The Epigenomic Landscape of Prokaryotes

DOE PAGES

Blow, Matthew J.; Clark, Tyson A.; Daum, Chris G.; ...

2016-02-12

DNA methylation acts in concert with restriction enzymes to protect the integrity of prokaryotic genomes. Studies in a limited number of organisms suggest that methylation also contributes to prokaryotic genome regulation, but the prevalence and properties of such non-restriction-associated methylation systems remain poorly understood. Here, we used single molecule, real-time sequencing to map DNA modifications including m6A, m4C, and m5C across the genomes of 230 diverse bacterial and archaeal species. We observed DNA methylation in nearly all (93%) organisms examined, and identified a total of 834 distinct reproducibly methylated motifs. This data enabled annotation of the DNA binding specificities ofmore » 620 DNA Methyltransferases (MTases), doubling known specificities for previously hard to study Type I, IIG and III MTases, and revealing their extraordinary diversity. Strikingly, 48% of organisms harbor active Type II MTases with no apparent cognate restriction enzyme. These active ‘orphan’ MTases are present in diverse bacterial and archaeal phyla and show motif specificities and methylation patterns consistent with functions in gene regulation and DNA replication. Our results reveal the pervasive presence of DNA methylation throughout the prokaryotic kingdoms, as well as the diversity of sequence specificities and potential functions of DNA methylation systems.« less

The Epigenomic Landscape of Prokaryotes

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

Blow, Matthew J.; Clark, Tyson A.; Daum, Chris G.

DNA methylation acts in concert with restriction enzymes to protect the integrity of prokaryotic genomes. Studies in a limited number of organisms suggest that methylation also contributes to prokaryotic genome regulation, but the prevalence and properties of such non-restriction-associated methylation systems remain poorly understood. Here, we used single molecule, real-time sequencing to map DNA modifications including m6A, m4C, and m5C across the genomes of 230 diverse bacterial and archaeal species. We observed DNA methylation in nearly all (93%) organisms examined, and identified a total of 834 distinct reproducibly methylated motifs. This data enabled annotation of the DNA binding specificities ofmore » 620 DNA Methyltransferases (MTases), doubling known specificities for previously hard to study Type I, IIG and III MTases, and revealing their extraordinary diversity. Strikingly, 48% of organisms harbor active Type II MTases with no apparent cognate restriction enzyme. These active ‘orphan’ MTases are present in diverse bacterial and archaeal phyla and show motif specificities and methylation patterns consistent with functions in gene regulation and DNA replication. Our results reveal the pervasive presence of DNA methylation throughout the prokaryotic kingdoms, as well as the diversity of sequence specificities and potential functions of DNA methylation systems.« less

Ketone bodies as epigenetic modifiers.

PubMed

Ruan, Hai-Bin; Crawford, Peter A

2018-07-01

Ketone body metabolism is a dynamic and integrated metabolic node in human physiology, whose roles include but extend beyond alternative fuel provision during carbohydrate restriction. Here we discuss the most recent observations suggesting that ketosis coordinates cellular function via epigenomic regulation. Ketosis has been linked to covalent modifications, including lysine acetylation, methylation, and hydroxybutyrylation, to key histones that serve as dynamic regulators of chromatin architecture and gene transcription. Although it remains to be fully established whether these changes to the epigenome are attributable to ketone bodies themselves or other aspects of ketotic states, the regulated genes mediate classical responses to carbohydrate restriction. Direct regulation of gene expression may occur in-vivo via through ketone body-mediated histone modifications during adherence to low-carbohydrate diets, fasting ketosis, exogenous ketone body therapy, and diabetic ketoacidosis. Additional convergent functional genomics, metabolomics, and proteomics studies are required in both animal models and in humans to identify the molecular mechanisms through which ketosis regulates nuclear signaling events in a myriad of conditions relevant to disease, and the contexts in which the benefits of ketosis might outweigh the risks.

Government Ownership Restrictions and Efficiency: The Case of the FCC's Dupoply Rule.

ERIC Educational Resources Information Center

Anderson, Keith B.; Woodbury, John R.

Recently the Federal Communications Commission (FCC) has been considering modifications to its regulations governing local and national media ownership and has indicated more interest in the efficiency consequences of the regulations, including those that might arise from common ownership of multiple radio stations. This paper seeks to determine…

75 FR 42598 - Modification of Restricted Area R-3404; Crane, IN

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-22

.... Navy prepared and published a Final Environmental Assessment (FEA) in June 2008 that analyzed the... Significant Impact (FONSI) based on the results of the FEA. In accordance with applicable CEQ regulations (40...

Computation of output feedback gains for linear stochastic systems using the Zangwill-Powell method

NASA Technical Reports Server (NTRS)

Kaufman, H.

1977-01-01

Because conventional optimal linear regulator theory results in a controller which requires the capability of measuring and/or estimating the entire state vector, it is of interest to consider procedures for computing controls which are restricted to be linear feedback functions of a lower dimensional output vector and which take into account the presence of measurement noise and process uncertainty. To this effect a stochastic linear model has been developed that accounts for process parameter and initial uncertainty, measurement noise, and a restricted number of measurable outputs. Optimization with respect to the corresponding output feedback gains was then performed for both finite and infinite time performance indices without gradient computation by using Zangwill's modification of a procedure originally proposed by Powell.

48 CFR 243.205-70 - Pricing of contract modifications.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Pricing of contract modifications. 243.205-70 Section 243.205-70 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 243.205-70...

Epigenetic modification and inheritance in sexual reversal of fish.

PubMed

Shao, Changwei; Li, Qiye; Chen, Songlin; Zhang, Pei; Lian, Jinmin; Hu, Qiaomu; Sun, Bing; Jin, Lijun; Liu, Shanshan; Wang, Zongji; Zhao, Hongmei; Jin, Zonghui; Liang, Zhuo; Li, Yangzhen; Zheng, Qiumei; Zhang, Yong; Wang, Jun; Zhang, Guojie

2014-04-01

Environmental sex determination (ESD) occurs in divergent, phylogenetically unrelated taxa, and in some species, co-occurs with genetic sex determination (GSD) mechanisms. Although epigenetic regulation in response to environmental effects has long been proposed to be associated with ESD, a systemic analysis on epigenetic regulation of ESD is still lacking. Using half-smooth tongue sole (Cynoglossus semilaevis) as a model-a marine fish that has both ZW chromosomal GSD and temperature-dependent ESD-we investigated the role of DNA methylation in transition from GSD to ESD. Comparative analysis of the gonadal DNA methylomes of pseudomale, female, and normal male fish revealed that genes in the sex determination pathways are the major targets of substantial methylation modification during sexual reversal. Methylation modification in pseudomales is globally inherited in their ZW offspring, which can naturally develop into pseudomales without temperature incubation. Transcriptome analysis revealed that dosage compensation occurs in a restricted, methylated cytosine enriched Z chromosomal region in pseudomale testes, achieving equal expression level in normal male testes. In contrast, female-specific W chromosomal genes are suppressed in pseudomales by methylation regulation. We conclude that epigenetic regulation plays multiple crucial roles in sexual reversal of tongue sole fish. We also offer the first clues on the mechanisms behind gene dosage balancing in an organism that undergoes sexual reversal. Finally, we suggest a causal link between the bias sex chromosome assortment in the offspring of a pseudomale family and the transgenerational epigenetic inheritance of sexual reversal in tongue sole fish.

48 CFR 243.205-70 - Pricing of contract modifications.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Pricing of contract modifications. 243.205-70 Section 243.205-70 Federal Acquisition Regulations System DEFENSE ACQUISITION... Pricing of contract modifications. Use the clause at 252.243-7001, Pricing of Contract Modifications, in...

15 CFR 971.415 - Duration of a permit.

Code of Federal Regulations, 2010 CFR

2010-01-01

... commercial recovery permit will be issued for a period of 20 years and for so long thereafter as hard mineral... ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY PERMITS Issuance/Transfer: Terms, Conditions and Restrictions Issuance/transfer, Modification/revision; Suspension/revocation § 971...

15 CFR 971.415 - Duration of a permit.

Code of Federal Regulations, 2012 CFR

2012-01-01

... commercial recovery permit will be issued for a period of 20 years and for so long thereafter as hard mineral... ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY PERMITS Issuance/Transfer: Terms, Conditions and Restrictions Issuance/transfer, Modification/revision; Suspension/revocation § 971...

15 CFR 971.415 - Duration of a permit.

Code of Federal Regulations, 2013 CFR

2013-01-01

... commercial recovery permit will be issued for a period of 20 years and for so long thereafter as hard mineral... ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY PERMITS Issuance/Transfer: Terms, Conditions and Restrictions Issuance/transfer, Modification/revision; Suspension/revocation § 971...

15 CFR 971.415 - Duration of a permit.

Code of Federal Regulations, 2014 CFR

2014-01-01

... commercial recovery permit will be issued for a period of 20 years and for so long thereafter as hard mineral... ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY PERMITS Issuance/Transfer: Terms, Conditions and Restrictions Issuance/transfer, Modification/revision; Suspension/revocation § 971...

15 CFR 971.415 - Duration of a permit.

Code of Federal Regulations, 2011 CFR

2011-01-01

... commercial recovery permit will be issued for a period of 20 years and for so long thereafter as hard mineral... ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY PERMITS Issuance/Transfer: Terms, Conditions and Restrictions Issuance/transfer, Modification/revision; Suspension/revocation § 971...

A controlled double-duration inducible gene expression system for cartilage tissue engineering.

PubMed

Ma, Ying; Li, Junxiang; Yao, Yi; Wei, Daixu; Wang, Rui; Wu, Qiong

2016-05-25

Cartilage engineering that combines competent seeding cells and a compatible scaffold is increasingly gaining popularity and is potentially useful for the treatment of various bone and cartilage diseases. Intensive efforts have been made by researchers to improve the viability and functionality of seeding cells of engineered constructs that are implanted into damaged cartilage. Here, we designed an integrative system combining gene engineering and the controlled-release concept to solve the problems of both seeding cell viability and functionality through precisely regulating the anti-apoptotic gene bcl-2 in the short-term and the chondrogenic master regulator Sox9 in the long-term. Both in vitro and in vivo experiments demonstrated that our system enhances the cell viability and chondrogenic effects of the engineered scaffold after introduction of the system while restricting anti-apoptotic gene expression to only the early stage, thereby preventing potential oncogenic and overdose effects. Our system was designed to be modular and can also be readily adapted to other tissue engineering applications with minor modification.

Temporal Regulation of the Bacillus subtilis Acetylome and Evidence for a Role of MreB Acetylation in Cell Wall Growth

PubMed Central

Carabetta, Valerie J.; Greco, Todd M.; Tanner, Andrew W.

2016-01-01

ABSTRACT Nε-Lysine acetylation has been recognized as a ubiquitous regulatory posttranslational modification that influences a variety of important biological processes in eukaryotic cells. Recently, it has been realized that acetylation is also prevalent in bacteria. Bacteria contain hundreds of acetylated proteins, with functions affecting diverse cellular pathways. Still, little is known about the regulation or biological relevance of nearly all of these modifications. Here we characterize the cellular growth-associated regulation of the Bacillus subtilis acetylome. Using acetylation enrichment and quantitative mass spectrometry, we investigate the logarithmic and stationary growth phases, identifying over 2,300 unique acetylation sites on proteins that function in essential cellular pathways. We determine an acetylation motif, EK(ac)(D/Y/E), which resembles the eukaryotic mitochondrial acetylation signature, and a distinct stationary-phase-enriched motif. By comparing the changes in acetylation with protein abundances, we discover a subset of critical acetylation events that are temporally regulated during cell growth. We functionally characterize the stationary-phase-enriched acetylation on the essential shape-determining protein MreB. Using bioinformatics, mutational analysis, and fluorescence microscopy, we define a potential role for the temporal acetylation of MreB in restricting cell wall growth and cell diameter. IMPORTANCE The past decade highlighted Nε-lysine acetylation as a prevalent posttranslational modification in bacteria. However, knowledge regarding the physiological importance and temporal regulation of acetylation has remained limited. To uncover potential regulatory roles for acetylation, we analyzed how acetylation patterns and abundances change between growth phases in B. subtilis. To demonstrate that the identification of cell growth-dependent modifications can point to critical regulatory acetylation events, we further characterized MreB, the cell shape-determining protein. Our findings led us to propose a role for MreB acetylation in controlling cell width by restricting cell wall growth. PMID:27376153

Temporal Regulation of the Bacillus subtilis Acetylome and Evidence for a Role of MreB Acetylation in Cell Wall Growth.

PubMed

Carabetta, Valerie J; Greco, Todd M; Tanner, Andrew W; Cristea, Ileana M; Dubnau, David

2016-05-01

N ε -Lysine acetylation has been recognized as a ubiquitous regulatory posttranslational modification that influences a variety of important biological processes in eukaryotic cells. Recently, it has been realized that acetylation is also prevalent in bacteria. Bacteria contain hundreds of acetylated proteins, with functions affecting diverse cellular pathways. Still, little is known about the regulation or biological relevance of nearly all of these modifications. Here we characterize the cellular growth-associated regulation of the Bacillus subtilis acetylome. Using acetylation enrichment and quantitative mass spectrometry, we investigate the logarithmic and stationary growth phases, identifying over 2,300 unique acetylation sites on proteins that function in essential cellular pathways. We determine an acetylation motif, EK(ac)(D/Y/E), which resembles the eukaryotic mitochondrial acetylation signature, and a distinct stationary-phase-enriched motif. By comparing the changes in acetylation with protein abundances, we discover a subset of critical acetylation events that are temporally regulated during cell growth. We functionally characterize the stationary-phase-enriched acetylation on the essential shape-determining protein MreB. Using bioinformatics, mutational analysis, and fluorescence microscopy, we define a potential role for the temporal acetylation of MreB in restricting cell wall growth and cell diameter. The past decade highlighted N ε -lysine acetylation as a prevalent posttranslational modification in bacteria. However, knowledge regarding the physiological importance and temporal regulation of acetylation has remained limited. To uncover potential regulatory roles for acetylation, we analyzed how acetylation patterns and abundances change between growth phases in B. subtilis . To demonstrate that the identification of cell growth-dependent modifications can point to critical regulatory acetylation events, we further characterized MreB, the cell shape-determining protein. Our findings led us to propose a role for MreB acetylation in controlling cell width by restricting cell wall growth.

48 CFR 342.7102 - Contract modifications.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Contract modifications. 342.7102 Section 342.7102 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES CONTRACT MANAGEMENT CONTRACT ADMINISTRATION Administrative Actions for Cost Overruns 342.7102 Contract modifications...

