone...

Induction of a Mitosis Delay and Cell Lysis by High-Level Secretion of Mouse α-Amylase from Saccharomyces cerevisiae

PubMed Central

Wang, Bi-Dar; Kuo, Tsong-Teh

2001-01-01

Some foreign proteins are produced in yeast in a cell cycle-dependent manner, but the cause of the cell cycle dependency is unknown. In this study, we found that Saccharomyces cerevisiae cells secreting high levels of mouse α-amylase have elongated buds and are delayed in cell cycle completion in mitosis. The delayed cell mitosis suggests that critical events during exit from mitosis might be disturbed. We found that the activities of PP2A (protein phosphatase 2A) and MPF (maturation-promoting factor) were reduced in α-amylase-oversecreting cells and that these cells showed a reduced level of assembly checkpoint protein Cdc55, compared to the accumulation in wild-type cells. MPF inactivation is due to inhibitory phosphorylation on Cdc28, as a cdc28 mutant which lacks an inhibitory phosphorylation site on Cdc28 prevents MPF inactivation and prevents the defective bud morphology induced by overproduction of α-amylase. Our data also suggest that high levels of α-amylase may downregulate PPH22, leading to cell lysis. In conclusion, overproduction of heterologous α-amylase in S. cerevisiae results in a negative regulation of PP2A, which causes mitotic delay and leads to cell lysis. PMID:11472949

Regulation of Cell Cycle and Stress Responses to Hydrostatic Pressure in Fission Yeast

PubMed Central

George, Vinoj T.; Brooks, Gavin

2007-01-01

We have investigated the cellular responses to hydrostatic pressure by using the fission yeast Schizosaccharomyces pombe as a model system. Exposure to sublethal levels of hydrostatic pressure resulted in G2 cell cycle delay. This delay resulted from Cdc2 tyrosine-15 (Y-15) phosphorylation, and it was abrogated by simultaneous disruption of the Cdc2 kinase regulators Cdc25 and Wee1. However, cell cycle delay was independent of the DNA damage, cytokinesis, and cell size checkpoints, suggesting a novel mechanism of Cdc2-Y15 phosphorylation in response to hydrostatic pressure. Spc1/Sty1 mitogen-activated protein (MAP) kinase, a conserved member of the eukaryotic stress-activated p38, mitogen-activated protein (MAP) kinase family, was rapidly activated after pressure stress, and it was required for cell cycle recovery under these conditions, in part through promoting polo kinase (Plo1) phosphorylation on serine 402. Moreover, the Spc1 MAP kinase pathway played a key role in maintaining cell viability under hydrostatic pressure stress through the bZip transcription factor, Atf1. Further analysis revealed that prestressing cells with heat increased barotolerance, suggesting adaptational cross-talk between these stress responses. These findings provide new insight into eukaryotic homeostasis after exposure to pressure stress. PMID:17699598

Large Eddy Simulations of Colorless Distributed Combustion Systems

NASA Astrophysics Data System (ADS)

Abdulrahman, Husam F.; Jaberi, Farhad; Gupta, Ashwani

2014-11-01

Development of efficient and low-emission colorless distributed combustion (CDC) systems for gas turbine applications require careful examination of the role of various flow and combustion parameters. Numerical simulations of CDC in a laboratory-scale combustor have been conducted to carefully examine the effects of these parameters on the CDC. The computational model is based on a hybrid modeling approach combining large eddy simulation (LES) with the filtered mass density function (FMDF) equations, solved with high order numerical methods and complex chemical kinetics. The simulated combustor operates based on the principle of high temperature air combustion (HiTAC) and has shown to significantly reduce the NOx, and CO emissions while improving the reaction pattern factor and stability without using any flame stabilizer and with low pressure drop and noise. The focus of the current work is to investigate the mixing of air and hydrocarbon fuels and the non-premixed and premixed reactions within the combustor by the LES/FMDF with the reduced chemical kinetic mechanisms for the same flow conditions and configurations investigated experimentally. The main goal is to develop better CDC with higher mixing and efficiency, ultra-low emission levels and optimum residence time. The computational results establish the consistency and the reliability of LES/FMDF and its Lagrangian-Eulerian numerical methodology.

Improving the seismic torsional behavior of plan-asymmetric, single-storey, concrete moment resisting buildings with fluid viscous dampers

NASA Astrophysics Data System (ADS)

Rofooei, Fayaz Rahimzadeh; Mohammadzadeh, Sahar

2016-03-01

The optimal distribution of fluid viscous dampers (FVD) in controlling the seismic response of eccentric, single-storey, moment resisting concrete structures is investigated using the previously defined center of damping constant (CDC). For this purpose, a number of structural models with different one-way stiffness and strength eccentricities are considered. Extensive nonlinear time history analyses are carried out for various arrangements of FVDs. It is shown that the arrangement of FVDs for controlling the torsional behavior due to asymmetry in the concrete structures is very dependent on the intensity of the peak ground acceleration (PGA) and the extent of the structural stiffness and strength eccentricities. The results indicate that, in the linear range of structural behavior the stiffness eccentricity es which is the main parameter in determining the location of optimal CDC, is found to be less or smaller than the optimal damping constant eccentricity e*d, i.e., |e*d| > |es|. But, in the nonlinear range of structural behavior where the strength eccentricity er is the dominant factor in determining the location of optimal CDC, |e*d| > |er|. It is also concluded that for the majority of the plan-asymmetric, concrete structures considered in this study with er ≠ 0, the optimal CDC approaches the center of mass as er decreases.

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.

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

RIT1 controls actin dynamics via complex formation with RAC1/CDC42 and PAK1.

PubMed

Meyer Zum Büschenfelde, Uta; Brandenstein, Laura Isabel; von Elsner, Leonie; Flato, Kristina; Holling, Tess; Zenker, Martin; Rosenberger, Georg; Kutsche, Kerstin

2018-05-01

RIT1 belongs to the RAS family of small GTPases. Germline and somatic RIT1 mutations have been identified in Noonan syndrome (NS) and cancer, respectively. By using heterologous expression systems and purified recombinant proteins, we identified the p21-activated kinase 1 (PAK1) as novel direct effector of RIT1. We found RIT1 also to directly interact with the RHO GTPases CDC42 and RAC1, both of which are crucial regulators of actin dynamics upstream of PAK1. These interactions are independent of the guanine nucleotide bound to RIT1. Disease-causing RIT1 mutations enhance protein-protein interaction between RIT1 and PAK1, CDC42 or RAC1 and uncouple complex formation from serum and growth factors. We show that the RIT1-PAK1 complex regulates cytoskeletal rearrangements as expression of wild-type RIT1 and its mutant forms resulted in dissolution of stress fibers and reduction of mature paxillin-containing focal adhesions in COS7 cells. This effect was prevented by co-expression of RIT1 with dominant-negative CDC42 or RAC1 and kinase-dead PAK1. By using a transwell migration assay, we show that RIT1 wildtype and the disease-associated variants enhance cell motility. Our work demonstrates a new function for RIT1 in controlling actin dynamics via acting in a signaling module containing PAK1 and RAC1/CDC42, and highlights defects in cell adhesion and migration as possible disease mechanism underlying NS.

