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.

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

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.

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...

[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.

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.

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.

Genomics and Public Health Research: Can the State Allow Access to Genomic Databases?

PubMed Central

Cousineau, J; Girard, N; Monardes, C; Leroux, T; Jean, M Stanton

2012-01-01

Because many diseases are multifactorial disorders, the scientific progress in genomics and genetics should be taken into consideration in public health research. In this context, genomic databases will constitute an important source of information. Consequently, it is important to identify and characterize the State’s role and authority on matters related to public health, in order to verify whether it has access to such databases while engaging in public health genomic research. We first consider the evolution of the concept of public health, as well as its core functions, using a comparative approach (e.g. WHO, PAHO, CDC and the Canadian province of Quebec). Following an analysis of relevant Quebec legislation, the precautionary principle is examined as a possible avenue to justify State access to and use of genomic databases for research purposes. Finally, we consider the Influenza pandemic plans developed by WHO, Canada, and Quebec, as examples of key tools framing public health decision-making process. We observed that State powers in public health, are not, in Quebec, well adapted to the expansion of genomics research. We propose that the scope of the concept of research in public health should be clear and include the following characteristics: a commitment to the health and well-being of the population and to their determinants; the inclusion of both applied research and basic research; and, an appropriate model of governance (authorization, follow-up, consent, etc.). We also suggest that the strategic approach version of the precautionary principle could guide collective choices in these matters. PMID:23113174

Differences in food environment perceptions and spatial attributes of food shopping between residents of low and high food access areas.

PubMed

Sohi, Inderbir; Bell, Bethany A; Liu, Jihong; Battersby, Sarah E; Liese, Angela D

2014-01-01

To explore potential differences in food shopping behaviors and healthy food availability perceptions between residents living in areas with low and high food access. A cross-sectional telephone survey to assess food shopping behaviors and perceptions. Data from an 8-county food environment field census used to define the Centers for Disease Control and Prevention (CDC) healthier food retail tract and US Department of Agriculture Economic Research Service food desert measure. A total of 968 residents in 8 South Carolina counties. Residents' food shopping behaviors and healthy food availability perceptions. Linear and logistic regression. Compared with residents in high food access areas, residents in low food access areas traveled farther to their primary food store (US Department of Agriculture Economic Research Service: 8.8 vs 7.1 miles, P = .03; CDC: 9.2 vs 6.1 miles, P < .001), accumulated more total shopping miles per week (CDC: 28.0 vs 15.4 miles; P < .001), and showed differences in perceived healthy food availability (P < .001) and shopping access (P < .001). These findings lend support to ongoing community and policy interventions aimed at reducing food access disparities. Copyright © 2014 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

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.

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

PubMed

Fernando, Daniel

2017-12-01

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

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.

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

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.

Differences in Food Environment Perceptions and Spatial Attributes of Food Shopping between Residents of Low and High Food Access Areas

PubMed Central

Sohi, Inderbir; Bell, Bethany A.; Liu, Jihong; Battersby, Sarah E.; Liese, Angela D.

2014-01-01

Objective To explore potential differences in food shopping behaviors and healthy food availability perceptions between residents living in areas with low and high food access. Design A cross-sectional telephone survey to assess food shopping behaviors and perceptions. Data from an eight-county food environment field census used to define the CDC (Centers for Disease Control and Prevention) healthier food retail tract and USDA ERS (United States Department of Agriculture Economic Research Service) food desert measure. Participants 968 residents in eight South Carolina counties. Main Outcome Measures Residents’ food shopping behaviors and healthy food availability perceptions. Analysis Linear and logistic regression. Results Compared to residents in high food access areas, residents in low food access areas traveled further to their primary food store (USDA ERS: 8.8 vs. 7.1 miles, p=0.03; CDC: 9.2 vs. 6.1 miles, p<0.001), accumulated more total shopping miles per week; CDC 28.0 vs. 15.4 miles, p<0.001) and showed differences in perceived healthy food availability (p<0.001) and shopping access (p<0.001). Conclusions and Implications These findings lend support to ongoing community and policy interventions aimed at reducing food access disparities. PMID:24560861

CDC, TJC Urge Providers To Up Their Game on Antibiotic Stewardship.

PubMed

Srinivasan, Arjun; Vento, Todd

2017-03-01

With data showing continued increases in the use of antibiotics, even in cases in which such prescribing is unnecessary and ill-advised, both the CDC and TJC are pushing initiatives aimed at improving antibiotic stewardship. The initiatives stress the importance of patient and provider education, the tracking of antibiotic use and resistance, and the need for top-level support. Although smaller hospitals face challenges in meeting the new standards, some health systems are getting around the problem through the use of telemedicine. The CDC is pushing hospitals to implement seven core elements that the agency maintains are critical to an effective antibiotic stewardship program. TJC has established a new standard requiring all hospitals to create antibiotic stewardship programs that are steered by a multidisciplinary team. Intermountain Healthcare in Salt Lake City is helping smaller hospitals in its network meet these new TJC and CDC directives by supplying support and expertise via telemedicine. The telehealth program also enables both emergency and inpatient providers to access infectious disease expertise when patients present with issues of concern.

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 120.851 - 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...

The education of physicians: a CDC perspective.

PubMed

Koo, Denise; Thacker, Stephen B

2008-04-01

The Centers for Disease Control and Prevention (CDC) strongly supports integrating population health perspectives into the education of physicians. Physicians with critical-thinking skills, a commitment to the health of a community, and a systems-based approach are critical partners for the agency in its mission to protect and promote the public's health. To cultivate such physicians, integrating population health concepts solely into undergraduate medical education would be inadequate. A multipronged approach that establishes and maintains population health concepts with physicians at all stages of their education is needed: before medical school, during medical school, during residency and fellowship, and in research and practice (particularly for faculty who train the next generation). The authors describe relevant, CDC-conducted or CDC-supported activities that support such physician education during all these stages. Based in part on recent, cutting-edge trends assimilating community health particularly into primary care residencies, the authors also offer ideas for new ways that CDC can participate in the development of physicians who are truly competent at both medicine and population health in an integrated fashion -- physicians who focus on and care for individual patients but who also take a broader population or community perspective and can act effectively in either arena. Physicians who take such a systems approach -- who view and understand medicine and public health as a continuum rather than as distinct arenas -- are sorely needed to help solve the current health system crisis and to contribute to improving health in other ways.

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...

78 FR 46953 - CDC and ATSDR Use of the SF-424 Research and Related Forms (Application Packages) in Grants.gov...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-02

... Use of the SF-424 Research and Related Forms (Application Packages) in Grants.gov and the eRA Commons... Management and Budget approved form sets available through Grants.gov . CDC and other agencies serviced by eRA use the `Competition ID' field of Grants.gov application packages for quick and easy...

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 120.823 - 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 120.823 - 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 120.821 - 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 120.821 - 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 120.821 - 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 120.851 - 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...

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.

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.

Reflections and Recommendations Based on a Migrant Health Center's Participation in a CDC Study.

ERIC Educational Resources Information Center

Nolon, Anne K.; O'Barr, James

Hudson Valley Migrant Health (HVMH) (a Public Health Service program) collaborated with the Center for Disease Control (CDC) and the New York State Department of Health (NYSDOH) on a study of the incidence of sexually transmitted diseases and tuberculosis among migrant farmworkers in the mid-Hudson region of New York. CDC research personnel…

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

PubMed

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

2016-01-01

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

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

PubMed Central

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

2016-01-01

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

CDC's Evolving Approach to Emergency Response.

PubMed

Redd, Stephen C; Frieden, Thomas R

The Centers for Disease Control and Prevention (CDC) transformed its approach to preparing for and responding to public health emergencies following the anthrax attacks of 2001. The Office of Public Health Preparedness and Response, an organizational home for emergency response at CDC, was established, and 4 programs were created or greatly expanded after the anthrax attacks: (1) an emergency management program, including an Emergency Operations Center; (2) increased support of state and local health department efforts to prepare for emergencies; (3) a greatly enlarged Strategic National Stockpile of medicines, vaccines, and medical equipment; and (4) a regulatory program to assure that work done on the most dangerous pathogens and toxins is done as safely and securely as possible. Following these changes, CDC led responses to 3 major public health emergencies: the 2009-10 H1N1 influenza pandemic, the 2014-16 Ebola epidemic in West Africa, and the ongoing Zika epidemic. This article reviews the programs of CDC's Office of Public Health Preparedness, the major responses, and how these responses have resulted in changes in CDC's approach to responding to public health emergencies.

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

PubMed

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

2015-12-01

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

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.

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 120.830 - 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 120.830 - 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...

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.

Depletion of cdc-25.3, a Caenorhabditis elegans orthologue of cdc25, increases physiological germline apoptosis.

PubMed

Sung, Minhee; Kawasaki, Ichiro; Shim, Yhong-Hee

2017-07-01

In Caenorhabditis elegans hermaphrodites, physiological germline apoptosis is higher in cdc-25.3 mutants than in wild-type. The elevated germline apoptosis in cdc-25.3 mutants seems to be induced by accumulation of double-stranded DNA breaks (DSBs). Both DNA damage and synapsis checkpoint genes are required to increase the germline apoptosis. Notably, the number of germ cells that lose P-granule components, PGL-1 and PGL-3, increase in cdc-25.3 mutants, and the increase in germline apoptosis requires the activity of SIR-2.1, a Sirtuin orthologue. These results suggest that elevation of germline apoptosis in cdc-25.3 mutants is induced by accumulation of DSBs, leading to a loss of PGL-1 and PGL-3 in germ cells, which promotes cytoplasmic translocation of SIR-2.1, and finally activates the core apoptotic machinery. © 2017 Federation of European Biochemical Societies.

Semantic representation of CDC-PHIN vocabulary using Simple Knowledge Organization System.

PubMed

Zhu, Min; Mirhaji, Parsa

2008-11-06

PHIN Vocabulary Access and Distribution System (VADS) promotes the use of standards based vocabulary within CDC information systems. However, the current PHIN vocabulary representation hinders its wide adoption. Simple Knowledge Organization System (SKOS) is a W3C draft specification to support the formal representation of Knowledge Organization Systems (KOS) within the framework of the Semantic Web. We present a method of adopting SKOS to represent PHIN vocabulary in order to enable automated information sharing and integration.

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

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 ...

UPEML: a machine-portable CDC Update emulator

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

Mehlhorn, T.A.; Young, M.F.

1984-12-01

UPEML is a machine-portable CDC Update emulation program. UPEML is written in ANSI standard Fortran-77 and is relatively simple and compact. It is capable of emulating a significant subset of the standard CDC Update functions including program library creation and subsequent modification. Machine-portability is an essential attribute of UPEML. It was written primarily to facilitate the use of CDC-based scientific packages on alternate computer systems such as the VAX 11/780 and the IBM 3081.

Research Issues in Information Access.

ERIC Educational Resources Information Center

Molholt, Pat

1989-01-01

Discusses traditional library approaches to access to information and the possible impact of information technologies, library automation, and artificial intelligence. Access issues raised by these technologies are identified and a research agenda to explore these issues is outlined. (31 references) (CLB)

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

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 120.810 - 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...

Open Access, Education Research, and Discovery

ERIC Educational Resources Information Center

Furlough, Michael

2010-01-01

Background/Context: The open access movement has successfully drawn attention to economic and political aspects of scholarly communication through a significant body of commentary that debates the merits of open access and the potential damage it may do to scholarly publishing. Researchers within the field of education research, notably John…

Enhancing Ocean Research Data Access

NASA Astrophysics Data System (ADS)

Chandler, Cynthia; Groman, Robert; Shepherd, Adam; Allison, Molly; Arko, Robert; Chen, Yu; Fox, Peter; Glover, David; Hitzler, Pascal; Leadbetter, Adam; Narock, Thomas; West, Patrick; Wiebe, Peter

2014-05-01

The Biological and Chemical Oceanography Data Management Office (BCO-DMO) works in partnership with ocean science investigators to publish data from research projects funded by the Biological and Chemical Oceanography Sections and the Office of Polar Programs Antarctic Organisms & Ecosystems Program at the U.S. National Science Foundation. Since 2006, researchers have been contributing data to the BCO-DMO data system, and it has developed into a rich repository of data from ocean, coastal and Great Lakes research programs. While the ultimate goal of the BCO-DMO is to ensure preservation of NSF funded project data and to provide open access to those data, achievement of those goals is attained through a series of related phases that benefits from active collaboration and cooperation with a large community of research scientists as well as curators of data and information at complementary data repositories. The BCO-DMO is just one of many intermediate data management centers created to facilitate long-term preservation of data and improve access to ocean research data. Through partnerships with other data management professionals and active involvement in local and global initiatives, BCO-DMO staff members are working to enhance access to ocean research data available from the online BCO-DMO data system. Continuing efforts in use of controlled vocabulary terms, development of ontology design patterns and publication of content as Linked Open Data are contributing to improved discovery and availability of BCO-DMO curated data and increased interoperability of related content available from distributed repositories. We will demonstrate how Semantic Web technologies (e.g. RDF/XML, SKOS, OWL and SPARQL) have been integrated into BCO-DMO data access and delivery systems to better serve the ocean research community and to contribute to an expanding global knowledge network.

Establishment of a cell model for screening antibody drugs against rheumatoid arthritis with ADCC and CDC.

PubMed

Yan, Li; Hu, Rui; Tu, Song; Cheng, Wen-Jun; Zheng, Qiong; Wang, Jun-Wen; Kan, Wu-Sheng; Ren, Yi-Jun

2015-01-01

TNFα played a dominant role in the development and progression of rheumatoid arthritis (RA). Clinical trials proved the efficacies of anti-TNFα agents for curing RA. However, most researchers were concentrating on their abilities of neutralizing TNFα, the potencies of different anti-TNFα agents varied a lot due to the antibody-dependent cell-mediated cytotoxicity (ADCC) or complement dependent cytotoxicity (CDC). For better understanding and differentiating the potentiality of various candidate anti-TNF reagents at the stage of new drug research and development, present study established a cell model expressing the transmembrane TNFα for usage in in vitro ADCC or CDC assay, meanwhile, the assay protocol described here could provide guidelines for screening macromolecular antibody drugs. A stable cell subline bearing transmembrane TNFα was first established by conventional transfection method, the expression of transmembrane TNFα was approved by flow cytometer, and the performance of the stable subline in ADCC and CDC assay was evaluated, using human peripheral blood mononuclear cells as effector cells, and Adalimumab as the anti-TNFα reagent. The stable cell subline demonstrated high level of surface expression of transmembrane TNFα, and Adalimumab exerted both ADCC and CDC effects on this cell model. In conclusion, the stable cell line we established in present research could be used in ADCC or CDC assay for screening antibody drugs, which would provide in-depth understanding of the potencies of candidate antibody drugs in addition to the traditional TNFα neutralizing assay.

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

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.

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.

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.

Science in Emergency Response at CDC: Structure and Functions.

PubMed

Iskander, John; Rose, Dale A; Ghiya, Neelam D

2017-09-01

Recent high-profile activations of the US Centers for Disease Control and Prevention (CDC) Emergency Operations Center (EOC) include responses to the West African Ebola and Zika virus epidemics. Within the EOC, emergency responses are organized according to the Incident Management System, which provides a standardized structure and chain of command, regardless of whether the EOC activation occurs in response to an outbreak, natural disaster, or other type of public health emergency. By embedding key scientific roles, such as the associate director for science, and functions within a Scientific Response Section, the current CDC emergency response structure ensures that both urgent and important science issues receive needed attention. Key functions during emergency responses include internal coordination of scientific work, data management, information dissemination, and scientific publication. We describe a case example involving the ongoing Zika virus response that demonstrates how the scientific response structure can be used to rapidly produce high-quality science needed to answer urgent public health questions and guide policy. Within the context of emergency response, longer-term priorities at CDC include both streamlining administrative requirements and funding mechanisms for scientific research.

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

PubMed

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

2018-04-17

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

Structure and functions of the chaperone-like p97/CDC48 in plants.

PubMed

Bègue, Hervé; Jeandroz, Sylvain; Blanchard, Cécile; Wendehenne, David; Rosnoblet, Claire

2017-01-01

The chaperone-like p97 is a member of the AAA+ ATPase enzyme family that contributes to numerous cellular activities. P97 has been broadly studied in mammals (VCP/p97) and yeasts (CDC48: Cell Division Cycle 48/p97) and numerous investigations highlighted that this protein is post-translationally regulated, is structured in homohexamer and interacts with partners and cofactors that direct it to distinct cellular signalization pathway including protein quality control and degradation, cell cycle regulation, genome stability, vesicular trafficking, autophagy and immunity. p97 is also conserved in plants (CDC48) but its functions are less understood. In the present review we intended to present the state of the art of the structure, regulation and functions of CDC48 in plants. Evidence accumulated underline that CDC48 plays a crucial role in development, cell cycle regulation and protein turnover in plants. Furthermore, its involvement in plant immunity has recently emerged and first interacting partners have been identified, shedding light on its putative cellular activities. Identification of emerging functions of CDC48 in plants opens new roads of research in immunity and provides new insights into the mechanisms of protein quality control. Copyright © 2016 Elsevier B.V. All rights reserved.

CDC's Emergency Management Program activities - worldwide, 2003-2012.

PubMed

2013-09-06

In 2003, recognizing the increasing frequency and complexity of disease outbreaks and disasters and a greater risk for terrorism, CDC established the Emergency Operations Center (EOC), bringing together CDC staff members who respond to public health emergencies to enhance communication and coordination. To complement the physical EOC environment, CDC implemented the Incident Management System (IMS), a staffing structure and set of standard operational protocols and services to support and monitor CDC program-led responses to complex public health emergencies. The EOC and IMS are key components of CDC's Emergency Management Program (EMP), which applies emergency management principles to public health practice. To enumerate activities conducted by the EMP during 2003-2012, CDC analyzed data from daily reports and activity logs. The results of this analysis determined that, during 2003-2012, the EMP fully activated the EOC and IMS on 55 occasions to support responses to infectious disease outbreaks, natural disasters, national security events (e.g., conventions, presidential addresses, and international summits), mass gatherings (e.g., large sports and social events), and man-made disasters. On 109 other occasions, the EMP was used to support emergency responses that did not require full EOC activation, and the EMP also conducted 30 exercises and drills. This report provides an overview of those 194 EMP activities.

NIH support of Centers for AIDS Research and Department of Health Collaborative Public Health Research: advancing CDC's Enhanced Comprehensive HIV Prevention Planning project.

PubMed

Greenberg, Alan E; Purcell, David W; Gordon, Christopher M; Flores, Stephen; Grossman, Cynthia; Fisher, Holly H; Barasky, Rebecca J

2013-11-01

The contributions reported in this supplemental issue highlight the relevance of NIH-funded CEWG research to health department–supported HIV prevention and care activities in the 9 US cities with the highest numbers of AIDS cases. The project findings have the potential to enhance ongoing HIV treatment and care services and to advance the wider scientific agenda. The HIV testing to care continuum, while providing a framework to help track progress on national goals, also can reflect the heterogeneities of local epidemics. The collaborative research that is highlighted in this issue not only reflects a locally driven research agenda but also demonstrates research methods, data collection tools, and collaborative processes that could be encouraged across jurisdictions. Projects such as these, capitalizing on the integrated efforts of NIH, CDC, DOH, and academic institutions, have the potential to contribute to improvements in the HIV care continuum in these communities, bringing us closer to realizing the HIV prevention and treatment goals of the NHAS.

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.

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 120.857 - 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 120.857 - 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...

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 120.829 - 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 120.829 - 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...

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

PubMed

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

2014-10-23

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

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 120.820 - 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 120.820 - 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...

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

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.

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

Correlates of Access to Business Research Databases

ERIC Educational Resources Information Center

Gottfried, John C.

2010-01-01

This study examines potential correlates of business research database access through academic libraries serving top business programs in the United States. Results indicate that greater access to research databases is related to enrollment in graduate business programs, but not to overall enrollment or status as a public or private institution.…

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

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.

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.

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

PubMed

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

1998-07-01

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

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

PubMed Central

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

1998-01-01

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

13 CFR 120.950 - SBA and CDC must appoint agents.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false SBA and CDC must appoint agents... Development Company Loan Program (504) Debenture Sales and Service Agents § 120.950 SBA and CDC must appoint agents. SBA and the CDC must appoint the following agents to facilitate the sale and service of the...

13 CFR 120.950 - SBA and CDC must appoint agents.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false SBA and CDC must appoint agents... Development Company Loan Program (504) Debenture Sales and Service Agents § 120.950 SBA and CDC must appoint agents. SBA and the CDC must appoint the following agents to facilitate the sale and service of the...

13 CFR 120.950 - SBA and CDC must appoint agents.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false SBA and CDC must appoint agents... Development Company Loan Program (504) Debenture Sales and Service Agents § 120.950 SBA and CDC must appoint agents. SBA and the CDC must appoint the following agents to facilitate the sale and service of the...

13 CFR 120.950 - SBA and CDC must appoint agents.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false SBA and CDC must appoint agents... Development Company Loan Program (504) Debenture Sales and Service Agents § 120.950 SBA and CDC must appoint agents. SBA and the CDC must appoint the following agents to facilitate the sale and service of the...

13 CFR 120.950 - SBA and CDC must appoint agents.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false SBA and CDC must appoint agents... Development Company Loan Program (504) Debenture Sales and Service Agents § 120.950 SBA and CDC must appoint agents. SBA and the CDC must appoint the following agents to facilitate the sale and service of the...

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

Supporting open access to clinical trial data for researchers: The Duke Clinical Research Institute-Bristol-Myers Squibb Supporting Open Access to Researchers Initiative.

PubMed

Pencina, Michael J; Louzao, Darcy M; McCourt, Brian J; Adams, Monique R; Tayyabkhan, Rehbar H; Ronco, Peter; Peterson, Eric D

2016-02-01

There are growing calls for sponsors to increase transparency by providing access to clinical trial data. In response, Bristol-Myers Squibb and the Duke Clinical Research Institute have collaborated on a new initiative, Supporting Open Access to Researchers. The aim is to facilitate open sharing of Bristol-Myers Squibb trial data with interested researchers. Key features of the Supporting Open Access to Researchers data sharing model include an independent review committee that ensures expert consideration of each proposal, stringent data deidentification/anonymization and protection of patient privacy, requirement of prespecified statistical analysis plans, and independent review of manuscripts before submission for publication. We believe that these approaches will promote open science by allowing investigators to verify trial results as well as to pursue interesting secondary uses of trial data without compromising scientific integrity. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Mechanism of Cdc42-induced actin polymerization in neutrophil extracts.

PubMed

Zigmond, S H; Joyce, M; Yang, C; Brown, K; Huang, M; Pring, M

1998-08-24

Cdc42, activated with GTPgammaS, induces actin polymerization in supernatants of lysed neutrophils. This polymerization, like that induced by agonists, requires elongation at filament barbed ends. To determine if creation of free barbed ends was sufficient to induce actin polymerization, free barbed ends in the form of spectrin-actin seeds or sheared F-actin filaments were added to cell supernatants. Neither induced polymerization. Furthermore, the presence of spectrin-actin seeds did not increase the rate of Cdc42-induced polymerization, suggesting that the presence of Cdc42 did not facilitate polymerization from spectrin-actin seeds such as might have been the case if Cdc42 inhibited capping or released G-actin from a sequestered pool. Electron microscopy revealed that Cdc42-induced filaments elongated rapidly, achieving a mean length greater than 1 micron in 15 s. The mean length of filaments formed from spectrin-actin seeds was <0.4 micron. Had spectrin-actin seeds elongated at comparable rates before they were capped, they would have induced longer filaments. There was little change in mean length of Cdc42-induced filaments between 15 s and 5 min, suggesting that the increase in F-actin over this time was due to an increase in filament number. These data suggest that Cdc42 induction of actin polymerization requires both creation of free barbed ends and facilitated elongation at these ends.

[Open access :an opportunity for biomedical research].

PubMed

Duchange, Nathalie; Autard, Delphine; Pinhas, Nicole

2008-01-01

Open access within the scientific community depends on the scientific context and the practices of the field. In the biomedical domain, the communication of research results is characterised by the importance of the peer reviewing process, the existence of a hierarchy among journals and the transfer of copyright to the editor. Biomedical publishing has become a lucrative market and the growth of electronic journals has not helped lower the costs. Indeed, it is difficult for today's public institutions to gain access to all the scientific literature. Open access is thus imperative, as demonstrated through the positions taken by a growing number of research funding bodies, the development of open access journals and efforts made in promoting open archives. This article describes the setting up of an Inserm portal for publication in the context of the French national protocol for open-access self-archiving and in an international context.

