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

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

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

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

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.

Protein a Immunoadsorption May Hamper the Decision to Transplant Due to Interference With CDC Crossmatch Results.

PubMed

Koefoed-Nielsen, Pernille; Bistrup, Claus; Christiansen, Mette

2017-06-01

Transplanting immunized patients requires immunological monitoring in the pretransplant phase to follow reduction of donor specific HLA antibodies (DSA) after Staphylococcus aureus protein A (SPA) immunoadsorption (IA) or therapeutic plasma exchange followed by IVIG and Rituximab administration. Pretreatment aims to significantly reduce DSA strength. The Tissue Typing Lab at Aarhus University Hospital performs immunological monitoring of approximately 150 kidney transplantation patients per year from two transplant centers. From 2012 to 2013, we experienced seven patients desensitized using SPA IA, initially presenting negative cytotoxic complement dependent (CDC) T-cell crossmatches but positive B and T cell flowcytometric crossmatch, who despite significant DSA reduction developed weakly positive CDC T-cell crossmatch shortly prior to transplantation. We hypothesised that leached SPA during IA could be the cause, as the complication was not observed in patients who received plasma exchanges. We found that the positive CDC was not donor specific and SPA column material incubated with control serum reproduced a positive CDC T-cell crossmatch. Finally, we detected leached SPA in one of the patient samples using a highly sensitive time-resolved fluorescent assay. In conclusion, the results emphasize the importance of carefully considering CDC crossmatch results subsequent to IA, before a planned transplantation is either postponed or cancelled. J. Clin. Apheresis 32:163-169, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

77 FR 39244 - Office for State, Tribal, Local and Territorial Support (OSTLTS); Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-02

... is for CDC/ATSDR leadership and staff to conduct government-to-government consultation with elected... provide a complementary venue wherein tribal representatives and CDC/ATSDR leadership and staff exchange... communities, and discuss collaborative approaches to addressing these issues and needs. Matters To Be...

Pneumococcal polysaccharide vaccine - what you need to know

MedlinePlus

... taken in its entirety from the CDC Pneumococcal Polysaccharide Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... statements/ppv.html CDC review information for Pneumococcal Polysaccharide VIS: Page last reviewed: April 24, 2015 Page ...

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

Health and Environment Linked for Information Exchange (HELIX)-Atlanta: A CDC-NASA Joint Environmental Public Health Tracking Collaborative Project

NASA Technical Reports Server (NTRS)

Al-Hamdan, Mohammad; Luvall, Jeff; Crosson, Bill; Estes, Maury; Limaye, Ashutosh; Quattrochi, Dale; Rickman, Doug

2008-01-01

HELIX-Atlanta was developed to support current and future state and local EPHT programs to implement data linking demonstration projects which could be part of the CDC EPHT Network. HELIX-Atlanta is a pilot linking project in Atlanta for CDC to learn about the challenges the states will encounter. NASA/MSFC and the CDC are partners in linking environmental and health data to enhance public health surveillance. The use of NASA technology creates value added geospatial products from existing environmental data sources to facilitate public health linkages. Proving the feasibility of the approach is the main objective

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.

Constitutional dynamic chemistry: bridge from supramolecular chemistry to adaptive chemistry.

PubMed

Lehn, Jean-Marie

2012-01-01

Supramolecular chemistry aims at implementing highly complex chemical systems from molecular components held together by non-covalent intermolecular forces and effecting molecular recognition, catalysis and transport processes. A further step consists in the investigation of chemical systems undergoing self-organization, i.e. systems capable of spontaneously generating well-defined functional supramolecular architectures by self-assembly from their components, thus behaving as programmed chemical systems. Supramolecular chemistry is intrinsically a dynamic chemistry in view of the lability of the interactions connecting the molecular components of a supramolecular entity and the resulting ability of supramolecular species to exchange their constituents. The same holds for molecular chemistry when the molecular entity contains covalent bonds that may form and break reversibility, so as to allow a continuous change in constitution by reorganization and exchange of building blocks. These features define a Constitutional Dynamic Chemistry (CDC) on both the molecular and supramolecular levels.CDC introduces a paradigm shift with respect to constitutionally static chemistry. The latter relies on design for the generation of a target entity, whereas CDC takes advantage of dynamic diversity to allow variation and selection. The implementation of selection in chemistry introduces a fundamental change in outlook. Whereas self-organization by design strives to achieve full control over the output molecular or supramolecular entity by explicit programming, self-organization with selection operates on dynamic constitutional diversity in response to either internal or external factors to achieve adaptation.The merging of the features: -information and programmability, -dynamics and reversibility, -constitution and structural diversity, points to the emergence of adaptive and evolutive chemistry, towards a chemistry of complex matter.

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].

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

Non-synonymous FGD3 Variant as Positional Candidate for Disproportional Tall Stature Accounting for a Carcass Weight QTL (CW-3) and Skeletal Dysplasia in Japanese Black Cattle

PubMed Central

Takasuga, Akiko; Sato, Kunio; Nakamura, Ryouichi; Saito, Yosuke; Sasaki, Shinji; Tsuji, Takehito; Suzuki, Akio; Kobayashi, Hiroshi; Matsuhashi, Tamako; Setoguchi, Koji; Okabe, Hiroshi; Ootsubo, Toshitake; Tabuchi, Ichiro; Fujita, Tatsuo; Watanabe, Naoto; Hirano, Takashi; Nishimura, Shota; Watanabe, Toshio; Hayakawa, Makio; Sugimoto, Yoshikazu; Kojima, Takatoshi

2015-01-01

Recessive skeletal dysplasia, characterized by joint- and/or hip bone-enlargement, was mapped within the critical region for a major quantitative trait locus (QTL) influencing carcass weight; previously named CW-3 in Japanese Black cattle. The risk allele was on the same chromosome as the Q allele that increases carcass weight. Phenotypic characterization revealed that the risk allele causes disproportional tall stature and bone size that increases carcass weight in heterozygous individuals but causes disproportionately narrow chest width in homozygotes. A non-synonymous variant of FGD3 was identified as a positional candidate quantitative trait nucleotide (QTN) and the corresponding mutant protein showed reduced activity as a guanine nucleotide exchange factor for Cdc42. FGD3 is expressed in the growth plate cartilage of femurs from bovine and mouse. Thus, loss of FDG3 activity may lead to subsequent loss of Cdc42 function. This would be consistent with the columnar disorganization of proliferating chondrocytes in chondrocyte-specific inactivated Cdc42 mutant mice. This is the first report showing association of FGD3 with skeletal dysplasia. PMID:26306008

Evaluation of a Pilot Surveillance System: Health and Environment Linked for Information Exchange in Atlanta (HELIX-Atlanta)

NASA Technical Reports Server (NTRS)

Meyer, P.; Shire, J.; Qualters, Judy; Daley, Randolph; Fiero, Leslie Todorov; Autry, Andy; Avchen, Rachel; Stock, Allison; Correa, Adolofo; Siffel, Csaba;

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.

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.

Centers for Disease Control and Prevention

MedlinePlus

... site content En español Centers for Disease Control and Prevention CDC 24/7: Saving Lives. Protecting People.™ Centers for Disease Control and Prevention. CDC twenty four seven. Saving Lives, ...

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

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.

Optimal experimental design in an epidermal growth factor receptor signalling and down-regulation model.

PubMed

Casey, F P; Baird, D; Feng, Q; Gutenkunst, R N; Waterfall, J J; Myers, C R; Brown, K S; Cerione, R A; Sethna, J P

2007-05-01

We apply the methods of optimal experimental design to a differential equation model for epidermal growth factor receptor signalling, trafficking and down-regulation. The model incorporates the role of a recently discovered protein complex made up of the E3 ubiquitin ligase, Cbl, the guanine exchange factor (GEF), Cool-1 (beta -Pix) and the Rho family G protein Cdc42. The complex has been suggested to be important in disrupting receptor down-regulation. We demonstrate that the model interactions can accurately reproduce the experimental observations, that they can be used to make predictions with accompanying uncertainties, and that we can apply ideas of optimal experimental design to suggest new experiments that reduce the uncertainty on unmeasurable components of the system.

An allosteric conduit facilitates dynamic multisite substrate recognition by the SCFCdc4 ubiquitin ligase

NASA Astrophysics Data System (ADS)

Csizmok, Veronika; Orlicky, Stephen; Cheng, Jing; Song, Jianhui; Bah, Alaji; Delgoshaie, Neda; Lin, Hong; Mittag, Tanja; Sicheri, Frank; Chan, Hue Sun; Tyers, Mike; Forman-Kay, Julie D.

2017-01-01

The ubiquitin ligase SCFCdc4 mediates phosphorylation-dependent elimination of numerous substrates by binding one or more Cdc4 phosphodegrons (CPDs). Methyl-based NMR analysis of the Cdc4 WD40 domain demonstrates that Cyclin E, Sic1 and Ash1 degrons have variable effects on the primary Cdc4WD40 binding pocket. Unexpectedly, a Sic1-derived multi-CPD substrate (pSic1) perturbs methyls around a previously documented allosteric binding site for the chemical inhibitor SCF-I2. NMR cross-saturation experiments confirm direct contact between pSic1 and the allosteric pocket. Phosphopeptide affinity measurements reveal negative allosteric communication between the primary CPD and allosteric pockets. Mathematical modelling indicates that the allosteric pocket may enhance ultrasensitivity by tethering pSic1 to Cdc4. These results suggest negative allosteric interaction between two distinct binding pockets on the Cdc4WD40 domain may facilitate dynamic exchange of multiple CPD sites to confer ultrasensitive dependence on substrate phosphorylation.

An extracellular-matrix-specific GEF-GAP interaction regulates Rho GTPase crosstalk for 3D collagen migration.

PubMed

Kutys, Matthew L; Yamada, Kenneth M

2014-09-01

Rho-family GTPases govern distinct types of cell migration on different extracellular matrix proteins in tissue culture or three-dimensional (3D) matrices. We searched for mechanisms selectively regulating 3D cell migration in different matrix environments and discovered a form of Cdc42-RhoA crosstalk governing cell migration through a specific pair of GTPase activator and inhibitor molecules. We first identified βPix, a guanine nucleotide exchange factor (GEF), as a specific regulator of migration in 3D collagen using an affinity-precipitation-based GEF screen. Knockdown of βPix specifically blocks cell migration in fibrillar collagen microenvironments, leading to hyperactive cellular protrusion accompanied by increased collagen matrix contraction. Live FRET imaging and RNAi knockdown linked this βPix knockdown phenotype to loss of polarized Cdc42 but not Rac1 activity, accompanied by enhanced, de-localized RhoA activity. Mechanistically, collagen phospho-regulates βPix, leading to its association with srGAP1, a GTPase-activating protein (GAP), needed to suppress RhoA activity. Our results reveal a matrix-specific pathway controlling migration involving a GEF-GAP interaction of βPix with srGAP1 that is critical for maintaining suppressive crosstalk between Cdc42 and RhoA during 3D collagen migration.

The Chromobacterium violaceum type III effector CopE, a guanine nucleotide exchange factor for Rac1 and Cdc42, is involved in bacterial invasion of epithelial cells and pathogenesis.

PubMed

Miki, Tsuyoshi; Akiba, Kinari; Iguchi, Mirei; Danbara, Hirofumi; Okada, Nobuhiko

2011-06-01

The type III secretion system (T3SS) encoded by Chromobacterium pathogenicity islands 1 and 1a (Cpi-1/-1a) is critical for Chromobacterium violaceum pathogenesis. T3SS-dependent virulence is commonly characterized by type III effector virulence function, but the full repertoire of the effector proteins of Cpi-1/-1a T3SS is unknown. In this study, we showed that expression of Cpi-1/-1a T3SS is controlled by the master regulator CilA. We used transcriptional profiling with DNA microarrays to define CilA regulon and identified genes encoding T3SS effectors whose translocation into host cells was dependent on Cpi-1/-1a T3SS. From these effectors, we found that CopE (CV0296) has similarities to a guanine nucleotide exchange factor (GEF) for Rho GTPases in its C-terminal portion. The N-terminal portions (1-81 amino acids) of CopE and a CivB as a putative chaperone were required for its translocation. CopE specifically activates Rac1 and Cdc42 followed by the induction of actin cytoskeletal rearrangement. Interestingly, C. violaceum invades human epithelial HeLa cells in a Cpi-1/-1a-encoded T3SS- and CopE-dependent manner. Finally, C. violaceum strains lacking copE and expressing a CopE-G168V deficient in GEF activity were attenuated for virulence in mice, suggesting that CopE contributes to the virulence of this pathogen. © 2011 Blackwell Publishing Ltd.

XL413, a cell division cycle 7 kinase inhibitor enhanced the anti-fibrotic effect of pirfenidone on TGF-β1-stimulated C3H10T1/2 cells via Smad2/4.

PubMed

Jin, Shu-fang; Ma, Hai-long; Liu, Zhong-long; Fu, Shui-ting; Zhang, Chen-ping; He, Yue

2015-12-10

Pirfenidone is an orally bioavailable synthetic compound with therapeutic potential for idiopathic pulmonary fibrosis. It is thought to act through antioxidant and anti-fibrotic pathways. Pirfenidone inhibits proliferation and/or myofibroblast differentiation of a wide range of cell types, however, little studies have analyzed the effect of pirfenidone on the mesenchymal stem cells, which play an important role on the origin of myofibroblasts. We recently found that pirfenidone had anti-proliferative activity via G1 phase arrest and cell division cycle 7 (Cdc7) kinase expression decrease in transforming growth factor-β1 (TGF-β1)-stimulated murine mesenchymal stem C3H10T1/2 cells. Pirfenidone also had inhibiting effect on the migration and α-SMA expression. Moreover, in this study we showed for the first time that Cdc7 inhibitor XL413 enhanced the anti-fibrotic activity of pirfenidone via depressed the expression of Smad2/4 proteins, and also prevented the nuclear accumulation and translocation of Smad2 protein. In conclusion, we demonstrated that pirfenidone inhibited proliferation, migration and differentiation of TGF-β1-stimulated C3H10T1/2 cells, which could be enhanced by Cdc7 inhibitor XL413, via Smad2/4. Combination with pirfenidone and XL413 might provide a potential candidate for the treatment of TGF-β1 associated fibrosis. It needs in vivo studies to further validate its therapeutic function and safety in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

Compairing Picture Exchange and Voice Output Communication Aids in Young Children with Autism

ERIC Educational Resources Information Center

Lorah, Elizabeth R.

2012-01-01

The Center for Disease Control estimates that one in 88 births result in a diagnosis of autism (CDC, 2012). Of those individuals diagnosed with autism approximately 25-61% fail to develop vocal output capabilities (Weitxz, Dexter, & Moore, 1997). The use of Augmentative and Alternative Communication (AAC) systems, such as Picture Exchange (PE)…

Involvement of Alpha-PAK-Interacting Exchange Factor in the PAK1–c-Jun NH2-Terminal Kinase 1 Activation and Apoptosis Induced by Benzo[a]pyrene

PubMed Central

Yoshii, Shigeto; Tanaka, Masamitsu; Otsuki, Yoshiro; Fujiyama, Toshiharu; Kataoka, Hideki; Arai, Hajime; Hanai, Hiroyuki; Sugimura, Haruhiko

2001-01-01

Benzo[a]pyrene [B(a)P], a potent procarcinogen found in combustion products such as diesel exhaust and cigarette smoke, has been recently shown to activate the c-Jun NH2-terminal kinase 1 (JNK1) and induce caspase-3-mediated apoptosis in Hepa1c1c7 cells. However, the molecules of the signaling pathway that control the mitogen-activated protein kinase cascades induced by B(a)P and the interaction between those and apoptosis by B(a)P have not been well defined. We report here that B(a)P promoted Cdc42/Rac1, p21-activated kinase 1 (PAK1), and JNK1 activities in 293T and HeLa cells. Moreover, alpha-PAK-interacting exchange factor (α PIX) mRNA and its protein expression were upregulated by B(a)P. While overexpression of an active mutant of α PIX (ΔCH) facilitated B(a)P-induced activation of Cdc42/Rac1, PAK1, and JNK1, overexpression of mutated αPIX (L383R, L384S), which lacks guanine nucleotide exchange factor activity, SH3 domain-deleted αPIX (Δ SH3), which lacks the ability to bind PAK, kinase-negative PAK1 (K299R), and kinase-negative SEK1 (K220A, K224L) inhibited B(a)P-triggered JNK1 activation. Interestingly, overexpression of αPIX (Δ CH) and a catalytically active mutant PAK1 (T423E) accelerated B(a)P-induced apoptosis in HeLa cells, whereas αPIX (Δ SH3), PAK1 (K299R), and SEK 1 (K220A, K224L) inhibited B(a)P-initiated apoptosis. Finally, a preferential caspase inhibitor, Z-Asp-CH2-DCB, strongly blocked the αPIX (Δ CH)-enhanced apoptosis in cells treated with B(a)P but did not block PAK1/JNK1 activation. Taken together, these results indicate that αPIX plays a crucial role in B(a)P-induced apoptosis through activation of the JNK1 pathway kinases. PMID:11564864

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

PubMed

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

2011-10-07

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

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

PubMed

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

2012-08-01

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

CDC WONDER: a cooperative processing architecture for public health.

PubMed Central

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

1994-01-01

CDC WONDER is an information management architecture designed for public health. It provides access to information and communications without the user's needing to know the location of data or communication pathways and mechanisms. CDC WONDER users have access to extractions from some 40 databases; electronic mail (e-mail); and surveillance data processing. System components include the Remote Client, the Communications Server, the Queue Managers, and Data Servers and Process Servers. The Remote Client software resides in the user's machine; other components are at the Centers for Disease Control and Prevention (CDC). The Remote Client, the Communications Server, and the Applications Server provide access to the information and functions in the Data Servers and Process Servers. The system architecture is based on cooperative processing, and components are coupled via pure message passing, using several protocols. This architecture allows flexibility in the choice of hardware and software. One system limitation is that final results from some subsystems are obtained slowly. Although designed for public health, CDC WONDER could be useful for other disciplines that need flexible, integrated information exchange. PMID:7719813

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

PubMed

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

2008-03-01

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

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.

Suppression of Chemotaxis by SSeCKS via Scaffolding of Phosphoinositol Phosphates and the Recruitment of the Cdc42 GEF, Frabin, to the Leading Edge

PubMed Central

Ko, Hyun-Kyung; Guo, Li-wu; Su, Bing; Gao, Lingqiu; Gelman, Irwin H.

2014-01-01

Chemotaxis is controlled by interactions between receptors, Rho-family GTPases, phosphatidylinositol 3-kinases, and cytoskeleton remodeling proteins. We investigated how the metastasis suppressor, SSeCKS, attenuates chemotaxis. Chemotaxis activity inversely correlated with SSeCKS levels in mouse embryo fibroblasts (MEF), DU145 and MDA-MB-231 cancer cells. SSeCKS loss induced chemotactic velocity and linear directionality, correlating with replacement of leading edge lamellipodia with fascin-enriched filopodia-like extensions, the formation of thickened longitudinal F-actin stress fibers reaching to filopodial tips, relative enrichments at the leading edge of phosphatidylinositol (3,4,5)P3 (PIP3), Akt, PKC-ζ, Cdc42-GTP and active Src (SrcpoY416), and a loss of Rac1. Leading edge lamellipodia and chemotaxis inhibition in SSeCKS-null MEF could be restored by full-length SSeCKS or SSeCKS deleted of its Src-binding domain (ΔSrc), but not by SSeCKS deleted of its three MARCKS (myristylated alanine-rich C kinase substrate) polybasic domains (ΔPBD), which bind PIP2 and PIP3. The enrichment of activated Cdc42 in SSeCKS-null leading edge filopodia correlated with recruitment of the Cdc42-specific guanine nucleotide exchange factor, Frabin, likely recruited via multiple PIP2/3-binding domains. Frabin knockdown in SSeCKS-null MEF restores leading edge lamellipodia and chemotaxis inhibition. However, SSeCKS failed to co-immunoprecipitate with Rac1, Cdc42 or Frabin. Consistent with the notion that chemotaxis is controlled by SSeCKS-PIP (vs. -Src) scaffolding activity, constitutively-active phosphatidylinositol 3-kinase could override the ability of the Src inhibitor, SKI-606, to suppress chemotaxis and filopodial enrichment of Frabin in SSeCKS-null MEF. Our data suggest a role for SSeCKS in controlling Rac1 vs. Cdc42-induced cellular dynamics at the leading chemotactic edge through the scaffolding of phospholipids and signal mediators, and through the reorganization of the actin cytoskeleton controlling directional movement. PMID:25356636

A reverse signaling pathway downstream of Sema4A controls cell migration via Scrib

PubMed Central

Yang, Lida; Kaur, Harmandeep; Pestel, Jenny; Looso, Mario; Nolte, Hendrik; Krishnan, Ramesh K.; Bünemann, Moritz; Offermanns, Stefan; Swiercz, Jakub M.

2017-01-01

Semaphorins comprise a large family of ligands that regulate key cellular functions through their receptors, plexins. In this study, we show that the transmembrane semaphorin 4A (Sema4A) can also function as a receptor, rather than a ligand, and transduce signals triggered by the binding of Plexin-B1 through reverse signaling. Functionally, reverse Sema4A signaling regulates the migration of various cancer cells as well as dendritic cells. By combining mass spectrometry analysis with small interfering RNA screening, we identify the polarity protein Scrib as a downstream effector of Sema4A. We further show that binding of Plexin-B1 to Sema4A promotes the interaction of Sema4A with Scrib, thereby removing Scrib from its complex with the Rac/Cdc42 exchange factor βPIX and decreasing the activity of the small guanosine triphosphatase Rac1 and Cdc42. Our data unravel a role for Plexin-B1 as a ligand and Sema4A as a receptor and characterize a reverse signaling pathway downstream of Sema4A, which controls cell migration. PMID:28007914

Effects of trimming weight-for-height data on growth-chart percentiles1–3

PubMed Central

Flegal, Katherine M; Carroll, Margaret D; Ogden, Cynthia L

2016-01-01

Background Before estimating smoothed percentiles of weight-for-height and BMI-for-age to construct the WHO growth charts, WHO excluded observations that were considered to represent unhealthy weights for height. Objective The objective was to estimate the effects of similar data trimming on empirical percentiles from the CDC growth-chart data set relative to the smoothed WHO percentiles for ages 24–59 mo. Design We used the nationally representative US weight and height data from 1971 to 1994, which was the source data for the 2000 CDC growth charts. Trimming cutoffs were calculated on the basis of weight-for-height for 9722 children aged 24–71 mo. Empirical percentiles for 7315 children aged 24–59 mo were compared with the corresponding smoothed WHO percentiles. Results Before trimming, the mean empirical percentiles for weight-for-height in the CDC data set were higher than the corresponding smoothed WHO percentiles. After trimming, the mean empirical 95th and 97th percentiles of weight-for-height were lower than the WHO percentiles, and the proportion of children in the CDC data set above the WHO 95th percentile decreased from 7% to 5%. The findings were similar for BMI-for-age. However, for weight-for-age, which had not been trimmed by the WHO, the empirical percentiles before trimming agreed closely with the upper percentiles from the WHO charts. Conclusion WHO data-trimming procedures may account for some of the differences between the WHO growth charts and the 2000 CDC growth charts. PMID:22990032

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.

Roles of STEF/Tiam1, guanine nucleotide exchange factors for Rac1, in regulation of growth cone morphology.

PubMed

Matsuo, Naoki; Terao, Mami; Nabeshima, Yo-ichi; Hoshino, Mikio

2003-09-01

Rho family GTPases are suggested to be pivotal for growth cone behavior, but regulation of their activities in response to environmental cues remains elusive. Here, we describe roles of STEF and Tiam1, guanine nucleotide exchange factors for Rac1, in neurite growth and growth cone remodeling. We reveal that, in primary hippocampal neurons, STEF/Tiam1 are localized within growth cones and essential for formation of growth cone lamellipodia, eventually contributing to neurite growth. Furthermore, experiments using a dominant-negative form demonstrate that STEF/Tiam1 mediate extracellular laminin signals to activate Rac1, promoting neurite growth in N1E-115 neuroblastoma cells. STEF/Tiam1 are revealed to mediate Cdc42 signal to activate Rac1 during lamellipodial formation. We also show that RhoA inhibits the STEF/Tiam1-Rac1 pathway. These data are used to propose a model that extracellular and intracellular information is integrated by STEF/Tiam1 to modulate the balance of Rho GTPase activities in the growth cone and, consequently, to control growth cone behavior.

ARC Events

Science.gov Websites

chair IEEE Technical Committee on Automotive Controls (Feb 2018, IEEE) Dr. Anna Stefanopoulou on research of sustainable vehicle technologies (Jan 24, 2018, WEMU) Stefanopoulou plenary at IEEE 56th CDC (Jan 17, 2018, ME) ARC Researchers at IEEE 56th Conf. Decision and Control (Dec 12-14, 2017, CDC) ARC

2,4-Dihydroxychalcone derivatives as novel potent cell division cycle 25B phosphatase inhibitors and protein tyrosine phosphatase 1B inhibitors.

PubMed

Xie, Chao; Sun, Yuan; Pan, Cheng-Yan; Tang, Li-Ming; Guan, Li-Ping

2014-04-01

Eleven 2,4-dihydroxychalcone compounds were synthesized and identified as reversible and competitive cell division cycle 25 (CDC25) B and protein tyrosine phosphatase (PTP) 1B inhibitors with inhibition values in the micromolar range. The results showed that nine compounds significantly inhibited CDC25B phosphatase, whereas seven compounds inhibited the activity against PTP1B in vitro. Compound 8 had the greatest inhibition activity against CDC25B and PTP1B in vitro, with percentage inhibition values of 97.5% and 96.3% at a dose of 20 microg/mL, respectively. Cytotoxic activity assays revealed that compound 8 was the most potent against HCT116, HeLa, and A549 cells. Furthermore, compound 8 exhibited potent antitumor activity in a colo205 xenograft model.

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.

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

SHARPS III Update Review--Autumn 1982.

DTIC Science & Technology

1982-09-14

SLD( 34) nP TAT 95 AVG SVL ISO POD 50, SNA --- 12KTS ------ 18KTS---.---24KTS ------------ CDC/COM- ALL 23/ 32 22/ 24 1/ 12 922/1190 SNR --- 12KTS...152 45 R79/ 966 8TPO 17/233 17/18Q 45 957/ 966 SMT 24/ 18 DO ; PSV 1 - 1 CDC 966 CDO 966 B-8 02HMC/FOTS 81032700Z MO 20.7/1523/ 27001 13.@ifOSS,.l*O...4HUA2Sl 4HO62U. ’.t4O6dI nATA 4AIJ /IS/% MARK /IS/* MAXSNT /91219 MAXSUP / ISO / 00 UF*11 DATA MAXSVS #75j’. MAXLEC ft5l 00 USFR.?35 U EMSNWO1JI

DNA replication initiator Cdc6 also regulates ribosomal DNA transcription initiation.

