MiR-7 inhibited peripheral nerve injury repair by affecting neural stem cells migration and proliferation through cdc42.

PubMed

Zhou, Nan; Hao, Shuang; Huang, Zongqiang; Wang, Weiwei; Yan, Penghui; Zhou, Wei; Zhu, Qihang; Liu, Xiaokang

2018-01-01

Objective Neural stem cells play an important role in the recovery and regeneration of peripheral nerve injury, and the microRNA-7 (miR-7) regulates differentiation of neural stem cells. This study aimed to explore the role of miR-7 in neural stem cells homing and proliferation and its influence on peripheral nerve injury repair. Methods The mice model of peripheral nerve injury was created by segmental sciatic nerve defect (sciatic nerve injury), and neural stem cells treatment was performed with a gelatin hydrogel conduit containing neural stem cells inserted into the sciatic nerve injury mice. The Sciatic Function Index was used to quantify sciatic nerve functional recovery in the mice. The messenger RNA and protein expression were detected by reverse transcription polymerase chain reaction and Western blot, respectively. Luciferase reporter assay was used to confirm the binding between miR-7 and the 3'UTR of cell division cycle protein 42 (cdc42). The neural stem cells migration and proliferation were analyzed by transwell assay and a Cell-LightTM EdU DNA Cell Proliferation kit, respectively. Results Neural stem cells treatment significantly promoted nerve repair in sciatic nerve injury mice. MiR-7 expression was decreased in sciatic nerve injury mice with neural stem cells treatment, and miR-7 mimic transfected into neural stem cells suppressed migration and proliferation, while miR-7 inhibitor promoted migration and proliferation. The expression level and effect of cdc42 on neural stem cells migration and proliferation were opposite to miR-7, and the luciferase reporter assay proved that cdc42 was a target of miR-7. Using co-transfection into neural stem cells, we found pcDNA3.1-cdc42 and si-cdc42 could reverse respectively the role of miR-7 mimic and miR-7 inhibitor on neural stem cells migration and proliferation. In addition, miR-7 mimic-transfected neural stem cells could abolish the protective role of neural stem cells on peripheral nerve injury. Conclusion MiR-7 inhibited peripheral nerve injury repair by affecting neural stem cells migration and proliferation through cdc42.

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

PubMed

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

2007-08-01

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

Inadequate Diagnosis and Treatment of Malaria Among Travelers Returning from Africa During the Ebola Epidemic--United States, 2014-2015.

PubMed

Tan, Kathrine R; Cullen, Karen A; Koumans, Emilia H; Arguin, Paul M

2016-01-22

Among 1,683 persons in the United States who developed malaria following international travel during 2012, more than half acquired disease in one of 16 countries in West Africa. Since March 2014, West Africa has experienced the world's largest epidemic of Ebola virus disease (Ebola), primarily affecting Guinea, Sierra Leone, and Liberia; in 2014, approximately 20,000 Ebola cases were reported. Both Ebola and malaria are often characterized by fever and malaise and can be clinically indistinguishable, especially early in the course of disease. Immediate laboratory testing is critical for diagnosis of both Ebola and malaria, so that appropriate lifesaving treatment can be initiated. CDC recommends prompt malaria testing of patients with fever and history of travel to an area that is endemic for malaria, using blood smear microscopy, with results available within a few hours. Empiric treatment of malaria is not recommended by CDC. Reverse transcription-polymerase chain reaction (RT-PCR) testing is recommended to diagnose Ebola. During the Ebola outbreak in West Africa, CDC received reports of delayed laboratory testing for malaria in travelers returning to the United States because of infection control concerns related to Ebola. CDC reviewed documented calls to its malaria consultation service and selected three patient cases to present as examples of deficiencies in the evaluation and treatment of malaria among travelers returning from Africa during the Ebola epidemic.

The electron is a catalyst

NASA Astrophysics Data System (ADS)

Studer, Armido; Curran, Dennis P.

2014-09-01

The electron is an efficient catalyst for conducting various types of radical cascade reaction that proceed by way of radical and radical ion intermediates. But because electrons are omnipresent, catalysis by electrons often passes unnoticed. In this Review, a simple analogy between acid/base catalysis and redox catalysis is presented. Conceptually, the electron is a catalyst in much the same way that a proton is a catalyst. The 'electron is a catalyst' paradigm unifies mechanistically an assortment of synthetic transformations that otherwise have little or no apparent relationship. Diverse radical cascades, including unimolecular radical substitution reactions (SRN1-type chemistry), base-promoted homolytic aromatic substitutions (BHAS), radical Heck-type reactions, radical cross-dehydrogenative couplings (CDC), direct arene trifluoromethylations and radical alkoxycarbonylations, can all be viewed as electron-catalysed reactions.

The Use of Modular Computer-Based Lessons in a Modification of the Classical Introductory Course in Organic Chemistry.

ERIC Educational Resources Information Center

Stotter, Philip L.; Culp, George H.

An experimental course in organic chemistry utilized computer-assisted instructional (CAI) techniques. The CAI lessons provided tutorial drill and practice and simulated experiments and reactions. The Conversational Language for Instruction and Computing was used, along with a CDC 6400-6600 system; students scheduled and completed the lessons at…

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

PubMed

Weems, Andrew; McMurray, Michael

2017-05-25

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

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

PubMed Central

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

2000-01-01

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

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

PubMed

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

2000-12-01

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

Colossal dielectric constant and relaxation behaviors in Pr:SrTiO{sub 3} ceramics

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

Liu Cheng; Liu Peng; Zhou Jianping

2010-05-15

Sr{sub 1-x}Pr{sub x}TiO{sub 3} ceramics (0.00{<=}x{<=}0.03) were prepared by a traditional solid-state reaction method. Two relaxation processes (marked as A and B) of the Sr{sub 0.09}Pr{sub 0.01}TiO{sub 3} ceramics were investigated by analyzing the E{sub a} values obtained from the Arrhenius law. Colossal dielectric constant (CDC) was first obtained in Sr{sub 0.09}Pr{sub 0.01}TiO{sub 3} ceramics, whose permittivity was up to 3000 (1 kHz, room temperature), greater than that of pure SrTiO{sub 3} ceramics and samples with more Pr addition (x=0.02 and 0.03). This CDC behavior was related to the internal barrier layer capacitance mechanism.

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

PubMed Central

Izumi, T; Maller, J L

1993-01-01

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

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

PubMed Central

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

1998-01-01

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

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.

Risk and Outbreak Communication: Lessons from Taiwan's Experiences in the Post-SARS Era.

PubMed

Hsu, Yu-Chen; Chen, Yu-Ling; Wei, Han-Ning; Yang, Yu-Wen; Chen, Ying-Hwei

In addition to the impact of a disease itself, public reaction could be considered another outbreak to be controlled during an epidemic. Taiwan's experience with SARS in 2003 highlighted the critical role played by the media during crisis communication. After the SARS outbreak, Taiwan's Centers for Disease Control (Taiwan CDC) followed the WHO outbreak communication guidelines on trust, early announcements, transparency, informing the public, and planning, in order to reform its risk communication systems. This article describes the risk communication framework in Taiwan, which has been used to respond to the 2009-2016 influenza epidemics, Ebola in West Africa (2014-16), and MERS-CoV in South Korea (2015) during the post-SARS era. Many communication strategies, ranging from traditional media to social and new media, have been implemented to improve transparency in public communication and promote civic engagement. Taiwan CDC will continue to maintain the strengths of its risk communication systems and resolve challenges as they emerge through active evaluation and monitoring of public opinion to advance Taiwan's capacity in outbreak communication and control. Moreover, Taiwan CDC will continue to implement the IHR (2005) and to promote a global community working together to fight shared risks and to reach the goal of "One World, One Health."

Risk and Outbreak Communication: Lessons from Taiwan's Experiences in the Post-SARS Era

PubMed Central

Chen, Yu-Ling; Wei, Han-Ning; Yang, Yu-Wen; Chen, Ying-Hwei

2017-01-01

In addition to the impact of a disease itself, public reaction could be considered another outbreak to be controlled during an epidemic. Taiwan's experience with SARS in 2003 highlighted the critical role played by the media during crisis communication. After the SARS outbreak, Taiwan's Centers for Disease Control (Taiwan CDC) followed the WHO outbreak communication guidelines on trust, early announcements, transparency, informing the public, and planning, in order to reform its risk communication systems. This article describes the risk communication framework in Taiwan, which has been used to respond to the 2009-2016 influenza epidemics, Ebola in West Africa (2014-16), and MERS-CoV in South Korea (2015) during the post-SARS era. Many communication strategies, ranging from traditional media to social and new media, have been implemented to improve transparency in public communication and promote civic engagement. Taiwan CDC will continue to maintain the strengths of its risk communication systems and resolve challenges as they emerge through active evaluation and monitoring of public opinion to advance Taiwan's capacity in outbreak communication and control. Moreover, Taiwan CDC will continue to implement the IHR (2005) and to promote a global community working together to fight shared risks and to reach the goal of “One World, One Health.” PMID:28418746

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.

'Repel all biters': an enhanced collection of endophilic Anopheles gambiae and Anopheles arabiensis in CDC light-traps, from the Kagera Region of Tanzania, in the presence of a combination mosquito net impregnated with piperonyl butoxide and permethrin.

PubMed

LeClair, Corey; Cronery, Judith; Kessy, Enock; Tomás, Elsa V E; Kulwa, Yohannes; Mosha, Franklin W; Rowland, Mark; Protopopoff, Natacha; Derek Charlwood, J

2017-08-15

Mosquito nets containing synergists designed to overcome metabolic resistance mechanisms in vectors have been developed. These may enhance excitability in the mosquitoes and affect how they respond to CDC light-traps. Investigating the behaviour of vectors of disease in relation to novel mosquito nets is, therefore, essential for the design of sampling and surveillance systems. In an initial experiment in Muleba, Tanzania, nine bedrooms from three housing clusters were sampled. CDC light-traps were operated indoors next to occupied untreated nets (UTN), Olyset ® long lasting insecticidal net (LLIN) and Olyset Plus ® LLIN containing piperonyl butoxide (PBO) synergist. Nets were rotated daily between the nine rooms over nine nights. A further series of experiments using the nets on alternate nights in a single room was undertaken during the short rains. Anopheles gambiae s.l. were collected in CDC light-traps, a window-trap and Furvela tent-trap. Anopheles gambiae s.l. were identified to species by polymerase chain reaction (PCR). In the initial experiment 97.7% of the 310 An. gambiae s.l. were An. gambiae s.s., the remainder being Anopheles arabiensis. The number of mosquitoes collected from 81 light-trap collections was greater in the presence of an Olyset [density rate ratio 1.81, 95% CI (1.22-2.67), p = 0.003] relative to an UTN. In a second experiment, in the wet season 84% of the 180 An. gambiae s.l. identified were An. arabiensis. The number of An. gambiae s.l. collected from a light-trap compared to a tent-trap was significantly higher when an Olyset Plus net was used compared to an UTN. Survival of the mosquitoes in the window trap was not reduced by the use of an Olyset Plus net in the bedroom relative to an Olyset net. Mosquitoes entering bedrooms, even those susceptible to pyrethroids, were not killed by contact with an Olyset Plus LLIN. The enhanced numbers of An. gambiae or An. arabiensis collected in light-traps when a treated net is used requires further experimentation and may be because of a heightened escape reaction on the part of the mosquito.

Basic Fibroblast Growth Factor Regulates Gene and Protein Expression Related to Proliferation, Differentiation, and Matrix Production of Human Dental Pulp Cells.

PubMed

Chang, Ya-Ching; Chang, Mei-Chi; Chen, Yi-Jane; Liou, Ji-Uei; Chang, Hsiao-Hua; Huang, Wei-Ling; Liao, Wan-Chuen; Chan, Chiu-Po; Jeng, Po-Yuan; Jeng, Jiiang-Huei

2017-06-01

Basic fibroblast growth factor (bFGF) plays differential effects on the proliferation, differentiation, and extracellular matrix turnover in various tissues. However, limited information is known about the effect of bFGF on dental pulp cells. The purposes of this study were to investigate whether bFGF influences the cell differentiation and extracellular matrix turnover of human dental pulp cells (HDPCs) and the related gene and protein expression as well as the role of the mitogen-activated protein kinase (MEK)/extracellular-signal regulated kinase (ERK) signaling pathway. The expression of fibroblast growth factor receptors (FGFRs) in HDPCs was also studied. The expression of FGFR1 and FGFR2 in HDPCs was investigated by reverse-transcription polymerase chain reaction. HDPCs were treated with different concentrations of bFGF. Cell proliferation was evaluated using the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Cell differentiation was evaluated using alkaline phosphatase (ALP) staining. Changes in messenger expression of cyclin B1 and tissue inhibitor of metalloproteinase (TIMP) 1 were determined by reverse-transcription polymerase chain reaction. Changes in protein expression of cdc2, TIMP-1, TIMP-2, and collagen I were determined by Western blotting. U0126 was used to clarify the role of MEK/ERK signaling. HDPCs expressed both FGFR1 and FGFR2. Cell viability was stimulated by 50-250 ng/mL bFGF. The expression and enzyme activities of ALP were inhibited by 10-500 ng/mL bFGF. At similar concentrations, bFGF stimulates cdc2, cyclin B1, and TIMP-1 messenger RNA and protein expression. bFGF showed little effect on TIMP-2 and partly inhibited collagen I expression of pulp cells. U0126 (a MEK/ERK inhibitor) attenuated the bFGF-induced increase of cyclin B1, cdc2, and TIMP-1. bFGF may be involved in pulpal repair and regeneration by activation of FGFRs to regulate cell growth; stimulate cdc2, cyclin B1, and TIMP-1 expression; and inhibit ALP. These events are partly associated with MEK/ERK signaling. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Ubiquitination of Cdc20 by the APC occurs through an intramolecular mechanism

PubMed Central

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

2012-01-01

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

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

PubMed

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

2015-01-16

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

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

PubMed

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

2014-07-01

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

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

PubMed

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

1998-04-15

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-12-07

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

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

PubMed

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

2011-01-01

Rho-type GTPases are key regulators that control eukaryotic cell polarity, but their role in fungal morphogenesis is only beginning to emerge. In this study, we investigate the role of the CDC-42 - RAC - CDC-24 module in Neurospora crassa. rac and cdc-42 deletion mutants are viable, but generate highly compact colonies with severe morphological defects. Double mutants carrying conditional and loss of function alleles of rac and cdc-42 are lethal, indicating that both GTPases share at least one common essential function. The defects of the GTPase mutants are phenocopied by deletion and conditional alleles of the guanine exchange factor (GEF) cdc-24, and in vitro GDP-GTP exchange assays identify CDC-24 as specific GEF for both CDC-42 and RAC. In vivo confocal microscopy shows that this module is organized as membrane-associated cap that covers the hyphal apex. However, the specific localization patterns of the three proteins are distinct, indicating different functions of RAC and CDC-42 within the hyphal tip. CDC-42 localized as confined apical membrane-associated crescent, while RAC labeled a membrane-associated ring excluding the region labeled by CDC42. The GEF CDC-24 occupied a strategic position, localizing as broad apical membrane-associated crescent and in the apical cytosol excluding the Spitzenkörper. RAC and CDC-42 also display distinct localization patterns during branch initiation and germ tube formation, with CDC-42 accumulating at the plasma membrane before RAC. Together with the distinct cellular defects of rac and cdc-42 mutants, these localizations suggest that CDC-42 is more important for polarity establishment, while the primary function of RAC may be maintaining polarity. In summary, this study identifies CDC-24 as essential regulator for RAC and CDC-42 that have common and distinct functions during polarity establishment and maintenance of cell polarity in N. crassa.

13 CFR 120.822 - CDC membership.

Code of Federal Regulations, 2011 CFR

2011-01-01

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

13 CFR 120.822 - CDC membership.

Code of Federal Regulations, 2010 CFR

2010-01-01

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

13 CFR 120.822 - CDC membership.

Code of Federal Regulations, 2014 CFR

2014-01-01

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

13 CFR 120.822 - CDC membership.

Code of Federal Regulations, 2012 CFR

2012-01-01

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

13 CFR 120.822 - CDC membership.

Code of Federal Regulations, 2013 CFR

2013-01-01

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

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

Code of Federal Regulations, 2013 CFR

2013-01-01

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

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

Code of Federal Regulations, 2014 CFR

2014-01-01

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

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

Code of Federal Regulations, 2011 CFR

2011-01-01

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

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

Code of Federal Regulations, 2012 CFR

2012-01-01

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

Facts about Botulism

MedlinePlus

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Injuries and Mass Casualty Events

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

PubMed

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

2009-05-01

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

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

PubMed Central

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

2012-01-01

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

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

PubMed

Marty, Amber J; Gauthier, Gregory M

2013-01-01

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

Particle-based simulations of polarity establishment reveal stochastic promotion of Turing pattern formation

PubMed Central

Ramirez, Samuel A.; Elston, Timothy C.

2018-01-01

Polarity establishment, the spontaneous generation of asymmetric molecular distributions, is a crucial component of many cellular functions. Saccharomyces cerevisiae (yeast) undergoes directed growth during budding and mating, and is an ideal model organism for studying polarization. In yeast and many other cell types, the Rho GTPase Cdc42 is the key molecular player in polarity establishment. During yeast polarization, multiple patches of Cdc42 initially form, then resolve into a single front. Because polarization relies on strong positive feedback, it is likely that the amplification of molecular-level fluctuations underlies the generation of multiple nascent patches. In the absence of spatial cues, these fluctuations may be key to driving polarization. Here we used particle-based simulations to investigate the role of stochastic effects in a Turing-type model of yeast polarity establishment. In the model, reactions take place either between two molecules on the membrane, or between a cytosolic and a membrane-bound molecule. Thus, we developed a computational platform that explicitly simulates molecules at and near the cell membrane, and implicitly handles molecules away from the membrane. To evaluate stochastic effects, we compared particle simulations to deterministic reaction-diffusion equation simulations. Defining macroscopic rate constants that are consistent with the microscopic parameters for this system is challenging, because diffusion occurs in two dimensions and particles exchange between the membrane and cytoplasm. We address this problem by empirically estimating macroscopic rate constants from appropriately designed particle-based simulations. Ultimately, we find that stochastic fluctuations speed polarity establishment and permit polarization in parameter regions predicted to be Turing stable. These effects can operate at Cdc42 abundances expected of yeast cells, and promote polarization on timescales consistent with experimental results. To our knowledge, our work represents the first particle-based simulations of a model for yeast polarization that is based on a Turing mechanism. PMID:29529021

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

PubMed Central

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

2010-01-01

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

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

PubMed

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

2010-07-02

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

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

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

NASA Astrophysics Data System (ADS)

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

2014-03-01

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

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

PubMed

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

1998-07-01

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

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

PubMed Central

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

1998-01-01

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

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

PubMed

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

2010-03-15

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

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

PubMed

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

2015-06-01

Eukaryotic cell cycle involves a number of protein kinases important for the onset and progression through mitosis, most of which are well characterized in the budding and fission yeasts and conserved in other fungi. However, unlike the model yeast and filamentous fungi that have a single Cdc2 essential for cell cycle progression, the wheat scab fungus Fusarium graminearum contains two CDC2 orthologs. The cdc2A and cdc2B mutants had no obvious defects in growth rate and conidiation but deletion of both of them is lethal, indicating that these two CDC2 orthologs have redundant functions during vegetative growth and asexual reproduction. However, whereas the cdc2B mutant was normal, the cdc2A mutant was significantly reduced in virulence and rarely produced ascospores. Although deletion of CDC2A had no obvious effect on the formation of penetration branches or hyphopodia, the cdc2A mutant was limited in the differentiation and growth of infectious growth in wheat tissues. Therefore, CDC2A plays stage-specific roles in cell cycle regulation during infectious growth and sexual reproduction. Both CDC2A and CDC2B are constitutively expressed but only CDC2A was up-regulated during plant infection and ascosporogenesis. Localization of Cdc2A- GFP to the nucleus but not Cdc2B-GFP was observed in vegetative hyphae, ascospores, and infectious hyphae. Complementation assays with chimeric fusion constructs showed that both the N- and C-terminal regions of Cdc2A are important for its functions in pathogenesis and ascosporogenesis but only the N-terminal region is important for its subcellular localization. Among the Sordariomycetes, only three Fusarium species closely related to F. graminearum have two CDC2 genes. Furthermore, F. graminearum uniquely has two Aurora kinase genes and one additional putative cyclin gene, and its orthologs of CAK1 and other four essential mitotic kinases in the budding yeast are dispensable for viability. Overall, our data indicate that cell cycle regulation is different between vegetative and infectious hyphae in F. graminearum and Cdc2A, possibly by interacting with a stage-specific cyclin, plays a more important role than Cdc2B during ascosporogenesis and plant infection.

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.

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

A Hydrazone-Based Covalent Organic Framework as an Efficient and Reusable Photocatalyst for the Cross-Dehydrogenative Coupling Reaction of N-Aryltetrahydroisoquinolines.