Regulation of Cdc42/Rac Signaling in the Establishment of Cell Polarity and Control of Cell Motility

DTIC Science & Technology

2004-08-01

Irazoqui Breast Cancer Predoctoral Traineeship Final Report Introduction Cdc42p, together with other polarity proteins, becomes polarized to a cap... Cancer Biology, Certificate in Cell and Molecular Biology. "* Awarded the Jane Coffin Childs Postdoctoral Fellowship for continuing research in the...Bemlp binds directly to both the Cdc42p-directed GEF Department of Pharmacology and Cancer Biology Duke University Medical Center, Durham, NC 27710

Comparing U.S. Injury Death Estimates from GBD 2015 and CDC WONDER.

PubMed

Wu, Yue; Cheng, Xunjie; Ning, Peishan; Cheng, Peixia; Schwebel, David C; Hu, Guoqing

2018-01-07

Objective : The purpose of the present study was to examine consistency in injury death statistics from the United States CDC Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) with those from GBD 2015 estimates. Methods : Differences in deaths and the percent difference in deaths between GBD 2015 and CDC WONDER were assessed, as were changes in deaths between 2000 and 2015 for the two datasets. Results : From 2000 to 2015, GBD 2015 estimates for the U.S. injury deaths were somewhat higher than CDC WONDER estimates in most categories, with the exception of deaths from falls and from forces of nature, war, and legal intervention in 2015. Encouragingly, the difference in total injury deaths between the two data sources narrowed from 44,897 (percent difference in deaths = 41%) in 2000 to 34,877 (percent difference in deaths = 25%) in 2015. Differences in deaths and percent difference in deaths between the two data sources varied greatly across injury cause and over the assessment years. The two data sources present consistent changes in direction from 2000 to 2015 for all injury causes except for forces of nature, war, and legal intervention, and adverse effects of medical treatment. Conclusions : We conclude that further studies are warranted to interpret the inconsistencies in data and develop estimation approaches that increase the consistency of the two datasets.

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...

Polo kinase Cdc5 is a central regulator of meiosis I

PubMed Central

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

2013-01-01

During meiosis, two consecutive rounds of chromosome segregation yield four haploid gametes from one diploid cell. The Polo kinase Cdc5 is required for meiotic progression, but how Cdc5 coordinates multiple cell-cycle events during meiosis I is not understood. Here we show that CDC5-dependent phosphorylation of Rec8, a subunit of the cohesin complex that links sister chromatids, is required for efficient cohesin removal from chromosome arms, which is a prerequisite for meiosis I chromosome segregation. CDC5 also establishes conditions for centromeric cohesin removal during meiosis II by promoting the degradation of Spo13, a protein that protects centromeric cohesin during meiosis I. Despite CDC5’s central role in meiosis I, the protein kinase is dispensable during meiosis II and does not even phosphorylate its meiosis I targets during the second meiotic division. We conclude that Cdc5 has evolved into a master regulator of the unique meiosis I chromosome segregation pattern. PMID:23918381

Supporting Public Access to Research Results

ERIC Educational Resources Information Center

Lapinski, P. Scott; Osterbur, David; Parker, Joshua; McCray, Alexa T.

2014-01-01

We posed the question of what services an academic library can best provide to support the NIH Public Access Policy. We approached the answer to this question through education, collaboration, and tool-building. As a result, over the last four years we have engaged over 1,500 participants in discussions of public access to research results, forged…

17 CFR 200.510 - Access by historical researchers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 17 Commodity and Securities Exchanges 2 2011-04-01 2011-04-01 false Access by historical researchers. 200.510 Section 200.510 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... Security Information and Material § 200.510 Access by historical researchers. (a) Persons outside the...

17 CFR 200.510 - Access by historical researchers.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 17 Commodity and Securities Exchanges 2 2012-04-01 2012-04-01 false Access by historical researchers. 200.510 Section 200.510 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... Security Information and Material § 200.510 Access by historical researchers. (a) Persons outside the...

17 CFR 200.510 - Access by historical researchers.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 17 Commodity and Securities Exchanges 2 2013-04-01 2013-04-01 false Access by historical researchers. 200.510 Section 200.510 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... Security Information and Material § 200.510 Access by historical researchers. (a) Persons outside the...

Transparency of Biobank Access in Canada: An Assessment of Industry Access and the Availability of Information on Access Policies and Resulting Research.

PubMed

Gibson, Shannon G; Axler, Renata E; Lemmens, Trudo

2017-12-01

A key issue impacting public trust in biobanks is how these resources are utilized, including who is given access to biobank data and samples. To assess the conditions under which researchers are given access to Canadian biobanks, we reviewed websites and contacted Canadian biobanks to determine the availability of information on access policies and procedures; research resulting from access biobank data and samples; and conditions on private industry access to biobanks. We also conducted expert interviews with key Canadian stakeholders ( n = 11) to obtain their perspectives on biobank transparency and access policies. Among 21 Canadian biobanks, there was wide variation in the access information made publicly available, and the majority of these allowed access by industry applicants. Biobanks should be governed by the principles of transparency, accountability, and accessibility, and attention must be given to the conditions around the commercialization of biobank-based research.

Mechanism of Cdc42-induced Actin Polymerization in Neutrophil Extracts

PubMed Central

Zigmond, Sally H.; Joyce, Michael; Yang, Changsong; Brown, Kevin; Huang, Minzhou; Pring, Martin

1998-01-01

Cdc42, activated with GTPγS, induces actin polymerization in supernatants of lysed neutrophils. This polymerization, like that induced by agonists, requires elongation at filament barbed ends. To determine if creation of free barbed ends was sufficient to induce actin polymerization, free barbed ends in the form of spectrin-actin seeds or sheared F-actin filaments were added to cell supernatants. Neither induced polymerization. Furthermore, the presence of spectrin-actin seeds did not increase the rate of Cdc42-induced polymerization, suggesting that the presence of Cdc42 did not facilitate polymerization from spectrin-actin seeds such as might have been the case if Cdc42 inhibited capping or released G-actin from a sequestered pool. Electron microscopy revealed that Cdc42-induced filaments elongated rapidly, achieving a mean length greater than 1 μm in 15 s. The mean length of filaments formed from spectrin-actin seeds was <0.4 μm. Had spectrin-actin seeds elongated at comparable rates before they were capped, they would have induced longer filaments. There was little change in mean length of Cdc42-induced filaments between 15 s and 5 min, suggesting that the increase in F-actin over this time was due to an increase in filament number. These data suggest that Cdc42 induction of actin polymerization requires both creation of free barbed ends and facilitated elongation at these ends. PMID:9722612

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

ERIC Educational Resources Information Center

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

2004-01-01

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

P97/CDC-48: proteostasis control in tumor cell biology.

PubMed

Fessart, Delphine; Marza, Esther; Taouji, Saïd; Delom, Frédéric; Chevet, Eric

2013-08-28

P97/CDC-48 is a prominent member of a highly evolutionary conserved Walker cassette - containing AAA+ATPases. It has been involved in numerous cellular processes ranging from the control of protein homeostasis to membrane trafficking through the intervention of specific accessory proteins. Expression of p97/CDC-48 in cancers has been correlated with tumor aggressiveness and prognosis, however the precise underlying molecular mechanisms remain to be characterized. Moreover p97/CDC-48 inhibitors were developed and are currently under intense investigation as anticancer drugs. Herein, we discuss the role of p97/CDC-48 in cancer development and its therapeutic potential in tumor cell biology. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Fission Yeast Apc15 Stabilizes MCC-Cdc20-APC/C Complexes, Ensuring Efficient Cdc20 Ubiquitination and Checkpoint Arrest.

PubMed

May, Karen M; Paldi, Flora; Hardwick, Kevin G

2017-04-24

During mitosis, cells must segregate the replicated copies of their genome to their daughter cells with extremely high fidelity. Segregation errors lead to an abnormal chromosome number (aneuploidy), which typically results in disease or cell death [1]. Chromosome segregation and anaphase onset are initiated through the action of the multi-subunit E3 ubiquitin ligase known as the anaphase-promoting complex or cyclosome (APC/C [2]). The APC/C is inhibited by the spindle checkpoint in the presence of kinetochore attachment defects [3, 4]. Here we demonstrate that two non-essential APC/C subunits (Apc14 and Apc15) regulate association of spindle checkpoint proteins, in the form of the mitotic checkpoint complex (MCC), with the APC/C. apc14Δ mutants display increased MCC association with the APC/C and are unable to silence the checkpoint efficiently. Conversely, apc15Δ mutants display reduced association between the MCC and APC/C, are defective in poly-ubiquitination of Cdc20, and are checkpoint defective. In vitro reconstitution studies have shown that human MCC-APC/C can contain two molecules of Cdc20 [5-7]. Using a yeast strain expressing two Cdc20 genes with different epitope tags, we show by co-immunoprecipitation that this is true in vivo. MCC binding to the second molecule of Cdc20 is mediated via the C-terminal KEN box in Mad3. Somewhat surprisingly, complexes containing both molecules of Cdc20 accumulate in apc15Δ cells, and the implications of this observation are discussed. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Accessibility | Frederick National Laboratory for Cancer Research

Cancer.gov

The Frederick National Laboratory for Cancer Research campus is making every effort to ensure that the information available on our website is accessible to all. If you use special adaptive equipment to access the web and encounter problems when usin

Open Access Publishing in Indian Premier Research Institutions

ERIC Educational Resources Information Center

Bhat, Mohammad Hanief

2009-01-01

Introduction: Publishing research findings in open access journals is a means of enhancing visibility and consequently increasing the impact of publications. This study provides an overview of open access publishing in premier research institutes of India. Method: The publication output of each institution from 2003 to 2007 was ascertained through…

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...

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...

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 120.827 - 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...

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 120.935 - 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...

Cell cycle sibling rivalry: Cdc2 vs. Cdk2.

PubMed

Kaldis, Philipp; Aleem, Eiman

2005-11-01

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

Subject Access to "Pornography" for Serious Research Purposes.

ERIC Educational Resources Information Center

Moya, Cynde

2001-01-01

Examines some of the research needs in academic disciplines for access to pornographic materials, and looks at tools, such as thesauri and Web directories, which have been built to help searchers find materials. Discusses research needs for access to materials; tools built by librarians to subject analyze material; and Internet words for indexing…

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.

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

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false SBA decision on application for a new CDC or for an existing CDC to expand Area of Operations. 120.837 Section 120.837 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504...

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

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

Devor, E.J.; Dill-Devor, R.M.

1994-09-01

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

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

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

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.

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

How accessible was information about H1N1 flu? Literacy assessments of CDC guidance documents for different audiences.

PubMed

Lagassé, Lisa P; Rimal, Rajiv N; Smith, Katherine C; Storey, J Douglas; Rhoades, Elizabeth; Barnett, Daniel J; Omer, Saad B; Links, Jonathan

2011-01-01

We assessed the literacy level and readability of online communications about H1N1/09 influenza issued by the Centers for Disease Control and Prevention (CDC) during the first month of outbreak. Documents were classified as targeting one of six audiences ranging in technical expertise. Flesch-Kincaid (FK) measure assessed literacy level for each group of documents. ANOVA models tested for differences in FK scores across target audiences and over time. Readability was assessed for documents targeting non-technical audiences using the Suitability Assessment of Materials (SAM). Overall, there was a main-effect by audience, F(5, 82) = 29.72, P<.001, but FK scores did not vary over time, F(2, 82) = .34, P>.05. A time-by-audience interaction was significant, F(10, 82) = 2.11, P<.05. Documents targeting non-technical audiences were found to be text-heavy and densely-formatted. The vocabulary and writing style were found to adequately reflect audience needs. The reading level of CDC guidance documents about H1N1/09 influenza varied appropriately according to the intended audience; sub-optimal formatting and layout may have rendered some text difficult to comprehend.

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.

Surgical site infection after breast surgery: impact of 2010 CDC reporting guidelines.

PubMed

Degnim, Amy C; Throckmorton, Alyssa D; Boostrom, Sarah Y; Boughey, Judy C; Holifield, Andrea; Baddour, Larry M; Hoskin, Tanya L

2012-12-01

Reported surgical site infection (SSI) rates after breast operations ranges 0.8-26 % in the literature. The aims of the present study were to characterize SSI after breast/axillary operations and determine the impact on the SSI rate of the 2010 Centers for Disease Control and Prevention (CDC) reporting guidelines that now specifically exclude cellulitis. Retrospective chart review identified 368 patients with 449 operated sides between July 2004 and June 2006. SSI was defined by CDC criteria: purulent drainage (category 1), positive aseptically collected culture (category 2), signs of inflammation with opening of incision and absence of negative culture (category 3), and physician diagnosis of infection (category 4). The impact of excluding cellulitis was assessed. Prior CDC reporting guidelines revealed that among 368 patients, 32 (8.7 %) experienced SSI in 33 (7.3 %) of 449 operated sides. Of these, 11 (33 %) met CDC criteria 1-3, while 22 (67 %) met CDC criterion 4. Excluding cellulitis cases per 2010 CDC SSI reporting guidelines eliminates 21 of the 22 infections previously meeting CDC criterion 4. Under the new reporting guidelines, the SSI rate is 12 (2.7 %) of 449 operated sides. SSI rates varied by procedure, but these differences were not statistically significant. Cellulitis after breast and axillary surgery is much more common than other criteria for SSI, and SSI rates are reduced almost threefold if cellulitis cases are excluded. Recently revised CDC reporting guidelines may result in underestimates of the clinical burden of SSI after breast/axillary surgery.

Phosphatidylserine and GTPase activation control Cdc42 nanoclustering to counter dissipative diffusion.

PubMed

Sartorel, Elodie; Ünlü, Caner; Jose, Mini; Massoni-Laporte, Aurélie; Meca, Julien; Sibarita, Jean-Baptiste; McCusker, Derek

2018-04-18

The anisotropic organization of plasma membrane constituents is indicative of mechanisms that drive the membrane away from equilibrium. However, defining these mechanisms is challenging due to the short spatio-temporal scales at which diffusion operates. Here, we use high-density single protein tracking combined with photoactivation localization microscopy (sptPALM) to monitor Cdc42 in budding yeast, a system in which Cdc42 exhibits anisotropic organization. Cdc42 exhibited reduced mobility at the cell pole, where it was organized in nanoclusters. The Cdc42 nanoclusters were larger at the cell pole than those observed elsewhere in the cell. These features were exacerbated in cells expressing Cdc42-GTP, and were dependent on the scaffold Bem1, which contributed to the range of mobility and nanocluster size exhibited by Cdc42. The lipid environment, in particular phosphatidylserine levels, also played a role in regulating Cdc42 nanoclustering. These studies reveal how the mobility of a Rho GTPase is controlled to counter the depletive effects of diffusion, thus stabilizing Cdc42 on the plasma membrane and sustaining cell polarity. Movie S1 Movie S1 sptPALM imaging of live yeast expressing Pil1-mEOS expressed at the genomic locus. Pil1-mEOS was simultaneously photo-converted with a 405 nm laser and imaged with a 561 nm laser using HiLo illumination. Images were acquired at 20 ms intervals, of which 300 frames are shown at 7 frames per second.

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.

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.

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

Code of Federal Regulations, 2012 CFR

2012-01-01

... fee and CDC fee. 120.972 Section 120.972 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION... and CDC fee. (a) Participation fee. For loans approved by SBA after September 30, 1996, SBA must... when the Third Party Lender occupies a senior credit position to SBA in the Project. (b) CDC fee. For...

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

Code of Federal Regulations, 2011 CFR

2011-01-01

... fee and CDC fee. 120.972 Section 120.972 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION... and CDC fee. (a) Participation fee. For loans approved by SBA after September 30, 1996, SBA must... when the Third Party Lender occupies a senior credit position to SBA in the Project. (b) CDC fee. For...

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

Code of Federal Regulations, 2014 CFR

2014-01-01

... fee and CDC fee. 120.972 Section 120.972 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION... and CDC fee. (a) Participation fee. For loans approved by SBA after September 30, 1996, SBA must... when the Third Party Lender occupies a senior credit position to SBA in the Project. (b) CDC fee. For...

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

Code of Federal Regulations, 2013 CFR

2013-01-01

... fee and CDC fee. 120.972 Section 120.972 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION... and CDC fee. (a) Participation fee. For loans approved by SBA after September 30, 1996, SBA must... when the Third Party Lender occupies a senior credit position to SBA in the Project. (b) CDC fee. For...

Portability studies of modular data base managers. Interim reports. [Running CDC's DATATRAN 2 on IBM 360/370 and IBM's JOSHUA on CDC computers

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

Kopp, H.J.; Mortensen, G.A.

1978-04-01

Approximately 60% of the full CDC 6600/7600 Datatran 2.0 capability was made operational on IBM 360/370 equipment. Sufficient capability was made operational to demonstrate adequate performance for modular program linking applications. Also demonstrated were the basic capabilities and performance required to support moderate-sized data base applications and moderately active scratch input/output applications. Approximately one to two calendar years are required to develop DATATRAN 2.0 capabilities fully for the entire spectrum of applications proposed. Included in the next stage of conversion should be syntax checking and syntax conversion features that would foster greater FORTRAN compatibility between IBM and CDC developed modules.more » The batch portion of the JOSHUA Modular System, which was developed by Savannah River Laboratory to run on an IBM computer, was examined for the feasibility of conversion to run on a Control Data Corporation (CDC) computer. Portions of the JOSHUA Precompiler were changed so as to be operable on the CDC computer. The Data Manager and Batch Monitor were also examined for conversion feasibility, but no changes were made in them. It appears to be feasible to convert the batch portion of the JOSHUA Modular System to run on a CDC computer with an estimated additional two to three man-years of effort. 9 tables.« 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.

CDC Vital Signs: Preventing Melanoma

MedlinePlus

... not use the device. Include warning statements in marketing materials about the risk of using the device. ... MB] en Español [PDF – 1.16 MB] CDC Digital Press Kit Read the MMWR Science Clips Language: ...

Embedded Carbide-derived Carbon (CDC) particles in polypyrrole (PPy) for linear actuator

NASA Astrophysics Data System (ADS)

Zondaka, Zane; Valner, Robert; Aabloo, Alvo; Tamm, Tarmo; Kiefer, Rudolf

2016-04-01

Conducting polymer linear actuators, for example sodium dodecylbenzenesulfonate (NaDBS) doped polypyrrole (PPy/DBS), have shown moderate strain and stress. The goal of this work was to increase the obtainable strain and stress by adding additional active material to PPy/DBS. In recent year's carbide-derived carbon (CDC)-based materials have been applied in actuators; however, the obtained displacement and actuation speed has been low comparing to conducting polymer based actuators. In the present work, a CDC-PPy hybrid was synthesized electrochemically and polyoxometalate (POM) - phosphotungstic acid - was used to attach charge to CDC particles. The CDC-POM served in the presence of NaDBS as an additional electrolyte. Cyclic voltammetry and chronopotentiometric electrochemomechanical deformation (ECMD) measurements were performed in Lithium bis(trifluoromethanesulfonyl)- imide (LiTFSI) aqueous electrolyte. The ECMD measurements revealed that the hybrid CDC-PPy material exhibited higher force and strain in comparison to PPy/DBS films. The new material was investigated by scanning electron microscopy (SEM) to evaluate CDC particle embedding in the polymer network.

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

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.

INFOL for the CDC 6400 Information Storage and Retrieval System. Reference Manual.

ERIC Educational Resources Information Center

Mittman, B.; And Others

INFOL for the CDC 6400 is a rewrite in FORTRAN IV of the CDC 3600/3800 INFOL (Information Oriented Language), a generalized information storage and retrieval system developed by the Control Data Corporation for the CDC 3600/3800 computer. With INFOL, selected pieces of information are extracted from a file and presented to the user quickly and…

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

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

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

Restricting access to publications from funded research: ethical issues and solutions.

PubMed

Manikandan, S; Vani, N Isai

2010-01-01

India is becoming one of the hubs of clinical research. Commensurate with these advances, the government funding for biomedical research in thrust areas is also increasing. The Indian Council of Medical Research (ICMR), Department of Biotechnology (DBT), Department of Science and Technology (DST) are some of the government organizations which provide financial support for various research projects. The results of the funded research projects are published in various international journals. Most of these journals have an access to paid subscribers only. Hence it is unethical to use the research grants from government (people's money) and not allow the scientific community free access to the results of the study. To tackle such issues, these agencies should sign the Berlin declaration and create open access repositories. A public access policy should be formulated and listed in JULIET. The funding bodies in India should also join Pubmed Central (PMC) to form PMC India so that every investigator who has received grants would submit the full text of the paper published from his study and these can be made freely accessible to everyone. Universities and research institutions should also develop institutional open access repositories. The public access policy has definitive advantages and should be implemented.

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

PubMed

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

2016-03-18

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

CDC Support for Global Public Health Emergency Management.

PubMed

Brencic, Daniel J; Pinto, Meredith; Gill, Adrienne; Kinzer, Michael H; Hernandez, Luis; Pasi, Omer G

2017-12-01

Recent pandemics and rapidly spreading outbreaks of infectious diseases have illustrated the interconnectedness of the world and the importance of improving the international community's ability to effectively respond. The Centers for Disease Control and Prevention (CDC), building on a strong foundation of lessons learned through previous emergencies, international recognition, and human and technical expertise, has aspired to support nations around the world to strengthen their public health emergency management (PHEM) capacity. PHEM principles streamline coordination and collaboration in responding to infectious disease outbreaks, which align with the core capacities outlined in the International Health Regulations 2005. CDC supports PHEM by providing in-country technical assistance, aiding the development of plans and procedures, and providing fellowship opportunities for public health emergency managers. To this end, CDC partners with US agencies, international partners, and multilateral organizations to support nations around the world to reduce illness and death from outbreaks of infectious diseases.

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

PubMed Central

Witte, Kristen; Strickland, Devin; Glotzer, Michael

2017-01-01

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

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

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

Cyclin A-mediated inhibition of intra-Golgi transport requires p34cdc2.

PubMed

Mackay, D; Kieckbusch, R; Adamczewski, J; Warren, G

1993-12-28

An in vitro assay was used to study the role of p34cdc2 in cyclin A-mediated vesicular transport inhibition. It was shown that the S-phase kinase p33cdk2 reduced the effect of cyclin A on transport assays performed with sHeLa cytosol, even though histone kinase was strongly activated. Also, transport with FT210 cytosol (which is temperature-sensitive for p34cdc2) was inhibited by cyclin A only at the permissive temperature. However, the phosphatase inhibitor microcystin inhibited transport without any requirement for p34cdc2 activity. These results show that transport is inhibited by cyclin A via p34cdc2, and also by another kinase, possibly downstream of p34cdc2.

Functional Dysregulation of CDC42 Causes Diverse Developmental Phenotypes.

PubMed

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

2018-01-17

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

Southwest Watershed Research Center Data Access Project

NASA Astrophysics Data System (ADS)

Nichols, M. H.; Anson, E.

2008-05-01

Hydrologic data, including rainfall and runoff data, have been collected on experimental watersheds operated by the U.S. Department of Agriculture Agricultural Research Service (USDA-ARS) in southern Arizona since the 1950s. These data are of national and international importance and make up one of the most comprehensive semiarid watershed data sets in the world. The USDA-ARS Southwest Watershed Research Center has recently developed an electronic data processing system that includes an online interface (http://tucson.ars.ag.gov/dap) to provide public access to the data. The goal of the system is to promote analyses and interpretations of historic and current data by improving data access. Data are collected from sensors in the field and are transmitted to computers in the office. The data are then processed, quality checked, and made available to users via the Internet. The publicly accessible part of the system consists of an interactive Web site, which provides an interface to the data, and a relational database, which is used to process, store, and manage data. The system was released to the public in October 2003, and since that time the online data access Web site has received more than 4500 visitors.

Leveraging geospatial data, technology, and methods for improving the health of communities: priorities and strategies from an expert panel convened by the CDC.

PubMed

Elmore, Kim; Flanagan, Barry; Jones, Nicholas F; Heitgerd, Janet L

2010-04-01

In 2008, CDC convened an expert panel to gather input on the use of geospatial science in surveillance, research and program activities focused on CDC's Healthy Communities Goal. The panel suggested six priorities: spatially enable and strengthen public health surveillance infrastructure; develop metrics for geospatial categorization of community health and health inequity; evaluate the feasibility and validity of standard metrics of community health and health inequities; support and develop GIScience and geospatial analysis; provide geospatial capacity building, training and education; and, engage non-traditional partners. Following the meeting, the strategies and action items suggested by the expert panel were reviewed by a CDC subcommittee to determine priorities relative to ongoing CDC geospatial activities, recognizing that many activities may need to occur either in parallel, or occur multiple times across phases. Phase A of the action items centers on developing leadership support. Phase B focuses on developing internal and external capacity in both physical (e.g., software and hardware) and intellectual infrastructure. Phase C of the action items plan concerns the development and integration of geospatial methods. In summary, the panel members provided critical input to the development of CDC's strategic thinking on integrating geospatial methods and research issues across program efforts in support of its Healthy Communities Goal.