RIT1 controls actin dynamics via complex formation with RAC1/CDC42 and PAK1

PubMed Central

von Elsner, Leonie; Flato, Kristina; Holling, Tess; Zenker, Martin; Rosenberger, Georg

2018-01-01

RIT1 belongs to the RAS family of small GTPases. Germline and somatic RIT1 mutations have been identified in Noonan syndrome (NS) and cancer, respectively. By using heterologous expression systems and purified recombinant proteins, we identified the p21-activated kinase 1 (PAK1) as novel direct effector of RIT1. We found RIT1 also to directly interact with the RHO GTPases CDC42 and RAC1, both of which are crucial regulators of actin dynamics upstream of PAK1. These interactions are independent of the guanine nucleotide bound to RIT1. Disease-causing RIT1 mutations enhance protein-protein interaction between RIT1 and PAK1, CDC42 or RAC1 and uncouple complex formation from serum and growth factors. We show that the RIT1-PAK1 complex regulates cytoskeletal rearrangements as expression of wild-type RIT1 and its mutant forms resulted in dissolution of stress fibers and reduction of mature paxillin-containing focal adhesions in COS7 cells. This effect was prevented by co-expression of RIT1 with dominant-negative CDC42 or RAC1 and kinase-dead PAK1. By using a transwell migration assay, we show that RIT1 wildtype and the disease-associated variants enhance cell motility. Our work demonstrates a new function for RIT1 in controlling actin dynamics via acting in a signaling module containing PAK1 and RAC1/CDC42, and highlights defects in cell adhesion and migration as possible disease mechanism underlying NS. PMID:29734338

25 CFR 559.6 - Does a tribe need to notify the Chairman if a facility license is terminated or not renewed or if...

Code of Federal Regulations, 2010 CFR

2010-04-01

... license is terminated or not renewed or if a gaming place, facility, or location closes or reopens? 559.6 Section 559.6 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR GAMING LICENSES AND... terminated or not renewed or if a gaming place, facility, or location closes or reopens? A tribe must notify...

Individual and Contextual Factors for Bullying and Peer Victimization: Implications for Prevention

ERIC Educational Resources Information Center

Vivolo, Alana M.; Holt, Melissa K.; Massetti, Greta M.

2011-01-01

The Division of Violence Prevention (DVP) at the Centers for Disease Control and Prevention (CDC) is committed to preventing youth violence. For the past decade, DVP has supported research on risk and protective factors associated with youth interpersonal violence and the development and evaluation of prevention programs. This commentary addresses…

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.

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.

6 CFR 37.15 - Physical security features for the driver's license or identification card.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 6 Domestic Security 1 2010-01-01 2010-01-01 false Physical security features for the driver's license or identification card. 37.15 Section 37.15 Domestic Security DEPARTMENT OF HOMELAND SECURITY..., Verification, and Card Issuance Requirements § 37.15 Physical security features for the driver's license or...

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...

Achieving recognition that mental health is part of the mission of CDC.

PubMed

Safran, Marc A

2009-11-01

For much of its history the U.S. Centers for Disease Control and Prevention (CDC) considered mental health to be outside of its mission. That assumption persisted even after CDC became a leading public health agency and began to face important mental health issues. This narrative describes how the organizational paradigm indicating that mental health was not mission related was challenged and superseded by a new paradigm recognizing mental health as part of CDC's public health mission. Even after the CDC Mental Health Work Group's establishment in 2000, CDC took eight more years to overcome powerful remnants of the old paradigm that had for so long excluded, minimized, or discouraged attention to mental health. The CDC Mental Health Work Group led the agency's mental health efforts without funding or dedicated staffing but with more than 100 CDC professionals from multiple disciplines and centers serving as voluntary members, in addition to their other CDC responsibilities.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-02

... announced below concerns Green Housing Study: Follow-up Measurements of Housing Factors and Respiratory... Respiratory Health of Children Located in Cincinnati and Boston (U01), FOA EH12-001.'' Contact Person for More...

21 CFR 515.21 - Refusal to approve a medicated feed mill license application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Refusal to approve a medicated feed mill license... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS MEDICATED FEED MILL LICENSE Administrative Actions on Licenses § 515.21 Refusal to approve a medicated feed mill license application. (a) The...

21 CFR 515.20 - Approval of medicated feed mill license applications.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Approval of medicated feed mill license... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS MEDICATED FEED MILL LICENSE Administrative Actions on Licenses § 515.20 Approval of medicated feed mill license applications. Within 90 days after an...

Role of phospholipase Cgamma1 in cell spreading requires association with a beta-Pix/GIT1-containing complex, leading to activation of Cdc42 and Rac1.

PubMed

Jones, Neil P; Katan, Matilda

2007-08-01

The significance of multiprotein signaling complexes in cell motility is becoming increasingly important. We have previously shown that phospholipase Cgamma1 (PLCgamma1) is critical for integrin-mediated cell spreading and motility (N. Jones et al., J. Cell Sci. 118:2695-2706, 2005). In the current study we show that, on a basement membrane-type matrix, PLCgamma1 associates with the adaptor protein GIT1 and the Rac1/Cdc42 guanine exchange factor beta-Pix; GIT1 and beta-Pix form tight complexes independently of PLCgamma1. The association of PLCgamma1 with the complex requires both GIT1 and beta-Pix and the specific array region (gammaSA) of PLCgamma1. Mutations of PLCgamma1 within the gammaSA region reveal that association with this complex is essential for the phosphorylation of PLCgamma1 and the progression to an elongated morphology after integrin engagement. Short interfering RNA (siRNA) depletion of either beta-Pix or GIT1 inhibited cell spreading in a fashion similar to that seen with siRNA against PLCgamma1. Furthermore, siRNA depletion of PLCgamma1, beta-Pix, or GIT1 inhibited Cdc42 and Rac1 activation, while constitutively active forms of Cdc42 or Rac1, but not RhoA, were able to rescue the elongation of these cells. Signaling of the PLCgamma1/GIT1/beta-Pix complex to Cdc42/Rac1 was found to involve the activation of calpains, calcium-dependent proteases. Therefore, we propose that the association of PLCgamma1 with complexes containing GIT1 and beta-Pix is essential for its role in integrin-mediated cell spreading and motility. As a component of this complex, PLCgamma1 is also involved in the activation of Cdc42 and Rac1.