PubMed

Huang, Shijiao; Xu, Xiaowei; Wang, Guopeng; Lu, Guoliang; Xie, Wenbing; Tao, Wei; Zhang, Hongyin; Jiang, Qing; Zhang, Chuanmao

2016-04-01

RNA-polymerase-I-dependent ribosomal DNA (rDNA) transcription is fundamental to rRNA processing, ribosome assembly and protein synthesis. However, how this process is initiated during the cell cycle is not fully understood. By performing a proteomic analysis of transcription factors that bind RNA polymerase I during rDNA transcription initiation, we identified that the DNA replication initiator Cdc6 interacts with RNA polymerase I and its co-factors, and promotes rDNA transcription in G1 phase in an ATPase-activity-dependent manner. We further showed that Cdc6 is targeted to the nucleolus during late mitosis and G1 phase in a manner that is dependent on B23 (also known as nucleophosmin, NPM1), and preferentially binds to the rDNA promoter through its ATP-binding domain. Overexpression of Cdc6 increases rDNA transcription, whereas knockdown of Cdc6 results in a decreased association of both RNA polymerase I and the RNA polymerase I transcription factor RRN3 with rDNA, and a reduction of rDNA transcription. Furthermore, depletion of Cdc6 impairs the interaction between RRN3 and RNA polymerase I. Taken together, our data demonstrate that Cdc6 also serves as a regulator of rDNA transcription initiation, and indicate a mechanism by which initiation of rDNA transcription and DNA replication can be coordinated in cells. © 2016. Published by The Company of Biologists Ltd.

An Assessment of Information Exchange Practices, Challenges, and Opportunities to Support US Disease Surveillance in 3 States.

PubMed

Garcia, Macarena C; Garrett, Nedra Y; Singletary, Vivian; Brown, Sheereen; Hennessy-Burt, Tamara; Haney, Gillian; Link, Kimberly; Tripp, Jennifer; Mac Kenzie, William R; Yoon, Paula

2017-12-07

State and local public health agencies collect and use surveillance data to identify outbreaks, track cases, investigate causes, and implement measures to protect the public-s health through various surveillance systems and data exchange practices. The purpose of this assessment was to better understand current practices at state and local public health agencies for collecting, managing, processing, reporting, and exchanging notifiable disease surveillance information. Over an 18-month period (January 2014-June 2015), we evaluated the process of data exchange between surveillance systems, reporting burdens, and challenges within 3 states (California, Idaho, and Massachusetts) that were using 3 different reporting systems. All 3 states use a combination of paper-based and electronic information systems for managing and exchanging data on reportable conditions within the state. The flow of data from local jurisdictions to the state health departments varies considerably. When state and local information systems are not interoperable, manual duplicative data entry and other work-arounds are often required. The results of the assessment show the complexity of disease reporting at the state and local levels and the multiple systems, processes, and resources engaged in preparing, processing, and transmitting data that limit interoperability and decrease efficiency. Through this structured assessment, the Centers for Disease Control and Prevention (CDC) has a better understanding of the complexities for surveillance of using commercial off-the-shelf data systems (California and Massachusetts), and CDC-developed National Electronic Disease Surveillance System Base System. More efficient data exchange and use of data will help facilitate interoperability between National Notifiable Diseases Surveillance Systems.

Atomistic simulations and network-based modeling of the Hsp90-Cdc37 chaperone binding with Cdk4 client protein: A mechanism of chaperoning kinase clients by exploiting weak spots of intrinsically dynamic kinase domains

PubMed Central

Czemeres, Josh; Buse, Kurt

2017-01-01

A fundamental role of the Hsp90 and Cdc37 chaperones in mediating conformational development and activation of diverse protein kinase clients is essential in signal transduction. There has been increasing evidence that the Hsp90-Cdc37 system executes its chaperoning duties by recognizing conformational instability of kinase clients and modulating their folding landscapes. The recent cryo-electron microscopy structure of the Hsp90-Cdc37-Cdk4 kinase complex has provided a framework for dissecting regulatory principles underlying differentiation and recruitment of protein kinase clients to the chaperone machinery. In this work, we have combined atomistic simulations with protein stability and network-based rigidity decomposition analyses to characterize dynamic factors underlying allosteric mechanism of the chaperone-kinase cycle and identify regulatory hotspots that control client recognition. Through comprehensive characterization of conformational dynamics and systematic identification of stabilization centers in the unbound and client- bound Hsp90 forms, we have simulated key stages of the allosteric mechanism, in which Hsp90 binding can induce instability and partial unfolding of Cdk4 client. Conformational landscapes of the Hsp90 and Cdk4 structures suggested that client binding can trigger coordinated dynamic changes and induce global rigidification of the Hsp90 inter-domain regions that is coupled with a concomitant increase in conformational flexibility of the kinase client. This process is allosteric in nature and can involve reciprocal dynamic exchanges that exert global effect on stability of the Hsp90 dimer, while promoting client instability. The network-based rigidity analysis and emulation of thermal unfolding of the Cdk4-cyclin D complex and Hsp90-Cdc37-Cdk4 complex revealed weak spots of kinase instability that are present in the native Cdk4 structure and are targeted by the chaperone during client recruitment. Our findings suggested that this mechanism may be exploited by the Hsp90-Cdc37 chaperone to recruit and protect intrinsically dynamic kinase clients from degradation. The results of this investigation are discussed and interpreted in the context of diverse experimental data, offering new insights into mechanisms of chaperone regulation and binding. PMID:29267381

Cadherin-11 regulates protrusive activity in Xenopus cranial neural crest cells upstream of Trio and the small GTPases.

PubMed

Kashef, Jubin; Köhler, Almut; Kuriyama, Sei; Alfandari, Dominique; Mayor, Roberto; Wedlich, Doris

2009-06-15

Xenopus Cadherin-11 (Xcad-11) is expressed when cranial neural crest cells (CNC) acquire motility. However, its function in stimulating cell migration is poorly understood. Here, we demonstrate that Xcad-11 initiates filopodia and lamellipodia formation, which is essential for CNC to populate pharyngeal pouches. We identified the cytoplasmic tail of Xcad-11 as both necessary and sufficient for proper CNC migration as long as it was linked to the plasma membrane. Our results showing that guanine nucleotide exchange factor (GEF)-Trio binds to Xcad-11 and can functionally substitute for it like constitutively active forms of RhoA, Rac, and cdc42 unravel a novel cadherin function.

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.

Chromatin-associated degradation is defined by UBXN-3/FAF1 to safeguard DNA replication fork progression.

PubMed

Franz, André; Pirson, Paul A; Pilger, Domenic; Halder, Swagata; Achuthankutty, Divya; Kashkar, Hamid; Ramadan, Kristijan; Hoppe, Thorsten

2016-02-04

The coordinated activity of DNA replication factors is a highly dynamic process that involves ubiquitin-dependent regulation. In this context, the ubiquitin-directed ATPase CDC-48/p97 recently emerged as a key regulator of chromatin-associated degradation in several of the DNA metabolic pathways that assure genome integrity. However, the spatiotemporal control of distinct CDC-48/p97 substrates in the chromatin environment remained unclear. Here, we report that progression of the DNA replication fork is coordinated by UBXN-3/FAF1. UBXN-3/FAF1 binds to the licensing factor CDT-1 and additional ubiquitylated proteins, thus promoting CDC-48/p97-dependent turnover and disassembly of DNA replication factor complexes. Consequently, inactivation of UBXN-3/FAF1 stabilizes CDT-1 and CDC-45/GINS on chromatin, causing severe defects in replication fork dynamics accompanied by pronounced replication stress and eventually resulting in genome instability. Our work identifies a critical substrate selection module of CDC-48/p97 required for chromatin-associated protein degradation in both Caenorhabditis elegans and humans, which is relevant to oncogenesis and aging.

Chromatin-associated degradation is defined by UBXN-3/FAF1 to safeguard DNA replication fork progression

PubMed Central

Franz, André; Pirson, Paul A.; Pilger, Domenic; Halder, Swagata; Achuthankutty, Divya; Kashkar, Hamid; Ramadan, Kristijan; Hoppe, Thorsten

2016-01-01

The coordinated activity of DNA replication factors is a highly dynamic process that involves ubiquitin-dependent regulation. In this context, the ubiquitin-directed ATPase CDC-48/p97 recently emerged as a key regulator of chromatin-associated degradation in several of the DNA metabolic pathways that assure genome integrity. However, the spatiotemporal control of distinct CDC-48/p97 substrates in the chromatin environment remained unclear. Here, we report that progression of the DNA replication fork is coordinated by UBXN-3/FAF1. UBXN-3/FAF1 binds to the licensing factor CDT-1 and additional ubiquitylated proteins, thus promoting CDC-48/p97-dependent turnover and disassembly of DNA replication factor complexes. Consequently, inactivation of UBXN-3/FAF1 stabilizes CDT-1 and CDC-45/GINS on chromatin, causing severe defects in replication fork dynamics accompanied by pronounced replication stress and eventually resulting in genome instability. Our work identifies a critical substrate selection module of CDC-48/p97 required for chromatin-associated protein degradation in both Caenorhabditis elegans and humans, which is relevant to oncogenesis and aging. PMID:26842564

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.

Environmental Public Health Tracking: Health and Environment Linked for Information Exchange-Atlanta (HEXIX-Atlanta: A cooperative Program Between CDC and NASA for Development of an Environmental Public Health Tracking Network in the Atlanta Metropolitan Area

NASA Technical Reports Server (NTRS)

Quattrochi, Dale A.; Niskar, Amanda Sue

2005-01-01

The Centers for Disease Control and Prevention (CDC) is coordinating HELIX- Atlanta to provide information regarding the five-county Metropolitan Atlanta Area (Clayton, Cobb, DeKalb, Fulton, and Gwinett) via a network of integrated environmental monitoring and public health data systems so that all sectors can take action to prevent and control environmentally related health effects. The HELIX-Atlanta Network is a tool to access interoperable information systems with optional information technology linkage functionality driven by scientific rationale. HELIX-Atlanta is a collaborative effort with local, state, federal, and academic partners, including the NASA Marshall Space Flight Center. The HELIX-Atlanta Partners identified the following HELIX-Atlanta initial focus areas: childhood lead poisoning, short-latency cancers, developmental disabilities, birth defects, vital records, respiratory health, age of housing, remote sensing data, and environmental monitoring, HELIX-Atlanta Partners identified and evaluated information systems containing information on the above focus areas. The information system evaluations resulted in recommendations for what resources would be needed to interoperate selected information systems in compliance with the CDC Public Health Information Network (PHIN). This presentation will discuss the collaborative process of building a network that links health and environment data for information exchange, including NASA remote sensing data, for use in HELIX-Atlanta.

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-08-01

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

Thrombin Promotes Sustained Signaling and Inflammatory Gene Expression through the CDC25 and Ras-associating Domains of Phospholipase Cϵ*

PubMed Central

Dusaban, Stephanie S.; Kunkel, Maya T.; Smrcka, Alan V.; Brown, Joan Heller

2015-01-01

Phospholipase C-epsilon (PLCϵ) plays a critical role in G-protein-coupled receptor-mediated inflammation. In addition to its ability to generate the second messengers inositol 1,4,5-trisphosphate and diacylglycerol, PLCϵ, unlike the other phospholipase C family members, is activated in a sustained manner. We hypothesized that the ability of PLCϵ to function as a guanine nucleotide exchange factor (GEF) for Rap1 supports sustained downstream signaling via feedback of Rap1 to the enzyme Ras-associating (RA2) domain. Using gene deletion and adenoviral rescue, we demonstrate that both the GEF (CDC25 homology domain) and RA2 domains of PLCϵ are required for long term protein kinase D (PKD) activation and subsequent induction of inflammatory genes. PLCϵ localization is largely intracellular and its compartmentalization could contribute to its sustained activation. Here we show that localization of PLCϵ to the Golgi is required for activation of PKD in this compartment as well as for subsequent induction of inflammatory genes. These data provide a molecular mechanism by which PLCϵ mediates sustained signaling and by which astrocytes mediate pathophysiological inflammatory responses. PMID:26350460

A reverse signaling pathway downstream of Sema4A controls cell migration via Scrib.

PubMed

Sun, Tianliang; Yang, Lida; Kaur, Harmandeep; Pestel, Jenny; Looso, Mario; Nolte, Hendrik; Krasel, Cornelius; Heil, Daniel; Krishnan, Ramesh K; Santoni, Marie-Josée; Borg, Jean-Paul; Bünemann, Moritz; Offermanns, Stefan; Swiercz, Jakub M; Worzfeld, Thomas

2017-01-02

Semaphorins comprise a large family of ligands that regulate key cellular functions through their receptors, plexins. In this study, we show that the transmembrane semaphorin 4A (Sema4A) can also function as a receptor, rather than a ligand, and transduce signals triggered by the binding of Plexin-B1 through reverse signaling. Functionally, reverse Sema4A signaling regulates the migration of various cancer cells as well as dendritic cells. By combining mass spectrometry analysis with small interfering RNA screening, we identify the polarity protein Scrib as a downstream effector of Sema4A. We further show that binding of Plexin-B1 to Sema4A promotes the interaction of Sema4A with Scrib, thereby removing Scrib from its complex with the Rac/Cdc42 exchange factor βPIX and decreasing the activity of the small guanosine triphosphatase Rac1 and Cdc42. Our data unravel a role for Plexin-B1 as a ligand and Sema4A as a receptor and characterize a reverse signaling pathway downstream of Sema4A, which controls cell migration. © 2017 Sun et al.

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.

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.

Cell adhesion controlled by adhesion G protein-coupled receptor GPR124/ADGRA2 is mediated by a protein complex comprising intersectins and Elmo-Dock.

PubMed

Hernández-Vásquez, Magda Nohemí; Adame-García, Sendi Rafael; Hamoud, Noumeira; Chidiac, Rony; Reyes-Cruz, Guadalupe; Gratton, Jean Philippe; Côté, Jean-François; Vázquez-Prado, José

2017-07-21

Developmental angiogenesis and the maintenance of the blood-brain barrier involve endothelial cell adhesion, which is linked to cytoskeletal dynamics. GPR124 (also known as TEM5/ADGRA2) is an adhesion G protein-coupled receptor family member that plays a pivotal role in brain angiogenesis and in ensuring a tight blood-brain barrier. However, the signaling properties of GPR124 remain poorly defined. Here, we show that ectopic expression of GPR124 promotes cell adhesion, additive to extracellular matrix-dependent effect, coupled with filopodia and lamellipodia formation and an enrichment of a pool of the G protein-coupled receptor at actin-rich cellular protrusions containing VASP, a filopodial marker. Accordingly, GPR124-expressing cells also displayed increased activation of both Rac and Cdc42 GTPases. Mechanistically, we uncover novel direct interactions between endogenous GPR124 and the Rho guanine nucleotide exchange factors Elmo/Dock and intersectin (ITSN). Small fragments of either Elmo or ITSN1 that bind GPR124 blocked GPR124-induced cell adhesion. In addition, Gβγ interacts with the C-terminal tail of GPR124 and promotes the formation of a GPR124-Elmo complex. Furthermore, GPR124 also promotes the activation of the Elmo-Dock complex, as measured by Elmo phosphorylation on a conserved C-terminal tyrosine residue. Interestingly, Elmo and ITSN1 also interact with each other independently of their GPR124-recognition regions. Moreover, endogenous phospho-Elmo and ITSN1 co-localize with GPR124 at lamellipodia of adhering endothelial cells, where GPR124 expression contributes to polarity acquisition during wound healing. Collectively, our results indicate that GPR124 promotes cell adhesion via Elmo-Dock and ITSN. This constitutes a previously unrecognized complex formed of atypical and conventional Rho guanine nucleotide exchange factors for Rac and Cdc42 that is putatively involved in GPR124-dependent angiogenic responses. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

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.

75 FR 54889 - Development of Set 24 Toxicological Profiles

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-09

... these documents will be available at the ATSDR Web site: http://www.atsdr.cdc.gov/toxpro2.html . Set 24... toxicological profiles for each substance included on the Priority List of Hazardous Substances ( http://www...

Impact of the mass media on calls to the CDC National AIDS Hotline.

PubMed

Fan, D P

1996-06-01

This paper considers new computer methodologies for assessing the impact of different types of public health information. The example used public service announcements (PSAs) and mass media news to predict the volume of attempts to call the CDC National AIDS Hotline from December 1992 through to the end of 1993. The analysis relied solely on data from electronic databases. Newspaper stories and television news transcripts were obtained from the NEXIS electronic database and were scored by machine for AIDS coverage. The PSA database was generated by computer monitoring of advertising distributed by the Centers for Disease Control and Prevention (CDC) and by others. The volume of call attempts was collected automatically by the public branch exchange (PBX) of the Hotline telephone system. The call attempts, the PSAs and the news story data were related to each other using both a standard time series method and the statistical model of ideodynamics. The analysis indicated that the only significant explanatory variable for the call attempts was PSAs produced by the CDC. One possible explanation was that these commercials all included the Hotline telephone number while the other information sources did not.

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

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.

Strategies Used in Natural Environments to Promote Communication Development in Young Children at Risk for Autism Spectrum Disorder

ERIC Educational Resources Information Center

Coogle, Christan Grygas; Floyd, Kim; Hanline, Mary Frances; Kellner-Hiczewski, Jacquie

2013-01-01

The Centers for Disease Control and Prevention (CDC) has documented that 1 in every 88 children is identified with an autism spectrum disorder (ASD; CDC, 2012). Autism is now recognized in children at an earlier age because most researchers agree autism can be reliably identified by the time children reach 24 months (Cox et al., 1999; Stone et…

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 ...

Cadherin-11 regulates protrusive activity in Xenopus cranial neural crest cells upstream of Trio and the small GTPases

PubMed Central

Kashef, Jubin; Köhler, Almut; Kuriyama, Sei; Alfandari, Dominique; Mayor, Roberto; Wedlich, Doris

2009-01-01

Xenopus Cadherin-11 (Xcad-11) is expressed when cranial neural crest cells (CNC) acquire motility. However, its function in stimulating cell migration is poorly understood. Here, we demonstrate that Xcad-11 initiates filopodia and lamellipodia formation, which is essential for CNC to populate pharyngeal pouches. We identified the cytoplasmic tail of Xcad-11 as both necessary and sufficient for proper CNC migration as long as it was linked to the plasma membrane. Our results showing that guanine nucleotide exchange factor (GEF)-Trio binds to Xcad-11 and can functionally substitute for it like constitutively active forms of RhoA, Rac, and cdc42 unravel a novel cadherin function. PMID:19528317

MCM interference during licensing of DNA replication in Xenopus egg extracts-Possible Role of a C-terminal region of MCM3.

PubMed

Mimura, Satoru; Kubota, Yumiko; Takisawa, Haruhiko

2018-01-01

The minichromosome maintenance (MCM) complex, consisting of six subunits, Mcm2-7, is loaded onto replication origins through loading factors (origin recognition complex [ORC], Cdc6, and Cdt1) and forms an MCM double hexamer that licenses the initiation of DNA replication. Previous studies with Xenopus egg extracts showed that loading factors, especially Cdc6, dissociate from chromatin on MCM loading, but the molecular mechanism and physiological significance remain largely unknown. Using a cell-free system for MCM loading onto plasmid DNA in Xenopus egg extracts, we found that MCM loaded onto DNA prevents DNA binding of the loading factors ORC, Cdc6, and Cdt1. We further report that a peptide of the C-terminal region of MCM3 (MCM3-C), previously implicated in the initial association with ORC/Cdc6 in budding yeast, prevents ORC/Cdc6/Cdt1 binding to DNA in the absence of MCM loading. ATP-γ-S suppresses inhibitory activities of both the MCM loaded onto DNA and the MCM3-C peptide. Other soluble factors in the extract, but neither MCM nor Cdt1, are required for the activity. Conservation of the amino acid sequences of MCM3-C and its activity in vertebrates implies a novel negative autoregulatory mechanism that interferes with MCM loading in the vicinity of licensed origins to ensure proper origin licensing.

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.

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.

A shot in the rear, not a shot in the dark: application of a mass clinic framework in a public health emergency.

PubMed

Erwin, Paul Campbell; Sheeler, Lorinda; Lott, John M

2009-01-01

An outbreak of foodborne hepatitis A infection compelled two regional health departments in eastern Tennessee to implement an emergency mass clinic for providing hepatitis immune serum globulin (ISG) to several thousand potentially exposed people. For the mass clinic framework, we utilized the smallpox post-event clinic plans of the Centers for Disease Control and Prevention (CDC), although the plans had only been exercised for smallpox. Following CDC's guidelines for staffing and organizing the mass clinic, we provided 5,038 doses of ISG during a total of 24 hours of clinic operation, using 3,467 person-hours, or 1.45 ISG doses per person-hour-very close to the 1.58 doses per person-hour targeted in CDC's smallpox post-event clinic plans. The mass clinic showed that CDC's smallpox post-event clinic guidelines were feasible, practical, and adaptable to other mass clinic situations.

The Use of GIS and Remotely Sensed Data in Environmental Public Health Tracking (EPHT): The HELIX-Atlanta Experience

NASA Technical Reports Server (NTRS)

Al-Hamdan, Mohammad Z.; Crosson, William L.; Limaye, Ashutosh S.; Estes, Maurice G., Jr.; Watts, Carol; Rickman, Douglas L.; Quattrochi, Dale A.; Qualters, Judith R.; Sinclair, Amber H.; Tolsma, Dennis D.;

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.

High-throughput screening identifies small molecules that bind to the RAS:SOS:RAS complex and perturb RAS signaling.

PubMed

Burns, Michael C; Howes, Jennifer E; Sun, Qi; Little, Andrew J; Camper, DeMarco V; Abbott, Jason R; Phan, Jason; Lee, Taekyu; Waterson, Alex G; Rossanese, Olivia W; Fesik, Stephen W

2018-05-01

K-RAS is mutated in approximately 30% of human cancers, resulting in increased RAS signaling and tumor growth. Thus, RAS is a highly validated therapeutic target, especially in tumors of the pancreas, lung and colon. Although directly targeting RAS has proven to be challenging, it may be possible to target other proteins involved in RAS signaling, such as the guanine nucleotide exchange factor Son of Sevenless (SOS). We have previously reported on the discovery of small molecules that bind to SOS1, activate SOS-mediated nucleotide exchange on RAS, and paradoxically inhibit ERK phosphorylation (Burns et al., PNAS, 2014). Here, we describe the discovery of additional, structurally diverse small molecules that also bind to SOS1 in the same pocket and elicit similar biological effects. We tested >160,000 compounds in a fluorescence-based assay to assess their effects on SOS-mediated nucleotide exchange. X-Ray structures revealed that these small molecules bind to the CDC25 domain of SOS1. Compounds that elicited high levels of nucleotide exchange activity in vitro increased RAS-GTP levels in cells, and inhibited phospho ERK levels at higher treatment concentrations. The identification of structurally diverse SOS1 binding ligands may assist in the discovery of new molecules designed to target RAS-driven tumors. Copyright © 2018 Elsevier Inc. All rights reserved.

Use of World Health Organization and CDC growth charts for children aged 0-59 months in the United States.

PubMed

Grummer-Strawn, Laurence M; Reinold, Chris; Krebs, Nancy F

2010-09-10

In April 2006, the World Health Organization (WHO) released new international growth charts for children aged 0-59 months. Similar to the 2000 CDC growth charts, these charts describe weight for age, length (or stature) for age, weight for length (or stature), and body mass index for age. Whereas the WHO charts are growth standards, describing the growth of healthy children in optimal conditions, the CDC charts are a growth reference, describing how certain children grew in a particular place and time. However, in practice, clinicians use growth charts as standards rather than references. In 2006, CDC, the National Institutes of Health, and the American Academy of Pediatrics convened an expert panel to review scientific evidence and discuss the potential use of the new WHO growth charts in clinical settings in the United States. On the basis of input from this expert panel, CDC recommends that clinicians in the United States use the 2006 WHO international growth charts, rather than the CDC growth charts, for children aged <24 months (available at https://www.cdc.gov/growthcharts). The CDC growth charts should continue to be used for the assessment of growth in persons aged 2--19 years. The recommendation to use the 2006 WHO international growth charts for children aged <24 months is based on several considerations, including the recognition that breastfeeding is the recommended standard for infant feeding. In the WHO charts, the healthy breastfed infant is intended to be the standard against which all other infants are compared; 100% of the reference population of infants were breastfed for 12 months and were predominantly breastfed for at least 4 months. When using the WHO growth charts to screen for possible abnormal or unhealthy growth, use of the 2.3rd and 97.7th percentiles (or ±2 standard deviations) are recommended, rather than the 5th and 95th percentiles. Clinicians should be aware that fewer U.S. children will be identified as underweight using the WHO charts, slower growth among breastfed infants during ages 3-18 months is normal, and gaining weight more rapidly than is indicated on the WHO charts might signal early signs of overweight.

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.

Carbachol-mediated endocytosis of NHE3 involves a clathrin-independent mechanism requiring lipid rafts and Cdc42.

PubMed

Zachos, Nicholas C; Alamelumangpuram, Bharath; Lee, Luke J; Wang, Peng; Kovbasnjuk, Olga

2014-01-01

In intestinal epithelial cells, acute regulation of the brush border Na(+)/H(+) exchanger, NHE3, usually occurs by changes in endocytosis and/or exocytosis. Constitutive NHE3 endocytosis involves clathrin. Carbachol (CCH), which elevates intracellular Ca(2+) ([Ca(2+)]i), decreases NHE3 activity and stimulates endocytosis; however, the mechanism involved in calcium-mediated endocytosis of NHE3 is unclear. A pool of NHE3 resides in lipid rafts, which contributes to basal, but not cAMP-mediated, NHE3 trafficking, suggesting that an alternative mechanism exists for NHE3 endocytosis. Cdc42 was demonstrated to play an integral role in some cases of cholesterol-sensitive, clathrin-independent endocytosis. Therefore, the current study was designed to test the hypotheses that (1) clathrin-mediated endocytosis (CME) is involved in constitutive, but not CCH-mediated, endocytosis of NHE3, and (2) CCH-mediated endocytosis of NHE3 occurs through a lipid raft, activated Cdc42-dependent pathway that does not involve clathrin. The role of Cdc42 and lipid rafts on NHE3 activity and endocytosis were investigated in polarized Caco-2/BBe cells using pharmacological and shRNA knockdown approaches. Basal NHE3 activity was increased in the presence of CME blockers (chlorpromazine; K(+) depletion) supporting previous reports that constitutive NHE3 endocytosis is clathrin dependent. In contrast, CCH-inhibition of NHE3 activity was abolished in Caco-2/BBe cells treated with MβCD (to disrupt lipid rafts) as well as in Cdc42 knockdown cells but was unaffected by CME blockers. CCH-mediated inhibition of NHE3 activity is not dependent on clathrin and involves lipid rafts and requires Cdc42. © 2014 S. Karger AG, Basel.