Inhibition of CDC25B Phosphatase Through Disruption of Protein–Protein Interaction

DOE PAGES

Lund, George; Dudkin, Sergii; Borkin, Dmitry; ...

2014-11-25

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

TRUMP; transient and steady state temperature distribution. [IBM360,370; CDC7600; FORTRAN IV (95%) and BAL (5%) (IBM); FORTRAN IV (CDC)

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

Elrod, D.C.; Turner, W.D.

TRUMP solves a general nonlinear parabolic partial differential equation describing flow in various kinds of potential fields, such as fields of temperature, pressure, or electricity and magnetism; simultaneously, it will solve two additional equations representing, in thermal problems, heat production by decomposition of two reactants having rate constants with a general Arrhenius temperature dependence. Steady-state and transient flow in one, two, or three dimensions are considered in geometrical configurations having simple or complex shapes and structures. Problem parameters may vary with spatial position, time, or primary dependent variables--temperature, pressure, or field strength. Initial conditions may vary with spatial position, andmore » among the criteria that may be specified for ending a problem are upper and lower limits on the size of the primary dependent variable, upper limits on the problem time or on the number of time-steps or on the computer time, and attainment of steady state.IBM360,370;CDC7600; FORTRAN IV (95%) and BAL (5%) (IBM); FORTRAN IV (CDC); OS/360 (IBM360), OS/370 (IBM370), SCOPE 2.1.5 (CDC7600); As dimensioned, the program requires 400K bytes of storage on an IBM370 and 145,100 (octal) words on a CDC7600.« less

Towards a joint approach for access to environmental research infrastructures

NASA Astrophysics Data System (ADS)

Mann, Ingrid; Tjulin, Anders; Pappalardo, Gelsomina; Gagliardi, Simone; Philippin, Sabine; Sellegri, Karine; Chabbi, Abad

2016-04-01

Geoscience is a multi-disciplinary field and in many cases its research benefits from considering different kinds of observational results. Geoscience observations are in some cases of direct interest also to the public. For these reasons effective knowledge transfer and access also across disciplines are especially important for research infrastructures (RIs) in the environmental domain. More generally, the ultimate success of a RI is measured by its scientific outcome and this is best achieved based on efficient access for a broad scientific community. In this presentation the authors report activities to develop governance tools so that the access to environmental RIs and to the data that they provide is common, fair and based on scientific rationale, regarding at the same time economically and technically reasonable use of limited resources. Implementing such governance tools will indeed foster and widen the access to RIs across environmental science domains while addressing societal challenges. The strategies also need to be flexible and sustainable over the expected lifetimes of the RIs. The reported activities involve researchers from different projects and environmental subdomains that come together in the project ENVRI_plus. ENVRI_plus is a Cluster project of RIs that brings together the current ESFRI roadmap RIs in the environmental domain and other relevant existing and developing RIs and projects. ENVRI_plus also offers opportunities for free-of-charge transnational access to four multi-disciplinary research platforms. These calls for access target research groups and companies wishing to conduct research or to test instruments for cross-disciplinary topics within the environmental domains atmosphere, biosphere, marine, and solid earth. They are initiated specifically to gain experience with access across different disciplines (further information is given at www.envriplus.eu). ENVRI_plus receives funding from the European Union's Horizon 2020 research

Linking NASA Environmental Data with a National Public Health Cohort Study and a CDC On-Line System to Enhance Public Health Decision Making

NASA Technical Reports Server (NTRS)

Al-Hamdan, Mohammad; Crosson, William; Economou, Sigrid; Estes, Maurice, Jr.; Estes, Sue; Hemmings, Sarah; Kent, Shia; Puckett, Mark; Quattrochi, Dale; Wade, Gina;

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.

Identification of Novel Targets of the Human Cell Cycle Regulatory Protein Cdc34

DTIC Science & Technology

1998-07-01

Bohman, for stains and plamids, J. La Baer for the cDNA library, C. Molina, H. P. Roest, J. Hoeijmaker, P. Sassone-Corsi for antisera, and to Shirong...mammalian CDC34 cell cycle gene. American Association of Cancer Research, 36, A191 (1995). Hershko, A., Role of ubiquitin-mediated proteolysis in cell

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.

Research of Medication Use during Pregnancy

MedlinePlus

... Podcasts and Videos Buttons CDC’s Work Pregnancy Homepage Research Recommend on Facebook Tweet Share Compartir CDC and ... registration. Studies from the Centers for Birth Defects Research and Prevention CDC funds the Centers for Birth ...

Communications and Web services: What do CDC users desire in partner relationship management and does CDC's PHIN Directory meet the need?

PubMed

Cervone, Maria A; Savel, Thomas G

2006-01-01

The National Center on Birth Defects and Developmental Disabilities (NCBDDD) at the Centers for Disease Control and Prevention (CDC) sought to establish a database to proactively manage their partner relationships with external organizations. A user needs analysis was conducted, and CDC's Public Health Information Network Directory (PHINDIR) was evaluated as a possible solution. PHINDIR could sufficiently maintain contact information but did not address customer relationships; however, its flexible architecture allows add-on applications via web services. Thus, NCBDDD's needs could be met via PHINDIR.

MSE55, a Cdc42 effector protein, induces long cellular extensions in fibroblasts

PubMed Central

Burbelo, Peter D.; Snow, Dianne M.; Bahou, Wadie; Spiegel, Sarah

1999-01-01

Cdc42 is a member of the Rho GTPase family that regulates multiple cellular activities, including actin polymerization, kinase-signaling activation, and cell polarization. MSE55 is a nonkinase CRIB (Cdc42/Rac interactive-binding) domain-containing molecule of unknown function. Using glutathione S-transferase-capture experiments, we show that MSE55 binds to Cdc42 in a GTP-dependent manner. MSE55 binding to Cdc42 required an intact CRIB domain, because a MSE55 CRIB domain mutant no longer interacted with Cdc42. To study the function of MSE55 we transfected either wild-type MSE55 or a MSE55 CRIB mutant into mammalian cells. In Cos-7 cells, wild-type MSE55 localized at membrane ruffles and increased membrane actin polymerization, whereas expression of the MSE55 CRIB mutant showed fewer membrane ruffles. In contrast to these results, MSE55 induced the formation of long, actin-based protrusions in NIH 3T3 cells as detected by immunofluorescence and live-cell video microscopy. MSE55-induced protrusion formation was blocked by expression of dominant-negative N17Cdc42, but not by expression of dominant-negative N17Rac. These findings indicate that MSE55 is a Cdc42 effector protein that mediates actin cytoskeleton reorganization at the plasma membrane. PMID:10430899

Human Cdc14A regulates Wee1 stability by counteracting CDK-mediated phosphorylation

PubMed Central

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

2012-01-01

The activity of Cdk1–cyclin B1 mitotic complexes is regulated by the balance between the counteracting activities of Wee1/Myt1 kinases and Cdc25 phosphatases. These kinases and phosphatases must be strictly regulated to ensure proper mitotic timing. One masterpiece of this regulatory network is Cdk1, which promotes Cdc25 activity and suppresses inhibitory Wee1/Myt1 kinases through direct phosphorylation. The Cdk1-dependent phosphorylation of Wee1 primes phosphorylation by additional kinases such as Plk1, triggering Wee1 degradation at the onset of mitosis. Here we report that Cdc14A plays an important role in the regulation of Wee1 stability. Depletion of Cdc14A results in a significant reduction in Wee1 protein levels. Cdc14A binds to Wee1 at its amino-terminal domain and reverses CDK-mediated Wee1 phosphorylation. In particular, we found that Cdc14A inhibits Wee1 degradation through the dephosphorylation of Ser-123 and Ser-139 residues. Thus the lack of phosphorylation of these two residues prevents the interaction with Plk1 and the consequent efficient Wee1 degradation at the onset of mitosis. These data support the hypothesis that Cdc14A counteracts Cdk1–cyclin B1 activity through Wee1 dephosphorylation. PMID:23051732

CDC-42 Orients Cell Migration during Epithelial Intercalation in the Caenorhabditis elegans Epidermis.

PubMed

Walck-Shannon, Elise; Lucas, Bethany; Chin-Sang, Ian; Reiner, David; Kumfer, Kraig; Cochran, Hunter; Bothfeld, William; Hardin, Jeff

2016-11-01

Cell intercalation is a highly directed cell rearrangement that is essential for animal morphogenesis. As such, intercalation requires orchestration of cell polarity across the plane of the tissue. CDC-42 is a Rho family GTPase with key functions in cell polarity, yet its role during epithelial intercalation has not been established because its roles early in embryogenesis have historically made it difficult to study. To circumvent these early requirements, in this paper we use tissue-specific and conditional loss-of-function approaches to identify a role for CDC-42 during intercalation of the Caenorhabditis elegans dorsal embryonic epidermis. CDC-42 activity is enriched in the medial tips of intercalating cells, which extend as cells migrate past one another. Moreover, CDC-42 is involved in both the efficient formation and orientation of cell tips during cell rearrangement. Using conditional loss-of-function we also show that the PAR complex functions in tip formation and orientation. Additionally, we find that the sole C. elegans Eph receptor, VAB-1, functions during this process in an Ephrin-independent manner. Using epistasis analysis, we find that vab-1 lies in the same genetic pathway as cdc-42 and is responsible for polarizing CDC-42 activity to the medial tip. Together, these data establish a previously uncharacterized role for polarized CDC-42, in conjunction with PAR-6, PAR-3 and an Eph receptor, during epithelial intercalation.

Cdc7 is required throughout the yeast S phase to activate replication origins.

PubMed

Donaldson, A D; Fangman, W L; Brewer, B J

1998-02-15

The long-standing conclusion that the Cdc7 kinase of Saccharomyces cerevisiae is required only to trigger S phase has been challenged by recent data that suggests it acts directly on individual replication origins. We tested the possibility that early- and late-activated origins have different requirements for Cdc7 activity. Cells carrying a cdc7(ts) allele were first arrested in G1 at the cdc7 block by incubation at 37 degrees C, and then were allowed to enter S phase by brief incubation at 23 degrees C. During the S phase, after return to 37 degrees C, early-firing replication origins were activated, but late origins failed to fire. Similarly, a plasmid with a late-activated origin was defective in replication. As a consequence of the origin activation defect, duplication of chromosomal sequences that are normally replicated from late origins was greatly delayed. Early-replicating regions of the genome duplicated at approximately their normal time. The requirements of early and late origins for Cdc7 appear to be temporally rather than quantitatively different, as reducing overall levels of Cdc7 by growth at semi-permissive temperature reduced activation at early and late origins approximately equally. Our results show that Cdc7 activates early and late origins separately, with late origins requiring the activity later in S phase to permit replication initiation.

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...

PORTABLE LISP; a list-processing interpreter. [CDC7600; PASCAL

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

Taylor, W.P.

The program constitutes a complete, basic LISP (LIST-Processing language) interpreter. LISP expressions are evaluated one by one with both the input expression and the resulting evaluated expression printed. Expressions are evaluated until a FIN card is encountered. Between expression evaluations a garbage-collection algorithm is invoked to recover list space used in the previous evaluation.CDC7600; PASCAL; SCOPE; The sample problem was executed in 7000 (octal) words of memory on a CDC7600.

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.

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 120.852 - 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 120.852 - 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...

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

Summary and Findings of the EPA and CDC Symposium on Air Pollution Exposure and Health

EPA Science Inventory

The U.S. Environmental Protection Agency (EPA) and the U.S. Centers for Disease Control (CDC) co-organized a symposium on "Air Pollution Exposure and Health" at Research Triangle Park, North Carolina on September 19–20, 2006. The symposium brought together health and environmenta...

Mobilising Open Access to Research Data: Recommendations from the RECODE project

NASA Astrophysics Data System (ADS)

Finn, Rachel; Sveinsdottir, Thordis

2015-04-01

This paper will introduce the findings and policy recommendations from the FP7 project RECODE (Policy RECommendations for Open Access to Research Data in Europe) which aims to leverage existing networks, communities and projects to address challenges within the open access and data dissemination and preservation sector. We will introduce the key recommendations, which provide solutions relevant to opening access to PSI. The project is built on case study research of five scientific disciplines with the aim of recognizing and working with disciplinary fragmentation associated with open access to research data. The RECODE findings revealed that the mobilisation of open access to research data requires a partnership approach for developing a coherent and flexible ecosystem that is easy and transparent to embed in research practice and process. As such, the development of open access to research data needs to be: • Informed by research practices and processes in different fields • Supported by an integrated institutional and technological data infrastructure and guided by ethical and regulatory frameworks • Underpinned by infrastructure and guiding frameworks that allow for differences in disciplinary research and data management practices • Characterised by a partnership approach involving the key stakeholders, researchers, and institutions The proposed presentation will examine each of these aspects in detail and use information and good practices from the RECODE project to consider how stakeholders within the PSI movement might action each of these points. It will also highlight areas where RECODE findings and good practice recommendations have clear relevance for the PSI sector.

CDC-42 Orients Cell Migration during Epithelial Intercalation in the Caenorhabditis elegans Epidermis

PubMed Central

Lucas, Bethany; Chin-Sang, Ian; Reiner, David; Kumfer, Kraig

2016-01-01

Cell intercalation is a highly directed cell rearrangement that is essential for animal morphogenesis. As such, intercalation requires orchestration of cell polarity across the plane of the tissue. CDC-42 is a Rho family GTPase with key functions in cell polarity, yet its role during epithelial intercalation has not been established because its roles early in embryogenesis have historically made it difficult to study. To circumvent these early requirements, in this paper we use tissue-specific and conditional loss-of-function approaches to identify a role for CDC-42 during intercalation of the Caenorhabditis elegans dorsal embryonic epidermis. CDC-42 activity is enriched in the medial tips of intercalating cells, which extend as cells migrate past one another. Moreover, CDC-42 is involved in both the efficient formation and orientation of cell tips during cell rearrangement. Using conditional loss-of-function we also show that the PAR complex functions in tip formation and orientation. Additionally, we find that the sole C. elegans Eph receptor, VAB-1, functions during this process in an Ephrin-independent manner. Using epistasis analysis, we find that vab-1 lies in the same genetic pathway as cdc-42 and is responsible for polarizing CDC-42 activity to the medial tip. Together, these data establish a previously uncharacterized role for polarized CDC-42, in conjunction with PAR-6, PAR-3 and an Eph receptor, during epithelial intercalation. PMID:27861585

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.

Driver or passenger effects of augmented c-Myc and Cdc20 in gliomagenesis.

PubMed

Ji, Ping; Zhou, Xinhui; Liu, Qun; Fuller, Gregory N; Phillips, Lynette M; Zhang, Wei

2016-04-26

Cdc20 and c-Myc are commonly overexpressed in a broad spectrum of cancers, including glioblastoma (GBM). Despite this clear association, whether c-Myc and Cdc20 overexpression is a driver or passenger event in gliomagenesis remains unclear. Both c-Myc and Cdc20 induced the proliferation of primary glial progenitor cells. c-Myc also promoted the formation of soft agar anchorage-independent colonies. In the RCAS/Ntv-a glia-specific transgenic mouse model, c-Myc increased the GBM incidence from 19.1% to 47.4% by 12 weeks of age when combined with kRas and Akt3 in Ntv-a INK4a-ARF (also known as CDKN2A)-null mice. In contrast, Cdc20 decreased the GBM incidence from 19.1% to 9.1%. Moreover, cell differentiation was modulated by c-Myc in kRas/Akt3-induced GBM on the basis of Nestin/GFAP expression (glial progenitor cell differentiation), while Cdc20 had no effect on primary glial progenitor cell differentiation. We used glial progenitor cells from Ntv-a newborn mice to evaluate the role of c-Myc and Cdc20 in the proliferation and transformation of GBM in vitro and in vivo. We further determined whether c-Myc and Cdc20 have a driver or passenger role in GBM development using kRas/Akt3 signals in a RCAS/Ntv-a mouse model. These results suggest that the driver or passenger of oncogene signaling is dependent on cellular status. c-Myc is a driver when combined with kRas/Akt3 oncogenic signals in gliomagenesis, whereas Cdc20 overexpression is a passenger. Inhibition of cell differentiation of c-Myc may be a target for anti-glioma therapy.

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 ...

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

CDC 2004 Programs in Brief.

ERIC Educational Resources Information Center

US Department of Health and Human Services, 2004

2004-01-01

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

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...

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.

In Vitro Methods for Comparing Target Binding and CDC Induction Between Therapeutic Antibodies: Applications in Biosimilarity Analysis.

PubMed

Salinas-Jazmín, Nohemi; González-González, Edith; Vásquez-Bochm, Luz X; Pérez-Tapia, Sonia M; Velasco-Velázquez, Marco A

2017-05-04

Therapeutic monoclonal antibodies (mAbs) are relevant to the treatment of different pathologies, including cancers. The development of biosimilar mAbs by pharmaceutical companies is a market opportunity, but it is also a strategy to increase drug accessibility and reduce therapy-associated costs. The protocols detailed here describe the evaluation of target binding and CDC induction by rituximab in Daudi cells. These two functions require different structural regions of the antibody and are relevant to the clinical effect induced by rituximab. The protocols allow the side-to-side comparison of a reference rituximab and a marketed rituximab biosimilar. The evaluated products showed differences both in target binding and CDC induction, suggesting that there are underlying physicochemical differences and highlighting the need to analyze the impact of those differences in the clinical setting. The methods reported here constitute simple and inexpensive in vitro models for the evaluation of the activity of rituximab biosimilars. Thus, they can be useful during biosimilar development, as well as for quality control in biosimilar production. Furthermore, the presented methods can be extrapolated to other therapeutic mAbs.

Implementation of the CDC translational informatics platform--from genetic variants to the national Swedish Rheumatology Quality Register.

PubMed

Abugessaisa, Imad; Gomez-Cabrero, David; Snir, Omri; Lindblad, Staffan; Klareskog, Lars; Malmström, Vivianne; Tegnér, Jesper

2013-04-02

Sequencing of the human genome and the subsequent analyses have produced immense volumes of data. The technological advances have opened new windows into genomics beyond the DNA sequence. In parallel, clinical practice generate large amounts of data. This represents an underused data source that has much greater potential in translational research than is currently realized. This research aims at implementing a translational medicine informatics platform to integrate clinical data (disease diagnosis, diseases activity and treatment) of Rheumatoid Arthritis (RA) patients from Karolinska University Hospital and their research database (biobanks, genotype variants and serology) at the Center for Molecular Medicine, Karolinska Institutet. Requirements engineering methods were utilized to identify user requirements. Unified Modeling Language and data modeling methods were used to model the universe of discourse and data sources. Oracle11g were used as the database management system, and the clinical development center (CDC) was used as the application interface. Patient data were anonymized, and we employed authorization and security methods to protect the system. We developed a user requirement matrix, which provided a framework for evaluating three translation informatics systems. The implementation of the CDC successfully integrated biological research database (15172 DNA, serum and synovial samples, 1436 cell samples and 65 SNPs per patient) and clinical database (5652 clinical visit) for the cohort of 379 patients presents three profiles. Basic functionalities provided by the translational medicine platform are research data management, development of bioinformatics workflow and analysis, sub-cohort selection, and re-use of clinical data in research settings. Finally, the system allowed researchers to extract subsets of attributes from cohorts according to specific biological, clinical, or statistical features. Research and clinical database integration is a real

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.

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.

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

NASA Technical Reports Server (NTRS)

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

1973-01-01

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

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.

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

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.

Research of Ad Hoc Networks Access Algorithm

NASA Astrophysics Data System (ADS)

Xiang, Ma

With the continuous development of mobile communication technology, Ad Hoc access network has become a hot research, Ad Hoc access network nodes can be used to expand capacity of multi-hop communication range of mobile communication system, even business adjacent to the community, improve edge data rates. When the ad hoc network is the access network of the internet, the gateway discovery protocol is very important to choose the most appropriate gateway to guarantee the connectivity between ad hoc network and IP based fixed networks. The paper proposes a QoS gateway discovery protocol which uses the time delay and stable route to the gateway selection conditions. And according to the gateway discovery protocol, it also proposes a fast handover scheme which can decrease the handover time and improve the handover efficiency.

CDC Vital Signs: Motor Vehicle Crash Deaths

MedlinePlus

... those that address: Primary enforcement of seat belt laws that cover everyone in every seat. Police officers ... seat belt use with primary enforcement seat belt laws that cover everyone in the vehicle. www.cdc. ...

Cloning, sequencing and phylogenetic analysis of the small GTPase gene cdc-42 from Ancylostoma caninum.

PubMed

Yang, Yurong; Zheng, Jing; Chen, Jiaxin

2012-12-01

CDC-42 is a member of the Rho GTPase subfamily that is involved in many signaling pathways, including mitosis, cell polarity, cell migration and cytoskeleton remodeling. Here, we present the first characterization of a full-length cDNA encoding the small GTPase cdc-42, designated as Accdc-42, isolated from the parasitic nematode Ancylostoma caninum. The encoded protein contains 191 amino acid residues with a predicted molecular weight of 21 kDa and displays a high level of identity with the Rho-family GTPase protein CDC-42. Phylogenetic analysis revealed that Accdc-42 was most closely related to Caenorhabditis briggsae cdc-42. Comparison with selected sequences from the free-living nematode Caenorhabditis elegans, Drosophila melanogaster, Xenopus laevis, Danio rerio, Mus musculus and human genomes showed that Accdc-42 is highly conserved. AcCDC-42 demonstrates the highest identity to CDC-42 from C. briggsae (94.2%), and it also exhibits 91.6% identity to CDC-42 from C. elegans and 91.1% from Brugia malayi. Additionally, the transcript of Accdc-42 was analyzed during the different developmental stages of the worm. Accdc-42 was expressed in the L1/L2 larvae, L3 larvae and female and male adults of A. caninum. Copyright © 2012 Elsevier Inc. All rights reserved.

Access and preservation of digital research content: Linked open data services - A research library perspective

NASA Astrophysics Data System (ADS)

Kraft, Angelina; Sens, Irina; Löwe, Peter; Dreyer, Britta

2016-04-01

Globally resolvable, persistent digital identifiers have become an essential tool to enable unambiguous links between published research results and their underlying digital resources. In addition, this unambiguous identification allows citation. In an ideal research world, any scientific content should be citable and the coherent content, as well as the citation itself, should be persistent. However, today's scientists do not just produce traditional research papers - they produce comprehensive digital collections of objects which, alongside digital texts, include digital resources such as research data, audiovisual media, digital lab journals, images, statistics and software code. Researchers start to look for services which allow management of these digital resources with minimum time investment. In light of this, we show how the German National Library of Science and Technology (TIB) develops supportive frameworks to accompany the life cycle of scientific knowledge generation and transfer. This includes technical infrastructures for • indexing, cataloguing, digital preservation, DOI names and licencing for text and digital objects (the TIB DOI registration, active since 2004) and • a digital repository for the deposition and provision of accessible, traceable and citeable research data (RADAR). One particular problem for the management of data originating from (collaborating) research infrastructures is their dynamic nature in terms of growth, access rights and quality. On a global scale, systems for access and preservation are in place for the big data domains (e.g. environmental sciences, space, climate). However, the stewardship for disciplines without a tradition of data sharing, including the fields of the so-called long tail, remains uncertain. The RADAR - Research Data Repository - project establishes a generic end-point data repository, which can be used in a collaborative way. RADAR enables clients to upload, edit, structure and describe their

An Accessible Proteogenomics Informatics Resource for Cancer Researchers.

PubMed

Chambers, Matthew C; Jagtap, Pratik D; Johnson, James E; McGowan, Thomas; Kumar, Praveen; Onsongo, Getiria; Guerrero, Candace R; Barsnes, Harald; Vaudel, Marc; Martens, Lennart; Grüning, Björn; Cooke, Ira R; Heydarian, Mohammad; Reddy, Karen L; Griffin, Timothy J

2017-11-01

Proteogenomics has emerged as a valuable approach in cancer research, which integrates genomic and transcriptomic data with mass spectrometry-based proteomics data to directly identify expressed, variant protein sequences that may have functional roles in cancer. This approach is computationally intensive, requiring integration of disparate software tools into sophisticated workflows, challenging its adoption by nonexpert, bench scientists. To address this need, we have developed an extensible, Galaxy-based resource aimed at providing more researchers access to, and training in, proteogenomic informatics. Our resource brings together software from several leading research groups to address two foundational aspects of proteogenomics: (i) generation of customized, annotated protein sequence databases from RNA-Seq data; and (ii) accurate matching of tandem mass spectrometry data to putative variants, followed by filtering to confirm their novelty. Directions for accessing software tools and workflows, along with instructional documentation, can be found at z.umn.edu/canresgithub. Cancer Res; 77(21); e43-46. ©2017 AACR . ©2017 American Association for Cancer Research.