48 CFR 342.7102 - Contract modifications.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Contract modifications. 342.7102 Section 342.7102 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES CONTRACT MANAGEMENT CONTRACT ADMINISTRATION Administrative Actions for Cost Overruns 342.7102 Contract modifications...

Behavior of restriction-modification systems as selfish mobile elements and their impact on genome evolution.

PubMed

Kobayashi, I

2001-09-15

Restriction-modification (RM) systems are composed of genes that encode a restriction enzyme and a modification methylase. RM systems sometimes behave as discrete units of life, like viruses and transposons. RM complexes attack invading DNA that has not been properly modified and thus may serve as a tool of defense for bacterial cells. However, any threat to their maintenance, such as a challenge by a competing genetic element (an incompatible plasmid or an allelic homologous stretch of DNA, for example) can lead to cell death through restriction breakage in the genome. This post-segregational or post-disturbance cell killing may provide the RM complexes (and any DNA linked with them) with a competitive advantage. There is evidence that they have undergone extensive horizontal transfer between genomes, as inferred from their sequence homology, codon usage bias and GC content difference. They are often linked with mobile genetic elements such as plasmids, viruses, transposons and integrons. The comparison of closely related bacterial genomes also suggests that, at times, RM genes themselves behave as mobile elements and cause genome rearrangements. Indeed some bacterial genomes that survived post-disturbance attack by an RM gene complex in the laboratory have experienced genome rearrangements. The avoidance of some restriction sites by bacterial genomes may result from selection by past restriction attacks. Both bacteriophages and bacteria also appear to use homologous recombination to cope with the selfish behavior of RM systems. RM systems compete with each other in several ways. One is competition for recognition sequences in post-segregational killing. Another is super-infection exclusion, that is, the killing of the cell carrying an RM system when it is infected with another RM system of the same regulatory specificity but of a different sequence specificity. The capacity of RM systems to act as selfish, mobile genetic elements may underlie the structure and function of RM enzymes.

Computation of output feedback gains for linear stochastic systems using the Zangnill-Powell Method

NASA Technical Reports Server (NTRS)

Kaufman, H.

1975-01-01

Because conventional optimal linear regulator theory results in a controller which requires the capability of measuring and/or estimating the entire state vector, it is of interest to consider procedures for computing controls which are restricted to be linear feedback functions of a lower dimensional output vector and which take into account the presence of measurement noise and process uncertainty. To this effect a stochastic linear model has been developed that accounts for process parameter and initial uncertainty, measurement noise, and a restricted number of measurable outputs. Optimization with respect to the corresponding output feedback gains was then performed for both finite and infinite time performance indices without gradient computation by using Zangwill's modification of a procedure originally proposed by Powell. Results using a seventh order process show the proposed procedures to be very effective.

48 CFR 225.7012 - Restriction on supercomputers.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Restriction on supercomputers. 225.7012 Section 225.7012 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS... supercomputers. ...

48 CFR 225.7012 - Restriction on supercomputers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Restriction on supercomputers. 225.7012 Section 225.7012 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS... supercomputers. ...

48 CFR 225.7012 - Restriction on supercomputers.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Restriction on supercomputers. 225.7012 Section 225.7012 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS... supercomputers. ...

48 CFR 225.7012 - Restriction on supercomputers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Restriction on supercomputers. 225.7012 Section 225.7012 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS... supercomputers. ...

48 CFR 225.7012 - Restriction on supercomputers.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Restriction on supercomputers. 225.7012 Section 225.7012 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS... supercomputers. ...

Comparative Genomics Reveals the Diversity of Restriction-Modification Systems and DNA Methylation Sites in Listeria monocytogenes.

PubMed

Chen, Poyin; den Bakker, Henk C; Korlach, Jonas; Kong, Nguyet; Storey, Dylan B; Paxinos, Ellen E; Ashby, Meredith; Clark, Tyson; Luong, Khai; Wiedmann, Martin; Weimer, Bart C

2017-02-01

Listeria monocytogenes is a bacterial pathogen that is found in a wide variety of anthropogenic and natural environments. Genome sequencing technologies are rapidly becoming a powerful tool in facilitating our understanding of how genotype, classification phenotypes, and virulence phenotypes interact to predict the health risks of individual bacterial isolates. Currently, 57 closed L. monocytogenes genomes are publicly available, representing three of the four phylogenetic lineages, and they suggest that L. monocytogenes has high genomic synteny. This study contributes an additional 15 closed L. monocytogenes genomes that were used to determine the associations between the genome and methylome with host invasion magnitude. In contrast to previous findings, large chromosomal inversions and rearrangements were detected in five isolates at the chromosome terminus and within rRNA genes, including a previously undescribed inversion within rRNA-encoding regions. Each isolate's epigenome contained highly diverse methyltransferase recognition sites, even within the same serotype and methylation pattern. Eleven strains contained a single chromosomally encoded methyltransferase, one strain contained two methylation systems (one system on a plasmid), and three strains exhibited no methylation, despite the occurrence of methyltransferase genes. In three isolates a new, unknown DNA modification was observed in addition to diverse methylation patterns, accompanied by a novel methylation system. Neither chromosome rearrangement nor strain-specific patterns of epigenome modification observed within virulence genes were correlated with serotype designation, clonal complex, or in vitro infectivity. These data suggest that genome diversity is larger than previously considered in L. monocytogenes and that as more genomes are sequenced, additional structure and methylation novelty will be observed in this organism. Listeria monocytogenes is the causative agent of listeriosis, a disease which manifests as gastroenteritis, meningoencephalitis, and abortion. Among Salmonella, Escherichia coli, Campylobacter, and Listeria-causing the most prevalent foodborne illnesses-infection by L. monocytogenes carries the highest mortality rate. The ability of L. monocytogenes to regulate its response to various harsh environments enables its persistence and transmission. Small-scale comparisons of L. monocytogenes focusing solely on genome contents reveal a highly syntenic genome yet fail to address the observed diversity in phenotypic regulation. This study provides a large-scale comparison of 302 L. monocytogenes isolates, revealing the importance of the epigenome and restriction-modification systems as major determinants of L. monocytogenes phylogenetic grouping and subsequent phenotypic expression. Further examination of virulence genes of select outbreak strains reveals an unprecedented diversity in methylation statuses despite high degrees of genome conservation. Copyright © 2017 American Society for Microbiology.

Role of transcriptional regulation in the evolution of plant phenotype: A dynamic systems approach.

PubMed

Rodríguez-Mega, Emiliano; Piñeyro-Nelson, Alma; Gutierrez, Crisanto; García-Ponce, Berenice; Sánchez, María De La Paz; Zluhan-Martínez, Estephania; Álvarez-Buylla, Elena R; Garay-Arroyo, Adriana

2015-03-02

A growing body of evidence suggests that alterations in transcriptional regulation of genes involved in modulating development are an important part of phenotypic evolution, and this can be documented among species and within populations. While the effects of differential transcriptional regulation in organismal development have been preferentially studied in animal systems, this phenomenon has also been addressed in plants. In this review, we summarize evidence for cis-regulatory mutations, trans-regulatory changes and epigenetic modifications as molecular events underlying important phenotypic alterations, and thus shaping the evolution of plant development. We postulate that a mechanistic understanding of why such molecular alterations have a key role in development, morphology and evolution will have to rely on dynamic models of complex regulatory networks that consider the concerted action of genetic and nongenetic components, and that also incorporate the restrictions underlying the genotype to phenotype mapping process. Developmental Dynamics, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

48 CFR 225.7003 - Restrictions on acquisition of specialty metals.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Restrictions on acquisition of specialty metals. 225.7003 Section 225.7003 Federal Acquisition Regulations System DEFENSE... Restrictions on acquisition of specialty metals. ...

48 CFR 225.7003 - Restrictions on acquisition of specialty metals.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Restrictions on acquisition of specialty metals. 225.7003 Section 225.7003 Federal Acquisition Regulations System DEFENSE... Restrictions on acquisition of specialty metals. ...

48 CFR 1403.570 - Restrictions on contractor advertising.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Restrictions on contractor advertising. 1403.570 Section 1403.570 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... 1403.570 Restrictions on contractor advertising. ...

48 CFR 1403.570 - Restrictions on contractor advertising.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Restrictions on contractor advertising. 1403.570 Section 1403.570 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... 1403.570 Restrictions on contractor advertising. ...

48 CFR 1403.570 - Restrictions on contractor advertising.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Restrictions on contractor advertising. 1403.570 Section 1403.570 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... 1403.570 Restrictions on contractor advertising. ...

48 CFR 1403.570 - Restrictions on contractor advertising.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Restrictions on contractor advertising. 1403.570 Section 1403.570 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... 1403.570 Restrictions on contractor advertising. ...

End-to-end system test for solid-state microdosemeters.

PubMed

Pisacane, V L; Dolecek, Q E; Malak, H; Dicello, J F

2010-08-01

The gold standard in microdosemeters has been the tissue equivalent proportional counter (TEPC) that utilises a gas cavity. An alternative is the solid-state microdosemeter that replaces the gas with a condensed phase (silicon) detector with microscopic sensitive volumes. Calibrations of gas and solid-state microdosemeters are generally carried out using radiation sources built into the detector that impose restrictions on their handling, transportation and licensing in accordance with the regulations from international, national and local nuclear regulatory bodies. Here a novel method is presented for carrying out a calibration and end-to-end system test of a microdosemeter using low-energy photons as the initiating energy source, thus obviating the need for a regulated ionising radiation source. This technique may be utilised to calibrate both a solid-state microdosemeter and, with modification, a TEPC with the higher average ionisation energy of a gas.

R Factor-Controlled Restriction and Modification of Deoxyribonucleic Acid: Restriction Mutants

PubMed Central

Yoshimori, Robert; Roulland-Dussoix, Daisy; Boyer, Herbert W.

1972-01-01

Restriction mutants of two different R factor-controlled host specificities (RI and RII) were isolated. All of the restriction mutants examined had a normal modification phenotype. No complementation was observed between the RI and RII host specificities. It is concluded that for each host specificity no protein subunit is shared by the restriction endonuclease and modification methylase. PMID:4565538

REBASE--a database for DNA restriction and modification: enzymes, genes and genomes.

PubMed

Roberts, Richard J; Vincze, Tamas; Posfai, Janos; Macelis, Dana

2015-01-01

REBASE is a comprehensive and fully curated database of information about the components of restriction-modification (RM) systems. It contains fully referenced information about recognition and cleavage sites for both restriction enzymes and methyltransferases as well as commercial availability, methylation sensitivity, crystal and sequence data. All genomes that are completely sequenced are analyzed for RM system components, and with the advent of PacBio sequencing, the recognition sequences of DNA methyltransferases (MTases) are appearing rapidly. Thus, Type I and Type III systems can now be characterized in terms of recognition specificity merely by DNA sequencing. The contents of REBASE may be browsed from the web http://rebase.neb.com and selected compilations can be downloaded by FTP (ftp.neb.com). Monthly updates are also available via email. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

48 CFR 422.404-6 - Modifications of wage determinations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Modifications of wage determinations. 422.404-6 Section 422.404-6 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE... Involving Construction 422.404-6 Modifications of wage determinations. HCA's are authorized to request...

48 CFR 622.404-6 - Modifications of wage determinations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Modifications of wage determinations. 622.404-6 Section 622.404-6 Federal Acquisition Regulations System DEPARTMENT OF STATE... Involving Construction 622.404-6 Modifications of wage determinations. The cognizant contracting activity is...

48 CFR 1422.404-6 - Modifications of wage determinations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Modifications of wage determinations. 1422.404-6 Section 1422.404-6 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... Involving Construction 1422.404-6 Modifications of wage determinations. The HCA is authorized to request an...

48 CFR 225.7015 - Restriction on overseas architect-engineer services.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Restriction on overseas architect-engineer services. 225.7015 Section 225.7015 Federal Acquisition Regulations System DEFENSE... on overseas architect-engineer services. For restriction on award of architect-engineer contracts to...

48 CFR 225.7015 - Restriction on overseas architect-engineer services.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Restriction on overseas architect-engineer services. 225.7015 Section 225.7015 Federal Acquisition Regulations System DEFENSE... on overseas architect-engineer services. For restriction on award of architect-engineer contracts to...

48 CFR 225.7015 - Restriction on overseas architect-engineer services.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Restriction on overseas architect-engineer services. 225.7015 Section 225.7015 Federal Acquisition Regulations System DEFENSE... on overseas architect-engineer services. For restriction on award of architect-engineer contracts to...

48 CFR 225.7015 - Restriction on overseas architect-engineer services.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Restriction on overseas architect-engineer services. 225.7015 Section 225.7015 Federal Acquisition Regulations System DEFENSE... on overseas architect-engineer services. For restriction on award of architect-engineer contracts to...

48 CFR 225.7015 - Restriction on overseas architect-engineer services.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Restriction on overseas architect-engineer services. 225.7015 Section 225.7015 Federal Acquisition Regulations System DEFENSE... on overseas architect-engineer services. For restriction on award of architect-engineer contracts to...

48 CFR 232.703-70 - Military construction appropriations act restriction.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Military construction appropriations act restriction. 232.703-70 Section 232.703-70 Federal Acquisition Regulations System DEFENSE... Contract Funding 232.703-70 Military construction appropriations act restriction. Annual military...

Host Specificity of Salmonella typhimurium Deoxyribonucleic Acid Restriction and Modification

PubMed Central

Slocum, Harvey; Boyer, Herbert W.

1973-01-01

The restriction and modification genes of Salmonella typhimurium which lie near the thr locus were transferred to a restrictionless mutant of Escherichia coli. These genes were found to be allelic to the E. coli K, B, and A restriction and modification genes. E. coli recombinants with the restriction and modification host specificity of S. typhimurium restricted phage λ that had been modified by each of the seven known host specificities of E. coli at efficiency of plating levels of about 10−2. Phage λ modified with the S. typhimurium host specificity was restricted by six of the seven E. coli host specificities but not by the RII (fi− R-factor controlled) host specificity. It is proposed that the restriction and modification enzymes of this S. typhimurium host specificity have two substrates, one of which is a substrate for the RII host specificity enzymes. PMID:4570605

SAMHD1 host restriction factor: a link with innate immune sensing of retrovirus infection.