Carbachol-Mediated Endocytosis of NHE3 Involves a Clathrin-Independent Mechanism Requiring Lipid Rafts and Cdc42

PubMed Central

Zachos, Nicholas C.; Alamelumangpuram, Bharath; Lee, Luke J.; Wang, Peng; Kovbasnjuk, Olga

2014-01-01

Background In intestinal epithelial cells, acute regulation of the brush border Na+/H+ exchanger, NHE3, usually occurs by changes in endocytosis and/or exocytosis. Constitutive NHE3 endocytosis involves clathrin. Carbachol (CCH), which elevates intracellular Ca2+ ([Ca2+]i), decreases NHE3 activity and stimulates endocytosis; however, the mechanism involved in calcium-mediated endocytosis of NHE3 is unclear. A pool of NHE3 resides in lipid rafts, which contributes to basal, but not cAMP-mediated, NHE3 trafficking, suggesting that an alternative mechanism exists for NHE3 endocytosis. Cdc42 was demonstrated to play an integral role in some cases of cholesterol-sensitive, clathrin-independent endocytosis. Therefore, the current study was designed to test the hypotheses that (1) clathrin-mediated endocytosis (CME) is involved in constitutive, but not CCH-mediated, endocytosis of NHE3, and (2) CCH-mediated endocytosis of NHE3 occurs through a lipid raft, activated Cdc42-dependent pathway that does not involve clathrin. Methods The role of Cdc42 and lipid rafts on NHE3 activity and endocytosis were investigated in polarized Caco-2/BBe cells using pharmacological and shRNA knockdown approaches. Results Basal NHE3 activity was increased in the presence of CME blockers (chlorpromazine; K+ depletion) supporting previous reports that constitutive NHE3 endocytosis is clathrin dependent. In contrast, CCH-inhibition of NHE3 activity was abolished in Caco-2/BBe cells treated with MβCD (to disrupt lipid rafts) as well as in Cdc42 knockdown cells but was unaffected by CME blockers. Conclusion CCH-mediated inhibition of NHE3 activity is not dependent on clathrin and involves lipid rafts and requires Cdc42. PMID:24713550

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.

Septation of infectious hyphae is critical for appressoria formation and virulence in the smut fungus Ustilago maydis.

PubMed

Freitag, Johannes; Lanver, Daniel; Böhmer, Christian; Schink, Kay Oliver; Bölker, Michael; Sandrock, Björn

2011-05-01

Differentiation of hyphae into specialized infection structures, known as appressoria, is a common feature of plant pathogenic fungi that penetrate the plant cuticle. Appressorium formation in U. maydis is triggered by environmental signals but the molecular mechanism of this hyphal differentiation is largely unknown. Infectious hyphae grow on the leaf surface by inserting regularly spaced retraction septa at the distal end of the tip cell leaving empty sections of collapsed hyphae behind. Here we show that formation of retraction septa is critical for appressorium formation and virulence in U. maydis. We demonstrate that the diaphanous-related formin Drf1 is necessary for actomyosin ring formation during septation of infectious hyphae. Drf1 acts as an effector of a Cdc42 GTPase signaling module, which also consists of the Cdc42-specific guanine nucleotide exchange factor Don1 and the Ste20-like kinase Don3. Deletion of drf1, don1 or don3 abolished formation of retraction septa resulting in reduced virulence. Appressorium formation in these mutants was not completely blocked but infection structures were found only at the tip of short filaments indicating that retraction septa are necessary for appressorium formation in extended infectious hyphae. In addition, appressoria of drf1 mutants penetrated the plant tissue less frequently.

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

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.

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.

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.

Diverged composition and regulation of the Trypanosoma brucei origin recognition complex that mediates DNA replication initiation

PubMed Central

Marques, Catarina A.; Tiengwe, Calvin; Lemgruber, Leandro; Damasceno, Jeziel D.; Scott, Alan; Paape, Daniel; Marcello, Lucio; McCulloch, Richard

2016-01-01

Abstract Initiation of DNA replication depends upon recognition of genomic sites, termed origins, by AAA+ ATPases. In prokaryotes a single factor binds each origin, whereas in eukaryotes this role is played by a six-protein origin recognition complex (ORC). Why eukaryotes evolved a multisubunit initiator, and the roles of each component, remains unclear. In Trypanosoma brucei, an ancient unicellular eukaryote, only one ORC-related initiator, TbORC1/CDC6, has been identified by sequence homology. Here we show that three TbORC1/CDC6-interacting factors also act in T. brucei nuclear DNA replication and demonstrate that TbORC1/CDC6 interacts in a high molecular complex in which a diverged Orc4 homologue and one replicative helicase subunit can also be found. Analysing the subcellular localization of four TbORC1/CDC6-interacting factors during the cell cycle reveals that one factor, TbORC1B, is not a static constituent of ORC but displays S-phase restricted nuclear localization and expression, suggesting it positively regulates replication. This work shows that ORC architecture and regulation are diverged features of DNA replication initiation in T. brucei, providing new insight into this key stage of eukaryotic genome copying. PMID:26951375

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 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

p21-Activated kinase (Pak) regulates airway smooth muscle contraction by regulating paxillin complexes that mediate actin polymerization.

PubMed

Zhang, Wenwu; Huang, Youliang; Gunst, Susan J

2016-09-01

In airway smooth muscle, tension development caused by a contractile stimulus requires phosphorylation of the 20 kDa myosin light chain (MLC), which activates crossbridge cycling and the polymerization of a pool of submembraneous actin. The p21-activated kinases (Paks) can regulate the contractility of smooth muscle and non-muscle cells, and there is evidence that this occurs through the regulation of MLC phosphorylation. We show that Pak has no effect on MLC phosphorylation during the contraction of airway smooth muscle, and that it regulates contraction by mediating actin polymerization. We find that Pak phosphorylates the adhesion junction protein, paxillin, on Ser273, which promotes the formation of a signalling complex that activates the small GTPase, cdc42, and the actin polymerization catalyst, neuronal Wiskott-Aldrich syndrome protein (N-WASP). These studies demonstrate a novel role for Pak in regulating the contractility of smooth muscle by regulating actin polymerization. The p21-activated kinases (Pak) can regulate contractility in smooth muscle and other cell and tissue types, but the mechanisms by which Paks regulate cell contractility are unclear. In airway smooth muscle, stimulus-induced contraction requires phosphorylation of the 20 kDa light chain of myosin, which activates crossbridge cycling, as well as the polymerization of a small pool of actin. The role of Pak in airway smooth muscle contraction was evaluated by inhibiting acetylcholine (ACh)-induced Pak activation through the expression of a kinase inactive mutant, Pak1 K299R, or by treating tissues with the Pak inhibitor, IPA3. Pak inhibition suppressed actin polymerization and contraction in response to ACh, but it did not affect myosin light chain phosphorylation. Pak activation induced paxillin phosphorylation on Ser273; the paxillin mutant, paxillin S273A, inhibited paxillin Ser273 phosphorylation and inhibited actin polymerization and contraction. Immunoprecipitation analysis of tissue extracts and proximity ligation assays in dissociated cells showed that Pak activation and paxillin Ser273 phosphorylation triggered the formation of an adhesion junction signalling complex with paxillin that included G-protein-coupled receptor kinase-interacting protein (GIT1) and the cdc42 guanine exchange factor, βPIX (Pak interactive exchange factor). Assembly of the Pak-GIT1-βPIX-paxillin complex was necessary for cdc42 and neuronal Wiskott-Aldrich syndrome protein (N-WASP) activation, actin polymerization and contraction in response to ACh. RhoA activation was also required for the recruitment of Pak to adhesion junctions, Pak activation, paxillin Ser273 phosphorylation and paxillin complex assembly. These studies demonstrate a novel role for Pak in the regulation of N-WASP activation, actin dynamics and cell contractility. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

p21‐Activated kinase (Pak) regulates airway smooth muscle contraction by regulating paxillin complexes that mediate actin polymerization

PubMed Central

Zhang, Wenwu; Huang, Youliang

2016-01-01

Key points In airway smooth muscle, tension development caused by a contractile stimulus requires phosphorylation of the 20 kDa myosin light chain (MLC), which activates crossbridge cycling and the polymerization of a pool of submembraneous actin.The p21‐activated kinases (Paks) can regulate the contractility of smooth muscle and non‐muscle cells, and there is evidence that this occurs through the regulation of MLC phosphorylation.We show that Pak has no effect on MLC phosphorylation during the contraction of airway smooth muscle, and that it regulates contraction by mediating actin polymerization.We find that Pak phosphorylates the adhesion junction protein, paxillin, on Ser273, which promotes the formation of a signalling complex that activates the small GTPase, cdc42, and the actin polymerization catalyst, neuronal Wiskott–Aldrich syndrome protein (N‐WASP).These studies demonstrate a novel role for Pak in regulating the contractility of smooth muscle by regulating actin polymerization. Abstract The p21‐activated kinases (Pak) can regulate contractility in smooth muscle and other cell and tissue types, but the mechanisms by which Paks regulate cell contractility are unclear. In airway smooth muscle, stimulus‐induced contraction requires phosphorylation of the 20 kDa light chain of myosin, which activates crossbridge cycling, as well as the polymerization of a small pool of actin. The role of Pak in airway smooth muscle contraction was evaluated by inhibiting acetylcholine (ACh)‐induced Pak activation through the expression of a kinase inactive mutant, Pak1 K299R, or by treating tissues with the Pak inhibitor, IPA3. Pak inhibition suppressed actin polymerization and contraction in response to ACh, but it did not affect myosin light chain phosphorylation. Pak activation induced paxillin phosphorylation on Ser273; the paxillin mutant, paxillin S273A, inhibited paxillin Ser273 phosphorylation and inhibited actin polymerization and contraction. Immunoprecipitation analysis of tissue extracts and proximity ligation assays in dissociated cells showed that Pak activation and paxillin Ser273 phosphorylation triggered the formation of an adhesion junction signalling complex with paxillin that included G‐protein‐coupled receptor kinase‐interacting protein (GIT1) and the cdc42 guanine exchange factor, βPIX (Pak interactive exchange factor). Assembly of the Pak–GIT1–βPIX–paxillin complex was necessary for cdc42 and neuronal Wiskott–Aldrich syndrome protein (N‐WASP) activation, actin polymerization and contraction in response to ACh. RhoA activation was also required for the recruitment of Pak to adhesion junctions, Pak activation, paxillin Ser273 phosphorylation and paxillin complex assembly. These studies demonstrate a novel role for Pak in the regulation of N‐WASP activation, actin dynamics and cell contractility. PMID:27038336

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

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

Evaluation of collection methods for Culex quinquefasciatus, Aedes aegypti, and Aedes simpsoni in northeastern Tanzania.

PubMed

Thornton, Jonathan Harold; Batengana, Bernard Malongo; Eiras, Alvaro Eduardo; Irish, Seth Robert

2016-12-01

In East Africa, significant morbidity and mortality are caused by infections spread by Culex quinquefasciatus and Aedes aegypti. Sticky traps have been shown to be effective tools for sampling populations of Aedes mosquitoes and have been found to catch Cx. quinquefasciatus. Thus, they could potentially be used to sample populations of this species. This study compared Sticky ovitraps (SO) and MosquiTraps (MQT) with the CDC Gravid trap (CDC-GT) for collection of Culex and Aedes mosquito populations in Tanzania. A follow-up experiment was carried out using traps set for a 24-h period to accommodate the oviposition habits of Aedes aegypti and Ae. simpsoni s.l. mosquitoes. The results showed that the CDC-GT caught significantly more Cx. quinquefasciatus and Ae. aegypti than the SO or MQT, but there was no significant difference in the number of mosquitoes caught between the two sticky traps or of Ae. simpsoni s.l. caught among the three trap types. The results suggest that CDC-GTs are the most appropriate in sampling of Cx. quinquefasciatus. Although CDC-GTs collected more Ae. aegypti than the sticky traps, the simplicity and cost benefit of sticky traps facilitates large scale studies. All three trap types should be considered for monitoring Aedes mosquitoes. © 2016 The Society for Vector Ecology.

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.

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.

Identification of a Novel, Putative Rho-specific GDP/GTP Exchange Factor and a RhoA-binding Protein: Control of Neuronal Morphology

PubMed Central

Gebbink, Martijn F.B.G.; Kranenburg, Onno; Poland, Mieke; van Horck, Francis P.G.; Houssa, Brahim; Moolenaar, Wouter H.

1997-01-01

The small GTP-binding protein Rho has been implicated in the control of neuronal morphology. In N1E-115 neuronal cells, the Rho-inactivating C3 toxin stimulates neurite outgrowth and prevents actomyosin-based neurite retraction and cell rounding induced by lysophosphatidic acid (LPA), sphingosine-1-phosphate, or thrombin acting on their cognate G protein–coupled receptors. We have identified a novel putative GDP/GTP exchange factor, RhoGEF (190 kD), that interacts with both wild-type and activated RhoA, but not with Rac or Cdc42. RhoGEF, like activated RhoA, mimics receptor stimulation in inducing cell rounding and in preventing neurite outgrowth. Furthermore, we have identified a 116-kD protein, p116Rip, that interacts with both the GDP- and GTP-bound forms of RhoA in N1E-115 cells. Overexpression of p116Rip stimulates cell flattening and neurite outgrowth in a similar way to dominant-negative RhoA and C3 toxin. Cells overexpressing p116Rip fail to change their shape in response to LPA, as is observed after Rho inactivation. Our results indicate that (a) RhoGEF may link G protein–coupled receptors to RhoA activation and ensuing neurite retraction and cell rounding; and (b) p116Rip inhibits RhoA-stimulated contractility and promotes neurite outgrowth. PMID:9199174

A High-Throughput Assay for Rho Guanine Nucleotide Exchange Factors Based on the Transcreener GDP Assay.

PubMed

Reichman, Melvin; Schabdach, Amanda; Kumar, Meera; Zielinski, Tom; Donover, Preston S; Laury-Kleintop, Lisa D; Lowery, Robert G

2015-12-01

Ras homologous (Rho) family GTPases act as molecular switches controlling cell growth, movement, and gene expression by cycling between inactive guanosine diphosphate (GDP)- and active guanosine triphosphate (GTP)-bound conformations. Guanine nucleotide exchange factors (GEFs) positively regulate Rho GTPases by accelerating GDP dissociation to allow formation of the active, GTP-bound complex. Rho proteins are directly involved in cancer pathways, especially cell migration and invasion, and inhibiting GEFs holds potential as a therapeutic strategy to diminish Rho-dependent oncogenesis. Methods for measuring GEF activity suitable for high-throughput screening (HTS) are limited. We developed a simple, generic biochemical assay method for measuring GEF activity based on the fact that GDP dissociation is generally the rate-limiting step in the Rho GTPase catalytic cycle, and thus addition of a GEF causes an increase in steady-state GTPase activity. We used the Transcreener GDP Assay, which relies on selective immunodetection of GDP, to measure the GEF-dependent stimulation of steady-state GTP hydrolysis by small GTPases using Dbs (Dbl's big sister) as a GEF for Cdc42, RhoA, and RhoB. The assay is well suited for HTS, with a homogenous format and far red fluorescence polarization (FP) readout, and it should be broadly applicable to diverse Rho GEF/GTPase pairs. © 2015 Society for Laboratory Automation and Screening.

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

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

PubMed Central

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

2004-01-01

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

[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.

Clinical outcomes and predictive factors related to good outcomes in plasma exchange in severe attack of NMOSD and long extensive transverse myelitis: Case series and review of the literature.

PubMed

Aungsumart, Saharat; Apiwattanakul, Metha

2017-04-01

To investigate the predictive factors associated with good outcomes of plasma exchange in severe attacks through neuromyelitis optica spectrum disorder (NMOSD) and long extensive transverse myelitis (LETM). In addition, to review the literature of predictive factors associated with the good outcomes of plasma exchange in central nervous system inflammatory demyelinating diseases (CNS IDDs). Retrospective study in 27 episodes of severe acute attacks myelitis and optic neuritis in 24 patients, including 20 patients with NMOSD seropositive, 1 patient with NMOSD seronegative and 3 patients with LETM. Plasma exchange was performed, reflecting poor responses to high-dose intravenous methylprednisolone (IVMP) therapy. The outcomes of the present study were the functional outcome improvements at 6 months after plasma exchange. The predictive factors of good outcomes after plasma exchange were determined in this cohort, and additional factors reported in the literature were reviewed. Plasma exchange was performed in 16 spinal cord attacks and 11 attacks of optic neuritis. Twenty patients were female (83%). The median age of the patients at the time of plasma exchange was 41 years old. The median disease duration was 0.6 years. The AQP4-IgG status was positive in 20 patients (83%). Plasma exchange following IVMP therapy led to a significant improvement in 81% of the cases after 6 months of follow up. A baseline Expanded Disability Status Scale (EDSS) score ≤6 before the attack was associated with significant improvement at 6 months (p=0.02, OR 58.33, 95%CI 1.92-1770). In addition, we reviewed the evidence for factors associated with good outcomes of plasma exchange in CNS IDDs, classified according to pre-plasma exchange, post-plasma exchange, and radiological features. Plasma exchange following IVMP therapy is effective as a treatment for patients experiencing a severe attack of NMOSD or LETM. The factors associated with good outcomes after plasma exchange in CNS IDDs are reviewed in the literature. We classified 3 different aspects, including pre-plasma exchange factors, based on minimal disability at baseline, preserved reflexes, early initiation, and short disease duration; post plasma exchange factors, including early improvement or lower disability at last follow up; and radiographic factors, for which the presence of active gadolinium lesions and the absence of spinal cord atrophy seem to be good outcomes for plasmapheresis. Copyright © 2017. Published by Elsevier B.V.

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.

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.

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

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.

Early Identification and Prevention of the Spread of Ebola - United States.

PubMed

Van Beneden, Chris A; Pietz, Harald; Kirkcaldy, Robert D; Koonin, Lisa M; Uyeki, Timothy M; Oster, Alexandra M; Levy, Deborah A; Glover, Maleeka; Arduino, Matthew J; Merlin, Toby L; Kuhar, David T; Kosmos, Christine; Bell, Beth P

2016-07-08

In response to the 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa, CDC prepared for the potential introduction of Ebola into the United States. The immediate goals were to rapidly identify and isolate any cases of Ebola, prevent transmission, and promote timely treatment of affected patients. CDC's technical expertise and the collaboration of multiple partners in state, local, and municipal public health departments; health care facilities; emergency medical services; and U.S. government agencies were essential to the domestic preparedness and response to the Ebola epidemic and relied on longstanding partnerships. CDC established a comprehensive response that included two new strategies: 1) active monitoring of travelers arriving from countries affected by Ebola and other persons at risk for Ebola and 2) a tiered system of hospital facility preparedness that enabled prioritization of training. CDC rapidly deployed a diagnostic assay for Ebola virus (EBOV) to public health laboratories. Guidance was developed to assist in evaluation of patients possibly infected with EBOV, for appropriate infection control, to support emergency responders, and for handling of infectious waste. CDC rapid response teams were formed to provide assistance within 24 hours to a health care facility managing a patient with Ebola. As a result of the collaborations to rapidly identify, isolate, and manage Ebola patients and the extensive preparations to prevent spread of EBOV, the United States is now better prepared to address the next global infectious disease threat.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).

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

Flight related tuberculosis contact investigations in the United States: comparative risk and economic analysis of alternate protocols.

PubMed

Marienau, Karen J; Cramer, Elaine H; Coleman, Margaret S; Marano, Nina; Cetron, Martin S

2014-01-01

In-flight transmission risk of Mycobacterium tuberculosis is not well defined, although studies suggest it is low. The impact of flight-related tuberculosis (TB) contact investigations (TBCIs) on TB prevention and control is not well established, and they compete for resources with activities with established benefits. We sought to determine the risks and cost-benefits of using more restrictive criteria in comparison to the Centers for Disease Control and Prevention (CDC) 2008 protocol for TBCIs. The risk-benefits of a modified CDC protocol were analyzed in comparison to the 2008 CDC protocol using data from flight-related TBCIs conducted in the United States from 2007 through 2009. We predicted the numbers and characteristics of case-travelers that would be identified using each protocol's criteria, and results of the associated passenger-contacts' TB screening tests. The economic analysis compared the costs of TBCIs to avoided costs of TB treatment and mortality using a Return on Investment model. The estimated in-flight transmission risk using a modified CDC protocol was 1.4%-19% versus 1.1%-24% for the 2008 protocol. Numbers of TBCIs and immediate costs to health departments were reduced by half. Long-term cost-benefits were comparable. CDC's modified protocol appears to be a feasible alternative that will conserve public health resources without jeopardizing the public's health. Published by Elsevier Ltd.

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.

Cryo-EM structure of a helicase loading intermediate containing ORC–Cdc6–Cdt1–MCM2-7 bound to DNA

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

Sun, Jingchuan; Evrin, Cecile; Samel, Stefan A.

2013-07-14

In eukaryotes, the Cdt1-bound replicative helicase core MCM2-7 is loaded onto DNA by the ORC–Cdc6 ATPase to form a prereplicative complex (pre-RC) with an MCM2-7 double hexamer encircling DNA. Using purified components in the presence of ATP-γS, we have captured in vitro an intermediate in pre-RC assembly that contains a complex between the ORC–Cdc6 and Cdt1–MCM2-7 heteroheptamers called the OCCM. Cryo-EM studies of this 14-subunit complex reveal that the two separate heptameric complexes are engaged extensively, with the ORC–Cdc6 N-terminal AAA+ domains latching onto the C-terminal AAA+ motor domains of the MCM2-7 hexamer. The conformation of ORC–Cdc6 undergoes a concertedmore » change into a right-handed spiral with helical symmetry that is identical to that of the DNA double helix. The resulting ORC–Cdc6 helicase loader shows a notable structural similarity to the replication factor C clamp loader, suggesting a conserved mechanism of action.« less

Cdc6-Induced Conformational Changes in ORC Bound to Origin DNA Revealed by Cryo-Electron Microscopy

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

Sun J.; Li H.; Kawakami, H.

2012-03-07

The eukaryotic origin recognition complex (ORC) interacts with and remodels origins of DNA replication prior to initiation in S phase. Here, we report a single-particle cryo-EM-derived structure of the supramolecular assembly comprising Saccharomyces cerevisiae ORC, the replication initiation factor Cdc6, and double-stranded ARS1 origin DNA in the presence of ATP{gamma}S. The six subunits of ORC are arranged as Orc1:Orc4:Orc5:Orc2:Orc3, with Orc6 binding to Orc2. Cdc6 binding changes the conformation of ORC, in particular reorienting the Orc1 N-terminal BAH domain. Segmentation of the 3D map of ORC-Cdc6 on DNA and docking with the crystal structure of the homologous archaeal Orc1/Cdc6 proteinmore » suggest an origin DNA binding model in which the DNA tracks along the interior surface of the crescent-like ORC. Thus, ORC bends and wraps the DNA. This model is consistent with the observation that binding of a single Cdc6 extends the ORC footprint on origin DNA from both ends.« less

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.

Experimental study on heat transfer performance of fin-tube exchanger and PSHE for waste heat recovery

NASA Astrophysics Data System (ADS)

Chen, Ting; Bae, Kyung Jin; Kwon, Oh Kyung

2018-02-01

In this paper, heat transfer characteristics of fin-tube heat exchanger and primary surface heat exchanger (PSHE) used in waste heat recovery were investigated experimentally. The flow in the fin-tube heat exchanger is cross flow and in PSHE counter flow. The variations of friction factor and Colburn j factor with air mass flow rate, and Nu number with Re number are presented. Various comparison methods are used to evaluate heat transfer performance, and the results show that the heat transfer rate of the PSHE is on average 17.3% larger than that of fin-tube heat exchanger when air mass flow rate is ranging from 1.24 to 3.45 kg/min. However, the PSHE causes higher pressure drop, and the fin-tube heat exchanger has a wider application range which leads to a 31.7% higher value of maximum heat transfer rate compared to that of the PSHE. Besides, under the same fan power per unit frontal surface, a higher heat transfer rate value is given in the fin-tube heat exchanger.

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.

Pattern of growth of very low birth weight preterm infants, assessed using the WHO Growth Standards, is associated with neurodevelopment.

PubMed

Nash, Andrea; Dunn, Michael; Asztalos, Elizabeth; Corey, Mary; Mulvihill-Jory, Bridget; O'Connor, Deborah L

2011-08-01

Several Canadian professional organizations recently recommended that the growth of preterm infants be monitored using the World Health Organization Growth Standards (WHO-GS) after hospital discharge. The WHO-GS are a prescriptive set of growth charts that describe how term infants should grow under ideal environmental conditions. Whether preterm infants following this pattern of growth have better outcomes than infants that do not has yet to be evaluated. Our aim was to determine whether the pattern of growth of very low birth weight (VLBW) infants during the first 2 years, assessed using the WHO-GS or the traditional Centers for Disease Control and Prevention reference growth charts (CDC-RGC), is associated with neurodevelopment. Pattern of weight, length, and head circumference gain of appropriate-for-gestation VLBW preterm infants (n = 289) from birth to 18-24 months corrected age was classified, using the WHO-GS and CDC-RGC, as sustained (change in Z-score ≤1 SD), decelerated (decline >1 SD), or accelerated (incline >1 SD). Development was assessed using the Bayley Scales of Infant and Toddler Development (BSID)-III at 18-24 months corrected age. Using the WHO-GS, children with a decelerated pattern of weight gain had lower cognitive (10 points), language (6 points), and motor (4 points) scores than infants with sustained weight gain (p < 0.05), even after adjustment for morbidities. No association was found using the CDC-RGC. In conclusion, a decelerated pattern of weight gain, determined with the WHO-GS, but not the CDC-GRC, is associated with poorer neurodevelopment scores on the BSID-III than a pattern of sustained growth.

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.

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.

Mangiferin induces cell cycle arrest at G2/M phase through ATR-Chk1 pathway in HL-60 leukemia cells.

PubMed

Peng, Z G; Yao, Y B; Yang, J; Tang, Y L; Huang, X

2015-05-12

This study aimed to determine the effect of mangiferin on the cell cycle in HL-60 leukemia cells and expression of the cell cycle-regulatory genes Wee1, Chk1 and CDC25C and to further investigate the molecular mechanisms of the antileukemic action of mangiferin. The inhibitory effect of mangiferin on HL-60 leukemia cell proliferation was determined by the MTT assay. The impact of mangiferin on the HL-60 cell cycle was evaluated by flow cytometry. After the cells were treated with different concentrations of mangiferin, the expression levels of Wee1, Chk1 and CDC25C mRNA were determined by RT-PCR, and Western blot was used to evaluate the expression levels of cdc25c, cyclin B1, and Akt proteins. The inhibition of HL-60 cell growth by mangiferin was dose- and time-dependent. After treatment for 24 h, cells in G2/M phase increased, and G2/M phase arrest appeared with increased mRNA expression of Wee1, Chk1 and CDC25C. Mangiferin inhibited Chk1 and cdc25c mRNA expression at high concentrations and induced Wee1 mRNA expression in a dose-dependent manner. It significantly inhibited ATR, Chk1, Wee1, Akt, and ERK1/2 phosphorylation but increased cdc2 and cyclin B1 phosphorylation. Furthermore, mangiferin reduced cdc25c, cyclin B1, and Akt protein levels while inducing Wee1 protein expression. It also antagonized the phosphorylation effect of vanadate on ATR, and the phosphorylation effect of EGF on Wee1. These findings indicated that mangiferin inhibits cell cycle progression through the ATR-Chk1 stress response DNA damage pathway, leading to cell cycle arrest at G2/M phase in leukemia cells.

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.

Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices

PubMed Central

Vellozzi, Claudia; Reingold, Arthur; Harris, Aaron; Haber, Penina; Ward, John W.; Nelson, Noele P.