PubMed

Liu, Wanting; Su, Qing; Ju, Pengyao; Guo, Bixuan; Zhou, Hui; Li, Guanghua; Wu, Qiaolin

2017-02-22

A hydrazone-based covalent organic framework (COF) was synthesized by condensation of 2,5-dimethoxyterephthalohydrazide with 1,3,5-triformylbenzene under solvothermal conditions. The COF material exhibits excellent porosity with a BET surface area of up to 1501 m 2  g -1 , high crystallinity, and good thermal and chemical stability. Moreover, it showed efficient photocatalytic activity towards cross-dehydrogenative coupling (CDC) reactions between tetrahydroisoquinolines and nucleophiles such as nitromethane, acetone, and phenylethyl ketone. The metal-free catalytic system also offers attractive advantages including simplicity of operation, wide substrate adaptability, ambient reaction conditions, and robust recycling capability of the catalyst, thus providing a promising platform for highly efficient and reusable photocatalysts. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

PubMed Central

Witte, Kristen; Strickland, Devin; Glotzer, Michael

2017-01-01

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

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

PubMed Central

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

2014-01-01

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

Transmission of vaccinia virus, possibly through sexual contact, to a woman at high risk for adverse complications.

PubMed

Said, Maria A; Haile, Charles; Palabindala, Venkataraman; Barker, Naomi; Myers, Robert; Thompson, Ruth; Wilson, Lucy; Allan-Martinez, Frances; Montgomery, Jay; Monroe, Benjamin; Tack, Danielle; Reynolds, Mary; Damon, Inger; Blythe, David

2013-12-01

Severe adverse events, including eczema vaccinatum (EV), can result after smallpox vaccination. Persons at risk for EV include those with underlying dermatologic conditions, such as atopic dermatitis. We investigated a case of vaccinia infection, possibly acquired during sexual contact with a recently vaccinated military service member, in a female Maryland resident with atopic dermatitis. The U.S. Department of Defense's Vaccine Healthcare Centers Network (VHCN) and the Centers for Disease Control and Prevention (CDC) worked in conjunction with the patient's physician and the Maryland Department of Health and Mental Hygiene (DHMH) to confirm the diagnosis, ensure treatment, and prevent further transmission. Specimens collected from the patient were tested at the DHMH laboratories and were positive by real-time polymerase chain reaction for nonvariola orthopoxvirus. Testing at the CDC verified the presence of vaccinia-specific DNA signatures. Continuing spread of the patient's lesions led to the administration of vaccinia immune globulin and strict infection control measures to prevent tertiary transmission to vulnerable family members, also with atopic dermatitis. VHCN contacted the service member to reinforce vaccination site care and hygiene. This case underscores the importance of prevaccination education for those receiving the smallpox vaccine to protect contacts at risk for developing severe adverse reactions. Reprint & Copyright © 2013 Association of Military Surgeons of the U.S.

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

PubMed

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

1998-03-31

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

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

PubMed

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

2010-02-28

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

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

PubMed Central

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

2001-01-01

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

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.

Copper oxide nanowires as better performance electrode material for supercapacitor application

NASA Astrophysics Data System (ADS)

Yar, A.; Dennis, J. O.; Mohamed, N. M.; Mian, M. U.; Irshad, M. I.; Mumtaz, A.

2016-11-01

Supercapacitors are highly attractive energy storage devices which are capable of delivering high power, with fast charging and long cycle life. Carbon based material rely on physical charging with less capacitance while metal oxide store charge by fast redox reaction with increased capacitance. Among metal oxide, copper oxide compounds are widely use in the form of nano and micro structures with no definite control over structure. In this work we utilized the well-controlled structure copper wires, originated from AAO template. Such well controlled structure offer better capacitance values due to easily excess of ions to the surface of wires. Performance of material was check in 3 M of potassium hydroxide (KOH). Specific capacitance (Cs) was calculated by using cyclic voltammetry (CV) and Charge discharge (CDC) test. The capacitance calculate on base on CV at 25 mV/s was 101.37 F/g while CDC showed the capacitance of 90 F/g at 2 A/g.

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

Code of Federal Regulations, 2014 CFR

2014-01-01

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

13 CFR 120.810 - Applications for certification as a CDC.

Code of Federal Regulations, 2011 CFR

2011-01-01

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

13 CFR 120.810 - Applications for certification as a CDC.

Code of Federal Regulations, 2012 CFR

2012-01-01

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

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

Code of Federal Regulations, 2010 CFR

2010-01-01

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

13 CFR 120.810 - Applications for certification as a CDC.

Code of Federal Regulations, 2014 CFR

2014-01-01

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

13 CFR 120.810 - Applications for certification as a CDC.

Code of Federal Regulations, 2013 CFR

2013-01-01

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

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

Code of Federal Regulations, 2011 CFR

2011-01-01

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

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

Code of Federal Regulations, 2013 CFR

2013-01-01

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

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

Code of Federal Regulations, 2012 CFR

2012-01-01

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

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

PubMed

Safran, Marc A

2009-11-01

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

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

PubMed

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

2016-06-01

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

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

PubMed

Thomas, A; Giesler, T; White, E

2000-11-02

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-07-26

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

13 CFR 120.823 - CDC Board of Directors.

Code of Federal Regulations, 2013 CFR

2013-01-01

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

13 CFR 120.851 - CDC ethical requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

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

13 CFR 120.823 - CDC Board of Directors.

Code of Federal Regulations, 2012 CFR

2012-01-01

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

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

Code of Federal Regulations, 2013 CFR

2013-01-01

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

13 CFR 120.851 - CDC ethical requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

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

13 CFR 120.851 - CDC ethical requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

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

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

Code of Federal Regulations, 2011 CFR

2011-01-01

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

13 CFR 120.823 - CDC Board of Directors.

Code of Federal Regulations, 2014 CFR

2014-01-01

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

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

Code of Federal Regulations, 2011 CFR

2011-01-01

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

13 CFR 120.821 - CDC Area of Operations.

Code of Federal Regulations, 2014 CFR

2014-01-01

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

13 CFR 120.823 - CDC Board of Directors.

Code of Federal Regulations, 2010 CFR

2010-01-01

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

13 CFR 120.821 - CDC Area of Operations.

Code of Federal Regulations, 2011 CFR

2011-01-01

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

13 CFR 120.823 - CDC Board of Directors.

Code of Federal Regulations, 2011 CFR

2011-01-01

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

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

Code of Federal Regulations, 2010 CFR

2010-01-01

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

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

Code of Federal Regulations, 2014 CFR

2014-01-01

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

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

Code of Federal Regulations, 2013 CFR

2013-01-01

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

13 CFR 120.821 - CDC Area of Operations.

Code of Federal Regulations, 2013 CFR

2013-01-01

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

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

Code of Federal Regulations, 2012 CFR

2012-01-01

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

13 CFR 120.821 - CDC Area of Operations.

Code of Federal Regulations, 2010 CFR

2010-01-01

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

13 CFR 120.821 - CDC Area of Operations.

Code of Federal Regulations, 2012 CFR

2012-01-01

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

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

Code of Federal Regulations, 2014 CFR

2014-01-01

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

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-05

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

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

PubMed

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

2017-01-22

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

Cdc13 N-Terminal Dimerization DNA Binding and Telomere Length Regulation

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

M Mitchell; J Smith; M Mason

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

Underage Drinking

MedlinePlus

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2017-03-01

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

Binding and inhibition of Cdc25 phosphatases by vitamin K analogues.

PubMed

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

2003-09-09

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

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

PubMed

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

2013-07-25

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

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

PubMed

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

2016-01-01

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

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

PubMed

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

2009-06-01

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

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

Code of Federal Regulations, 2012 CFR

2012-01-01

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

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

Code of Federal Regulations, 2012 CFR

2012-07-01

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

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

Code of Federal Regulations, 2012 CFR

2012-01-01

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

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

Code of Federal Regulations, 2014 CFR

2014-07-01

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

42 CFR 73.7 - Registration and related security risk assessments.

Code of Federal Regulations, 2010 CFR

2010-10-01

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

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-11

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

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

Code of Federal Regulations, 2010 CFR

2010-01-01

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

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

Code of Federal Regulations, 2014 CFR

2014-01-01

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

13 CFR 120.830 - Reports a CDC must submit.

Code of Federal Regulations, 2014 CFR

2014-01-01

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

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

Code of Federal Regulations, 2011 CFR

2011-01-01

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

42 CFR 73.7 - Registration and related security risk assessments.

Code of Federal Regulations, 2011 CFR

2011-10-01

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

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

Code of Federal Regulations, 2010 CFR

2010-01-01

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

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

Code of Federal Regulations, 2014 CFR

2014-01-01

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

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

Code of Federal Regulations, 2013 CFR

2013-01-01

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

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

Code of Federal Regulations, 2013 CFR

2013-01-01

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

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

Code of Federal Regulations, 2010 CFR

2010-01-01

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

13 CFR 120.830 - Reports a CDC must submit.

Code of Federal Regulations, 2013 CFR

2013-01-01

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

13 CFR 120.830 - Reports a CDC must submit.

Code of Federal Regulations, 2011 CFR

2011-01-01

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

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

Code of Federal Regulations, 2012 CFR

2012-01-01

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

13 CFR 120.830 - Reports a CDC must submit.

Code of Federal Regulations, 2012 CFR

2012-01-01

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

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

Code of Federal Regulations, 2013 CFR

2013-07-01

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

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

Code of Federal Regulations, 2011 CFR

2011-01-01

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

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

Code of Federal Regulations, 2013 CFR

2013-01-01

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

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

Code of Federal Regulations, 2014 CFR

2014-01-01

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

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

Code of Federal Regulations, 2011 CFR

2011-01-01

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

42 CFR 73.7 - Registration and related security risk assessments.

Code of Federal Regulations, 2012 CFR

2012-10-01

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

Norovirus

MedlinePlus

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

Tribology of carbide derived carbon films synthesized on tungsten carbide

NASA Astrophysics Data System (ADS)

Tlustochowicz, Marcin

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

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

PubMed

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

2010-01-01

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

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

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

Sun, Jia; Yang, Yuting; Wan, Ke

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

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

PubMed

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

2011-10-07

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

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

PubMed

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

2012-08-01

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

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

PubMed

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

2016-03-12

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

Using Repellent Products to Protect against Mosquito-Borne Illnesses

MedlinePlus

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

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

MedlinePlus

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

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

PubMed

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

2017-05-01

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

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

PubMed Central

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

2010-01-01

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

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

PubMed Central

Stern, Bodo; Nurse, Paul

1998-01-01

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

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

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

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

2015-01-16

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

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

PubMed

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

2014-07-08

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

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

PubMed

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

2018-06-01

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

Rho GTPase protein Cdc42 is critical for postnatal cartilage development

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

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

2016-02-19

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

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

PubMed Central

Caligiuri, M; Connolly, T; Beach, D

1997-01-01

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

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

PubMed

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

1998-07-01

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

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

PubMed Central

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

1998-01-01

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

Cdc13 prevents telomere uncapping and Rad50-dependent homologous recombination

PubMed Central

Grandin, Nathalie; Damon, Christelle; Charbonneau, Michel

2001-01-01

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

Role of cdc25 Phosphatases in Human Breast Cancer

DTIC Science & Technology

2008-05-01

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

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

PubMed Central

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

2007-01-01

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

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

PubMed

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

2017-04-01

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

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

PubMed

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

2014-12-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed Central

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

1997-01-01

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

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

PubMed

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

2018-03-01

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

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

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

Li, Yuefeng; Zhu, Xiaolan; Xu, Wenlin

2013-02-15

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

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

PubMed Central

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

2014-01-01

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

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

PubMed Central

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

2002-01-01

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

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

PubMed

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

2012-02-01

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

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

PubMed Central

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

2012-01-01

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

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

PubMed

Garmaroodi, Hamid S; Taga, Masatoki

2015-10-01

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

Comparative analysis of expression of two p97 homologues in Caenorhabditis elegans

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

Yamauchi, Seiji; Yamanaka, Kunitoshi; Ogura, Teru

2006-06-30

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

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

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

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

McKnight, A.L.

1979-08-01

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

Cell cycle regulation in Schizosaccharomyces pombe.

PubMed

Moser, B A; Russell, P

2000-12-01

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

CDC20 maintains tumor initiating cells

PubMed Central

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

2015-01-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2017-07-14

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

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

PubMed

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

2012-08-01

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

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

PubMed

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

1999-04-08

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

13 CFR 120.851 - CDC ethical requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

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

13 CFR 120.851 - CDC ethical requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

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

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

Code of Federal Regulations, 2014 CFR

2014-07-01

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

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

Code of Federal Regulations, 2011 CFR

2011-07-01

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

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

Code of Federal Regulations, 2010 CFR

2010-07-01

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

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

Code of Federal Regulations, 2013 CFR

2013-07-01

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

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

Code of Federal Regulations, 2012 CFR

2012-07-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-11-22

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

Cdc48 regulates a deubiquitylase cascade critical for mitochondrial fusion

PubMed Central

den Brave, Fabian

2018-01-01

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

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

PubMed

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

2017-06-01

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

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

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2012-01-18

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

13 CFR 120.926 - Referral fee.

Code of Federal Regulations, 2014 CFR

2014-01-01

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

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13 CFR 120.926 - Referral fee.

Code of Federal Regulations, 2013 CFR

2013-01-01

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

13 CFR 120.926 - Referral fee.

Code of Federal Regulations, 2011 CFR

2011-01-01

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

13 CFR 120.926 - Referral fee.

Code of Federal Regulations, 2012 CFR

2012-01-01

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

13 CFR 120.926 - Referral fee.

Code of Federal Regulations, 2010 CFR

2010-01-01

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

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.

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

PubMed Central

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

2010-01-01

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

Cdc7 kinase - a new target for drug development.

PubMed

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

2010-01-01

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

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

PubMed Central

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

2013-01-01

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

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.

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

PubMed Central

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

2007-01-01

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

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

PubMed

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

2009-10-15

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

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

PubMed

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

2018-04-17

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

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

PubMed

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

2016-10-01

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

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2015-01-01

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

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

PubMed

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

2012-02-25

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

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

PubMed

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

2017-07-01

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

Carbide derived carbon from MAX-phases and their separation applications

NASA Astrophysics Data System (ADS)

Hoffman, Elizabeth N.

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

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

PubMed

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

2008-03-01

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

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

PubMed Central

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

2009-01-01

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

76 FR 5377 - Agency Forms Undergoing Paperwork Reduction Act Review

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13 CFR 120.950 - SBA and CDC must appoint agents.

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

PubMed

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

2014-10-23

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

Bordetella Pertussis is an Uncommon Pathogen in Children Hospitalized with Bronchiolitis During the Winter Season

PubMed Central

Piedra, Pedro A.; Mansbach, Jonathan M.; Jewell, Alan M.; Thakar, Sneha D.; Grant, Cameron C.; Sullivan, Ashley F.; Espinola, Janice A.; Camargo, Carlos A.

2015-01-01

Background In the United States (U.S.), Bordetella pertussis incidence has increased. Cough and apnea are common findings in pertussis and also in bronchiolitis, the most common cause of hospitalization in U.S. infants. The objective was to determine the prevalence of B. pertussis infection in children hospitalized with bronchiolitis and to describe its clinical course. Methods Children hospitalized with bronchiolitis and age <2 years were eligible for a prospective, multicenter cohort study during three consecutive winter seasons (November to March) from 2007 to 2010. 16 sites in 12 states participated using a standardized enrollment protocol. Families were asked the 2010 Centers for Disease Control and Prevention (CDC) pertussis classification questions. Nasopharyngeal aspirates were obtained and tested by real time polymerase chain reaction for 16 viruses, Mycoplama pneumoniae and B. pertussis. Results 2068 (94%) of 2,207 children had one or more respiratory pathogens. B. pertussis was identified in 4 children (0.2%; 95% CI, 0.1–0.5%) with 3 having a viral co-infection. All 4 were younger than four months; 2 met the CDC definition of probable pertussis, and 3 had received at least one dose of an acellular pertussis vaccine. During the hospitalization, 2 had paroxysmal cough, 1 required ICU care, and the median length of stay was 13 days. Conclusion Our data support that B. pertussis is an uncommon pathogen in U.S. children hospitalized with bronchiolitis in the winter. Making a diagnosis of pertussis can be challenging because the disease can be atypical, and may not meet the CDC definition of probable infection. PMID:25970109

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

PubMed Central

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

2013-01-01

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

Engineering and public health at CDC.

PubMed

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

2006-12-22

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

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

PubMed Central

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

2011-01-01

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

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

PubMed

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

2014-05-01

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

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

PubMed Central

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

2004-01-01

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

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

USDA-ARS?s Scientific Manuscript database

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

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2011-10-06

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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…

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.

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

PubMed Central

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

2017-01-01

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

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

PubMed

Rock, Jeremy M; Amon, Angelika

2011-09-15

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

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

PubMed Central

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

1991-01-01

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

Polo kinase Cdc5 is a central regulator of meiosis I

PubMed Central

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

2013-01-01

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

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

PubMed

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

2016-01-01

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

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

PubMed Central

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

2016-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2016-04-01

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

Mumps Photos

MedlinePlus

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Family History

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Underage Drinking

MedlinePlus

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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.

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

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

Berg, D.E.

1981-02-01

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

Photos of Shingles

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Unintentional Drowning

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Chickenpox (Varicella) Complications

MedlinePlus

... Search The CDC Cancel Submit Search The CDC Chickenpox (Varicella) Note: Javascript is disabled or is not ... message, please visit this page: About CDC.gov . Chickenpox Home About Chickenpox Signs & Symptoms Complications Transmission Prevention & ...

Malaria Surveillance - United States, 2014.

PubMed

Mace, Kimberly E; Arguin, Paul M

2017-05-26

Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles mosquito. The majority of malaria infections in the United States occur among persons who have traveled to regions with ongoing malaria transmission. However, malaria is occasionally acquired by persons who have not traveled out of the country through exposure to infected blood products, congenital transmission, laboratory exposure, or local mosquitoborne transmission. Malaria surveillance in the United States is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers. This report summarizes cases in persons with onset of illness in 2014 and trends during previous years. Malaria cases diagnosed by blood film, polymerase chain reaction, or rapid diagnostic tests are reported to local and state health departments by health care providers or laboratory staff. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System, National Notifiable Diseases Surveillance System, or direct CDC consultations. CDC conducts antimalarial drug resistance marker testing on blood samples submitted by health care providers or local or state health departments. Data from these reporting systems serve as the basis for this report. CDC received reports of 1,724 confirmed malaria cases, including one congenital case and two cryptic cases, with onset of symptoms in 2014 among persons in the United States. The number of confirmed cases in 2014 is consistent with the number of confirmed cases reported in 2013 (n = 1,741; this number has been updated from a previous publication to account for delayed reporting for persons with symptom onset occurring in late 2013). Plasmodium falciparum, P. vivax, P. ovale, and P. malariae were identified in 66.1%, 13.3%, 5.2%, and 2.7% of cases, respectively. Less than 1.0% of patients were infected with two species. The infecting species was unreported or undetermined in 11.7% of cases. CDC provided diagnostic assistance for 14.2% of confirmed cases and tested 12.0% of P. falciparum specimens for antimalarial resistance markers. Of patients who reported purpose of travel, 57.5% were visiting friends and relatives (VFR). Among U.S. residents for whom information on chemoprophylaxis use and travel region was known, 7.8% reported that they initiated and adhered to a chemoprophylaxis drug regimen recommended by CDC for the regions to which they had traveled. Thirty-two cases were among pregnant women, none of whom had adhered to chemoprophylaxis. Among all reported cases, 17.0% were classified as severe illness, and five persons with malaria died. CDC received 137 P. falciparum-positive samples for the detection of antimalarial resistance markers (although some loci for chloroquine and mefloquine were untestable for up to nine samples). Of the 137 samples tested, 131 (95.6%) had genetic polymorphisms associated with pyrimethamine drug resistance, 96 (70.0%) with sulfadoxine resistance, 77 (57.5%) with chloroquine resistance, three (2.3%) with mefloquine drug resistance, one (<1.0%) with atovaquone resistance, and two (1.4%) with artemisinin resistance. The overall trend of malaria cases has been increasing since 1973; the number of cases reported in 2014 is the fourth highest annual total since then. Despite progress in reducing global prevalence of malaria, the disease remains endemic in many regions and use of appropriate prevention measures by travelers is still inadequate. Completion of data elements on the malaria case report form increased slightly in 2014 compared with 2013, but still remains unacceptably low. In 2014, at least one essential element (i.e., species, travel history, or resident status) was missing in 21.3% of case report forms. Incomplete reporting compromises efforts to examine trends in malaria cases and prevent infections. VFR travelers continue to be a difficult population to reach with effective malaria prevention strategies. Evidence-based prevention strategies that effectively target VFR travelers need to be developed and implemented to have a substantial impact on the number of imported malaria cases in the United States. Fewer U.S. resident patients reported taking chemoprophylaxis in 2014 (27.2%) compared with 2013 (28.6%), and adherence was poor among those who did take chemoprophylaxis. Proper use of malaria chemoprophylaxis will prevent the majority of malaria illnesses and reduce risk for severe disease (https://www.cdc.gov/malaria/travelers/drugs.html). Malaria infections can be fatal if not diagnosed and treated promptly with antimalarial medications appropriate for the patient's age and medical history, likely country of malaria acquisition, and previous use of antimalarial chemoprophylaxis. Recent molecular laboratory advances have enabled CDC to identify and conduct molecular surveillance of antimalarial drug resistance markers (https://www.cdc.gov/malaria/features/ars.html) and improve the ability of CDC to track, guide treatment, and manage drug resistance in malaria parasites both domestically and globally. For this effort to be successful, specimens should be submitted for all cases diagnosed in the United States. Clinicians should consult CDC Guidelines for Treatment of Malaria in the United States and contact the CDC Malaria Hotline for case management advice, when needed. Malaria treatment recommendations can be obtained online at https://www.cdc.gov/malaria/diagnosis_treatment/ or by calling the Malaria Hotline at 770-488-7788 or toll-free at 855-856-4713.