Part II: managing perioperative hyperglycemia in total hip and knee replacement surgeries.

PubMed

Agos, Florence; Shoda, Casey; Bransford, Deborah

2014-09-01

Perioperative hyperglycemia management is an important factor in reducing the risk of surgical site infections (SSIs) in all patients regardless of existing history of diabetes. Reduction of SSIs is one of the quality indicators reported by the National Healthcare Safety Networks of the Centers for Disease Control and Prevention (CDC). In 2009 and 2010, the orthopedic surgical unit had an increased number of SSIs above the CDC benchmark. This article describes the impact of an evidence-based practice standard for perioperative hyperglycemia management in the reduction of SSIs in patients having total hip and knee replacement surgery. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

The association of periodontal disease with kidney function decline: a longitudinal retrospective analysis of the MrOS dental study.

PubMed

Grubbs, Vanessa; Vittinghoff, Eric; Taylor, George; Kritz-Silverstein, Donna; Powe, Neil; Bibbins-Domingo, Kirsten; Ishani, Areef; Cummings, Steven R

2016-03-01

Identifying modifiable risk factors for chronic kidney disease (CKD) is essential for reducing its burden. Periodontal disease is common, modifiable and has been implicated as a novel potential CKD risk factor, but evidence of its association with kidney function decline over time is limited. In a longitudinal retrospective cohort of 761 elderly men with preserved kidney function [estimated glomerular filtration rate > 60 mL/min/1.73 m(2) using a calibrated creatinine and cystatin C (eGFRcr-cys) equation] at baseline, we performed multivariable Poisson's regression to examine the association of severe periodontal disease with incident CKD, defined as incident eGFRcr-cys <60 mL/min/1.73 m(2) and rapid (>5% annualized) eGFRcr-cys decline. Severe periodontal disease was defined in two ways: (i) ≥5 mm proximal attachment loss in 30% of teeth examined (European Workshop in Periodontology Group C, European Workshop); and (ii) 2+ interproximal sites with attachment loss ≥6 mm and 1+ interproximal sites with probing depth ≥5 mm (Centers for Disease Control/American Academy of Periodontology, CDC/AAP). At baseline, the mean age was 73.4 (SD 4.8) years, the median eGFRcr-cys was 82.4 mL/min/1.73 m(2), and 35.5 and 25.4% of participants had severe periodontal disease by European Workshop and CDC/AAP criteria, respectively. After a mean follow-up of 4.9 years (SD 0.3), 56 (7.4%) participants had incident CKD. Severe periodontal disease was associated with a 2-fold greater rate of incident CKD [incidence rate ratio (IRR) 2.01 (1.21-3.44), P = 0.007] after adjusting for confounders compared with not severe periodontal disease by European Workshop criteria but did not reach statistical significance by CDC/AAP criteria [IRR 1.10 (0.63-1.91), P = 0.9]. Severe periodontal disease may be associated with incident clinically significant kidney function decline among a cohort of elderly men. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Creep relaxation of fuel pin bending and ovalling stresses. [BEND code, OVAL code, MARC-CDC code

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

Chan, D.P.; Jackson, R.J.

1981-10-01

Analytical methods for calculating fuel pin cladding bending and ovalling stresses due to pin bundle-duct mechanical interaction taking into account nonlinear creep are presented. Calculated results are in agreement with finite element results by MARC-CDC program. The methods are used to investigate the effect of creep on the FTR fuel cladding bending and ovalling stresses. It is concluded that the cladding of 316 SS 20 percent CW and reference design has high creep rates in the FTR core region to keep the bending and ovalling stresses to acceptable levels. 6 refs.

Study of the Regulation of Telomere Replication by Characterizing the Cdc-13p Pathway in Yeast

DTIC Science & Technology

2002-01-01

cdcl3A strains carrying a centromere plasmid with mutant cdc13 1.6 - alleles (cdcl3-50 and cdcl3-523) that disrupted in- teraction of Cdcl3Np with...Estlp was expressed from 5). HA-Cdcl3-lp (Fig. 7, lane 2) and HA-Cdcl3-2p (Fig. 7, the centromere plasmid pKT/EST1 (Mitchell et al. 1993) lane 3) also...mediated telomere lengthening. For the plants the need for Estlp in telomere maintenance POLl mutations, this TLCl-dependent length increase (Evans and

MXLKID: a maximum likelihood parameter identifier. [In LRLTRAN for CDC 7600

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

Gavel, D.T.

MXLKID (MaXimum LiKelihood IDentifier) is a computer program designed to identify unknown parameters in a nonlinear dynamic system. Using noisy measurement data from the system, the maximum likelihood identifier computes a likelihood function (LF). Identification of system parameters is accomplished by maximizing the LF with respect to the parameters. The main body of this report briefly summarizes the maximum likelihood technique and gives instructions and examples for running the MXLKID program. MXLKID is implemented LRLTRAN on the CDC7600 computer at LLNL. A detailed mathematical description of the algorithm is given in the appendices. 24 figures, 6 tables.