2018-01-01

Summary Hepatitis B virus (HBV) is transmitted via blood or sexual contact. Persons with chronic HBV infection are at increased risk for cirrhosis and liver cancer and require medical care. This report updates and summarizes previously published recommendations from the Advisory Committee on Immunization Practices (ACIP) and CDC regarding the prevention of HBV infection in the United States. ACIP recommends testing all pregnant women for hepatitis B surface antigen (HBsAg), and testing HBsAg-positive pregnant women for hepatitis B virus deoxyribonucleic acid (HBV DNA); administration of HepB vaccine and hepatitis B immune globulin (HBIG) for infants born to HBV-infected women within 12 hours of birth, followed by completion of the vaccine series and postvaccination serologic testing; universal hepatitis B vaccination within 24 hours of birth, followed by completion of the vaccine series; and vaccination of children and adolescents aged <19 years who have not been vaccinated previously. ACIP recommends vaccination of adults at risk for HBV infection, including universal vaccination of adults in settings in which a high proportion have risk factors for HBV infection and vaccination of adults requesting protection from HBV without acknowledgment of a specific risk factor. These recommendations also provide CDC guidance for postexposure prophylaxis following occupational and other exposures. This report also briefly summarizes previously published American Association for the Study of Liver Diseasest guidelines for maternal antiviral therapy to reduce perinatal HBV transmission. PMID:29939980

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.

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.

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.

Thermal-hydraulic behavior of a mixed chevron single-pass plate-and-frame heat exchanger

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

Manglik, R.M.; Muley, A.

1995-12-31

Effective heat exchange is very critical for improving the process efficiency and operating economy of chemical and process plants. Here, experimental friction factor and heat transfer data for single-phase water flows in a plate-and-frame heat exchanger are presented. A mixed chevron plate arrangement with {beta} = 30{degree}/60{degree} in a single-pass U-type, counterflow configuration is employed. The friction factor and heat transfer data are for isothermal flow and cooling conditions, respectively, and the flow rates correspond to transition and turbulent flow regimes (300 < Re < 6,000 and 2.4 < Pr < 4.5). Based on these data, Nusselt number and frictionmore » factor correlations for fully developed turbulent flows (Re {ge} 1,000) are presented. The results highlight the effects of {beta} on the thermal-hydraulic performance, transition to turbulent flows, and the relative impact of using symmetric or mixed chevron plate arrangements.« less

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.

Clostridium difficile colonization and disease in patients undergoing hematopoietic stem cell transplantation.

PubMed

Bruminhent, Jackrapong; Wang, Zi-Xuan; Hu, Carol; Wagner, John; Sunday, Richard; Bobik, Brent; Hegarty, Sarah; Keith, Scott; Alpdogan, Seyfettin; Carabasi, Matthew; Filicko-O'Hara, Joanne; Flomenberg, Neal; Kasner, Margaret; Outschoorn, Ubaldo Martinez; Weiss, Mark; Flomenberg, Phyllis

2014-09-01

There was an increase in the Clostridium difficile infection (CDI) rate in our bone marrow transplantation unit. To evaluate the role of unit-based transmission, C. difficile screening was performed on adult patients admitted for hematopoietic stem cell transplantation (HSCT) over a 2-year period, and C. difficile isolates were typed. C. difficile testing was performed using a 2-step C. difficile glutamate dehydrogenase antigen plus toxin A/B enzyme immunoassay (EIA) and cytotoxin assay (or molecular toxin assay). Multilocus sequence typing (MLST) was performed on toxin-positive whole stool samples. A retrospective chart review was performed on all patients with a positive toxin assay. Sixteen of 150 patients (10.7%) had toxigenic C. difficile colonization (CDC) on admission. The overall incidence of CDI within 100 days after HSCT was 24.7% (37 of 150). The median time to diagnosis of CDI was 3.5 days after HSCT. In an adjusted logistic regression model, CDC on admission was a significant risk factor for CDI (odds ratio, 68.5; 95% confidence interval, 11.4 to 416.2). MLST on 22 unit patient toxin-positive stool specimens revealed 15 distinct strain types. Further analysis identified at least 1 potential cross-transmission event; some events may have been missed because of incomplete typing from other specimens. Despite aggressive infection control interventions, there was no decline in the number of CDI cases during the study period. These data suggest that prior CDC plays a major role in CDI rates in this high-risk patient population. It remains unclear if CDI was cross-transmitted in the unit. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Cyclic stretch-induced the cytoskeleton rearrangement and gene expression of cytoskeletal regulators in human periodontal ligament cells.

PubMed

Wu, Yaqin; Zhuang, Jiabao; Zhao, Dan; Zhang, Fuqiang; Ma, Jiayin; Xu, Chun

2017-10-01

This study aimed to explore the mechanism of the stretch-induced cell realignment and cytoskeletal rearrangement by identifying several mechanoresponsive genes related to cytoskeletal regulators in human PDL cells. After the cells were stretched by 1, 10 and 20% strains for 0.5, 1, 2, 4, 6, 12 or 24 h, the changes of the morphology and content of microfilaments were recorded and calculated. Meanwhile, the expression of 84 key genes encoding cytoskeletal regulators after 6 and 24 h stretches with 20% strain was detected by using real-time PCR array. Western blot was applied to identify the protein expression level of several cytoskeletal regulators encoded by these differentially expressed genes. The confocal fluorescent staining results confirmed that stretch-induced realignment of cells and rearrangement of microfilaments. Among the 84 genes screened, one gene was up-regulated while two genes were down-regulated after 6 h stretch. Meanwhile, three genes were up-regulated while two genes were down-regulated after 24 h stretch. These genes displaying differential expression included genes regulating polymerization/depolymerization of microfilaments (CDC42EP2, FNBP1L, NCK2, PIKFYVE, WASL), polymerization/depolymerization of microtubules (STMN1), interacting between microfilaments and microtubules (MACF1), as well as a phosphatase (PPP1R12B). Among the proteins encoded by these genes, the protein expression level of Cdc42 effector protein-2 (encoded by CDC42EP2) and Stathmin-1 (encoded by STMN1) was down-regulated, while the protein expression level of N-WASP (encoded by WASL) was up-regulated. The present study confirmed the cyclic stretch-induced cellular realignment and rearrangement of microfilaments in the human PDL cells and indicated several force-sensitive genes with regard to cytoskeletal regulators.

Self-reported discrimination and health-related quality of life among Whites, Blacks, Mexicans and Central Americans.

PubMed

Otiniano, Angie Denisse; Gee, Gilbert C

2012-04-01

This study investigates whether self-reported racial discrimination is related to poor health-related quality of life (HRQoL). Analyses focused on Whites (n = 52,571), Blacks (n = 4,343), Mexicans (n = 12,336), Central Americans (n = 1,504), Multi-ethnic Latinos (n = 1,102), and Other Latinos (n = 1,828) who participated in the 2003 and 2005 California Health Interview survey. Logistic and negative binomial regression was used to examine the association between HRQoL (assessed with the CDC unhealthy days measures) and self-reported racial discrimination. Discrimination was reported by 10% of Whites, 57% of Blacks, and 24-31% of the Latino groups. These reports were associated with increased number of unhealthy days, disability days, and poor self-rated health, even after, controlling for education and other factors. This association did not consistently vary by race/ethnicity. Racial discrimination may be a risk factor for poor HRQoL among diverse groups. Future research should examine the factors that may reduce potential exposure to racial discrimination.

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.

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

PubMed

Laufer, Christin B; Carroll, Matthew B

2015-10-01

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

40 CFR 141.154 - Required additional health information.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 24 2012-07-01 2012-07-01 false Required additional health information... Required additional health information. (a) All reports must prominently display the following language... from their health care providers. EPA/CDC guidelines on appropriate means to lessen the risk of...

40 CFR 141.154 - Required additional health information.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 24 2013-07-01 2013-07-01 false Required additional health information... Required additional health information. (a) All reports must prominently display the following language... from their health care providers. EPA/CDC guidelines on appropriate means to lessen the risk of...

Profiles of Global Gene Expression in Ionizing-Radiation–Damaged Human Diploid Fibroblasts Reveal Synchronization behind the G1 Checkpoint in a G0-like State of Quiescence

PubMed Central

Zhou, Tong; Chou, Jeff W.; Simpson, Dennis A.; Zhou, Yingchun; Mullen, Thomas E.; Medeiros, Margarida; Bushel, Pierre R.; Paules, Richard S.; Yang, Xuebin; Hurban, Patrick; Lobenhofer, Edward K.; Kaufmann, William K.

2006-01-01

Cell cycle arrest and stereotypic transcriptional responses to DNA damage induced by ionizing radiation (IR) were quantified in telomerase-expressing human diploid fibroblasts. Analysis of cytotoxicity demonstrated that 1.5 Gy IR inactivated colony formation by 40–45% in three fibroblast lines; this dose was used in all subsequent analyses. Fibroblasts exhibited > 90% arrest of progression from G2 to M at 2 hr post-IR and a similarly severe arrest of progression from G1 to S at 6 and 12 hr post-IR. Normal rates of DNA synthesis and mitosis 6 and 12 hr post-IR caused the S and M compartments to empty by > 70% at 24 hr. Global gene expression was analyzed in IR-treated cells. A microarray analysis algorithm, EPIG, identified nine IR-responsive patterns of gene expression that were common to the three fibroblast lines, including a dominant p53-dependent G1 checkpoint response. Many p53 target genes, such as CDKN1A, GADD45, BTG2, and PLK3, were significantly up-regulated at 2 hr post-IR. Many genes whose expression is regulated by E2F family transcription factors, including CDK2, CCNE1, CDC6, CDC2, MCM2, were significantly down-regulated at 24 hr post-IR. Numerous genes that participate in DNA metabolism were also markedly repressed in arrested fibroblasts apparently as a result of cell synchronization behind the G1 checkpoint. However, cluster and principal component analyses of gene expression revealed a profile 24 hr post-IR with similarity to that of G0 growth quiescence. The results reveal a highly stereotypic pattern of response to IR in human diploid fibroblasts that reflects primarily synchronization behind the G1 checkpoint but with prominent induction of additional markers of G0 quiescence such as GAS1. PMID:16581545

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.

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.

17 CFR 5.24 - Applicability of other parts of this chapter

Code of Federal Regulations, 2011 CFR

2011-04-01

... 17 Commodity and Securities Exchanges 1 2011-04-01 2011-04-01 false Applicability of other parts of this chapter 5.24 Section 5.24 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION OFF-EXCHANGE FOREIGN CURRENCY TRANSACTIONS § 5.24 Applicability of other parts of this chapter...

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

Origin Licensing Requires ATP Binding and Hydrolysis by the MCM Replicative Helicase

PubMed Central

Coster, Gideon; Frigola, Jordi; Beuron, Fabienne; Morris, Edward P.; Diffley, John F.X.

2014-01-01

Summary Loading of the six related Minichromosome Maintenance (MCM) proteins as head-to-head double hexamers during DNA replication origin licensing is crucial for ensuring once-per-cell-cycle DNA replication in eukaryotic cells. Assembly of these prereplicative complexes (pre-RCs) requires the Origin Recognition Complex (ORC), Cdc6, and Cdt1. ORC, Cdc6, and MCM are members of the AAA+ family of ATPases, and pre-RC assembly requires ATP hydrolysis. Here we show that ORC and Cdc6 mutants defective in ATP hydrolysis are competent for origin licensing. However, ATP hydrolysis by Cdc6 is required to release nonproductive licensing intermediates. We show that ATP binding stabilizes the wild-type MCM hexamer. Moreover, by analyzing MCM containing mutant subunits, we show that ATP binding and hydrolysis by MCM are required for Cdt1 release and double hexamer formation. This work alters our view of how ATP is used by licensing factors to assemble pre-RCs. PMID:25087873

Weak ferromagnetic order breaking the threefold rotational symmetry of the underlying kagome lattice in CdC u3(OH) 6(NO3)2.H2O

NASA Astrophysics Data System (ADS)

Okuma, Ryutaro; Yajima, Takeshi; Nishio-Hamane, Daisuke; Okubo, Tsuyoshi; Hiroi, Zenji

2017-03-01

Novel magnetic phases are expected to occur in highly frustrated spin systems. Here, we study the structurally perfect kagome antiferromagnet CdC u3(OH) 6(NO3)2.H2O by magnetization, magnetic torque, and heat capacity measurements using single crystals. An antiferromagnetic order accompanied by a small spontaneous magnetization that surprisingly is confined in the kagome plane sets in at TN˜4 K , well below the nearest-neighbor exchange interaction J /kB=45 K . This suggests that a unique "q =0 " type 120∘ spin structure with "negative" (downward) vector chirality, which breaks the underlying threefold rotational symmetry of the kagome lattice and thus allows a spin canting within the plane, is exceptionally realized in this compound rather than a common one with "positive" (upward) vector chirality. The origin is discussed in terms of the Dzyaloshinskii-Moriya interaction.

ECT2 and RASAL2 mediate mesenchymal-amoeboid transition in human astrocytoma cells.

PubMed

Weeks, Adrienne; Okolowsky, Nadia; Golbourn, Brian; Ivanchuk, Stacey; Smith, Christian; Rutka, James T

2012-08-01

Malignant astrocytomas are highly invasive brain tumors. The Rho family of cytoskeletal GTPases are key regulators of astrocytoma migration and invasion; expression of the guanine nucleotide exchange factor ECT2 is elevated in primary astrocytomas and predicts both survival and malignancy. Mice bearing orthotopically implanted astrocytoma cells with diminished ECT2 levels following ECT2 knockdown exhibit longer survival. Although ECT2 is normally expressed in the nucleus, we show that ECT2 is aberrantly localized to the cytoplasm in both astrocytoma cell lines and primary human astrocytomas, and colocalizes with RAC1 and CDC42 at the leading edge of migrating astrocytoma cells. Inhibition of ECT2 expression by RNA interference resulted in decreased RAC1 and CDC42 activity, but no change in RHO activity, suggesting that ECT2 is capable of activating these pro-migratory Rho family members. ECT2 overexpression in astrocytoma cells resulted in a transition to an amoeboid phenotype that was abolished with the ROCK inhibitor, Y-27632. Cytoplasmic fractionation of astrocytoma cells followed by ECT2 immunoprecipitation and mass spectrometry were used to identify protein-binding partners that modulate the activity of ECT2 toward RAC1 and RHO/ROCK. We identified RASAL2 as an ECT2-interacting protein that regulates RHO activity in astrocytoma cells. RASAL2 knockdown leads to a conversion to an amoeboid phenotype. Our studies reveal that ECT2 has a novel role in mesenchymal-amoeboid transition in human astrocytoma cells. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Diagnostic doses and times for Phlebotomus papatasi and Lutzomyia longipalpis sand flies (Diptera: Psychodidae: Phlebotominae) using the CDC bottle bioassay to assess insecticide resistance.

PubMed

Denlinger, David S; Creswell, Joseph A; Anderson, J Laine; Reese, Conor K; Bernhardt, Scott A

2016-04-15

Insecticide resistance to synthetic chemical insecticides is a worldwide concern in phlebotomine sand flies (Diptera: Psychodidae), the vectors of Leishmania spp. parasites. The CDC bottle bioassay assesses resistance by testing populations against verified diagnostic doses and diagnostic times for an insecticide, but the assay has been used limitedly with sand flies. The objective of this study was to determine diagnostic doses and diagnostic times for laboratory Lutzomyia longipalpis (Lutz & Nieva) and Phlebotomus papatasi (Scopoli) to ten insecticides, including pyrethroids, organophosphates, carbamates, and DDT, that are used worldwide to control vectors. Bioassays were conducted in 1,000-ml glass bottles each containing 10-25 sand flies from laboratory colonies of L. longipalpis or P. papatasi. Four pyrethroids, three organophosphates, two carbamates and one organochlorine, were evaluated. A series of concentrations were tested for each insecticide, and four replicates were conducted for each concentration. Diagnostic doses were determined only during the exposure bioassay for the organophosphates and carbamates. For the pyrethroids and DDT, diagnostic doses were determined for both the exposure bioassay and after a 24-hour recovery period. Both species are highly susceptible to the carbamates as their diagnostic doses are under 7.0 μg/ml. Both species are also highly susceptible to DDT during the exposure assay as their diagnostic doses are 7.5 μg/ml, yet their diagnostic doses for the 24-h recovery period are 650.0 μg/ml for Lu. longipalpis and 470.0 μg/ml for P. papatasi. Diagnostic doses and diagnostic times can now be incorporated into vector management programs that use the CDC bottle bioassay to assess insecticide resistance in field populations of Lu. longipalpis and P. papatasi. These findings provide initial starting points for determining diagnostic doses and diagnostic times for other sand fly vector species and wild populations using the CDC bottle bioassay.

Ventriculostomy-associated infection: a new, standardized reporting definition and institutional experience.

PubMed

Gozal, Yair M; Farley, Chad W; Hanseman, Dennis J; Harwell, Daniel; Magner, Mark; Andaluz, Norberto; Shutter, Lori

2014-08-01

Shortcomings created by the lack of both a uniform definition of ventriculostomy-associated infection (VAI) and reporting standards have led to widely ranging infections rates (2-24%) whose significance is uncertain. We propose a standardized definition of VAI and a consistent reporting format compliant with Centers for Disease Control and Prevention (CDC) for device-related infections. Using those parameters to establish an infection-control surveillance program, we report our 4-year institutional VAI rates. In this prospective study covering ventriculostomy utilization (October 2006-December 2010), 498 patients had a total of 4,673 ventriculostomy days. By review of the literature and our institutional analysis, we defined VAI as a positive CSF culture in a patient with ventriculostomy catheter, plus one or more of the following (1) fever recorded >101.5 °F or (2) cerebrospinal fluid (CSF) glucose level, either <50 mg/dL or <50% of a serum glucose level drawn within 24 h of the CSF glucose. In a report format that is CDC compliant, rates of VAI are reported. Among our patients, the CDC-compliant infection rate was 2.14 per 1,000 ventriculostomy days. Of the 10 VAIs occurring in 498 patients during 4,673 ventriculostomy days, this 2.0% infection rate was lower than the previously reported 8.8% composite rates of VAI. Average duration of ventriculostomy was 9.4 days. Neither antibiotic-impregnated catheters nor periprocedural or prophylactic antibiotics were used. Our standardized VAI definition and CDC format seems promising toward facilitating future study and guideline development. Given our strict protocol of sterile catheter placement and care, and our institution's low 2.0% infection rates, we propose an infection-rate target of ≤5 per 1,000 device days. Our results suggest that the use of antibiotics or antibiotic-impregnated catheters is unwarranted--a positive given concerns of evolving anti-microbial resistance.

Postdischarge growth assessment in very low birth weight infants.

PubMed

Park, Joon-Sik; Han, Jungho; Shin, Jeong Eun; Lee, Soon Min; Eun, Ho Seon; Park, Min-Soo; Park, Kook-In; Namgung, Ran

2017-03-01

The goal of nutritional support for very-low-birth-weight (VLBW) infants from birth to term is to match the in utero growth rates; however, this is rarely achieved. We evaluated postdischarge growth patterns and growth failure in 81 Korean VLBW infants through a retrospective study. Weight and height were measured and calculated based on age percentile distribution every 3 months until age 24 months. Growth failure was defined as weight and height below the 10th percentile at 24 months. For the subgroup analysis, small-for-gestational age (SGA) and extremely low birth weight (ELBW) infants were evaluated. The growth patterns based on the Korean, World Health Organization (WHO), or Centers for Disease Control and Prevention (CDC) standard were serially compared over time. At postconception age (PCA) 40 weeks, 47 (58%) and 45 infants (55%) showed growth failure in terms of weight and height, respectively. At PCA 24 months, 20 infants (24%) showed growth failure for weight and 14 (18%) for height. Growth failure rates were higher for the SGA infants than for the appropriate-weight-for-gestational age infants at PCA 24 months ( P =0.045 for weight and P =0.038 for height). Growth failure rates were higher for the ELBW infants than for the non-ELBW infants at PCA 24 months ( P <0.001 for weight and P =0.003 for height). Significant differences were found among the WHO, CDC, and Korean standards ( P <0.001). Advancements in neonatal care have improved the catch-up growth of VLBW infants, but this is insufficient. Careful observation and aggressive interventions, especially in SGA and ELBW infants, are needed.

Using secure web services to visualize poison center data for nationwide biosurveillance: a case study.

PubMed

Savel, Thomas G; Bronstein, Alvin; Duck, William; Rhodes, M Barry; Lee, Brian; Stinn, John; Worthen, Katherine

2010-01-01

Real-time surveillance systems are valuable for timely response to public health emergencies. It has been challenging to leverage existing surveillance systems in state and local communities, and, using a centralized architecture, add new data sources and analytical capacity. Because this centralized model has proven to be difficult to maintain and enhance, the US Centers for Disease Control and Prevention (CDC) has been examining the ability to use a federated model based on secure web services architecture, with data stewardship remaining with the data provider. As a case study for this approach, the American Association of Poison Control Centers and the CDC extended an existing data warehouse via a secure web service, and shared aggregate clinical effects and case counts data by geographic region and time period. To visualize these data, CDC developed a web browser-based interface, Quicksilver, which leveraged the Google Maps API and Flot, a javascript plotting library. Two iterations of the NPDS web service were completed in 12 weeks. The visualization client, Quicksilver, was developed in four months. This implementation of web services combined with a visualization client represents incremental positive progress in transitioning national data sources like BioSense and NPDS to a federated data exchange model. Quicksilver effectively demonstrates how the use of secure web services in conjunction with a lightweight, rapidly deployed visualization client can easily integrate isolated data sources for biosurveillance.

Colorectal liver metastases: contrast agent diffusion coefficient for quantification of contrast enhancement heterogeneity at MR imaging.

PubMed

Jia, Guang; O'Dell, Craig; Heverhagen, Johannes T; Yang, Xiangyu; Liang, Jiachao; Jacko, Richard V; Sammet, Steffen; Pellas, Theodore; Cole, Patricia; Knopp, Michael V

2008-09-01

To describe and determine the reproducibility of a simplified model to quantitatively measure heterogeneous intralesion contrast agent diffusion in colorectal liver metastases. This HIPAA-compliant retrospective study received institutional review board approval, and written informed consent was obtained from 14 patients (mean age, 61 years +/- 9 [standard deviation]; range, 41-78 years), including 10 men (mean age, 65 years +/- 8; range, 47-78 years) and four women (mean age, 54 years +/- 9; range, 41-59 years), with colorectal liver metastases. Magnetic resonance (MR) imaging was performed twice (first baseline MR image [B(1)] and second baseline MR image [B(2)]) in a single target lesion prior to therapy. Dynamic contrast material-enhanced MR imaging was performed by using a saturation-recovery fast gradient-echo sequence. A simplified contrast agent diffusion model was proposed, and a contrast agent diffusion coefficient (CDC) was calculated. The reproducibility of the CDC measurement was evaluated by using the Bland-Altman plot and a linear regression model. The mean CDC was 0.22 mm(2)/sec (range, 0.01-0.73 mm(2)/sec) on B(1) and 0.24 mm(2)/sec (range, 0.01-0.71 mm(2)/sec) on B(2), with an intraclass correlation coefficient of 0.91 (P < .0001). Bland-Altman plot showed good agreement, with a mean difference in measurement pairs of 0.017 mm(2)/sec +/- 0.096. The slope from the linear regression model was 0.89 (95% confidence interval: 0.63, 1.15) and the intercept was 0.01 (95% confidence interval: -0.08, 0.09). The CDC enables a quantitative description of contrast enhancement heterogeneity in lesions. Given the high reproducibility of the CDC metric, CDC appears promising for further qualification as an imaging biomarker of change measurement in response assessment. http://radiology.rsnajnls.org/cgi/content/full/248/3/901/DC1. RSNA, 2008

FgBud3, a Rho4-Interacting Guanine Nucleotide Exchange Factor, Is Involved in Polarity Growth, Cell Division and Pathogenicity of Fusarium graminearum.

PubMed

Zhang, Chengkang; Luo, Zenghong; He, Dongdong; Su, Li; Yin, Hui; Wang, Guo; Liu, Hong; Rensing, Christopher; Wang, Zonghua

2018-01-01

Rho GTPases are signaling macromolecules that are associated with developmental progression and pathogenesis of Fusarium graminearum . Generally, enzymatic activities of Rho GTPases are regulated by Rho GTPase guanine nucleotide exchange factors (RhoGEFs). In this study, we identified a putative RhoGEF encoding gene ( FgBUD3 ) in F. graminearum database and proceeded further by using a functional genetic approach to generate FgBUD3 targeted gene deletion mutant. Phenotypic analysis results showed that the deletion of FgBUD3 caused severe reduction in growth of FgBUD3 mutant generated during this study. We also observed that the deletion of FgBUD3 completely abolished sexual reproduction and triggered the production of abnormal asexual spores with nearly no septum in ΔFgbud3 strain. Further results obtained from infection assays conducted during this research revealed that the FgBUD3 defective mutant lost its pathogenicity on wheat and hence, suggests FgBud3 plays an essential role in the pathogenicity of F. graminearum . Additional, results derived from yeast two-hybrid assays revealed that FgBud3 strongly interacted with FgRho4 compared to the interaction with FgRho2, FgRho3, and FgCdc42. Moreover, we found that FgBud3 interacted with both GTP-bound and GDP-bound form of FgRho4. From these results, we subsequently concluded that, the Rho4-interacting GEF protein FgBud3 crucially promotes vegetative growth, asexual and sexual development, cell division and pathogenicity in F. graminearum .

17 CFR 270.24b-2 - Filing copies of sales literature.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Filing copies of sales literature. 270.24b-2 Section 270.24b-2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... literature. Copies of material filed with the Commission for the sole purpose of complying with section 24(b...

17 CFR 270.24b-2 - Filing copies of sales literature.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Filing copies of sales literature. 270.24b-2 Section 270.24b-2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... literature. Copies of material filed with the Commission for the sole purpose of complying with section 24(b...

17 CFR 270.24b-2 - Filing copies of sales literature.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Filing copies of sales literature. 270.24b-2 Section 270.24b-2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... literature. Copies of material filed with the Commission for the sole purpose of complying with section 24(b...

17 CFR 270.24b-2 - Filing copies of sales literature.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Filing copies of sales literature. 270.24b-2 Section 270.24b-2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... literature. Copies of material filed with the Commission for the sole purpose of complying with section 24(b...

17 CFR 270.24b-2 - Filing copies of sales literature.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Filing copies of sales literature. 270.24b-2 Section 270.24b-2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... literature. Copies of material filed with the Commission for the sole purpose of complying with section 24(b...

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

In Vivo and In Vitro Suppression of Hepatocellular Carcinoma by EF24, a Curcumin Analog

PubMed Central

Wang, Luoluo; Tian, Lantian; Song, Ruipeng; Han, Tianwen; Pan, Shangha; Liu, Lianxin

2012-01-01

The synthetic compound 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24) is a potent analog of curcumin that exhibits enhanced biological activity and bioavailability without increasing toxicity. EF24 exerts antitumor activity by arresting the cell cycle and inducing apoptosis, suppressing many types of cancer cells in vitro. The antiproliferative and antiangiogenic properties of EF24 provide theoretical support for its development and application to liver cancers. We investigated the in vitro and in vivo activities of EF24 on liver cancer to better understand its therapeutic effects and mechanisms. EF24 induced significant apoptosis and G2/M-phase cell cycle arrest in mouse liver cancer cell lines, Hepa1-6 and H22. The expression levels of G2/M cell cycle regulating factors, cyclin B1 and Cdc2, were significantly decreased, pp53, p53, and p21 were significantly increased in EF24-treated cells. In addition, EF24 treatment significantly reduced Bcl-2 concomitant with an increase in Bax, enhanced the release of cytochrome c from the mitochondria into the cytosol, resulting in an upregulation of cleaved-caspase-3, which promoted poly (ADP-ribose) polymerase cleavage. EF24-treated cells also displayed decreases in phosphorylated Akt, phosphorylated extracellular signal-regulated kinase and vascular endothelial growth factor. Our in vitro protein expression data were confirmed in vivo using a subcutaneous hepatocellular carcinoma (HCC) tumor model. This mouse HCC model confirmed that total body weight was unchanged following EF24 treatment, although tumor weight was significantly decreased. Using an orthotopic HCC model, EF24 significantly reduced the liver/body weight ratio and relative tumor areas compared to the control group. In situ detection of apoptotic cells and quantification of Ki-67, a biomarker of cell proliferation, all indicated significant tumor suppression with EF24 treatment. These results suggest that EF24 exhibits anti-tumor activity on liver cancer cells via mitochondria-dependent apoptosis and inducing cell cycle arrest coupled with antiangiogenesis. The demonstrated activities of EF24 support its further evaluation as a treatment for human liver cancers. PMID:23118928

In vivo and in vitro suppression of hepatocellular carcinoma by EF24, a curcumin analog.