When are food deserts? Integrating time into research on food accessibility.

PubMed

Widener, Michael J; Shannon, Jerry

2014-11-01

The food desert concept is used as a means for defining regions as having inadequate spatial and socioeconomic access to vendors selling nutritious foods. This primarily aggregate-level and static method for understanding the food environment is commonly used by researchers and policy makers seeking to improve health outcomes of those affected by reduced access. However, recent research findings have brought the association between living in a food desert and adverse health outcomes into question. In this viewpoint, we put forward the idea that the food desert concept, and food accessibility research more generally, should be expanded to include a temporal component, and note potential avenues for future research. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2016-01-01

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

Contents, Followers, and Retweets of the Centers for Disease Control and Prevention’s Office of Advanced Molecular Detection (@CDC_AMD) Twitter Profile: Cross-Sectional Study

PubMed Central

Blankenship, Elizabeth B; Goff, Mary Elizabeth; Guinn, Amy J; Saroha, Nitin; Tse, Zion Tsz Ho

2018-01-01

Background The Office of Advanced Molecular Detection (OAMD), Centers for Disease Control and Prevention (CDC), manages a Twitter profile (@CDC_AMD). To our knowledge, no prior study has analyzed a CDC Twitter handle’s entire contents and all followers. Objective This study aimed to describe the contents and followers of the Twitter profile @CDC_AMD and to assess if attaching photos or videos to tweets posted by @CDC_AMD would increase retweet frequency. Methods Data of @CDC_AMD were retrieved on November 21, 2016. All followers (N=809) were manually categorized. All tweets (N=768) were manually coded for contents and whether photos or videos were attached. Retweet count for each tweet was recorded. Negative binomial regression models were applied to both the original and the retweet corpora. Results Among the 809 followers, 26.0% (210/809) were individual health professionals, 11.6% (94/809) nongovernmental organizations, 3.3% (27/809) government agencies’ accounts, 3.3% (27/809) accounts of media organizations and journalists, and 0.9% (7/809) academic journals, with 54.9% (444/809) categorized as miscellaneous. A total of 46.9% (360/768) of @CDC_AMD’s tweets referred to the Office’s website and their current research; 17.6% (135/768) referred to their scientists’ publications. Moreover, 80% (69/86) of tweets retweeted by @CDC_AMD fell into the miscellaneous category. In addition, 43.4% (333/768) of the tweets contained photos or videos, whereas the remaining 56.6% (435/768) did not. Attaching photos or videos to original @CDC_AMD tweets increases the number of retweets by 37% (probability ratio=1.37, 95% CI 1.13-1.67, P=.002). Content topics did not explain or modify this association. Conclusions This study confirms CDC health communicators’ experience that original tweets created by @CDC_AMD Twitter profile sharing images or videos (or their links) received more retweets. The current policy of attaching images to tweets should be encouraged. PMID

13 CFR 120.180 - Lender and CDC compliance with Loan Program Requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Lender and CDC compliance with... Program Requirements § 120.180 Lender and CDC compliance with Loan Program Requirements. Lenders must... are revised from time to time. CDCs must comply and maintain familiarity with Loan Program...

13 CFR 120.180 - Lender and CDC compliance with Loan Program Requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Lender and CDC compliance with... Program Requirements § 120.180 Lender and CDC compliance with Loan Program Requirements. Lenders must... are revised from time to time. CDCs must comply and maintain familiarity with Loan Program...

13 CFR 120.180 - Lender and CDC compliance with Loan Program Requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Lender and CDC compliance with... Program Requirements § 120.180 Lender and CDC compliance with Loan Program Requirements. Lenders must... are revised from time to time. CDCs must comply and maintain familiarity with Loan Program...

13 CFR 120.180 - Lender and CDC compliance with Loan Program Requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Lender and CDC compliance with... Program Requirements § 120.180 Lender and CDC compliance with Loan Program Requirements. Lenders must... are revised from time to time. CDCs must comply and maintain familiarity with Loan Program...

13 CFR 120.180 - Lender and CDC compliance with Loan Program Requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Lender and CDC compliance with... Program Requirements § 120.180 Lender and CDC compliance with Loan Program Requirements. Lenders must... are revised from time to time. CDCs must comply and maintain familiarity with Loan Program...

Open Access to research data - final perspectives from the RECODE project

NASA Astrophysics Data System (ADS)

Bigagli, Lorenzo; Sondervan, Jeroen

2015-04-01

Many networks, initiatives, and communities are addressing the key barriers to Open Access to data in scientific research. These organizations are typically heterogeneous and fragmented by discipline, location, sector (publishers, academics, data centers, etc.), as well as by other features. Besides, they often work in isolation, or with limited contacts with one another. The Policy RECommendations for Open Access to Research Data in Europe (RECODE) project, which will conclude in the first half of 2015, has scoped and addressed the challenges related to Open Access, dissemination and preservation of scientific data, leveraging the existing networks, initiatives, and communities. The overall objective of RECODE was to identify a series of targeted and over-arching policy recommendations for Open Access to European research data based on existing good practice. RECODE has undertaken a review of the existing state of the art and examined five case studies in different scientific disciplines: particle physics and astrophysics, clinical research, medicine and technical physiology (bioengineering), humanities (archaeology), and environmental sciences (Earth Observation). In particular for the latter discipline, GEOSS has been an optimal test bed for investigating the importance of technical and multidisciplinary interoperability, and what the challenges are in sharing and providing Open Access to research data from a variety of sources, and in a variety of formats. RECODE has identified five main technological and infrastructural challenges: • Heterogeneity - relates to interoperability, usability, accessibility, discoverability; • Sustainability - relates to obsolescence, curation, updates/upgrades, persistence, preservation; • Volume - also related to Big Data, which is somehow implied by Open Data; in our context, it relates to discoverability, accessibility (indexing), bandwidth, storage, scalability, energy footprint; • Quality - relates to completeness

Cdc2/cyclin B1 regulates centrosomal Nlp proteolysis and subcellular localization.

PubMed

Zhao, Xuelian; Jin, Shunqian; Song, Yongmei; Zhan, Qimin

2010-11-01

The formation of proper mitotic spindles is required for appropriate chromosome segregation during cell division. Aberrant spindle formation often causes aneuploidy and results in tumorigenesis. However, the underlying mechanism of regulating spindle formation and chromosome separation remains to be further defined. Centrosomal Nlp (ninein-like protein) is a recently characterized BRCA1-regulated centrosomal protein and plays an important role in centrosome maturation and spindle formation. In this study, we show that Nlp can be phosphorylated by cell cycle protein kinase Cdc2/cyclin B1. The phosphorylation sites of Nlp are mapped at Ser185 and Ser589. Interestingly, the Cdc2/cyclin B1 phosphorylation site Ser185 of Nlp is required for its recognition by PLK1, which enable Nlp depart from centrosomes to allow the establishment of a mitotic scaffold at the onset of mitosis . PLK1 fails to dissociate the Nlp mutant lacking Ser185 from centrosome, suggesting that Cdc2/cyclin B1 might serve as a primary kinase of PLK1 in regulating Nlp subcellular localization. However, the phosphorylation at the site Ser589 by Cdc2/cyclin B1 plays an important role in Nlp protein stability probably due to its effect on protein degradation. Furthermore, we show that deregulated expression or subcellular localization of Nlp lead to multinuclei in cells, indicating that scheduled levels of Nlp and proper subcellular localization of Nlp are critical for successful completion of normal cell mitosis, These findings demonstrate that Cdc2/cyclin B1 is a key regulator in maintaining appropriate degradation and subcellular localization of Nlp, providing novel insights into understanding on the role of Cdc2/cyclin B1 in mitotic progression.

[Prokaryotic expression and histological localization of the Taenia solium CDC37 gene].

PubMed

Huang, Jiang; Li, Bo; Dai, Jia-Lin; Zhang, Ai-Hua

2013-02-01

To express Taenia solium gene encoding cell division cycle 37 protein (TsCDC37) and investigate its antigenicity and localization in adults of Taenia solium. The complete coding sequence of TsCDC37 was amplified by PCR based on the recombinant plasmid clone from the cDNA library of adult Taenia solium. The PCR product was cloned into a prokaryotic expression vector pET-28a (+). The recombinant expression plasmid was identified by PCR, double endonuclease digestion and sequencing. The recombinant plasmid was transformed into E. coli BL21/DE3 and followed by expression of the protein induced by IPTG. The mice were immunized subcutaneously with purified recombinant TsCDC37 formulated in Freund's adjuvant. The antigenicity of the recombinant protein was examined by Western blotting. The localization of TsCDC37 in adult worms was demonstrated by immunofluorescent technique. The recombinant expression vector was constructed successfully. The recombinant protein was about M(r) 52 000, it was then purified and specifically recognized by immuno sera of SD rats and sera from patients infected with Taenia solium, Taenia saginata or Taenia asiatica. The immunofluorescence assay revealed that TsCDC37 located at the tegument of T. solium adult and the eggs. TsCDC37 gene has been expressed with immunoreactivity. The recombinant protein is mainly expressed in tegument and egg, and is a common antigen of the three human taenia cestodes.

BCO-DMO: Enabling Access to Federally Funded Research Data

NASA Astrophysics Data System (ADS)

Kinkade, D.; Allison, M. D.; Chandler, C. L.; Groman, R. C.; Rauch, S.; Shepherd, A.; Gegg, S. R.; Wiebe, P. H.; Glover, D. M.

2013-12-01

In a February, 2013 memo1, the White House Office of Science and Technology Policy (OSTP) outlined principles and objectives to increase access by the public to federally funded research publications and data. Such access is intended to drive innovation by allowing private and commercial efforts to take full advantage of existing resources, thereby maximizing Federal research dollars and efforts. The Biological and Chemical Oceanography Data Management Office (BCO-DMO; bco-dmo.org) serves as a model resource for organizations seeking compliance with the OSTP policy. BCO-DMO works closely with scientific investigators to publish their data from research projects funded by the National Science Foundation (NSF), within the Biological and Chemical Oceanography Sections (OCE) and the Division of Polar Programs Antarctic Organisms & Ecosystems Program (PLR). BCO-DMO addresses many of the OSTP objectives for public access to digital scientific data: (1) Marine biogeochemical and ecological data and metadata are disseminated via a public website, and curated on intermediate time frames; (2) Preservation needs are met by collaborating with appropriate national data facilities for data archive; (3) Cost and administrative burden associated with data management is minimized by the use of one dedicated office providing hundreds of NSF investigators support for data management plan development, data organization, metadata generation and deposition of data and metadata into the BCO-DMO repository; (4) Recognition of intellectual property is reinforced through the office's citation policy and the use of digital object identifiers (DOIs); (5) Education and training in data stewardship and use of the BCO-DMO system is provided by office staff through a variety of venues. Oceanographic research data and metadata from thousands of datasets generated by hundreds of investigators are now available through BCO-DMO. 1 White House Office of Science and Technology Policy, Memorandum for

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

PubMed Central

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

2017-01-01

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

Serine/Threonine Kinase Unc-51-like Kinase-1 (Ulk1) Phosphorylates the Co-chaperone Cell Division Cycle Protein 37 (Cdc37) and Thereby Disrupts the Stability of Cdc37 Client Proteins.

PubMed

Li, Ran; Yuan, Fengjie; Fu, Wan; Zhang, Luyao; Zhang, Nan; Wang, Yanan; Ma, Ke; Li, Xue; Wang, Lina; Zhu, Wei-Guo; Zhao, Ying

2017-02-17

The serine/threonine kinase Unc-51-like kinase-1 (Ulk1) is thought to be essential for induction of autophagy, an intracellular bulk degradation process that is activated by various stresses. Although several proteins have been suggested as Ulk1 substrates during autophagic process, it still remains largely unknown about Ulk1's physiological substrates. Here, by performing in vitro and in vivo phosphorylation assay, we report that the co-chaperone cell division cycle protein 37 (Cdc37) is a Ulk1 substrate. Ulk1-mediated phosphorylation of Ser-339 in Cdc37 compromised the recruitment of client kinases to a complex comprising Cdc37 and heat shock protein 90 (Hsp90) but only modestly affected Cdc37 binding to Hsp90. Because the recruitment of protein kinase clients to the Hsp90 complex is essential for their stability and functions, Ser-339 phosphorylation of Cdc37 disrupts its ability as a co-chaperone to coordinate Hsp90. Hsp90 inhibitors are cancer chemotherapeutic agents by inducing depletion of clients, many of which are oncogenes. Upon treatment with an Hsp90 inhibitor in cancer cells, Ulk1 promoted the degradation of Hsp90-Cdc37 client kinases, resulting in increased cellular sensitivity to Hsp90 inhibitors. Thus, our study provides evidence for an anti-proliferative role of Ulk1 in response to Hsp90 inhibition in cancer cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

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

PubMed

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

2017-08-01

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

NCAR Johns Hopkins/CDC Climate and Health Summer Institute

NASA Technical Reports Server (NTRS)

Mearns, Linda O.

2005-01-01

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

Contents, Followers, and Retweets of the Centers for Disease Control and Prevention's Office of Advanced Molecular Detection (@CDC_AMD) Twitter Profile: Cross-Sectional Study.

PubMed

Fung, Isaac Chun-Hai; Jackson, Ashley M; Mullican, Lindsay A; Blankenship, Elizabeth B; Goff, Mary Elizabeth; Guinn, Amy J; Saroha, Nitin; Tse, Zion Tsz Ho

2018-04-02

The Office of Advanced Molecular Detection (OAMD), Centers for Disease Control and Prevention (CDC), manages a Twitter profile (@CDC_AMD). To our knowledge, no prior study has analyzed a CDC Twitter handle's entire contents and all followers. This study aimed to describe the contents and followers of the Twitter profile @CDC_AMD and to assess if attaching photos or videos to tweets posted by @CDC_AMD would increase retweet frequency. Data of @CDC_AMD were retrieved on November 21, 2016. All followers (N=809) were manually categorized. All tweets (N=768) were manually coded for contents and whether photos or videos were attached. Retweet count for each tweet was recorded. Negative binomial regression models were applied to both the original and the retweet corpora. Among the 809 followers, 26.0% (210/809) were individual health professionals, 11.6% (94/809) nongovernmental organizations, 3.3% (27/809) government agencies' accounts, 3.3% (27/809) accounts of media organizations and journalists, and 0.9% (7/809) academic journals, with 54.9% (444/809) categorized as miscellaneous. A total of 46.9% (360/768) of @CDC_AMD's tweets referred to the Office's website and their current research; 17.6% (135/768) referred to their scientists' publications. Moreover, 80% (69/86) of tweets retweeted by @CDC_AMD fell into the miscellaneous category. In addition, 43.4% (333/768) of the tweets contained photos or videos, whereas the remaining 56.6% (435/768) did not. Attaching photos or videos to original @CDC_AMD tweets increases the number of retweets by 37% (probability ratio=1.37, 95% CI 1.13-1.67, P=.002). Content topics did not explain or modify this association. This study confirms CDC health communicators' experience that original tweets created by @CDC_AMD Twitter profile sharing images or videos (or their links) received more retweets. The current policy of attaching images to tweets should be encouraged. ©Isaac Chun-Hai Fung, Ashley M Jackson, Lindsay A Mullican

Access to and use of research by rural nurses.

PubMed

Winters, C A; Lee, H J; Besel, J; Strand, A; Echeverri, R; Jorgensen, K P; Dea, J E

2007-01-01

The use of relevant research findings to inform clinical practice is important for nurses, regardless of setting. Although there have been studies addressing the use of research among various practitioners, little is known about how nurses in rural areas access health information (specifically research findings), nor how such findings are incorporated into daily practice. The purpose of this study was to explore rural nurses' access, use and perceived usefulness of research for rural practice. The study was conducted in a sparsely populated state located in the western part of the USA. An ethnographic method was chosen to answer the research questions for this descriptive study. Semi-structured interviews were conducted with 29 rural nurses from nine communities by graduate nursing students enrolled in a rural nursing course following in-class instruction and practice. Field notes taken by the students supplemented the interview data. The students' notes included a windshield survey or description of the context and location within which the participants lived and/or practiced as well as the interviewers' observations, thoughts and impressions about the research project. Interviews were audiotaped and transcribed verbatim. Once transcribed, the interview narratives, windshield data and field notes were analyzed by the students for common themes; the students then wrote and submitted papers to the faculty addressing the themes that emerged from their interviews. The analysis conducted by the faculty members included four sources of data: transcriptions of interviews; field notes; windshield data; and students' papers. The process of identifying themes was facilitated by using the software program NUD*IST (QSR International; Melbourne, VIC, Australia). Demographic information was entered into the Statistical Package for Social Scientists (SPSS Inc; Chicago, IL, USA) to compile descriptive information about the sample. Twenty-seven female and two male nurses

Analysis of Airport Access - A Methods Review and Research Program

DOT National Transportation Integrated Search

1971-10-01

The report points up the differences and similarities between airport access travel and general urban trip making. Models and surveys developed for, or applicable, to airport access planning are reviewed. A research proram is proposed which would gen...

13 CFR 120.975 - CDC Liquidation of loans and debt collection litigation.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false CDC Liquidation of loans and debt... BUSINESS LOANS Development Company Loan Program (504) Authority of Cdcs to Perform Liquidation and Debt Collection Litigation § 120.975 CDC Liquidation of loans and debt collection litigation. (a) PCLP CDCs. If a...

13 CFR 120.975 - CDC Liquidation of loans and debt collection litigation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false CDC Liquidation of loans and debt... BUSINESS LOANS Development Company Loan Program (504) Authority of Cdcs to Perform Liquidation and Debt Collection Litigation § 120.975 CDC Liquidation of loans and debt collection litigation. (a) PCLP CDCs. If a...

13 CFR 120.975 - CDC Liquidation of loans and debt collection litigation.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false CDC Liquidation of loans and debt... BUSINESS LOANS Development Company Loan Program (504) Authority of Cdcs to Perform Liquidation and Debt Collection Litigation § 120.975 CDC Liquidation of loans and debt collection litigation. (a) PCLP CDCs. If a...

13 CFR 120.975 - CDC Liquidation of loans and debt collection litigation.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false CDC Liquidation of loans and debt... BUSINESS LOANS Development Company Loan Program (504) Authority of Cdcs to Perform Liquidation and Debt Collection Litigation § 120.975 CDC Liquidation of loans and debt collection litigation. (a) PCLP CDCs. If a...

13 CFR 120.975 - CDC Liquidation of loans and debt collection litigation.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false CDC Liquidation of loans and debt... BUSINESS LOANS Development Company Loan Program (504) Authority of Cdcs to Perform Liquidation and Debt Collection Litigation § 120.975 CDC Liquidation of loans and debt collection litigation. (a) PCLP CDCs. If a...

Providing Data Access for Interdisciplinary Research

NASA Astrophysics Data System (ADS)

Hooper, R. P.; Couch, A.

2012-12-01

Developing an interdisciplinary understanding of human and environmental interactions with water requires access to a variety of data kinds collected by various organizations. The CUAHSI Hydrologic Information System (HIS) is a standards-based, services-oriented architecture designed for time-series data. Such data represents an important type of data in water studies. Through the efforts of HIS, a standard transmission language, WaterML2, has been adopted by the Open Geospatial Consortium and is under consideration by the World Meteorologic Organization as an international standards. Web services have also been developed to retrieve data and metadata. HIS is completed with a metadata catalog, hosted by San Diego Supercomputing Center, which indexes more than 20 million time series provided from over 90 different services. This catalog is supported through a hierarchically organized controlled vocabulary that is open for community input and mediation. Data publishers include federal agencies, universities, state agencies, and non-profit organizations such as watershed associations. Accessing data from such a broad spectrum of sources through a uniform service standard promises to truly transform the way in which hydrologic research is done. CUAHSI HIS is a large-scale prototype at this time, but a proposal is under consideration by the National Science Foundation to operationalize HIS through a data facility, tentatively called the CUAHSI Water Data Center. Establishing HIS is an important step to enable research into human-environment interactions with water, but it is only one step. Other data structures will need to be made accessible and interoperable to support this research. Some data—such as two-dimensional GIS coverages—already have widely used standards for transmission and sharing. The US Federal government has long operated a clearinghouse for federal geographic data that is now being augmented with other services such as ArcGIS OnLine. Other data

CDC's Response to Zika: Enjoy Your Vacation

MedlinePlus

... travel notices: cdc. gov/ travel Pack to prevent • Insect repellent (Look for these ingredients: DEET, picaridin, IR3535, oil ... if you might have sex) Protect yourself • Use insect repellent. Reapply as directed. Remember to apply sunscreen first ...

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

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

Cdc42 regulates junctional actin but not cell polarization in the Caenorhabditis elegans epidermis

PubMed Central

Zilberman, Yuliya; Abrams, Joshua; Anderson, Dorian C.

2017-01-01

During morphogenesis, adherens junctions (AJs) remodel to allow changes in cell shape and position while preserving adhesion. Here, we examine the function of Rho guanosine triphosphatase CDC-42 in AJ formation and regulation during Caenorhabditis elegans embryo elongation, a process driven by asymmetric epidermal cell shape changes. cdc-42 mutant embryos arrest during elongation with epidermal ruptures. Unexpectedly, we find using time-lapse fluorescence imaging that cdc-42 is not required for epidermal cell polarization or junction assembly, but rather is needed for proper junctional actin regulation during elongation. We show that the RhoGAP PAC-1/ARHGAP21 inhibits CDC-42 activity at AJs, and loss of PAC-1 or the interacting linker protein PICC-1/CCDC85A-C blocks elongation in embryos with compromised AJ function. pac-1 embryos exhibit dynamic accumulations of junctional F-actin and an increase in AJ protein levels. Our findings identify a previously unrecognized molecular mechanism for inhibiting junctional CDC-42 to control actin organization and AJ protein levels during epithelial morphogenesis. PMID:28903999

Implementation of the CDC translational informatics platform - from genetic variants to the national Swedish Rheumatology Quality Register

PubMed Central

2013-01-01

Background Sequencing of the human genome and the subsequent analyses have produced immense volumes of data. The technological advances have opened new windows into genomics beyond the DNA sequence. In parallel, clinical practice generate large amounts of data. This represents an underused data source that has much greater potential in translational research than is currently realized. This research aims at implementing a translational medicine informatics platform to integrate clinical data (disease diagnosis, diseases activity and treatment) of Rheumatoid Arthritis (RA) patients from Karolinska University Hospital and their research database (biobanks, genotype variants and serology) at the Center for Molecular Medicine, Karolinska Institutet. Methods Requirements engineering methods were utilized to identify user requirements. Unified Modeling Language and data modeling methods were used to model the universe of discourse and data sources. Oracle11g were used as the database management system, and the clinical development center (CDC) was used as the application interface. Patient data were anonymized, and we employed authorization and security methods to protect the system. Results We developed a user requirement matrix, which provided a framework for evaluating three translation informatics systems. The implementation of the CDC successfully integrated biological research database (15172 DNA, serum and synovial samples, 1436 cell samples and 65 SNPs per patient) and clinical database (5652 clinical visit) for the cohort of 379 patients presents three profiles. Basic functionalities provided by the translational medicine platform are research data management, development of bioinformatics workflow and analysis, sub-cohort selection, and re-use of clinical data in research settings. Finally, the system allowed researchers to extract subsets of attributes from cohorts according to specific biological, clinical, or statistical features. Conclusions Research and

78 FR 64503 - Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-29

... Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC) Cancellation: This notice... Information: Gayle Hickman, Committee Management Specialist, Office Chief of Staff, CDC, 1600 Clifton Road [email protected]cdc.gov . This notice is published less than the required 15 days prior to the start of the announced...

Increasing Access to Atmospheric Science Research at NASA Langley Research Center

NASA Astrophysics Data System (ADS)

Chambers, L. H.; Bethea, K. L.; LaPan, J. C.