Structure-Activity Relationship Studies on the Mosquito Toxicity and Biting Deterrency of Callicarpenal Derivatives

DTIC Science & Technology

2009-01-01

peer-reviewed, scientific literature [1]. Also recognized by the CDC as effective insect repellents are those containing oil of lemon eucalyptus ...The United States Centers for Disease Control and Prevention (CDC) recommend the use of products containing active ingredients which have been...95% C.I.)a) Slope (SE) c2 1 5.13 (1.83–7.26) 23.91 (15.98–87.90) 2.46 (0.73) 0.32 2 5.87 (4.98–6.88) 12.49 (9.98–18.59) 5.01 (0.83) 0.56 3 19.62

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

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

Yi, Xiu-Chun; Xi, Fu-Gui; Wang, Kun

From a new dicarboxylate ligand, 9H-carbazole-2,7-dicarboxylic acid (2,7-H{sub 2}CDC), three Zn(II) metal-organic frameworks were synthesized in the absence or presence of ditopic N-donor ligands. They are formulated as [Zn{sub 5}(μ{sub 3}-OH){sub 2}(2,7-CDC){sub 4}(DEF){sub 2}] (1) (DEF=N,N-diethylformamide), [Zn{sub 2}(2,7-CDC){sub 2}(DABCO)(H{sub 2}O)]·5DMF·H{sub 2}O (2) (DABCO=1-diaza-bicyclo[2.2.2]octane, DMF=N,N-dimethylformamide), and [Zn{sub 2}(2,7-CDC){sub 2}(bpea)]·3DMA·2 H{sub 2}O (3) (bpea=1,2-bis(4-pyridyl)ethylane, DMA=N,N-dimethylacetamide). Compounds 1 and 3 display the 3D pcu frameworks. In 1 the unusual pentanuclear [Zn{sub 5}(μ{sub 3}-OH){sub 2}(COO){sub 8}] secondary building units (SBUs) are linked by dicarboxylate ligands. Differently, in 3 the well-known paddle–wheel [Zn{sub 2}(COO){sub 4}] SBUs are linked by dicarboxylate and dipyridyl ligands. Compound 2more » shows the rare self-catenated 3D alb-3,6-C2/c net topology based on the dinuclear paddle–wheel SBU and a mononuclear unit. The stability and fluorescent properties of the compounds have been studied. - Graphical abstract: A new dicarboxylate ligand, 9H-carbazole-2,7-dicarboxylic acid, was used to construct Zn(II) metal-organic frameworks, including a novel self-catenated network with the rare 3D alb-3,6-C2/c net and two pcu-type networks based on an unprecedented pentanuclear clusters and the common paddle–wheel units. The compounds show blue fluorescent properties. Display Omitted - Highlights: • MOFs with a new carbazole-based dicarboxylate ligand. • New pentanuclear [Zn{sub 5}(μ{sub 3}-OH){sub 2}(COO){sub 8}] secondary building unit. • The rare self-catenated 3D alb-3,6-C2/c net.« 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/ ...

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.

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.

Interfaces in Composites. Volume 170. Materials Research Society Symposium Proceedings Held in Boston, Massachusetts on 27-29 November 1989

DTIC Science & Technology

1990-11-21

buckled coatings is obtained: G - H(ao-6 c )(do 0/dc-do c/dc)%-( o -0C) 2 (dz/dc)](l-a)h/2c (4) where % is c 2b 2(l+v)+c4 (-v)]/ E (c 2-b 2). To determine...pressure on the fiber, o , that results from a cooling differential of AT Is (9): I 20 q. = [ E 2 .(% - a5 ,) + Er(a - atr)]*AT (9) where a% is the...calculated by rule-of-mixtures, these fracture energies can be expressed in terms of critical stress intensity factors: Go + AGb ( o +AKb) 2 / E (3

21 CFR 515.24 - Notice of revocation of a medicated feed mill license.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Notice of revocation of a medicated feed mill... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS MEDICATED FEED MILL LICENSE Administrative Actions on Licenses § 515.24 Notice of revocation of a medicated feed mill license. When a license...

47 CFR 25.143 - Licensing provisions for the 1.6/2.4 GHz Mobile-Satellite Service and 2 GHz Mobile-Satellite...

Code of Federal Regulations, 2013 CFR

2013-10-01

... authorization with no further action required on the Commission's part. (f) Safety and distress communications... 47 Telecommunication 2 2013-10-01 2013-10-01 false Licensing provisions for the 1.6/2.4 GHz Mobile... COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES SATELLITE COMMUNICATIONS Applications and Licenses...

47 CFR 25.143 - Licensing provisions for the 1.6/2.4 GHz Mobile-Satellite Service and 2 GHz Mobile-Satellite...

Code of Federal Regulations, 2014 CFR

2014-10-01

... space stations authorized by the Commission. (d)-(e) [Reserved] (f) Safety and distress communications... 47 Telecommunication 2 2014-10-01 2014-10-01 false Licensing provisions for the 1.6/2.4 GHz Mobile... COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES SATELLITE COMMUNICATIONS Applications and Licenses...

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...

77 FR 65720 - Biweekly Notice; Applications and Amendments to Facility Operating Licenses and Combined Licenses...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-30

... transmission, the E-Filing system time-stamps the document and sends the submitter an email notice confirming... hot channel factor, nuclear enthalpy rise hot channel factor, loss of coolant accident peak cladding...

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

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

PubMed Central

Gómez-Campos, Rossana; Lee Andruske, Cinthya; Hespanhol, Jefferson; Sulla Torres, Jose; Arruda, Miguel; Luarte-Rocha, Cristian; Cossio-Bolaños, Marco Antonio

2015-01-01

The measurement of waist circumference (WC) is considered to be an important means to control overweight and obesity in children and adolescents. The objectives of the study were to (a) compare the WC measurements of Chilean students with the international CDC-2012 standard and other international standards, and (b) propose a specific measurement value for the WC of Chilean students based on age and sex. A total of 3892 students (6 to 18 years old) were assessed. Weight, height, body mass index (BMI), and WC were measured. WC was compared with the CDC-2012 international standard. Percentiles were constructed based on the LMS method. Chilean males had a greater WC during infancy. Subsequently, in late adolescence, males showed values lower than those of the international standards. Chilean females demonstrated values similar to the standards until the age of 12. Subsequently, females showed lower values. The 85th and 95th percentiles were adopted as cutoff points for evaluating overweight and obesity based on age and sex. The WC of Chilean students differs from the CDC-2012 curves. The regional norms proposed are a means to identify children and adolescents with a high risk of suffering from overweight and obesity disorders. PMID:26184250

Synthesis, structure and properties of zinc(II) coordination polymers with 9H-carbazole-2,7-dicarboxylic acid

NASA Astrophysics Data System (ADS)

Yi, Xiu-Chun; Xi, Fu-Gui; Wang, Kun; Su, Zhao; Gao, En-Qing

2013-10-01

From a new dicarboxylate ligand, 9H-carbazole-2,7-dicarboxylic acid (2,7-H2CDC), three Zn(II) metal-organic frameworks were synthesized in the absence or presence of ditopic N-donor ligands. They are formulated as [Zn5(μ3-OH)2(2,7-CDC)4(DEF)2] (1) (DEF=N,N-diethylformamide), [Zn2(2,7-CDC)2(DABCO)(H2O)]·5DMF·H2O (2) (DABCO=1-diaza-bicyclo[2.2.2]octane, DMF=N,N-dimethylformamide), and [Zn2(2,7-CDC)2(bpea)]·3DMA·2 H2O (3) (bpea=1,2-bis(4-pyridyl)ethylane, DMA=N,N-dimethylacetamide). Compounds 1 and 3 display the 3D pcu frameworks. In 1 the unusual pentanuclear [Zn5(μ3-OH)2(COO)8] secondary building units (SBUs) are linked by dicarboxylate ligands. Differently, in 3 the well-known paddle-wheel [Zn2(COO)4] SBUs are linked by dicarboxylate and dipyridyl ligands. Compound 2 shows the rare self-catenated 3D alb-3,6-C2/c net topology based on the dinuclear paddle-wheel SBU and a mononuclear unit. The stability and fluorescent properties of the compounds have been studied.