PubMed

Sze, Alexandre; Olagnier, David; Lin, Rongtuan; van Grevenynghe, Julien; Hiscott, John

2013-12-13

SAMHD1 [sterile alpha motif and histidine-aspartic domain (HD) containing protein 1] is the most recent addition to a unique group of host restriction factors that limit retroviral replication at distinct stages of the viral life cycle. SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase that degrades the intracellular pool of deoxynucleoside triphosphates available during early reverse transcription. SAMHD1 activity is blocked by the Vpx accessory function present in human immunodeficiency virus type 2 and SIVsm. Mutations in SAMHD1 are associated with the autoimmune disorder Aicardi-Goutières syndrome, thus emphasizing its role in regulation of the immune response. SAMHD1 antiretroviral activity is modulated by post-translational modifications, cell-cycle-dependent functions and cytokine-mediated changes. Innate receptors that sense retroviral DNA intermediates are the focus of intense study, and recent studies have established a link among SAMHD1 restriction, innate sensing of DNA and protective immune responses. Cell-cycle-dependent regulation of SAMHD1 by phosphorylation and the increasingly broad range of viruses inhibited by SAMHD1 further emphasize the importance of these mechanisms of host restriction. This review highlights current knowledge regarding SAMHD1 regulation and its impact on innate immune signaling and retroviral restriction. © 2013.

75 FR 26025 - Regulation of Fuels and Fuel Additives: Modifications to Renewable Fuel Standard Program

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-10

... information whose disclosure is restricted by statute. Certain other material, such as copyrighted material, will be publicly available only in hard copy. Publicly available docket materials are available either... materials, as provided in 40 CFR part 2. IV. Renewable Fuel Standard (RFS2) Program Amendments EPA is taking...

Glucosamine Treatment-mediated O-GlcNAc Modification of Paxillin Depends on Adhesion State of Rat Insulinoma INS-1 Cells*

PubMed Central

Kwak, Tae Kyoung; Kim, Hyeonjung; Jung, Oisun; Lee, Sin-Ae; Kang, Minkyung; Kim, Hyun Jeong; Park, Ji-Min; Kim, Sung-Hoon; Lee, Jung Weon

2010-01-01

Protein-protein interactions and/or signaling activities at focal adhesions, where integrin-mediated adhesion to extracellular matrix occurs, are critical for the regulation of adhesion-dependent cellular functions. Although the phosphorylation and activities of focal adhesion molecules have been intensively studied, the effects of the O-GlcNAc modification of their Ser/Thr residues on cellular functions have been largely unexplored. We investigated the effects of O-GlcNAc modification on actin reorganization and morphology of rat insulinoma INS-1 cells after glucosamine (GlcN) treatment. We found that paxillin, a key adaptor molecule in focal adhesions, could be modified by O-GlcNAc in INS-1 cells treated with GlcN and in pancreatic islets from mice treated with streptozotocin. Ser-84/85 in human paxillin appeared to be modified by O-GlcNAc, which was inversely correlated to Ser-85 phosphorylation (Ser-83 in rat paxillin). Integrin-mediated adhesion signaling inhibited the GlcN treatment-enhanced O-GlcNAc modification of paxillin. Adherent INS-1 cells treated with GlcN showed restricted protrusions, whereas untreated cells showed active protrusions for multiple-elongated morphologies. Upon GlcN treatment, expression of a triple mutation (S83A/S84A/S85A) resulted in no further restriction of protrusions. Together these observations suggest that murine pancreatic β cells may have restricted actin organization upon GlcN treatment by virtue of the O-GlcNAc modification of paxillin, which can be antagonized by a persistent cell adhesion process. PMID:20829364

Gene expression in spider appendages reveals reversal of exd/hth spatial specificity, altered leg gap gene dynamics, and suggests divergent distal morphogen signaling.

PubMed

Prpic, Nikola-Michael; Janssen, Ralf; Wigand, Barbara; Klingler, Martin; Damen, Wim G M

2003-12-01

Leg development in Drosophila has been studied in much detail. However, Drosophila limbs form in the larva as imaginal discs and not during embryogenesis as in most other arthropods. Here, we analyze appendage genes in the spider Cupiennius salei and the beetle Tribolium castaneum. Differences in decapentaplegic (dpp) expression suggest a different mode of distal morphogen signaling suitable for the specific geometry of growing limb buds. Also, expression of the proximal genes homothorax (hth) and extradenticle (exd) is significantly altered: in the spider, exd is restricted to the proximal leg and hth expression extends distally, while in insects, exd is expressed in the entire leg and hth is restricted to proximal parts. This reversal of spatial specificity demonstrates an evolutionary shift, which is nevertheless compatible with a conserved role of this gene pair as instructor of proximal fate. Different expression dynamics of dachshund and Distal-less point to modifications in the regulation of the leg gap gene system. We comment on the significance of this finding for attempts to homologize leg segments in different arthropod classes. Comparison of the expression profiles of H15 and optomotor-blind to the Drosophila patterns suggests modifications also in the dorsal-ventral patterning system of the legs. Together, our results suggest alterations in many components of the leg developmental system, namely proximal-distal and dorsal-ventral patterning, and leg segmentation. Thus, the leg developmental system exhibits a propensity to evolutionary change, which probably forms the basis for the impressive diversity of arthropod leg morphologies.

Addendum to the Closure Report for Corrective Action Unit 262: Area 25 Septic Systems and Underground Discharge Point, Nevada Test Site, Nevada

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

Lynn Kidman

2008-10-01

This document constitutes an addendum to the July 2003, Closure Report for Corrective Action Unit 262: Area 25 Septic Systems and Underground Discharge Point as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. The approval of the UR Modification document constituted approval of each of the recommended UR modifications.

Characterization of a restriction-modification system of the thermotolerant methylotroph Bacillus methanolicus.

PubMed Central

Cue, D; Lam, H; Hanson, R S; Flickinger, M C

1996-01-01

We report the isolation of a restriction endonuclease, BmeTI, an isoschizomer of BclI, that recognizes the DNA sequence 5' TGATCA 3'. We also report that BmeTI sites are modified to TGm6ATCA. These findings provide the basis for devising strategies to prevent BmeTI restriction of any DNA introduced into Bacillus methanolicus. PMID:8975604

48 CFR 52.225-13 - Restrictions on Certain Foreign Purchases.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Restrictions on Certain Foreign Purchases. 52.225-13 Section 52.225-13 Federal Acquisition Regulations System FEDERAL ACQUISITION... Clauses 52.225-13 Restrictions on Certain Foreign Purchases. As prescribed in 25.1103(a), insert the...

Function and regulation of clustered regularly interspaced short palindromic repeats (CRISPR) / CRISPR associated (Cas) systems.

PubMed

Richter, Corinna; Chang, James T; Fineran, Peter C

2012-10-19

Phages are the most abundant biological entities on earth and pose a constant challenge to their bacterial hosts. Thus, bacteria have evolved numerous 'innate' mechanisms of defense against phage, such as abortive infection or restriction/modification systems. In contrast, the clustered regularly interspaced short palindromic repeats (CRISPR) systems provide acquired, yet heritable, sequence-specific 'adaptive' immunity against phage and other horizontally-acquired elements, such as plasmids. Resistance is acquired following viral infection or plasmid uptake when a short sequence of the foreign genome is added to the CRISPR array. CRISPRs are then transcribed and processed, generally by CRISPR associated (Cas) proteins, into short interfering RNAs (crRNAs), which form part of a ribonucleoprotein complex. This complex guides the crRNA to the complementary invading nucleic acid and targets this for degradation. Recently, there have been rapid advances in our understanding of CRISPR/Cas systems. In this review, we will present the current model(s) of the molecular events involved in both the acquisition of immunity and interference stages and will also address recent progress in our knowledge of the regulation of CRISPR/Cas systems.

48 CFR 227.7107-3 - Approval of restricted designs.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Approval of restricted designs. 227.7107-3 Section 227.7107-3 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Technical Data 227.7107-3 Approval of...

48 CFR 227.7107-3 - Approval of restricted designs.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Approval of restricted designs. 227.7107-3 Section 227.7107-3 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Technical Data 227.7107-3 Approval of...

48 CFR 252.227-7024 - Notice and approval of restricted designs.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Notice and approval of restricted designs. 252.227-7024 Section 252.227-7024 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions And Clauses...

48 CFR 252.227-7024 - Notice and approval of restricted designs.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Notice and approval of restricted designs. 252.227-7024 Section 252.227-7024 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions And Clauses...

CRISPR-Cas and Restriction-Modification Act Additively against Conjugative Antibiotic Resistance Plasmid Transfer in Enterococcus faecalis.

PubMed

Price, Valerie J; Huo, Wenwen; Sharifi, Ardalan; Palmer, Kelli L

2016-01-01

Enterococcus faecalis is an opportunistic pathogen and a leading cause of nosocomial infections. Conjugative pheromone-responsive plasmids are narrow-host-range mobile genetic elements (MGEs) that are rapid disseminators of antibiotic resistance in the faecalis species. Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas and restriction-modification confer acquired and innate immunity, respectively, against MGE acquisition in bacteria. Most multidrug-resistant E. faecalis isolates lack CRISPR-Cas and possess an orphan locus lacking cas genes, CRISPR2, that is of unknown function. Little is known about restriction-modification defense in E. faecalis. Here, we explore the hypothesis that multidrug-resistant E. faecalis strains are immunocompromised. We assessed MGE acquisition by E. faecalis T11, a strain closely related to the multidrug-resistant hospital isolate V583 but which lacks the ~620 kb of horizontally acquired genome content that characterizes V583. T11 possesses the E. faecalis CRISPR3-cas locus and a predicted restriction-modification system, neither of which occurs in V583. We demonstrate that CRISPR-Cas and restriction-modification together confer a 4-log reduction in acquisition of the pheromone-responsive plasmid pAM714 in biofilm matings. Additionally, we show that the orphan CRISPR2 locus is functional for genome defense against another pheromone-responsive plasmid, pCF10, only in the presence of cas9 derived from the E. faecalis CRISPR1-cas locus, which most multidrug-resistant E. faecalis isolates lack. Overall, our work demonstrated that the loss of only two loci led to a dramatic reduction in genome defense against a clinically relevant MGE, highlighting the critical importance of the E. faecalis accessory genome in modulating horizontal gene transfer. Our results rationalize the development of antimicrobial strategies that capitalize upon the immunocompromised status of multidrug-resistant E. faecalis. IMPORTANCE Enterococcus faecalis is a bacterium that normally inhabits the gastrointestinal tracts of humans and other animals. Although these bacteria are members of our native gut flora, they can cause life-threatening infections in hospitalized patients. Antibiotic resistance genes appear to be readily shared among high-risk E. faecalis strains, and multidrug resistance in these bacteria limits treatment options for infections. Here, we find that CRISPR-Cas and restriction-modification systems, which function as adaptive and innate immune systems in bacteria, significantly impact the spread of antibiotic resistance genes in E. faecalis populations. The loss of these systems in high-risk E. faecalis suggests that they are immunocompromised, a tradeoff that allows them to readily acquire new genes and adapt to new antibiotics.

Modification of P-selectin glycoprotein ligand-1 with a natural killer cell-restricted sulfated lactosamine creates an alternate ligand for L-selectin

PubMed Central

André, Pascale; Spertini, Olivier; Guia, Sophie; Rihet, Pascal; Dignat-George, Françoise; Brailly, Hervé; Sampol, José; Anderson, Paul J.; Vivier, Eric

2000-01-01

Natural killer (NK) cells are components of the innate immune system that can recognize and kill virally infected cells, tumor cells, and allogeneic cells without prior sensitization. NK cells also elaborate cytokines (e.g., interferon-γ and tumor necrosis factor-α) and chemokines (e.g., macrophage inflammatory protein-1α) that promote the acquisition of antigen-specific immunity. NK cell differentiation is accompanied by the cell surface expression of a mucin-like glycoprotein bearing an NK cell-restricted keratan sulfate-related lactosamine carbohydrate, the PEN5 epitope. Here, we report that PEN5 is a post-translational modification of P-selectin glycoprotein ligand-1 (PSGL-1). The PEN5 epitope creates on PSGL-1 a unique binding site for L-selectin, which is independent of PSGL-1 tyrosine sulfation. On the surface of NK cells, the expression of PEN5 is coordinated with the disappearance of L-selectin and the up-regulation of Killer cell Ig-like Receptors (KIR). These results indicate that NK cell differentiation is accompanied by the acquisition of a unique carbohydrate, PEN5, that can serve as part of a combination code to deliver KIR+ NK cells to specific tissues. PMID:10725346

Glycation inhibitors extend yeast chronological lifespan by reducing advanced glycation end products and by back regulation of proteins involved in mitochondrial respiration.

PubMed

Kazi, Rubina S; Banarjee, Reema M; Deshmukh, Arati B; Patil, Gouri V; Jagadeeshaprasad, Mashanipalya G; Kulkarni, Mahesh J

2017-03-06

Advanced Glycation End products (AGEs) are implicated in aging process. Thus, reducing AGEs by using glycation inhibitors may help in attenuating the aging process. In this study using Saccharomyces cerevisiae yeast system, we show that Aminoguanidine (AMG), a well-known glycation inhibitor, decreases the AGE modification of proteins in non-calorie restriction (NR) (2% glucose) and extends chronological lifespan (CLS) similar to that of calorie restriction (CR) condition (0.5% glucose). Proteomic analysis revealed that AMG back regulates the expression of differentially expressed proteins especially those involved in mitochondrial respiration in NR condition, suggesting that it switches metabolism from fermentation to respiration, mimicking CR. AMG induced back regulation of differentially expressed proteins could be possibly due to its chemical effect or indirectly by glycation inhibition. To delineate this, Metformin (MET), a structural analog of AMG and a mild glycation inhibitor and Hydralazine (HYD), another potent glycation inhibitor but not structural analog of AMG were used. HYD was more effective than MET in mimicking AMG suggesting that glycation inhibition was responsible for restoration of differentially expressed proteins. Thus glycation inhibitors particularly AMG, HYD and MET extend yeast CLS by reducing AGEs, modulating the expression of proteins involved in mitochondrial respiration and possibly by scavenging glucose. This study reports the role of glycation in aging process. In the non-caloric restriction condition, carbohydrates such as glucose promote protein glycation and reduce CLS. While, the inhibitors of glycation such as AMG, HYD, MET mimic the caloric restriction condition by back regulating deregulated proteins involved in mitochondrial respiration which could facilitate shift of metabolism from fermentation to respiration and extend yeast CLS. These findings suggest that glycation inhibitors can be potential molecules that can be used in management of aging. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of a restriction modification system from the commensal Escherichia coli strain A0 34/86 (O83:K24:H31).