2013-12-01

The Science Directorate (SD) at NASA's Langley Research Center conducts cutting edge research in fundamental atmospheric science topics including radiation and climate, air quality, active remote sensing, and upper atmospheric composition. These topics matter to the public, as they improve our understanding of our home planet. Thus, we have had ongoing efforts to improve public access to the results of our research. These efforts have accelerated with the release of the February OSTP memo. Our efforts can be grouped in two main categories: 1. Visual presentation techniques to improve science understanding: For fundamental concepts such as the Earth's energy budget, we have worked to display information in a more "digestible" way for lay audiences with more pictures and fewer words. These audiences are iPad-lovers and TV-watchers with shorter attention spans than audiences of the past. They are also educators and students who need a basic understanding of a concept delivered briefly to fit into busy classroom schedules. We seek to reach them with a quick, visual message packed with important information. This presentation will share several examples of visual techniques, such as infographics (e.g., a history of lidar at Langley and a timeline of atmospheric research, ozone garden diagrams (http://science-edu.larc.nasa.gov/ozonegarden/ozone-cycle.php); history of lidar at LaRC; DISCOVER-AQ maps. It will also share examples of animations and interactive graphics (DISCOVER-AQ); and customized presentations (e.g., to explain the energy budget or to give a general overview of research). One of the challenges we face is a required culture shift between the way scientists traditionally share knowledge with each other and the way these public audiences ingest knowledge. A cross-disciplinary communications team in SD is crucial to bridge that gap. 2. Lay research summaries to make research more accessible: Peer-reviewed publications are a primary product of the SD, with more

In an Age of Open Access to Research Policies: Physician and Public Health NGO Staff Research Use and Policy Awareness.

PubMed

Moorhead, Laura L; Holzmeyer, Cheryl; Maggio, Lauren A; Steinberg, Ryan M; Willinsky, John

2015-01-01

Through funding agency and publisher policies, an increasing proportion of the health sciences literature is being made open access. Such an increase in access raises questions about the awareness and potential utilization of this literature by those working in health fields. A sample of physicians (N=336) and public health non-governmental organization (NGO) staff (N=92) were provided with relatively complete access to the research literature indexed in PubMed, as well as access to the point-of-care service UpToDate, for up to one year, with their usage monitored through the tracking of web-log data. The physicians also participated in a one-month trial of relatively complete or limited access. The study found that participants' research interests were not satisfied by article abstracts alone nor, in the case of the physicians, by a clinical summary service such as UpToDate. On average, a third of the physicians viewed research a little more frequently than once a week, while two-thirds of the public health NGO staff viewed more than three articles a week. Those articles were published since the 2008 adoption of the NIH Public Access Policy, as well as prior to 2008 and during the maximum 12-month embargo period. A portion of the articles in each period was already open access, but complete access encouraged a viewing of more research articles. Those working in health fields will utilize more research in the course of their work as a result of (a) increasing open access to research, (b) improving awareness of and preparation for this access, and (c) adjusting public and open access policies to maximize the extent of potential access, through reduction in embargo periods and access to pre-policy literature.

In an Age of Open Access to Research Policies: Physician and Public Health NGO Staff Research Use and Policy Awareness

PubMed Central

Maggio, Lauren A.; Steinberg, Ryan M.; Willinsky, John

2015-01-01

Introduction Through funding agency and publisher policies, an increasing proportion of the health sciences literature is being made open access. Such an increase in access raises questions about the awareness and potential utilization of this literature by those working in health fields. Methods A sample of physicians (N=336) and public health non-governmental organization (NGO) staff (N=92) were provided with relatively complete access to the research literature indexed in PubMed, as well as access to the point-of-care service UpToDate, for up to one year, with their usage monitored through the tracking of web-log data. The physicians also participated in a one-month trial of relatively complete or limited access. Results The study found that participants' research interests were not satisfied by article abstracts alone nor, in the case of the physicians, by a clinical summary service such as UpToDate. On average, a third of the physicians viewed research a little more frequently than once a week, while two-thirds of the public health NGO staff viewed more than three articles a week. Those articles were published since the 2008 adoption of the NIH Public Access Policy, as well as prior to 2008 and during the maximum 12-month embargo period. A portion of the articles in each period was already open access, but complete access encouraged a viewing of more research articles. Conclusion Those working in health fields will utilize more research in the course of their work as a result of (a) increasing open access to research, (b) improving awareness of and preparation for this access, and (c) adjusting public and open access policies to maximize the extent of potential access, through reduction in embargo periods and access to pre-policy literature. PMID:26200794

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-27

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

Mechanisms of Cdc42-mediated rat MSC differentiation on micro/nano-textured topography.

PubMed

Li, Guangwen; Song, Yanyan; Shi, Mengqi; Du, Yuanhong; Wang, Wei; Zhang, Yumei

2017-02-01

Micro/nano-textured titanium surface topography promotes osteoblast differentiation and the Wnt/β-catenin signaling pathway. However, the response of rat bone mesenchymal stem cells (MSCs) to micro/nano-textured topography, and the underlying mechanisms of its effects, are not well understood. We hypothesized that cell division cycle 42 protein (Cdc42), a key member of the Rho GTPases family, may regulate rat MSCs morphology and osteogenic differentiation by micro/nano-textured topography, and that crosstalk between Cdc42 and Wnt/β-catenin is the underlying mechanism. To confirm the hypothesis, we first tested rat MSCs' morphology, cytoskeleton, and osteogenic differentiation on micro/nano-textured topography. We then examined the cells' Wnt pathway and Cdc42 signaling activity. The results show that micro/nano-textured topography enhances MSCs' osteogenic differentiation. In addition, the cells' morphology and cytoskeletal reorganization were dramatically different on smooth surfaces and micropitted/nanotubular topography. Ligands of the canonical Wnt pathway, as well as accumulation of β-catenin in the nucleus, were up-regulated by micro/nano-textured topography. Cdc42 protein expression was markedly increased under these conditions; conversely, Cdc42 silencing significantly depressed the enhancement of MSCs osteogenic differentiation by micro/nano-textured topography. Moreover, Cdc42si attenuated p-GSK3β activation and resulted in β-catenin cytoplasmic degradation on the micro/nano-textured topography. Our results indicate that Cdc42 is a key modulator of rat MSCs morphology and cytoskeletal reorganization, and that crosstalk between Cdc42 and Wnt/β-catenin signaling though GSK3β regulates MSCs osteogenic differentiation by implant topographical cues. Topographical modification at micro- and nanoscale is widely applied to enhance the tissue integration properties of biomaterials. However, the response of bone mesenchymal stem cells (MSCs) to the micro

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

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-06

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

Parkin Regulates Mitosis and Genomic Stability through Cdc20/Cdh1.

PubMed

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

2015-10-01

Mutations in the E3 ubiquitin ligase Parkin have been linked to familial Parkinson's disease. Parkin has also been implicated in mitosis through mechanisms that are unclear. Here we show that Parkin interacts with anaphase promoting complex/cyclosome (APC/C) coactivators Cdc20 and Cdh1 to mediate the degradation of several key mitotic regulators independent of APC/C. We demonstrate that ordered progression through mitosis is orchestrated by two distinct E3 ligases through the shared use of Cdc20 and Cdh1. Furthermore, Parkin is phosphorylated and activated by polo-like kinase 1 (Plk1) during mitosis. Parkin deficiency results in overexpression of its substrates, mitotic defects, genomic instability, and tumorigenesis. These results suggest that the Parkin-Cdc20/Cdh1 complex is an important regulator of mitosis. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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...

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.

Stakeholder values and ecosystems in developing open access to research data.

NASA Astrophysics Data System (ADS)

Wessels, Bridgette; Sveinsdottir, Thordis; Smallwood, Rod

2014-05-01

One aspect of understanding how to develop open access to research data is to understand the values of stakeholders in the emerging open data ecosystem. The EU FP7 funded project Policy RECommendations for Open Access to Research Data in Europe (RECODE) (Grant Agreement No: 321463) undertook such research to identify stakeholder values and mapped the emerging ecosystem. In this paper we outline and discuss the findings of this research. We address three key objectives, which are: (a) the identification and mapping of the diverse range of stakeholder values in Open Access data and data dissemination and preservation; (b) mapping stakeholder values on to research ecosystems using case studies from different disciplinary perspectives; and (c) evaluate and identify good practice in addressing conflicting value chains and stakeholder fragmentation. The research was structured on three related actions: (a) an analysis of policy and related documents and protocols, in order to map the formal expression of values and motivations; (b) conducting five case studies in particle physics, health sciences, bioengineering, environmental research and archaeology. These explored issues of data size; quality control, ethics and data security; replication of large datasets; interoperability; and the preservation of diverse types of data; and (c) undertaking a validation and dissemination workshop that sought to better understand how to match policies with stakeholder drivers and motivations to increase their effectiveness in promoting Open Access to research data. The research findings include that there is clearly an overall drive for Open Data Access within the policy documents, which is part of a wider drive for open science in general. This is underpinned by the view of science as an open enterprise. Although there is a strong argument for publicly funded science to be made open to the public the details of how to make research data open as yet still unclear. Our research found

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.

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

The prolyl isomerase Pin1 modulates development of CD8+ cDC in mice.

PubMed

Barberi, Theresa J; Dunkle, Alexis; He, You-Wen; Racioppi, Luigi; Means, Anthony R

2012-01-01

Pin1 has previously been described to regulate cells that participate in both innate and adaptive immunity. Thus far, however, no role for Pin1 has been described in modulating conventional dendritic cells, innate antigen presenting cells that potently activate naïve T cells, thereby bridging innate and adaptive immune responses. When challenged with LPS, Pin1-null mice failed to accumulate spleen conventional dendritic cells (cDC). Analysis of steady-state spleen DC populations revealed that Pin1-null mice had fewer CD8+ cDC. This defect was recapitulated by culturing Pin1-null bone marrow with the DC-instructive cytokine Flt3 Ligand. Additionally, injection of Flt3 Ligand for 9 days failed to induce robust expansion of CD8+ cDC in Pin1-null mice. Upon infection with Listeria monocytogenes, Pin1-null mice were defective in stimulating proliferation of adoptively transferred WT CD8+ T cells, suggesting that decreases in Pin1 null CD8+ cDC may affect T cell responses to infection in vivo. Finally, upon analyzing expression of proteins involved in DC development, elevated expression of PU.1 was detected in Pin1-null cells, which resulted from an increase in PU.1 protein half-life. We have identified a novel role for Pin1 as a modulator of CD8+ cDC development. Consistent with reduced numbers of CD8+ cDC in Pin1-null mice, we find that the absence of Pin1 impairs CD8+ T cell proliferation in response to infection with Listeria monocytogenes. These data suggest that, via regulation of CD8+ cDC production, Pin1 may serve as an important modulator of adaptive immunity.

Hot spot variability and lithography process window investigation by CDU improvement using CDC technique

NASA Astrophysics Data System (ADS)

Thamm, Thomas; Geh, Bernd; Djordjevic Kaufmann, Marija; Seltmann, Rolf; Bitensky, Alla; Sczyrba, Martin; Samy, Aravind Narayana

2018-03-01

Within the current paper, we will concentrate on the well-known CDC technique from Carl Zeiss to improve the CD distribution of the wafer by improving the reticle CDU and its impact on hotspots and Litho process window. The CDC technique uses an ultra-short pulse laser technology, which generates a micro-level Shade-In-Element (also known as "Pixels") into the mask quartz bulk material. These scatter centers are able to selectively attenuate certain areas of the reticle in higher resolution compared to other methods and thus improve the CD uniformity. In a first section, we compare the CDC technique with scanner dose correction schemes. It becomes obvious, that the CDC technique has unique advantages with respect to spatial resolution and intra-field flexibility over scanner correction schemes, however, due to the scanner flexibility across wafer both methods are rather complementary than competing. In a second section we show that a reference feature based correction scheme can be used to improve the CDU of a full chip with multiple different features that have different MEEF and dose sensitivities. In detail we will discuss the impact of forward scattering light originated by the CDC pixels on the illumination source and the related proximity signature. We will show that the impact on proximity is small compared to the CDU benefit of the CDC technique. Finally we show to which extend the reduced variability across reticle will result in a better common electrical process window of a whole chip design on the whole reticle field on wafer. Finally we will discuss electrical verification results between masks with purposely made bad CDU that got repaired by the CDC technique versus inherently good "golden" masks on a complex logic device. No yield difference is observed between the repaired bad masks and the masks with good CDU.

CDC's strategic plan for bioterrorism preparedness and response.

PubMed

Koplan, J

2001-01-01

The Department of Health and Human Services (DHHS) has played a critical lead role over the past two years in fostering activities associated with the medical and public health response to bioterrorism. Based on a charge from Secretary Donna Shalala in 1998, the Centers for Disease Control and Prevention (CDC) is leading public health efforts to strengthen the nation's capacity to detect and respond to a bioterrorist event. As a result of our efforts, federal, state, and local communities are improving their public health capacities to respond to these types of emergencies. For many of us in public health, developing plans and capacities to respond to acts of bioterrorism is an extension of our long-standing roles and responsibilities. These are stated in the CDC Mission Statement: to promote health and quality of life by preventing and controlling disease, injury, and disability, and the Bioterrorism Mission: to lead the public health effort in enhancing readiness to detect and respond to bioterrorism. CDC's infectious diseases control efforts are summarized below: --Initially formed to address malaria control in 1946; --Established the epidemic Intelligence Service in 1951; --Participated in global smallpox eradication and other immunization programs; --Estimated 800-1,000 + field investigations/year since late 1990s; --New diseases: Legionnaire's Disease, toxic shock syndrome, Lyme disease, HIV, hantavirus pulmonary syndrome, West Nile, etc. -- Today: focus on emerging infections and bioterrorism. Over the past 50 years, CDC has seen a decline in the incidence of some infectious diseases and an increase in some, whereas others continue to present on a more unpredictable basis (i.e., hantavirus). Outbreak identification, investigation, and control have been an integral part of what we do for more than 50 years. We estimate that 800 to 1,000 field investigations have occurred every year since the late 1990s. Today, however, we have a new focus on emerging

CDC's strategic plan for bioterrorism preparedness and response.

PubMed Central

Koplan, J

2001-01-01

The Department of Health and Human Services (DHHS) has played a critical lead role over the past two years in fostering activities associated with the medical and public health response to bioterrorism. Based on a charge from Secretary Donna Shalala in 1998, the Centers for Disease Control and Prevention (CDC) is leading public health efforts to strengthen the nation's capacity to detect and respond to a bioterrorist event. As a result of our efforts, federal, state, and local communities are improving their public health capacities to respond to these types of emergencies. For many of us in public health, developing plans and capacities to respond to acts of bioterrorism is an extension of our long-standing roles and responsibilities. These are stated in the CDC Mission Statement: to promote health and quality of life by preventing and controlling disease, injury, and disability, and the Bioterrorism Mission: to lead the public health effort in enhancing readiness to detect and respond to bioterrorism. CDC's infectious diseases control efforts are summarized below: --Initially formed to address malaria control in 1946; --Established the epidemic Intelligence Service in 1951; --Participated in global smallpox eradication and other immunization programs; --Estimated 800-1,000 + field investigations/year since late 1990s; --New diseases: Legionnaire's Disease, toxic shock syndrome, Lyme disease, HIV, hantavirus pulmonary syndrome, West Nile, etc. -- Today: focus on emerging infections and bioterrorism. Over the past 50 years, CDC has seen a decline in the incidence of some infectious diseases and an increase in some, whereas others continue to present on a more unpredictable basis (i.e., hantavirus). Outbreak identification, investigation, and control have been an integral part of what we do for more than 50 years. We estimate that 800 to 1,000 field investigations have occurred every year since the late 1990s. Today, however, we have a new focus on emerging

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-DP10-1014 AGENCY... Funding Opportunity CDC-RFA- DP10-1014. It is the intent of CDC to provide continuation funding to one (1... published in the above referenced REACH CORE Funding Opportunity Announcement (FOA). Award Information...

75 FR 53703 - Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)-Health...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-01

... Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)--Health Disparities...), the CDC announces the following meeting of the aforementioned subcommittee: Time and Date: 2 p.m.-3 p.m., September 23, 2010. Place: The teleconference will originate at the CDC. Status: Open to the...

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.

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

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

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.

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

PubMed

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

2014-05-01

Cell polarization relies on small GTPases, such as Cdc42, which can break symmetry through self-organizing principles, and landmarks that define the axis of polarity. In fission yeast, microtubules deliver the Tea1-Tea4 complex to mark cell poles for growth, but how this complex activates Cdc42 is unknown. Here, we show that ectopic targeting of Tea4 to cell sides promotes the local activation of Cdc42 and cell growth. This activity requires that Tea4 binds the type I phosphatase (PP1) catalytic subunit Dis2 or Sds21, and ectopic targeting of either catalytic subunit is similarly instructive for growth. The Cdc42 guanine-nucleotide-exchange factor Gef1 and the GTPase-activating protein Rga4 are required for Tea4-PP1-dependent ectopic growth. Gef1 is recruited to ectopic Tea4 and Dis2 locations to promote Cdc42 activation. By contrast, Rga4 is locally excluded by Tea4, and its forced colocalization with Tea4 blocks ectopic growth, indicating that Rga4 must be present, but at sites distinct from Tea4. Thus, a Tea4-PP1 landmark promotes local Cdc42 activation and growth both through Cdc42 GEF recruitment and by creating a local trough in a Cdc42 GAP.

NASA Plan for Increasing Access to the Results of Scientific Research

NASA Technical Reports Server (NTRS)

2014-01-01

This plan is issued in response to the Executive Office of the President's February 22, 2013, Office of Science and Technology Policy (OSTP) Memorandum for the Heads of Executive Departments and Agencies, "Increasing Access to the Results of Federally Funded Scientific Research." Through this memorandum, OSTP directed all agencies with more than $100 million in annual research and development expenditures to prepare a plan for improving the public's access to the results of federally funded research. The National Aeronautics and Space Administration (NASA) invests on the order of $3 billion annually in fundamental and applied research and technology development1 across a broad range of topics, including space and Earth sciences, life and physical sciences, human health, aeronautics, and technology. Promoting the full and open sharing of data with research communities, private industry, academia, and the general public is one of NASA's longstanding core values. For example, NASA's space and suborbital mission personnel routinely process, archive, and distribute their data to researchers around the globe. This plan expands the breadth of NASA's open-access culture to include data and publications for all of the scientific research that the Agency sponsors.

UPEML Version 2. 0: A machine-portable CDC Update emulator

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

Mehlhorn, T.A.; Young, M.F.

1987-05-01

UPEML is a machine-portable CDC Update emulation program. UPEML is written in ANSI standard Fortran-77 and is relatively simple and compact. It is capable of emulating a significant subset of the standard CDC Update functions, including program library creation and subsequent modification. Machine-portability is an essential attribute of UPEML. UPEML was written primarily to facilitate the use of CDC-based scientific packages on alternate computer systems such as the VAX 11/780 and the IBM 3081. UPEML has also been successfully used on the multiprocessor ELXSI, on CRAYs under both COS and CTSS operating systems, on APOLLO workstations, and on the HP-9000.more » Version 2.0 includes enhanced error checking, full ASCI character support, a program library audit capability, and a partial update option in which only selected or modified decks are written to the compile file. Further enhancements include checks for overlapping corrections, processing of nested calls to common decks, and reads and addfiles from alternate input files.« less

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

The cdc2-related protein p40MO15 is the catalytic subunit of a protein kinase that can activate p33cdk2 and p34cdc2.

PubMed Central

Poon, R Y; Yamashita, K; Adamczewski, J P; Hunt, T; Shuttleworth, J

1993-01-01

Activation of the cyclin-dependent protein kinases p34cdc2 and p33cdk2 requires binding with a cyclin partner and phosphorylation on the first threonine residue in the sequence THEVVTLWYRAPE. We present evidence that this threonine residue, number 160 in p33cdk2, can be specifically phosphorylated by a cdc2-related protein kinase from Xenopus oocytes called p40MO15. Binding to cyclin A and phosphorylation of this threonine are both required to activate fully the histone H1 kinase activity of p33cdk2. In cell extracts, a portion of p40MO15 is found in a high molecular weight complex that is considerably more active than a lower molecular weight form. Wild-type MO15 protein expressed in bacteria does not possess kinase activity, but acquires p33cdk2-T160 kinase activity after incubation with cell extract and ATP. We conclude that p40MO15 corresponds to CAK (cdc2/cdk2 activating kinase) and speculate that, like p33cdk2 and p34cdc2, p40MO15 requires activation by phosphorylation and association with a companion subunit. Images PMID:8393783

The cdc2-related protein p40MO15 is the catalytic subunit of a protein kinase that can activate p33cdk2 and p34cdc2.

PubMed

Poon, R Y; Yamashita, K; Adamczewski, J P; Hunt, T; Shuttleworth, J

1993-08-01

Activation of the cyclin-dependent protein kinases p34cdc2 and p33cdk2 requires binding with a cyclin partner and phosphorylation on the first threonine residue in the sequence THEVVTLWYRAPE. We present evidence that this threonine residue, number 160 in p33cdk2, can be specifically phosphorylated by a cdc2-related protein kinase from Xenopus oocytes called p40MO15. Binding to cyclin A and phosphorylation of this threonine are both required to activate fully the histone H1 kinase activity of p33cdk2. In cell extracts, a portion of p40MO15 is found in a high molecular weight complex that is considerably more active than a lower molecular weight form. Wild-type MO15 protein expressed in bacteria does not possess kinase activity, but acquires p33cdk2-T160 kinase activity after incubation with cell extract and ATP. We conclude that p40MO15 corresponds to CAK (cdc2/cdk2 activating kinase) and speculate that, like p33cdk2 and p34cdc2, p40MO15 requires activation by phosphorylation and association with a companion subunit.

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

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

PubMed

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

2000-12-01

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

UPEML Version 3.0: A machine-portable CDC update emulator

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

Mehlhorn, T.A.; Haill, T.A.

1992-04-01

UPEML is a machine-portable program that emulates a subset of the functions of the standard CDC Update. Machine-portability has been achieved by conforming to ANSI standards for Fortran-77. UPEML is compact and fairly efficient; however, it only allows a restricted syntax as compared with the CDC Update. This program was written primarily to facilitate the use of CDC-based scientific packages on alternate computer systems such as the VAX/VMS mainframes and UNIX workstations. UPEML has also been successfully used on the multiprocessor ELXSI, on CRAYs under both UNICOS and CTSS operating systems, and on Sun, HP, Stardent and IBM workstations. UPEMLmore » was originally released with the ITS electron/photon Monte Carlo transport package, which was developed on a CDC-7600 and makes extensive use of conditional file structure to combine several problem geometry and machine options into a single program file. UPEML 3.0 is an enhanced version of the original code and is being independently released for use at any installation or with any code package. Version 3.0 includes enhanced error checking, full ASCII character support, a program library audit capability, and a partial update option in which only selected or modified decks are written to the complete file. Version 3.0 also checks for overlapping corrections, allows processing of pested calls to common decks, and allows the use of alternate files in READ and ADDFILE commands. Finally, UPEML Version 3.0 allows the assignment of input and output files at runtime on the control line.« less

UPEML Version 3. 0: A machine-portable CDC update emulator

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

Mehlhorn, T.A.; Haill, T.A.

1992-04-01

UPEML is a machine-portable program that emulates a subset of the functions of the standard CDC Update. Machine-portability has been achieved by conforming to ANSI standards for Fortran-77. UPEML is compact and fairly efficient; however, it only allows a restricted syntax as compared with the CDC Update. This program was written primarily to facilitate the use of CDC-based scientific packages on alternate computer systems such as the VAX/VMS mainframes and UNIX workstations. UPEML has also been successfully used on the multiprocessor ELXSI, on CRAYs under both UNICOS and CTSS operating systems, and on Sun, HP, Stardent and IBM workstations. UPEMLmore » was originally released with the ITS electron/photon Monte Carlo transport package, which was developed on a CDC-7600 and makes extensive use of conditional file structure to combine several problem geometry and machine options into a single program file. UPEML 3.0 is an enhanced version of the original code and is being independently released for use at any installation or with any code package. Version 3.0 includes enhanced error checking, full ASCII character support, a program library audit capability, and a partial update option in which only selected or modified decks are written to the complete file. Version 3.0 also checks for overlapping corrections, allows processing of pested calls to common decks, and allows the use of alternate files in READ and ADDFILE commands. Finally, UPEML Version 3.0 allows the assignment of input and output files at runtime on the control line.« less

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

PubMed

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

2017-07-01

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

FDA-CDC Antimicrobial Resistance Isolate Bank: a Publicly Available Resource To Support Research, Development, and Regulatory Requirements.

PubMed

Lutgring, Joseph D; Machado, María-José; Benahmed, Faiza H; Conville, Patricia; Shawar, Ribhi M; Patel, Jean; Brown, Allison C

2018-02-01

The FDA-CDC Antimicrobial Resistance Isolate Bank was created in July 2015 as a publicly available resource to combat antimicrobial resistance. It is a curated repository of bacterial isolates with an assortment of clinically important resistance mechanisms that have been phenotypically and genotypically characterized. In the first 2 years of operation, the bank offered 14 panels comprising 496 unique isolates and had filled 486 orders from 394 institutions throughout the United States. New panels are being added. Copyright © 2018 American Society for Microbiology.