Synergistic Blockade of Mitotic Exit by Two Chemical Inhibitors of the APC/C

PubMed Central

Sackton, Katharine L.; Dimova, Nevena; Zeng, Xing; Tian, Wei; Zhang, Mengmeng; Sackton, Timothy B.; Meaders, Johnathan; Pfaff, Kathleen L.; Sigoillot, Frederic; Yu, Hongtao; Luo, Xuelian; King, Randall W.

2014-01-01

Summary Protein machines are multi-subunit protein complexes that orchestrate highly regulated biochemical tasks. An example is the Anaphase-Promoting Complex/Cyclosome (APC/C), a thirteen-subunit ubiquitin ligase that initiates the metaphase-anaphase transition and mitotic exit by targeting proteins such as securin and cyclin B1 for ubiquitin-dependent destruction by the proteasome1,2. Because blocking mitotic exit is an effective approach for inducing tumor cell death3,4, the APC/C represents a potential novel target for cancer therapy. APC/C activation in mitosis requires binding of Cdc205, which forms a co-receptor with the APC/C to recognize substrates containing a Destruction box (D-box)6-14. Here we demonstrate that we can synergistically inhibit APC/C-dependent proteolysis and mitotic exit by simultaneously disrupting two protein-protein interactions within the APC/C-Cdc20-substrate ternary complex. We identified a small molecule, called apcin (APC inhibitor), which binds to Cdc20 and competitively inhibits the ubiquitylation of D-box-containing substrates. Analysis of the crystal structure of the apcin-Cdc20 complex suggests that apcin occupies the D-box-binding pocket on the side face of the WD40-domain. The ability of apcin to block mitotic exit is synergistically amplified by co-addition of tosyl-L-arginine methyl ester (TAME), a small molecule that blocks the APC/C-Cdc20 interaction15,16. This work suggests that simultaneous disruption of multiple, weak protein-protein interactions is an effective approach for inactivating a protein machine. PMID:25156254

Classification of infections in intensive care units: a comparison of current definition of hospital-acquired infections and carrier state criterion.

PubMed

Zurek, Jiří; Fedora, Michal

2012-06-01

The rate of nosocomial infection appears to depend on whether it is calculated using the Center for Disease Control (CDC) or carrier state criteria. The objective of this study was to differentiate between primary endogenous (PE), secondary endogenous (SE) and exogenous (EX) infections, and to compare this classification with CDC criteria for nosocomial infections. Children hospitalized for more than 72 h at pediatric intensive care unit during 2004-2005 were enrolled. Children, who had the infection before the admission, and or did not develop an infection within the hospitalization were excluded. Surveillance samples were sampled on admission, and then twice a week. Diagnostic samples were obtained when infection was suspected based on the clinical condition and laboratory findings. Infections were evaluated as PE, SE and EX, and their incidences were compared with CDC criteria for nosocomial infections. One hundred seventy eight patients were enrolled in the study. Forty-four patients (24.7%) develop infection. Twenty-seven patients (61.3%) had PE, 10 patients (22.7%) had SE, and 7 patients (15.9%) had EX infection. Secondary endogenous and EX infections are considered as nosocomial, thus 17 patients (38.6%) had a nosocomial infection. Thirty-one patients (70.5%) met CDC criteria for nosocomial infections. Seventeen patients (55%) were classified as PE, and 14 patients (45%) as SE or EX infections. Seventy percent of infections (31 out of 44 patients) met the CDC criteria for nosocomial infections, but only 39% of infections (17 out of 44 patients) were classified as nosocomial based on carrier state classification.

Sexual Violence

MedlinePlus

... References 1. Black MC, Basile KC, Breiding MJ, Smith SG, Walters ML, Merrick MT, Chen J, Stevens ... cdc.gov/mmwr/preview/mmwrhtml/ss5806a1.htm 6. Smith SG. Breiding MJ. Chronic disease and health behaviours ...

Spatial control of translation repression and polarized growth by conserved NDR kinase Orb6 and RNA-binding protein Sts5.

PubMed

Nuñez, Illyce; Rodriguez Pino, Marbelys; Wiley, David J; Das, Maitreyi E; Chen, Chuan; Goshima, Tetsuya; Kume, Kazunori; Hirata, Dai; Toda, Takashi; Verde, Fulvia

2016-07-30

RNA-binding proteins contribute to the formation of ribonucleoprotein (RNP) granules by phase transition, but regulatory mechanisms are not fully understood. Conserved fission yeast NDR (Nuclear Dbf2-Related) kinase Orb6 governs cell morphogenesis in part by spatially controlling Cdc42 GTPase. Here we describe a novel, independent function for Orb6 kinase in negatively regulating the recruitment of RNA-binding protein Sts5 into RNPs to promote polarized cell growth. We find that Orb6 kinase inhibits Sts5 recruitment into granules, its association with processing (P) bodies, and degradation of Sts5-bound mRNAs by promoting Sts5 interaction with 14-3-3 protein Rad24. Many Sts5-bound mRNAs encode essential factors for polarized cell growth, and Orb6 kinase spatially and temporally controls the extent of Sts5 granule formation. Disruption of this control system affects cell morphology and alters the pattern of polarized cell growth, revealing a role for Orb6 kinase in the spatial control of translational repression that enables normal cell morphogenesis.

Overweight and Obesity Prevalence Among School-Aged Nunavik Inuit Children According to Three Body Mass Index Classification Systems.