Malaria Surveillance — United States, 2014

PubMed Central

Arguin, Paul M.

2017-01-01

Problem/Condition Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles mosquito. The majority of malaria infections in the United States occur among persons who have traveled to regions with ongoing malaria transmission. However, malaria is occasionally acquired by persons who have not traveled out of the country through exposure to infected blood products, congenital transmission, laboratory exposure, or local mosquitoborne transmission. Malaria surveillance in the United States is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers. Period Covered This report summarizes cases in persons with onset of illness in 2014 and trends during previous years. Description of System Malaria cases diagnosed by blood film, polymerase chain reaction, or rapid diagnostic tests are reported to local and state health departments by health care providers or laboratory staff. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System, National Notifiable Diseases Surveillance System, or direct CDC consultations. CDC conducts antimalarial drug resistance marker testing on blood samples submitted by health care providers or local or state health departments. Data from these reporting systems serve as the basis for this report. Results CDC received reports of 1,724 confirmed malaria cases, including one congenital case and two cryptic cases, with onset of symptoms in 2014 among persons in the United States. The number of confirmed cases in 2014 is consistent with the number of confirmed cases reported in 2013 (n = 1,741; this number has been updated from a previous publication to account for delayed reporting for persons with symptom onset occurring in late 2013). Plasmodium falciparum, P. vivax, P. ovale, and P. malariae were identified in 66.1%, 13.3%, 5.2%, and 2.7% of cases, respectively. Less than 1.0% of patients were infected with two species. The infecting species was unreported or undetermined in 11.7% of cases. CDC provided diagnostic assistance for 14.2% of confirmed cases and tested 12.0% of P. falciparum specimens for antimalarial resistance markers. Of patients who reported purpose of travel, 57.5% were visiting friends and relatives (VFR). Among U.S. residents for whom information on chemoprophylaxis use and travel region was known, 7.8% reported that they initiated and adhered to a chemoprophylaxis drug regimen recommended by CDC for the regions to which they had traveled. Thirty-two cases were among pregnant women, none of whom had adhered to chemoprophylaxis. Among all reported cases, 17.0% were classified as severe illness, and five persons with malaria died. CDC received 137 P. falciparum-positive samples for the detection of antimalarial resistance markers (although some loci for chloroquine and mefloquine were untestable for up to nine samples). Of the 137 samples tested, 131 (95.6%) had genetic polymorphisms associated with pyrimethamine drug resistance, 96 (70.0%) with sulfadoxine resistance, 77 (57.5%) with chloroquine resistance, three (2.3%) with mefloquine drug resistance, one (<1.0%) with atovaquone resistance, and two (1.4%) with artemisinin resistance. Interpretation The overall trend of malaria cases has been increasing since 1973; the number of cases reported in 2014 is the fourth highest annual total since then. Despite progress in reducing global prevalence of malaria, the disease remains endemic in many regions and use of appropriate prevention measures by travelers is still inadequate. Public Health Action Completion of data elements on the malaria case report form increased slightly in 2014 compared with 2013, but still remains unacceptably low. In 2014, at least one essential element (i.e., species, travel history, or resident status) was missing in 21.3% of case report forms. Incomplete reporting compromises efforts to examine trends in malaria cases and prevent infections. VFR travelers continue to be a difficult population to reach with effective malaria prevention strategies. Evidence-based prevention strategies that effectively target VFR travelers need to be developed and implemented to have a substantial impact on the number of imported malaria cases in the United States. Fewer U.S. resident patients reported taking chemoprophylaxis in 2014 (27.2%) compared with 2013 (28.6%), and adherence was poor among those who did take chemoprophylaxis. Proper use of malaria chemoprophylaxis will prevent the majority of malaria illnesses and reduce risk for severe disease (https://www.cdc.gov/malaria/travelers/drugs.html). Malaria infections can be fatal if not diagnosed and treated promptly with antimalarial medications appropriate for the patient’s age and medical history, likely country of malaria acquisition, and previous use of antimalarial chemoprophylaxis. Recent molecular laboratory advances have enabled CDC to identify and conduct molecular surveillance of antimalarial drug resistance markers (https://www.cdc.gov/malaria/features/ars.html) and improve the ability of CDC to track, guide treatment, and manage drug resistance in malaria parasites both domestically and globally. For this effort to be successful, specimens should be submitted for all cases diagnosed in the United States. Clinicians should consult CDC Guidelines for Treatment of Malaria in the United States and contact the CDC Malaria Hotline for case management advice, when needed. Malaria treatment recommendations can be obtained online at https://www.cdc.gov/malaria/diagnosis_treatment/ or by calling the Malaria Hotline at 770-488-7788 or toll-free at 855-856-4713. PMID:28542123

Smallpox vaccination and adverse reactions. Guidance for clinicians.

PubMed

Cono, Joanne; Casey, Christine G; Bell, David M

2003-02-21

The guidance in this report is for evaluation and treatment of patients with complications from smallpox vaccination in the preoutbreak setting. Information is also included related to reporting adverse events and seeking specialized consultation and therapies for these events. The frequencies of smallpox vaccine-associated adverse events were identified in studies of the 1960s. Because of the unknown prevalence of risk factors among today's population, precise predictions of adverse reaction rates after smallpox vaccination are unavailable. The majority of adverse events are minor, but the less-frequent serious adverse reactions require immediate evaluation for diagnosis and treatment. Agents for treatment of certain vaccine-associated severe adverse reactions are vaccinia immune globulin (VIG), the first-line therapy, and cidofovir, the second-line therapy. These agents will be available under Investigational New Drug (IND) protocols from CDC and the U.S. Department of Defense (DoD). Smallpox vaccination in the preoutbreak setting is contraindicated for persons who have the following conditions or have a close contact with the following conditions: 1) a history of atopic dermatitis (commonly referred to as eczema), irrespective of disease severity or activity; 2) active acute, chronic, or exfoliative skin conditions that disrupt the epidermis; 3) pregnant women or women who desire to become pregnant in the 28 days after vaccination; and 4) persons who are immunocompromised as a result of human immunodeficiency virus or acquired immunodeficiency syndrome, autoimmune conditions, cancer, radiation treatment, immunosuppressive medications, or other immunodeficiencies. Additional contraindications that apply only to vaccination candidates but do not include their close contacts are persons with smallpox vaccine-component allergies, women who are breastfeeding, those taking topical ocular steroid medications, those with moderate-to-severe intercurrent illness, and persons aged < 18 years. In addition, history of Darier disease is a contraindication in a potential vaccinee and a contraindication if a household contact has active disease. In the event of a smallpox outbreak, outbreak-specific guidance will be disseminated by CDC regarding populations to be vaccinated and specific contraindications to vaccination. Vaccinia can be transmitted from a vaccinee's unhealed vaccination site to other persons by close contact and can lead to the same adverse events as in the vaccinee. To avoid transmission of vaccinia virus (found in the smallpox vaccine) from vaccinees to their close contacts, vaccinees should wash their hands with warm soapy water or hand rubs containing > or = 60% alcohol immediately after they touch their vaccination site or change their vaccination site bandages. Used bandages should be placed in sealed plastic bags and can be disposed of in household trash. Smallpox vaccine adverse reactions are diagnosed on the basis of clinical examination and history, and certain reactions can be managed by observation and supportive care. Adverse reactions that are usually self-limited include fever, headache, fatigue, myalgia, chills, local skin reactions, nonspecific rashes, erythema multiforme, lymphadenopathy, and pain at the vaccination site. Other reactions are most often diagnosed through a complete history and physical and might require additional therapies (e.g., VIG, a first-line therapy and cidofovir, a second-line therapy). Adverse reactions that might require further evaluation or therapy include inadvertent inoculation, generalized vaccinia (GV), eczema vaccinatum (EV), progressive vaccinia (PV), postvaccinial central nervous system disease, and fetal vaccinia. Inadvertent inoculation occurs when vaccinia virus is transferred from a vaccination site to a second location on the vaccinee or to a close contact. Usually, this condition is self-limited and no additional care is needed. Inoculations of the eye and eyelid require evaluation by an ophthalmologist and might require therapy with topical antiviral or antibacterial medications, VIG, or topical steroids. GV is characterized by a disseminated maculopapular or vesicular rash, frequently on an erythematous base, which usually occurs 6-9 days after first-time vaccination. This condition is usually self-limited and benign, although treatment with VIG might be required when the patient is systemically ill or found to have an underlying immunocompromising condition. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. EV occurs among persons with a history of atopic dermatitis (eczema), irrespective of disease severity or activity, and is a localized or generalized papular, vesicular, or pustular rash, which can occur anywhere on the body, with a predilection for areas of previous atopic dermatitis lesions. Patients with EV are often systemically ill and usually require VIG. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. PV is a rare, severe, and often fatal complication among persons with immunodeficiencies, characterized by painless progressive necrosis at the vaccination site with or without metastases to distant sites (e.g., skin, bones, and other viscera). This disease carries a high mortality rate, and management of PV should include aggressive therapy with VIG, intensive monitoring, and tertiary-level supportive care. Anecdotal experience suggests that, despite treatment with VIG, persons with cell-mediated immune deficits have a poorer prognosis than those with humoral deficits. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. Central nervous system disease, which includes postvaccinial encephalopathy (PVE) and postvaccinial encephalomyelitis (or encephalitis) (PVEM), occur after smallpox vaccination. PVE is most common among infants aged < 12 months. Clinical symptoms of central nervous system disease indicate cerebral or cerebellar dysfunction with headache, fever, vomiting, altered mental status, lethargy, seizures, and coma. PVE and PVEM are not believed to be a result of replicating vaccinia virus and are diagnoses of exclusion. Although no specific therapy exists for PVE or PVEM, supportive care, anticonvulsants, and intensive care might be required. Fetal vaccinia, resulting from vaccinial transmission from mother to fetus, is a rare, but serious, complication of smallpox vaccination during pregnancy or shortly before conception. It is manifested by skin lesions and organ involvement, and often results in fetal or neonatal death. No known reliable intrauterine diagnostic test is available to confirm fetal infection. Given the rarity of congenital vaccinia among live-born infants, vaccination during pregnancy should not ordinarily be a reason to consider termination of pregnancy. No known indication exists for routine, prophylactic use of VIG in an unintentionally vaccinated pregnant woman; however, VIG should not be withheld if a pregnant woman develops a condition where VIG is needed. Other less-common adverse events after smallpox vaccination have been reported to occur in temporal association with smallpox vaccination, but causality has not been established. Prophylactic treatment with VIG is not recommended for persons or close contacts with contraindications to smallpox vaccination who are inadvertently inoculated or exposed. These persons should be followed closely for early recognition of adverse reactions that might develop, and clinicians are encouraged to enroll these persons in the CDC registry by calling the Clinician Information Line at 877-554-4625. To request clinical consultation and IND therapies for vaccinia-related adverse reactions for civilians, contact your state health department or CDC's Clinician Information Line (877-554-4625). Clinical evaluation tools are available at http.//www.bt.cdc.gov/agent/smallpox/vaccination/clineval. Clinical specimen-collection guidance is available at http://www.bt.cdc.gov/agent/smallpox/vaccination/vaccinia-specimen-collection.asp. Physicians at military medical facilities can request VIG or cidofovir by calling the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) at 301-619-2257 or 888-USA-RIID.

PAX8 (+)/p63 (-) immunostaining pattern in renal collecting duct carcinoma (CDC): a useful immunoprofile in the differential diagnosis of CDC versus urothelial carcinoma of upper urinary tract.

PubMed

Albadine, Roula; Schultz, Luciana; Illei, Peter; Ertoy, Dilek; Hicks, Jessica; Sharma, Rajni; Epstein, Jonathan I; Netto, George J

2010-07-01

Collecting duct carcinoma (CDC) is a relatively rare but aggressive type of renal malignancy with variable morphologic features. One of the World Health Organization diagnostic criteria for CDC is the exclusion of urothelial carcinoma of renal pelvis from the differential diagnosis. PAX8 is a novel lineage restricted transcription factor expressed in renal tubules. We investigated the expression pattern of PAX8 in CDC and its utility, in combination with p63, in resolving the differential diagnosis of CDC versus upper tract urothelial carcinoma (UUC). Archival tissues from 21 CDC and 34 UUC were retrieved from our institutional files. Immunohistochemistry for PAX8 and p63 were performed on routine and tissue microarray sections using standard immunohistochemistry protocol. Intensity of nuclear staining was evaluated for each marker and assigned an incremental 0, 1+, 2+, and 3+ score. Extent of staining was categorized as focal (<25%), nonfocal (25% to 75%), or diffuse (>75%). CDC: All 21 (100%) CDC were positive for PAX8. Intensity of expression was moderate to strong (2+/3+) in 19 cases (90%). Extent of staining was diffuse in 13 of 21 tumors. The p63 was positive in 3 of 21 (14%) CDC cases (PAX8+/p63+). UUC: The 34 UUC included 5 pT1, 4 pT2, and 25 pT3/pT4 tumors. Thirty-one of 34 (91.2%) UUC were negative for PAX8, whereas 33 of 34 (97%) were p63 positive. Staining intensity was moderate in 15 cases (44%), of which 12 were nonfocal or diffuse. The unique p63-negative UUC was a pT1 tumor that was also negative for PAX8 (PAX8-/p63-). We propose the use of the combination of PAX8 and p63 in the diagnosis of poorly differentiated renal sinus epithelial neoplasms where the differential diagnosis includes CDC versus UUC. The immunoprofile of PAX8+/p63- supports the diagnosis of CDC with a sensitivity of 85.7% and a specificity of 100%. In contrast, a (PAX8-/p63+) profile supports the diagnosis of UUC with a sensitivity of 88.2% and a specificity of 100%. The inverse PAX8/p63 expression seen in CDC and UUC supports a renal tubular rather than an urothelial differentiation in CDC given the nephric lineage restriction of PAX8.

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

Code of Federal Regulations, 2011 CFR

2011-01-01

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

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

Code of Federal Regulations, 2010 CFR

2010-01-01

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

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

Code of Federal Regulations, 2014 CFR

2014-01-01

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

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

Code of Federal Regulations, 2012 CFR

2012-01-01

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

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

Code of Federal Regulations, 2013 CFR

2013-01-01

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

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

Code of Federal Regulations, 2010 CFR

2010-01-01

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

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

PubMed Central

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

2018-01-01

Background The Office of Advanced Molecular Detection (OAMD), Centers for Disease Control and Prevention (CDC), manages a Twitter profile (@CDC_AMD). To our knowledge, no prior study has analyzed a CDC Twitter handle’s entire contents and all followers. Objective This study aimed to describe the contents and followers of the Twitter profile @CDC_AMD and to assess if attaching photos or videos to tweets posted by @CDC_AMD would increase retweet frequency. Methods Data of @CDC_AMD were retrieved on November 21, 2016. All followers (N=809) were manually categorized. All tweets (N=768) were manually coded for contents and whether photos or videos were attached. Retweet count for each tweet was recorded. Negative binomial regression models were applied to both the original and the retweet corpora. Results Among the 809 followers, 26.0% (210/809) were individual health professionals, 11.6% (94/809) nongovernmental organizations, 3.3% (27/809) government agencies’ accounts, 3.3% (27/809) accounts of media organizations and journalists, and 0.9% (7/809) academic journals, with 54.9% (444/809) categorized as miscellaneous. A total of 46.9% (360/768) of @CDC_AMD’s tweets referred to the Office’s website and their current research; 17.6% (135/768) referred to their scientists’ publications. Moreover, 80% (69/86) of tweets retweeted by @CDC_AMD fell into the miscellaneous category. In addition, 43.4% (333/768) of the tweets contained photos or videos, whereas the remaining 56.6% (435/768) did not. Attaching photos or videos to original @CDC_AMD tweets increases the number of retweets by 37% (probability ratio=1.37, 95% CI 1.13-1.67, P=.002). Content topics did not explain or modify this association. Conclusions This study confirms CDC health communicators’ experience that original tweets created by @CDC_AMD Twitter profile sharing images or videos (or their links) received more retweets. The current policy of attaching images to tweets should be encouraged. PMID:29610112

Articular cartilage-derived cells hold a strong osteogenic differentiation potential in comparison to mesenchymal stem cells in vitro

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

Salamon, Achim, E-mail: achim.salamon@med.uni-rostock.de; Jonitz-Heincke, Anika, E-mail: anika.jonitz@med.uni-rostock.de; Adam, Stefanie, E-mail: stefanie.adam@med.uni-rostock.de

Cartilaginous matrix-degenerative diseases like osteoarthritis (OA) are characterized by gradual cartilage erosion, and also by increased presence of cells with mesenchymal stem cell (MSC) character within the affected tissues. Moreover, primary chondrocytes long since are known to de-differentiate in vitro and to be chondrogenically re-differentiable. Since both findings appear to conflict with each other, we quantitatively assessed the mesenchymal differentiation potential of OA patient cartilage-derived cells (CDC) towards the osteogenic and adipogenic lineage in vitro and compared it to that of MSC isolated from adipose tissue (adMSC) of healthy donors. We analyzed expression of MSC markers CD29, CD44, CD105, andmore » CD166, and, following osteogenic and adipogenic induction in vitro, quantified their expression of osteogenic and adipogenic differentiation markers. Furthermore, CDC phenotype and proliferation were monitored. We found that CDC exhibit an MSC CD marker expression pattern similar to adMSC and a similar increase in proliferation rate during osteogenic differentiation. In contrast, the marked reduction of proliferation observed during adipogenic differentiation of adMSC was absent in CDC. Quantification of differentiation markers revealed a strong osteogenic differentiation potential for CDC, however almost no capacity for adipogenic differentiation. Since in the pathogenesis of OA, cartilage degeneration coincides with high bone turnover rates, the high osteogenic differentiation potential of OA patient-derived CDC may affect clinical therapeutic regimens aiming at autologous cartilage regeneration in these patients. - Highlights: • We analyze the mesenchymal differentiation capacity of cartilage-derived cells (CDC). • CDC express mesenchymal stem cell (MSC) markers CD29, CD44, CD105, and CD166. • CDC and MSC proliferation is reduced in adipogenesis and increased in osteogenesis. • Adipogenic differentiation is virtually absent in CDC, but strong in MSC. • Osteogenic differentiation is significantly stronger for CDC than for MSC.« less

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

NASA Astrophysics Data System (ADS)

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

2018-01-01

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

WISEWOMAN: Frequently Asked Questions

MedlinePlus

... FAQs CDC-RFA-DP18-1816: WISEWOMAN Related CDC Web Sites Division for Heart Disease and Stroke Prevention ... and tribal organizations. Top of Page Related CDC Web Sites Division for Heart Disease and Stroke Prevention ...

Preparing for Assisted Reproductive Technology

MedlinePlus

... CDC Cancel Submit Search The CDC Assisted Reproductive Technology (ART) Note: Javascript is disabled or is not ... visit this page: About CDC.gov . Assisted Reproductive Technology (ART) What Is ART Patient Resources Preparing for ...

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.

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

PubMed Central

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

2016-01-01

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

Mechanism of APC/CCDC20 activation by mitotic phosphorylation.