PubMed

Liu, Haitao; Liang, Yingjian; Wang, Luoluo; Tian, Lantian; Song, Ruipeng; Han, Tianwen; Pan, Shangha; Liu, Lianxin

2012-01-01

The synthetic compound 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24) is a potent analog of curcumin that exhibits enhanced biological activity and bioavailability without increasing toxicity. EF24 exerts antitumor activity by arresting the cell cycle and inducing apoptosis, suppressing many types of cancer cells in vitro. The antiproliferative and antiangiogenic properties of EF24 provide theoretical support for its development and application to liver cancers. We investigated the in vitro and in vivo activities of EF24 on liver cancer to better understand its therapeutic effects and mechanisms. EF24 induced significant apoptosis and G2/M-phase cell cycle arrest in mouse liver cancer cell lines, Hepa1-6 and H22. The expression levels of G2/M cell cycle regulating factors, cyclin B1 and Cdc2, were significantly decreased, pp53, p53, and p21 were significantly increased in EF24-treated cells. In addition, EF24 treatment significantly reduced Bcl-2 concomitant with an increase in Bax, enhanced the release of cytochrome c from the mitochondria into the cytosol, resulting in an upregulation of cleaved-caspase-3, which promoted poly (ADP-ribose) polymerase cleavage. EF24-treated cells also displayed decreases in phosphorylated Akt, phosphorylated extracellular signal-regulated kinase and vascular endothelial growth factor. Our in vitro protein expression data were confirmed in vivo using a subcutaneous hepatocellular carcinoma (HCC) tumor model. This mouse HCC model confirmed that total body weight was unchanged following EF24 treatment, although tumor weight was significantly decreased. Using an orthotopic HCC model, EF24 significantly reduced the liver/body weight ratio and relative tumor areas compared to the control group. In situ detection of apoptotic cells and quantification of Ki-67, a biomarker of cell proliferation, all indicated significant tumor suppression with EF24 treatment. These results suggest that EF24 exhibits anti-tumor activity on liver cancer cells via mitochondria-dependent apoptosis and inducing cell cycle arrest coupled with antiangiogenesis. The demonstrated activities of EF24 support its further evaluation as a treatment for human liver cancers.

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.

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.

Exchange Sex Among Persons Who Inject Drugs in the New York Metropolitan Area: The Importance of Local Context, Gender and Sexual Identity.

PubMed

Walters, Suzan M; Rivera, Alexis V; Reilly, Kathleen H; Anderson, Bridget J; Bolden, Barbara; Wogayehu, Afework; Neaigus, Alan; Braunstein, Sarah

2018-02-21

Exchanging sex for money or drugs is known to increase risk for HIV among persons who inject drugs (PWID). To better understand determinants of exchange sex among PWID we examined factors associated with exchange sex in the New York metropolitan area-defined as New York City (NYC), NY; Newark, NJ; and Long Island, NY-using data from the 2012 National HIV Behavioral Surveillance system cycle on injection drug use. Of the 1160 PWID in this analysis, 24% reported exchange sex, with differences in gender and sexual identity by location. In multivariable analysis gay/bisexual men, heterosexual women, and lesbian, gay, or bisexual (LGB) women were more likely to exchange sex compared to heterosexual men. Exchange sex was also associated with race/ethnicity, homelessness, incarceration, location, and non-injection crack and cocaine use. We find that heterosexual women and LGB women who injected drugs residing in Newark were more likely to report exchange sex compared to NYC. This study highlights how local conditions impact exchange sex.

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

PubMed

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

2016-01-01

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

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.

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.

Dbl oncogene expression in MCF-10 A epithelial cells disrupts mammary acinar architecture, induces EMT and angiogenic factor secretion

PubMed Central

Vanni, Cristina; Ognibene, Marzia; Finetti, Federica; Mancini, Patrizia; Cabodi, Sara; Segalerba, Daniela; Torrisi, Maria Rosaria; Donnini, Sandra; Bosco, Maria Carla; Varesio, Luigi; Eva, Alessandra

2015-01-01

The proteins of the Dbl family are guanine nucleotide exchange factors (GEFs) of Rho GTPases and are known to be involved in cell growth regulation. Alterations of the normal function of these proteins lead to pathological processes such as developmental disorders, neoplastic transformation, and tumor metastasis. We have previously demonstrated that expression of Dbl oncogene in lens epithelial cells modulates genes encoding proteins involved in epithelial-mesenchymal-transition (EMT) and induces angiogenesis in the lens. Our present study was undertaken to investigate the role of Dbl oncogene in epithelial cells transformation, providing new insights into carcinoma progression.To assess how Dbl oncogene can modulate EMT, cell migration, morphogenesis, and expression of pro-apoptotic and angiogenic factors we utilized bi- and 3-dimensional cultures of MCF-10 A cells. We show that upon Dbl expression MCF-10 A cells undergo EMT. In addition, we found that Dbl overexpression sustains Cdc42 and Rac activation inducing morphological alterations, characterized by the presence of lamellipodia and conferring a high migratory capacity to the cells. Moreover, Dbl expressing MCF-10 A cells form altered 3D structures and can induce angiogenesis by producing proangiogenic factors such as CCL2. These results support a role for Dbl oncogene in epithelial cell differentiation and transformation and suggest the relevance of GEF deregulation in tumor onset and progression. PMID:25723869

Evaluation of heterocyclic steroids and curcumin derivatives as anti-breast cancer agents: Studying the effect on apoptosis in MCF-7 breast cancer cells.

PubMed

Elmegeed, Gamal A; Yahya, Shaymaa M M; Abd-Elhalim, Mervat M; Mohamed, Mervat S; Mohareb, Rafat M; Elsayed, Ghada H

2016-11-01

Anticancer agents consisting of hybrid molecules are used to improve effectiveness and diminish drug resistance. The current study aimed to introduce newly synthesized hetero-steroids of promising anticancer effects. Besides, the pro-apoptotic effects of new compounds were investigated extensively. Several pyrimidino-, triazolopyrimidino-, pyridazino-, and curcumin-steroid derivatives were synthesized, elucidated and confirmed using the spectral and analytical data. The synthesized hetero-steroids, compounds 9, 10, 11, 12, 13, 14, 15, 18, 20, 21, 22 and 24, were tested for their cytotoxic effects versus human breast cancer cells (MCF-7) using neutral red supravital dye uptake assay. Compound 24 (IC50=18μM) showed more inhibitory influence on MCF-7 growth. Using QRT-PCR (Quantitative real time-polymerase chain reaction), CCND1, Survivin, BCL-2, CDC2, P21 and P53, genes expression levels were investigated. The study results disclose that compounds 4, 7, 18, 24 knocked down the expression levels of CCND1, Survivin, BCL-2 and CDC2. However, P21 and P53 were up-regulated by compounds 21, 22. This study introduced promising pro-apoptotic anticancer agents acting through the modulation of key regulators of apoptosis and cell cycle genes. Copyright © 2016 Elsevier Inc. All rights reserved.

HIV heterosexual transmission to stable sexual partners of HIV-infected Brazilian hemophiliacs.

PubMed

Nicolau, J E; Benard, G; Fonseca, L A; Casseb, J S; Sato, M N; Cianga, M; Tanji, M M; Lorenzi, T F; Duarte, A J

1996-01-01

Nineteen Brazilian HIV-infected hemophiliacs and their stable heterosexual sexual partners were studied with the aim of assessing the rate of HIV transmission in this at risk group. The mean length of relationship between couples was 7.4 years. The hemophiliac men were Class II (n = 6), III (n = 11) and IVa (n = 2) of the CDC classification. They had decreased CD4+ and elevated CD8+ cell numbers; five had p24 antigenemia. We found 3 HIV-infected women (15.8 percent) by routine and confirmatory tests, a prevalence similar to that seen in other countries. They were asymptomatic and had no detectable p24 antigenemia. The 3 seropositive women's partners were Class II and III-CDC, and had normal CD4+ and CD8+ values and no p24 antigenemia. All seronegative women also had normal CD4+ and CD8+ numbers, except for elevated CD8+ cells in three of them, but immune abnormalities had already been seen in some seronegative partners at high risk for HIV infection. Our results reinforce previous suggestions that heterosexual transmission to stable female partners occurs preferentially early after initiation of sexual exposure, and possibly when the transmitter had high levels of viremia and regular sexual activity.

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.

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.

Automotive Research Center

Science.gov Websites

7, 2018, LA Times) Dr. Jason Siegel to chair IEEE Technical Committee on Automotive Controls (Feb 2018, IEEE) Dr. Anna Stefanopoulou on research of sustainable vehicle technologies (Jan 24, 2018, WEMU ) Stefanopoulou plenary at IEEE 56th CDC (Jan 17, 2018, ME) ARC Researchers at IEEE 56th Conf. Decision and

Youth Risk Behavior Surveillance--United States, 1999. CDC Surveillance Summaries.

ERIC Educational Resources Information Center

MMWR: Morbidity and Morality Weekly Report, 2000

2000-01-01

In the United States, approximately three-fourths of all deaths among persons aged 10-24 years result from only four causes: motor-vehicle crashes, other unintentional injuries, homicide, and suicide. Results from this 1999 national Youth Risk Behavior Survey demonstrate that numerous high school students engage in behaviors that increase the…

Near Real-Time Surveillance of U.S. Norovirus Outbreaks by the Norovirus Sentinel Testing and Tracking Network - United States, August 2009-July 2015.

PubMed

Shah, Minesh P; Wikswo, Mary E; Barclay, Leslie; Kambhampati, Anita; Shioda, Kayoko; Parashar, Umesh D; Vinjé, Jan; Hall, Aron J

2017-02-24

Norovirus is the leading cause of endemic and epidemic acute gastroenteritis in the United States (1). New variant strains of norovirus GII.4 emerge every 2-4 years (2-4) and are often associated with increased disease and health care visits (5-7). Since 2009, CDC has obtained epidemiologic data on norovirus outbreaks from state health departments through the National Outbreak Reporting System (NORS) (8) and laboratory data through CaliciNet (9). NORS is a web-based platform for reporting waterborne, foodborne, and enteric disease outbreaks of all etiologies, including norovirus, to CDC. CaliciNet, a nationwide electronic surveillance system of local and state public health and regulatory agency laboratories, collects genetic sequences of norovirus strains associated with gastroenteritis outbreaks. Because these two independent reporting systems contain complementary data, integration of NORS and CaliciNet records could provide valuable public health information about norovirus outbreaks. However, reporting lags and inconsistent identification codes in NORS and CaliciNet records have been an obstacle to developing an integrated surveillance system.

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.

17 CFR 4.24 - General disclosures required.

Code of Federal Regulations, 2012 CFR

2012-04-01

... STATEMENT CANNOT DISCLOSE ALL THE RISKS AND OTHER FACTORS NECESSARY TO EVALUATE YOUR PARTICIPATION IN THIS... TREATED AS A COMMODITY CUSTOMER CLAIM FOR PURPOSES OF SUBCHAPTER IV OF CHAPTER 7 OF THE BANKRUPTCY CODE... and/or retail foreign exchange dealer by an introducing broker (such as payment for order flow or soft...

17 CFR 4.24 - General disclosures required.

Code of Federal Regulations, 2011 CFR

2011-04-01

... STATEMENT CANNOT DISCLOSE ALL THE RISKS AND OTHER FACTORS NECESSARY TO EVALUATE YOUR PARTICIPATION IN THIS... TREATED AS A COMMODITY CUSTOMER CLAIM FOR PURPOSES OF SUBCHAPTER IV OF CHAPTER 7 OF THE BANKRUPTCY CODE... and/or retail foreign exchange dealer by an introducing broker (such as payment for order flow or soft...

Conclusions about differences in linear growth between Bangladeshi boys and girls depend on the growth reference used.

PubMed

Moestue, H; de Pee, S; Hall, A; Hye, A; Sultana, N; Ishtiaque, M Z; Huq, N; Bloem, M W

2004-05-01

To examine sex differences in height-for-age z-scores and the percentage stunting among Bangladeshi children estimated using three growth references. Data collected between 1990 and 1999 by Helen Keller International's nutritional surveillance system in rural Bangladesh were analyzed for 504 358 children aged 6-59 months. Height-for-age z-scores were estimated using the 1977 NCHS, 2000 CDC and 1990 British growth references. The shape of the growth curves for Bangladeshi boys and girls, and their positions relative to one another, depend on which of the three growth references is used. At 6 months of age the British reference showed no sex difference whereas the NCHS and CDC showed girls to have higher average z-scores than boys by 0.14 and 0.28 s.d., respectively. While all references showed a faster deterioration of girls' z-scores from 6 to 24 months, the magnitude and direction of the sex differences, and how they changed with age, were different. There was greater disagreement about girls' z-scores than boys. Discontinuities at 24 months in the NCHS and CDC produced jagged curves whereas the British curves were smooth. The assessment of sex differences in linear growth depends on the growth reference used. Reasons for the different results need to be determined and may aid the final development of the new WHO international growth reference and the guidelines for its use. The findings suggest that anthropometry as a tool to explore the effects of societal gender inequality must be used with caution.

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

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.

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 ...

Highly tritiated water processing by isotopic exchange

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

Shu, W.M.; Willms, R.S.; Glugla, M.

2015-03-15

Highly tritiated water (HTW) is produced in fusion machines and one of the promising technologies to process it is isotopic exchange. 3 kinds of Pt-catalyzed zeolite (13X-APG, CBV-100-CY and HiSiv-1000) were tested as candidates for isotopic exchange of highly tritiated water (HTW), and CBV-100-CY (Na-Y type with a SiO{sub 2}/Al{sub 2}O{sub 3} ratio of ∼ 5.0) shows the best performance. Small-scale tritium testing indicates that this method is efficient for reaching an exchange factor (EF) of 100. Full-scale non-tritium testing implies that an EF of 300 can be achieved in 24 hours of operation if a temperature gradient is appliedmore » along the column. For the isotopic exchange, deuterium recycled from the Isotope Separation System (deuterium with 1% T and/or 200 ppm T) should be employed, and the tritiated water regenerated from the Pt-catalyzed zeolite bed after isotopic exchange should be transferred to Water Detritiation System (WDS) for further processing.« less

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.

Research management peer exchange hosted by the Oregon Department of Transportation, August 24-27, 2009.

DOT National Transportation Integrated Search

2009-08-01

The team began this peer exchange with a review of the most recent Oregon Peer Exchange conducted in : October 24-29, 2004. : The primary focus of the current peer exchange at Oregon DOT was Research Project Selection. : However, all aspects of the r...

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.

CDC Screening Recommendation for Baby Boomers and Hepatitis C Virus Testing in the US Military Health System.

PubMed

Manjelievskaia, Janna; Brown, Derek; Shriver, Craig D; Zhu, Kangmin

Chronic hepatitis C virus (HCV) is the most common blood-borne infection in the United States, with an estimated 2.7 to 3.9 million cases as of 2014. In August 2012, the Centers for Disease Control and Prevention (CDC) recommended 1-time HCV testing of all baby boomers. The objectives of this study were to (1) determine the proportion of people screened for HCV in the US Department of Defense Military Health System before and after the CDC screening recommendation for baby boomers and (2) assess whether certain patient or system factors were associated with screening for HCV before and after August 2012. We used a dataset containing 5% of beneficiaries randomly selected from the Military Health System Data Repository medical claims database for the period July 2011 through September 2013. Of 108 223 people eligible for HCV screening during the first period (July 2011 through July 2012), 1812 (1.7%) were screened. Of 109 768 people eligible during the second period (September 2012 through September 2013), 2599 (2.4%) were screened. HCV screening receipt was related to benefit type (Prime before August 2012: adjusted odds ratio [aOR] = 2.16; 95% confidence interval [CI], 1.89-2.46; Prime after August 2012: aOR = 1.93; 95% CI, 1.73-2.16) and care source (direct care before August 2012: aOR = 1.80; 95% CI, 1.57-2.07; direct care after August 2012: aOR = 2.45; 95% CI, 2.18-2.75); male sex (aOR = 1.17; 95% CI, 1.06-1.29) and black race (aOR = 1.20; 95% CI, 1.05-1.37) were associated with HCV testing only before August 2012. Interventions should be implemented to increase awareness and knowledge of the current national HCV testing recommendation among baby boomers to seek out testing and health care providers to perform screening.

Using Secure Web Services to Visualize Poison Center Data for Nationwide Biosurveillance: A Case Study

PubMed Central

Savel, Thomas G; Bronstein, Alvin; Duck, William; Rhodes, M. Barry; Lee, Brian; Stinn, John; Worthen, Katherine

2010-01-01

Objectives Real-time surveillance systems are valuable for timely response to public health emergencies. It has been challenging to leverage existing surveillance systems in state and local communities, and, using a centralized architecture, add new data sources and analytical capacity. Because this centralized model has proven to be difficult to maintain and enhance, the US Centers for Disease Control and Prevention (CDC) has been examining the ability to use a federated model based on secure web services architecture, with data stewardship remaining with the data provider. Methods As a case study for this approach, the American Association of Poison Control Centers and the CDC extended an existing data warehouse via a secure web service, and shared aggregate clinical effects and case counts data by geographic region and time period. To visualize these data, CDC developed a web browser-based interface, Quicksilver, which leveraged the Google Maps API and Flot, a javascript plotting library. Results Two iterations of the NPDS web service were completed in 12 weeks. The visualization client, Quicksilver, was developed in four months. Discussion This implementation of web services combined with a visualization client represents incremental positive progress in transitioning national data sources like BioSense and NPDS to a federated data exchange model. Conclusion Quicksilver effectively demonstrates how the use of secure web services in conjunction with a lightweight, rapidly deployed visualization client can easily integrate isolated data sources for biosurveillance. PMID:23569581

Coupling between p210bcr-abl and Shc and Grb2 adaptor proteins in hematopoietic cells permits growth factor receptor-independent link to ras activation pathway.

PubMed

Tauchi, T; Boswell, H S; Leibowitz, D; Broxmeyer, H E

1994-01-01

Enforced expression of p210bcr-abl transforms interleukin 3 (IL-3)-dependent hematopoietic cell lines to growth factor-independent proliferation. It has been demonstrated that nonreceptor tyrosine kinase oncogenes may couple to the p21ras pathway to exert their transforming effect. In particular, p210bcr-abl was recently found to effect p21ras activation in hematopoietic cells. In this context, experiments were performed to evaluate a protein signaling pathway by which p210bcr-abl might regulate p21ras. It was asked whether Shc p46/p52, a protein containing a src-homology region 2 (SH2) domain, and known to function upstream from p21ras, might form specific complexes with p210bcr-abl and thus, possibly alter p21ras activity by coupling to the guanine nucleotide exchange factor (Sos/CDC25) through the Grb2 protein-Sos complex. This latter complex has been previously demonstrated to occur ubiquitously. We found that p210bcr-abl formed a specific complex with Shc and with Grb2 in three different murine cell lines transfected with a p210bcr-abl expression vector. There appeared to be a higher order complex containing Shc, Grb2, and bcr-abl proteins. In contrast to p210bcr-abl transformed cells, in which there was constitutive tight association between Grb2 and Shc, binding between Grb2 and Shc was Steel factor (SLF)-dependent in a SLF-responsive, nontransformed parental cell line. The SLF-dependent association between Grb2 and Shc in nontransformed cells involved formation of a complex of Grb2 with c-kit receptor after SLF treatment. Thus, p210bcr-abl appears to function in a hematopoietic p21ras activation pathway to allow growth factor-independent coupling between Grb2, which exists in a complex with the guanine nucleotide exchange factor (Sos), and p21ras. Shc may not be required for Grb2-c-kit interaction, because it fails to bind strongly to c-kit.

[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.

17 CFR 270.8b-24 - Summaries or outlines of documents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Summaries or outlines of documents. 270.8b-24 Section 270.8b-24 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... statement shall be made, in succinct and condensed form, as to the most important provisions of the document...

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.

Social network-related risk factors for bloodborne virus infections among injection drug users receiving syringes through secondary exchange.

PubMed

De, Prithwish; Cox, Joseph; Boivin, Jean-François; Platt, Robert W; Jolly, Ann M

2008-01-01

Secondary syringe exchange (SSE) refers to the exchange of sterile syringes between injection drug users (IDUs). To date there has been limited examination of SSE in relation to the social networks of IDUs. This study aimed to identify characteristics of drug injecting networks associated with the receipt of syringes through SSE. Active IDUs were recruited from syringe exchange and methadone treatment programs in Montreal, Canada, between April 2004 and January 2005. Information on each participant and on their drug-injecting networks was elicited using a structured, interviewer-administered questionnaire. Subjects' network characteristics were examined in relation to SSE using regression models with generalized estimating equations. Of 218 participants, 126 were SSE recipients with 186 IDUs in their injecting networks. The 92 non-recipients reported 188 network IDUs. Networks of SSE recipients and non-recipients were similar with regard to network size and demographics of network members. In multivariate analyses adjusted for age and gender, SSE recipients were more likely than non-recipients to self-report being HIV-positive (OR=3.56 [1.54-8.23]); require or provide help with injecting (OR=3.74 [2.01-6.95]); have a social network member who is a sexual partner (OR=1.90 [1.11-3.24]), who currently attends a syringe exchange or methadone program (OR=2.33 [1.16-4.70]), injects daily (OR=1.77 [1.11-2.84]), and shares syringes with the subject (OR=2.24 [1.13-4.46]). SSE is associated with several injection-related risk factors that could be used to help focus public health interventions for risk reduction. Since SSE offers an opportunity for the dissemination of important prevention messages, SSE-based networks should be used to improve public health interventions. This approach can optimize the benefits of SSE while minimizing the potential risks associated with the practice of secondary exchange.

Aviation-Related Wildland Firefighter Fatalities--United States, 2000-2013.

PubMed

Butler, Corey R; O'Connor, Mary B; Lincoln, Jennifer M

2015-07-31

Airplanes and helicopters are integral to the management and suppression of wildfires, often operating in high-risk, low-altitude environments. To update data on aviation-related wildland firefighting fatalities, identify risk factors, and make recommendations for improved safety, CDC's National Institute for Occupational Safety and Health (NIOSH) analyzed reports from multiple data sources for the period 2000-2013. Among 298 wildland firefighter fatalities identified during 2000-2013, 78 (26.2%) were aviation-related occupational fatalities that occurred during 41 separate events involving 42 aircraft. Aircraft crashes accounted for 38 events. Pilots, copilots, and flight engineers represented 53 (68%) of the aviation-related fatalities. The leading causes of fatal aircraft crashes were engine, structure, or component failure (24%); pilot loss of control (24%); failure to maintain clearance from terrain, water, or objects (20%); and hazardous weather (15%). To reduce fatalities from aviation-related wildland firefighting activities, stringent safety guidelines need to be followed during all phases of firefighting, including training exercises. Crew resource management techniques, which use all available resources, information, equipment, and personnel to achieve safe and efficient flight operations, can be applied to firefighting operations.

Quantifying the risk of human Toxoplasma gondii infection due to consumption of fresh pork in the United States

USDA-ARS?s Scientific Manuscript database

Toxoplasma gondii is one of the leading foodborne pathogens in the United States. The Centers for Disease Control and Prevention (CDC) reported that T. gondii accounts for 24% of deaths due to foodborne illness in the United States. Consumption of undercooked pork products in which T. gondii has enc...

Tornado disaster--Kansas, 1991.

PubMed

1992-03-13

On April 26, 1991, 54 tornadoes swept across six midwestern states, causing 24 deaths and more than 200 injuries, requiring disaster-relief services for more than 8000 persons, and causing property damage of more than $250 million. In Kansas, one tornado, with wind speeds exceeding 260 mph, caused 17 deaths. The 46-mile path of the tornado led through Andover, Kansas (Butler County) (population: 4300), where the town's only outdoor warning siren failed. A mobile-home park (MHP) in Andover with 244 homes and one community storm shelter was struck by the tornado, resulting in the destruction of 205 (84%) of these homes. This report summarizes a poststorm survey, conducted by local health departments, the Kansas Department of Health and Environment, the American Red Cross, and CDC, to identify risk factors for injury and death among persons in the MHP.

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.

Ferromagnetism observed in silicon-carbide-derived carbon

NASA Astrophysics Data System (ADS)

Peng, Bo; Zhang, Yuming; Wang, Yutian; Guo, Hui; Yuan, Lei; Jia, Renxu

2018-02-01

Carbide-derived carbon (CDC) is prepared by etching high purity 4H-SiC single crystals in a mixed atmosphere of 5% Cl2 and 95% Ar for 120 min and 240 min. The secondary ion mass spectroscopy (SIMS) bulk analysis technique excludes the possibility of ferromagnetic transition metal (TM) contamination arising during the experimental process. The paramagnetic and ferromagnetic components are separated from the measured magnetization-magnetic field curves of the samples. Through the use of the Brillouin function, paramagnetic centers carrying a magnetic moment of ˜1.3 μB are fitted. A resolvable hysteresis loop in the low magnetic field area is preserved at room temperature. The temperature dependence of the relative intensity of the Lorentzian-like electron spin resonance (ESR) line observed by electron spin spectroscopy reveals the existence of exchange interaction between the localized paramagnetic centers. First-principles calculations show the dominant configuration of defects in the graphitic CDC films. By calculating the energy difference between the antiferromagnetic and ferromagnetic phases, we deduce that the ferromagnetic coupling is sensitive to the concentration of defects.

Suicide rates in China, 2004-2014: comparing data from two sample-based mortality surveillance systems.

PubMed

Sha, Feng; Chang, Qingsong; Law, Yik Wa; Hong, Qi; Yip, Paul S F

2018-02-13

The decreasing suicide rate in China has been regarded as a major contributor to the decline of global suicide rate in the past decade. However, previous estimations on China's suicide rates might not be accurate, since often they were based on the data from the Ministry of Health's Vital Registration ("MOH-VR") System, which is biased towards the better-off population. This study aims to compare suicide data extracted from the MOH-VR System with a more representative mortality surveillance system, namely the Center for Disease Control and Prevention's Disease Surveillance Points ("CDC-DSP") System, and update China's national and subnational suicide rates in the period of 2004-2014. The CDC-DSP data are obtained from the National Cause-of-Death Surveillance Dataset (2004-2014) and the MOH-VR data are from the Chinese Health Statistics Yearbooks (2005-2012) and the China Health and Family Planning Statistics Yearbooks (2013-2015). First, a negative binomial regression model was used to test the associations between the source of data (CDC-DSP/MOH-VR) and suicide rates in 2004-2014. Joinpoint regression analyses and Kitagawa's decomposition method are then applied to analyze the trends of the crude suicide rates. Both systems indicated China's suicide rates decreased over the study period. However, before the two systems merged in 2013, the CDC-DSP System reported significantly higher national suicide rates (IRR = 1.18, 95% Confidence Interval [CI]: 1.13-1.24) and rural suicide rates (IRR = 1.29, 95% CI: 1.21-1.38) than the MOH-VR System. The CDC-DSP System also showed significant reversing points in 2011 (95% CI: 2006-2012) and 2006 (95% CI: 2006-2008) on the rural and urban suicide trends. Moreover, the suicide rates in the east and central urban regions were reversed in 2011 and 2008. The biased MOH-VR System underestimated China's national and rural suicide rates. Although not widely appreciated in the field of suicide research, the CDC-DSP System provides more accurate estimations on China's suicide rates and is recommended for future studies to monitor the reversing trends of suicide rates in China's more developed areas.