PubMed

Weiserová, Marie; Ryu, Junichi

2008-06-27

Type I restriction-modification (R-M) systems are the most complex restriction enzymes discovered to date. Recent years have witnessed a renaissance of interest in R-M enzymes Type I. The massive ongoing sequencing programmes leading to discovery of, so far, more than 1 000 putative enzymes in a broad range of microorganisms including pathogenic bacteria, revealed that these enzymes are widely represented in nature. The aim of this study was characterisation of a putative R-M system EcoA0ORF42P identified in the commensal Escherichia coli A0 34/86 (O83: K24: H31) strain, which is efficiently used at Czech paediatric clinics for prophylaxis and treatment of nosocomial infections and diarrhoea of preterm and newborn infants. We have characterised a restriction-modification system EcoA0ORF42P of the commensal Escherichia coli strain A0 34/86 (O83: K24: H31). This system, designated as EcoAO83I, is a new functional member of the Type IB family, whose specificity differs from those of known Type IB enzymes, as was demonstrated by an immunological cross-reactivity and a complementation assay. Using the plasmid transformation method and the RM search computer program, we identified the DNA recognition sequence of the EcoAO83I as GGA(8N)ATGC. In consistence with the amino acids alignment data, the 3' TRD component of the recognition sequence is identical to the sequence recognized by the EcoEI enzyme. The A-T (modified adenine) distance is identical to that in the EcoAI and EcoEI recognition sites, which also indicates that this system is a Type IB member. Interestingly, the recognition sequence we determined here is identical to the previously reported prototype sequence for Eco377I and its isoschizomers. Putative restriction-modification system EcoA0ORF42P in the commensal Escherichia coli strain A0 34/86 (O83: K24: H31) was found to be a member of the Type IB family and was designated as EcoAO83I. Combination of the classical biochemical and bacterial genetics approaches with comparative genomics might contribute effectively to further classification of many other putative Type-I enzymes, especially in clinical samples.

REDOX REGULATION OF SIRT1 IN INFLAMMATION AND CELLULAR SENESCENCE

PubMed Central

Hwang, Jae-woong; Yao, Hongwei; Caito, Samuel; Sundar, Isaac K.; Rahman, Irfan

2013-01-01

Sirtuin1 (SIRT1) regulates inflammation, aging (lifespan and healthspan), calorie restriction/energetics, mitochondrial biogenesis, stress resistance, cellular senescence, endothelial functions, apoptosis/autophagy, and circadian rhythms through deacetylation of transcription factors and histones. SIRT1 level and activity are decreased in chronic inflammatory conditions and aging where oxidative stress occurs. SIRT1 is regulated by a NAD+-dependent DNA repair enzyme poly(ADP-ribose)-polymerase-1 (PARP-1), and subsequent NAD+ depletion by oxidative stresses may have consequent effects on inflammatory and stress responses as well as cellular senescence. SIRT1 has been shown to undergo covalent oxidative modifications by cigarette smoke-derived oxidants/aldehydes, leading to post-translational modifications, inactivation, and protein degradation. Furthermore, oxidant/carbonyl stress-mediated reduction of SIRT1 leads to the loss of its control on acetylation of target proteins including p53, RelA/p65 and FOXO3, thereby enhancing the inflammatory, pro-senescent and apoptotic responses, as well as endothelial dysfunction. In this review, the mechanisms of cigarette smoke/oxidant-mediated redox post-translational modifications of SIRT1 and its role in PARP1, NF-κB activation, FOXO3 and eNOS regulation, as well as chromatin remodeling/histone modifications during inflammaging are discussed. Furthermore, we also discussed various novel ways to activate SIRT1 either directly or indirectly, which may have therapeutic potential in attenuating inflammation and premature senescence involved in chronic lung diseases. PMID:23542362

48 CFR 225.7009 - Restriction on ball and roller bearings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Restriction on ball and roller bearings. 225.7009 Section 225.7009 Federal Acquisition Regulations System DEFENSE ACQUISITION... roller bearings. ...

Cloning of developmentally regulated flagellin genes from Caulobacter crescentus via immunoprecipitation of polyribosomes.

PubMed Central

Milhausen, M; Gill, P R; Parker, G; Agabian, N

1982-01-01

Immunoprecipitation of Caulobacter crescentus polyribosomes with antiflagellin antibody provided RNA for the synthesis of cDNA probes that were used to identify three specific EcoRI restriction fragments (6.8, 10, and 22 kilobases) in genomic digests of Caulobacter DNA. The RNA was present only in polyribosomes isolated from a time interval in the Caulobacter cell cycle that was coincident with flagellin polypeptide synthesis. The structural gene for Mr 27,500 flagellin polypeptide was assigned to a region of the 10-kilobase EcoRI restriction fragment by DNA sequence analysis. Analysis of mutants defective in motility further established a correlation between the Mr 27,500 flagellin gene and the flaE gene locus [Johnson, R. C. & Ely, B. (1979) J. Bacteriol. 137, 627-634]. The other EcoRI fragments that hybridize with the immunoprecipitated polyribosome-derived cDNA probe are also temporally regulated and have features that suggest they encode other polypeptides associated with the flagellum. Modifications were required to adapt the procedure of immunoprecipitation of polyribosomes for use with Caulobacter and should be applicable to the production of specific structural gene probes from other prokaryotic systems. Images PMID:6294658

48 CFR 225.7005 - Restriction on certain chemical weapons antidote.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Restriction on certain chemical weapons antidote. 225.7005 Section 225.7005 Federal Acquisition Regulations System DEFENSE... on certain chemical weapons antidote. ...

48 CFR 225.7005 - Restriction on certain chemical weapons antidote.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Restriction on certain chemical weapons antidote. 225.7005 Section 225.7005 Federal Acquisition Regulations System DEFENSE... on certain chemical weapons antidote. ...

48 CFR 225.7005 - Restriction on certain chemical weapons antidote.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Restriction on certain chemical weapons antidote. 225.7005 Section 225.7005 Federal Acquisition Regulations System DEFENSE... on certain chemical weapons antidote. ...

48 CFR 225.7005 - Restriction on certain chemical weapons antidote.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Restriction on certain chemical weapons antidote. 225.7005 Section 225.7005 Federal Acquisition Regulations System DEFENSE... on certain chemical weapons antidote. ...

48 CFR 225.7005 - Restriction on certain chemical weapons antidote.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Restriction on certain chemical weapons antidote. 225.7005 Section 225.7005 Federal Acquisition Regulations System DEFENSE... on certain chemical weapons antidote. ...

Comparative genome and methylome analysis reveals restriction/modification system diversity in the gut commensal Bifidobacterium breve

PubMed Central

Bottacini, Francesca; Morrissey, Ruth; Roberts, Richard John; James, Kieran; van Breen, Justin; Egan, Muireann; Lambert, Jolanda; van Limpt, Kees; Knol, Jan; Motherway, Mary O’Connell; van Sinderen, Douwe

2018-01-01

Abstract Bifidobacterium breve represents one of the most abundant bifidobacterial species in the gastro-intestinal tract of breast-fed infants, where their presence is believed to exert beneficial effects. In the present study whole genome sequencing, employing the PacBio Single Molecule, Real-Time (SMRT) sequencing platform, combined with comparative genome analysis allowed the most extensive genetic investigation of this taxon. Our findings demonstrate that genes encoding Restriction/Modification (R/M) systems constitute a substantial part of the B. breve variable gene content (or variome). Using the methylome data generated by SMRT sequencing, combined with targeted Illumina bisulfite sequencing (BS-seq) and comparative genome analysis, we were able to detect methylation recognition motifs and assign these to identified B. breve R/M systems, where in several cases such assignments were confirmed by restriction analysis. Furthermore, we show that R/M systems typically impose a very significant barrier to genetic accessibility of B. breve strains, and that cloning of a methyltransferase-encoding gene may overcome such a barrier, thus allowing future functional investigations of members of this species. PMID:29294107

Effect of site-specific modification on restriction endonucleases and DNA modification methyltransferases.

PubMed Central

McClelland, M; Nelson, M; Raschke, E

1994-01-01

Restriction endonucleases have site-specific interactions with DNA that can often be inhibited by site-specific DNA methylation and other site-specific DNA modifications. However, such inhibition cannot generally be predicted. The empirically acquired data on these effects are tabulated for over 320 restriction endonucleases. In addition, a table of known site-specific DNA modification methyltransferases and their specificities is presented along with EMBL database accession numbers for cloned genes. PMID:7937074

Genome-Nuclear Lamina Interactions Regulate Cardiac Stem Cell Lineage Restriction.

PubMed

Poleshko, Andrey; Shah, Parisha P; Gupta, Mudit; Babu, Apoorva; Morley, Michael P; Manderfield, Lauren J; Ifkovits, Jamie L; Calderon, Damelys; Aghajanian, Haig; Sierra-Pagán, Javier E; Sun, Zheng; Wang, Qiaohong; Li, Li; Dubois, Nicole C; Morrisey, Edward E; Lazar, Mitchell A; Smith, Cheryl L; Epstein, Jonathan A; Jain, Rajan

2017-10-19

Progenitor cells differentiate into specialized cell types through coordinated expression of lineage-specific genes and modification of complex chromatin configurations. We demonstrate that a histone deacetylase (Hdac3) organizes heterochromatin at the nuclear lamina during cardiac progenitor lineage restriction. Specification of cardiomyocytes is associated with reorganization of peripheral heterochromatin, and independent of deacetylase activity, Hdac3 tethers peripheral heterochromatin containing lineage-relevant genes to the nuclear lamina. Deletion of Hdac3 in cardiac progenitor cells releases genomic regions from the nuclear periphery, leading to precocious cardiac gene expression and differentiation into cardiomyocytes; in contrast, restricting Hdac3 to the nuclear periphery rescues myogenesis in progenitors otherwise lacking Hdac3. Our results suggest that availability of genomic regions for activation by lineage-specific factors is regulated in part through dynamic chromatin-nuclear lamina interactions and that competence of a progenitor cell to respond to differentiation signals may depend upon coordinated movement of responding gene loci away from the nuclear periphery. Copyright © 2017 Elsevier Inc. All rights reserved.

Behavior of restriction–modification systems as selfish mobile elements and their impact on genome evolution

PubMed Central

Kobayashi, Ichizo

2001-01-01

Restriction–modification (RM) systems are composed of genes that encode a restriction enzyme and a modification methylase. RM systems sometimes behave as discrete units of life, like viruses and transposons. RM complexes attack invading DNA that has not been properly modified and thus may serve as a tool of defense for bacterial cells. However, any threat to their maintenance, such as a challenge by a competing genetic element (an incompatible plasmid or an allelic homologous stretch of DNA, for example) can lead to cell death through restriction breakage in the genome. This post-segregational or post-disturbance cell killing may provide the RM complexes (and any DNA linked with them) with a competitive advantage. There is evidence that they have undergone extensive horizontal transfer between genomes, as inferred from their sequence homology, codon usage bias and GC content difference. They are often linked with mobile genetic elements such as plasmids, viruses, transposons and integrons. The comparison of closely related bacterial genomes also suggests that, at times, RM genes themselves behave as mobile elements and cause genome rearrangements. Indeed some bacterial genomes that survived post-disturbance attack by an RM gene complex in the laboratory have experienced genome rearrangements. The avoidance of some restriction sites by bacterial genomes may result from selection by past restriction attacks. Both bacteriophages and bacteria also appear to use homologous recombination to cope with the selfish behavior of RM systems. RM systems compete with each other in several ways. One is competition for recognition sequences in post-segregational killing. Another is super-infection exclusion, that is, the killing of the cell carrying an RM system when it is infected with another RM system of the same regulatory specificity but of a different sequence specificity. The capacity of RM systems to act as selfish, mobile genetic elements may underlie the structure and function of RM enzymes. PMID:11557807

48 CFR 225.7006 - Restriction on air circuit breakers for naval vessels.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Restriction on air circuit breakers for naval vessels. 225.7006 Section 225.7006 Federal Acquisition Regulations System DEFENSE... on air circuit breakers for naval vessels. ...

48 CFR 225.7006 - Restriction on air circuit breakers for naval vessels.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Restriction on air circuit breakers for naval vessels. 225.7006 Section 225.7006 Federal Acquisition Regulations System DEFENSE... on air circuit breakers for naval vessels. ...

48 CFR 225.7011 - Restriction on carbon, alloy, and armor steel plate.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Restriction on carbon, alloy, and armor steel plate. 225.7011 Section 225.7011 Federal Acquisition Regulations System DEFENSE... on carbon, alloy, and armor steel plate. ...

48 CFR 225.7011 - Restriction on carbon, alloy, and armor steel plate.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Restriction on carbon, alloy, and armor steel plate. 225.7011 Section 225.7011 Federal Acquisition Regulations System DEFENSE... on carbon, alloy, and armor steel plate. ...

48 CFR 225.7011 - Restriction on carbon, alloy, and armor steel plate.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Restriction on carbon, alloy, and armor steel plate. 225.7011 Section 225.7011 Federal Acquisition Regulations System DEFENSE... on carbon, alloy, and armor steel plate. ...

48 CFR 225.7011 - Restriction on carbon, alloy, and armor steel plate.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Restriction on carbon, alloy, and armor steel plate. 225.7011 Section 225.7011 Federal Acquisition Regulations System DEFENSE... on carbon, alloy, and armor steel plate. ...

48 CFR 225.7011 - Restriction on carbon, alloy, and armor steel plate.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Restriction on carbon, alloy, and armor steel plate. 225.7011 Section 225.7011 Federal Acquisition Regulations System DEFENSE... on carbon, alloy, and armor steel plate. ...

48 CFR 814.304 - Submission, modification, and withdrawal of bids.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Submission, modification, and withdrawal of bids. 814.304 Section 814.304 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Submission of Bids 814.304...

Function and Regulation of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) / CRISPR Associated (Cas) Systems

PubMed Central

Richter, Corinna; Chang, James T.; Fineran, Peter C.