PubMed

Qiao, Renping; Weissmann, Florian; Yamaguchi, Masaya; Brown, Nicholas G; VanderLinden, Ryan; Imre, Richard; Jarvis, Marc A; Brunner, Michael R; Davidson, Iain F; Litos, Gabriele; Haselbach, David; Mechtler, Karl; Stark, Holger; Schulman, Brenda A; Peters, Jan-Michael

2016-05-10

Chromosome segregation and mitotic exit are initiated by the 1.2-MDa ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome) and its coactivator CDC20 (cell division cycle 20). To avoid chromosome missegregation, APC/C(CDC20) activation is tightly controlled. CDC20 only associates with APC/C in mitosis when APC/C has become phosphorylated and is further inhibited by a mitotic checkpoint complex until all chromosomes are bioriented on the spindle. APC/C contains 14 different types of subunits, most of which are phosphorylated in mitosis on multiple sites. However, it is unknown which of these phospho-sites enable APC/C(CDC20) activation and by which mechanism. Here we have identified 68 evolutionarily conserved mitotic phospho-sites on human APC/C bound to CDC20 and have used the biGBac technique to generate 47 APC/C mutants in which either all 68 sites or subsets of them were replaced by nonphosphorylatable or phospho-mimicking residues. The characterization of these complexes in substrate ubiquitination and degradation assays indicates that phosphorylation of an N-terminal loop region in APC1 is sufficient for binding and activation of APC/C by CDC20. Deletion of the N-terminal APC1 loop enables APC/C(CDC20) activation in the absence of mitotic phosphorylation or phospho-mimicking mutations. These results indicate that binding of CDC20 to APC/C is normally prevented by an autoinhibitory loop in APC1 and that its mitotic phosphorylation relieves this inhibition. The predicted location of the N-terminal APC1 loop implies that this loop controls interactions between the N-terminal domain of CDC20 and APC1 and APC8. These results reveal how APC/C phosphorylation enables CDC20 to bind and activate the APC/C in mitosis.

Sternal wound infection after cardiac surgery: incidence and risk factors according to clinical presentation.

PubMed

Lemaignen, A; Birgand, G; Ghodhbane, W; Alkhoder, S; Lolom, I; Belorgey, S; Lescure, F-X; Armand-Lefevre, L; Raffoul, R; Dilly, M-P; Nataf, P; Lucet, J C

2015-07-01

The incidence of surgical site infection (SSI) after cardiac surgery depends on the definition used. A distinction is generally made between mediastinitis, as defined by the US Centers for Disease Control and Prevention (CDC), and superficial SSI. Our objective was to decipher these entities in terms of presentation and risk factors. We performed a 7-year single centre analysis of prospective surveillance of patients with cardiac surgery via median sternotomy. SSI was defined as the need for reoperation due to infection. Among 7170 patients, 292 (4.1%) developed SSI, including 145 CDC-defined mediastinitis (CDC-positive SSI, 2.0%) and 147 superficial SSI without associated bloodstream infection (CDC-negative SSI, 2.1%). Median time to reoperation for CDC-negative SSI was 18 days (interquartile range, 14-26) and 16 (interquartile range, 11-24) for CDC-positive SSI (p 0.02). Microorganisms associated with CDC-negative SSI were mainly skin commensals (62/147, 41%) or originated in the digestive tract (62/147, 42%); only six were due to Staphylococcus aureus (4%), while CDC-positive SSI were mostly due to S. aureus (52/145, 36%) and germs from the digestive tract (52/145, 36%). Risk factors for SSI were older age, obesity, chronic obstructive bronchopneumonia, diabetes mellitus, critical preoperative state, postoperative vasopressive support, transfusion or prolonged ventilation and coronary artery bypass grafting, especially if using both internal thoracic arteries in female patients. The number of internal thoracic arteries used and factors affecting wound healing were primarily associated with CDC-negative SSI, whereas comorbidities and perioperative complications were mainly associated with CDC-positive SSI. These 2 entities differed in time to revision surgery, bacteriology and risk factors, suggesting a differing pathophysiology. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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

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

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

1994-09-01

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

Influenza (flu) vaccine (Inactivated or Recombinant): What you need to know

MedlinePlus

... taken in its entirety from the CDC Inactivated Influenza Vaccine Information Statement (VIS) www.cdc.gov/vaccines/hcp/vis/vis-statements/flu.html CDC review information for Inactivated Influenza VIS: ...

Measuring Physical Activity Intensity

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Herpes Can Happen to Anyone: Share Facts, Not Fears

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... promiscuous. Links Oral Herpes Sexually Transmitted Diseases Genital Herpes (CDC) Genital Herpes Fact Sheet (CDC) What You Need to Know About Genital Herpes Video (CDC) References Vaccination to Reduce Reactivation of ...

Polio vaccine - what you need to know

MedlinePlus

... is taken in its entirety from the CDC Polio Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... statements/ipv.html CDC review information for the Polio VIS: Page last reviewed: July 20, 2016 Page ...

78 FR 949 - Office for State, Tribal, Local and Territorial Support (OSTLTS)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-07

... understanding and comprehension. CDC believes that consultation is integral to a deliberative process that...: a listening session with the director of CDC, roundtable discussions with CDC senior leadership and...

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

PubMed

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

2012-12-01

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

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

PubMed

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

2018-04-18

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

The Cytokinin Requirement for Cell Division in Cultured Nicotiana plumbaginifolia Cells Can Be Satisfied by Yeast Cdc25 Protein Tyrosine Phosphatase. Implications for Mechanisms of Cytokinin Response and Plant Development

PubMed Central

Zhang, Kerong; Diederich, Ludger; John, Peter C.L.

2005-01-01

Cultured cells of Nicotiana plumbaginifolia, when deprived of exogenous cytokinin, arrest in G2 phase prior to mitosis and then contain cyclin-dependent protein kinase (CDK) that is inactive because phosphorylated on tyrosine (Tyr). The action of cytokinin in stimulating the activation of CDK by removal of inhibitory phosphorylation from Tyr is not a secondary downstream consequence of other hormone actions but is the key primary effect of the hormone in its stimulation of cell proliferation, since cytokinin could be replaced by expression of cdc25, which encodes the main Cdc2 (CDK)-Tyr dephosphorylating enzyme of yeast (Saccharomyces cerevisiae). The cdc25 gene, under control of a steroid-inducible promoter, induced a rise in cdc25 mRNA, accumulation of p67Cdc25 protein, and increase in Cdc25 phosphatase activity that was measured in vitro with Tyr-phosphorylated Cdc2 as substrate. Cdc25 phosphatase activity peaked during mitotic prophase at the time CDK activation was most rapid. Mitosis that was induced by cytokinin also involved increase in endogenous plant CDK Tyr phosphatase activity during prophase, therefore indicating that this is a normal part of plant mitosis. These results suggest a biochemical mechanism for several previously described transgene phenotypes in whole plants and suggest that a primary signal from cytokinin leading to progression through mitosis is the activation of CDK by dephosphorylation of Tyr. PMID:15618425

The cytokinin requirement for cell division in cultured Nicotiana plumbaginifolia cells can be satisfied by yeast Cdc25 protein tyrosine phosphatase: implications for mechanisms of cytokinin response and plant development.

PubMed

Zhang, Kerong; Diederich, Ludger; John, Peter C L

2005-01-01

Cultured cells of Nicotiana plumbaginifolia, when deprived of exogenous cytokinin, arrest in G2 phase prior to mitosis and then contain cyclin-dependent protein kinase (CDK) that is inactive because phosphorylated on tyrosine (Tyr). The action of cytokinin in stimulating the activation of CDK by removal of inhibitory phosphorylation from Tyr is not a secondary downstream consequence of other hormone actions but is the key primary effect of the hormone in its stimulation of cell proliferation, since cytokinin could be replaced by expression of cdc25, which encodes the main Cdc2 (CDK)-Tyr dephosphorylating enzyme of yeast (Saccharomyces cerevisiae). The cdc25 gene, under control of a steroid-inducible promoter, induced a rise in cdc25 mRNA, accumulation of p67(Cdc25) protein, and increase in Cdc25 phosphatase activity that was measured in vitro with Tyr-phosphorylated Cdc2 as substrate. Cdc25 phosphatase activity peaked during mitotic prophase at the time CDK activation was most rapid. Mitosis that was induced by cytokinin also involved increase in endogenous plant CDK Tyr phosphatase activity during prophase, therefore indicating that this is a normal part of plant mitosis. These results suggest a biochemical mechanism for several previously described transgene phenotypes in whole plants and suggest that a primary signal from cytokinin leading to progression through mitosis is the activation of CDK by dephosphorylation of Tyr.

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

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

PubMed

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

2017-07-15

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

Human Cdc14A regulates Wee1 stability by counteracting CDK-mediated phosphorylation

PubMed Central

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

2012-01-01

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

Clostridium difficile colitis in patients after kidney and pancreas–kidney transplantation

PubMed Central

Keven, K.; Basu, A.; Re, L.; Tan, H.; Marcos, A.; Fung, J.J.; Starzl, T.E.; Simmons, R.L.; Shapiro, R.

2010-01-01

Limited data exist about Clostridium difficile colitis (CDC) in solid organ transplant patients. Between 1/1/99 and 12/31/02, 600 kidney and 102 pancreas–kidney allograft recipients were transplanted. Thirty-nine (5.5%) of these patients had CDC on the basis of clinical and laboratory findings. Of these 39 patients, 35 have information available for review. CDC developed at a median of 30 days after transplantation, and the patients undergoing pancreas–kidney transplantation had a slightly higher incidence of CDC than recipients of kidney alone (7.8% vs. 4.5%, P> 0.05). All but one patient presented with diarrhea. Twenty-four patients (64.9%) were diagnosed in the hospital, and CDC occurred during first hospitalization in 14 patients (40%). Treatment was with oral metronidazole (M) in 33 patients (94%)and M + oral vancomycin (M + V) in 2 patients. Eight patients had recurrent CDC, which occurred at a median of 30 days (range 15–314) after the first episode. Two patients (5.7%) developed fulminant CDC, presented with toxic megacolon, and underwent colectomy. One of them died; the other patient survived after colectomy. CDC should be considered as a diagnosis in transplant patients with history of diarrhea after antibiotic use, and should be treated aggressively before the infection becomes complicated. PMID:15225221

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

PubMed

Yang, Yurong; Zheng, Jing; Chen, Jiaxin

2012-12-01

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

LIN-23, an E3 Ubiquitin Ligase Component, Is Required for the Repression of CDC-25.2 Activity during Intestinal Development in Caenorhabditis elegans.

PubMed

Son, Miseol; Kawasaki, Ichiro; Oh, Bong-Kyeong; Shim, Yhong-Hee

2016-11-30

Caenorhabditis elegans ( C. elegans ) utilizes two different cell-cycle modes, binucleations during the L1 larval stage and endoreduplications at four larval moltings, for its postembryonic intestinal development. Previous genetic studies indicated that CDC-25.2 is specifically required for binucleations at the L1 larval stage and is repressed before endoreduplications. Furthermore, LIN-23, the C. elegans β-TrCP ortholog, appears to function as a repressor of CDC-25.2 to prevent excess intestinal divisions. We previously reported that intestinal hyperplasia in lin-23(e1883) mutants was effectively suppressed by the RNAi depletion of cdc-25.2 . Nevertheless, LIN-23 targeting CDC-25.2 for ubiquitination as a component of E3 ubiquitin ligase has not yet been tested. In this study, LIN-23 is shown to be the major E3 ubiquitin ligase component, recognizing CDC-25.2 to repress their activities for proper transition of cell-cycle modes during the C. elegans postembryonic intestinal development. In addition, for the first time that LIN-23 physically interacts with both CDC-25.1 and CDC-25.2 and facilitates ubiquitination for timely regulation of their activities during the intestinal development.

Pneumococcal polysaccharide vaccine - what you need to know

MedlinePlus

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

HPV (Human Papillomavirus) vaccine - what you need to know

MedlinePlus

... taken in its entirety from the CDC HPV (Human Papillomavirus) Vaccine Information Statement (VIS): www.cdc.gov/ ... statements/hpv.html . CDC review information for HPV (Human Papillomavirus) VIS: Page last reviewed: December 2, 2016 ...

Varicella (chickenpox) vaccine - what you need to know

MedlinePlus

... is taken in its entirety from the CDC Chickenpox Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... statements/varicella.html CDC review information for the Chickenpox VIS: Page last reviewed: February 12, 2018 Page ...

78 FR 75923 - Office for State, Tribal, Local and Territorial Support (OSTLTS)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-13

... among parties that leads to mutual understanding and comprehension. CDC believes that consultation is..., tribes and CDC leaders will engage in a listening session with CDC's director and roundtable discussions...

Simultaneous detection and serotyping of dengue infection using single tube multiplex CDC Dengue Real-Time RT-PCR from India.

PubMed

Sharma, Shashi; Tandel, Kundan; Danwe, Surabhi; Bhatt, Puneet; Dash, P K; Ranjan, Praveer; Rathi, K R; Gupta, Rajiv Mohan; Parida, M M

2018-03-01

Four antigenically different dengue virus serotypes (DENV-1, DENV-2, DENV-3 and DENV-4) are known to cause infections in humans. Some of these are known to cause more severe disease than the others. Chances for developing Dengue hemorrhagic fever-dengue shock syndrome (DHF-DSS) increases significantly with history of previous infection with one of the four serotypes. Therefore, early diagnosis, serotyping and providing early warning of dengue fever epidemics to concerned authorities becomes very important for better patient outcome and to curb the rapid spread in the community. During the 2014 outbreak, a total of 100 samples from suspected cases of dengue were collected. NS1 antigen based rapid test was used for serological diagnosis. Dengue complex one step reverse transcription-polymerase chain reaction was performed to look for presence of viral RNA. Single tube multiplex RT-PCR was also performed to look for infecting serotype. CDC Dengue Multiplex Real Time PCR assay was performed for rapid diagnosis and simultaneous serotyping of the dengue virus. Out of the 100 samples screened, 69 were found to be positive by NS1Ag Rapid test. 34 samples were found positive by dengue consensus RT-PCR assay. 22 samples were found to be positive by single tube Dengue multiplex RT-PCR assay. Serotype DEN-2 was present in maximum numbers followed by DEN-3. 44 samples were found positive by DENV CDC Multiplex Real time PCR assay. DEN-2 was found in maximum numbers followed by DEN-1. Dengue remains to be an important health problem in India and across the globe. Few serotypes of dengue are more dangerous than the others. Rapid diagnosis and serotyping remains the key for better patient management and prevention of disease spreading in the community. Highly sensitive, specific and rapid CDC real time RT-PCR assay was found to be most promising tool among all available molecular diagnostic methods. This will serve a rapid and reliable simultaneous dengue virus detection as well serotyping assay in near future for rapid identification of dengue suspected sample screening.

A human monoclonal autoantibody to a nucleolar structure.

PubMed Central

Gonzalez, M F; Wichmann, I; Yelamos, J; Melero, J; Magariño, R; Sanchez-Roman, J; Nuñez-Roldan, A; Sanchez, B

1992-01-01

Peripheral blood lymphocytes from a scleroderma patient (CDC) were isolated, transformed with Epstein-Barr virus and fused to the heteromyeloma SHM-D33. Supernatants from cultures were screened for autoantibody production against nucleoprotamine by ELISA. Positive wells were cloned by limiting dilution. After cloning, supernatants from two wells were positive for the nucleoprotamine assay. One named CDC-1 has been studied in our laboratory. CDC-1 recognized a nucleolar antigen by indirect immunofluorescence. By using an ELISA with purified recombinant antigens, CDC-1 reacted against Ro/SS-A, U1 (RNP) and Sm. By immunoblotting using a lysate of MOLT-4 cell line, CDC-1 was able to react against a structure of 60 kD. When the antigen recognized by CDC-1 was purified, SDS-PAGE under reducing conditions with purified antigen and subsequent silver staining of the gel allowed us to detect three bands at 60, 55 and 39 kD, respectively. A screening by ELISA with previously characterized antisera against our purified antigen demonstrated reactivity of the CDC-1 antigen with those antisera able to recognize Ro/SS-A. Images Fig. 1 Fig. 2 Fig. 3 PMID:1572098

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

PubMed Central

Cox, Dianne; Hodgson, Louis

2014-01-01

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

Cdc42 and formin activity control non-muscle myosin dynamics during Drosophila heart morphogenesis

PubMed Central

Vogler, Georg; Liu, Jiandong; Iafe, Timothy W.; Migh, Ede; Mihály, József

2014-01-01

During heart formation, a network of transcription factors and signaling pathways guide cardiac cell fate and differentiation, but the genetic mechanisms orchestrating heart assembly and lumen formation remain unclear. Here, we show that the small GTPase Cdc42 is essential for Drosophila melanogaster heart morphogenesis and lumen formation. Cdc42 genetically interacts with the cardiogenic transcription factor tinman; with dDAAM which belongs to the family of actin organizing formins; and with zipper, which encodes nonmuscle myosin II. Zipper is required for heart lumen formation, and its spatiotemporal activity at the prospective luminal surface is controlled by Cdc42. Heart-specific expression of activated Cdc42, or the regulatory formins dDAAM and Diaphanous caused mislocalization of Zipper and induced ectopic heart lumina, as characterized by luminal markers such as the extracellular matrix protein Slit. Placement of Slit at the lumen surface depends on Cdc42 and formin function. Thus, Cdc42 and formins play pivotal roles in heart lumen formation through the spatiotemporal regulation of the actomyosin network. PMID:25267295

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

PubMed

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

2014-01-01

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

Rodent Control: Seal Up! Trap Up! Clean Up!

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Infection Control: The Use and Handling of Toothbrushes

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Pneumococcal conjugate vaccine (PCV13) - What you need to know

MedlinePlus

... the CDC Information Statement (VIS): www.cdc.gov/vaccines/hcp/vis/vis-statements/pcv13.html CDC review ... at the highest risk. Before there was a vaccine, the United States saw: more than 700 cases ...

Hepatitis B vaccine - what you need to know

MedlinePlus

... is taken in its entirety from the CDC Hepatitis B Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... statements/hep-b.html CDC review information for Hepatitis B VIS: Page last reviewed: July 20, 2016 Page ...

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

PubMed Central

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

2008-01-01

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

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

PubMed

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

2017-03-04

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

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

PubMed Central

2017-01-01

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

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

PubMed

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

2017-07-01

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

Evaluation of Commercially Available Chikungunya Virus Immunoglobulin M Detection Assays

PubMed Central

Johnson, Barbara W.; Goodman, Christin H.; Holloway, Kimberly; de Salazar, P. Martinez; Valadere, Anne M.; Drebot, Michael A.

2016-01-01

Commercial chikungunya virus (CHIKV)–specific IgM detection kits were evaluated at the Centers for Disease Control and Prevention (CDC), the Public Health Agency of Canada National Microbiology Laboratory, and the Caribbean Public Health Agency (CARPHA). The Euroimmun Anti-CHIKV IgM ELISA kit had ≥ 95% concordance with all three reference laboratory results. The limit of detection for low CHIK IgM+ samples, as measured by serial dilution of seven sera up to 1:12,800 ranged from 1:800 to 1:3,200. The Euroimmun IIFT kit evaluated at CDC and CARPHA performed well, but required more retesting of equivocal results. The InBios CHIKjj Detect MAC-ELISA had 100% and 98% concordance with CDC and CARPHA results, respectively, and had equal sensitivity to the CDC MAC-ELISA to 1:12,800 dilution in serially diluted samples. The Abcam Anti-CHIKV IgM ELISA had high performance at CARPHA, but at CDC, performance was inconsistent between lots. After replacement of the biotinylated IgM antibody controls with serum containing CHIKV-specific IgM and additional quality assurance/control measures, the Abcam kit was rereleased and reevaluated at CDC. The reformatted Abcam kit had 97% concordance with CDC results and limit of detection of 1:800 to 1:3,200. Two rapid tests and three other CHIKV MAC-ELISAs evaluated at CDC had low sensitivity, as the CDC CHIKV IgM in-house positive controls were below the level of detection. In conclusion, laboratories have options for CHIKV serological diagnosis using validated commercial kits. PMID:26976887

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

PubMed

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

2013-01-01

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

Antigen Presenting Properties of a Myeloid Dendritic-Like Cell in Murine Spleen.

PubMed

Hey, Ying-Ying; O'Neill, Helen C

This paper distinguishes a rare subset of myeloid dendritic-like cells found in mouse spleen from conventional (c) dendritic cells (DC) in terms of phenotype, function and gene expression. These cells are tentatively named "L-DC" since they resemble dendritic-like cells produced in longterm cultures of spleen. L-DC can be distinguished on the basis of their unique phenotype as CD11bhiCD11cloMHCII-CD43+Ly6C-Ly6G-Siglec-F- cells. They demonstrate similar ability as cDC to uptake and retain complex antigens like mannan via mannose receptors, but much lower ability to endocytose and retain soluble antigen. While L-DC differ from cDC by their inability to activate CD4+ T cells, they are capable of antigen cross-presentation for activation of CD8+ T cells, although less effectively so than the cDC subsets. In terms of gene expression, CD8- cDC and CD8+ cDC are quite distinct from L-DC. CD8+ cDC are distinguishable from the other two subsets by expression of CD24a, Clec9a, Xcr1 and Tlr11, while CD8- cDC are distinguished by expression of Ccnd1 and H-2Eb2. L-DC are distinct from the two cDC subsets through upregulated expression of Clec4a3, Emr4, Itgam, Csf1r and CD300ld. The L-DC gene profile is quite distinct from that of cDC, confirming a myeloid cell type with distinct antigen presenting properties.