Global gene expression analysis combined with a genomics approach for the identification of signal transduction networks involved in postnatal mouse myocardial proliferation and development.

PubMed

Wang, Ruoxin; Su, Chao; Wang, Xinting; Fu, Qiang; Gao, Xingjie; Zhang, Chunyan; Yang, Jie; Yang, Xi; Wei, Minxin

2018-01-01

Mammalian cardiomyocytes may permanently lose their ability to proliferate after birth. Therefore, studying the proliferation and growth arrest of cardiomyocytes during the postnatal period may enhance the current understanding regarding this molecular mechanism. The present study identified the differentially expressed genes in hearts obtained from 24 h‑old mice, which contain proliferative cardiomyocytes; 7‑day‑old mice, in which the cardiomyocytes are undergoing a proliferative burst; and 10‑week‑old mice, which contain growth‑arrested cardiomyocytes, using global gene expression analysis. Furthermore, myocardial proliferation and growth arrest were analyzed from numerous perspectives, including Gene Ontology annotation, cluster analysis, pathway enrichment and network construction. The results of a Gene Ontology analysis indicated that, with increasing age, enriched gene function was not only associated with cell cycle, cell division and mitosis, but was also associated with metabolic processes and protein synthesis. In the pathway analysis, 'cell cycle', proliferation pathways, such as the 'PI3K‑AKT signaling pathway', and 'metabolic pathways' were well represented. Notably, the cluster analysis revealed that bone morphogenetic protein (BMP)1, BMP10, cyclin E2, E2F transcription factor 1 and insulin like growth factor 1 exhibited increased expression in hearts obtained from 7‑day‑old mice. In addition, the signal transduction pathway associated with the cell cycle was identified. The present study primarily focused on genes with altered expression, including downregulated anaphase promoting complex subunit 1, cell division cycle (CDC20), cyclin dependent kinase 1, MYC proto-oncogene, bHLH transcription factor and CDC25C, and upregulated growth arrest and DNA damage inducible α in 10-week group, which may serve important roles in postnatal myocardial cell cycle arrest. In conclusion, these data may provide important information regarding myocardial proliferation and development.

The first 24 hours of the World Trade Center attacks of 2001--the Centers for Disease Control and Prevention emergency phase response.

PubMed

Cruz, Miguel A; Burger, Ronald; Keim, Mark

2007-01-01

On 11 September 2001, terrorists hijacked two passenger planes and crashed them into the two towers of the World Trade Center (WTC) in New York City. These synchronized attacks were the largest act of terrorism ever committed on US soil. The impacts, fires, and subsequent collapse of the towers killed and injured thousands of people. Within minutes after the first plane crashed into the WTC, the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, initiated one of the largest public health responses in its history. Staff of the CDC provided technical assistance on several key public health issues. During the acute phase of the event, CDC personnel assisted with: (1) assessing hospital capacity; (2) establishing injury and disease surveillance activities; (3) deploying emergency coordinators/liaisons to facilitate inter-agency coordination with the affected jurisdictions; and (4) arranging rapid delivery of emergency medical supplies, therapeutics, and personal protective equipment. This incident highlighted the need for adequate planning for all potential hazards and the importance of interagency and interdepartmental coordination in preparing for and responding to public health emergencies.

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 Climate Data Centre of Deutscher Wetterdienst (DWD)

NASA Astrophysics Data System (ADS)

Kaspar, F.; Schreiber, K.-J.; Behrendt, J.

2010-09-01

In 2009 the German meteorological service (Deutscher Wetterdienst, DWD) has started to set up a Climate Data Centre (CDC) in order to provide unified access to its variety of climate data especially to users from research, educational and public institutions. CDC acts as a central point of contact to various data collections of DWD. These include observations from German weather stations and DWD's observatories, special data as e.g. from hydroclimatology, agro-climatology and medical climatology, but also from international activities of DWD, such as the Global Precipitation Climatology Center (GPCC), EUMETSAT's Satellite Application Facility on Climate Monitoring (CM-SAF) or marine climatological data (ship and buoy observations) of the Global Collecting Centre for Marine Climatological Data. Data are based on conventional surface observations over land and ocean as well as on various remote sensing methods, such as satellite observation. The major part consists of climate data from the past, but CDC will also include results from scenario calculations and projections for the future. In addition to pure observational data, CDC offers derived statistical parameters and spatial analyses as gridded datasets. As first step, a central data catalogue provides standardised descriptions and information on data access. It follows national and international rules for the description of geo-referenced data (GDI-DE; INSPIRE). The individual data providers of DWD can use the catalogue to easily edit and publish their metadata in a unified way. These metadata contain information on data access, data policy, data quality, spatial and temporal coverage, responsible persons, etc. The catalogue is based on an open source software product (geonetwork-opensource) that is also used by a large number of international organizations. Metadata can be exchanged (harvested) between these catalogues. This will allow implementing a structure that provides search capabilities over institutions. The software also allows implementing web-based mapping services and group-specific data access policies.

Field evaluation of four widely used mosquito traps in Central Europe

PubMed Central

2014-01-01

Background To monitor adult mosquitoes several trapping devices are available. These are differently constructed and use various mechanisms for mosquito attraction, thus resulting in different trapping sensitivities and efficacies for the various species. Mosquito monitoring and surveillance programs in Europe use various types of mosquito traps, but only a few comparisons have been conducted so far. This study compared the performance of four commercial trapping devices, which are commonly used in Europe. Methods Four different traps, Biogents Sentinel trap (BG trap), Heavy Duty Encephalitis Vector Survey trap (EVS trap), Centres for Disease Control miniature light trap (CDC trap) and Mosquito Magnet Patriot Mosquito trap (MM trap) were compared in a 4 × 4 latin square study. In the years 2012 and 2013, more than seventy 24-hour trap comparisons were conducted at ten different locations in northern and southern Germany, representing urban, forest and floodplain biotopes. Results Per 24-hour trapping period, the BG trap caught the widest range of mosquito species, the highest number of individuals of the genus Culex as well as the highest number of individuals of the species Ochlerotatus cantans, Aedes cinereus/geminus, Oc. communis and Culex pipiens/torrentium. The CDC trap revealed best performance for Aedes vexans, whereas the MM trap was most efficient for mosquitoes of the genus Anopheles and the species Oc. geniculatus. The EVS trap did not catch more individuals of any genus or species compared to the other three trapping devices. The BG trap caught the highest number of individuals per trapping period in urban environments as well as in wet forest, while the CDC trap caught the highest number of individuals in the floodplain biotopes. Additionally, the BG trap was most efficient for the number of mosquito species in urban locations. Conclusion The BG trap showed a significantly better or similar performance compared to the CDC, EVS or MM trap with regard to trapping efficacy for most common mosquito species in Germany, including diversity of mosquito species and number of mosquitoes per trapping period. Thus, the BG trap is probably the best solution for general monitoring or surveillance programs of adult mosquitoes in Central Europe. PMID:24924481

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.

Characteristics associated with regional health information organization viability.

PubMed

Adler-Milstein, Julia; Landefeld, John; Jha, Ashish K

2010-01-01

Regional Health Information Organizations (RHIOs) will likely play a key role in our nation's effort to catalyze health information exchange. Yet we know little about why some efforts succeed while others fail. We sought to identify factors associated with RHIO viability. Using data from a national survey of RHIOs that we conducted in mid-2008, we examined factors associated with becoming operational and factors associated with financial viability. We used multivariate logistic regression models to identify unique predictors. We classified RHIOs actively facilitating data exchange as operational and measured financial viability as the percent of operating costs covered by revenue from participants in data exchange (0-24%, 25-74%, 75-100%). Predictors included breadth of participants, breadth of data exchanged, whether the RHIO focused on a specific population, whether RHIO participants had a history of collaborating, and sources of revenue during the planning phase. Exchanging a narrow set of data and involving a broad group of stakeholders were independently associated with a higher likelihood of being operational. Involving hospitals and ambulatory physicians, and securing early funding from participants were associated with a higher likelihood of financial viability, while early grant funding seemed to diminish the likelihood. Finding ways to help RHIOs become operational and self-sustaining will bolster the current approach to nationwide health information exchange. Our work suggests that convening a broad coalition of stakeholders to focus on a narrow set of data is an important step in helping RHIOs become operational. Convincing stakeholders to financially commit early in the process may help RHIOs become self-sustaining.

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).

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.

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

Study of blood pressure and blood sugar levels in adolescence and comparison with body mass index.

PubMed

Borade, Ashwin; Kadam, Gauri Shashank; Bhide, Gayatri; Dhongade, Ram

2011-07-01

Worldwide prevalence of overweight and obesity is increasing and its consequences prompted the WHO to designate obesity as a global epidemic in 2002. Being overweight is a risk factor for significant illness, especially diabetes and hypertension in adult life. To study the blood pressure and blood sugar levels and lifestyle parameters in adolescence and comparison with body mass index. In a prospective case control study, out of the 1000 screened, a total of 200 adolescents were considered out of which 100 were with high body mass index (BMI) and the other 100 were with normal BMI. Height, weight, BMI, waist hip ratio (WHR), blood pressure (BP), BSL, and associated risk factors like physical activity, fast food consumption, and computer/television watching were measured and screened. 109 (54.5%) males and 91 (45.5%) females were included. Maximum number [90 (45%)] of adolescents screened were in the age group of 17-19 years, while 54 (27%) and 56 (28%) adolescents were in the age group of 10-13 years and 14-16 years, respectively. According to CDC charts 2000, prevalence of overweight was 24% which was double when compared to WHO charts 2007. There was significant difference in prevalence of obesity; according to CDC chart it was 26%, whereas according to WHO chart it was 39%. The difference in blood pressures between cases and controls as per both CDC and WHO charts was found to be statistically significant (P < 0.0001). Positive family history of hypertension has a highly significant correlation (P < 0.001) with BMI. Blood sugar level (BSL) was significantly higher in cases (high BMI) when compared to controls (normal BMI). The comparison of WHR in the study group showed highly significant correlation ( P < 0.0001) between cases and controls. The present study shows highly significant correlation of physical activity ( P < 0.0001) and fast food ( P < 0.05) between cases and controls, whereas there was no significant correlation of computer/television watching ( P > 0.05) with BMI. The adolescents seem to have become heavier owing to environmental influences on growth patterns. So, a consideration should be given to shift the cut-offs for overweight and obesity to higher BMI percentiles if recent growth charts are to be followed. Adolescents with a BMI above the 95 th percentile (obese) are most likely to have obesity-related health risks.

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.

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

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.

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

PubMed

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

2014-07-01

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

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

PubMed

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

1998-04-15

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

Health and Environment Linked for Information Exchange in Atlanta (HELIX-Atlanta): A Pilot Tracking System

NASA Technical Reports Server (NTRS)

Rickman, Doug; Shire, J.; Qualters, J.; Mitchell, K.; Pollard, S.; Rao, R.; Kajumba, N.; Quattrochi, D.; Estes, M., Jr.; Meyer, P.;

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.

Performance of the AMY central drift chamber in a high magnetic field

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

Ueno, Koji

1988-01-01

This note describes the design characteristics of the AMY central drift changer (CDC) and its performance during its operation for the first year since it was installed in the AMY solenoid on October 24, 1986. In general, the chamber has performed according to our original specifications, providing us with good efficiency and excellent spatial resolution. 5 figs.

Gauging Media Influence on Adolescent Suicide Rates

ERIC Educational Resources Information Center

Siegel, Darren; McCabe, Paul C.

2009-01-01

The "Morbidity and Mortality Weekly Report" published by the Centers for Disease Control (CDC) reported that in 2004, suicide was the third leading cause of death among 10- to 24-year olds and accounted for 4,599 deaths. From 2003 to 2004, suicide rates of females age 10-14 years and 15-19 years and males age 15-19 years increased significantly.…

Suicide Prevention for Counselors Working with Youth in Secondary and Post-Secondary School

ERIC Educational Resources Information Center

Wiley, Cindy

2012-01-01

According to the latest statistics, suicide is the 3rd leading cause of death in those aged 15-24 (CDC, 2010), when many are enrolled in secondary and post-secondary institutions. Because of such alarming statistics, the need for prevention education is great. However, many counselors and educators feel ill- equipped in prevention and intervention…

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: ...

Mutations in six nephrosis genes delineate a pathogenic pathway amenable to treatment.

PubMed

Ashraf, Shazia; Kudo, Hiroki; Rao, Jia; Kikuchi, Atsuo; Widmeier, Eugen; Lawson, Jennifer A; Tan, Weizhen; Hermle, Tobias; Warejko, Jillian K; Shril, Shirlee; Airik, Merlin; Jobst-Schwan, Tilman; Lovric, Svjetlana; Braun, Daniela A; Gee, Heon Yung; Schapiro, David; Majmundar, Amar J; Sadowski, Carolin E; Pabst, Werner L; Daga, Ankana; van der Ven, Amelie T; Schmidt, Johanna M; Low, Boon Chuan; Gupta, Anjali Bansal; Tripathi, Brajendra K; Wong, Jenny; Campbell, Kirk; Metcalfe, Kay; Schanze, Denny; Niihori, Tetsuya; Kaito, Hiroshi; Nozu, Kandai; Tsukaguchi, Hiroyasu; Tanaka, Ryojiro; Hamahira, Kiyoshi; Kobayashi, Yasuko; Takizawa, Takumi; Funayama, Ryo; Nakayama, Keiko; Aoki, Yoko; Kumagai, Naonori; Iijima, Kazumoto; Fehrenbach, Henry; Kari, Jameela A; El Desoky, Sherif; Jalalah, Sawsan; Bogdanovic, Radovan; Stajić, Nataša; Zappel, Hildegard; Rakhmetova, Assel; Wassmer, Sharon-Rose; Jungraithmayr, Therese; Strehlau, Juergen; Kumar, Aravind Selvin; Bagga, Arvind; Soliman, Neveen A; Mane, Shrikant M; Kaufman, Lewis; Lowy, Douglas R; Jairajpuri, Mohamad A; Lifton, Richard P; Pei, York; Zenker, Martin; Kure, Shigeo; Hildebrandt, Friedhelm

2018-05-17

No efficient treatment exists for nephrotic syndrome (NS), a frequent cause of chronic kidney disease. Here we show mutations in six different genes (MAGI2, TNS2, DLC1, CDK20, ITSN1, ITSN2) as causing NS in 17 families with partially treatment-sensitive NS (pTSNS). These proteins interact and we delineate their roles in Rho-like small GTPase (RLSG) activity, and demonstrate deficiency for mutants of pTSNS patients. We find that CDK20 regulates DLC1. Knockdown of MAGI2, DLC1, or CDK20 in cultured podocytes reduces migration rate. Treatment with dexamethasone abolishes RhoA activation by knockdown of DLC1 or CDK20 indicating that steroid treatment in patients with pTSNS and mutations in these genes is mediated by this RLSG module. Furthermore, we discover ITSN1 and ITSN2 as podocytic guanine nucleotide exchange factors for Cdc42. We generate Itsn2-L knockout mice that recapitulate the mild NS phenotype. We, thus, define a functional network of RhoA regulation, thereby revealing potential therapeutic targets.

T cell receptor-driven transendothelial migration of human effector memory CD4 T cells involves Vav, Rac and Myosin IIA

PubMed Central

Manes, Thomas D.; Pober, Jordan S.

2013-01-01

Human effector memory (EM) CD4 T cells may be recruited from the blood into a site of inflammation in response either to inflammatory chemokines displayed on or specific antigen presented by venular endothelial cells (ECs), designated as chemokine-driven or TCR-driven transendothelial migration (TEM), respectively. We have previously described differences in the morphological appearance of transmigrating T cells as well as in the molecules that mediate T cell-EC interactions distinguishing these two pathways. Here we report that TCR-driven TEM requires ZAP-70-dependent activation of a pathway involving Vav, Rac and myosin IIA. Chemokine-driven TEM also utilizes ZAP-70, albeit in a quantitatively and spatially different manner of activation, and is independent of Vav, Rac and mysosin IIA, depending instead on an as yet unidentified GTP exchange factor that activates Cdc42. The differential use of small Rho family GTPases to activate the cytoskeleton is consistent with the morphological differences observed in T cells that undergo TEM in response to these distinct recruitment signals. PMID:23420881

Why Sleep Matters-The Economic Costs of Insufficient Sleep: A Cross-Country Comparative Analysis.

PubMed

Hafner, Marco; Stepanek, Martin; Taylor, Jirka; Troxel, Wendy M; van Stolk, Christian

2017-01-01

The Centers for Disease Control and Prevention (CDC) in the United States has declared insufficient sleep a "public health problem." Indeed, according to a recent CDC study, more than a third of American adults are not getting enough sleep on a regular basis. However, insufficient sleep is not exclusively a US problem, and equally concerns other industrialised countries such as the United Kingdom, Japan, Germany, or Canada. According to some evidence, the proportion of people sleeping less than the recommended hours of sleep is rising and associated with lifestyle factors related to a modern 24/7 society, such as psychosocial stress, alcohol consumption, smoking, lack of physical activity and excessive electronic media use, among others. This is alarming as insufficient sleep has been found to be associated with a range of negative health and social outcomes, including success at school and in the labour market. Over the last few decades, for example, there has been growing evidence suggesting a strong association between short sleep duration and elevated mortality risks. Given the potential adverse effects of insufficient sleep on health, well-being and productivity, the consequences of sleep-deprivation have far-reaching economic consequences. Hence, in order to raise awareness of the scale of insufficient sleep as a public-health issue, comparative quantitative figures need to be provided for policy- and decision-makers, as well as recommendations and potential solutions that can help tackling the problem.

Why Sleep Matters—The Economic Costs of Insufficient Sleep

PubMed Central

Hafner, Marco; Stepanek, Martin; Taylor, Jirka; Troxel, Wendy M.; van Stolk, Christian

2017-01-01

Abstract The Centers for Disease Control and Prevention (CDC) in the United States has declared insufficient sleep a “public health problem.” Indeed, according to a recent CDC study, more than a third of American adults are not getting enough sleep on a regular basis. However, insufficient sleep is not exclusively a US problem, and equally concerns other industrialised countries such as the United Kingdom, Japan, Germany, or Canada. According to some evidence, the proportion of people sleeping less than the recommended hours of sleep is rising and associated with lifestyle factors related to a modern 24/7 society, such as psychosocial stress, alcohol consumption, smoking, lack of physical activity and excessive electronic media use, among others. This is alarming as insufficient sleep has been found to be associated with a range of negative health and social outcomes, including success at school and in the labour market. Over the last few decades, for example, there has been growing evidence suggesting a strong association between short sleep duration and elevated mortality risks. Given the potential adverse effects of insufficient sleep on health, well-being and productivity, the consequences of sleep-deprivation have far-reaching economic consequences. Hence, in order to raise awareness of the scale of insufficient sleep as a public-health issue, comparative quantitative figures need to be provided for policy- and decision-makers, as well as recommendations and potential solutions that can help tackling the problem. PMID:28983434

Dressing wear time after breast reconstruction: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background One of the major risk variables for surgical site infection is wound management. Understanding infection risk factors for breast operations is essential in order to develop infection-prevention strategies and improve surgical outcomes. The aim of this trial is to assess the influence of dressing wear time on surgical site infection rates and skin colonization. Patients’ perception at self-assessment will also be analyzed. Methods/Design This is a two-arm randomized controlled trial. Two hundred breast cancer patients undergoing immediate or delayed breast reconstruction will be prospectively enrolled. Patients will be randomly allocated to group I (dressing removed on postoperative day one) or group II (dressing removed on postoperative day six). Surgical site infections will be defined by standard criteria from the Centers for Disease Control and Prevention (CDC). Skin colonization will be assessed by culture of samples collected at predefined time points. Patients will score dressing wear time with regard to safety, comfort and convenience. Discussion The evidence to support dressing standards for breast surgery wounds is empiric and scarce. CDC recommends protecting, with a sterile dressing for 24 to 48 hours postoperatively, a primarily closed incision, but there is no recommendation to cover this kind of incision beyond 48 hours, or on the appropriate time to shower or bathe with an uncovered incision. The results of the ongoing trial may support standard recommendations regarding dressing wear time after breast reconstruction. Trial registration ClinicalTrials.gov identifier: http://NCT01148823. PMID:23432779

Injuries and Mass Casualty Events

MedlinePlus

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

Leptin Induces Sca-1+ Progenitor Cell Migration Enhancing Neointimal Lesions in Vessel-Injury Mouse Models

PubMed Central

Xie, Yao; Potter, Claire M.F.; Le Bras, Alexandra; Nowak, Witold N.; Gu, Wenduo; Bhaloo, Shirin Issa; Zhang, Zhongyi; Hu, Yanhua; Zhang, Li

2017-01-01

Objective— Leptin is an adipokine initially thought to be a metabolic factor. Recent publications have shown its roles in inflammation and vascular disease, to which Sca-1+ vascular progenitor cells within the vessel wall may contribute. We sought to elucidate the effects of leptin on Sca-1+ progenitor cells migration and neointimal formation and to understand the underlying mechanisms. Approach and Results— Sca-1+ progenitor cells from the vessel wall of Lepr+/+ and Lepr−/− mice were cultured and purified. The migration of Lepr+/+ Sca-1+ progenitor cells in vitro was markedly induced by leptin. Western blotting and kinase assays revealed that leptin induced the activation of phosphorylated signal transducer and activator of transcription 3, phosphorylated extracellular signal–regulated kinases 1/2, pFAK (phosphorylated focal adhesion kinase), and Rac1 (ras-related C3 botulinum toxin substrate 1)/Cdc42 (cell division control protein 42 homolog). In a mouse femoral artery guidewire injury model, an increased expression of leptin in both injured vessels and serum was observed 24 hours post-surgery. RFP (red fluorescent protein)-Sca-1+ progenitor cells in Matrigel were applied to the adventitia of the injured femoral artery. RFP+ cells were observed in the intima 24 hours post-surgery, subsequently increasing neointimal lesions at 2 weeks when compared with the arteries without seeded cells. This increase was reduced by pre-treatment of Sca-1+ cells with a leptin antagonist. Guidewire injury could only induce minor neointima in Lepr−/− mice 2 weeks post-surgery. However, transplantation of Lepr+/+ Sca-1+ progenitor cells into the adventitial side of injured artery in Lepr−/− mice significantly enhanced neointimal formation. Conclusions— Upregulation of leptin levels in both the vessel wall and the circulation after vessel injury promoted the migration of Sca-1+ progenitor cells via leptin receptor–dependent signal transducer and activator of transcription 3- Rac1/Cdc42-ERK (extracellular signal–regulated kinase)-FAK pathways, which enhanced neointimal formation. PMID:28935755

Leptin Induces Sca-1+ Progenitor Cell Migration Enhancing Neointimal Lesions in Vessel-Injury Mouse Models.

PubMed

Xie, Yao; Potter, Claire M F; Le Bras, Alexandra; Nowak, Witold N; Gu, Wenduo; Bhaloo, Shirin Issa; Zhang, Zhongyi; Hu, Yanhua; Zhang, Li; Xu, Qingbo

2017-11-01

Leptin is an adipokine initially thought to be a metabolic factor. Recent publications have shown its roles in inflammation and vascular disease, to which Sca-1 + vascular progenitor cells within the vessel wall may contribute. We sought to elucidate the effects of leptin on Sca-1 + progenitor cells migration and neointimal formation and to understand the underlying mechanisms. Sca-1 + progenitor cells from the vessel wall of Lepr +/+ and Lepr -/- mice were cultured and purified. The migration of Lepr +/+ Sca-1 + progenitor cells in vitro was markedly induced by leptin. Western blotting and kinase assays revealed that leptin induced the activation of phosphorylated signal transducer and activator of transcription 3, phosphorylated extracellular signal-regulated kinases 1/2, pFAK (phosphorylated focal adhesion kinase), and Rac1 (ras-related C3 botulinum toxin substrate 1)/Cdc42 (cell division control protein 42 homolog). In a mouse femoral artery guidewire injury model, an increased expression of leptin in both injured vessels and serum was observed 24 hours post-surgery. RFP (red fluorescent protein)-Sca-1 + progenitor cells in Matrigel were applied to the adventitia of the injured femoral artery. RFP + cells were observed in the intima 24 hours post-surgery, subsequently increasing neointimal lesions at 2 weeks when compared with the arteries without seeded cells. This increase was reduced by pre-treatment of Sca-1 + cells with a leptin antagonist. Guidewire injury could only induce minor neointima in Lepr -/- mice 2 weeks post-surgery. However, transplantation of Lepr +/+ Sca-1 + progenitor cells into the adventitial side of injured artery in Lepr -/- mice significantly enhanced neointimal formation. Upregulation of leptin levels in both the vessel wall and the circulation after vessel injury promoted the migration of Sca-1 + progenitor cells via leptin receptor-dependent signal transducer and activator of transcription 3- Rac1/Cdc42-ERK (extracellular signal-regulated kinase)-FAK pathways, which enhanced neointimal formation. © 2017 The Authors.

[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.

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 ...

17 CFR 200.24a - Director of the Office of Consumer Affairs.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Consumer Affairs. 200.24a Section 200.24a Commodity and Securities Exchanges SECURITIES AND EXCHANGE... General Organization § 200.24a Director of the Office of Consumer Affairs. The Director of the Office of Consumer Affairs is responsible to the Chairman for the Commission's investor education and consumer...

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

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

Carbon nanotube heat-exchange systems

DOEpatents

Hendricks, Terry Joseph; Heben, Michael J.

2008-11-11

A carbon nanotube heat-exchange system (10) and method for producing the same. One embodiment of the carbon nanotube heat-exchange system (10) comprises a microchannel structure (24) having an inlet end (30) and an outlet end (32), the inlet end (30) providing a cooling fluid into the microchannel structure (24) and the outlet end (32) discharging the cooling fluid from the microchannel structure (24). At least one flow path (28) is defined in the microchannel structure (24), fluidically connecting the inlet end (30) to the outlet end (32) of the microchannel structure (24). A carbon nanotube structure (26) is provided in thermal contact with the microchannel structure (24), the carbon nanotube structure (26) receiving heat from the cooling fluid in the microchannel structure (24) and dissipating the heat into an external medium (19).

First Record of Psorophora albipes in Quintana Roo, Mexico.

PubMed

Chan-Chable, Rahuel J; Ortega-Morales, Aldo I; Martínez-Arce, Arely

2016-09-01

In Mexico the Psorophora genus includes 24 species divided into 3 subgenera: Grabhamia, Janthinosoma, and Psorophora. Some species occur in the Nearctic region of the country (northern Mexico), whereas other species occur in the Neotropical region (southern Mexico), and a few species occur in both regions. In Quintana Roo, Mexico, 7 species have been previously recorded: Ps. confinnis s.s., Ps. champerico, Ps. cyanescens, Ps. ferox, Ps. lutzii, Ps. ciliata, and Ps. lineata. In October 2013, 24 females of Ps. albipes were collected using CDC light traps. This is the first record of this species in Quintana Roo.