2012-01-01

Phages are the most abundant biological entities on earth and pose a constant challenge to their bacterial hosts. Thus, bacteria have evolved numerous ‘innate’ mechanisms of defense against phage, such as abortive infection or restriction/modification systems. In contrast, the clustered regularly interspaced short palindromic repeats (CRISPR) systems provide acquired, yet heritable, sequence-specific ‘adaptive’ immunity against phage and other horizontally-acquired elements, such as plasmids. Resistance is acquired following viral infection or plasmid uptake when a short sequence of the foreign genome is added to the CRISPR array. CRISPRs are then transcribed and processed, generally by CRISPR associated (Cas) proteins, into short interfering RNAs (crRNAs), which form part of a ribonucleoprotein complex. This complex guides the crRNA to the complementary invading nucleic acid and targets this for degradation. Recently, there have been rapid advances in our understanding of CRISPR/Cas systems. In this review, we will present the current model(s) of the molecular events involved in both the acquisition of immunity and interference stages and will also address recent progress in our knowledge of the regulation of CRISPR/Cas systems. PMID:23202464

48 CFR 801.602-83 - Documents to submit for legal or technical review-contract modifications.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Documents to submit for legal or technical review-contract modifications. 801.602-83 Section 801.602-83 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL DEPARTMENT OF VETERANS AFFAIRS ACQUISITION...

48 CFR 801.602-83 - Documents to submit for legal or technical review-contract modifications.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Documents to submit for legal or technical review-contract modifications. 801.602-83 Section 801.602-83 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL DEPARTMENT OF VETERANS AFFAIRS ACQUISITION...

48 CFR 801.602-83 - Documents to submit for legal or technical review-contract modifications.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Documents to submit for legal or technical review-contract modifications. 801.602-83 Section 801.602-83 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL DEPARTMENT OF VETERANS AFFAIRS ACQUISITION...

48 CFR 801.602-83 - Documents to submit for legal or technical review-contract modifications.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Documents to submit for legal or technical review-contract modifications. 801.602-83 Section 801.602-83 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL DEPARTMENT OF VETERANS AFFAIRS ACQUISITION...

48 CFR 801.602-83 - Documents to submit for legal or technical review-contract modifications.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Documents to submit for legal or technical review-contract modifications. 801.602-83 Section 801.602-83 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL DEPARTMENT OF VETERANS AFFAIRS ACQUISITION...

KpnBI is the prototype of a new family (IE) of bacterial type I restriction-modification system

PubMed Central

Chin, V.; Valinluck, V.; Magaki, S.; Ryu, J.

2004-01-01

KpnBI is a restriction-modification (R-M) system recognized in the GM236 strain of Klebsiella pneumoniae. Here, the KpnBI modification genes were cloned into a plasmid using a modification expression screening method. The modification genes that consist of both hsdM (2631 bp) and hsdS (1344 bp) genes were identified on an 8.2 kb EcoRI chromosomal fragment. These two genes overlap by one base and share the same promoter located upstream of the hsdM gene. Using recently developed plasmid R-M tests and a computer program RM Search, the DNA recognition sequence for the KpnBI enzymes was identified as a new 8 nt sequence containing one degenerate base with a 6 nt spacer, CAAANNNNNNRTCA. From Dam methylation and HindIII sensitivity tests, the methylation loci were predicted to be the italicized third adenine in the 5′ specific region and the adenine opposite the italicized thymine in the 3′ specific region. Combined with previous sequence data for hsdR, we concluded that the KpnBI system is a typical type I R-M system. The deduced amino acid sequences of the three subunits of the KpnBI system show only limited homologies (25 to 33% identity) at best, to the four previously categorized type I families (IA, IB, IC, and ID). Furthermore, their identity scores to other uncharacterized putative genome type I sequences were 53% at maximum. Therefore, we propose that KpnBI is the prototype of a new ‘type IE’ family. PMID:15475385

N6-methyladenine: a conserved and dynamic DNA mark

PubMed Central

O’Brown, Zach Klapholz; Greer, Eric Lieberman

2017-01-01

Chromatin, consisting of deoxyribonucleic acid (DNA) wrapped around histone proteins, facilitates DNA compaction and allows identical DNA code to confer many different cellular phenotypes. This biological versatility is accomplished in large part by post-translational modifications to histones and chemical modifications to DNA. These modifications direct the cellular machinery to expand or compact specific chromatin regions, and mark regions of the DNA as important for cellular functions. While each of the four bases that make up DNA can be modified (Iyer et al. 2011), this chapter will focus on methylation of the 6th position on adenines (6mA), as this modification has been poorly characterized in recently evolved eukaryotes but shows promise as a new conserved layer of epigenetic regulation. 6mA was previously thought to be restricted to unicellular organisms, but recent work has revealed its presence in more recently evolved metazoa. Here, we will briefly describe the history of 6mA, examine its evolutionary conservation, and evaluate the current methods for detecting 6mA. We will discuss the enzymes that bind and regulate this mark and finally examine known and potential functions of 6mA in eukaryotes. PMID:27826841

Restriction-modification mediated barriers to exogenous DNA uptake and incorporation employed by Prevotella intermedia.

PubMed

Johnston, Christopher D; Skeete, Chelsey A; Fomenkov, Alexey; Roberts, Richard J; Rittling, Susan R

2017-01-01

Prevotella intermedia, a major periodontal pathogen, is increasingly implicated in human respiratory tract and cystic fibrosis lung infections. Nevertheless, the specific mechanisms employed by this pathogen remain only partially characterized and poorly understood, largely due to its total lack of genetic accessibility. Here, using Single Molecule, Real-Time (SMRT) genome and methylome sequencing, bisulfite sequencing, in addition to cloning and restriction analysis, we define the specific genetic barriers to exogenous DNA present in two of the most widespread laboratory strains, P. intermedia ATCC 25611 and P. intermedia Strain 17. We identified and characterized multiple restriction-modification (R-M) systems, some of which are considerably divergent between the two strains. We propose that these R-M systems are the root cause of the P. intermedia transformation barrier. Additionally, we note the presence of conserved Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) systems in both strains, which could provide a further barrier to exogenous DNA uptake and incorporation. This work will provide a valuable resource during the development of a genetic system for P. intermedia, which will be required for fundamental investigation of this organism's physiology, metabolism, and pathogenesis in human disease.

Restriction-modification mediated barriers to exogenous DNA uptake and incorporation employed by Prevotella intermedia

PubMed Central

Skeete, Chelsey A.; Fomenkov, Alexey; Roberts, Richard J.; Rittling, Susan R.

2017-01-01

Prevotella intermedia, a major periodontal pathogen, is increasingly implicated in human respiratory tract and cystic fibrosis lung infections. Nevertheless, the specific mechanisms employed by this pathogen remain only partially characterized and poorly understood, largely due to its total lack of genetic accessibility. Here, using Single Molecule, Real-Time (SMRT) genome and methylome sequencing, bisulfite sequencing, in addition to cloning and restriction analysis, we define the specific genetic barriers to exogenous DNA present in two of the most widespread laboratory strains, P. intermedia ATCC 25611 and P. intermedia Strain 17. We identified and characterized multiple restriction-modification (R-M) systems, some of which are considerably divergent between the two strains. We propose that these R-M systems are the root cause of the P. intermedia transformation barrier. Additionally, we note the presence of conserved Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) systems in both strains, which could provide a further barrier to exogenous DNA uptake and incorporation. This work will provide a valuable resource during the development of a genetic system for P. intermedia, which will be required for fundamental investigation of this organism’s physiology, metabolism, and pathogenesis in human disease. PMID:28934361

Exploring bacterial epigenomics in the next-generation sequencing era: a new approach for an emerging frontier.

PubMed

Chen, Poyin; Jeannotte, Richard; Weimer, Bart C

2014-05-01

Epigenetics has an important role for the success of foodborne pathogen persistence in diverse host niches. Substantial challenges exist in determining DNA methylation to situation-specific phenotypic traits. DNA modification, mediated by restriction-modification systems, functions as an immune response against antagonistic external DNA, and bacteriophage-acquired methyltransferases (MTase) and orphan MTases - those lacking the cognate restriction endonuclease - facilitate evolution of new phenotypes via gene expression modulation via DNA and RNA modifications, including methylation and phosphorothioation. Recent establishment of large-scale genome sequencing projects will result in a significant increase in genome availability that will lead to new demands for data analysis including new predictive bioinformatics approaches that can be verified with traditional scientific rigor. Sequencing technologies that detect modification coupled with mass spectrometry to discover new adducts is a powerful tactic to study bacterial epigenetics, which is poised to make novel and far-reaching discoveries that link biological significance and the bacterial epigenome. Copyright © 2014 Elsevier Ltd. All rights reserved.

Intrauterine Growth Restriction: Hungry for an Answer

PubMed Central

Chu, Alison

2016-01-01

Intrauterine growth restriction (IUGR) has been defined in several ways, but in general describes a condition in which the fetus exhibits poor growth in utero. This complication of pregnancy poses a significant public health burden as well as increased morbidity and mortality for the offspring. In human IUGR, alteration in fetal glucose and insulin homeostasis occurs in an effort to conserve energy and survive at the expense of fetal growth in an environment of inadequate nutrient provision. Several animal models of IUGR have been utilized to study the effects of IUGR on fetal glucose handling, as well as the postnatal reprogramming of energy metabolite handling, which may be unmasked in adulthood as a maladaptive propensity for cardiometabolic disease. This developmental programming may be mediated in part by epigenetic modification of essential regulators of glucose homeostasis. Several pharmacological therapies and nonpharmacological lifestyle modifications have shown early promise in mitigating the risk for or severity of adult metabolic phenotypes but still require further study of unanticipated and/or untoward side effects. PMID:26889018

76 FR 21943 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-19

... Discontinuance or Modification of a Railroad Signal System Pursuant to Title 49 Code of Federal Regulations (CFR... Administration (FRA) seeking approval for the discontinuance or modification of the signal system, as detailed... block signal system (ABS) on three sections of the Roseburg Subdivision and on one section of the...

Convergence of DNA methylation and phosphorothioation epigenetics in bacterial genomes.

PubMed

Chen, Chao; Wang, Lianrong; Chen, Si; Wu, Xiaolin; Gu, Meijia; Chen, Xi; Jiang, Susu; Wang, Yunfu; Deng, Zixin; Dedon, Peter C; Chen, Shi

2017-04-25

Explosive growth in the study of microbial epigenetics has revealed a diversity of chemical structures and biological functions of DNA modifications in restriction-modification (R-M) and basic genetic processes. Here, we describe the discovery of shared consensus sequences for two seemingly unrelated DNA modification systems, 6m A methylation and phosphorothioation (PT), in which sulfur replaces a nonbridging oxygen in the DNA backbone. Mass spectrometric analysis of DNA from Escherichia coli B7A and Salmonella enterica serovar Cerro 87, strains possessing PT-based R-M genes, revealed d(G PS 6m A) dinucleotides in the G PS 6m AAC consensus representing ∼5% of the 1,100 to 1,300 PT-modified d(G PS A) motifs per genome, with 6m A arising from a yet-to-be-identified methyltransferase. To further explore PT and 6m A in another consensus sequence, G PS 6m ATC, we engineered a strain of E. coli HST04 to express Dnd genes from Hahella chejuensis KCTC2396 (PT in G PS ATC) and Dam methyltransferase from E. coli DH10B ( 6m A in G 6m ATC). Based on this model, in vitro studies revealed reduced Dam activity in G PS ATC-containing oligonucleotides whereas single-molecule real-time sequencing of HST04 DNA revealed 6m A in all 2,058 G PS ATC sites (5% of 37,698 total GATC sites). This model system also revealed temperature-sensitive restriction by DndFGH in KCTC2396 and B7A, which was exploited to discover that 6m A can substitute for PT to confer resistance to restriction by the DndFGH system. These results point to complex but unappreciated interactions between DNA modification systems and raise the possibility of coevolution of interacting systems to facilitate the function of each.

48 CFR 3.104-3 - Statutory and related prohibitions, restrictions, and requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Statutory and related prohibitions, restrictions, and requirements. 3.104-3 Section 3.104-3 Federal Acquisition Regulations System... disclosing procurement information (subsection 27(a) of the Act). (1) A person described in paragraph (a)(2...

Maternal Caloric Restriction Implemented during the Preconceptional and Pregnancy Period Alters Hypothalamic and Hippocampal Endocannabinoid Levels at Birth and Induces Overweight and Increased Adiposity at Adulthood in Male Rat Offspring

PubMed Central

Ramírez-López, María Teresa; Vázquez, Mariam; Bindila, Laura; Lomazzo, Ermelinda; Hofmann, Clementine; Blanco, Rosarío Noemí; Alén, Francisco; Antón, María; Decara, Juan; Arco, Rocío; Ouro, Daniel; Orio, Laura; Suárez, Juan; Lutz, Beat; Gómez de Heras, Raquel; Rodríguez de Fonseca, Fernando

2016-01-01

Exposure to inadequate nutritional conditions in critical windows of development has been associated to disturbances on metabolism and behavior in the offspring later in life. The role of the endocannabinoid system, a known regulator of energy expenditure and adaptive behaviors, in the modulation of these processes is unknown. In the present study, we investigated the impact of exposing rat dams to diet restriction (20% less calories than standard diet) during pre-gestational and gestational periods on: (a) neonatal outcomes; (b) endocannabinoid content in hypothalamus, hippocampus and olfactory bulb at birth; (c) metabolism-related parameters; and (d) behavior in adult male offspring. We found that calorie-restricted dams tended to have a reduced litter size, although the offspring showed normal weight at birth. Pups from calorie-restricted dams also exhibited a strong decrease in the levels of anandamide (AEA), 2-arachidonoylglycerol (2-AG), arachidonic acid (AA) and palmitoylethanolamide (PEA) in the hypothalamus at birth. Additionally, pups from diet-restricted dams displayed reduced levels of AEA in the hippocampus without significant differences in the olfactory bulb. Moreover, offspring exhibited increased weight gain, body weight and adiposity in adulthood as well as increased anxiety-related responses. We propose that endocannabinoid signaling is altered by a maternal caloric restriction implemented during the preconceptional and pregnancy periods, which might lead to modifications of the hypothalamic and hippocampal circuits, potentially contributing to the long-term effects found in the adult offspring. PMID:27847471

75 FR 71487 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-23

... Discontinuance or Modification of a Railroad Signal System Pursuant to Title 49 Code of Federal Regulations (CFR... Administration (FRA) seeking approval for the discontinuance or modification of a signal system, as detailed below. Docket Number FRA-2010-0159 Applicant: BNSF Railway, Mr. James LeVere, AVP Signals, BNSF Railway...

76 FR 4416 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-25

... Discontinuance or Modification of a Railroad Signal System Pursuant to Title 49 Code of Federal Regulations (CFR... Administration (FRA) seeking approval for the discontinuance or modification of the signal system. [Docket Number...--Signal/Comm./TCO, 1400 Douglas Street, Mail Stop 0910, Omaha, Nebraska 68179. The Union Pacific Railroad...