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

PubMed

Boekhout, Michiel; Wolthuis, Rob

2015-04-15

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

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

PubMed

Salsi, Valentina; Fantini, Sebastian; Zappavigna, Vincenzo

2016-09-01

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

Cdc1 removes the ethanolamine phosphate of the first mannose of GPI anchors and thereby facilitates the integration of GPI proteins into the yeast cell wall

PubMed Central

Vazquez, Hector M.; Vionnet, Christine; Roubaty, Carole; Conzelmann, Andreas

2014-01-01

Temperature-sensitive cdc1ts mutants are reported to stop the cell cycle upon a shift to 30°C in early G2, that is, as small budded cells having completed DNA replication but unable to duplicate the spindle pole body. A recent report showed that PGAP5, a human homologue of CDC1, acts as a phosphodiesterase removing an ethanolamine phosphate (EtN-P) from mannose 2 of the glycosylphosphatidylinositol (GPI) anchor, thus permitting efficient endoplasmic reticulum (ER)-to-Golgi transport of GPI proteins. We find that the essential CDC1 gene can be deleted in mcd4∆ cells, which do not attach EtN-P to mannose 1 of the GPI anchor, suggesting that Cdc1 removes the EtN-P added by Mcd4. Cdc1-314ts mutants do not accumulate GPI proteins in the ER but have a partial secretion block later in the secretory pathway. Growth tests and the genetic interaction profile of cdc1-314ts pinpoint a distinct cell wall defect. Osmotic support restores GPI protein secretion and actin polarization but not growth. Cell walls of cdc1-314ts mutants contain large amounts of GPI proteins that are easily released by β-glucanases and not attached to cell wall β1,6-glucans and that retain their original GPI anchor lipid. This suggests that the presumed transglycosidases Dfg5 and Dcw1 of cdc1-314ts transfer GPI proteins to cell wall β1,6-glucans inefficiently. PMID:25165136

Origin of giant dielectric permittivity and weak ferromagnetic behavior in (1-x)LaFeO3-xBaTiO3 (0.0 ≤ x ≤ 0.25) solid solutions

NASA Astrophysics Data System (ADS)

Sreenivasu, T.; Tirupathi, P.; Prabahar, K.; Suryanarayana, B.; Chandra Mouli, K.

The solid solutions of (1-x) LaFeO3-xBaTiO3 (0.0≤x≤0.25) have been synthesized successfully by the conventional solid-state reaction method. Room temperature (RT) X-ray diffraction studies reveal the stabilization of orthorhombic phase with Pbnm space group. Complete solubility in the perovskite series was demonstrated up to x=0.25. The dielectric permittivity shows colossal dielectric constant (CDC) at RT. The doping of BaTiO3 in LaFeO3 exhibit pronounced CDC up to a composition x=0.15, further it starts to decrease. The frequency-dependent dielectric loss exhibits polaronic conduction, which can attribute to presence of multiple valence of iron. The relaxation frequency and polaronic conduction mechanism was shifted towards RT as function of x. Moreover, large magnetic moment with weak ferromagnetic behavior is observed in doped LaFeO3 solid solution, which might be the destruction of spin cycloid structure due to insertion of Ti in Fe-O-Fe network of LaFeO3.

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

PubMed

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

2018-04-02

The Office of Advanced Molecular Detection (OAMD), Centers for Disease Control and Prevention (CDC), manages a Twitter profile (@CDC_AMD). To our knowledge, no prior study has analyzed a CDC Twitter handle's entire contents and all followers. This study aimed to describe the contents and followers of the Twitter profile @CDC_AMD and to assess if attaching photos or videos to tweets posted by @CDC_AMD would increase retweet frequency. Data of @CDC_AMD were retrieved on November 21, 2016. All followers (N=809) were manually categorized. All tweets (N=768) were manually coded for contents and whether photos or videos were attached. Retweet count for each tweet was recorded. Negative binomial regression models were applied to both the original and the retweet corpora. Among the 809 followers, 26.0% (210/809) were individual health professionals, 11.6% (94/809) nongovernmental organizations, 3.3% (27/809) government agencies' accounts, 3.3% (27/809) accounts of media organizations and journalists, and 0.9% (7/809) academic journals, with 54.9% (444/809) categorized as miscellaneous. A total of 46.9% (360/768) of @CDC_AMD's tweets referred to the Office's website and their current research; 17.6% (135/768) referred to their scientists' publications. Moreover, 80% (69/86) of tweets retweeted by @CDC_AMD fell into the miscellaneous category. In addition, 43.4% (333/768) of the tweets contained photos or videos, whereas the remaining 56.6% (435/768) did not. Attaching photos or videos to original @CDC_AMD tweets increases the number of retweets by 37% (probability ratio=1.37, 95% CI 1.13-1.67, P=.002). Content topics did not explain or modify this association. This study confirms CDC health communicators' experience that original tweets created by @CDC_AMD Twitter profile sharing images or videos (or their links) received more retweets. The current policy of attaching images to tweets should be encouraged. ©Isaac Chun-Hai Fung, Ashley M Jackson, Lindsay A Mullican, Elizabeth B Blankenship, Mary Elizabeth Goff, Amy J Guinn, Nitin Saroha, Zion Tsz Ho Tse. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 02.04.2018.

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.

UPEML: a machine-portable CDC Update emulator

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

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

1984-12-01

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

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

PubMed

Martini, Leila; Presley, David; Klieger, Sarah; Burris, Scott

2016-11-01

The Centers for Disease Control and Prevention (CDC) conducts research on legal epidemiology, the scientific study of law as a factor in the cause, distribution, and prevention of disease. This study describes a scan of articles written by CDC staff members to characterize the frequency and key features of legal epidemiology articles and their distribution across CDC departments and divisions. CDC librarians searched an internal repository for journal articles by CDC staff published from January 1, 2011, to May 31, 2015. Researchers reviewed and coded the abstracts to produce data on key features of the articles. Researchers identified 158 CDC-authored legal epidemiology articles published in 83 journals, most frequently in Preventing Chronic Disease (14 publications), Journal of Public Health Management Practice (10 publications), and Morbidity and Mortality Weekly Report (9 publications). Most articles concerned the use and impact of law as a deliberate tool of intervention. Thirteen articles addressed the legal infrastructure of public health, and 3 assessed the incidental or unintended effects of nonhealth laws. CDC-authored articles encompassed policy making, implementation, and impact. Literature reviews and studies mapping laws across multiple jurisdictions constituted one-quarter of all publications. Studies addressed laws at the international, national, state, local, and organizational levels. Results of the scan can be used to identify opportunities for the agency to better support research, professional development, networking, publication, and tracking of publication in this emerging field.

Molecular Mapping of Flowering Time Major Genes and QTLs in Chickpea (Cicer arietinum L.)

PubMed Central

Mallikarjuna, Bingi P.; Samineni, Srinivasan; Thudi, Mahendar; Sajja, Sobhan B.; Khan, Aamir W.; Patil, Ayyanagowda; Viswanatha, Kannalli P.; Varshney, Rajeev K.; Gaur, Pooran M.

2017-01-01

Flowering time is an important trait for adaptation and productivity of chickpea in the arid and the semi-arid environments. This study was conducted for molecular mapping of genes/quantitative trait loci (QTLs) controlling flowering time in chickpea using F2 populations derived from four crosses (ICCV 96029 × CDC Frontier, ICC 5810 × CDC Frontier, BGD 132 × CDC Frontier and ICC 16641 × CDC Frontier). Genetic studies revealed monogenic control of flowering time in the crosses ICCV 96029 × CDC Frontier, BGD 132 × CDC Frontier and ICC 16641 × CDC Frontier, while digenic control with complementary gene action in ICC 5810 × CDC Frontier. The intraspecific genetic maps developed from these crosses consisted 75, 75, 68 and 67 markers spanning 248.8 cM, 331.4 cM, 311.1 cM and 385.1 cM, respectively. A consensus map spanning 363.8 cM with 109 loci was constructed by integrating four genetic maps. Major QTLs corresponding to flowering time genes efl-1 from ICCV 96029, efl-3 from BGD 132 and efl-4 from ICC 16641 were mapped on CaLG04, CaLG08 and CaLG06, respectively. The QTLs and linked markers identified in this study can be used in marker-assisted breeding for developing early maturing chickpea. PMID:28729871

Cross-species and tissue variations in cyanide detoxification rates in rodents and non-human primates on protein-restricted diet.

PubMed

Kimani, S; Moterroso, V; Morales, P; Wagner, J; Kipruto, S; Bukachi, F; Maitai, C; Tshala-Katumbay, D

2014-04-01

We sought to elucidate the impact of diet, cyanide or cyanate exposure on mammalian cyanide detoxification capabilities (CDC). Male rats (~8 weeks old) (N=52) on 75% sulfur amino acid (SAA)-deficient diet were treated with NaCN (2.5mg/kg bw) or NaOCN (50mg/kg bw) for 6 weeks. Macaca fascicularis monkeys (~12 years old) (N=12) were exclusively fed cassava for 5 weeks. CDC was assessed in plasma, or spinal cord, or brain. In rats, NaCN induced seizures under SAA-restricted diet whereas NaOCN induced motor deficits. No deficits were observed in non-human primates. Under normal diet, the CDC were up to ~80× faster in the nervous system (14 ms to produce one μmol of thiocyanate from the detoxification of cyanide) relative to plasma. Spinal cord CDC was impaired by NaCN, NaOCN, or SAA deficiency. In M. fascicularis, plasma CDC changed proportionally to total proteins (r=0.43; p<0.001). The plasma CDC was ~2× relative to that of rodents. The nervous system susceptibility to cyanide may result from a "multiple hit" by the toxicity of cyanide or its cyanate metabolite, the influences of dietary deficiencies, and the tissue variations in CDC. Chronic dietary reliance on cassava may cause metabolic derangement including poor CDC. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cross-species and tissue variations in cyanide detoxification rates in rodents and non-human primates on protein-restricted diet

PubMed Central

Kimani, S.; Moterroso, V.; Morales, P.; Wagner, J.; Kipruto, S.; Bukachi, F.; Maitai, C.; Tshala-Katumbay, D.

2014-01-01

We sought to elucidate the impact of diet, cyanide or cyanate exposure on mammalian cyanide detoxification capabilities (CDC). Male rats (~8 weeks old) (N=52) on 75% sulfur amino acid (SAA)-deficient diet were treated with NaCN (2.5 mg/kg bw) or NaOCN (50 mg/kg bw) for 6 weeks. Macaca fascicularis monkeys (~12 years old) (N=12) were exclusively fed cassava for 5 weeks. CDC was assessed in plasma, or spinal cord, or brain. In rats, NaCN induced seizures under SAA-restricted diet whereas NaOCN induced motor deficits. No deficits were observed in non-human primates. Under normal diet, the CDC were up to ~ 80X faster in the nervous system (14 milliseconds to produce one μmol of thiocyanate from the detoxification of cyanide) relative to plasma. Spinal cord CDC was impaired by NaCN, NaOCN, or SAA deficiency. In macaca fascicularis, plasma CDC changed proportionally to total proteins (r=0.43; p<0.001). The plasma CDC was ~ 2X relative to that of rodents. The nervous system susceptibility to cyanide may result from a “multiple hit” by the toxicity of cyanide or its cyanate metabolite, the influences of dietary deficiencies, and the tissue variations in CDC. Chronic dietary reliance on cassava may cause metabolic derangement including poor CDC. PMID:24500607

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

PubMed

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

2016-11-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

1998-02-15

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

Mechanism of Cdc42-induced Actin Polymerization in Neutrophil Extracts

PubMed Central

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

1998-01-01

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

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.

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

PubMed Central

Bernazzani, Sarina M.

2018-01-01

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

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

PubMed

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

2018-04-01

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

Malaria Surveillance - United States, 2015.

PubMed

Mace, Kimberly E; Arguin, Paul M; Tan, Kathrine R

2018-05-04

Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles species mosquito. The majority of malaria infections in the United States occur among persons who have traveled to regions with ongoing malaria transmission. However, malaria is occasionally acquired by persons who have not traveled out of the country through exposure to infected blood products, congenital transmission, laboratory exposure, or local mosquitoborne transmission. Malaria surveillance in the United States is conducted to provide information on its occurrence (e.g., temporal, geographic, and demographic), guide prevention and treatment recommendations for travelers and patients, and facilitate transmission control measures if locally acquired cases are identified. This report summarizes confirmed malaria cases in persons with onset of illness in 2015 and summarizes trends in previous years. Malaria cases diagnosed by blood film microscopy, polymerase chain reaction, or rapid diagnostic tests are reported to local and state health departments by health care providers or laboratory staff members. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS), the National Notifiable Diseases Surveillance System (NNDSS), or direct CDC consultations. CDC reference laboratories provide diagnostic assistance and conduct antimalarial drug resistance marker testing on blood samples submitted by health care providers or local or state health departments. This report summarizes data from the integration of all NMSS and NNDSS cases, CDC reference laboratory reports, and CDC clinical consultations. CDC received reports of 1,517 confirmed malaria cases, including one congenital case, with an onset of symptoms in 2015 among persons who received their diagnoses in the United States. Although the number of malaria cases diagnosed in the United States has been increasing since the mid-1970s, the number of cases decreased by 208 from 2014 to 2015. Among the regions of acquisition (Africa, West Africa, Asia, Central America, the Caribbean, South America, Oceania, and the Middle East), the only region with significantly fewer imported cases in 2015 compared with 2014 was West Africa (781 versus 969). Plasmodium falciparum, P. vivax, P. ovale, and P. malariae were identified in 67.4%, 11.7%, 4.1%, and 3.1% of cases, respectively. Less than 1% of patients were infected by two species. The infecting species was unreported or undetermined in 12.9% of cases. CDC provided diagnostic assistance for 13.1% of patients with confirmed cases and tested 15.0% of P. falciparum specimens for antimalarial resistance markers. Of the U.S. resident patients who reported purpose of travel, 68.4% were visiting friends or relatives. A lower proportion of U.S. residents with malaria reported taking any chemoprophylaxis in 2015 (26.5%) compared with 2014 (32.5%), and adherence was poor in this group. Among the U.S residents for whom information on chemoprophylaxis use and travel region were known, 95.3% of patients with malaria did not adhere to or did not take a CDC-recommended chemoprophylaxis regimen. Among women with malaria, 32 were pregnant, and none had adhered to chemoprophylaxis. A total of 23 malaria cases occurred among U.S. military personnel in 2015. Three cases of malaria were imported from the approximately 3,000 military personnel deployed to an Ebola-affected country; two of these were not P. falciparum species, and one species was unspecified. Among all reported cases in 2015, 17.1% were classified as severe illnesses and 11 persons died, compared with an average of 6.1 deaths per year during 2000-2014. In 2015, CDC received 153 P. falciparum-positive samples for surveillance of antimalarial resistance markers (although certain loci were untestable for some samples); genetic polymorphisms associated with resistance to pyrimethamine were identified in 132 (86.3%), to sulfadoxine in 112 (73.7%), to chloroquine in 48 (31.4%), to mefloquine in six (4.3%), and to artemisinin in one (<1%), and no sample had resistance to atovaquone. Completion of data elements on the malaria case report form decreased from 2014 to 2015 and remains low, with 24.2% of case report forms missing at least one key element (species, travel history, and resident status). The decrease in malaria cases from 2014 to 2015 is associated with a decrease in imported cases from West Africa. This finding might be related to altered or curtailed travel to Ebola-affected countries in in this region. Despite progress in reducing malaria worldwide, the disease remains endemic in many regions, and the use of appropriate prevention measures by travelers is still inadequate. The best way to prevent malaria is to take chemoprophylaxis medication during travel to a country where malaria is endemic. As demonstrated by the U.S. military during the Ebola response, use of chemoprophylaxis and other protection measures is possible in stressful environments, and this can prevent malaria, especially P. falciparum, even in high transmission areas. Detailed recommendations for preventing malaria are available to the general public at the CDC website (https://www.cdc.gov/malaria/travelers/drugs.html). Malaria infections can be fatal if not diagnosed and treated promptly with antimalarial medications appropriate for the patient's age and medical history, the likely country of malaria acquisition, and previous use of antimalarial chemoprophylaxis. Health care providers should consult the CDC Guidelines for Treatment of Malaria in the United States and contact the CDC's Malaria Hotline for case management advice when needed. Malaria treatment recommendations are available online (https://www.cdc.gov/malaria/diagnosis_treatment) and from the Malaria Hotline (770-488-7788 or toll-free at 855-856-4713). Persons submitting malaria case reports (care providers, laboratories, and state and local public health officials) should provide complete information because incomplete reporting compromises case investigations and efforts to prevent infections and examine trends in malaria cases. Compliance with recommended malaria prevention strategies is low among U.S. travelers visiting friends and relatives. Evidence-based prevention strategies that effectively target travelers who are visiting friends and relatives need to be developed and implemented to reduce the numbers of imported malaria cases in the United States. Molecular surveillance of antimalarial drug resistance markers (https://www.cdc.gov/malaria/features/ars.html) has enabled CDC to track, guide treatment, and manage drug resistance in malaria parasites both domestically and internationally. More samples are needed to improve the completeness of antimalarial drug resistance marker analysis; therefore, CDC requests that blood specimens be submitted for all cases diagnosed in the United States.

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

PubMed Central

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

2012-01-01

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

Aortic Curvature Instead of Angulation Allows Improved Estimation of the True Aorto-iliac Trajectory.

PubMed

Schuurmann, R C L; Kuster, L; Slump, C H; Vahl, A; van den Heuvel, D A F; Ouriel, K; de Vries, J-P P M

2016-02-01

Supra- and infrarenal aortic neck angulation have been associated with complications after endovascular aortic aneurysm repair. However, a uniform angulation measurement method is lacking and the concept of angulation suggests a triangular oversimplification of the aortic anatomy. (Semi-)automated calculation of curvature along the center luminal line describes the actual trajectory of the aorta. This study proposes a methodology for calculating aortic (neck) curvature and suggests an additional method based on available tools in current workstations: curvature by digital calipers (CDC). Proprietary custom software was developed for automatic calculation of the severity and location of the largest supra- and infrarenal curvature over the center luminal line. Twenty-four patients with severe supra- or infrarenal angulations (≥45°) and 11 patients with small to moderate angulations (<45°) were included. Both CDC and angulation were measured by two independent observers on the pre- and postoperative computed tomographic angiography scans. The relationships between actual curvature and CDC and angulation were visualized and tested with Pearson's correlation coefficient. The CDC was also fully automatically calculated with proprietary custom software. The difference between manual and automatic determination of CDC was tested with a paired Student t test. A p-value was considered significant when two-tailed α < .05. The correlation between actual curvature and manual CDC is strong (.586-.962) and even stronger for automatic CDC (.865-.961). The correlation between actual curvature and angulation is much lower (.410-.737). Flow direction angulation values overestimate CDC measurements by 60%, with larger variance. No significant difference was found in automatically calculated CDC values and manually measured CDC values. Curvature calculation of the aortic neck improves determination of the true aortic trajectory. Automatic calculation of the actual curvature is preferable, but measurement or calculation of the curvature by digital calipers is a valid alternative if actual curvature is not at hand. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Quantitative framework for ordered degradation of APC/C substrates.

PubMed

Lu, Dan; Girard, Juliet R; Li, Weihan; Mizrak, Arda; Morgan, David O

2015-11-16

During cell-cycle progression, substrates of a single master regulatory enzyme can be modified in a specific order. Here, we used experimental and computational approaches to dissect the quantitative mechanisms underlying the ordered degradation of the substrates of the ubiquitin ligase APC/C(Cdc20), a key regulator of chromosome segregation in mitosis. We show experimentally that the rate of catalysis varies with different substrates of APC/C(Cdc20). Using a computational model based on multi-step ubiquitination, we then show how changes in the interaction between a single substrate and APC/C(Cdc20) can alter the timing of degradation onset relative to APC/C(Cdc20) activation, while ensuring a fast degradation rate. Degradation timing and dynamics depend on substrate affinity for the enzyme as well as the catalytic rate at which the substrate is modified. When two substrates share the same pool of APC/C(Cdc20), their relative enzyme affinities and rates of catalysis influence the partitioning of APC/C(Cdc20) among substrates, resulting in substrate competition. Depending on how APC/C(Cdc20) is partitioned among its substrates, competition can have minor or major effects on the degradation of certain substrates. We show experimentally that increased expression of the early APC/C(Cdc20) substrate Clb5 does not delay the degradation of the later substrate securin, arguing against a role for competition with Clb5 in establishing securin degradation timing. The degradation timing of APC/C(Cdc20) substrates depends on the multi-step nature of ubiquitination, differences in substrate-APC/C(Cdc20) interactions, and competition among substrates. Our studies provide a conceptual framework for understanding how ordered modification can be established among substrates of the same regulatory enzyme, and facilitate our understanding of how precise temporal control is achieved by a small number of master regulators to ensure a successful cell division cycle.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-10-01

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

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.

Characterization of C-terminal adaptors, UFD-2 and UFD-3, of CDC-48 on the polyglutamine aggregation in C. elegans.