PubMed

Medehouenou, Thierry Comlan Marc; Ayotte, Pierre; St-Jean, Audray; Meziou, Salma; Roy, Cynthia; Muckle, Gina; Lucas, Michel

2015-07-01

Little is known about the suitability of three commonly used body mass index (BMI) classification system for Indigenous children. This study aims to estimate overweight and obesity prevalence among school-aged Nunavik Inuit children according to International Obesity Task Force (IOTF), Centers for Disease Control and Prevention (CDC), and World Health Organization (WHO) BMI classification systems, to measure agreement between those classification systems, and to investigate whether BMI status as defined by these classification systems is associated with levels of metabolic and inflammatory biomarkers. Data were collected on 290 school-aged children (aged 8-14 years; 50.7% girls) from the Nunavik Child Development Study with data collected in 2005-2010. Anthropometric parameters were measured and blood sampled. Participants were classified as normal weight, overweight, and obese according to BMI classification systems. Weighted kappa (κw) statistics assessed agreement between different BMI classification systems, and multivariate analysis of variance ascertained their relationship with metabolic and inflammatory biomarkers. The combined prevalence rate of overweight/obesity was 26.9% (with 6.6% obesity) with IOTF, 24.1% (11.0%) with CDC, and 40.4% (12.8%) with WHO classification systems. Agreement was the highest between IOTF and CDC (κw = .87) classifications, and substantial for IOTF and WHO (κw = .69) and for CDC and WHO (κw = .73). Insulin and high-sensitivity C-reactive protein plasma levels were significantly higher from normal weight to obesity, regardless of classification system. Among obese subjects, higher insulin level was observed with IOTF. Compared with other systems, IOTF classification appears to be more specific to identify overweight and obesity in Inuit children. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Interactions between Eu{sup 3+} ions in inorganic-organic hybrid materials

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

Pelle, Fabienne, E-mail: fabienne-pelle@chimie-paristech.f; Aschehoug, Patrick; Surble, Suzy

2010-04-15

The optical properties of two-dimensional lanthanide dicarboxylates EuBDC or Eu{sub 2}(H{sub 2}O){sub 2}(O{sub 2}C-C{sub 6}H{sub 4}-CO{sub 2}){sub 3} and EuCDC (denoted also MIL94) or Eu{sub 2}(H{sub 2}O){sub 4}(O{sub 2}C-C{sub 6}H{sub 10}-CO{sub 2}){sub 3}.2H{sub 2}O are reported. The structures are built up from dimers of corner-sharing polyhedra and 1,3-benzenedicarboxylate (BDC) for EuBDC and from dimers of edge-sharing polyhedra and 1,3-benzenedicarboxylate (CDC) for EuCDC. The high Eu{sup 3+} concentration and the weak luminescence quenching allow the study of Eu{sup 3+} interactions. Anti-Stokes spectra from {sup 5}D{sub 1} are observed with excitation in {sup 5}D{sub 0}. These results are very unusual for Eu{supmore » 3+} ions and reflect strong interactions between ions within a dimer. Excitation spectrum of the Eu{sup 3+} luminescence strongly differs in both compounds in the UV range. In case of EuBDC, an efficient sensitization of the luminescence due to the ligand is observed between 250 and 350 nm while only 4f-4f transitions are recorded on the Eu{sup 3+} excitation spectrum in EuCDC. The efficiency of the sensitization of the rare earth by the host is discussed by taking into account the geometrical arrangement and the electronic delocalization of the ligands. - Graphical abstract: Excitation spectra monitoring the {sup 5}D{sub 0}->{sup 7}F{sub 2} transition with a dimer structure.« less

Defining overweight and obesity among Greek children living in Thessaloniki: International versus local reference standards

PubMed Central

Christoforidis, A; Dimitriadou, M; Papadopolou, E; Stilpnopoulou, D; Katzos, G; Athanassiou-Metaxa, M

2011-01-01

Background: 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. Methods: 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: 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. Conclusions: 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. PMID:22110296

Visual impairment and road traffic accidents among drivers in Jimma Town, Southwest Ethiopia.

PubMed

Biza, Mohamed; Mossie, Andualem; Woldemichael, Kifle; Gelaw, Yeshigeta

2013-04-01

Vision play a vital role in driving where good and efficient visual functioning of the driver is essential. Any significant loss of visual function will diminish a driver's ability to operate a motor vehicle safely and will thus contribute to road traffic injury. However, there is little evidence indicating that defects of vision alone cause road traffic accidents. To determine the impact of visual impairment and other factors on road traffic accident among vehicle drivers. A cross-sectional descriptive study was conducted on 249 sampled drivers in Southwest Ethiopia. A pretested interviewer led questionnaire was used for interview and vision tests were done using Snellen's acuity chart and Ishihara pseudo-isochromatic plates. Statistical analyses were performed using SPSS version 16.0. The mean age of drivers was 33.6 years (SD +/- 10.3). The relative frequency of self reported road traffic accident was 15.3%. The prevalence of uncorrected binocular visual impairment was 1.6% and there was a significant association between visual impairment and road traffic accident (P < 0.05). Uncorrected refractive error was seen in 7.6% and 8.8% of drivers in the right and left eyes respectively, and 3.2% of them had vision less than what is required to obtain driving license (visual acuity of 6/12). None of the drivers with refractive errors were wearing appropriate corrections. Color vision impairment was seen in 1.6% of the drivers. A significant proportion (9.6%) of the drivers did not have eye exam for their driving license. Uncorrected binocular visual impairment was strongly associated with road traffic accident. There is need for consistent inspection and screening, strict rules and regulations of licensing and health education for drivers to minimize road traffic accident.

Using Repellent Products to Protect against Mosquito-Borne Illnesses

MedlinePlus

... Illnesses More Information CDC-Avoid Mosquito Bites CDC-Dengue CDC-Zika Virus CDC-Mosquito bite prevention for ... how to protect against the mosquitoes that transmit dengue, Zika, and other viral diseases ( Aedes albopictus and ...

CDC Health Disparities and Inequalities Report--U.S. 2013

MedlinePlus

... Health Literacy Health Equity CDC Health Disparities & Inequalities Report (CHDIR) Recommend on Facebook Tweet Share Compartir On ... More Information CDC Releases Second Health Disparities & Inequalities Report - United States, 2013 CDC and its partners work ...