75 FR 43610 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-26

... Discontinuance or Modification of a Railroad Signal System Pursuant to Title 49 Code of Federal Regulations (CFR... Administration (FRA), seeking approval for the discontinuance or modification of the signal system or relief from... Transportation, Inc., Mr. Joseph S. Ivanyo, Chief Engineer, Communications and Signals, 500 Water Street, SC J...

Type III restriction-modification enzymes: a historical perspective.

PubMed

Rao, Desirazu N; Dryden, David T F; Bheemanaik, Shivakumara

2014-01-01

Restriction endonucleases interact with DNA at specific sites leading to cleavage of DNA. Bacterial DNA is protected from restriction endonuclease cleavage by modifying the DNA using a DNA methyltransferase. Based on their molecular structure, sequence recognition, cleavage position and cofactor requirements, restriction-modification (R-M) systems are classified into four groups. Type III R-M enzymes need to interact with two separate unmethylated DNA sequences in inversely repeated head-to-head orientations for efficient cleavage to occur at a defined location (25-27 bp downstream of one of the recognition sites). Like the Type I R-M enzymes, Type III R-M enzymes possess a sequence-specific ATPase activity for DNA cleavage. ATP hydrolysis is required for the long-distance communication between the sites before cleavage. Different models, based on 1D diffusion and/or 3D-DNA looping, exist to explain how the long-distance interaction between the two recognition sites takes place. Type III R-M systems are found in most sequenced bacteria. Genome sequencing of many pathogenic bacteria also shows the presence of a number of phase-variable Type III R-M systems, which play a role in virulence. A growing number of these enzymes are being subjected to biochemical and genetic studies, which, when combined with ongoing structural analyses, promise to provide details for mechanisms of DNA recognition and catalysis.

Y-12 Industrial Landfill V. Permit application modifications

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

NONE

1995-09-01

This report contains the modifications in operations and design to meet the Tennessee Department of Environment and Conversation (TDEC) July 10, 1993, amendments to the regulations for Class 2 landfills. These modifications, though extensive in design and construction cost, are considered minor revisions and should not require a processing fee. Area 1 of ILF V, comprising approximately 20% of the ILF V footprint, was designed and submitted to TDEC prior to the implementation of current regulations. This initial area was constructed with a compacted clay liner and leachate collection system, and became operational in April 1994. The current regulations requiremore » landfills to have a composite liner with leachate collection system and closure cap. Modifications to upgrade Areas 2 and 3 of ILF V to meet the current TDEC requirements are included.« less

48 CFR 43.103 - Types of contract modifications.

Code of Federal Regulations, 2010 CFR

2010-10-01

... only by the contracting officer. Unilateral modifications are used, for example, to— (1) Make... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Types of contract... CONTRACT MANAGEMENT CONTRACT MODIFICATIONS General 43.103 Types of contract modifications. Contract...

48 CFR 43.103 - Types of contract modifications.

Code of Federal Regulations, 2011 CFR

2011-10-01

... only by the contracting officer. Unilateral modifications are used, for example, to— (1) Make... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Types of contract... CONTRACT MANAGEMENT CONTRACT MODIFICATIONS General 43.103 Types of contract modifications. Contract...

48 CFR 243.205 - Contract clauses.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Contract clauses. 243.205 Section 243.205 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 243.205 Contract clauses. ...

48 CFR 243.205 - Contract clauses.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Contract clauses. 243.205 Section 243.205 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 243.205 Contract clauses. ...

12 CFR 239.8 - Operating restrictions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 4 2012-01-01 2012-01-01 false Operating restrictions. 239.8 Section 239.8 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM (CONTINUED) MUTUAL HOLDING COMPANIES (REGULATION MM) Mutual Holding Companies § 239.8 Operating restrictions...

12 CFR 239.8 - Operating restrictions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 4 2013-01-01 2013-01-01 false Operating restrictions. 239.8 Section 239.8 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM (CONTINUED) MUTUAL HOLDING COMPANIES (REGULATION MM) Mutual Holding Companies § 239.8 Operating restrictions...

12 CFR 239.8 - Operating restrictions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 4 2014-01-01 2014-01-01 false Operating restrictions. 239.8 Section 239.8 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM (CONTINUED) MUTUAL HOLDING COMPANIES (REGULATION MM) Mutual Holding Companies § 239.8 Operating restrictions...

48 CFR 225.7014 - Restrictions on military construction.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Restrictions on military..., Appropriations Acts, and Other Statutory Restrictions on Foreign Acquisition 225.7014 Restrictions on military construction. (a) For restriction on award of military construction contracts to be performed in the United...

Epigenetic modifications: basic mechanisms and role in cardiovascular disease (2013 Grover Conference series).

PubMed

Loscalzo, Joseph; Handy, Diane E

2014-06-01

Epigenetics refers to heritable traits that are not a consequence of DNA sequence. Three classes of epigenetic regulation exist: DNA methylation, histone modification, and noncoding RNA action. In the cardiovascular system, epigenetic regulation affects development, differentiation, and disease propensity or expression. Defining the determinants of epigenetic regulation offers opportunities for novel strategies for disease prevention and treatment.

Cysteine Oxidative Post-translational Modifications: Emerging Regulation in the Cardiovascular System

PubMed Central

Chung, Heaseung S.; Wang, Sheng-Bing; Venkatraman, Vidya; Murray, Christopher I.; Van Eyk, Jennifer E.

2014-01-01

In the cardiovascular system, changes in the oxidative balance can affect many aspects of cellular physiology through redox-signaling. Depending on the magnitude, fluctuations in the cell's production of reactive oxygen and nitrogen species can regulate normal metabolic processes, activate protective mechanisms, or be cytotoxic. Reactive oxygen and nitrogen species can have many effects including the post-translational modification of proteins at critical cysteine (Cys) thiols. A subset can act as redox-switches, which elicit functional effects in response to changes in oxidative state. While the general concepts of redox-signaling have been established, the identity and function of many regulatory switches remains unclear. Characterizing the effects of individual modifications is the key to understanding how the cell interprets oxidative signals under physiological and pathological conditions. Here, we review the various Cys oxidative post-translational modifications (Ox-PTMs) and their ability to function as redox-switches that regulate the cell's response to oxidative stimuli. In addition, we discuss how these modifications have the potential to influence other post-translational modifications' signaling pathways though cross-talk. Finally, we review the growing number of tools being developed to identify and quantify the various Cys Ox-PTMs and how this will advance our understanding of redox-regulation. PMID:23329793

Genetic diversity of the HpyC1I restriction modification system in Helicobacter pylori.

PubMed

Lehours, Philippe; Dupouy, Sandrine; Chaineux, Julien; Ruskoné-Fourmestraux, Agnès; Delchier, Jean-Charles; Morgner, Andrea; Mégraud, Francis; Ménard, Armelle

2007-04-01

Helicobacter pylori is unique because of the unusually high number and diversity of its restriction modification (R-M) systems. HpyC1I R-M was recently characterized and contains an endonuclease which is an isoschizomer of the endonuclease BccI. This R-M is involved in adherence to gastric epithelial cells, a crucial step in bacterial pathogenesis. This observation illustrates the fact that R-M systems have other putative biological functions in addition to protecting the bacterial genome from external DNA. The genomic diversity of HpyC1I R-M was evaluated more precisely on a large collection of H. pylori strains by PCR, susceptibility to BccI digestion and sequencing. The results obtained support the mechanism of gain and loss of this R-M system in the H. pylori genome, and suggest that it is an ancestral system which gradually disappears during H. pylori evolution, following successive steps: (1) inactivation of the endonuclease gene, followed or accompanied by: (2) inactivation of the methyltransferase genes, and then: (3) definitive loss, leaving only short endonuclease remnant sequences.

The restriction-modification genes of Escherichia coli K-12 may not be selfish: they do not resist loss and are readily replaced by alleles conferring different specificities.

PubMed

O'Neill, M; Chen, A; Murray, N E

1997-12-23

Type II restriction and modification (R-M) genes have been described as selfish because they have been shown to impose selection for the maintenance of the plasmid that encodes them. In our experiments, the type I R-M system EcoKI does not behave in the same way. The genes specifying EcoKI are, however, normally residents of the chromosome and therefore our analyses were extended to monitor the deletion of chromosomal genes rather than loss of plasmid vector. If EcoKI were to behave in the same way as the plasmid-encoded type II R-M systems, the loss of the relevant chromosomal genes by mutation or recombination should lead to cell death because the cell would become deficient in modification enzyme and the bacterial chromosome would be vulnerable to the restriction endonuclease. Our data contradict this prediction; they reveal that functional type I R-M genes in the chromosome are readily replaced by mutant alleles and by alleles encoding a type I R-M system of different specificity. The acquisition of allelic genes conferring a new sequence specificity, but not the loss of the resident genes, is dependent on the product of an unlinked gene, one predicted [Prakash-Cheng, A., Chung, S. S. & Ryu, J. (1993) Mol. Gen. Genet. 241, 491-496] to be relevant to control of expression of the genes that encode EcoKI. Our evidence suggests that not all R-M systems are evolving as "selfish" units; rather, the diversity and distribution of the family of type I enzymes we have investigated require an alternative selective pressure.

Involvement of the Cannabinoid CB1 Receptor in Modulation of Dopamine Output in the Prefrontal Cortex Associated with Food Restriction in Rats

PubMed Central

Biggio, Francesca; Utzeri, Cinzia; Lallai, Valeria; Licheri, Valentina; Lutzu, Stefano; Mostallino, Maria Cristina; Secci, Pietro Paolo; Biggio, Giovanni; Sanna, Enrico

2014-01-01

Increase in dopamine output on corticolimbic structures, such as medial prefrontal cortex (mPFC) and nucleus accumbens, has been related to reward effects associated with palatable food or food presentation after a fasting period. The endocannabinoid system regulates feeding behavior through a modulatory action on different neurotransmitter systems, including the dopaminergic system. To elucidate the involvement of type 1 cannabinoid receptors in the regulation of dopamine output in the mPFC associated with feeding in hungry rats, we restricted the food availability to a 2-h period daily for 3 weeks. In food-restricted rats the extracellular dopamine concentration in the mPFC increased starting 80 min before food presentation and returned to baseline after food removal. These changes were attenuated in animals treated with the CB1 receptor antagonist SR141716. To better understand how food restriction can change the response of mesocortical dopaminergic neurons, we studied several components of the neuronal circuit that regulates dopamine output in the mPFC. Patch-clamp experiments revealed that the inhibitory effect of the CB1 receptor agonist WIN 55,212-2 on GABAergic sIPSC frequency was diminished in mPFC neurons of FR compared to fed ad libitum rats. The basal sIPSC frequency resulted reduced in mPFC neurons of food-restricted rats, suggestive of an altered regulation of presynaptic GABA release; these changes were accompanied by an enhanced excitability of mPFC and ventral tegmental area neurons. Finally, type 1 cannabinoid receptor expression in the mPFC was reduced in food-restricted rats. Together, our data support an involvement of the endocannabinoid system in regulation of dopamine release in the mPFC through changes in GABA inhibitory synapses and suggest that the emphasized feeding-associated increase in dopamine output in the mPFC of food-restricted rats might be correlated with an altered expression and function of type 1 cannabinoid receptor in this brain region. PMID:24632810

Involvement of the cannabinoid CB1 receptor in modulation of dopamine output in the prefrontal cortex associated with food restriction in rats.

PubMed

Dazzi, Laura; Talani, Giuseppe; Biggio, Francesca; Utzeri, Cinzia; Lallai, Valeria; Licheri, Valentina; Lutzu, Stefano; Mostallino, Maria Cristina; Secci, Pietro Paolo; Biggio, Giovanni; Sanna, Enrico

2014-01-01

Increase in dopamine output on corticolimbic structures, such as medial prefrontal cortex (mPFC) and nucleus accumbens, has been related to reward effects associated with palatable food or food presentation after a fasting period. The endocannabinoid system regulates feeding behavior through a modulatory action on different neurotransmitter systems, including the dopaminergic system. To elucidate the involvement of type 1 cannabinoid receptors in the regulation of dopamine output in the mPFC associated with feeding in hungry rats, we restricted the food availability to a 2-h period daily for 3 weeks. In food-restricted rats the extracellular dopamine concentration in the mPFC increased starting 80 min before food presentation and returned to baseline after food removal. These changes were attenuated in animals treated with the CB1 receptor antagonist SR141716. To better understand how food restriction can change the response of mesocortical dopaminergic neurons, we studied several components of the neuronal circuit that regulates dopamine output in the mPFC. Patch-clamp experiments revealed that the inhibitory effect of the CB1 receptor agonist WIN 55,212-2 on GABAergic sIPSC frequency was diminished in mPFC neurons of FR compared to fed ad libitum rats. The basal sIPSC frequency resulted reduced in mPFC neurons of food-restricted rats, suggestive of an altered regulation of presynaptic GABA release; these changes were accompanied by an enhanced excitability of mPFC and ventral tegmental area neurons. Finally, type 1 cannabinoid receptor expression in the mPFC was reduced in food-restricted rats. Together, our data support an involvement of the endocannabinoid system in regulation of dopamine release in the mPFC through changes in GABA inhibitory synapses and suggest that the emphasized feeding-associated increase in dopamine output in the mPFC of food-restricted rats might be correlated with an altered expression and function of type 1 cannabinoid receptor in this brain region.

48 CFR 1852.232-70 - NASA modification of FAR 52.232-12.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false NASA modification of FAR... Provisions and Clauses 1852.232-70 NASA modification of FAR 52.232-12. As prescribed at 1832.412-70, make the following modifications: NASA Modification of FAR 52.232-12, (MAR 1998) (a) Basic Clause. (1) In paragraph...

48 CFR 1852.232-70 - NASA modification of FAR 52.232-12.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false NASA modification of FAR... Provisions and Clauses 1852.232-70 NASA modification of FAR 52.232-12. As prescribed at 1832.412-70, make the following modifications: NASA Modification of FAR 52.232-12, (MAR 1998) (a) Basic Clause. (1) In paragraph...

48 CFR 1852.232-70 - NASA modification of FAR 52.232-12.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false NASA modification of FAR... Provisions and Clauses 1852.232-70 NASA modification of FAR 52.232-12. As prescribed at 1832.412-70, make the following modifications: NASA Modification of FAR 52.232-12, (MAR 1998) (a) Basic Clause. (1) In paragraph...