Estimating Contraceptive Needs and Increasing Access to Contraception in Response to the Zika Virus Disease Outbreak--Puerto Rico, 2016.

PubMed

Tepper, Naomi K; Goldberg, Howard I; Bernal, Manuel I Vargas; Rivera, Brenda; Frey, Meghan T; Malave, Claritsa; Renquist, Christina M; Bracero, Nabal Jose; Dominguez, Kenneth L; Sanchez, Ramon E; Shapiro-Mendoza, Carrie K; Rodriguez, Blanca R Cuevas; Simeone, Regina M; Pesik, Nicki T; Barfield, Wanda D; Ko, Jean Y; Galang, Romeo R; Perez-Padilla, Janice; Polen, Kara N D; Honein, Margaret A; Rasmussen, Sonja A; Jamieson, Denise J

2016-04-01

Zika virus is a flavivirus transmitted primarily by Aedes species mosquitoes. Increasing evidence links Zika virus infection during pregnancy to adverse pregnancy and birth outcomes, including pregnancy loss, intrauterine growth restriction, eye defects, congenital brain abnormalities, and other fetal abnormalities. The virus has also been determined to be sexually transmitted. Because of the potential risks associated with Zika virus infection during pregnancy, CDC has recommended that health care providers discuss prevention of unintended pregnancy with women and couples who reside in areas of active Zika virus transmission and do not want to become pregnant. However, limitations in access to contraception in some of these areas might affect the ability to prevent an unintended pregnancy. As of March 16, 2016, the highest number of Zika virus disease cases in the United States and U.S. territories were reported from Puerto Rico. The number of cases will likely rise with increasing mosquito activity in affected areas, resulting in increased risk for transmission to pregnant women. High rates of unintended and adolescent pregnancies in Puerto Rico suggest that, in the context of this outbreak, access to contraception might need to be improved. CDC estimates that 138,000 women of reproductive age (aged 15-44 years) in Puerto Rico do not desire pregnancy and are not using one of the most effective or moderately effective contraceptive methods, and therefore might experience an unintended pregnancy. CDC and other federal and local partners are seeking to expand access to contraception for these persons. Such efforts have the potential to increase contraceptive access and use, reduce unintended pregnancies, and lead to fewer adverse pregnancy and birth outcomes associated with Zika virus infection during pregnancy. The assessment of challenges and resources related to contraceptive access in Puerto Rico might be a useful model for other areas with active transmission

The Yeast Polo Kinase Cdc5 Regulates the Shape of the Mitotic Nucleus

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

Walters, Alison D.; May, Christopher K.; Dauster, Emma S.

Abnormal nuclear size and shape are hallmarks of aging and cancer. However, the mechanisms regulating nuclear morphology and nuclear envelope (NE) expansion are poorly understood. In metazoans, the NE disassembles prior to chromosome segregation and reassembles at the end of mitosis. In budding yeast, the NE remains intact. The nucleus elongates as chromosomes segregate and then divides at the end of mitosis to form two daughter nuclei without NE disassembly. The budding yeast nucleus also undergoes remodeling during a mitotic arrest; the NE continues to expand despite the pause in chromosome segregation, forming a nuclear extension, or "flare," that encompassesmore » the nucleolus. The distinct nucleolar localization of the mitotic flare indicates that the NE is compartmentalized and that there is a mechanism by which NE expansion is confined to the region adjacent to the nucleolus. Here we show that mitotic flare formation is dependent on the yeast polo kinase Cdc5. This function of Cdc5 is independent of its known mitotic roles, including rDNA condensation. High-resolution imaging revealed that following Cdc5 inactivation, nuclei expand isometrically rather than forming a flare, indicating that Cdc5 is needed for NE compartmentalization. Lastly, even in an uninterrupted cell cycle, a small NE expansion occurs adjacent to the nucleolus prior to anaphase in a Cdc5-dependent manner. Our data provide the first evidence that polo kinase, a key regulator of mitosis, plays a role in regulating nuclear morphology and NE expansion.« less

The Yeast Polo Kinase Cdc5 Regulates the Shape of the Mitotic Nucleus

DOE PAGES

Walters, Alison D.; May, Christopher K.; Dauster, Emma S.; ...

2014-11-20

Abnormal nuclear size and shape are hallmarks of aging and cancer. However, the mechanisms regulating nuclear morphology and nuclear envelope (NE) expansion are poorly understood. In metazoans, the NE disassembles prior to chromosome segregation and reassembles at the end of mitosis. In budding yeast, the NE remains intact. The nucleus elongates as chromosomes segregate and then divides at the end of mitosis to form two daughter nuclei without NE disassembly. The budding yeast nucleus also undergoes remodeling during a mitotic arrest; the NE continues to expand despite the pause in chromosome segregation, forming a nuclear extension, or "flare," that encompassesmore » the nucleolus. The distinct nucleolar localization of the mitotic flare indicates that the NE is compartmentalized and that there is a mechanism by which NE expansion is confined to the region adjacent to the nucleolus. Here we show that mitotic flare formation is dependent on the yeast polo kinase Cdc5. This function of Cdc5 is independent of its known mitotic roles, including rDNA condensation. High-resolution imaging revealed that following Cdc5 inactivation, nuclei expand isometrically rather than forming a flare, indicating that Cdc5 is needed for NE compartmentalization. Lastly, even in an uninterrupted cell cycle, a small NE expansion occurs adjacent to the nucleolus prior to anaphase in a Cdc5-dependent manner. Our data provide the first evidence that polo kinase, a key regulator of mitosis, plays a role in regulating nuclear morphology and NE expansion.« less

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.

In vitro fusion of endocytic vesicles is inhibited by cyclin A-cdc2 kinase.

PubMed Central

Woodman, P G; Adamczewski, J P; Hunt, T; Warren, G

1993-01-01

Receptor-mediated endocytosis and recycling are inhibited in mitotic mammalian cells, and previous studies have shown that inhibition of endocytic vesicle fusion in vitro occurs via cyclin B-cdc2 kinase. To test for the ability of cyclin A-cdc2 kinase to inhibit endocytic vesicle fusion, we employed recombinant cyclin A proteins. Addition of cyclin A to interphase extracts activated a histone kinase and markedly reduced the efficiency of endocytic vesicle fusion. By a number of criteria, inhibition of fusion was shown to be due to the action of cyclin A, via the mitosis-specific cdc2 kinase, and not an indirect effect through cyclin B. Two-stage incubations were used to demonstrate that at least one target of cyclin A-cdc2 kinase is a cytosolic component of the fusion apparatus. Reconstitution experiments showed that this component was also modified in mitotic cytosols and was unaffected by N-ethyl maleimide treatment. Images PMID:8334308

In vitro fusion of endocytic vesicles is inhibited by cyclin A-cdc2 kinase.

PubMed

Woodman, P G; Adamczewski, J P; Hunt, T; Warren, G

1993-05-01

Receptor-mediated endocytosis and recycling are inhibited in mitotic mammalian cells, and previous studies have shown that inhibition of endocytic vesicle fusion in vitro occurs via cyclin B-cdc2 kinase. To test for the ability of cyclin A-cdc2 kinase to inhibit endocytic vesicle fusion, we employed recombinant cyclin A proteins. Addition of cyclin A to interphase extracts activated a histone kinase and markedly reduced the efficiency of endocytic vesicle fusion. By a number of criteria, inhibition of fusion was shown to be due to the action of cyclin A, via the mitosis-specific cdc2 kinase, and not an indirect effect through cyclin B. Two-stage incubations were used to demonstrate that at least one target of cyclin A-cdc2 kinase is a cytosolic component of the fusion apparatus. Reconstitution experiments showed that this component was also modified in mitotic cytosols and was unaffected by N-ethyl maleimide treatment.

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.

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

Cdc7-Dbf4 Regulates NDT80 Transcription as Well as Reductional Segregation during Budding Yeast Meiosis

PubMed Central

Lo, Hsiao-Chi; Wan, Lihong; Rosebrock, Adam; Futcher, Bruce

2008-01-01

In budding yeast, as in other eukaryotes, the Cdc7 protein kinase is important for initiation of DNA synthesis in vegetative cells. In addition, Cdc7 has crucial meiotic functions: it facilitates premeiotic DNA replication, and it is essential for the initiation of recombination. This work uses a chemical genetic approach to demonstrate that Cdc7 kinase has additional roles in meiosis. First, Cdc7 allows expression of NDT80, a meiosis-specific transcriptional activator required for the induction of genes involved in exit from pachytene, meiotic progression, and spore formation. Second, Cdc7 is necessary for recruitment of monopolin to sister kinetochores, and it is necessary for the reductional segregation occurring at meiosis I. The use of the same kinase to regulate several distinct meiosis-specific processes may be important for the coordination of these processes during meiosis. PMID:18768747

Wee1 and Cdc25 are controlled by conserved PP2A-dependent mechanisms in fission yeast.

PubMed

Lucena, Rafael; Alcaide-Gavilán, Maria; Anastasia, Steph D; Kellogg, Douglas R

2017-03-04

Wee1 and Cdc25 are conserved regulators of mitosis. Wee1 is a kinase that delays mitosis via inhibitory phosphorylation of Cdk1, while Cdc25 is a phosphatase that promotes mitosis by removing the inhibitory phosphorylation. Although Wee1 and Cdc25 are conserved proteins, it has remained unclear whether their functions and regulation are conserved across diverse species. Here, we analyzed regulation of Wee1 and Cdc25 in fission yeast. Both proteins undergo dramatic cell cycle-dependent changes in phosphorylation that are dependent upon PP2A associated with the regulatory subunit Pab1. The mechanisms that control Wee1 and Cdc25 in fission yeast appear to share similarities to those in budding yeast and vertebrates, which suggests that there may be common mechanisms that control mitotic entry in all eukaryotic cells.

Wee1 and Cdc25 are controlled by conserved PP2A-dependent mechanisms in fission yeast

PubMed Central

2017-01-01

ABSTRACT Wee1 and Cdc25 are conserved regulators of mitosis. Wee1 is a kinase that delays mitosis via inhibitory phosphorylation of Cdk1, while Cdc25 is a phosphatase that promotes mitosis by removing the inhibitory phosphorylation. Although Wee1 and Cdc25 are conserved proteins, it has remained unclear whether their functions and regulation are conserved across diverse species. Here, we analyzed regulation of Wee1 and Cdc25 in fission yeast. Both proteins undergo dramatic cell cycle-dependent changes in phosphorylation that are dependent upon PP2A associated with the regulatory subunit Pab1. The mechanisms that control Wee1 and Cdc25 in fission yeast appear to share similarities to those in budding yeast and vertebrates, which suggests that there may be common mechanisms that control mitotic entry in all eukaryotic cells. PMID:28103117

Characterization of cyclin-dependent kinases and Cdc2/Cdc28 kinase subunits in Trichomonas vaginalis.

PubMed

Amador, Erick; López-Pacheco, Karla; Morales, Nataly; Coria, Roberto; López-Villaseñor, Imelda

2017-04-01

Cyclin-dependent kinases (CDKs) have important roles in regulating key checkpoints between stages of the cell cycle. Their activity is tightly regulated through a variety of mechanisms, including through binding with cyclin proteins and the Cdc2/Cdc28 kinase subunit (CKS), and their phosphorylation at specific amino acids. Studies of the components involved in cell cycle control in parasitic protozoa are limited. Trichomonas vaginalis is the causative agent of trichomoniasis in humans and is therefore important in public health; however, some of the basic biological processes used by this organism have not been defined. Here, we characterized proteins potentially involved in cell cycle regulation in T. vaginalis. Three genes encoding protein kinases were identified in the T. vaginalis genome, and the corresponding recombinant proteins (TvCRK1, TvCRK2, TvCRK5) were studied. These proteins displayed similar sequence features to CDKs. Two genes encoding CKSs were also identified, and the corresponding recombinant proteins were found to interact with TvCRK1 and TvCRK2 by a yeast two-hybrid system. One putative cyclin B protein from T. vaginalis was found to bind to and activate the kinase activities of TvCRK1 and TvCRK5, but not TvCRK2. This work is the first characterization of proteins involved in cell cycle control in T. vaginalis.

Spatial control of active CDC-42 during collective migration of hypodermal cells in Caenorhabditis elegans.

PubMed

Ouellette, Marie-Hélène; Martin, Emmanuel; Lacoste-Caron, Germain; Hamiche, Karim; Jenna, Sarah

2016-08-01

Collective epithelial cell migration requires the maintenance of cell-cell junctions while enabling the generation of actin-rich protrusions at the leading edge of migrating cells. Ventral enclosure of Caenorhabditis elegans embryos depends on the collective migration of anterior-positioned leading hypodermal cells towards the ventral midline where they form new junctions with their contralateral neighbours. In this study, we characterized the zygotic function of RGA-7/SPV-1, a CDC-42/Cdc42 and RHO-1/RhoA-specific Rho GTPase-activating protein, which controls the formation of actin-rich protrusions at the leading edge of leading hypodermal cells and the formation of new junctions between contralateral cells. We show that RGA-7 controls these processes in an antagonistic manner with the CDC-42's effector WSP-1/N-WASP and the CDC-42-binding proteins TOCA-1/2/TOCA1. RGA-7 is recruited to spatially distinct locations at junctions between adjacent leading cells, where it promotes the accumulation of clusters of activated CDC-42. It also inhibits the spreading of these clusters towards the leading edge of the junctions and regulates their accumulation and distribution at new junctions formed between contralateral leading cells. Our study suggests that RGA-7 controls collective migration and junction formation between epithelial cells by spatially restricting active CDC-42 within cell-cell junctions. © The Author (2015). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

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.

Access to Essential Medicines in Pakistan: Policy and Health Systems Research Concerns

PubMed Central

Zaidi, Shehla; Bigdeli, Maryam; Aleem, Noureen; Rashidian, Arash

2013-01-01

Introduction Inadequate access to essential medicines is a common issue within developing countries. Policy response is constrained, amongst other factors, by a dearth of in-depth country level evidence. We share here i) gaps related to access to essential medicine in Pakistan; and ii) prioritization of emerging policy and research concerns. Methods An exploratory research was carried out using a health systems perspective and applying the WHO Framework for Equitable Access to Essential Medicine. Methods involved key informant interviews with policy makers, providers, industry, NGOs, experts and development partners, review of published and grey literature, and consultative prioritization in stakeholder’s Roundtable. Findings A synthesis of evidence found major gaps in essential medicine access in Pakistan driven by weaknesses in the health care system as well as weak pharmaceutical regulation. 7 major policy concerns and 11 emerging research concerns were identified through consultative Roundtable. These related to weaknesses in medicine registration and quality assurance systems, unclear and counterproductive pricing policies, irrational prescribing and sub-optimal drug availability. Available research, both locally and globally, fails to target most of the identified policy concerns, tending to concentrate on irrational prescriptions. It overlooks trans-disciplinary areas of policy effectiveness surveillance, consumer behavior, operational pilots and pricing interventions review. Conclusion Experience from Pakistan shows that policy concerns related to essential medicine access need integrated responses across various components of the health systems, are poorly addressed by existing evidence, and require an expanded health systems research agenda. PMID:23717442

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

An attenuated strain of Bacillus anthracis (CDC 684) has a large chromosomal inversion and altered growth kinetics

PubMed Central

2011-01-01

Background An isolate originally labeled Bacillus megaterium CDC 684 was found to contain both pXO1 and pXO2, was non-hemolytic, sensitive to gamma-phage, and produced both the protective antigen and the poly-D-glutamic acid capsule. These phenotypes prompted Ezzell et al., (J. Clin. Microbiol. 28:223) to reclassify this isolate to Bacillus anthracis in 1990. Results We demonstrate that despite these B. anthracis features, the isolate is severely attenuated in a guinea pig model. This prompted whole genome sequencing and closure. The comparative analysis of CDC 684 to other sequenced B. anthracis isolates and further analysis reveals: a) CDC 684 is a close relative of a virulent strain, Vollum A0488; b) CDC 684 defines a new B. anthracis lineage (at least 51 SNPs) that includes 15 other isolates; c) the genome of CDC 684 contains a large chromosomal inversion that spans 3.3 Mbp; d) this inversion has caused a displacement of the usual spatial orientation of the origin of replication (ori) to the termination of replication (ter) from 180° in wild-type B. anthracis to 120° in CDC 684 and e) this isolate also has altered growth kinetics in liquid media. Conclusions We propose two alternative hypotheses explaining the attenuated phenotype of this isolate. Hypothesis 1 suggests that the skewed ori/ter relationship in CDC 684 has altered its DNA replication and/or transcriptome processes resulting in altered growth kinetics and virulence capacity. Hypothesis 2 suggests that one or more of the single nucleotide polymorphisms in CDC 684 has altered the expression of a regulatory element or other genes necessary for virulence. PMID:21962024

The PP2AB56 phosphatase promotes the association of Cdc20 with APC/C in mitosis.

PubMed

Lee, Sun Joo; Rodriguez-Bravo, Veronica; Kim, Hyunjung; Datta, Sutirtha; Foley, Emily A

2017-05-15

PP2A comprising B56 regulatory subunit isoforms (PP2A B56 ) is a serine/threonine phosphatase essential for mitosis. At the kinetochore, PP2A B56 both stabilizes microtubule binding and promotes silencing of the spindle assembly checkpoint (SAC) through its association with the SAC protein BubR1. Cells depleted of the B56 regulatory subunits of PP2A are delayed in activation of Cdc20-containing APC/C (APC/C Cdc20 ), which is an essential step for mitotic exit. It has been hypothesized that this delay arises from increased production of the mitotic checkpoint complex (MCC), an APC/C Cdc20 inhibitor formed at unattached kinetochores through SAC signaling. In contrast to this prediction, we show that depletion of B56 subunits does not increase the amount or stability of the MCC. Rather, delays in APC/C Cdc20 activation in B56-depleted cells correlate with impaired Cdc20 binding to APC/C. Stimulation of APC/C Cdc20 assembly does not require binding between PP2A B56 and BubR1, and thus this contribution of PP2A B56 towards mitotic exit is distinct from its functions at kinetochores. PP2A B56 associates with APC/C constitutively in a BubR1-independent manner. A mitotic phosphorylation site on Cdc20, known to be a substrate of PP2A B56 , modulates APC/C Cdc20 assembly. These results elucidate the contributions of PP2A B56 towards completion of mitosis. © 2017. Published by The Company of Biologists Ltd.

An attenuated strain of Bacillus anthracis (CDC 684) has a large chromosomal inversion and altered growth kinetics.

PubMed

Okinaka, Richard T; Price, Erin P; Wolken, Spenser R; Gruendike, Jeffrey M; Chung, Wai Kwan; Pearson, Talima; Xie, Gary; Munk, Chris; Hill, Karen K; Challacombe, Jean; Ivins, Bruce E; Schupp, James M; Beckstrom-Sternberg, Stephen M; Friedlander, Arthur; Keim, Paul

2011-09-30

An isolate originally labeled Bacillus megaterium CDC 684 was found to contain both pXO1 and pXO2, was non-hemolytic, sensitive to gamma-phage, and produced both the protective antigen and the poly-D-glutamic acid capsule. These phenotypes prompted Ezzell et al., (J. Clin. Microbiol. 28:223) to reclassify this isolate to Bacillus anthracis in 1990. We demonstrate that despite these B. anthracis features, the isolate is severely attenuated in a guinea pig model. This prompted whole genome sequencing and closure. The comparative analysis of CDC 684 to other sequenced B. anthracis isolates and further analysis reveals: a) CDC 684 is a close relative of a virulent strain, Vollum A0488; b) CDC 684 defines a new B. anthracis lineage (at least 51 SNPs) that includes 15 other isolates; c) the genome of CDC 684 contains a large chromosomal inversion that spans 3.3 Mbp; d) this inversion has caused a displacement of the usual spatial orientation of the origin of replication (ori) to the termination of replication (ter) from 180° in wild-type B. anthracis to 120° in CDC 684 and e) this isolate also has altered growth kinetics in liquid media. We propose two alternative hypotheses explaining the attenuated phenotype of this isolate. Hypothesis 1 suggests that the skewed ori/ter relationship in CDC 684 has altered its DNA replication and/or transcriptome processes resulting in altered growth kinetics and virulence capacity. Hypothesis 2 suggests that one or more of the single nucleotide polymorphisms in CDC 684 has altered the expression of a regulatory element or other genes necessary for virulence.

Epithelial junction formation requires confinement of Cdc42 activity by a novel SH3BP1 complex

PubMed Central

Elbediwy, Ahmed; Zihni, Ceniz; Terry, Stephen J.; Clark, Peter

2012-01-01

Epithelial cell–cell adhesion and morphogenesis require dynamic control of actin-driven membrane remodeling. The Rho guanosine triphosphatase (GTPase) Cdc42 regulates sequential molecular processes during cell–cell junction formation; hence, mechanisms must exist that inactivate Cdc42 in a temporally and spatially controlled manner. In this paper, we identify SH3BP1, a GTPase-activating protein for Cdc42 and Rac, as a regulator of junction assembly and epithelial morphogenesis using a functional small interfering ribonucleic acid screen. Depletion of SH3BP1 resulted in loss of spatial control of Cdc42 activity, stalled membrane remodeling, and enhanced growth of filopodia. SH3BP1 formed a complex with JACOP/paracingulin, a junctional adaptor, and CD2AP, a scaffolding protein; both were required for normal Cdc42 signaling and junction formation. The filamentous actin–capping protein CapZ also associated with the SH3BP1 complex and was required for control of actin remodeling. Epithelial junction formation and morphogenesis thus require a dual activity complex, containing SH3BP1 and CapZ, that is recruited to sites of active membrane remodeling to guide Cdc42 signaling and cytoskeletal dynamics. PMID:22891260

Is the 2000 CDC growth reference appropriate for developing countries?

PubMed

Roberfroid, Dominique; Lerude, Marie-Paule; Pérez-Cueto, Armando; Kolsteren, Patrick

2006-04-01

In 2000, the Centers for Disease Control and Prevention (CDC) produced a revised growth reference. This has already been used in different settings outside the USA. Using data obtained during a nutritional survey in Madagascar, we compare results produced by using both the 2000 CDC and the 1978 National Center for Health Statistics (NCHS)/World Health Organization (WHO) growth references. We show that changing the reference has an important impact on nutritional diagnosis. In particular, the prevalence of wasting is greatly increased. This could generate substantial operational and clinical difficulties. We recommend continued use of the 1978 NCHS/WHO reference until release of the new WHO multi-country growth charts.

Perspectives on Open Access Opportunities for IS Research Publication: Potential Benefits for Researchers, Educators, and Students

ERIC Educational Resources Information Center

Woszczynski, Amy B.; Whitman, Michael E.

2016-01-01

Access to current research materials, pedagogical best practices, and relevant knowledge has become problematic as journal subscription costs have increased. Increasing delays in the traditional publication timeline, coupled with high subscription costs, have resulted in a diminished ability for IS faculty and their students to access the most…

The Impact of Climate Change on Infectious Disease Transmission: Perceptions of CDC Health Professionals in Shanxi Province, China

PubMed Central

Wei, Junni; Hansen, Alana; Zhang, Ying; Li, Hong; Liu, Qiyong; Sun, Yehuan; Xue, Shulian; Zhao, Shufang; Bi, Peng

2014-01-01

There have been increasing concerns about the challenge of emerging and re-emerging infectious diseases due to climate change, especially in developing countries including China. Health professionals play a significant role in the battle to control and prevent infectious diseases. This study therefore aims to investigate the perceptions and attitudes of health professionals at the Centers for Disease Control and Prevention (CDC) in different levels in China, and to consider adaptation measures to deal with the challenge of climate change. In 2013, a cross-sectional questionnaire survey was undertaken among 314 staff in CDCs in Shanxi Province, China, whose routine work involves disease control and prevention. Data were analyzed using descriptive methods and logistic regression. A majority of the CDC staff were aware of the health risks from climate change, especially its impacts on infectious disease transmission in their jurisdictions, and believed climate change might bring about both temporal and spatial change in transmission patterns. It was thought that adaptation measures should be established including: strengthening/improving currently existing disease surveillance systems and vector monitoring; building CDC capacity in terms of infrastructure and in-house health professional training; development and refinement of relevant legislation, policies and guidelines; better coordination among various government departments; the involvement of the community in infectious disease interventions; and collaborative research with other institutions. This study provides a snapshot of the understanding of CDC staff regarding climate change risks relevant to infectious diseases and adaptation in China. Results may help inform future efforts to develop adaptation measures to minimize infectious disease risks due to climate change. PMID:25285440

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

PubMed

Wei, Junni; Hansen, Alana; Zhang, Ying; Li, Hong; Liu, Qiyong; Sun, Yehuan; Xue, Shulian; Zhao, Shufang; Bi, Peng

2014-01-01

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

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 to CRAY FORTRAN conversion manual

NASA Technical Reports Server (NTRS)

Mcgary, C.; Diebert, D.