Forkhead Box M1 Is Regulated by Heat Shock Factor 1 and Promotes Glioma Cells Survival under Heat Shock Stress*

PubMed Central

Dai, Bingbing; Gong, Aihua; Jing, Zhitao; Aldape, Kenneth D.; Kang, Shin-Hyuk; Sawaya, Raymond; Huang, Suyun

2013-01-01

The forkhead box M1 (FoxM1) is a key transcription factor regulating multiple aspects of cell biology. Prior studies have shown that FoxM1 is overexpressed in a variety of human tumors, including brain tumor, and plays a critical role in cancer development and progression. In this study we found that FoxM1 was up-regulated by heat shock factor 1 (HSF1) under heat shock stress condition in multiple cell lines. Knockdown of HSF1 with HSF1 siRNA or inhibition of HSF1 with a HSF1 inhibitor abrogated heat shock-induced expression of FoxM1. Genetic deletion of HSF1 in mouse embryo fibroblast cells also abolished heat shock stress-induced FoxM1 expression. Moreover, we showed that HSF1 directly bound to FoxM1 promoter and increased FoxM1 promoter activity. Furthermore, we demonstrated that FoxM1 was required for the G2-M phase progression through regulating Cdc2, Cdc20, and Cdc25B under a mild heat shock stress but enhanced cell survival under lethal heat shock stress condition. Finally, in human glioblastoma specimens, FoxM1 overexpression correlated with elevated HSF1 expression. Our results indicate that FoxM1 is regulated by HSF1 and is critical for HSF1-mediated heat shock response. We demonstrated a novel mechanism of stress resistance controlled by HSF1 and a new HSF-FoxM1 connection that mediates cellular thermotolerance. PMID:23192351

Caregiver perceptions of child nutritional status in Magallanes, Chile

PubMed Central

Heitzinger, Kristen; Vélez, Juan Carlos; Parra, Sonia G.; Barbosa, Clarita; Fitzpatrick, Annette L.

2012-01-01

Background We aimed to identify risk factors for childhood overweight and obesity and the accuracy of caregivers’ perceptions of their child’s nutritional status in the Magallanes region, Patagonia, Chile. Methods Heights and weights of children attending day care centers and elementary schools were collected and caregivers completed questionnaires regarding their child’s health and behavior. The child’s nutritional status was diagnosed using the 2006 WHO Child Growth Standards (for children under age 6) and the CDC 2000 Growth Charts (for children age 6 and older). Logistic regression was used to evaluate factors related to childhood overweight/obesity and weight underestimation by caregivers of overweight or obese children. Results Of the 795 children included in the study, 247 (31.1%) were overweight and 223 (28.1%) were obese. Risk factors for overweight/obesity included younger age and being perceived to eat more than normal by the caregiver. Caregivers were less likely to underestimate their child’s weight if the child was older or if the caregiver believed the child ate more than a normal amount. Conclusions There is a high prevalence of overweight and obesity among children in Magallanes and the majority of caregivers underestimate the extent of the problem in their children. PMID:24548582

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

Rsr1 Focuses Cdc42 Activity at Hyphal Tips and Promotes Maintenance of Hyphal Development in Candida albicans

PubMed Central

Pulver, Rebecca; Heisel, Timothy; Gonia, Sara; Robins, Robert; Norton, Jennifer; Haynes, Paula

2013-01-01

The extremely elongated morphology of fungal hyphae is dependent on the cell's ability to assemble and maintain polarized growth machinery over multiple cell cycles. The different morphologies of the fungus Candida albicans make it an excellent model organism in which to study the spatiotemporal requirements for constitutive polarized growth and the generation of different cell shapes. In C. albicans, deletion of the landmark protein Rsr1 causes defects in morphogenesis that are not predicted from study of the orthologous protein in the related yeast Saccharomyces cerevisiae, thus suggesting that Rsr1 has expanded functions during polarized growth in C. albicans. Here, we show that Rsr1 activity localizes to hyphal tips by the differential localization of the Rsr1 GTPase-activating protein (GAP), Bud2, and guanine nucleotide exchange factor (GEF), Bud5. In addition, we find that Rsr1 is needed to maintain the focused localization of hyphal polarity structures and proteins, including Bem1, a marker of the active GTP-bound form of the Rho GTPase, Cdc42. Further, our results indicate that tip-localized Cdc42 clusters are associated with the cell's ability to express a hyphal transcriptional program and that the ability to generate a focused Cdc42 cluster in early hyphae (germ tubes) is needed to maintain hyphal morphogenesis over time. We propose that in C. albicans, Rsr1 “fine-tunes” the distribution of Cdc42 activity and that self-organizing (Rsr1-independent) mechanisms of polarized growth are not sufficient to generate narrow cell shapes or to provide feedback to the transcriptional program during hyphal morphogenesis. PMID:23223038

Cardiovascular, diabetes, and cancer strips: evidences, mechanisms, and classifications

PubMed Central

Wu, Qing-Hua; Hu, Da-Yi

2014-01-01

Objectives To report and name firstly that there are cardiovascular disease (CVD), diabetes mellitus (DM) and cancers (CDC) strips; and disclose their mechanisms, classifications, and clinical significances. Study design Narrative and systematic review study and interpretive analysis. Methods Data sources and study selection: to collect and present related evidences on CDC strips from evidence-based, open-access, both Chinese- and English-language literatures in recent 10 years on clinical trials from PubMed according to keywords “CVD, DM and cancers” as well as authors’ extensive clinical experience with the treatment of more than fifty thousands of patients with CVD, diabetes and cancers over the past decades, and analyze their related mechanisms and categories which based on authors’ previous works. Data extraction: data were mainly extracted from 48 articles which are listed in the reference section of this review. Qualitative, quantitative and mixed data were included, narratively and systematically reviewed. Results With several conceptual and technical breakthrough, authors present related evidences on CDC strips, these are, CVD and DM, DM and cancers, cancers and CVD linked, respectively; And “Bad SEED” +/– “bad soil” theory or doctrine may explain this phenomenon due to “internal environmental injure, abnormal or unbalance” in human body resulting from the role of risk factors (RFs) related multi-pathways and multi-targets, which including organ & tissue (e.g., vascular-specific), cell and gene-based mechanisms. Their classifications include main strips/type B, and Branches/type A as showed by tables and figures in this article. Conclusions There are CDC strips and related mechanisms and classifications. CDC strips may help us to understand, prevent, and control related common non-communicable diseases (NCDs) as well as these high risk strips. PMID:25276377

Assembly interdependence among the S. cerevisiae bud neck ring proteins Elm1p, Hsl1p and Cdc12p.