78 FR 17410 - Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention-Health...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-21

... Information: Leandris Liburd, Ph.D., M.P.H., M.A., Designated Federal Officer, Health Disparities Subcommittee... subcommittee: Time and Date: 9:00 a.m.-4:45 p.m. EDT, April 24, 2013. Place: CDC, Building 19, Rooms 245 and... participate during the public comment, which is tentatively scheduled from 4:30 to 4:40 p.m. This meeting is...

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

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.

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

PubMed

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

1998-03-31

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

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

PubMed

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

2010-02-28

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

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

17 CFR 41.24 - Rule amendments to security futures products.

Code of Federal Regulations, 2010 CFR

2010-04-01

... rule amendment relating to a security futures product if the registered derivatives transaction... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Rule amendments to security futures products. 41.24 Section 41.24 Commodity and Securities Exchanges COMMODITY FUTURES TRADING...

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

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…

Deuterium enrichment of polycyclic aromatic hydrocarbons by photochemically induced exchange with deuterium-rich cosmic ices

NASA Technical Reports Server (NTRS)

Sandford, S. A.; Bernstein, M. P.; Allamandola, L. J.; Gillette, J. S.; Zare, R. N.

2000-01-01

The polycyclic aromatic hydrocarbon (PAH) coronene (C24H12) frozen in D2O ice in a ratio of less than 1 part in 500 rapidly exchanges its hydrogen atoms with the deuterium in the ice at interstellar temperatures and pressures when exposed to ultraviolet radiation. Exchange occurs via three different chemical processes: D atom addition, D atom exchange at oxidized edge sites, and D atom exchange at aromatic edge sites. Observed exchange rates for coronene (C24H12)-D2O and d12-coronene (C24D12)-H2O isotopic substitution experiments show that PAHs in interstellar ices could easily attain the D/H levels observed in meteorites. These results may have important consequences for the abundance of deuterium observed in aromatic materials in the interstellar medium and in meteorites. These exchange mechanisms produce deuteration in characteristic molecular locations on the PAHs that may distinguish them from previously postulated processes for D enrichment of PAHs.

Discrepancy in reports of support exchanges between parents and adult offspring: within- and between-family differences.

PubMed

Kim, Kyungmin; Zarit, Steven H; Birditt, Kira S; Fingerman, Karen L

2014-04-01

Using data from 929 parent-child dyads nested in 458 three-generation families (aged 76 for the oldest generation, 50 for the middle generation, and 24 for the youngest generation), this study investigated how discrepancies in reports of support that parents and their adult offspring exchanged with one another vary both within and between families, and what factors explain variations in dyadic discrepancies. We found substantial within- and between-family differences in dyadic discrepancies in reports of support exchanges. For downward exchanges (from parents to offspring), both dyad-specific characteristics within a family (e.g., gender composition, relative levels of relationship quality, and family obligation) and shared family characteristics (e.g., average levels of relationship quality) showed significant effects on dyadic discrepancies. For upward exchanges (from offspring to parents), however, only dyad-specific characteristics (e.g., gender composition, coresidence, relative levels of positive relationship quality, and family obligation) were significantly associated with discrepancies. Discrepancies in support exchanges were mainly associated with dyad-specific characteristics, but they also appeared to be influenced by family emotional environments. The use of multiple informants revealed that families differ in discrepancies in reports of exchanges, which has implications for quality of family life as well as future exchanges. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Discrepancy in Reports of Support Exchanges between Parents and Adult Offspring: Within- and Between-Family Differences

PubMed Central

Kim, Kyungmin; Zarit, Steven H.; Birditt, Kira S.; Fingerman, Karen L.

2014-01-01

Using data from 929 parent-child dyads nested in 458 three-generation families (aged 76 for the oldest generation, 50 for the middle generation, and 24 for the youngest generation), this study investigated how discrepancies in reports of support that parents and their adult offspring exchanged with one another vary both within and between families, and what factors explain variations in dyadic discrepancies. We found substantial within- and between-family differences in dyadic discrepancies in reports of support exchanges. For downward exchanges (from parents to offspring), both dyad-specific characteristics within a family (e.g., gender composition, relative levels of relationship quality, and family obligation) and shared family characteristics (e.g., average levels of relationship quality) showed significant effects on dyadic discrepancies. For upward exchanges (from offspring to parents), however, only dyad-specific characteristics (e.g., gender composition, coresidence, relative levels of positive relationship quality, and family obligation) were significantly associated with discrepancies. Discrepancies in support exchanges were mainly associated with dyad-specific characteristics, but they also appeared to be influenced by family emotional environments. The use of multiple informants revealed that families differ in discrepancies in reports of exchanges, which has implications for quality of family life as well as future exchanges. PMID:24548009

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.

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.

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.

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...

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

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.

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.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-07-26

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

13 CFR 120.823 - CDC Board of Directors.

Code of Federal Regulations, 2013 CFR

2013-01-01

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

13 CFR 120.851 - CDC ethical requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

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

13 CFR 120.823 - CDC Board of Directors.

Code of Federal Regulations, 2012 CFR

2012-01-01

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

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

Code of Federal Regulations, 2013 CFR

2013-01-01

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

13 CFR 120.851 - CDC ethical requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

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

13 CFR 120.851 - CDC ethical requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

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

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

Code of Federal Regulations, 2011 CFR

2011-01-01

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

13 CFR 120.823 - CDC Board of Directors.

Code of Federal Regulations, 2014 CFR

2014-01-01

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

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

Code of Federal Regulations, 2011 CFR

2011-01-01

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

13 CFR 120.821 - CDC Area of Operations.

Code of Federal Regulations, 2014 CFR

2014-01-01

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

13 CFR 120.823 - CDC Board of Directors.

Code of Federal Regulations, 2010 CFR

2010-01-01

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

13 CFR 120.821 - CDC Area of Operations.

Code of Federal Regulations, 2011 CFR

2011-01-01

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

13 CFR 120.823 - CDC Board of Directors.

Code of Federal Regulations, 2011 CFR

2011-01-01

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

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

Code of Federal Regulations, 2010 CFR

2010-01-01

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

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

Code of Federal Regulations, 2014 CFR

2014-01-01

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

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

Code of Federal Regulations, 2013 CFR

2013-01-01

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

13 CFR 120.821 - CDC Area of Operations.

Code of Federal Regulations, 2013 CFR

2013-01-01

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

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

Code of Federal Regulations, 2012 CFR

2012-01-01

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

13 CFR 120.821 - CDC Area of Operations.

Code of Federal Regulations, 2010 CFR

2010-01-01

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

13 CFR 120.821 - CDC Area of Operations.

Code of Federal Regulations, 2012 CFR

2012-01-01

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

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

Code of Federal Regulations, 2014 CFR

2014-01-01

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

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-05

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

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

PubMed

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

2017-01-22

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

Cdc13 N-Terminal Dimerization DNA Binding and Telomere Length Regulation

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

M Mitchell; J Smith; M Mason

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

Underage Drinking

MedlinePlus

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

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.

Apoptosis and Tumor Progression in Prostate Cancer

DTIC Science & Technology

2006-02-01

KLIP1; FLJ23468 MLF1 interacting protein NM_001071 0.248 TS; TMS; TSase; HsT422; MGC88736 thymidylate synthetase NM_001255 0.24 p55CDC; MGC102824...repeat-containing 5 (survivin) NM_016359 0.0747 LNP; ANKT; SAPL; BM037; Q0310; FLJ13421; PRO0310p1 nucleolar and spindle associated protein 1 NM_024629 0.0569 KLIP1; FLJ23468 MLF1 interacting protein

17 CFR 260.7a-24 - Words relating to periods of time in the past.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Words relating to periods of time in the past. 260.7a-24 Section 260.7a-24 Commodity and Securities Exchanges SECURITIES AND... Requirements As to Contents § 260.7a-24 Words relating to periods of time in the past. Unless the context...

24-Methylenecycloartanyl ferulate, a major compound of γ-oryzanol, promotes parvin-beta expression through an interaction with peroxisome proliferator-activated receptor-gamma 2 in human breast cancer cells

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

Kim, Heon Woong; Lim, Eun Joung; Jang, Hwan Hee

2015-12-25

Parvin-β is an adaptor protein that binds to integrin-linked kinase (ILK) and is significantly downregulated in breast tumors and breast cancer cell lines. We treated the breast cancer cell line MCF7 with 24-methylenecycloartanyl ferulate (24-MCF), a γ-oryzanol compound. We observed upregulation of parvin-β (GenBank Accession No. (AF237769)) and peroxisome proliferator-activated receptor (PPAR)-γ2 (GenBank Accession No. (NM-015869)). Among γ-oryzanol compounds, only treatment with 24-MCF led to the formation of reverse transcription-PCR products of parvin-β (650 and 500 bp) and PPAR-γ2 (580 bp) in MCF7 cells, but not in T47D, SK-BR-3, or MDA-MB-231 cells. 24-MCF treatment increased the mRNA and protein levels of parvin-β inmore » MCF7 cells in a dose-dependent manner. We hypothesized that there is a correlation between parvin-β expression and induction of PPAR-γ2. This hypothesis was investigated by using a promoter-reporter assay, chromatin immunoprecipitation, and an electrophoretic mobility shift assay. 24-MCF treatment induced binding of PPAR-γ2 to a peroxisome proliferator response element-like cis-element (ACTAGGACAAAGGACA) in the parvin-β promoter in MCF7 cells in a dose-dependent manner. 24-MCF treatment significantly decreased anchorage-independent growth and inhibited cell movement in comparison to control treatment with dimethyl sulfoxide. 24-MCF treatment reduced the levels of GTP-bound Rac1 and Cdc42. Evaluation of Akt1 inhibition by 24-MCF revealed that the half maximal effective concentration was 33.3 μM. Docking evaluations revealed that 24-MCF binds to the ATP-binding site of Akt1(PDB ID: (3OCB)) and the compound binding energy is -8.870 kcal/mol. Taken together, our results indicate that 24-MCF treatment increases parvin-β expression, which may inhibit ILK downstream signaling. - Highlights: • Treatment with 24-MCF increases gene expression of parvin-β and PPAR-ϒ2 in MCF7 cells. • PPAR-ϒ2 interacts with the parvin-β gene via its peroxisome proliferator response element-like cis-element. • 24-MCF treatment inhibits anchorage-dependent growth of MCF7 cells. • 24-MCF treatment inhibits MCF7 cell migration and Rac1 and Cdc42 activation. • 24-MCF may be a new ATP-competitive Akt1 inhibitor that binds to the ATP-binding site of Akt1.« less

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...

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 ...

Geochemical modulation of bioavailability and toxicity of nitroaromatic compounds to aquatic plants.

PubMed

Roberts, Michael G; Rugh, Clayton L; Li, Hui; Teppen, Brian J; Boyd, Stephen A

2007-03-01

Nitroaromatic compounds (NACs) are prominent soil and sediment contaminants that are strongly adsorbed by smectites at extents that depend on hydration properties of the exchangeable cation. Potassium smectites adsorb nitroaromatics much more strongly than calcium smectites, so that adjustment of K+ versus Ca2+ occupation on cation exchange sites in smectites can be used to modulate the retention and release of nitroaromatics. We suggest that this modulation can be used to advantageously manage the bioavailability and toxicity of NACs during bioremedation. We have measured the toxicity of 2,4-dinitrotoluene (2,4-DNT) to duckweed grown in smectite suspensions and utilized Ca2+/K+ exchange to retain or release 2,4-DNT. Retention by potassium smectite reduced bioavailability and hence toxicity to duckweed. Addition of Ca2+ to replace K+ by ion exchange released adsorbed 2,4-DNT, which is toxic to duckweed. So smectites can be used to sequester or release 2,4-DNT predictably and provide means to control bioavailability and environmental toxicity.

Environmental Public Health Surveillance for Exposure to Respiratory Health Hazards: A Joint NASA/CDC Project to Use Remote Sensing Data for Estimating Airborne Particulate Matter Over the Atlanta, Georgia Metropolitan Area

NASA Technical Reports Server (NTRS)

Quattrochi, Dale A.; Al-Hamdan, Mohammad; Estes, Maurice; Crosson, William

2007-01-01

As part of the National Environmental Public Health Tracking Network (EPHTN) the National Center for Environmental Health (NCEH) at the Centers for Disease Control and Prevention (CDC) is leading a project called Health and Environment Linked for Information Exchange (HELiX-Atlanta). The goal of developing the National Environmental Public Health Tracking Network is to improve the health of communities. Currently, few systems exist at the state or national level to concurrently track many of the exposures and health effects that might be associated with environmental hazards. An additional challenge is estimating exposure to environmental hazards such as particulate matter whose aerodynamic diameter is less than or equal to 2.5 micrometers (PM2.5). HELIX-Atlanta's goal is to examine the feasibility of building an integrated electronic health and environmental data network in five counties of Metropolitan Atlanta, GA. NASA Marshall Space Flight Center (NASA/MSFC) is collaborating with CDC to combine NASA earth science satellite observations related to air quality and environmental monitoring data to model surface estimates of PM2.5 concentrations that can be linked with clinic visits for asthma. While use of the Air Quality System (AQS) PM2.5 data alone could meet HELIX-Atlanta specifications, there are only five AQS sites in the Atlanta area, thus the spatial coverage is not ideal. We are using NASA Moderate Resolution Imaging Spectroradiometer (MODIS) satellite Aerosol Optical Depth (AOD) data for estimating daily ground level PM2.5 at 10 km resolution over the metropolitan Atlanta area supplementing the AQS ground observations and filling their spatial and temporal gaps.

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

Psychometrics of a brief measure of emotional self-efficacy among adolescents from the United States.

PubMed

Valois, Robert F; Zullig, Keith J

2013-10-01

Preliminary data were collected to evaluate the psychometric properties of an emotional self-efficacy (ESE) measure in a sample of 3836 public high school adolescents who completed the Centers for Disease Control and Prevention (CDC) Youth Risk Behavior Survey in South Carolina. Principal axis factor analysis was followed by a 4-way between-groups analysis of variance (ANOVA) testing for differences in total score means on selected demographic estimates and their interactions. Relationships between total score and selected risk behaviors were examined through a series of 1-way ANOVA procedures and subsequent Tukey Honest Significant Difference (HSD) tests. Factor analysis results suggested that a 1-factor model best explained factor structure of the scale items (factor loadings .64 to .71, eigenvalue = 3.24, h(2)  = .46). Girls reported a significantly higher mean total ESE rating than boys; White students reported a significantly higher mean total ESE rating than Black students. Statistically significant lower mean total ESE ratings were also noted for those who reported physical fighting, lifetime alcohol use, and sexual intercourse. This 7-item scale is a reliable measure and could aid school health researchers and mental health practitioners in psychosocial screening and as an outcome of social and emotional learning as a brief measure of adolescent ESE. © 2013, American School Health Association.

Characteristics of Black Men Who Have Sex With Men in Baltimore, Philadelphia, and Washington, D.C.: Geographic Diversity in Socio-Demographics and HIV Transmission Risk.

PubMed

German, Danielle; Brady, Kathleen; Kuo, Irene; Opoku, Jenevieve; Flynn, Colin; Patrick, Rudy; Park, Ju Nyeong; Adams, Joella; Carroll, Makeda; Simmons, Ron; Smith, Carlton R; Davis, Wendy W

2017-07-01

Baltimore, Philadelphia, and Washington, DC are geographically proximate cities with high HIV prevalence, including among black men who have sex with men (BMSM). Using data collected among BMSM in CDC's National HIV Behavioral Surveillance project, we compared socio-demographic characteristics, HIV risk behaviors, and service utilization to explore similarities and differences that could inform local and regional HIV intervention approaches. BMSM were recruited through venue time location sampling, June-December, 2011. Participants completed identical socio-behavioral surveys and voluntary HIV testing. Analyses were conducted among the full sample and those aged 18-24. Participants included 159 (DC), 364 (Baltimore), and 331 (Philadelphia) eligible BMSM. HIV prevalence was 23.1% (DC), 48.0% (Baltimore), 14.6% (Philadelphia) with 30.6%, 69.0%, 33.3% unrecognized HIV infection, respectively. Among BMSM 18-24, HIV prevalence was 11.1% (DC), 38.9% (Baltimore), 9.6% (Philadelphia) with unrecognized HIV infection 0.0%, 73.8%, 60.0% respectively. Compared with the other 2 cities, Baltimore participants were less likely to identify as gay/homosexual; more likely to report unemployment, incarceration, homelessness, sex exchange; and least likely to use the internet for partners. DC participants were more likely to have a college degree and employment. Philadelphia participants were more likely to report gay/homosexual identity, receptive condomless anal sex, having only main partners, and bars/clubs as partner meeting places. Sexually transmitted disease testing was universally low. Analyses showed especially high HIV prevalence among BMSM in Baltimore including among young BMSM. Socio-demographic characteristics and HIV infection correlates differed across cities but unrecognized HIV infection and unknown partner status were universally high.

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

Effect of a Matter of Balance programme on avoidance behaviour due to fear of falling in older adults.

PubMed

Sartor-Glittenberg, Cecelia; Bordenave, Elton; Bay, Curt; Bordenave, Lori; Alexander, Jeffrey L

2018-05-01

Fear of falling (FOF) is associated with restricted activities, increased risk of falling, and decreased quality of life. A Matter of Balance (AMOB) is an evidence-based programme designed to decrease FOF. The current study investigated the influence of the AMOB on activity avoidance caused by FOF in older adults using the Fear of Falling Avoidance Behavior Questionnaire (FFABQ), health-related quality of life, and a question regarding concerns about falling. Participants of this quasi-experimental, one-group, pretest-post-test study design were older adults from community sites in the Phoenix, Arizona, metropolitan area. Participants attended the AMOB programme, which consisted of one weekly 2-h session for 8 weeks. At the beginning and end of the programme, participants completed the standard AMOB assessments, the FFABQ, the Centers for Disease Control Core Healthy Days Measure (CDC HRQOL-4), and a question regarding concerns about falling. Sixty-three participants completed the study; their mean ± SD age was 75.3 ± 7.1 years (range: 60.0-90.0 years), and 84.1% were women. The FFABQ scores decreased from baseline (24.4 ± 12.7 points) to post-AMOB (20.1 ± 11.9 points; t = 2.62, P = 0.01). No changes in any of the CDC HRQOL-4 questions were noted (CDC HRQOL-4 question (Q)1 (z = -1.41, P = 0.16), CDC HRQOL-4 Q2 and Q3 summary index (z = -1.60, P = 0.11), and CDC HRQOL-4 Q4 (z = -0.97, P = 0.33)). Concerns about falling decreased from baseline (3.4 ± 0.9 points) to post-AMOB (2.8 ± 0.8 points; z = -4.09, P < 0.001). Avoidance behaviour caused by FOF, as measured by the FFABQ, and concerns about falling decreased in community-dwelling older adults who participated in the AMOB. Findings support the efficacy of the AMOB for reducing both avoidance behaviour caused by FOF and concerns about falling through an approach that combines education and exercise. © 2018 Japanese Psychogeriatric Society.

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

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.

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

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

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

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

2015-01-16

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

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

PubMed

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

2014-07-08

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

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

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

PubMed

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

2018-06-01

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

DEC/SOL: solution of dense systems of linear algebraic equations. [In Fortran IV and compass for CDC 7600; DECST and SOLST for CDC STAR

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

Hindmarsh, A.C.; Sloan, L.J.; Dubois, P.F.

1978-12-01

This report supersedes the original version, dated June 1976. It describes four versions of a pair of subroutines for solving N x N systems of linear algebraic equations. In each case, the first routine, DEC, performs an LU decomposition of the matrix with partial pivoting, and the second, SOL, computes the solution vector by back-substitution. The first version is in Fortran IV, and is derived from routines DECOMP and SOLVE written by C.B. Moler. The second is a version for the CDC 7600 computer using STACKLIB. The third is a hand-coded (Compass) version for the 7600. The fourth is amore » vectorized version for the CDC STAR, renamed DECST and SOLST. Comparative tests on these routines are also described. The Compass version is faster than the others on the 7600 by factors of up to 5. The major revisions to the original report, and to the subroutines described, are an updated description of the availability of each version of DEC/SOL; correction of some errors in the Compass version, as altered so as to be compatible with FTN; and a new STAR version, which runs much faster than the earlier one. The standard Fortran version, the Fortran/STACKLIB version, and the object code generated from the Compass version and available in STACKLIB have not been changed.« less

Promotion of neurite and filopodium formation by CD47: roles of integrins, Rac, and Cdc42.

PubMed

Miyashita, Motoaki; Ohnishi, Hiroshi; Okazawa, Hideki; Tomonaga, Hiroyasu; Hayashi, Akiko; Fujimoto, Tetsuro-Takahiro; Furuya, Nobuhiko; Matozaki, Takashi

2004-08-01

Axon extension during development is guided by many factors, but the signaling mechanisms responsible for its regulation remain largely unknown. We have now investigated the role of the transmembrane protein CD47 in this process in N1E-115 neuroblastoma cells. Forced expression of CD47 induced the formation of neurites and filopodia. Furthermore, an Fc fusion protein containing the extracellular region of the CD47 ligand SHPS-1 induced filopodium formation, and this effect was enhanced by CD47 overexpression. SHPS-1-Fc also promoted neurite and filopodium formation triggered by serum deprivation. Inhibition of Rac or Cdc42 preferentially blocked CD47-induced formation of neurites and filopodia, respectively. Overexpression of CD47 resulted in the activation of both Rac and Cdc42. The extracellular region of CD47 was sufficient for the induction of neurite formation by forced expression, but the entire structure of CD47 was required for enhancement of filopodium formation by SHPS-1-Fc. Neurite formation induced by CD47 was also inhibited by a mAb to the integrin beta3 subunit. These results indicate that the interaction of SHPS-1 with CD47 promotes neurite and filopodium formation through the activation of Rac and Cdc42, and that integrins containing the beta3 subunit participate in the effect of CD47 on neurite formation.

Sustained Delivery of Activated Rho GTPases and BDNF Promotes Axon Growth in CSPG-Rich Regions Following Spinal Cord Injury

PubMed Central

Jain, Anjana; McKeon, Robert J.; Brady-Kalnay, Susann M.; Bellamkonda, Ravi V.

2011-01-01

Background Spinal cord injury (SCI) often results in permanent functional loss. This physical trauma leads to secondary events, such as the deposition of inhibitory chondroitin sulfate proteoglycan (CSPG) within astroglial scar tissue at the lesion. Methodology/Principal Findings We examined whether local delivery of constitutively active (CA) Rho GTPases, Cdc42 and Rac1 to the lesion site alleviated CSPG-mediated inhibition of regenerating axons. A dorsal over-hemisection lesion was created in the rat spinal cord and the resulting cavity was conformally filled with an in situ gelling hydrogel combined with lipid microtubes that slowly released constitutively active (CA) Cdc42, Rac1, or Brain-derived neurotrophic factor (BDNF). Treatment with BDNF, CA-Cdc42, or CA-Rac1 reduced the number of GFAP-positive astrocytes, as well as CSPG deposition, at the interface of the implanted hydrogel and host tissue. Neurofilament 160kDa positively stained axons traversed the glial scar extensively, entering the hydrogel-filled cavity in the treatments with BDNF and CA-Rho GTPases. The treated animals had a higher percentage of axons from the corticospinal tract that traversed the CSPG-rich regions located proximal to the lesion site. Conclusion Local delivery of CA-Cdc42, CA-Rac1, and BDNF may have a significant therapeutic role in overcoming CSPG-mediated regenerative failure after SCI. PMID:21283639

Condomless anal intercourse among males and females at high risk for heterosexual HIV infection

PubMed Central

German, Danielle; Nguyen, Trang; Ogbue, Christine Powell; Flynn, Colin

2015-01-01

Background Understanding and addressing heterosexual HIV transmission requires attention to the range and context of heterosexual sexual behaviors. We sought to determine population-based prevalence of condomless anal intercourse (CAI) among individuals at increased heterosexual HIV risk in Baltimore and to identify demographic, behavioral, and health related correlates. Methods Data were from a cross-sectional study of 185 males and 198 females at increased heterosexual risk for HIV recruited using respondent driven sampling as part of CDC's National HIV Behavioral Surveillance Project in Baltimore, August-December 2010. Bivariate and multivariate logistic regression examined factors associated with heterosexual CAI. Results The sample was majority African-American, with mean age of 38 among men and 34 among women. Forty-two percent of men (95% C.I.: 30.9, 52.0%) and 38% of women (95% C.I.: 29.4, 47.2%) reported any CAI in the past year, with variance by partner type and gender. Among men, CAI was significantly associated with homelessness, casual and exchange partners, same sex partner in past year, and substance use. Among women, CAI was significantly associated with lower education, casual and exchange partners, same sex partner in past year, multiple partners, and substance use. In adjusted gender-specific models, males and females with increasing numbers of partners were more likely to engage in CAI. Conclusions It is important to recognize the efficiency of transmission of HIV and other STIs through CAI. There is a need to broaden heterosexual sexual health promotion and HIV/STI prevention to adequately and appropriately address risks and prevention strategies for anal intercourse. PMID:25970308

Rho GTPase protein Cdc42 is critical for postnatal cartilage development

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

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

2016-02-19

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

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

PubMed Central

Caligiuri, M; Connolly, T; Beach, D

1997-01-01

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

Cdc13 prevents telomere uncapping and Rad50-dependent homologous recombination

PubMed Central

Grandin, Nathalie; Damon, Christelle; Charbonneau, Michel

2001-01-01

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

Mosquito vectors of West Nile virus during an epizootic outbreak in Puerto Rico.

PubMed

Barrera, R; MacKay, A; Amador, M; Vasquez, J; Smith, J; Díaz, A; Acevedo, V; Cabán, B; Hunsperger, E A; Muñoz-Jordán, J L

2010-11-01

The purpose of this investigation was to identify the mosquito (Diptera: Culicidae) vectors of West Nile virus (WNV; family Flaviviridae, genus Flavivirus) during an epizootic WNV outbreak in eastern Puerto Rico in 2007. In June 2006, 12 sentinel chicken pens with five chickens per pen were deployed in six types of habitats: herbaceous wetlands, mangrove forests, deciduous forests, evergreen forests, rural areas, and urban areas. Once WNV seroconversion in chickens was detected in June 2007, we began trapping mosquitoes using Centers for Disease Control and Prevention (CDC) miniature (light/CO2-baited) traps, CMT-20 collapsible mosquito (CO2- and ISCA SkinLure-baited) traps, and CDC gravid (hay infusion-baited) traps. We placed the CDC miniature traps both 2-4 m and >30 m from the chicken pens, the collapsible traps 2-4 m from the pens, and the gravid traps in backyards of houses with sentinel chicken pens and in a wetland adjacent to an urban area. We found numerous blood-engorged mosquitoes in the traps nearest to the sentinel chickens and reasoned that any such mosquitoes with a disseminated WNV infection likely served as vectors for the transmission of WNV to the sentinels. We used reverse transcriptase-polymerase chain reaction and isolation (C636) on pools of heads, thoraxes/ abdomens, and legs of collected blood-engorged mosquitoes to determine whether the mosquitoes carried WNV. We detected WNV-disseminated infections in and obtained WNV isolates from Culex nigripalpus Theo (minimum infection rate [MIR] 1.1-9.7/1,000), Culex bahamensis Dyar and Knab (MIR 1.8-6.0/1,000), and Aedes taeniorhynchus (Wied.) (MIR 0.34-0.36/1,000). WNV was also identified in and isolated from the pool of thoraxes and abdomens of Culex quinquefasciatus Say (4.17/1,000) and identified in one pool of thoraxes and abdomens of Culex habilitator Dyar and Knab (13.39/1,000). Accumulated evidence since 2002 suggests that WNV has not become endemic in Puerto Rico.