1983-01-01

Documentation describing software differences between two general purpose computers for scientific applications is presented. Descriptions of the use of the FORTRAN and FORTRAN 77 high level programming language on a CDC 7600 under SCOPE and a CRAY XMP under COS are offered. Itemized differences of the FORTRAN language sets of the two machines are also included. The material is accompanied by numerous examples of preferred programming techniques for the two machines.

Veterinary medicine and public health at CDC.

PubMed

King, Lonnie J

2006-12-22

People readily associate the role of veterinarians with private veterinary practice focused on pets and farm animals, but the true dimensions and contributions of veterinary medicine are much broader and reflect expanding societal needs and contemporary challenges to animal and human health and to the environment. Veterinary medicine has responsibilities in biomedical research; ecosystem management; public health; food and agricultural systems; and care of companion animals, wildlife, exotic animals, and food animals. The expanding role of veterinarians at CDC reflects an appreciation for this variety of contributions. Veterinarians' educational background in basic biomedical and clinical sciences compare with that of physicians. However, unlike their counterparts in human medicine, veterinarians must be familiar with multiple species, and their training emphasizes comparative medicine. Veterinarians are competent in preventive medicine, population health, parasitology, zoonoses, and epidemiology, which serve them well for careers in public health. The history and tradition of the profession always have focused on protecting and improving both animal health and human health.

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

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.

Gaining Research Access into the Lives of Muslim Girls: Researchers Negotiating "Muslimness", Modesty, "Inshallah", and "Haram"

ERIC Educational Resources Information Center

Hamzeh, Manal Z.; Oliver, Kimberly

2010-01-01

This paper explores the process of gaining research access into the lives of Muslim girls in the southwest USA. We discuss four emerging "entry markers" that challenged the process of gaining and sustaining access over a period of 14 months. These included being Muslim enough, being modest enough, "inshallah" ("Allah"…

South Asian Nomads--A Literature Review. CREATE Pathways to Access. Research Monograph No. 58

ERIC Educational Resources Information Center

Sharma, Anita

2011-01-01

This review of literature on South Asian nomads is part of a series of monographs on educational access published by the Consortium for Research on Educational Access Transitions and Equity (CREATE). In the context of India, most recent work has focused on access to the education system for the poor. CREATE research in India has focused on …

The Cdc45/RecJ-like protein forms a complex with GINS and MCM, and is important for DNA replication in Thermococcus kodakarensis.

PubMed

Nagata, Mariko; Ishino, Sonoko; Yamagami, Takeshi; Ogino, Hiromi; Simons, Jan-Robert; Kanai, Tamotsu; Atomi, Haruyuki; Ishino, Yoshizumi

2017-10-13

The archaeal minichromosome maintenance (MCM) has DNA helicase activity, which is stimulated by GINS in several archaea. In the eukaryotic replicative helicase complex, Cdc45 forms a complex with MCM and GINS, named as CMG (Cdc45-MCM-GINS). Cdc45 shares sequence similarity with bacterial RecJ. A Cdc45/RecJ-like protein from Thermococcus kodakarensis shows a bacterial RecJ-like exonuclease activity, which is stimulated by GINS in vitro. Therefore, this archaeal Cdc45/RecJ is designated as GAN, from GINS-associated nuclease. In this study, we identified the CMG-like complex in T. kodakarensis cells. The GAN·GINS complex stimulated the MCM helicase, but MCM did not affect the nuclease activity of GAN in vitro. The gene disruption analysis showed that GAN was non-essential for its viability but the Δgan mutant did not grow at 93°C. Furthermore, the Δgan mutant showed a clear retardation in growth as compared with the parent cells under optimal conditions at 85°C. These deficiencies were recovered by introducing the gan gene encoding the nuclease deficient GAN protein back to the genome. These results suggest that the replicative helicase complex without GAN may become unstable and ineffective in replication fork progression. The nuclease activity of GAN is not related to the growth defects of the Δgan mutant cells. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

A New Genetically Encoded Single-Chain Biosensor for Cdc42 Based on FRET, Useful for Live-Cell Imaging

PubMed Central

Cox, Dianne; Hodgson, Louis

2014-01-01

Cdc42 is critical in a myriad of cellular morphogenic processes, requiring precisely regulated activation dynamics to affect specific cellular events. To facilitate direct observations of Cdc42 activation in live cells, we developed and validated a new biosensor of Cdc42 activation. The biosensor is genetically encoded, of single-chain design and capable of correctly localizing to membrane compartments as well as interacting with its upstream regulators including the guanine nucleotide dissociation inhibitor. We characterized this new biosensor in motile mouse embryonic fibroblasts and observed robust activation dynamics at leading edge protrusions, similar to those previously observed for endogenous Cdc42 using the organic dye-based biosensor system. We then extended our validations and observations of Cdc42 activity to macrophages, and show that this new biosensor is able to detect differential activation patterns during phagocytosis and cytokine stimulation. Furthermore, we observe for the first time, a highly transient and localized activation of Cdc42 during podosome formation in macrophages, which was previously hypothesized but never directly visualized. PMID:24798463

A new genetically encoded single-chain biosensor for Cdc42 based on FRET, useful for live-cell imaging.

PubMed

Hanna, Samer; Miskolci, Veronika; Cox, Dianne; Hodgson, Louis

2014-01-01

Cdc42 is critical in a myriad of cellular morphogenic processes, requiring precisely regulated activation dynamics to affect specific cellular events. To facilitate direct observations of Cdc42 activation in live cells, we developed and validated a new biosensor of Cdc42 activation. The biosensor is genetically encoded, of single-chain design and capable of correctly localizing to membrane compartments as well as interacting with its upstream regulators including the guanine nucleotide dissociation inhibitor. We characterized this new biosensor in motile mouse embryonic fibroblasts and observed robust activation dynamics at leading edge protrusions, similar to those previously observed for endogenous Cdc42 using the organic dye-based biosensor system. We then extended our validations and observations of Cdc42 activity to macrophages, and show that this new biosensor is able to detect differential activation patterns during phagocytosis and cytokine stimulation. Furthermore, we observe for the first time, a highly transient and localized activation of Cdc42 during podosome formation in macrophages, which was previously hypothesized but never directly visualized.

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

PubMed Central

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

2004-01-01

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

Weekly Surveillance Reports - MeCDC; DHHS Maine

Science.gov Websites

Division of the Maine Department of Health and Human Services Contact EPI | News | Online services | Publications | Subject index Search EPI Search Maine CDC Home Health Topics A-Z Data/Reports For Health Care Curricula Train the Trainer School Health Videos Information for Laboratories 211 logo Social Services Help

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

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.

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.

Micro-supercapacitors from carbide derived carbon (CDC) films on silicon chips

NASA Astrophysics Data System (ADS)

Huang, Peihua; Heon, Min; Pech, David; Brunet, Magali; Taberna, Pierre-Louis; Gogotsi, Yury; Lofland, Samuel; Hettinger, Jeffrey D.; Simon, Patrice

2013-03-01

Interdigitated on-chip micro-supercapacitors based on Carbide Derived Carbon (CDC) films were fabricated and tested. A titanium carbide (TiC) film was patterned and treated with chlorine to obtain a TiC derived carbon (TiC-CDC) film, followed by the deposition of two types of current collectors (Ti/Au and Al) using standard micro-fabrication processes. CDC based micro-supercapacitors were electrochemically characterized by cyclic voltammetry and impedance spectroscopy using a 1 M tetraethylammonium tetrafluoroborate, NEt4BF4, in propylene carbonate (PC) electrolyte. A capacitance of 0.78 mF for the device and 1.5 mF cm-2 as the specific capacitance for the footprint of the device was measured for a 2 V potential range at 100 mV s-1. A specific energy of 3.0 mJ cm-2 and a specific power of 84 mW cm-2 were calculated for the devices. These devices provide a pathway for fabricating pure carbon-based micro-supercapacitors by micro-fabrication, and can be used for powering micro-electromechanical systems (MEMS) and electronic devices.

Emerging technologies and web accessibility: research challenges and opportunities focussing on vision issues.

PubMed

Harper, Simon; Yesilada, Yeliz

2012-01-01

This is a technological review paper focussed on identifying both the research challenges and opportunities for further investigation arising from emerging technologies, and it does not aim to propose any recommendation or standard. It is focussed on blind and partially sighted World Wide Web (Web) users along with others who use assistive technologies. The Web is a fast moving interdisciplinary domain in which new technologies, techniques and research is in perpetual development. It is often difficult to maintain a holistic view of new developments within the multiple domains which together make up the Web. This suggests that knowledge of the current developments and predictions of future developments are additionally important for the accessibility community. Web accessibility has previously been characterised by the correction of our past mistakes to make the current Web fulfil the original vision of access for all. New technologies were not designed with accessibility in mind and technologies that could be useful for addressing accessibility issues were not identified or adopted by the accessibility community. We wish to enable the research community to undertake preventative measures and proactively address challenges, while recognising opportunities, before they become unpreventable or require retrospective technological enhancement. This article then reviews emerging trends within the Web and Web Accessibility domains.

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

PubMed

Rock, Jeremy M; Amon, Angelika

2011-09-15

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

[Differences in magnitude of nutritional status in Chilean school children according to CDC and WHO 2005-2008 reference].

PubMed

Vásquez, Fabián; Cerda Rioseco, Ricardo; Andrade, Margarita; Morales, Gladys; Gálvez, Patricia; Orellana, Yasna; Leyton, Bárbara

2013-01-01

Further discussions are needed regarding the magnitude of nutritional problems diagnosed using CDC or WHO, against the existence of new biological or statistical definitions of obesity. To compare the evolution of the prevalence of nutritional status among schoolchildren in first grade, from 2005 to 2008, according to CDC and WHO. Retrospective cohort study, of 140.265 students of both sexes of first grade, evaluated from 2005- 2008, whose anthropometric data (weight and height), were obtained from annual registration system of school nutrition. To classify the nutritional status of children, CDC and WHO patterns were used. The mean BMI was slightly different and lower in girls than in boys, in 2005 and 2006. During 2007 and 2008 the average BMI in girls reached the observed in males. There was a higher prevalence of underweight according to WHO (p=0,03), with a tendency to decrease in the subsequent years. The prevalence of normality was greater according to the CDC criteria, with a reduction between 2005 and 2007 and an increase in 2008 (P < 0,001). There was a lower prevalence of overweight according to CDC criteria (P < 0,001), with an increase between 2005 and 2007, both CDC and WHO. The prevalence of obesity was lower according to the WHO criteria, and there were not statistically significant differences when comparing the CDC pattern. By comparing both patterns, CDC tends to overestimate the normal and underestimate the overweight, while obesity was not significant differences. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

The CDC Hemophilia A Mutation Project (CHAMP) Mutation List: a New Online Resource

PubMed Central

Payne, Amanda B.; Miller, Connie H.; Kelly, Fiona M.; Soucie, J. Michael; Hooper, W. Craig

2015-01-01

Genotyping efforts in hemophilia A (HA) populations in many countries have identified large numbers of unique mutations in the Factor VIII gene (F8). To assist HA researchers conducting genotyping analyses, we have developed a listing of F8 mutations including those listed in existing locus-specific databases as well as those identified in patient populations and reported in the literature. Each mutation was reviewed and uniquely identified using Human Genome Variation Society (HGVS) nomenclature standards for coding DNA and predicted protein changes as well as traditional nomenclature based on the mature, processed protein. Listings also include the associated hemophilia severity classified by International Society of Thrombosis and Haemostasis (ISTH) criteria, associations of the mutations with inhibitors, and reference information. The mutation list currently contains 2,537 unique mutations known to cause HA. HA severity caused by the mutation is available for 2,022 mutations (80%) and information on inhibitors is available for 1,816 mutations (72%). The CDC Hemophilia A Mutation Project (CHAMP) Mutation List is available at http://www.cdc.gov/hemophiliamutations for download and search and will be updated quarterly based on periodic literature reviews and submitted reports. PMID:23280990

User`s manual for the CDC-1 digitizer controller

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

Ferron, J.R.

1994-09-01

A detailed description of how to use the CDC-1 digitizer controller is given. The CDC-1 is used with the CAMAC format digitizer models in the TRAQ series (manufactured by DSP Technology Inc.), the DAD-1 data acquisition daughter board, and the Intel i860-based SuperCard-2 (manufactured, by CSP Inc.) to form a high speed data acquisition and real time analysis system. Data can be transferred to the memory on the SuperCard-2 at a rate as high as 40 million 14-bit samples per second. Depending on the model of TRAQ digitizer in use, digitizing rates up to 3.33 MHz are supported (with eightmore » data channels), or, for instance, at a sample rate of 100 kHz, 384 data channels can be acquired.« less

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

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

Ma, Yong-Cheng; Su, Nan; Shi, Xiao-Jing

2015-01-15

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

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.

M0899; hoh; steam tables 14. 5-2538 psia. [CDC6600; FORTRAN IV

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

Lynn, L.L.

By making calls on a subroutine called HOH, M0899 edits thermodynamic and transport properties of water over the range 14.5 to 2538 psia and up to 608 degrees Fahrenheit below saturation and 932 degrees Fahrenheit above saturation.CDC6600; FORTRAN IV; SCOPE 2.0; On the CDC6600 a FORTRAN IV compiler plus about 3000 storage locations for subroutine HOH and 10,000 locations for the main program.

Health communication takes on new dimensions at CDC.

PubMed

Roper, W L

1993-01-01

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

Health communication takes on new dimensions at CDC.

PubMed Central

Roper, W L

1993-01-01

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

Research access to privately owned wetland basins in the prairie pothole region of the United States

USGS Publications Warehouse

Fellows, David P.; Buhl, Thomas K.

1995-01-01

We describe efforts to obtain access for research to 81 wetland basins on 69 farms in four zones of the Prairie Pothole Region of North Dakota, South Dakota, and Minnesota. Access was obtained to 54% of the farms in areas where land was intensively cropped and 87% of farms in areas of low cropping intensity. On average, 1.35 operators had to be contacted and 1.70 interviews were required to obtain a decision on access to a farm. On 77% of the farms, cooperators placed at least one restriction on access, most commonly requiring walking access only or notification before nighttime work. Cost of obtaining access averaged $265/farm in wages and travel expenses. No cooperators were willing to sign written access agreements. Operators rescinded access to four farms and drained three wetland basins during the first year; six of the seven sites lost were in the intensively cropped portion of a low-wetland-density zone. The difficulty of obtaining and retaining research access to privately owned wetland basins in intensively cropped areas may be related to landowner attitudes towards wetlands. Researchers may have to rely on remote sensing or consider payment for access to secure representative research sites in such areas. Unwillingness of cooperators to sign access agreements may jeopardize research by the newly formed National Biological Service and other resource management agencies.

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

PubMed

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

2015-06-04

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

Implementing post-trial access plans for HIV prevention research.

PubMed

Paul, Amy; Merritt, Maria W; Sugarman, Jeremy

2018-05-01

Ethics guidance increasingly recognises that researchers and sponsors have obligations to consider provisions for post-trial access (PTA) to interventions that are found to be beneficial in research. Yet, there is little information regarding whether and how such plans can actually be implemented. Understanding practical experiences of developing and implementing these plans is critical to both optimising their implementation and informing conceptual work related to PTA. This viewpoint is informed by experiences with developing and implementing PTA plans for six large-scale multicentre HIV prevention trials supported by the HIV Prevention Trials Network. These experiences suggest that planning and implementing PTA often involve challenges of planning under uncertainty and confronting practical barriers to accessing healthcare systems. Even in relatively favourable circumstances where a tested intervention medication is approved and available in the local healthcare system, system-level barriers can threaten the viability of PTA plans. The aggregate experience across these HIV prevention trials suggests that simply referring participants to local healthcare systems for PTA will not necessarily result in continued access to beneficial interventions for trial participants. Serious commitments to PTA will require additional efforts to learn from future approaches, measuring the success of PTA plans with dedicated follow-up and further developing normative guidance to help research stakeholders navigate the complex practical challenges of realising PTA. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

The Use of the Data-to-Action Framework in the Evaluation of CDC's DELTA FOCUS Program.

PubMed

Armstead, Theresa L; Kearns, Megan; Rambo, Kirsten; Estefan, Lianne Fuino; Dills, Jenny; Rivera, Moira S; El-Beshti, Rasha

The Centers for Disease Control and Prevention's (CDC's) Domestic Violence Prevention Enhancements and Leadership Through Alliances, Focusing on Outcomes for Communities United with States (DELTA FOCUS) program is a 5-year cooperative agreement (2013-2018) funding 10 state domestic violence coalitions and local coordinated community response teams to engage in primary prevention of intimate partner violence. Grantees' prevention strategies were often developmental and emergent; therefore, CDC's approach to program oversight, administration, and support to grantees required a flexible approach. CDC staff adopted a Data-to-Action Framework for the DELTA FOCUS program evaluation that supported a culture of learning to meet dynamic and unexpected information needs. Briefly, a Data-to-Action Framework involves the collection and use of information in real time for program improvement. Utilizing this framework, the DELTA FOCUS data-to-action process yielded important insights into CDC's ongoing technical assistance, improved program accountability by providing useful materials, and information for internal agency leadership, and helped build a learning community among grantees. CDC and other funders, as decision makers, can promote program improvements that are data-informed by incorporating internal processes supportive of ongoing data collection and review.

Lesbian, Gay, Bisexual, and Transgender Health

MedlinePlus

... of HIV prevention interventions with evidence of effectiveness [Internet]. Atlanta: CDC; 2017. Available from: https://www.cdc.gov/hiv/research/interventionresearch/compendium/ 16 Ponce NA, Cochran SD, Pizer JC, et al. The effects of unequal access to health insurance for same-sex couples in ...

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

PubMed

Bai, Zhiyong; Grant, Barth D

2015-03-24

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

Two autowire versions for CDC-3200 and IBM-360

NASA Technical Reports Server (NTRS)

Billingsley, J. B.

1972-01-01

Microelectronics program was initiated to evaluate circuitry, packaging methods, and fabrication approaches necessary to produce completely procured logic system. Two autowire programs were developed for CDC-3200 and IBM-360 computers for use in designing logic systems.

Survey of Airport Access Analysis Techniques - Models, Data and a Research Program

DOT National Transportation Integrated Search

1972-06-01

The report points up the differences and similarities between airport access travel and general urban trip making. Models and surveys developed for, or applicable, to airport access planning are reviewed. A research program is proposed which would ge...

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

PubMed Central

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

2015-01-01

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

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

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.

Joint Statement on Insect Repellents by EPA and CDC

EPA Pesticide Factsheets

The EPA and the CDC are recommending the public to use insect repellents and take other precautions to avoid biting insects that carry serious diseases. This statement discusses diseases of concern, government roles, and repellent selection and use.

Enabling cross-disciplinary research by linking data to Open Access publications

NASA Astrophysics Data System (ADS)

Rettberg, N.

2012-04-01

OpenAIREplus focuses on the linking of research data to associated publications. The interlinking of research objects has implications for optimising the research process, allowing the sharing, enrichment and reuse of data, and ultimately serving to make open data an essential part of first class research. The growing call for more concrete data management and sharing plans, apparent at funder and national level, is complemented by the increasing support for a scientific infrastructure that supports the seamless access to a range of research materials. This paper will describe the recently launched OpenAIREplus and will detail how it plans to achieve its goals of developing an Open Access participatory infrastructure for scientific information. OpenAIREplus extends the current collaborative OpenAIRE project, which provides European researchers with a service network for the deposit of peer-reviewed FP7 grant-funded Open Access publications. This new project will focus on opening up the infrastructure to data sources from subject-specific communities to provide metadata about research data and publications, facilitating the linking between these objects. The ability to link within a publication out to a citable database, or other research data material, is fairly innovative and this project will enable users to search, browse, view, and create relationships between different information objects. In this regard, OpenAIREplus will build on prototypes of so-called "Enhanced Publications", originally conceived in the DRIVER-II project. OpenAIREplus recognizes the importance of representing the context of publications and datasets, thus linking to resources about the authors, their affiliation, location, project data and funding. The project will explore how links between text-based publications and research data are managed in different scientific fields. This complements a previous study in OpenAIRE on current disciplinary practices and future needs for infrastructural

[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.

RT11LIB: a library of subroutines for transferring data between a PDP-11 and CDC-6600

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

Jones, H.D.

1978-01-01

RT11LIB is a library of subroutines available to CDC 6600 users for the purpose of transferring data or program listings between a PDP-11 and a CDC 6600. These subroutines, operating on a CDC 6600 under the NOS/BE or SCOPE 3.4 operating systems, read or write magnetic tapes that are compatible with the PDP-11's RT11 operating system. Data written on the tape by the PDP-11 can be read by these subroutines and then translated into CDC 6600 format for subsequent data analysis. The translation process provides for many data formats, including byte, integer, floating point, and character string formats. Alternatively, datamore » from the CDC 6600 can be translated into PDP-11 format then written onto the tape for subsequent use on the PDP-11. This facility allows a program punched on a card deck by a keypunch operator to be transferred to the PDP-11, even though the PDP-11 is not itself equipped with a card reader.« less

Expression of motility-related molecule Cdc42 in endometrial tissue in women with adenomyosis and ovarian endometriomata.

PubMed

Goteri, Gaia; Ciavattini, Andrea; Lucarini, Guendalina; Montik, Nina; Filosa, Alessandra; Stramazzotti, Daniela; Biagini, Graziella; Tranquilli, Andrea Luigi

2006-09-01

To evaluate Cdc42 expression in eutopic and ectopic endometrial tissue in patients with adenomyosis and ovarian endometriotic cysts compared with patients without endometriosis. Experimental retrospective study. University hospital. Twenty-four patients with adenomyosis, 19 with ovarian endometriomata, and 9 with fibroids or benign ovarian cysts. Hysterectomy and bilateral oophorectomy. Immunostaining for Cdc42 of eutopic and ectopic endometrial tissues. In eutopic endometrium of patients with adenomyosis and with fibroids or benign ovarian cysts, the intensity of Cdc42 immunostaining was weaker, especially in the specialized stromal cells, compared with cases with ovarian endometriosis (chi(2) test, P=.003). Expression of Cdc42 in eutopic endometrium showed a trend to be higher in the secretory than in the proliferative phase and in patients with ovarian endometriotic cysts compared with patients with adenomyosis (unpaired t test, P=.005), especially in the proliferative phase. An abnormally high expression of Cdc42 in eutopic endometrium in the secretory phase may contribute to the development of ovarian endometriosis, but it does not seem to be involved in the pathogenesis of adenomyosis.

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

The impact of free access to the scientific literature: a review of recent research.

PubMed

Davis, Philip M; Walters, William H

2011-07-01

The paper reviews recent studies that evaluate the impact of free access (open access) on the behavior of scientists as authors, readers, and citers in developed and developing nations. It also examines the extent to which the biomedical literature is used by the general public. The paper is a critical review of the literature, with systematic description of key studies. Researchers report that their access to the scientific literature is generally good and improving. For authors, the access status of a journal is not an important consideration when deciding where to publish. There is clear evidence that free access increases the number of article downloads, although its impact on article citations is not clear. Recent studies indicate that large citation advantages are simply artifacts of the failure to adequately control for confounding variables. The effect of free access on the general public's use of the primary medical literature has not been thoroughly evaluated. Recent studies provide little evidence to support the idea that there is a crisis in access to the scholarly literature. Further research is needed to investigate whether free access is making a difference in non-research contexts and to better understand the dissemination of scientific literature through peer-to-peer networks and other informal mechanisms.

The impact of free access to the scientific literature: a review of recent research

PubMed Central

Walters, William H

2011-01-01

Objectives: The paper reviews recent studies that evaluate the impact of free access (open access) on the behavior of scientists as authors, readers, and citers in developed and developing nations. It also examines the extent to which the biomedical literature is used by the general public. Method: The paper is a critical review of the literature, with systematic description of key studies. Results: Researchers report that their access to the scientific literature is generally good and improving. For authors, the access status of a journal is not an important consideration when deciding where to publish. There is clear evidence that free access increases the number of article downloads, although its impact on article citations is not clear. Recent studies indicate that large citation advantages are simply artifacts of the failure to adequately control for confounding variables. The effect of free access on the general public's use of the primary medical literature has not been thoroughly evaluated. Conclusions: Recent studies provide little evidence to support the idea that there is a crisis in access to the scholarly literature. Further research is needed to investigate whether free access is making a difference in non-research contexts and to better understand the dissemination of scientific literature through peer-to-peer networks and other informal mechanisms. PMID:21753913

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

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.