PubMed

Murayama, Yuki; Ogura, Teru; Yamanaka, Kunitoshi

2015-03-27

CDC-48 (also called VCP or p97 in mammals and Cdc48p in yeast) is a AAA (ATPases associated with diverse cellular activities) chaperone and participates in a wide range of cellular activities including modulation of protein complexes and protein aggregates. UFD-2 and UFD-3, C-terminal adaptors for CDC-48, reportedly bind to CDC-48 in a mutually exclusive manner and they may modulate the fate of substrates for CDC-48. However, their cellular functions have not yet been elucidated. In this study, we found that CDC-48 preferentially interacts with UFD-3 in Caenorhabditis elegans. We also found that the number of polyglutamine (polyQ) aggregates was reduced in the ufd-3 deletion mutant but not in the ufd-2 deletion mutant. Furthermore, the lifespan and motility of the ufd-3 deletion mutant, where polyQ40::GFP was expressed, were greatly decreased. Taken together, we propose that UFD-3 may promote the formation of polyQ aggregates to reduce the polyQ toxicity in C. elegans. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed

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

2017-01-01

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

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

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

Centers for Disease Control and Prevention, Office of Minority Health & Health Equity (OMHHE)

MedlinePlus

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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.

Malaria surveillance - United States, 2008.

PubMed

Mali, Sonja; Steele, Stefanie; Slutsker, Laurence; Arguin, Paul M

2010-06-25

Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles species mosquito. The majority of malaria infections in the United States occur among persons who have traveled to areas with ongoing malaria transmission. In the United States, cases can occur through exposure to infected blood products, congenital transmission, or local mosquitoborne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers. This report summarizes cases in patients with onset of illness in 2008 and summarizes trends during previous years. Malaria cases diagnosed by blood film, polymerase chain reaction, or rapid diagnostic tests are mandated to be reported to local and state health departments by health-care providers or laboratory staff members. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS), National Notifiable Diseases Surveillance System (NNDSS), and direct CDC consultations. Data from these reporting systems are the basis for this report. CDC received reports of 1,298 cases of malaria with an onset of symptoms in 2008 among patients in the United States, a decrease of 13.8% from the 1,505 cases reported for 2007 (p<0.001). These cases included one cryptic [corrected] case, one congenital case, and two fatal cases. Plasmodium falciparum, P. vivax, P. malariae, and P. ovale were identified in 40.6%, 14.6%, 1.5%, and 1.4% of cases, respectively. The first documented case of simian malaria, P. knowlesi, was reported in a U.S. traveler. Eight (0.6%) of the 1,298 patients were infected by two or more species. The infecting species was unreported or undetermined in 41.2% of cases. Based on estimated volume of travel from the World Tourism Organization, the highest estimated relative case rates of malaria among travelers occurred among those returning from countries in West Africa. A total of 508 U.S. civilians acquired malaria abroad; among the 480 civilians for whom chemoprophylaxis information was known, 344 (71.7%) reported that they had not followed a chemoprophylactic drug regimen recommended by CDC for the area to which they had traveled. Fourteen cases were reported in pregnant women, among whom none adhered to a complete prevention drug regimen. A significant decrease in the number of malaria cases occurred from 2007 to 2008. No change occurred in the proportions of cases caused by the various Plasmodium species. U.S. civilians traveling to countries in West Africa had the highest estimated relative case rates. In the majority of reported cases, U.S. civilians who acquired malaria abroad had not adhered to a chemoprophylaxis regimen that was appropriate for the country in which they acquired the infection. Persons traveling to an area in which malaria is endemic should take steps to prevent malaria, which might include taking one of the recommended chemoprophylaxis regimens appropriate for the region of travel and using personal protection measures to prevent mosquito bites. Any person who has been to a malarious area and who subsequently develops a fever or influenza-like symptoms should seek medical care immediately and report their travel history to the clinician; investigation should always include blood-film tests for malaria with results available immediately. Malaria infections can be fatal if not diagnosed and treated promptly. Malaria prevention recommendations are available from CDC online (http://wwwn.cdc.gov/travel/contentDiseases.aspx#malaria) or by calling the Malaria Hotline (telephone 770-488-7788). Malaria treatment recommendations can be obtained from CDC online (http://www.cdc.gov/malaria/diagnosis_treatment/treatment.htm) or by calling the Malaria Hotline.

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

PubMed Central

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

2014-01-01

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

Indirubin, an acting component of indigo naturalis, inhibits EGFR activation and EGF-induced CDC25B gene expression in epidermal keratinocytes.

PubMed

Hsieh, Wan-Ling; Lin, Yin-Ku; Tsai, Chi-Neu; Wang, Ta-Min; Chen, Tzu-Ya; Pang, Jong-Hwei S

2012-08-01

Topical indigo naturalis ointment is clinically proved to be an effective therapy for plaque-type psoriasis. Indirubin, as the active component of indigo naturalis, inhibits cell proliferation of epidermal keratinocytes. However, the detailed underlying mechanism is not fully understood. To further investigate the anti-proliferating effects of indigo naturalis and indirubin on epidermal keratinocytes. The decreased expression of CDC25B in indigo naturalis- or indirubin-treated epidermal keratinocytes, as revealed by cDNA microarray analysis, was studied. The CDC25B expression was examined under different serum concentrations and compared between primary and immortalized keratinocytes. The activation of EGFR and the effect of EGF on the cell proliferation and CDC25B expression were also investigated in epidermal keratinocytes. RT/real-time PCR and western blot method were used to analyze the CDC25B expression at the mRNA and protein levels, respectively. Indigo naturalis and indirubin were confirmed to down-regulate CDC25B expression significantly at both the mRNA and protein levels. The growth-dependent expression of CDC25B was demonstrated by the increased expression in serum-stimulated and immortalized keratinocytes. The activation of EGF receptor, known to be highly expressed in psoriatic lesions, was inhibited by indigo naturalis or indirubin. The cell proliferation and CDC25B expression of epidermal keratinocytes were induced by EGF alone and confirmed to be inhibited by indigo naturalis or indirubin. Except being a common therapeutic target in various cancers, CDC25B also plays an important role in the hyper-proliferation of epidermal keratinocytes which can be suppressed by anti-psoriatic drug indigo naturalis and its component, indirubin. Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. 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.

The multislice CT findings of renal carcinoma associated with XP11.2 translocation/TFE gene fusion and collecting duct carcinoma.

PubMed

Zhu, Qing-Qiang; Wang, Zhong-Qiu; Zhu, Wen-Rong; Chen, Wen-Xin; Wu, Jing-Tao

2013-04-01

Renal cell carcinoma associated with Xp11.2 translocation and TFE gene fusion (Xp11.2/TFE RCC), and collecting duct carcinoma (CDC) are uncommon subtypes of renal cell carcinomas. To investigate the multislice CT (MSCT) characteristics of these two tumor types. Nine patients with Xp11.2/TFE RCC and 10 patients with CDC were studied retrospectively. MSCT was undertaken to investigate differences in tumor characteristics and enhancement patterns. All patients had single tumors centered in the renal medulla. Two patients with each tumor type had lymph node involvement and there was a single case of hepatic metastasis (Xp11.2/TFE RCC). The mean tumor diameter of Xp11.2/TFE RCC tumors was significantly larger than for CDC tumors. Two patients with Xp11.2/TFE RCC had cystic components as did eight patients with CDC (P < 0.05). Calcifications were present in six patients, each with CDC. Clear tumor boundaries were visible in two patients with CDC and in nine with Xp11.2/TFE RCC (P < 0.05). The density of Xp11.2/TFE RCC tumors was greater than that of CDC tumors, normal renal cortex, or medulla on unenhanced CT. Enhancement was higher with Xp11.2/TFE RCC than with CDC tumors during all phases. Xp11.2/TFE RCC enhancement was higher than in the renal medulla during cortical and medullary phase but lower than in normal renal medulla during the delayed phase. CDC tumor enhancement was lower than that for normal renal medulla during all enhanced phases. Both tumor types originated from the renal medulla. Distinguishing features included density on unenhanced CT, enhancement patterns, and capsule signs. Identifying these differences may aid diagnosis.

ATP depletion during mitotic arrest induces mitotic slippage and APC/CCdh1-dependent cyclin B1 degradation.

PubMed

Park, Yun Yeon; Ahn, Ju-Hyun; Cho, Min-Guk; Lee, Jae-Ho

2018-04-27

ATP depletion inhibits cell cycle progression, especially during the G1 phase and the G2 to M transition. However, the effect of ATP depletion on mitotic progression remains unclear. We observed that the reduction of ATP after prometaphase by simultaneous treatment with 2-deoxyglucose and NaN 3 did not arrest mitotic progression. Interestingly, ATP depletion during nocodazole-induced prometaphase arrest resulted in mitotic slippage, as indicated by a reduction in mitotic cells, APC/C-dependent degradation of cyclin B1, increased cell attachment, and increased nuclear membrane reassembly. Additionally, cells successfully progressed through the cell cycle after mitotic slippage, as indicated by EdU incorporation and time-lapse imaging. Although degradation of cyclin B during normal mitotic progression is primarily regulated by APC/C Cdc20 , we observed an unexpected decrease in Cdc20 prior to degradation of cyclin B during mitotic slippage. This decrease in Cdc20 was followed by a change in the binding partner preference of APC/C from Cdc20 to Cdh1; consequently, APC/C Cdh1 , but not APC/C Cdc20 , facilitated cyclin B degradation following ATP depletion. Pulse-chase analysis revealed that ATP depletion significantly abrogated global translation, including the translation of Cdc20 and Cdh1. Additionally, the half-life of Cdh1 was much longer than that of Cdc20. These data suggest that ATP depletion during mitotic arrest induces mitotic slippage facilitated by APC/C Cdh1 -dependent cyclin B degradation, which follows a decrease in Cdc20 resulting from reduced global translation and the differences in the half-lives of the Cdc20 and Cdh1 proteins.

Monitoring Influenza Activity in the United States: A Comparison of Traditional Surveillance Systems with Google Flu Trends

PubMed Central

Ortiz, Justin R.; Zhou, Hong; Shay, David K.; Neuzil, Kathleen M.; Fowlkes, Ashley L.; Goss, Christopher H.

2011-01-01

Background Google Flu Trends was developed to estimate US influenza-like illness (ILI) rates from internet searches; however ILI does not necessarily correlate with actual influenza virus infections. Methods and Findings Influenza activity data from 2003–04 through 2007–08 were obtained from three US surveillance systems: Google Flu Trends, CDC Outpatient ILI Surveillance Network (CDC ILI Surveillance), and US Influenza Virologic Surveillance System (CDC Virus Surveillance). Pearson's correlation coefficients with 95% confidence intervals (95% CI) were calculated to compare surveillance data. An analysis was performed to investigate outlier observations and determine the extent to which they affected the correlations between surveillance data. Pearson's correlation coefficient describing Google Flu Trends and CDC Virus Surveillance over the study period was 0.72 (95% CI: 0.64, 0.79). The correlation between CDC ILI Surveillance and CDC Virus Surveillance over the same period was 0.85 (95% CI: 0.81, 0.89). Most of the outlier observations in both comparisons were from the 2003–04 influenza season. Exclusion of the outlier observations did not substantially improve the correlation between Google Flu Trends and CDC Virus Surveillance (0.82; 95% CI: 0.76, 0.87) or CDC ILI Surveillance and CDC Virus Surveillance (0.86; 95%CI: 0.82, 0.90). Conclusions This analysis demonstrates that while Google Flu Trends is highly correlated with rates of ILI, it has a lower correlation with surveillance for laboratory-confirmed influenza. Most of the outlier observations occurred during the 2003–04 influenza season that was characterized by early and intense influenza activity, which potentially altered health care seeking behavior, physician testing practices, and internet search behavior. PMID:21556151

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.

Assignment of C1q-binding HLA antibodies as unacceptable HLA antigens avoids positive CDC-crossmatches prior to transplantation of deceased donor organs.

PubMed

Juhl, David; Marget, Matthias; Hallensleben, Michael; Görg, Siegfried; Ziemann, Malte

2017-03-01

Soon, a virtual crossmatch shall replace the complement-dependent cytotoxicity (CDC) allocation crossmatch in the Eurotransplant region. To prevent positive CDC-crossmatches in the recipient centre, careful definition of unacceptable antigens is necessary. For highly sensitized patients, this is difficult by CDC alone. Assignment of all antibodies detected by sensitive assays, however, could prevent organ allocation. To assess the usefulness of the Luminex C1q-assay to prevent positive CDC-crossmatches, all CDC-crossmatches performed prior to deceased kidney transplantation in a 16-month-period were reviewed. Sera causing positive crossmatches were investigated by the C1q-assay. 31 out of 1432 crossmatches (2.2%) were positive. Sera involved in 26 positive crossmatches were available. C1q-binding donor-specific antibodies were detected in 19 sera (73.1%). The other sera were from recipients without any HLA antibodies detectable by CDC or common solid phase assays. Three patients had known Non-HLA antibodies causing positive CDC-results. Four crossmatches were only weak positive. Therefore, avoidance of donors with HLA antigens against whom C1q-binding antibodies were detected would have prevented all positive crossmatches due to HLA antibodies. Provided that all HLA specificities against which antibodies are detected by the Luminex C1q-assay are considered as unacceptable antigens, CDC-crossmatches prior to transplantation might safely be omitted in many patients. They should be maintained in highly immunized patients, however, for whom assignment of all C1q-positive antibodies as unacceptable antigens could lead to a significant delay or even prevention of transplantation. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

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

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.

78 FR 40743 - Advisory Committee on Childhood Lead Poisoning Prevention (ACCLPP)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-08

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention (CDC) Advisory... Advisory Committee Act (Pub. L. 92-463), the CDC, National Center for Environmental Health (NCEH) announces... the Director, CDC, regarding new scientific knowledge and technological developments and their...

76 FR 78263 - Advisory Committee on Childhood Lead Poisoning Prevention (ACCLPP)

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention (CDC) Advisory... Advisory Committee Act (Pub. L. 92-463), the CDC, National Center for Environmental Health (NCEH) announces... Director, CDC, regarding new scientific knowledge and technological developments and their practical...

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

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.

Properties of Cadmium-(bis)dodecylthiolate and Polymeric Composites Based on It

PubMed Central

Agareva, Nadezhda; Smirnov, Anton A.; Afanasiev, Andrey; Sologubov, Semen; Markin, Alexey; Salomatina, Evgenia; Smirnova, Larisa; Bityurin, Nikita

2015-01-01

We study the thermo-physical and photoluminescence (PL) properties of cadmium-(bis)dodecylthiolate (Cd(C12H25S)2). Significant attention is drawn to characterization of Cd(C12H25S)2 by different methods. The laser-induced PLs of Cd(C12H25S)2 and Cd(C12H25S)2/(polymethyl methacrylate) (PMMA) composites are studied. Samples of Cd(C12H25S)2/PMMA are synthesized by the polymerization method. Ultraviolet (UV)-pulsed laser irradiation of the samples under relatively small fluences leads to the formation of induced PL with the maximum near the wavelength of 600 nm. This process can be attributed to the transformation of Cd(C12H25S)2 within the precursor grains. Another PL peak at 450–500 nm, which appears under the higher fluences, relies on the formation of CdS complexes with a significant impact of the polymer matrix. PMID:28793738

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.

A hot-spot mutation in CDC42 (p.Tyr64Cys) and novel phenotypes in the third patient with Takenouchi-Kosaki syndrome.

PubMed

Motokawa, Midori; Watanabe, Satoshi; Nakatomi, Akiko; Kondoh, Tatsuro; Matsumoto, Tadashi; Morifuji, Kanako; Sawada, Hirotake; Nishimura, Toyoki; Nunoi, Hiroyuki; Yoshiura, Koh-Ichiro; Moriuchi, Hiroyuki; Dateki, Sumito

2018-03-01

Takenouchi-Kosaki syndrome (TKS) is a congenital malformation syndrome characterized by severe developmental delay, macrothrombocytopenia, camptodactyly, sensorineural hearing loss, and dysmorphic facial features. Recently, a heterozygous de novo mutation (p.Tyr64Cys) in the CDC42 gene, which encodes a key small GTP-binding protein of the Rho-subfamily, was identified in two unrelated patients with TKS. We herein report a third patient with TKS who had the same heterozygous CDC42 mutation. The phenotype of the patient was very similar to those of the two previously reported patients with TKS; however, she also demonstrated novel clinical manifestations, such as congenital hypothyroidism and immunological disturbance. Thus, despite the heterozygous mutation of CDC42 (p.Tyr64Cys) likely being a hot-spot mutation for TKS, its phenotype may be variable. Further studies and the accumulation of patients with CDC42 mutations are needed to clarify the phenotype in patients with TKS and the pathophysiological roles of the CDC42 mutation.

Structure of human Cdc45 and implications for CMG helicase function

PubMed Central

Simon, Aline C.; Sannino, Vincenzo; Costanzo, Vincenzo; Pellegrini, Luca

2016-01-01

Cell division cycle protein 45 (Cdc45) is required for DNA synthesis during genome duplication, as a component of the Cdc45-MCM-GINS (CMG) helicase. Despite its essential biological function, its biochemical role in DNA replication has remained elusive. Here we report the 2.1-Å crystal structure of human Cdc45, which confirms its evolutionary link with the bacterial RecJ nuclease and reveals several unexpected features that underpin its function in eukaryotic DNA replication. These include a long-range interaction between N- and C-terminal DHH domains, blocking access to the DNA-binding groove of its RecJ-like fold, and a helical insertion in its N-terminal DHH domain, which appears poised for replisome interactions. In combination with available electron microscopy data, we validate by mutational analysis the mechanism of Cdc45 association with the MCM ring and GINS co-activator, critical for CMG assembly. These findings provide an indispensable molecular basis to rationalize the essential role of Cdc45 in genomic duplication. PMID:27189187

Angiotensin II-Induced End-Organ Damage in Mice Is Attenuated by Human Exosomes and by an Exosomal Y RNA Fragment.

PubMed

Cambier, Linda; Giani, Jorge F; Liu, Weixin; Ijichi, Takeshi; Echavez, Antonio K; Valle, Jackelyn; Marbán, Eduardo

2018-06-04

Hypertension often leads to cardiovascular disease and kidney dysfunction. Exosomes secreted from cardiosphere-derived cells (CDC-exo) and their most abundant small RNA constituent, the Y RNA fragment EV-YF1, exert therapeutic benefits after myocardial infarction. Here, we investigated the effects of CDC-exo and EV-YF1, each administered individually, in a model of cardiac hypertrophy and kidney injury induced by chronic infusion of Ang (angiotensin) II. After 2 weeks of Ang II, multiple doses of CDC-exo or EV-YF1 were administered retro-orbitally. Ang II infusion induced an elevation in systolic blood pressure that was not affected by CDC-exo or EV-YF1. Echocardiography confirmed that Ang II infusion led to cardiac hypertrophy. CDC-exo and EV-YF1 both attenuated cardiac hypertrophy and reduced cardiac inflammation and fibrosis. In addition, both CDC-exo and EV-YF1 improved kidney function and diminished renal inflammation and fibrosis. The beneficial effects of CDC-exo and EV-YF1 were associated with changes in the expression of the anti-inflammatory cytokine IL (interleukin)-10 in plasma, heart, spleen, and kidney. In summary, infusions of CDC-exo or EV-YF1 attenuated cardiac hypertrophy and renal injury induced by Ang II infusion, without affecting blood pressure, in association with altered IL-10 expression. Exosomes and their defined noncoding RNA contents may represent potential new therapeutic approaches for hypertension-associated cardiovascular and renal damage. © 2018 American Heart Association, Inc.

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

PubMed Central

Martini, Leila; Presley, David; Klieger, Sarah

2016-01-01

Objective: The Centers for Disease Control and Prevention (CDC) conducts research on legal epidemiology, the scientific study of law as a factor in the cause, distribution, and prevention of disease. This study describes a scan of articles written by CDC staff members to characterize the frequency and key features of legal epidemiology articles and their distribution across CDC departments and divisions. Methods: CDC librarians searched an internal repository for journal articles by CDC staff published from January 1, 2011, to May 31, 2015. Researchers reviewed and coded the abstracts to produce data on key features of the articles. Results: Researchers identified 158 CDC-authored legal epidemiology articles published in 83 journals, most frequently in Preventing Chronic Disease (14 publications), Journal of Public Health Management Practice (10 publications), and Morbidity and Mortality Weekly Report (9 publications). Most articles concerned the use and impact of law as a deliberate tool of intervention. Thirteen articles addressed the legal infrastructure of public health, and 3 assessed the incidental or unintended effects of nonhealth laws. CDC-authored articles encompassed policy making, implementation, and impact. Literature reviews and studies mapping laws across multiple jurisdictions constituted one-quarter of all publications. Studies addressed laws at the international, national, state, local, and organizational levels. Conclusion: Results of the scan can be used to identify opportunities for the agency to better support research, professional development, networking, publication, and tracking of publication in this emerging field. PMID:28123227

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

PubMed

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

2014-03-01

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

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

75 FR 22416 - Statement of Organization, Functions, and Delegations of Authority

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-28

... Document Management System; (13) develops and distributes leadership reports, including the Secretary's 90... principal advisor to the Director, CDC, on internal and external affairs of CDC; (2) convenes key leadership for assessment, management, mitigation options, and resolution of issues and initiatives affecting CDC...