Assessing Insecticide Susceptibility of Laboratory Lutzomyia longipalpis and Phlebotomus papatasi Sand Flies (Diptera: Psychodidae: Phlebotominae)

PubMed Central

Denlinger, David S.; Lozano-Fuentes, Saul; Lawyer, Phillip G.; Black, William C.; Bernhardt, Scott A.

2015-01-01

Chemical insecticides are effective for controlling Lutzomyia and Phlebotomus sand fly (Diptera: Psychodidae) vectors of Leishmania parasites. However, repeated use of certain insecticides has led to tolerance and resistance. The objective of this study was to determine lethal concentrations (LCs) and lethal exposure times (LTs) to assess levels of susceptibility of laboratory Lutzomyia longipalpis (Lutz and Nieva) and Phlebotomus papatasi (Scopoli) to 10 insecticides using a modified version of the World Health Organization (WHO) exposure kit assay and Centers for Disease Control and Prevention (CDC) bottle bioassay. Sand flies were exposed to insecticides coated on the interior of 0.5-gallon and 1,000-ml glass bottles. Following exposure, the flies were allowed to recover for 24 h, after which mortality was recorded. From dose–response survival curves for L. longipalpis and P. papatasi generated with the QCal software, LCs causing 50, 90, and 95% mortality were determined for each insecticide. The LCs and LTs from this study will be useful as baseline reference points for future studies using the CDC bottle bioassays to assess insecticide susceptibility of sand fly populations in the field. There is a need for a larger repository of sand fly insecticide susceptibility data from the CDC bottle bioassays, including a range of LCs and LTs for more sand fly species with more insecticides. Such a repository would be a valuable tool for vector management. PMID:26336231

LETTER TO THE EDITOR: Two-centre exchange integrals for complex exponent Slater orbitals

NASA Astrophysics Data System (ADS)

Kuang, Jiyun; Lin, C. D.

1996-12-01

The one-dimensional integral representation for the Fourier transform of a two-centre product of B functions (finite linear combinations of Slater orbitals) with real parameters is generalized to include B functions with complex parameters. This one-dimensional integral representation allows for an efficient method of calculating two-centre exchange integrals with plane-wave electronic translational factors (ETF) over Slater orbitals of real/complex exponents. This method is a significant improvement on the previous two-dimensional quadrature method of the integrals. A new basis set of the form 0953-4075/29/24/005/img1 is proposed to improve the description of pseudo-continuum states in the close-coupling treatment of ion - atom collisions.

CYK-4 regulates Rac, but not Rho, during cytokinesis

PubMed Central

Zhuravlev, Yelena; Hirsch, Sophia M.; Jordan, Shawn N.; Dumont, Julien; Shirasu-Hiza, Mimi; Canman, Julie C.

2017-01-01

Cytokinesis is driven by constriction of an actomyosin contractile ring that is controlled by Rho-family small GTPases. Rho, activated by the guanine-nucleotide exchange factor ECT-2, is upstream of both myosin-II activation and diaphanous formin-mediated filamentous actin (f-actin) assembly, which drive ring constriction. The role for Rac and its regulators is more controversial, but, based on the finding that Rac inactivation can rescue cytokinesis failure when the GTPase-activating protein (GAP) CYK-4 is disrupted, Rac activity was proposed to be inhibitory to contractile ring constriction and thus specifically inactivated by CYK-4 at the division plane. An alternative model proposes that Rac inactivation generally rescues cytokinesis failure by reducing cortical tension, thus making it easier for the cell to divide when ring constriction is compromised. In this alternative model, CYK-4 was instead proposed to activate Rho by binding ECT-2. Using a combination of time-lapse in vivo single-cell analysis and Caenorhabditis elegans genetics, our evidence does not support this alternative model. First, we found that Rac disruption does not generally rescue cytokinesis failure: inhibition of Rac specifically rescues cytokinesis failure due to disruption of CYK-4 or ECT-2 but does not rescue cytokinesis failure due to disruption of two other contractile ring components, the Rho effectors diaphanous formin and myosin-II. Second, if CYK-4 regulates cytokinesis through Rho rather than Rac, then CYK-4 inhibition should decrease levels of downstream targets of Rho. Inconsistent with this, we found no change in the levels of f-actin or myosin-II at the division plane when CYK-4 GAP activity was reduced, suggesting that CYK-4 is not upstream of ECT-2/Rho activation. Instead, we found that the rescue of cytokinesis in CYK-4 mutants by Rac inactivation was Cdc42 dependent. Together our data suggest that CYK-4 GAP activity opposes Rac (and perhaps Cdc42) during cytokinesis. PMID:28298491

Role of cdc25 Phosphatases in Human Breast Cancer

DTIC Science & Technology

2007-05-01

cellular response to 5-fluorouracil or hydroxyurea . MCF-10A cells were infected with the indicated adenoviruses for 24 hr and then treated with...doxorubicin, 5-fluorouracil, or hydroxyurea for 48 hr. Cells were stained with propidium iodide prior to flow-cytometry analyses. In order to investigate...of two chemotherapeutic agents, 5- fluorouracil (5-FU, 50 μM), an inhibitor of pyrimidine synthesis, or hydroxyurea (HU, 2mM), an inhibitor of both

Role of cdc25 Phosphatases in Human Breast Cancer

DTIC Science & Technology

2008-05-01

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

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

PubMed Central

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

2007-01-01

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

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

PubMed

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

2017-04-01

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

Rac1/RhoA antagonism defines cell-to-cell heterogeneity during epidermal morphogenesis in nematodes

PubMed Central

Ouellette, Marie-Hélène

2016-01-01

The antagonism between the GTPases Rac1 and RhoA controls cell-to-cell heterogeneity in isogenic populations of cells in vitro and epithelial morphogenesis in vivo. Its involvement in the regulation of cell-to-cell heterogeneity during epidermal morphogenesis has, however, never been addressed. We used a quantitative cell imaging approach to characterize epidermal morphogenesis at a single-cell level during early elongation of Caenorhabditis elegans embryos. This study reveals that a Rac1-like pathway, involving the Rac/Cdc42 guanine-exchange factor β-PIX/PIX-1 and effector PAK1/PAK-1, and a RhoA-like pathway, involving ROCK/LET-502, control the remodeling of apical junctions and the formation of basolateral protrusions in distinct subsets of hypodermal cells. In these contexts, protrusions adopt lamellipodia or an amoeboid morphology. We propose that lamella formation may reduce tension building at cell–cell junctions during morphogenesis. Cell-autonomous antagonism between these pathways enables cells to switch between Rac1- and RhoA-like morphogenetic programs. This study identifies the first case of cell-to-cell heterogeneity controlled by Rac1/RhoA antagonism during epidermal morphogenesis. PMID:27821782

Social Exchange and Sexual Behavior in Young Women's Premarital Relationships in Kenya.

PubMed

Luke, Nancy; Goldberg, Rachel E; Mberu, Blessing U; Zulu, Eliya M

2011-10-01

Transactional sex, or the exchange of money and gifts for sexual activities within nonmarital relationships, has been widely considered a contributing factor to the disproportionate prevalence of HIV/AIDS among young women in sub-Saharan Africa. This study applied social exchange theory to premarital relationships in order to investigate the linkages between a variety of young women's resources-including employment and material transfers from male partners-and sexual behaviors. Data on the first month of premarital relationships (N=551 relationships) were collected from a random sample of young adult women ages 18-24 in Kisumu, Kenya, using a retrospective life history calendar. Consistent with the hypotheses, results showed that young women's income increases the likelihood of safer sexual activities, including delaying sex and using condoms consistently. Material transfers from the male partner displayed the opposite effect, supporting the view that resources obtained from within the relationship decrease young women's negotiating power.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2018-03-01

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

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

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

Li, Yuefeng; Zhu, Xiaolan; Xu, Wenlin

2013-02-15

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

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

PubMed Central

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

2014-01-01

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

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

PubMed Central

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

2002-01-01

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

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

PubMed Central

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

2017-01-01

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

Stonefish toxin defines an ancient branch of the perforin-like superfamily

PubMed Central

Ellisdon, Andrew M.; Reboul, Cyril F.; Huynh, Kitmun; Oellig, Christine A.; Winter, Kelly L.; Hodgson, Wayne C.; Seymour, Jamie; Dearden, Peter K.; Tweten, Rodney K.; Whisstock, James C.; McGowan, Sheena

2015-01-01

The lethal factor in stonefish venom is stonustoxin (SNTX), a heterodimeric cytolytic protein that induces cardiovascular collapse in humans and native predators. Here, using X-ray crystallography, we make the unexpected finding that SNTX is a pore-forming member of an ancient branch of the Membrane Attack Complex-Perforin/Cholesterol-Dependent Cytolysin (MACPF/CDC) superfamily. SNTX comprises two homologous subunits (α and β), each of which comprises an N-terminal pore-forming MACPF/CDC domain, a central focal adhesion-targeting domain, a thioredoxin domain, and a C-terminal tripartite motif family-like PRY SPla and the RYanodine Receptor immune recognition domain. Crucially, the structure reveals that the two MACPF domains are in complex with one another and arranged into a stable early prepore-like assembly. These data provide long sought after near-atomic resolution insights into how MACPF/CDC proteins assemble into prepores on the surface of membranes. Furthermore, our analyses reveal that SNTX-like MACPF/CDCs are distributed throughout eukaryotic life and play a broader, possibly immune-related function outside venom. PMID:26627714

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

PubMed

Geisler, William M

2015-12-15

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

An Analysis of International Air Freight Forwarding Support for the United States Navy.

DTIC Science & Technology

1985-06-01

2. The Role of IATA in Ratemaking ... ...... 23 3. Current Environment ..... ........... 24 III. BURLINGTON-NORTHERN AIR FREIGHT, INCORPORATED . . 28...Postgraduate School Library, Defense Logistics Studies Information Exchange, service guides provided by air freight forwarders, and MAC airlift data. Additional...carrier is permitted access [Ref. 16]. 2. The Role of IATA in Ratemaking Factors other than shipper demand and carrier costs affect international freight

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

PubMed

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

2012-02-01

Cell-cycle progression is governed by a series of essential regulatory proteins. Two major regulators are cell-division cycle protein 20 (CDC20) and its homologue, CDC20 homologue 1 (CDH1), which activate the anaphase-promoting complex/cyclosome (APC/C) in mitosis, and facilitate degradation of mitotic APC/C substrates. The malaria parasite, Plasmodium, is a haploid organism which, during its life-cycle undergoes two stages of mitosis; one associated with asexual multiplication and the other with male gametogenesis. Cell-cycle regulation and DNA replication in Plasmodium was recently shown to be dependent on the activity of a number of protein kinases. However, the function of cell division cycle proteins that are also involved in this process, such as CDC20 and CDH1 is totally unknown. Here we examine the role of a putative CDC20/CDH1 in the rodent malaria Plasmodium berghei (Pb) using reverse genetics. Phylogenetic analysis identified a single putative Plasmodium CDC20/CDH1 homologue (termed CDC20 for simplicity) suggesting that Plasmodium APC/C has only one regulator. In our genetic approach to delete the endogenous cdc20 gene of P. berghei, we demonstrate that PbCDC20 plays a vital role in male gametogenesis, but is not essential for mitosis in the asexual blood stage. Furthermore, qRT-PCR analysis in parasite lines with deletions of two kinase genes involved in male sexual development (map2 and cdpk4), showed a significant increase in cdc20 transcription in activated gametocytes. DNA replication and ultra structural analyses of cdc20 and map2 mutants showed similar blockage of nuclear division at the nuclear spindle/kinetochore stage. CDC20 was phosphorylated in asexual and sexual stages, but the level of modification was higher in activated gametocytes and ookinetes. Changes in global protein phosphorylation patterns in the Δcdc20 mutant parasites were largely different from those observed in the Δmap2 mutant. This suggests that CDC20 and MAP2 are both likely to play independent but vital roles in male gametogenesis.

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

PubMed Central

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

2012-01-01

Cell-cycle progression is governed by a series of essential regulatory proteins. Two major regulators are cell-division cycle protein 20 (CDC20) and its homologue, CDC20 homologue 1 (CDH1), which activate the anaphase-promoting complex/cyclosome (APC/C) in mitosis, and facilitate degradation of mitotic APC/C substrates. The malaria parasite, Plasmodium, is a haploid organism which, during its life-cycle undergoes two stages of mitosis; one associated with asexual multiplication and the other with male gametogenesis. Cell-cycle regulation and DNA replication in Plasmodium was recently shown to be dependent on the activity of a number of protein kinases. However, the function of cell division cycle proteins that are also involved in this process, such as CDC20 and CDH1 is totally unknown. Here we examine the role of a putative CDC20/CDH1 in the rodent malaria Plasmodium berghei (Pb) using reverse genetics. Phylogenetic analysis identified a single putative Plasmodium CDC20/CDH1 homologue (termed CDC20 for simplicity) suggesting that Plasmodium APC/C has only one regulator. In our genetic approach to delete the endogenous cdc20 gene of P. berghei, we demonstrate that PbCDC20 plays a vital role in male gametogenesis, but is not essential for mitosis in the asexual blood stage. Furthermore, qRT-PCR analysis in parasite lines with deletions of two kinase genes involved in male sexual development (map2 and cdpk4), showed a significant increase in cdc20 transcription in activated gametocytes. DNA replication and ultra structural analyses of cdc20 and map2 mutants showed similar blockage of nuclear division at the nuclear spindle/kinetochore stage. CDC20 was phosphorylated in asexual and sexual stages, but the level of modification was higher in activated gametocytes and ookinetes. Changes in global protein phosphorylation patterns in the Δcdc20 mutant parasites were largely different from those observed in the Δmap2 mutant. This suggests that CDC20 and MAP2 are both likely to play independent but vital roles in male gametogenesis. PMID:22383885

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

PubMed

Garmaroodi, Hamid S; Taga, Masatoki

2015-10-01

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

Comparative analysis of expression of two p97 homologues in Caenorhabditis elegans

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

Yamauchi, Seiji; Yamanaka, Kunitoshi; Ogura, Teru

2006-06-30

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

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-10

... scientific basis for communication and marketing practice; (2) guides CIOs on applying measures of... and marketing research to interested professionals at CDC, its partners, and other stakeholders; and... media channels, including CDC.gov top tier, CDC en Espanol, mobile apps, and CDC Connects; (4...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-01

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

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

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

McKnight, A.L.

1979-08-01

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

Cell cycle regulation in Schizosaccharomyces pombe.

PubMed

Moser, B A; Russell, P

2000-12-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2017-07-14

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

Effects of SASH1 on melanoma cell proliferation and apoptosis in vitro.

PubMed

Lin, Sheyu; Zhang, Junyu; Xu, Jiawei; Wang, Honglian; Sang, Qing; Xing, Qinghe; He, Lin

2012-12-01

The SAM and SH3 domain containing 1 (SASH1) gene was originally identified as a potential tumor suppressor gene in breast cancer, mapped on chromosome 6q24.3. The expression of SASH1 plays a prognostic role in human colon cancer. Its expression is frequently downregulated in several human malignancies. However, the biological function of SASH1 in melanoma cells is yet to be determined. In this study, in order to investigate the tumor suppressive effects of the SASH1 gene, an A-375 stable melanoma cell line was established, overexpressing the SASH1 gene. The stable cell line was examined using proliferation assay, apoptosis assay, cell cycle analysis and real-time PCR. The results indicated that the tumor suppressive activity of SASH1 derived from G2/M arrest in A-375 cells, and that the phosphorylation of Cdc2 or the disruption of cyclin B-Cdc2 binding may be responsible for the G2/M arrest.

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.

Design of exchange-correlation functionals through the correlation factor approach

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

Pavlíková Přecechtělová, Jana, E-mail: j.precechtelova@gmail.com, E-mail: Matthias.Ernzerhof@UMontreal.ca; Institut für Chemie, Theoretische Chemie / Quantenchemie, Sekr. C7, Technische Universität Berlin, Straße des 17. Juni 135, 10623 Berlin; Bahmann, Hilke

The correlation factor model is developed in which the spherically averaged exchange-correlation hole of Kohn-Sham theory is factorized into an exchange hole model and a correlation factor. The exchange hole model reproduces the exact exchange energy per particle. The correlation factor is constructed in such a manner that the exchange-correlation energy correctly reduces to exact exchange in the high density and rapidly varying limits. Four different correlation factor models are presented which satisfy varying sets of physical constraints. Three models are free from empirical adjustments to experimental data, while one correlation factor model draws on one empirical parameter. The correlationmore » factor models are derived in detail and the resulting exchange-correlation holes are analyzed. Furthermore, the exchange-correlation energies obtained from the correlation factor models are employed to calculate total energies, atomization energies, and barrier heights. It is shown that accurate, non-empirical functionals can be constructed building on exact exchange. Avenues for further improvements are outlined as well.« less

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

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

PubMed

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

2012-08-01

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

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

PubMed

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

1999-04-08

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

13 CFR 120.851 - CDC ethical requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

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

13 CFR 120.851 - CDC ethical requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

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

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

Code of Federal Regulations, 2014 CFR

2014-07-01

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

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

Code of Federal Regulations, 2011 CFR

2011-07-01

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

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

Code of Federal Regulations, 2010 CFR

2010-07-01

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

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

Code of Federal Regulations, 2013 CFR

2013-07-01

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

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

Code of Federal Regulations, 2012 CFR

2012-07-01

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

Metabolic Syndrome Prevalence by Race/Ethnicity and Sex in the United States, National Health and Nutrition Examination ...

MedlinePlus

... factors on the prevalence of metabolic syndrome. Top Methods Study design and participants Since 1959, the National ... 2016. https://www.cdc.gov/Nchs/Nhanes/survey_methods.htm. Accessed November 1, 2016. Current population survey ( ...

42 CFR 34.3 - Scope of examinations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... outbreak investigations and response efforts; effectiveness of containment and control measures; and the... all applicable additional requirements for medical screening and testing, and will post these at the...) Risk-based approach. (1) HHS/CDC will use the medical and epidemiological factors listed in paragraph...

42 CFR 34.3 - Scope of examinations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... outbreak investigations and response efforts; effectiveness of containment and control measures; and the... all applicable additional requirements for medical screening and testing, and will post these at the...) Risk-based approach. (1) HHS/CDC will use the medical and epidemiological factors listed in paragraph...

42 CFR 34.3 - Scope of examinations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... outbreak investigations and response efforts; effectiveness of containment and control measures; and the... all applicable additional requirements for medical screening and testing, and will post these at the...) Risk-based approach. (1) HHS/CDC will use the medical and epidemiological factors listed in paragraph...

42 CFR 34.3 - Scope of examinations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... outbreak investigations and response efforts; effectiveness of containment and control measures; and the... all applicable additional requirements for medical screening and testing, and will post these at the...) Risk-based approach. (1) HHS/CDC will use the medical and epidemiological factors listed in paragraph...

42 CFR 34.3 - Scope of examinations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... outbreak investigations and response efforts; effectiveness of containment and control measures; and the... all applicable additional requirements for medical screening and testing, and will post these at the...) Risk-based approach. (1) HHS/CDC will use the medical and epidemiological factors listed in paragraph...

Antibody-catalyzed benzoin oxidation as a mechanistic probe for nucleophilic catalysis by an active site lysine.

PubMed

Sklute, Genia; Oizerowich, Rachel; Shulman, Hagit; Keinan, Ehud

2004-05-03

Aldolase antibody 24H6, which was obtained by reactive immunization against a 1,3-diketone hapten, is shown to catalyze additional reactions, including H/D exchange and oxidation reactions. Comparison of the H/D exchange reaction at the alpha-position of a wide range of aldehydes and ketones by 24H6 and by other aldolase antibodies, such as 38C2, pointed at the significantly larger size of the 24H6 active site. This property allowed for the catalysis of the oxidation of substituted benzoins to benzils by potassium ferricyanide. This reaction was used as a mechanistic probe to learn about the initial steps of the 24H6-catalyzed aldol condensation reaction. The Hammett correlation (rho=4.7) of log(k(cat)) versus the substituent constant, sigma, revealed that the reaction involves rapid formation of a Schiff base intermediate from the ketone and an active site lysine residue. The rate-limiting step in this oxidation reaction is the conversion of the Schiff base to an enamine intermediate. In addition, linear correlation (rho=3.13) was found between log(K(M)) and sigma, indicating that electronic rather than steric factors are dominant in the antibody-substrate binding phenomenon and confirming that the reversible formation of a Schiff base intermediate comprises part of the substrate-binding mechanism.

Influence of the bud neck on nuclear envelope fission in Saccharomyces cerevisiae.

PubMed

Melloy, Patricia G; Rose, Mark D

2017-09-15

Studies have shown that nuclear envelope fission (karyokinesis) in budding yeast depends on cytokinesis, but not distinguished whether this was a direct requirement, indirect, because of cell cycle arrest, or due to bud neck-localized proteins impacting both processes. To determine the requirements for karyokinesis, we examined mutants conditionally defective for bud emergence and/or nuclear migration. The common mutant phenotype was completion of the nuclear division cycle within the mother cell, but karyokinesis did not occur. In the cdc24 swe1 mutant, at the non-permissive temperature, multiple nuclei accumulated within the unbudded cell, with connected nuclear envelopes. Upon return to the permissive temperature, the cdc24 swe1 mutant initiated bud emergence, but only the nucleus spanning the neck underwent fission suggesting that the bud neck region is important for fission initiation. The neck may be critical for either mechanical reasons, as the contractile ring might facilitate fission, or for regulatory reasons, as the site of a protein network regulating nuclear envelope fission, mitotic exit, and cytokinesis. We also found that 77-85% of pairs of septin mutant nuclei completed nuclear envelope fission. In addition, 27% of myo1Δ mutant nuclei completed karyokinesis. These data suggested that fission is not dependent on mechanical contraction at the bud neck, but was instead controlled by regulatory proteins there. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical usefulness of a functional assay for the von Willebrand factor cleaving protease (ADAMTS 13) and its inhibitor in a patient with thrombotic thrombocytopenic purpura.

PubMed

Rick, M E; Austin, H; Leitman, S F; Krizek, D M; Aronson, D L

2004-02-01

Decreased von Willebrand factor cleaving protease activity (VWFCP, ADAMTS 13) leads to persistence of unusually large multimers of von Willebrand factor that bind to platelets, causing platelet aggregates, microangiopathic hemolysis, and thrombocytopenia in patients with thrombotic thrombocytopenic purpura (TTP). The clinical value of measuring ADAMTS 13 and its inhibitor is not fully defined; the case reported here illustrates the usefulness of the assay to help confirm the clinical diagnosis in a patient with other potential causes for thrombotic microangiopathy; the assay also helped in making treatment decisions. A patient with systemic lupus erythematosis (SLE) presented with fever and abdominal pain, thrombocytopenia, and anemia. Thrombotic microangiopathy was diagnosed by the appearance of schistocytes, decreasing platelet count, and evidence of hemolysis. ADAMTS 13 was decreased and an inhibitor was demonstrated in the patient's initial blood sample within 24 hr of admission. Plasma exchange was initiated, and serial assays showed increased ADAMTS 13 activity and decreased inhibitor after each plasma exchange; there was a rebound in inhibitor and a decrease in ADAMTS 13 activity prior to the next exchange that lessened over time. Increasing levels of protease activity correlated with clinical and laboratory improvement. Measurement of ADAMTS 13 activity and its inhibitor aided in the diagnosis of this complicated case of a patient with other potential causes for microangiopathic hemolysis. Subsequent levels correlated with the clinical course, and disappearance of the inhibitor indicated that long-term plasma exchange or other immunosuppressive treatment was not needed.

Cdc48 regulates a deubiquitylase cascade critical for mitochondrial fusion

PubMed Central

den Brave, Fabian

2018-01-01

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

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

PubMed

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

2017-06-01

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

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

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-18

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

13 CFR 120.926 - Referral fee.

Code of Federal Regulations, 2014 CFR

2014-01-01

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

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-02

... Intent To Award Affordable Care Act Funding, Funding Opportunity Announcement CDC-RFA-DP09-905 AGENCY: Centers for Disease Control and Prevention (CDC), Department of Health and Human Services (HHS). ACTION: Notice. SUMMARY: This notice provides notice of CDC's intent to fund continuation cooperative agreement...

13 CFR 120.926 - Referral fee.

Code of Federal Regulations, 2013 CFR

2013-01-01

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

13 CFR 120.926 - Referral fee.

Code of Federal Regulations, 2011 CFR

2011-01-01

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

13 CFR 120.926 - Referral fee.

Code of Federal Regulations, 2012 CFR

2012-01-01

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

13 CFR 120.926 - Referral fee.

Code of Federal Regulations, 2010 CFR

2010-01-01

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

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

PubMed Central

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

2010-01-01

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

Cdc7 kinase - a new target for drug development.

PubMed

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

2010-01-01

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

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2017-04-07

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

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

PubMed

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

2011-01-01

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

Dendritic spine geometry can localize GTPase signaling in neurons

PubMed Central

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

2015-01-01

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

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

PubMed Central

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

2007-01-01

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

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

PubMed

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

2009-10-15

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

Gene and Protein Expression in Response to Different Growth Temperatures and Oxygen Availability in Burkholderia thailandensis

PubMed Central

Peano, Clelia; Chiaramonte, Fabrizio; Motta, Sara; Pietrelli, Alessandro; Jaillon, Sebastien; Rossi, Elio; Consolandi, Clarissa; Champion, Olivia L.; Michell, Stephen L.; Freddi, Luca; Falciola, Luigi; Basilico, Fabrizio; Garlanda, Cecilia; Mauri, Pierluigi; De Bellis, Gianluca; Landini, Paolo

2014-01-01

Burkholderia thailandensis, although normally avirulent for mammals, can infect macrophages in vitro and has occasionally been reported to cause pneumonia in humans. It is therefore used as a model organism for the human pathogen B. pseudomallei, to which it is closely related phylogenetically. We characterized the B. thailandensis clinical isolate CDC2721121 (BtCDC272) at the genome level and studied its response to environmental cues associated with human host colonization, namely, temperature and oxygen limitation. Effects of the different growth conditions on BtCDC272 were studied through whole genome transcription studies and analysis of proteins associated with the bacterial cell surface. We found that growth at 37°C, compared to 28°C, negatively affected cell motility and flagella production through a mechanism involving regulation of the flagellin-encoding fliC gene at the mRNA stability level. Growth in oxygen-limiting conditions, in contrast, stimulated various processes linked to virulence, such as lipopolysaccharide production and expression of genes encoding protein secretion systems. Consistent with these observations, BtCDC272 grown in oxygen limitation was more resistant to phagocytosis and strongly induced the production of inflammatory cytokines from murine macrophages. Our results suggest that, while temperature sensing is important for regulation of B. thailandensis cell motility, oxygen limitation has a deeper impact on its physiology and constitutes a crucial environmental signal for the production of virulence factors. PMID:24671187

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

PubMed Central

2017-01-01

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

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

PubMed

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

2017-01-01

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