PubMed

Thomas, Courtney L; Blacketer, Melissa J; Edgington, Nicholas P; Myers, Alan M

2003-07-15

In Saccharomyces cerevisiae, a complex comprising more than 20 different polypeptides assembles in a ring at the neck between the mother cell and the bud. This complex functions to coordinate cell morphology with cell division. Relatively little is known about this control system, including the physical relationships between the components of the neck ring. This study addressed the assembly interactions of three components of the ring, specifically the protein kinases Elm1p and Hsl1p and the septin Cdc12p. Specific amino acid substitutions in each of these three proteins were identified that either cause or suppress a characteristic phenotype of abnormally elongated cells and delay in the G(2)-M transition. Each protein was fused to green fluorescent protein, and its ability to localize at the neck was monitored in vivo in cells of various genotypes. Localization of Hsl1p to the neck requires Elm1p function. Elm1p localized normally in the absence of Hsl1p, although a specific point mutation in Hsl1p clearly affected Elm1p localization. The cdc12-122 mutation prevented assembly of Elm1p or Hsl1p into the neck ring. Normal assembly of Cdc12p at the neck was dependent upon Elm1p and also, to a smaller extent, on Hsl1p. Ectopic localization of Cdc12p at the bud tip was observed frequently in elm1 mutants and also, to a lesser extent, in hsl1 mutants. Thus, Elm1p is a key factor in the assembly and/or maintenance of Hsl1p, as well as at least one septin, into the bud neck ring. Copyright 2003 John Wiley & Sons, Ltd.

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

Spontaneous and electric field-controlled front-rear polarization of human keratinocytes.

PubMed

Saltukoglu, Deniz; Grünewald, Julian; Strohmeyer, Nico; Bensch, Robert; Ulbrich, Maximilian H; Ronneberger, Olaf; Simons, Matias

2015-12-01

It has long been known that electrical fields (EFs) are able to influence the direction of migrating cells, a process commonly referred to as electrotaxis or galvanotaxis. Most studies have focused on migrating cells equipped with an existing polarity before EF application, making it difficult to delineate EF-specific pathways. Here we study the initial events in front-rear organization of spreading keratinocytes to dissect the molecular requirements for random and EF-controlled polarization. We find that Arp2/3-dependent protrusive forces and Rac1/Cdc42 activity were generally required for both forms of polarization but were dispensable for controlling the direction of EF-controlled polarization. By contrast, we found a crucial role for extracellular pH as well as G protein coupled-receptor (GPCR) or purinergic signaling in the control of directionality. The normal direction of polarization toward the cathode was reverted by lowering extracellular pH. Polarization toward the anode was also seen at neutral pH when GPCR or purinergic signaling was inhibited. However, the stepwise increase of extracellular pH in this scenario led to restoration of cathodal polarization. Overall our work puts forward a model in which the EF uses distinct polarization pathways. The cathodal pathway involves GPCR/purinergic signaling and is dominant over the anodal pathway at neutral pH. © 2015 Saltukoglu et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

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.

Identification of Cell Cycle-regulated Genes in Fission YeastD⃞

PubMed Central

Peng, Xu; Karuturi, R. Krishna Murthy; Miller, Lance D.; Lin, Kui; Jia, Yonghui; Kondu, Pinar; Wang, Long; Wong, Lim-Soon; Liu, Edison T.; Balasubramanian, Mohan K.; Liu, Jianhua

2005-01-01

Cell cycle progression is both regulated and accompanied by periodic changes in the expression levels of a large number of genes. To investigate cell cycle-regulated transcriptional programs in the fission yeast Schizosaccharomyces pombe, we developed a whole-genome oligonucleotide-based DNA microarray. Microarray analysis of both wild-type and cdc25 mutant cell cultures was performed to identify transcripts whose levels oscillated during the cell cycle. Using an unsupervised algorithm, we identified 747 genes that met the criteria for cell cycle-regulated expression. Peaks of gene expression were found to be distributed throughout the entire cell cycle. Furthermore, we found that four promoter motifs exhibited strong association with cell cycle phase-specific expression. Examination of the regulation of MCB motif-containing genes through the perturbation of DNA synthesis control/MCB-binding factor (DSC/MBF)-mediated transcription in arrested synchronous cdc10 mutant cell cultures revealed a subset of functional targets of the DSC/MBF transcription factor complex, as well as certain gene promoter requirements. Finally, we compared our data with those for the budding yeast Saccharomyces cerevisiae and found ∼140 genes that are cell cycle regulated in both yeasts, suggesting that these genes may play an evolutionarily conserved role in regulation of cell cycle-specific processes. Our complete data sets are available at http://giscompute.gis.a-star.edu.sg/~gisljh/CDC. PMID:15616197

Requirements for Notification, Evaluation and Reduction of Lead-Based Paint Hazards in Federally Owned Residential Property and Housing Receiving Federal Assistance; Response to Elevated Blood Lead Levels. Final rule.

PubMed

2017-01-13

This final rule amends HUD's lead-based paint regulations to reduce blood lead levels in children under age six (6) who reside in federally-owned or -assisted pre-1978 housing, formally adopting a revised definition of "elevated blood lead level" (EBLL) in children under the age of six (6), in accordance with Centers for Disease Control and Prevention (CDC) guidance. It also establishes more comprehensive testing and evaluation procedures for the housing where such children reside. This final rule also addresses certain additional elements of the CDC guidance pertaining to assisted housing and makes technical corrections and clarifications. This final rule, which follows HUD's September 1, 2016, proposed rule, takes into consideration public comments submitted in response to the proposed rule.

Mechanism of Archaeal MCM Helicase Recruitment to DNA Replication Origins

PubMed Central

Samson, Rachel Y.; Abeyrathne, Priyanka D.; Bell, Stephen D.

2015-01-01

Summary Cellular DNA replication origins direct the recruitment of replicative helicases via the action of initiator proteins belonging to the AAA+ superfamily of ATPases. Archaea have a simplified subset of the eukaryotic DNA replication machinery proteins and possess initiators that appear ancestral to both eukaryotic Orc1 and Cdc6. We have reconstituted origin-dependent recruitment of the homohexameric archaeal MCM in vitro with purified recombinant proteins. Using this system, we reveal that archaeal Orc1-1 fulfills both Orc1 and Cdc6 functions by binding to a replication origin and directly recruiting MCM helicase. We identify the interaction interface between these proteins and reveal how ATP binding by Orc1-1 modulates recruitment of MCM. Additionally, we provide evidence that an open-ring form of the archaeal MCM homohexamer is loaded at origins. PMID:26725007

14 CFR 420.6-420.14 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false [Reserved] 420.6-420.14 Section 420.6-420.14 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION LICENSING LICENSE TO OPERATE A LAUNCH SITE General §§ 420.6-420.14 [Reserved] ...