48 CFR 1852.232-70 - NASA modification of FAR 52.232-12.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false NASA modification of FAR... Provisions and Clauses 1852.232-70 NASA modification of FAR 52.232-12. As prescribed at 1832.412-70, make the following modifications: NASA Modification of FAR 52.232-12, (MAR 1998) (a) Basic Clause. (1) In paragraph...

48 CFR 2143.101 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Definitions. 2143.101 Section 2143.101 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT, FEDERAL EMPLOYEES GROUP LIFE INSURANCE FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT CONTRACT MODIFICATIONS General...

48 CFR 970.4302 - Changes.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Changes. 970.4302 Section 970.4302 Federal Acquisition Regulations System DEPARTMENT OF ENERGY AGENCY SUPPLEMENTARY REGULATIONS DOE MANAGEMENT AND OPERATING CONTRACTS Contract Modifications 970.4302 Changes. ...

Therapeutic charm of quercetin and its derivatives: a review of research and patents.

PubMed

Sharma, Ajay; Kashyap, Dharambir; Sak, Katrin; Tuli, Hardeep Singh; Sharma, Anil K

2018-01-01

Bioactive polyphenolic compounds derived from plants are being utilized for prevention of various chronic diseases including cancer and cardiovascular disorders. Quercetin, a potential poly-phenolic flavonol, found in onions, apples and berries, has been implicated against cancer proliferation, chronic inflammation and various other oxidative manifestations. Evidences suggested that quercetin negatively regulates the numerous crucial signaling pathways associated with life-threatening diseases. Major signaling pathways including NF-κB, MAPK, PI3K-AKT and mTOR are found to be regulated by quercetin. In addition, several patents have reported recently on quercetin derivatives describing wide therapeutic applications such as anticancer/antiproliferatory, antioxidative/antiaging, antiviral, anti-inflammatory, cardioprotective. Present review emphasizes the chemistry and sources of quercetin followed by description of its broad-spectrum therapeutic potential along with proposed mechanisms of action. Furthermore, this review also highlights the important modifications in the basic chemical structure of quercetin in terms of published patents. Insolubility of the bioactive compounds restricts their medicinal importance which could be overcome by modifications in the chemical structure of so-called derivatives. Most of the patents deal with the modifications in chemical structure of quercetin mainly at hydroxyl groups and C-6 and C-7 positions.

48 CFR 243.205-71 - Requests for equitable adjustment.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Requests for equitable adjustment. 243.205-71 Section 243.205-71 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 243.205-71...

48 CFR 243.205-71 - Requests for equitable adjustment.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Requests for equitable adjustment. 243.205-71 Section 243.205-71 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 243.205-71...

78 FR 63866 - Modification of Restricted Areas R-6901A & R-6901B; Fort McCoy, WI

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-25

...-0838; Airspace Docket No. 12-AGL-17] Modification of Restricted Areas R-6901A & R-6901B; Fort McCoy, WI...: This action amends Restricted Areas R-6901A and R-6901B, Fort McCoy, WI, to accurately identify the... 44597, December 11, 1986) modifying the boundaries and time of designation of the existing R-6901, Fort...

48 CFR 552.203-71 - Restriction on Advertising.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Restriction on Advertising... Restriction on Advertising. As prescribed in 503.570-2, insert the following clause: Restriction on Advertising (SEP 1999) The Contractor shall not refer to this contract in commercial advertising or similar...

48 CFR 552.203-71 - Restriction on Advertising.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Restriction on Advertising... Restriction on Advertising. As prescribed in 503.570-2, insert the following clause: Restriction on Advertising (SEP 1999) The Contractor shall not refer to this contract in commercial advertising or similar...

48 CFR 552.203-71 - Restriction on Advertising.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Restriction on Advertising... Restriction on Advertising. As prescribed in 503.570-2, insert the following clause: Restriction on Advertising (SEP 1999) The Contractor shall not refer to this contract in commercial advertising or similar...

48 CFR 552.203-71 - Restriction on Advertising.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Restriction on Advertising... Restriction on Advertising. As prescribed in 503.570-2, insert the following clause: Restriction on Advertising (SEP 1999) The Contractor shall not refer to this contract in commercial advertising or similar...

48 CFR 552.203-71 - Restriction on Advertising.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Restriction on Advertising... Restriction on Advertising. As prescribed in 503.570-2, insert the following clause: Restriction on Advertising (SEP 1999) The Contractor shall not refer to this contract in commercial advertising or similar...

48 CFR 538.7003 - Policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Policy. 538.7003 Section 538.7003 Federal Acquisition Regulations System GENERAL SERVICES ADMINISTRATION SPECIAL CATEGORIES OF... entities, the contracting officer must make minor modifications to certain Federal Acquisition Regulation...

48 CFR 538.7103 - Policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Policy. 538.7103 Section 538.7103 Federal Acquisition Regulations System GENERAL SERVICES ADMINISTRATION SPECIAL CATEGORIES OF... entities, the contracting officer must make minor modifications to certain Federal Acquisition Regulation...

48 CFR 2143.205 - Contract clause.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Contract clause. 2143.205 Section 2143.205 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT, FEDERAL EMPLOYEES GROUP LIFE INSURANCE FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change...

48 CFR 2143.205 - Contract clause.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Contract clause. 2143.205 Section 2143.205 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT, FEDERAL EMPLOYEES GROUP LIFE INSURANCE FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change...

48 CFR 243.204-71 - Certification of requests for equitable adjustment.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Certification of requests for equitable adjustment. 243.204-71 Section 243.204-71 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders...

48 CFR 243.204-70-4 - Limitations on obligations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Limitations on obligations. 243.204-70-4 Section 243.204-70-4 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 243.204-70...

48 CFR 243.204-71 - Certification of requests for equitable adjustment.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Certification of requests for equitable adjustment. 243.204-71 Section 243.204-71 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders...

48 CFR 243.204-70-4 - Limitations on obligations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Limitations on obligations. 243.204-70-4 Section 243.204-70-4 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 243.204-70...

48 CFR 1852.232-70 - NASA modification of FAR 52.232-12.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true NASA modification of FAR 52... Provisions and Clauses 1852.232-70 NASA modification of FAR 52.232-12. As prescribed at 1832.412-70, make the following modifications: NASA Modification of FAR 52.232-12, (MAR 1998) (a) Basic Clause. (1) In paragraph...

Strand-specific RNA-seq analysis of the Lactobacillus delbrueckii subsp. bulgaricus transcriptome.

PubMed

Zheng, Huajun; Liu, Enuo; Shi, Tao; Ye, Luyi; Konno, Tomonobu; Oda, Munehiro; Ji, Zai-Si

2016-02-01

Lactobacillus delbrueckii subsp. bulgaricus 2038 (Lb. bulgaricus 2038) is an industrial bacterium that is used as a starter for dairy products. We proposed several hypotheses concerning its industrial features previously. Here, we utilized RNA-seq to explore the transcriptome of Lb. bulgaricus 2038 from four different growth phases under whey conditions. The most abundantly expressed genes in the four stages were mainly involved in translation (for the logarithmic stage), glycolysis (for control/lag stages), lactic acid production (all the four stages), and 10-formyl tetrahydrofolate production (for the stationary stage). The high expression of genes like d-lactate dehydrogenase was thought as a result of energy production, and consistent expression of EPS synthesis genes, the restriction-modification (RM) system and the CRISPR/Cas system were validated for explaining the advantage of this strain in yoghurt production. Several postulations, like NADPH production through GapN bypass, converting aspartate into carbon-skeleton intermediates, and formate production through degrading GTP, were proved not working under these culture conditions. The high expression of helicase genes and co-expressed amino acids/oligopeptides transporting proteins indicated that the helicase might mediate the strain obtaining nitrogen source from the environment. The transport system of Lb. bulgaricus 2038 was found to be regulated by antisense RNA, hinting the potential application of non-coding RNA in regulating lactic acid bacteria (LAB) gene expression. Our study has primarily uncovered Lb. bulgaricus 2038 transcriptome, which could gain a better understanding of the regulation system in Lb. bulgaricus and promote its industrial application.

Modify the Histone to Win the Battle: Chromatin Dynamics in Plant–Pathogen Interactions

PubMed Central

Ramirez-Prado, Juan S.; Piquerez, Sophie J. M.; Bendahmane, Abdelhafid; Hirt, Heribert; Raynaud, Cécile; Benhamed, Moussa

2018-01-01

Relying on an immune system comes with a high energetic cost for plants. Defense responses in these organisms are therefore highly regulated and fine-tuned, permitting them to respond pertinently to the attack of a microbial pathogen. In recent years, the importance of the physical modification of chromatin, a highly organized structure composed of genomic DNA and its interacting proteins, has become evident in the research field of plant–pathogen interactions. Several processes, including DNA methylation, changes in histone density and variants, and various histone modifications, have been described as regulators of various developmental and defense responses. Herein, we review the state of the art in the epigenomic aspects of plant immunity, focusing on chromatin modifications, chromatin modifiers, and their physiological consequences. In addition, we explore the exciting field of understanding how plant pathogens have adapted to manipulate the plant epigenomic regulation in order to weaken their immune system and thrive in their host, as well as how histone modifications in eukaryotic pathogens are involved in the regulation of their virulence. PMID:29616066

The Helicobacter pylori HpyAXII restriction–modification system limits exogenous DNA uptake by targeting GTAC sites but shows asymmetric conservation of the DNA methyltransferase and restriction endonuclease components

PubMed Central

Humbert, Olivier; Salama, Nina R.

2008-01-01

The naturally competent organism Helicobacter pylori encodes a large number of restriction–modification (R–M) systems that consist of a restriction endonuclease and a DNA methyltransferase. R–M systems are not only believed to limit DNA exchange among bacteria but may also have other cellular functions. We report a previously uncharacterized H. pylori type II R–M system, M.HpyAXII/R.HpyAXII. We show that this system targets GTAC sites, which are rare in the H. pylori chromosome but numerous in ribosomal RNA genes. As predicted, this type II R–M system showed attributes of a selfish element. Deletion of the methyltransferase M.HpyAXII is lethal when associated with an active endonuclease R.HpyAXII unless compensated by adaptive mutation or gene amplification. R.HpyAXII effectively restricted both unmethylated plasmid and chromosomal DNA during natural transformation and was predicted to belong to the novel ‘half pipe’ structural family of endonucleases. Analysis of a panel of clinical isolates revealed that R.HpyAXII was functional in a small number of H. pylori strains (18.9%, n = 37), whereas the activity of M.HpyAXII was highly conserved (92%, n = 50), suggesting that GTAC methylation confers a selective advantage to H. pylori. However, M.HpyAXII activity did not enhance H. pylori fitness during stomach colonization of a mouse infection model. PMID:18978016

A Novel Tool for Microbial Genome Editing Using the Restriction-Modification System.

PubMed

Bai, Hua; Deng, Aihua; Liu, Shuwen; Cui, Di; Qiu, Qidi; Wang, Laiyou; Yang, Zhao; Wu, Jie; Shang, Xiuling; Zhang, Yun; Wen, Tingyi

2018-01-19

Scarless genetic manipulation of genomes is an essential tool for biological research. The restriction-modification (R-M) system is a defense system in bacteria that protects against invading genomes on the basis of its ability to distinguish foreign DNA from self DNA. Here, we designed an R-M system-mediated genome editing (RMGE) technique for scarless genetic manipulation in different microorganisms. For bacteria with Type IV REase, an RMGE technique using the inducible DNA methyltransferase gene, bceSIIM (RMGE-bceSIIM), as the counter-selection cassette was developed to edit the genome of Escherichia coli. For bacteria without Type IV REase, an RMGE technique based on a restriction endonuclease (RMGE-mcrA) was established in Bacillus subtilis. These techniques were successfully used for gene deletion and replacement with nearly 100% counter-selection efficiencies, which were higher and more stable compared to conventional methods. Furthermore, precise point mutation without limiting sites was achieved in E. coli using RMGE-bceSIIM to introduce a single base mutation of A128C into the rpsL gene. In addition, the RMGE-mcrA technique was applied to delete the CAN1 gene in Saccharomyces cerevisiae DAY414 with 100% counter-selection efficiency. The effectiveness of the RMGE technique in E. coli, B. subtilis, and S. cerevisiae suggests the potential universal usefulness of this technique for microbial genome manipulation.

48 CFR 252.227-7024 - Notice and approval of restricted designs.

Code of Federal Regulations, 2010 CFR

2010-10-01

... restricted designs. 252.227-7024 Section 252.227-7024 Federal Acquisition Regulations System DEFENSE... CLAUSES Text of Provisions And Clauses 252.227-7024 Notice and approval of restricted designs. As prescribed at 227.7107-3, use the following clause: Notice and Approval of Restricted Designs (APR 1984) In...

48 CFR 252.227-7037 - Validation of restrictive markings on technical data.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Validation of restrictive... AND CONTRACT CLAUSES Text of Provisions And Clauses 252.227-7037 Validation of restrictive markings on... following clause: Validation of Restrictive Markings on Technical Data (APR 2012) (a) Definitions. The terms...

48 CFR 252.227-7037 - Validation of restrictive markings on technical data.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Validation of restrictive... AND CONTRACT CLAUSES Text of Provisions And Clauses 252.227-7037 Validation of restrictive markings on... following clause: Validation of Restrictive Markings on Technical Data (JUN 2013) (a) Definitions. The terms...

48 CFR 252.227-7037 - Validation of restrictive markings on technical data.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Validation of restrictive... AND CONTRACT CLAUSES Text of Provisions And Clauses 252.227-7037 Validation of restrictive markings on... following clause: Validation of Restrictive Markings on Technical Data (JUN 2013) (a) Definitions. The terms...

48 CFR 252.227-7037 - Validation of restrictive markings on technical data.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Validation of restrictive... AND CONTRACT CLAUSES Text of Provisions And Clauses 252.227-7037 Validation of restrictive markings on... following clause: Validation of Restrictive Markings on Technical Data (SEP 2011) (a) Definitions. The terms...

48 CFR 252.227-7037 - Validation of restrictive markings on technical data.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Validation of restrictive... AND CONTRACT CLAUSES Text of Provisions And Clauses 252.227-7037 Validation of restrictive markings on... following clause: Validation of Restrictive Markings on Technical Data (SEP 1999) (a) Definitions. The terms...

48 CFR 3443.106 - Contract clause.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Contract clause. 3443.106 Section 3443.106 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION ACQUISITION REGULATION CONTRACT MANAGEMENT CONTRACT MODIFICATIONS 3443.106 Contract clause. The contracting officer shall insert...