Accession Medical Standards Analysis and Research Activity (AMSARA)

DTIC Science & Technology

2004-01-01

young adults with psychiatric disorders 15. SUBJECT TERMS Accession, medical, standards, attrition, waiver, discharge, hospitalization, disability...86 Research to Develop a Screening Test for Detection of Psychiatric Disorders in Young Adults ...secondary to organic or functional mental disorders that interfere with work or school after age 12 or current use of medication to improve or maintain

Ama1p-activated anaphase-promoting complex regulates the destruction of Cdc20p during meiosis II

PubMed Central

Tan, Grace S.; Magurno, Jennifer; Cooper, Katrina F.

2011-01-01

The execution of meiotic divisions in Saccharomyces cerevisiae is regulated by anaphase-promoting complex/cyclosome (APC/C)–mediated protein degradation. During meiosis, the APC/C is activated by association with Cdc20p or the meiosis-specific activator Ama1p. We present evidence that, as cells exit from meiosis II, APC/CAma1 mediates Cdc20p destruction. APC/CAma1 recognizes two degrons on Cdc20p, the destruction box and destruction degron, with either domain being sufficient to mediate Cdc20p destruction. Cdc20p does not need to associate with the APC/C to bind Ama1p or be destroyed. Coimmunoprecipitation analyses showed that the diverged amino-terminal region of Ama1p recognizes both Cdc20p and Clb1p, a previously identified substrate of APC/CAma1. Domain swap experiments revealed that the C-terminal WD region of Cdh1p, when fused to the N-terminal region of Ama1p, could direct most of Ama1p functions, although at a reduced level. In addition, this fusion protein cannot complement the spore wall defect in ama1Δ strains, indicating that substrate specificity is also derived from the WD repeat domain. These findings provide a mechanism to temporally down-regulate APC/CCdc20 activity as the cells complete meiosis II and form spores. PMID:21118994

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

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

Hypermatrix scheme for finite element systems on CDC STAR-100 computer

NASA Technical Reports Server (NTRS)

Noor, A. K.; Voigt, S. J.

1975-01-01

A study is made of the adaptation of the hypermatrix (block matrix) scheme for solving large systems of finite element equations to the CDC STAR-100 computer. Discussion is focused on the organization of the hypermatrix computation using Cholesky decomposition and the mode of storage of the different submatrices to take advantage of the STAR pipeline (streaming) capability. Consideration is also given to the associated data handling problems and the means of balancing the I/Q and cpu times in the solution process. Numerical examples are presented showing anticipated gain in cpu speed over the CDC 6600 to be obtained by using the proposed algorithms on the STAR computer.

13 CFR 120.810 - Applications for certification as a CDC.

Code of Federal Regulations, 2010 CFR

2010-01-01

... LOANS Development Company Loan Program (504) Certification Procedures to Become A Cdc § 120.810... District Office serving the jurisdiction in which the applicant has or proposes to locate its headquarters...

SIRT6 inhibits colorectal cancer stem cell proliferation by targeting CDC25A

PubMed Central

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

2018-01-01

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

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

PubMed Central

Bai, Zhiyong; Grant, Barth D.

2015-01-01

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

75 FR 7606 - Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-22

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC): Notice of Charter Renewal.... Contact Person for More Information: Anne C. Haddix, PhD, Designated Federal Officer, ACD, CDC, 1600...

An interactive NASTRAN preprocessor. [graphic display of undeformed structure using CDC 6000 series computer

NASA Technical Reports Server (NTRS)

Smith, W. W.

1973-01-01

A Langley Research Center version of NASTRAN Level 15.1.0 designed to provide the analyst with an added tool for debugging massive NASTRAN input data is described. The program checks all NASTRAN input data cards and displays on a CRT the graphic representation of the undeformed structure. In addition, the program permits the display and alteration of input data and allows reexecution without physically resubmitting the job. Core requirements on the CDC 6000 computer are approximately 77,000 octal words of central memory.

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

PubMed

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

2009-08-01

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

Open Access to Research Articles and Data: Library Roles

NASA Astrophysics Data System (ADS)

Joseph, Heather

2015-08-01

Over the past decade, a handful of key developments have caused scholars and researchers to rethink not only the way they conduct their work, but also the way in which they communicate it to others. The advent of the Internet has provided unprecedented opportunities for immediate, cost effective global connectivity, opening up new possibilities for collaboration and communication. This has resulted in scholarship increasingly being conducted in the online environment, and a vast amount of new digital information being generated and made widely available to those interested in using it. Additionally, the Internet is a dynamic environment, with new channels for producing and sharing information in a myriad of formats emerging frequently.In higher education, the momentum of the burgeoning movement towards "open" sharing of information of all kinds continues to gain traction. In particular, advancements in the areas of opening up access to articles and reserch data are increasingly visible. In both of these areas, academic and research libraries are playing important, central roles in promoting the awareness of the potential costs and benefits of a more open research environment, as well as defining new roles for libraries in this digital environment.As this push for grater openness continues, these fronts are intersecting in interesting and potentially transformative ways. The Open Access and Open Data movements share fundamental philosophical commonalities that make collaboration a natural outcome. Both movements place a premium on reducing barriers to discovering and accessing pertinent digital information. Perhaps even more significantly, both explicitly recognize that enabling productive use of digital information is key to unlocking its full value. As a result of these shared priorities, there are a wide variety of common strategies that libraries can take to help advance research, presenting new opportunities for deeper collaboration to take place.This talk will

COMCAN; COMCAN2A; system safety common cause analysis. [IBM360; CDC CYBER176,175; FORTRAN IV (30%) and BAL (70%) (IBM360), FORTRAN IV (97%) and COMPASS (3%) (CDC CYBER176)

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

Burdick, G.R.; Wilson, J.R.

COMCAN2A and COMCAN are designed to analyze complex systems such as nuclear plants for common causes of failure. A common cause event, or common mode failure, is a secondary cause that could contribute to the failure of more than one component and violates the assumption of independence. Analysis of such events is an integral part of system reliability and safety analysis. A significant common cause event is a secondary cause common to all basic events in one or more minimal cut sets. Minimal cut sets containing events from components sharing a common location or a common link are called commonmore » cause candidates. Components share a common location if no barrier insulates any one of them from the secondary cause. A common link is a dependency among components which cannot be removed by a physical barrier (e.g., a common energy source or common maintenance instructions).IBM360;CDC CYBER176,175; FORTRAN IV (30%) and BAL (70%) (IBM360), FORTRAN IV (97%) and COMPASS (3%) (CDC CYBER176).; OS/360 (IBM360) and NOS/BE 1.4 (CDC CYBER176), NOS 1.3 (CDC CYBER175); 140K bytes of memory for COMCAN and 242K (octal) words of memory for COMCAN2A.« less

Nek2A destruction marks APC/C activation at the prophase-to-prometaphase transition by spindle-checkpoint-restricted Cdc20.

PubMed

Boekhout, Michiel; Wolthuis, Rob

2015-04-15

Nek2 isoform A (Nek2A) is a presumed substrate of the anaphase-promoting complex/cyclosome containing Cdc20 (APC/C(Cdc20)). Nek2A, like cyclin A, is degraded in mitosis while the spindle checkpoint is active. Cyclin A prevents spindle checkpoint proteins from binding to Cdc20 and is recruited to the APC/C in prometaphase. We found that Nek2A and cyclin A avoid being stabilized by the spindle checkpoint in different ways. First, enhancing mitotic checkpoint complex (MCC) formation by nocodazole treatment inhibited the degradation of geminin and cyclin A, whereas Nek2A disappeared at a normal rate. Second, depleting Cdc20 effectively stabilized cyclin A but not Nek2A. Nevertheless, Nek2A destruction crucially depended on Cdc20 binding to the APC/C. Third, in contrast to cyclin A, Nek2A was recruited to the APC/C before the start of mitosis. Interestingly, the spindle checkpoint very effectively stabilized an APC/C-binding mutant of Nek2A, which required the Nek2A KEN box. Apparently, in cells, the spindle checkpoint primarily prevents Cdc20 from binding destruction motifs. Nek2A disappearance marks the prophase-to-prometaphase transition, when Cdc20, regardless of the spindle checkpoint, activates the APC/C. However, Mad2 depletion accelerated Nek2A destruction, showing that spindle checkpoint release further increases APC/C(Cdc20) catalytic activity. © 2015. Published by The Company of Biologists Ltd.

NUP98 fusion oncoproteins interact with the APC/C(Cdc20) as a pseudosubstrate and prevent mitotic checkpoint complex binding.

PubMed

Salsi, Valentina; Fantini, Sebastian; Zappavigna, Vincenzo

2016-09-01

NUP98 is a recurrent partner gene in translocations causing acute myeloid leukemias and myelodisplastic syndrome. The expression of NUP98 fusion oncoproteins has been shown to induce mitotic spindle defects and chromosome missegregation, which correlate with the capability of NUP98 fusions to cause mitotic checkpoint attenuation. We show that NUP98 oncoproteins physically interact with the APC/C(Cdc20) in the absence of the NUP98 partner protein RAE1, and prevent the binding of the mitotic checkpoint complex to the APC/C(Cdc20). NUP98 oncoproteins require the GLEBS-like domain present in their NUP98 moiety to bind the APC/C(Cdc20). We found that NUP98 wild-type is a substrate of APC/C(Cdc20) prior to mitotic entry, and that its binding to APC/C(Cdc20) is controlled via phosphorylation of a PEST sequence located within its C-terminal portion. We identify S606, within the PEST sequence, as a key target site, whose phosphorylation modulates the capability of NUP98 to interact with APC/C(Cdc20). We finally provide evidence for an involvement of the peptidyl-prolyl isomerase PIN1 in modulating the possible conformational changes within NUP98 that lead to its dissociation from the APC/C(Cdc20) during mitosis. Our results provide novel insight into the mechanisms underlying the aberrant capability of NUP98 oncoproteins to interact with APC/C(Cdc20) and to interfere with its function.

Hsp90 interaction with Cdc2 and Plo1 kinases contributes to actomyosin ring condensation in fission yeast.

PubMed

Santino, Andrea; Tallada, Victor A; Jimenez, Juan; Garzón, Andrés

2012-08-01

In Schizosaccharomyces pombe, cytokinesis occurs by ordered recruitment of actomyosin components at the division site, followed by lateral condensation to produce a ring-like structure early in anaphase, which eventually matures and contracts at the end of mitosis. We found that in temperature-sensitive hsp90-w1 mutant cells, encoding an Hsp90 mutant protein, ring components were recruited to form a cortical network at the division site, but this network failed to condense into a compact ring, suggesting a role for Hsp90 in this particular step. hsp90-w1 mutant shows strong genetic interaction with specific mutant alleles of the fission yeast cdc2, such as cdc2-33. Interestingly, actomyosin ring defects in hsp90-w1 cdc2-33 mutant cells resembled that of hsp90-w1 single mutant at restrictive temperature. Noteworthy, similar genetic interaction was found with a mutant allele of polo-like kinase, plo1-ts4, suggesting that Hsp90 collaborates with Cdc2 and Plo1 cell cycle kinases to condense medial ring components. In vitro analyses suggested that Cdc2 and Plo1 physically interact with Hsp90. Association of Cdc2 to Hsp90 was ATP independent, while Plo1 binds to this chaperone in an ATP-dependent manner, indicating that these two kinases interact with different Hsp90 complexes. Overall, our analyses of hsp90-w1 reveal a possible role for this chaperone in medial ring condensation in association with Cdc2 and Plo1 kinases.

The Prevention Research Centers Healthy Aging Research Network.

PubMed

Lang, Jason E; Anderson, Lynda; LoGerfo, James; Sharkey, Joseph; Belansky, Elaine; Bryant, Lucinda; Prohaska, Tom; Altpeter, Mary; Marshall, Victor; Satariano, William; Ivey, Susan; Bayles, Constance; Pluto, Delores; Wilcox, Sara; Goins, R Turner; Byrd, Robert C

2006-01-01

The Prevention Research Centers Healthy Aging Research Network (PRC-HAN), funded by the Centers for Disease Control and Prevention's (CDC's) Healthy Aging program, was created in 2001 to help develop partnerships and create a research agenda that promotes healthy aging. The nine universities that participate in the network use their expertise in aging research to collaborate with their communities and other partners to develop and implement health promotion interventions for older adults at the individual, organizational, environmental, and policy levels. The population of older adults in the United States is growing rapidly; approximately 20% of Americans will be aged 65 years or older by 2030. The health and economic impact of an aging society compel the CDC and the public health community to place increased emphasis on preventing unnecessary disease, disability, and injury among older Americans. The PRC-HAN has a broad research agenda that addresses health-promoting skills and behaviors, disease and syndrome topics, and knowledge domains. The network chose physical activity for older adults as its initial focus for research and has initiated two networkwide projects: a comprehensive, multisite survey that collected information on the capacity, content, and accessibility of physical activity programs for older adults and a peer-reviewed publication that describes the role of public health in promoting physical activity among older adults. In addition to participating in the core research area, each network member works independently with its community committee on PRC-HAN activities. As a result, the network is 1) expanding prevention research for older adults and their communities; 2) promoting the translation and dissemination of findings to key stakeholders; 3) strengthening PRC-HAN capacity through partnerships and expanded funding; and 4) stimulating the adoption of policies and programs by engaging policymakers, planners, and practitioners. In 2003, the PRC

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

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC) In accordance with section... Ethics Subcommittee, as well as an update from the CDC Director. The agenda is subject to change as...

Phosphatidylserine is polarized and required for proper Cdc42 localization and for development of cell polarity.

PubMed

Fairn, Gregory D; Hermansson, Martin; Somerharju, Pentti; Grinstein, Sergio

2011-10-02

Polarity is key to the function of eukaryotic cells. On the establishment of a polarity axis, cells can vectorially target secretion, generating an asymmetric distribution of plasma membrane proteins. From Saccharomyces cerevisiae to mammals, the small GTPase Cdc42 is a pivotal regulator of polarity. We used a fluorescent probe to visualize the distribution of phosphatidylserine in live S. cerevisiae. Remarkably, phosphatidylserine was polarized in the plasma membrane, accumulating in bud necks, the bud cortex and the tips of mating projections. Polarization required vectorial delivery of phosphatidylserine-containing secretory vesicles, and phosphatidylserine was largely excluded from endocytic vesicles, contributing to its polarized retention. Mutants lacking phosphatidylserine synthase had impaired polarization of the Cdc42 complex, leading to a delay in bud emergence, and defective mating. The addition of lysophosphatidylserine resulted in resynthesis and polarization of phosphatidylserine, as well as repolarization of Cdc42. The results indicate that phosphatidylserine--and presumably its polarization--are required for optimal Cdc42 targeting and activation during cell division and mating.

40 CFR 11.6 - Access by historical researchers and former Government officials.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Access by historical researchers and former Government officials. 11.6 Section 11.6 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL SECURITY CLASSIFICATION REGULATIONS PURSUANT TO EXECUTIVE ORDER 11652 § 11.6 Access by historical...

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.

Cdk1 Regulates the Temporal Recruitment of Telomerase and Cdc13-Stn1-Ten1 Complex for Telomere Replication

PubMed Central

Liu, Chang-Ching; Gopalakrishnan, Veena; Poon, Lai-Fong; Yan, TingDong

2014-01-01

In budding yeast (Saccharomyces cerevisiae), the cell cycle-dependent telomere elongation by telomerase is controlled by the cyclin-dependent kinase 1 (Cdk1). The telomere length homeostasis is balanced between telomerase-unextendable and telomerase-extendable states that both require Cdc13. The recruitment of telomerase complex by Cdc13 promotes telomere elongation, while the formation of Cdc13-Stn1-Ten1 (CST) complex at the telomere blocks telomere elongation by telomerase. However, the cellular signaling that regulates the timing of the telomerase-extendable and telomerase-unextendable states is largely unknown. Phosphorylation of Cdc13 by Cdk1 promotes the interaction between Cdc13 and Est1 and hence telomere elongation. Here, we show that Cdk1 also phosphorylates Stn1 at threonine 223 and serine 250 both in vitro and in vivo, and these phosphorylation events are essential for the stability of the CST complexes at the telomeres. By controlling the timing of Cdc13 and Stn1 phosphorylations during cell cycle progression, Cdk1 regulates the temporal recruitment of telomerase complexes and CST complexes to the telomeres to facilitate telomere maintenance. PMID:24164896

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

Code of Federal Regulations, 2011 CFR

2011-01-01

... 504 loan outside of a CDC's Area of Operations. 120.839 Section 120.839 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Extending A Cdc's Area of Operations § 120.839 Case-by-case application to make a 504 loan outside of a CDC's Area of...

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

Code of Federal Regulations, 2010 CFR

2010-01-01

... 504 loan outside of a CDC's Area of Operations. 120.839 Section 120.839 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Extending A Cdc's Area of Operations § 120.839 Case-by-case application to make a 504 loan outside of a CDC's Area of...

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

Code of Federal Regulations, 2014 CFR

2014-01-01

... 504 loan outside of a CDC's Area of Operations. 120.839 Section 120.839 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Extending A Cdc's Area of Operations § 120.839 Case-by-case application to make a 504 loan outside of a CDC's Area of...

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

Code of Federal Regulations, 2012 CFR

2012-01-01

... 504 loan outside of a CDC's Area of Operations. 120.839 Section 120.839 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Extending A Cdc's Area of Operations § 120.839 Case-by-case application to make a 504 loan outside of a CDC's Area of...

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

Code of Federal Regulations, 2013 CFR

2013-01-01

... 504 loan outside of a CDC's Area of Operations. 120.839 Section 120.839 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Extending A Cdc's Area of Operations § 120.839 Case-by-case application to make a 504 loan outside of a CDC's Area of...

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

76 FR 22708 - Centers for Disease Control and Prevention/Health Resources and Services Administration (CDC/HRSA...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-22

... Prevention Activities from both CHAC Workgroups on Sexual Health and Viral Hepatitis; (3) Update on CDC HIV... Priorities and Coordination of Media and Social Marketing related to HIV, STD and Viral Hepatitis prevention... INFORMATION: Margie Scott-Cseh, CDC, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention...

Accessible transportation technologies research initiative : advancing mobility solutions for travelers with disabilities.

DOT National Transportation Integrated Search

2016-01-01

The Accessible Transportation Technologies Research Initiative (ATTRI) improves the mobility of travelers with disabilities through research, development, and implementation of transformative technologies, applications, or systems for people of all a...

"Know More Hepatitis:" CDC's National Education Campaign to Increase Hepatitis C Testing Among People Born Between 1945 and 1965.

PubMed

Jorgensen, Cynthia; Carnes, C Amanda; Downs, Alycia

2016-01-01

In 2012, CDC issued recommendations calling for those born between 1945 and 1965, or baby boomers, to get tested for the hepatitis C virus. To help implement this recommendation, CDC developed "Know More Hepatitis," a multimedia national education campaign. Guided by behavioral science theories and formative research, the campaign used multiple strategies to reach baby boomers and health-care providers with messages encouraging baby boomers to get tested for hepatitis C. With a limited campaign budget, the "Know More Hepatitis" campaign relied mostly on donated time and space from broadcast and print outlets. Donated placements totaled approximately $14.7 million, which reflected a more than 12-to-1 return on the campaign investment. This effort was supplemented with a small, paid digital advertising campaign. Combining audience impressions from both paid and donated campaign efforts resulted in more than 1.2 billion audience impressions.

Access to Archived Astronaut Data for Human Research Program Researchers: Update on Progress and Process Improvements

NASA Technical Reports Server (NTRS)

Lee, L. R.; Montague, K. A.; Charvat, J. M.; Wear, M. L.; Thomas, D. M.; Van Baalen, M.

2016-01-01

Since the 2010 NASA directive to make the Life Sciences Data Archive (LSDA) and Lifetime Surveillance of Astronaut Health (LSAH) data archives more accessible by the research and operational communities, demand for astronaut medical data has increased greatly. LSAH and LSDA personnel are working with Human Research Program on many fronts to improve data access and decrease lead time for release of data. Some examples include the following: Feasibility reviews for NASA Research Announcement (NRA) data mining proposals; Improved communication, support for researchers, and process improvements for retrospective Institutional Review Board (IRB) protocols; Supplemental data sharing for flight investigators versus purely retrospective studies; Work with the Multilateral Human Research Panel for Exploration (MHRPE) to develop acceptable data sharing and crew consent processes and to organize inter-agency data coordinators to facilitate requests for international crewmember data. Current metrics on data requests crew consenting will be presented, along with limitations on contacting crew to obtain consent. Categories of medical monitoring data available for request will be presented as well as flow diagrams detailing data request processing and approval steps.

Poor Access for African Researchers to African Emergency Care Publications: A Cross-sectional Study.

PubMed

Bruijns, Stevan R; Maesela, Mmapeladi; Sinha, Suniti; Banner, Megan

2017-10-01

Based on relative population size and burden of disease, emergency care publication outputs from low- and middle-income regions are disproportionately lower than those of high-income regions. Ironically, outputs from regions with higher publication rates are often less relevant in the African context. As a result, the dissemination of and access to local research is essential to local researchers, but the cost of this access (actual and cost-wise) remains unknown. The aim of this study was to describe access to African emergency care publications in terms of publisher-based access (open access or subscription) and alternate access (self-archived or author provided), as well as the cost of access. We conducted a retrospective, cross-sectional study using all emergency medicine publications included in Scopus between 2011 and 2015. A sequential search strategy described access to each article, and we calculated mean article charges against the purchasing power parity index (used to describe out-of-pocket expense). We included 666 publications from 49 journals, of which 395 (59.3%) were open access. For subscription-based articles, 106 (39.1%) were self-archived, 60 (22.1%) were author-provided, and 105 (38.8%) were inaccessible. Mean article access cost was $36.44, and mean processing charge was $2,319.34. Using the purchasing power parity index it was calculated that equivalent out-of-pocket expenditure for South African, Ghanaian and Tanzanian authors would respectively be $15.77, $10.44 and $13.04 for access, and $1,004.02, $664.36 and $830.27 for processing. Based on this, the corrected cost of a single-unit article access or process charge for South African, Ghanaian and Tanzanian authors, respectively, was 2.3, 3.5 and 2.8 times higher than the standard rate. One in six African emergency care publications are inaccessible outside institutional library subscriptions; additionally, the cost of access to publications in low- and middle-income countries appears

Cdc45 (cell division cycle protein 45) guards the gate of the Eukaryote Replisome helicase stabilizing leading strand engagement

PubMed Central

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

2015-01-01

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

NOAA Office of Exploration and Research > Data Access > Overview

Science.gov Websites

Management of Environmental Data and Information and related Procedural Directives inform OER INFORMATION ON THE NOAA OFFICE OF OCEAN EXPLORATION AND RESEARCH, VISIT: OCEANEXPLORER.NOAA.GOV weather oceans Science Overview Data Access Overview Operational Data Management Publications Education Overview Alliance

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

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.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Advisory Committee to the Director (ACD), Centers for Disease Control (CDC) and Prevention--Ethics Subcommittee (ES..., CDC, regarding a broad range of public health ethics questions and issues arising from programs...

77 FR 34046 - Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)-Ethics...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-08

... Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)--Ethics Subcommittee (ES... ACD, CDC, regarding a broad range of public health ethics questions and issues arising from programs... ethics standards to the accreditation process for public health departments; ethical considerations...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Advisory Committee to the Director (ACD), Centers for Disease Control (CDC) and Prevention--Ethics Subcommittee (ES); Correction AGENCY: Centers for Disease Control and Prevention (CDC), HHS. ACTION: Notice of meeting; meeting...

MaizeGDB: enabling access to basic, translational, and applied research information

USDA-ARS?s Scientific Manuscript database

MaizeGDB is the Maize Genetics and Genomics Database (available online at http://www.maizegdb.org). The MaizeGDB project is not simply an online database and website but rather an information service to maize researchers that supports customized data access and analysis needs to individual research...

49 CFR 8.29 - Access by historical researchers and former Presidential appointees.

Code of Federal Regulations, 2010 CFR

2010-10-01

... branch who are engaged in historical research projects may have access to classified information provided... to persons who are conducting historical research as private individuals or under private sponsorship and do not apply to research conducted under Government contract or sponsorship. The provisions are...

49 CFR 8.29 - Access by historical researchers and former Presidential appointees.

Code of Federal Regulations, 2011 CFR

2011-10-01

... branch who are engaged in historical research projects may have access to classified information provided... to persons who are conducting historical research as private individuals or under private sponsorship and do not apply to research conducted under Government contract or sponsorship. The provisions are...

Regulation of Mih1/Cdc25 by protein phosphatase 2A and casein kinase 1

PubMed Central

Pal, Gayatri; Paraz, Maria T.Z.; Kellogg, Douglas R.

2008-01-01