Cross-dehydrogenative coupling and oxidative-amination reactions of ethers and alcohols with aromatics and heteroaromatics

PubMed Central

Vuram, Prasanna K.

2017-01-01

Cross-dehydrogenative coupling (CDC) is a process in which, typically, a C–C bond is formed at the expense of two C–H bonds, either catalyzed by metals or other organic compounds, or via uncatalyzed processes. In this perspective, we present various modes of C–H bond-activation at sp3 centers adjacent to ether oxygen atoms, followed by C–C bond formation with aromatic systems as well as with heteroaromatic systems. C–N bond-formation with NH-containing heteroaromatics, leading to hemiaminal ethers, is also an event that can occur analogously to C–C bond formation, but at the expense of C–H and N–H bonds. A large variety of hemiaminal ether-forming reactions have recently appeared in the literature and this perspective also includes this complementary chemistry. In addition, the participation of C–H bonds in alcohols in such processes is also described. Facile access to a wide range of compounds can be attained through these processes, rendering such reactions useful for synthetic applications via Csp3 bond activations. PMID:28970941

77 FR 33465 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-06

... on proposed data collection projects, the Centers for Disease Control and Prevention (CDC) will... Kimberly S. Lane, 1600 Clifton Road, MS-D74, Atlanta, GA 30333 or send an email to [email protected]cdc.gov . Comments... (NCIPC), Centers for Disease Control and Prevention (CDC). [[Page 33466

Medications that Weaken Your Immune System and Fungal Infections

MedlinePlus

... Listen Watch RSS ABOUT About CDC Jobs Funding LEGAL Policies Privacy FOIA No Fear Act OIG 1600 Clifton Road Atlanta , GA 30329-4027 USA 800-CDC-INFO (800-232-4636) , TTY: 888-232-6348 Email CDC-INFO U.S. Department of Health & Human Services HHS/Open USA.gov Top

13 CFR 120.825 - Financial ability to operate.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.825 Financial ability to operate. A CDC must be able to sustain its operations continuously, with reliable sources of... funds generated from 503 and 504 loan activity by a CDC remaining after payment of staff and overhead...

13 CFR 120.841 - Qualifications for the ALP.

Code of Federal Regulations, 2014 CFR

2014-01-01

.... An applicant for ALP status must show that it substantially meets the following criteria: (a) CDC staff experience. The CDC's staff must have well-trained, qualified loan officers who are knowledgeable concerning SBA's lending policies and procedures for the 504 program. The CDC must have at least one loan...

13 CFR 120.825 - Financial ability to operate.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.825 Financial ability to operate. A CDC must be able to sustain its operations continuously, with reliable sources of... funds generated from 503 and 504 loan activity by a CDC remaining after payment of staff and overhead...

7 CFR 331.5 - Exemptions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... reported to APHIS or CDC by telephone, facsimile, or e-mail. This report must be followed by submission of APHIS/CDC Form 4 within 7 calendar days after identification. Less stringent reporting may be required during agricultural emergencies or outbreaks, or in endemic areas. A copy of APHIS/CDC Form 4 must be...

13 CFR 120.540 - Liquidation and litigation plans.

Code of Federal Regulations, 2011 CFR

2011-01-01

... liquidation through the review of liquidation plans which all Authorized CDC Liquidators and certain Lenders... plan. An Authorized CDC Liquidator and a Lender for a loan made under its authority as a CLP Lender... receive SBA's written approval of that plan. (c) Litigation plan. An Authorized CDC Liquidator and a...

7 CFR 331.5 - Exemptions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... reported to APHIS or CDC by telephone, facsimile, or e-mail. This report must be followed by submission of APHIS/CDC Form 4 within 7 calendar days after identification. Less stringent reporting may be required during agricultural emergencies or outbreaks, or in endemic areas. A copy of APHIS/CDC Form 4 must be...

13 CFR 120.841 - Qualifications for the ALP.

Code of Federal Regulations, 2012 CFR

2012-01-01

.... An applicant for ALP status must show that it substantially meets the following criteria: (a) CDC staff experience. The CDC's staff must have well-trained, qualified loan officers who are knowledgeable concerning SBA's lending policies and procedures for the 504 program. The CDC must have at least one loan...

13 CFR 120.841 - Qualifications for the ALP.

Code of Federal Regulations, 2013 CFR

2013-01-01

.... An applicant for ALP status must show that it substantially meets the following criteria: (a) CDC staff experience. The CDC's staff must have well-trained, qualified loan officers who are knowledgeable concerning SBA's lending policies and procedures for the 504 program. The CDC must have at least one loan...

7 CFR 331.5 - Exemptions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... reported to APHIS or CDC by telephone, facsimile, or e-mail. This report must be followed by submission of APHIS/CDC Form 4 within 7 calendar days after identification. Less stringent reporting may be required during agricultural emergencies or outbreaks, or in endemic areas. A copy of APHIS/CDC Form 4 must be...

13 CFR 120.841 - Qualifications for the ALP.

Code of Federal Regulations, 2011 CFR

2011-01-01

.... An applicant for ALP status must show that it substantially meets the following criteria: (a) CDC staff experience. The CDC's staff must have well-trained, qualified loan officers who are knowledgeable concerning SBA's lending policies and procedures for the 504 program. The CDC must have at least one loan...

13 CFR 120.825 - Financial ability to operate.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.825 Financial ability to operate. A CDC must be able to sustain its operations continuously, with reliable sources of... funds generated from 503 and 504 loan activity by a CDC remaining after payment of staff and overhead...

13 CFR 120.540 - Liquidation and litigation plans.

Code of Federal Regulations, 2012 CFR

2012-01-01

... liquidation through the review of liquidation plans which all Authorized CDC Liquidators and certain Lenders... plan. An Authorized CDC Liquidator and a Lender for a loan made under its authority as a CLP Lender... receive SBA's written approval of that plan. (c) Litigation plan. An Authorized CDC Liquidator and a...

13 CFR 120.540 - Liquidation and litigation plans.

Code of Federal Regulations, 2014 CFR

2014-01-01

... liquidation through the review of liquidation plans which all Authorized CDC Liquidators and certain Lenders... plan. An Authorized CDC Liquidator and a Lender for a loan made under its authority as a CLP Lender... receive SBA's written approval of that plan. (c) Litigation plan. An Authorized CDC Liquidator and a...

7 CFR 331.5 - Exemptions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... reported to APHIS or CDC by telephone, facsimile, or e-mail. This report must be followed by submission of APHIS/CDC Form 4 within 7 calendar days after identification. Less stringent reporting may be required during agricultural emergencies or outbreaks, or in endemic areas. A copy of APHIS/CDC Form 4 must be...

13 CFR 120.540 - Liquidation and litigation plans.

Code of Federal Regulations, 2010 CFR

2010-01-01

... liquidation through the review of liquidation plans which all Authorized CDC Liquidators and certain Lenders... plan. An Authorized CDC Liquidator and a Lender for a loan made under its authority as a CLP Lender... receive SBA's written approval of that plan. (c) Litigation plan. An Authorized CDC Liquidator and a...

42 CFR 37.52 - Proficiency in the use of systems for classifying the pneumoconioses.

Code of Federal Regulations, 2013 CFR

2013-10-01

... must be on the Roentgenographic Interpretation Form (Form CDC/NIOSH (M)2.8), or; (ii) Satisfactory... using an Interpreting Physician Certification Document (Form CDC/NIOSH (M)2.12). 2 NIOSH Safety and Health Topic. Chest Radiography: Radiographic Classification [http://www.cdc.gov/niosh/topics...

13 CFR 120.825 - Financial ability to operate.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.825 Financial ability to operate. A CDC must be able to sustain its operations continuously, with reliable sources of... funds generated from 503 and 504 loan activity by a CDC remaining after payment of staff and overhead...

13 CFR 120.825 - Financial ability to operate.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.825 Financial ability to operate. A CDC must be able to sustain its operations continuously, with reliable sources of... funds generated from 503 and 504 loan activity by a CDC remaining after payment of staff and overhead...

13 CFR 120.540 - Liquidation and litigation plans.

Code of Federal Regulations, 2013 CFR

2013-01-01

... liquidation through the review of liquidation plans which all Authorized CDC Liquidators and certain Lenders... plan. An Authorized CDC Liquidator and a Lender for a loan made under its authority as a CLP Lender... receive SBA's written approval of that plan. (c) Litigation plan. An Authorized CDC Liquidator and a...

42 CFR 37.52 - Proficiency in the use of systems for classifying the pneumoconioses.

Code of Federal Regulations, 2014 CFR

2014-10-01

... must be on the Radiographic Interpretation Form (Form CDC/NIOSH (M)2.8), or; (ii) Satisfactory... using an Interpreting Physician Certification Document (Form CDC/NIOSH (M)2.12). 2 NIOSH Safety and Health Topic. Chest Radiography: Radiographic Classification [http://www.cdc.gov/niosh/topics...

Implementation of the Hong Kong Language Policy in Pre-School Settings

ERIC Educational Resources Information Center

Leung, Cheung-Shing Sam; Lim, Swee Eng Audrey; Li, Yuen Ling

2013-01-01

In the past, the Curriculum Development Council in Hong Kong [Curriculum Development Council (CDC). (1996). "Guide to the Pre-Primary Curriculum." Hong Kong: Government Printer; CDC. (2000). "Consultation Document: Learning to Learn: The Way Forward in Curriculum Development." Hong Kong: Government Printer; CDC. (2001).…

7 CFR 331.5 - Exemptions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... reported to APHIS or CDC by telephone, facsimile, or e-mail. This report must be followed by submission of APHIS/CDC Form 4 within 7 calendar days after identification. Less stringent reporting may be required during agricultural emergencies or outbreaks, or in endemic areas. A copy of APHIS/CDC Form 4 must be...

75 FR 5087 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention [60Day-10-10BG... on proposed data collection projects, the Centers for Disease Control and Prevention (CDC) will... Health (NCEH), Centers for Disease Control and Prevention (CDC). Background and Brief Description The CDC...

Front-end electronics of the Belle II drift chamber

NASA Astrophysics Data System (ADS)

Shimazaki, Shoichi; Taniguchi, Takashi; Uchida, Tomohisa; Ikeno, Masahiro; Taniguchi, Nanae; Tanaka, Manobu M.

2014-01-01

This paper describes the performance of the Belle II central drift chamber (CDC) front-end electronics. The front-end electronics consists of a current sensitive preamplifier, a 1/t cancellation circuit, baseline restorers, a comparator for timing measurement and an analog buffer for the dE/dx measurement on a CDC readout card. The CDC readout card is located on the endplate of the CDC. Mass production will be completed after the performance of the chip is verified. The electrical performance and results of a neutron/gamma-ray irradiation test are reported here.

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

PubMed

Kobayashi, Junya; Matsuura, Yoshiyuki

2017-10-01

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

Requirements for facilities transferring or receiving select agents. Final rule.

PubMed

2001-08-31

CDC administers regulations that govern the transfer of certain biological agents and toxins ("select agents"). These regulations require entities that transfer or receive select agents to register with CDC and comply with biosafety standards contained in the Third Edition of the CDC/NIH publication "Biosafety in Microbiological and Biomedical Laboratories ("BMBL")." On October 28,1999, CDC published a Notice of Proposed Rulemaking ("NPRM") seeking both to revise the biosafety standards facilities must follow when handling select agents and to provide new biosecurity standards for such facilities. These new standards are contained in the Fourth Edition of BMBL, which the NPRM proposed to incorporate by reference, thereby replacing the Third Edition. No comments were received in response to this proposal. CDC is therefore amending its regulations to incorporate the Fourth Edition.

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.

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.

Distinct DC subsets regulate adaptive Th1 and 2 responses during Trichuris muris infection.

PubMed

Demiri, M; Müller-Luda, K; Agace, W W; Svensson-Frej, M

2017-10-01

Low- and high-dose infections with the murine large intestinal nematode Trichuris muris are associated with induction of adaptive Th1 and Th2 responses, respectively, in mesenteric lymph nodes (MLN). Classical dendritic cells (cDC) accumulate in the large intestinal mucosa and MLN upon T. muris infection, yet their role in driving adaptive responses to infection remains largely unknown. We performed low- and high-dose T. muris infections of mice deficient in defined cDC subsets to investigate their role in induction of adaptive immune responses. Mice lacking IRF4-dependent cDC failed to clear a high-dose infection and displayed impaired Th2 responses. Conversely, mice lacking IRF8-dependent cDC cleared a low-dose infection and displayed an impaired Th1 response while increased production of Th2 cytokines. Finally, mice lacking both IRF4- and IRF8-dependent cDC were able to generate a Th2 response and clear a low-dose infection. Collectively, these results suggest that IRF4- and IRF8-dependent cDC act antagonistically during T. muris infection, and demonstrate that intestinal Th2 responses can be generated towards T. muris in the absence of IRF4-dependent cDC. © 2017 John Wiley & Sons Ltd.

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.

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-06-01

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

Online Reports of Foodborne Illness Capture Foods Implicated in Official Foodborne Outbreak Reports

PubMed Central

Nsoesie, Elaine O.; Gordon, Sheryl A.; Brownstein, John S.

2014-01-01

Objective Traditional surveillance systems only capture a fraction of the estimated 48 million yearly cases of foodborne illness in the United States. We assessed whether foodservice reviews on Yelp.com (a business review site) can be used to support foodborne illness surveillance efforts. Methods We obtained reviews from 2005–2012 of 5824 foodservice businesses closest to 29 colleges. After extracting recent reviews describing episodes of foodborne illness, we compared implicated foods to foods in outbreak reports from the U.S. Centers for Disease Control and Prevention (CDC). Results Broadly, the distribution of implicated foods across five categories was as follows: aquatic (16% Yelp, 12% CDC), dairy-eggs (23% Yelp, 23% CDC), fruits-nuts (7% Yelp, 7% CDC), meat-poultry (32% Yelp, 33% CDC), and vegetables (22% Yelp, 25% CDC). The distribution of foods across 19 more specific food categories was also similar, with spearman correlations ranging from 0.60 to 0.85 for 2006–2011. The most implicated food categories in both Yelp and CDC were beef, dairy, grains-beans, poultry and vine-stalk. Conclusions Based on observations in this study and the increased usage of social media, we posit that online illness reports could complement traditional surveillance systems by providing near real-time information on foodborne illnesses, implicated foods and locations. PMID:25124281

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

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

PubMed

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

2018-05-15

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

Malaria Surveillance — United States, 2015

PubMed Central

Arguin, Paul M.; Tan, Kathrine R.

2018-01-01

Problem/Condition Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles species mosquito. The majority of malaria infections in the United States occur among persons who have traveled to regions with ongoing malaria transmission. However, malaria is occasionally acquired by persons who have not traveled out of the country through exposure to infected blood products, congenital transmission, laboratory exposure, or local mosquitoborne transmission. Malaria surveillance in the United States is conducted to provide information on its occurrence (e.g., temporal, geographic, and demographic), guide prevention and treatment recommendations for travelers and patients, and facilitate transmission control measures if locally acquired cases are identified. Period Covered This report summarizes confirmed malaria cases in persons with onset of illness in 2015 and summarizes trends in previous years. Description of System Malaria cases diagnosed by blood film microscopy, polymerase chain reaction, or rapid diagnostic tests are reported to local and state health departments by health care providers or laboratory staff members. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS), the National Notifiable Diseases Surveillance System (NNDSS), or direct CDC consultations. CDC reference laboratories provide diagnostic assistance and conduct antimalarial drug resistance marker testing on blood samples submitted by health care providers or local or state health departments. This report summarizes data from the integration of all NMSS and NNDSS cases, CDC reference laboratory reports, and CDC clinical consultations. Results CDC received reports of 1,517 confirmed malaria cases, including one congenital case, with an onset of symptoms in 2015 among persons who received their diagnoses in the United States. Although the number of malaria cases diagnosed in the United States has been increasing since the mid-1970s, the number of cases decreased by 208 from 2014 to 2015. Among the regions of acquisition (Africa, West Africa, Asia, Central America, the Caribbean, South America, Oceania, and the Middle East), the only region with significantly fewer imported cases in 2015 compared with 2014 was West Africa (781 versus 969). Plasmodium falciparum, P. vivax, P. ovale, and P. malariae were identified in 67.4%, 11.7%, 4.1%, and 3.1% of cases, respectively. Less than 1% of patients were infected by two species. The infecting species was unreported or undetermined in 12.9% of cases. CDC provided diagnostic assistance for 13.1% of patients with confirmed cases and tested 15.0% of P. falciparum specimens for antimalarial resistance markers. Of the U.S. resident patients who reported purpose of travel, 68.4% were visiting friends or relatives. A lower proportion of U.S. residents with malaria reported taking any chemoprophylaxis in 2015 (26.5%) compared with 2014 (32.5%), and adherence was poor in this group. Among the U.S residents for whom information on chemoprophylaxis use and travel region were known, 95.3% of patients with malaria did not adhere to or did not take a CDC-recommended chemoprophylaxis regimen. Among women with malaria, 32 were pregnant, and none had adhered to chemoprophylaxis. A total of 23 malaria cases occurred among U.S. military personnel in 2015. Three cases of malaria were imported from the approximately 3,000 military personnel deployed to an Ebola-affected country; two of these were not P. falciparum species, and one species was unspecified. Among all reported cases in 2015, 17.1% were classified as severe illnesses and 11 persons died, compared with an average of 6.1 deaths per year during 2000–2014. In 2015, CDC received 153 P. falciparum-positive samples for surveillance of antimalarial resistance markers (although certain loci were untestable for some samples); genetic polymorphisms associated with resistance to pyrimethamine were identified in 132 (86.3%), to sulfadoxine in 112 (73.7%), to chloroquine in 48 (31.4%), to mefloquine in six (4.3%), and to artemisinin in one (<1%), and no sample had resistance to atovaquone. Completion of data elements on the malaria case report form decreased from 2014 to 2015 and remains low, with 24.2% of case report forms missing at least one key element (species, travel history, and resident status). Interpretation The decrease in malaria cases from 2014 to 2015 is associated with a decrease in imported cases from West Africa. This finding might be related to altered or curtailed travel to Ebola-affected countries in in this region. Despite progress in reducing malaria worldwide, the disease remains endemic in many regions, and the use of appropriate prevention measures by travelers is still inadequate. Public Health Actions The best way to prevent malaria is to take chemoprophylaxis medication during travel to a country where malaria is endemic. As demonstrated by the U.S. military during the Ebola response, use of chemoprophylaxis and other protection measures is possible in stressful environments, and this can prevent malaria, especially P. falciparum, even in high transmission areas. Detailed recommendations for preventing malaria are available to the general public at the CDC website (https://www.cdc.gov/malaria/travelers/drugs.html). Malaria infections can be fatal if not diagnosed and treated promptly with antimalarial medications appropriate for the patient’s age and medical history, the likely country of malaria acquisition, and previous use of antimalarial chemoprophylaxis. Health care providers should consult the CDC Guidelines for Treatment of Malaria in the United States and contact the CDC’s Malaria Hotline for case management advice when needed. Malaria treatment recommendations are available online (https://www.cdc.gov/malaria/diagnosis_treatment) and from the Malaria Hotline (770-488-7788 or toll-free at 855-856-4713). Persons submitting malaria case reports (care providers, laboratories, and state and local public health officials) should provide complete information because incomplete reporting compromises case investigations and efforts to prevent infections and examine trends in malaria cases. Compliance with recommended malaria prevention strategies is low among U.S. travelers visiting friends and relatives. Evidence-based prevention strategies that effectively target travelers who are visiting friends and relatives need to be developed and implemented to reduce the numbers of imported malaria cases in the United States. Molecular surveillance of antimalarial drug resistance markers (https://www.cdc.gov/malaria/features/ars.html) has enabled CDC to track, guide treatment, and manage drug resistance in malaria parasites both domestically and internationally. More samples are needed to improve the completeness of antimalarial drug resistance marker analysis; therefore, CDC requests that blood specimens be submitted for all cases diagnosed in the United States. PMID:29723168

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

PubMed

Baldwin, Grant; Breiding, Matt; Sleet, David

2016-06-30

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

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.

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.

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.

Targeted Approaches to Overcoming Endocrine Resistance in Breast Cancer

DTIC Science & Technology

2011-08-01

NM_001012271 BUB1 BUB1 budding uninhibited by benzimidazoles 1 homolog AF053305 CDC20 Cell division cycle 20 homolog BG256659 CDC25B Cell division cycle...by benzimidazoles 1 homolog), BIRC5/ Survivin, CDCA8 (cell division cycle-associated protein 8), AURKB (aurora kinase B), CDC25B (cell division cycle

A Public Health Approach to Injury Prevention: The U.S. Military Experience

DTIC Science & Technology

2010-01-01

Center for Injury Prevention and Control. CDC in- jury research agenda, 2009– 2018 . Atlanta GA: USDHHS, CDC, 2009. http://www.cdc.gov/injury/index.html...secrets. Philadephia PA: Hanley & Belfus, 1994. 20. Micheli LJ. The sports medicine bible . New York: HarperCollins Publishers, 1995. 21. Peterson L

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...

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...

77 FR 2549 - Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)-Ethics...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-18

... Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)--Ethics Subcommittee (ES... will provide counsel to the ACD, CDC, regarding a broad range of public health ethics questions and... territorial health departments in their efforts to address public health ethics challenges, approaches for...

76 FR 29755 - Advisory Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)-Ethics...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-23

... Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)--Ethics Subcommittee (ES... of public health ethics questions and issues arising from programs, scientists and practitioners... April 28, 2011, ACD, CDC meeting; discussion of next steps on addressing potential public health ethical...

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...

13 CFR 120.101 - Credit not available elsewhere.

Code of Federal Regulations, 2014 CFR

2014-01-01

... available on reasonable terms from non-Federal sources. SBA requires the Lender or CDC to certify or... periods of time. Submission of an application to SBA by a Lender or CDC constitutes certification by the Lender or CDC that it has examined the availability of credit to the applicant, has based its...

42 CFR 73.16 - Transfers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... section and must be authorized by CDC or APHIS prior to the transfer. 4 4 This section does not cover... transferred without prior authorization from CDC or APHIS provided that, at least seven calendar days prior to the transfer, the sender reports to CDC or APHIS the select agent or toxin to be transferred and the...

13 CFR 120.101 - Credit not available elsewhere.

Code of Federal Regulations, 2010 CFR

2010-01-01

... available on reasonable terms from non-Federal sources. SBA requires the Lender or CDC to certify or... periods of time. Submission of an application to SBA by a Lender or CDC constitutes certification by the Lender or CDC that it has examined the availability of credit to the applicant, has based its...

13 CFR 120.101 - Credit not available elsewhere.

Code of Federal Regulations, 2012 CFR

2012-01-01

... available on reasonable terms from non-Federal sources. SBA requires the Lender or CDC to certify or... periods of time. Submission of an application to SBA by a Lender or CDC constitutes certification by the Lender or CDC that it has examined the availability of credit to the applicant, has based its...

13 CFR 120.892 - Certifications of no adverse change.

Code of Federal Regulations, 2014 CFR

2014-01-01

... loan closing: (a) The interim lender must certify to the CDC that it has no knowledge of any unremedied...; (b) The Borrower (or Operating Company) must certify to the CDC that there has been no unremedied... CDC must issue an opinion to the best of its knowledge that there has been no unremedied substantial...

9 CFR 121.16 - Transfers.

Code of Federal Regulations, 2010 CFR

2010-01-01

... section and must be authorized by APHIS or CDC prior to the transfer. 14 14 The requirements of this... proficiency testing may be transferred without prior authorization from APHIS or CDC provided that, at least 7 calendar days prior to the transfer, the sender reports to APHIS or CDC the select agent or toxin to be...

75 FR 39265 - Request for Nominations of Candidates To Serve on the Board of Scientific Counselors (BSC...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-08

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention (CDC) Request... Secretary, HHS; the Director, CDC and the Director, NCEH/ATSDR, regarding program goals, objectives... Management Specialist, NCEH/ ATSDR, CDC, 4770 Buford Highway (MS-F61), Chamblee, Georgia 30341. (E- mail...

42 CFR 73.5 - Exemptions for HHS select agents and toxins.

Code of Federal Regulations, 2010 CFR

2010-10-01

... the select agent or toxin is reported to CDC or APHIS and to other appropriate authorities when... minor (Alastrim), or Yersinia pestis. This report must be followed by submission of APHIS/CDC Form 4.../CDC Form 4 must be submitted within seven calendar days after identification. (iii) Less stringent...

7 CFR 331.16 - Transfers.

Code of Federal Regulations, 2014 CFR

2014-01-01

... or CDC prior to the transfer. 7 7 The requirements of this section do not apply to transfers within a... authorization for a transfer, APHIS/CDC Form 2 must be submitted. (e) After authorization is provided by APHIS or CDC, the packaging of the select agent(s) and toxin(s) is performed by an individual approved by...

13 CFR 120.938 - Default.

Code of Federal Regulations, 2014 CFR

2014-01-01

... investor for any premium paid. (b) If a CDC defaults on a Debenture, SBA generally shall limit its recovery to the payments made by the small business to the CDC on the loan made from the Debenture proceeds, and the collateral securing the defaulted loan. However, SBA will look to the CDC for the entire...

13 CFR 120.938 - Default.

Code of Federal Regulations, 2010 CFR

2010-01-01

... investor for any premium paid. (b) If a CDC defaults on a Debenture, SBA generally shall limit its recovery to the payments made by the small business to the CDC on the loan made from the Debenture proceeds, and the collateral securing the defaulted loan. However, SBA will look to the CDC for the entire...

13 CFR 120.960 - Responsibility for closing.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Development Company Loan Program (504) Closings § 120.960 Responsibility for closing. (a) The CDC is responsible for the 504 loan closing. (b) The Debenture closing is the joint responsibility of the CDC and SBA... 504 loan to another CDC; or cancel its guarantee of the Debenture, prior to sale, if any of the...

42 CFR 73.16 - Transfers.

Code of Federal Regulations, 2013 CFR

2013-10-01

... section and must be authorized by CDC or APHIS prior to the transfer. 4 4 This section does not cover... transferred without prior authorization from CDC or APHIS provided that, at least seven calendar days prior to the transfer, the sender reports to CDC or APHIS the select agent or toxin to be transferred and the...

Sleep in Individuals with Cri du Chat Syndrome: A Comparative Study

ERIC Educational Resources Information Center

Maas, A. P. H. M.; Didden, R.; Korzilius, H.; Braam, W.; Smits, M. G.; Curfs, L. M. G.

2009-01-01

Background: Sleep problems are common in individuals with intellectual disability. Little is known about sleep in children and adults with Cri du Chat syndrome (CDC). Method: Sleep was investigated in 30 individuals with CDC using a sleep questionnaire. Sleep problems and sleep behaviours in individuals with CDC were compared with individuals with…

13 CFR 120.892 - Certifications of no adverse change.

Code of Federal Regulations, 2013 CFR

2013-01-01

... loan closing: (a) The interim lender must certify to the CDC that it has no knowledge of any unremedied...; (b) The Borrower (or Operating Company) must certify to the CDC that there has been no unremedied... CDC must issue an opinion to the best of its knowledge that there has been no unremedied substantial...

13 CFR 120.10 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... through notice and comment. Associate. (1) An Associate of a Lender or CDC is: (i) An officer, director, key employee, or holder of 20 percent or more of the value of the Lender's or CDC's stock or debt... continues as long as the certification, participation agreement, or loan is outstanding: (i) For a CDC, the...

42 CFR 73.5 - Exemptions for HHS select agents and toxins.

Code of Federal Regulations, 2014 CFR

2014-10-01

... the select agent or toxin is reported to CDC or APHIS and to other appropriate authorities when... followed by submission of APHIS/CDC Form 4 within seven calendar days after identification. (ii) For all other HHS select agents or toxins, APHIS/CDC Form 4 must be submitted within seven calendar days after...

13 CFR 120.954 - Central Servicing Agent.

Code of Federal Regulations, 2013 CFR

2013-01-01

... the orderly flow of funds among Borrowers, CDCs, and SBA. The CDC and Borrower must enter into an individual Servicing Agent Agreement with the CSA for each 504 loan, constituting acceptance by the CDC and... loan. At SBA's direction, the CSA must pay to the CDC servicing each loan the interest accruing in the...

78 FR 5185 - Notice of Availability of Final Environmental Assessment (FINAL EA) and a Finding of No...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-24

... Metropolitan Sewer District of Greater Cincinnati Easement on HHS/CDC/NIOSH Taft North Campus, Cincinnati, OH AGENCY: Centers for Disease Control and Prevention (CDC), Department of Health and Human Services (HHS... Significant Impact (FONSI) for Metropolitan Sewer District of Greater Cincinnati Easement on HHS/CDC/NIOSH...

13 CFR 120.802 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... geographic area where SBA has approved a CDC's request to provide 504 program services to small businesses on a permanent basis. The minimum Area of Operations is the State in which the CDC is incorporated... obligation issued by a CDC and guaranteed 100 percent by SBA, the proceeds of which are used to fund a 504...

13 CFR 120.802 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... geographic area where SBA has approved a CDC's request to provide 504 program services to small businesses on a permanent basis. The minimum Area of Operations is the State in which the CDC is incorporated... obligation issued by a CDC and guaranteed 100 percent by SBA, the proceeds of which are used to fund a 504...

13 CFR 120.101 - Credit not available elsewhere.

Code of Federal Regulations, 2013 CFR

2013-01-01

... available on reasonable terms from non-Federal sources. SBA requires the Lender or CDC to certify or... periods of time. Submission of an application to SBA by a Lender or CDC constitutes certification by the Lender or CDC that it has examined the availability of credit to the applicant, has based its...

42 CFR 73.5 - Exemptions for HHS select agents and toxins.

Code of Federal Regulations, 2013 CFR

2013-10-01

... the select agent or toxin is reported to CDC or APHIS and to other appropriate authorities when... followed by submission of APHIS/CDC Form 4 within seven calendar days after identification. (ii) For all other HHS select agents or toxins, APHIS/CDC Form 4 must be submitted within seven calendar days after...

13 CFR 120.10 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... through notice and comment. Associate. (1) An Associate of a Lender or CDC is: (i) An officer, director, key employee, or holder of 20 percent or more of the value of the Lender's or CDC's stock or debt... continues as long as the certification, participation agreement, or loan is outstanding: (i) For a CDC, the...

13 CFR 120.101 - Credit not available elsewhere.

Code of Federal Regulations, 2011 CFR

2011-01-01

... available on reasonable terms from non-Federal sources. SBA requires the Lender or CDC to certify or... periods of time. Submission of an application to SBA by a Lender or CDC constitutes certification by the Lender or CDC that it has examined the availability of credit to the applicant, has based its...

9 CFR 121.16 - Transfers.

Code of Federal Regulations, 2012 CFR

2012-01-01

... section and must be authorized by APHIS or CDC prior to the transfer. 14 14 The requirements of this... proficiency testing may be transferred without prior authorization from APHIS or CDC provided that, at least 7 calendar days prior to the transfer, the sender reports to APHIS or CDC the select agent or toxin to be...

13 CFR 120.960 - Responsibility for closing.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Development Company Loan Program (504) Closings § 120.960 Responsibility for closing. (a) The CDC is responsible for the 504 loan closing. (b) The Debenture closing is the joint responsibility of the CDC and SBA... 504 loan to another CDC; or cancel its guarantee of the Debenture, prior to sale, if any of the...

13 CFR 120.892 - Certifications of no adverse change.

Code of Federal Regulations, 2012 CFR

2012-01-01

... loan closing: (a) The interim lender must certify to the CDC that it has no knowledge of any unremedied...; (b) The Borrower (or Operating Company) must certify to the CDC that there has been no unremedied... CDC must issue an opinion to the best of its knowledge that there has been no unremedied substantial...

42 CFR 73.16 - Transfers.

Code of Federal Regulations, 2012 CFR

2012-10-01

... section and must be authorized by CDC or APHIS prior to the transfer. 4 4 This section does not cover... transferred without prior authorization from CDC or APHIS provided that, at least seven calendar days prior to the transfer, the sender reports to CDC or APHIS the select agent or toxin to be transferred and the...

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 120.10 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... through notice and comment. Associate. (1) An Associate of a Lender or CDC is: (i) An officer, director, key employee, or holder of 20 percent or more of the value of the Lender's or CDC's stock or debt... continues as long as the certification, participation agreement, or loan is outstanding: (i) For a CDC, the...

42 CFR 73.16 - Transfers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... section and must be authorized by CDC or APHIS prior to the transfer. 4 4 This section does not cover... transferred without prior authorization from CDC or APHIS provided that, at least seven calendar days prior to the transfer, the sender reports to CDC or APHIS the select agent or toxin to be transferred and the...

9 CFR 121.16 - Transfers.

Code of Federal Regulations, 2013 CFR

2013-01-01

... section and must be authorized by APHIS or CDC prior to the transfer. 12 12 The requirements of this... proficiency testing may be transferred without prior authorization from APHIS or CDC provided that, at least 7 calendar days prior to the transfer, the sender reports to APHIS or CDC the select agent or toxin to be...

13 CFR 120.892 - Certifications of no adverse change.

Code of Federal Regulations, 2011 CFR

2011-01-01

... loan closing: (a) The interim lender must certify to the CDC that it has no knowledge of any unremedied...; (b) The Borrower (or Operating Company) must certify to the CDC that there has been no unremedied... CDC must issue an opinion to the best of its knowledge that there has been no unremedied substantial...

13 CFR 120.938 - Default.

Code of Federal Regulations, 2011 CFR

2011-01-01

... investor for any premium paid. (b) If a CDC defaults on a Debenture, SBA generally shall limit its recovery to the payments made by the small business to the CDC on the loan made from the Debenture proceeds, and the collateral securing the defaulted loan. However, SBA will look to the CDC for the entire...

13 CFR 120.954 - Central Servicing Agent.

Code of Federal Regulations, 2014 CFR

2014-01-01

... the orderly flow of funds among Borrowers, CDCs, and SBA. The CDC and Borrower must enter into an individual Servicing Agent Agreement with the CSA for each 504 loan, constituting acceptance by the CDC and... loan. At SBA's direction, the CSA must pay to the CDC servicing each loan the interest accruing in the...

7 CFR 331.16 - Transfers.

Code of Federal Regulations, 2011 CFR

2011-01-01

... or CDC prior to the transfer. 8 8 The requirements of this section do not apply to transfers within a... authorization for a transfer, APHIS/CDC Form 2 must be submitted. (e) The recipient must submit a completed APHIS/CDC Form 2 within 2 business days of receipt of a select agent or toxin. (f) The recipient must...

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

Code of Federal Regulations, 2011 CFR

2011-10-01

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

13 CFR 120.10 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... through notice and comment. Associate. (1) An Associate of a Lender or CDC is: (i) An officer, director, key employee, or holder of 20 percent or more of the value of the Lender's or CDC's stock or debt... continues as long as the certification, participation agreement, or loan is outstanding: (i) For a CDC, the...

9 CFR 121.16 - Transfers.

Code of Federal Regulations, 2014 CFR

2014-01-01

... section and must be authorized by APHIS or CDC prior to the transfer. 12 12 The requirements of this... proficiency testing may be transferred without prior authorization from APHIS or CDC provided that, at least 7 calendar days prior to the transfer, the sender reports to APHIS or CDC the select agent or toxin to be...

13 CFR 120.802 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... geographic area where SBA has approved a CDC's request to provide 504 program services to small businesses on a permanent basis. The minimum Area of Operations is the State in which the CDC is incorporated... obligation issued by a CDC and guaranteed 100 percent by SBA, the proceeds of which are used to fund a 504...

13 CFR 120.960 - Responsibility for closing.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Development Company Loan Program (504) Closings § 120.960 Responsibility for closing. (a) The CDC is responsible for the 504 loan closing. (b) The Debenture closing is the joint responsibility of the CDC and SBA... 504 loan to another CDC; or cancel its guarantee of the Debenture, prior to sale, if any of the...

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

Code of Federal Regulations, 2010 CFR

2010-10-01

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

13 CFR 120.960 - Responsibility for closing.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Development Company Loan Program (504) Closings § 120.960 Responsibility for closing. (a) The CDC is responsible for the 504 loan closing. (b) The Debenture closing is the joint responsibility of the CDC and SBA... 504 loan to another CDC; or cancel its guarantee of the Debenture, prior to sale, if any of the...

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...

7 CFR 331.16 - Transfers.

Code of Federal Regulations, 2010 CFR

2010-01-01

... or CDC prior to the transfer. 8 8 The requirements of this section do not apply to transfers within a... authorization for a transfer, APHIS/CDC Form 2 must be submitted. (e) The recipient must submit a completed APHIS/CDC Form 2 within 2 business days of receipt of a select agent or toxin. (f) The recipient must...

42 CFR 73.16 - Transfers.

Code of Federal Regulations, 2014 CFR

2014-10-01

... section and must be authorized by CDC or APHIS prior to the transfer. 4 4 This section does not cover... transferred without prior authorization from CDC or APHIS provided that, at least seven calendar days prior to the transfer, the sender reports to CDC or APHIS the select agent or toxin to be transferred and the...

42 CFR 73.9 - Responsible Official.

Code of Federal Regulations, 2011 CFR

2011-10-01

... reported by submission of APHIS/CDC Form 4 within seven calendar days after identification. A copy of the... any other select agent or toxin, APHIS/CDC Form 4 must be submitted within seven calendar days after... agent or toxin, APHIS/CDC Form 4 must be submitted within 90 calendar days of receipt of the agent or...

13 CFR 120.938 - Default.

Code of Federal Regulations, 2013 CFR

2013-01-01

... investor for any premium paid. (b) If a CDC defaults on a Debenture, SBA generally shall limit its recovery to the payments made by the small business to the CDC on the loan made from the Debenture proceeds, and the collateral securing the defaulted loan. However, SBA will look to the CDC for the entire...

13 CFR 120.954 - Central Servicing Agent.

Code of Federal Regulations, 2011 CFR

2011-01-01

... the orderly flow of funds among Borrowers, CDCs, and SBA. The CDC and Borrower must enter into an individual Servicing Agent Agreement with the CSA for each 504 loan, constituting acceptance by the CDC and... loan. At SBA's direction, the CSA must pay to the CDC servicing each loan the interest accruing in the...

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

Code of Federal Regulations, 2012 CFR

2012-10-01

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

13 CFR 120.960 - Responsibility for closing.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Development Company Loan Program (504) Closings § 120.960 Responsibility for closing. (a) The CDC is responsible for the 504 loan closing. (b) The Debenture closing is the joint responsibility of the CDC and SBA... 504 loan to another CDC; or cancel its guarantee of the Debenture, prior to sale, if any of the...

13 CFR 120.954 - Central Servicing Agent.

Code of Federal Regulations, 2010 CFR

2010-01-01

... the orderly flow of funds among Borrowers, CDCs, and SBA. The CDC and Borrower must enter into an individual Servicing Agent Agreement with the CSA for each 504 loan, constituting acceptance by the CDC and... loan. At SBA's direction, the CSA must pay to the CDC servicing each loan the interest accruing in the...

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 120.938 - Default.

Code of Federal Regulations, 2012 CFR

2012-01-01

... investor for any premium paid. (b) If a CDC defaults on a Debenture, SBA generally shall limit its recovery to the payments made by the small business to the CDC on the loan made from the Debenture proceeds, and the collateral securing the defaulted loan. However, SBA will look to the CDC for the entire...

7 CFR 331.16 - Transfers.

Code of Federal Regulations, 2013 CFR

2013-01-01

... or CDC prior to the transfer. 7 7 The requirements of this section do not apply to transfers within a... authorization for a transfer, APHIS/CDC Form 2 must be submitted. (e) After authorization is provided by APHIS or CDC, the packaging of the select agent(s) and toxin(s) is performed by an individual approved by...

13 CFR 120.892 - Certifications of no adverse change.

Code of Federal Regulations, 2010 CFR

2010-01-01

... loan closing: (a) The interim lender must certify to the CDC that it has no knowledge of any unremedied...; (b) The Borrower (or Operating Company) must certify to the CDC that there has been no unremedied... CDC must issue an opinion to the best of its knowledge that there has been no unremedied substantial...

9 CFR 121.16 - Transfers.

Code of Federal Regulations, 2011 CFR

2011-01-01

... section and must be authorized by APHIS or CDC prior to the transfer. 14 14 The requirements of this... proficiency testing may be transferred without prior authorization from APHIS or CDC provided that, at least 7 calendar days prior to the transfer, the sender reports to APHIS or CDC the select agent or toxin to be...

13 CFR 120.802 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... geographic area where SBA has approved a CDC's request to provide 504 program services to small businesses on a permanent basis. The minimum Area of Operations is the State in which the CDC is incorporated... obligation issued by a CDC and guaranteed 100 percent by SBA, the proceeds of which are used to fund a 504...

7 CFR 331.16 - Transfers.

Code of Federal Regulations, 2012 CFR

2012-01-01

... or CDC prior to the transfer. 8 8 The requirements of this section do not apply to transfers within a... authorization for a transfer, APHIS/CDC Form 2 must be submitted. (e) The recipient must submit a completed APHIS/CDC Form 2 within 2 business days of receipt of a select agent or toxin. (f) The recipient must...

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...

13 CFR 120.954 - Central Servicing Agent.

Code of Federal Regulations, 2012 CFR

2012-01-01

... the orderly flow of funds among Borrowers, CDCs, and SBA. The CDC and Borrower must enter into an individual Servicing Agent Agreement with the CSA for each 504 loan, constituting acceptance by the CDC and... loan. At SBA's direction, the CSA must pay to the CDC servicing each loan the interest accruing in the...