Dietary protein restriction causes modification in aluminum-induced alteration in glutamate and GABA system of rat brain

PubMed Central

Nayak, Prasunpriya; Chatterjee, Ajay K

2003-01-01

Background Alteration of glutamate and γ-aminobutyrate system have been reported to be associated with neurodegenerative disorders and have been postulated to be involved in aluminum-induced neurotoxicity as well. Aluminum, an well known and commonly exposed neurotoxin, was found to alter glutamate and γ-aminobutyrate levels as well as activities of associated enzymes with regional specificity. Protein malnutrition also reported to alter glutamate level and some of its metabolic enzymes. Thus the region-wise study of levels of brain glutamate and γ-aminobutyrate system in protein adequacy and inadequacy may be worthwhile to understand the mechanism of aluminum-induced neurotoxicity. Results Protein restriction does not have any significant impact on regional aluminum and γ-aminobutyrate contents of rat brain. Significant interaction of dietary protein restriction and aluminum intoxication to alter regional brain glutamate level was observed in the tested brain regions except cerebellum. Alteration in glutamate α-decarboxylase and γ-aminobutyrate transaminase activities were found to be significantly influenced by interaction of aluminum intoxication and dietary protein restriction in all the tested brain regions. In case of regional brain succinic semialdehyde content, this interaction was significant only in cerebrum and thalamic area. Conclusion The alterations of regional brain glutamate and γ-aminobutyrate levels by aluminum are region specific as well as dependent on dietary protein intake. The impact of aluminum exposure on the metabolism of these amino acid neurotransmitters are also influenced by dietary protein level. Thus, modification of dietary protein level or manipulation of the brain amino acid homeostasis by any other means may be an useful tool to find out a path to restrict amino acid neurotransmitter alterations in aluminum-associated neurodisorders. PMID:12657166

The G1 restriction point as critical regulator of neocortical neuronogenesis

NASA Technical Reports Server (NTRS)

Caviness, V. S. Jr; Takahashi, T.; Nowakowski, R. S.

1999-01-01

Neuronogenesis in the pseudostratified ventricular epithelium is the initial process in a succession of histogenetic events which give rise to the laminate neocortex. Here we review experimental findings in mouse which support the thesis that the restriction point of the G1 phase of the cell cycle is the critical point of regulation of the overall neuronogenetic process. The neuronogenetic interval in mouse spans 6 days. In the course of these 6 days the founder population and its progeny execute 11 cell cycles. With each successive cycle there is an increase in the fraction of postmitotic cells which leaves the cycle (the Q fraction) and also an increase in the length of the cell cycle due to an increase in the length of the G1 phase of the cycle. Q corresponds to the probability that postmitotic cells will exit the cycle at the restriction point of the G1 phase of the cell cycle. Q increases non-linearly, but the rate of change of Q with cycle (i.e., the first derivative) over the course of the neuronogenetic interval is a constant, k, which appears to be set principally by cell internal mechanisms which are species specific. Q also seems to be modulated, but at low amplitude, by a balance of mitogenic and antimitogenic influences acting from without the cell. We suggest that intracellular signal transduction systems control a general advance of Q during development and thereby determine the general developmental plan (i.e., cell number and laminar composition) of the neocortex and that external mitogens and anti-mitogens modulate this advance regionally and temporally and thereby produce regional modifications of the general plan.

48 CFR 1643.205-70 - Contract clause.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Contract clause. 1643.205-70 Section 1643.205-70 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Changes 1643.205...

48 CFR 1643.205-70 - Contract clause.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Contract clause. 1643.205-70 Section 1643.205-70 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Changes 1643.205...

48 CFR 1643.205-70 - Contract clause.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Contract clause. 1643.205-70 Section 1643.205-70 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Changes 1643.205...

48 CFR 1643.205-70 - Contract clause.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Contract clause. 1643.205-70 Section 1643.205-70 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Changes 1643.205...

48 CFR 1643.205-70 - Contract clause.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Contract clause. 1643.205-70 Section 1643.205-70 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Changes 1643.205...

48 CFR 225.7003-2 - Restrictions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Section 225.7003-2 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Authorization Acts, Appropriations Acts, and...) Missile or space systems. (3) Ships. (4) Tank or automotive items. (5) Weapon systems. (6) Ammunition. (b...

48 CFR 225.7003-2 - Restrictions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Section 225.7003-2 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Authorization Acts, Appropriations Acts, and...) Missile or space systems. (3) Ships. (4) Tank or automotive items. (5) Weapon systems. (6) Ammunition. (b...

48 CFR 225.7003-2 - Restrictions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Section 225.7003-2 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Authorization Acts, Appropriations Acts, and...) Missile or space systems. (3) Ships. (4) Tank or automotive items. (5) Weapon systems. (6) Ammunition. (b...

48 CFR 225.7003-2 - Restrictions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Section 225.7003-2 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Authorization Acts, Appropriations Acts, and...) Missile or space systems. (3) Ships. (4) Tank or automotive items. (5) Weapon systems. (6) Ammunition. (b...

48 CFR 225.7003-2 - Restrictions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Section 225.7003-2 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Authorization Acts, Appropriations Acts, and...) Missile or space systems. (3) Ships. (4) Tank or automotive items. (5) Weapon systems. (6) Ammunition. (b...

48 CFR 643.102 - Policy.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Policy. 643.102 Section 643.102 Federal Acquisition Regulations System DEPARTMENT OF STATE CONTRACT MANAGEMENT CONTRACT MODIFICATIONS General 643.102 Policy. ...

48 CFR 27.404-2 - Limited rights data and restricted computer software.

Code of Federal Regulations, 2011 CFR

2011-10-01

... restricted computer software. 27.404-2 Section 27.404-2 Federal Acquisition Regulations System FEDERAL... Copyrights 27.404-2 Limited rights data and restricted computer software. (a) General. The basic clause at 52... restricted computer software by withholding the data from the Government and instead delivering form, fit...

48 CFR 27.404-2 - Limited rights data and restricted computer software.

Code of Federal Regulations, 2014 CFR

2014-10-01

... restricted computer software. 27.404-2 Section 27.404-2 Federal Acquisition Regulations System FEDERAL... Copyrights 27.404-2 Limited rights data and restricted computer software. (a) General. The basic clause at 52... restricted computer software by withholding the data from the Government and instead delivering form, fit...

48 CFR 27.404-2 - Limited rights data and restricted computer software.

Code of Federal Regulations, 2012 CFR

2012-10-01

... restricted computer software. 27.404-2 Section 27.404-2 Federal Acquisition Regulations System FEDERAL... Copyrights 27.404-2 Limited rights data and restricted computer software. (a) General. The basic clause at 52... restricted computer software by withholding the data from the Government and instead delivering form, fit...

48 CFR 27.404-2 - Limited rights data and restricted computer software.

Code of Federal Regulations, 2013 CFR

2013-10-01

... restricted computer software. 27.404-2 Section 27.404-2 Federal Acquisition Regulations System FEDERAL... Copyrights 27.404-2 Limited rights data and restricted computer software. (a) General. The basic clause at 52... restricted computer software by withholding the data from the Government and instead delivering form, fit...

48 CFR 27.404-2 - Limited rights data and restricted computer software.

Code of Federal Regulations, 2010 CFR

2010-10-01

... restricted computer software. 27.404-2 Section 27.404-2 Federal Acquisition Regulations System FEDERAL... Copyrights 27.404-2 Limited rights data and restricted computer software. (a) General. The basic clause at 52... restricted computer software by withholding the data from the Government and instead delivering form, fit...

48 CFR 43.202 - Authority to issue change orders.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Authority to issue change orders. 43.202 Section 43.202 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 43.202 Authority to issue change orders. Change...

48 CFR 43.202 - Authority to issue change orders.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Authority to issue change orders. 43.202 Section 43.202 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 43.202 Authority to issue change orders. Change...

The Catalytic and Non-catalytic Functions of the Brahma Chromatin-Remodeling Protein Collaborate to Fine-Tune Circadian Transcription in Drosophila

PubMed Central

Kwok, Rosanna S.; Li, Ying H.; Lei, Anna J.; Edery, Isaac; Chiu, Joanna C.

2015-01-01

Daily rhythms in gene expression play a critical role in the progression of circadian clocks, and are under regulation by transcription factor binding, histone modifications, RNA polymerase II (RNAPII) recruitment and elongation, and post-transcriptional mechanisms. Although previous studies have shown that clock-controlled genes exhibit rhythmic chromatin modifications, less is known about the functions performed by chromatin remodelers in animal clockwork. Here we have identified the Brahma (Brm) complex as a regulator of the Drosophila clock. In Drosophila, CLOCK (CLK) is the master transcriptional activator driving cyclical gene expression by participating in an auto-inhibitory feedback loop that involves stimulating the expression of the main negative regulators, period (per) and timeless (tim). BRM functions catalytically to increase nucleosome density at the promoters of per and tim, creating an overall restrictive chromatin landscape to limit transcriptional output during the active phase of cycling gene expression. In addition, the non-catalytic function of BRM regulates the level and binding of CLK to target promoters and maintains transient RNAPII stalling at the per promoter, likely by recruiting repressive and pausing factors. By disentangling its catalytic versus non-catalytic functions at the promoters of CLK target genes, we uncovered a multi-leveled mechanism in which BRM fine-tunes circadian transcription. PMID:26132408

48 CFR 252.236-7000 - Modification proposals-price breakdown.

Code of Federal Regulations, 2010 CFR

2010-10-01

...-price breakdown. 252.236-7000 Section 252.236-7000 Federal Acquisition Regulations System DEFENSE... CLAUSES Text of Provisions And Clauses 252.236-7000 Modification proposals—price breakdown. As prescribed in 236.570(a), use the following clause: Modification Proposals—Price Breakdown (DEC 1991) (a) The...

48 CFR 243.204-70-7 - Plans and reports.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Plans and reports. 243.204-70-7 Section 243.204-70-7 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 243.204-70-7 Plans and reports. To provide for enhanced...

48 CFR 243.204-70-7 - Plans and reports.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Plans and reports. 243.204-70-7 Section 243.204-70-7 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 243.204-70-7 Plans and reports. To provide for enhanced...

Osmotic Homeostasis

PubMed Central

Zeidel, Mark L.

2015-01-01

Alterations in water homeostasis can disturb cell size and function. Although most cells can internally regulate cell volume in response to osmolar stress, neurons are particularly at risk given a combination of complex cell function and space restriction within the calvarium. Thus, regulating water balance is fundamental to survival. Through specialized neuronal “osmoreceptors” that sense changes in plasma osmolality, vasopressin release and thirst are titrated in order to achieve water balance. Fine-tuning of water absorption occurs along the collecting duct, and depends on unique structural modifications of renal tubular epithelium that confer a wide range of water permeability. In this article, we review the mechanisms that ensure water homeostasis as well as the fundamentals of disorders of water balance. PMID:25078421

41 CFR 101-39.104-1 - Consolidations into a fleet management system.

Code of Federal Regulations, 2011 CFR

2011-07-01

... fleet management system. 101-39.104-1 Section 101-39.104-1 Public Contracts and Property Management Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS AVIATION, TRANSPORTATION, AND MOTOR VEHICLES 39-INTERAGENCY FLEET MANAGEMENT SYSTEMS 39.1-Establishment, Modification, and...

48 CFR 243.204-70 - Definitization of change orders.

Code of Federal Regulations, 2010 CFR

2010-10-01

... REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 243.204-70 Definitization of change orders. ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Definitization of change...

48 CFR 243.204-70 - Definitization of change orders.

Code of Federal Regulations, 2011 CFR

2011-10-01

... REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 243.204-70 Definitization of change orders. ... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Definitization of change...

Identification of a DNA restriction-modification system in Pectobacterium carotovorum strains isolated from Poland.

PubMed

Waleron, K; Waleron, M; Osipiuk, J; Podhajska, A J; Lojkowska, E

2006-02-01

Polish isolates of pectinolytic bacteria from the species Pectobacterium carotovorum were screened for the presence of a DNA restriction-modification (R-M) system. Eighty-nine strains of P. carotovorum were isolated from infected potato plants. Sixty-six strains belonged to P. carotovorum ssp. atrosepticum and 23 to P. carotovorum ssp. carotovorum. The presence of restriction enzyme Pca17AI, which is an isoschizomer of EcoRII endonuclease, was observed in all isolates of P. c. atrosepticum but not in P. c. carotovorum. The biochemical properties, PCR amplification, and sequences of the Pca17AI restriction endonuclease and methyltransferase genes were compared with the prototype EcoRII R-M system genes. Only when DNA isolated from cells of P. c. atrosepticum was used as a template, amplification of a 680 bp homologous to the gene coding EcoRII endonuclease. Endonuclease Pca17AI, having a relatively low temperature optimum, was identified. PCR amplification revealed that the nucleotide sequence of genes for EcoRII and Pca17AI R-M are different. Dcm methylation was observed in all strains of Pectobacterium and other Erwinia species tested. The sequence of a DNA fragment coding Dcm methylase in P. carotovorum was different from that of Escherichia coli. Pca17AI is the first psychrophilic isoschizomer of EcoRII endonuclease. The presence of specific Dcm methylation in chromosomal DNA isolated from P. carotovorum is described for the first time. A 680 bp PCR product, unique for P. c. atrosepticum strains, could serve as a molecular marker for detection of these bacteria in environmental samples.

48 CFR 217.7103-6 - Modification of master agreements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Modification of master... Master Agreement for Repair and Alteration of Vessels 217.7103-6 Modification of master agreements. (a) Review each master agreement at least annually before the anniversary of its effective date and revise it...

48 CFR 217.7103-6 - Modification of master agreements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Modification of master... Master Agreement for Repair and Alteration of Vessels 217.7103-6 Modification of master agreements. (a) Review each master agreement at least annually before the anniversary of its effective date and revise it...

48 CFR 217.7103-6 - Modification of master agreements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Modification of master... Master Agreement for Repair and Alteration of Vessels 217.7103-6 Modification of master agreements. (a) Review each master agreement at least annually before the anniversary of its effective date and revise it...

48 CFR 217.7103-6 - Modification of master agreements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Modification of master... Master Agreement for Repair and Alteration of Vessels 217.7103-6 Modification of master agreements. (a) Review each master agreement at least annually before the anniversary of its effective date and revise it...

48 CFR 217.7103-6 - Modification of master agreements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Modification of master... Master Agreement for Repair and Alteration of Vessels 217.7103-6 Modification of master agreements. (a) Review each master agreement at least annually before the anniversary of its effective date and revise it...

48 CFR 52.215-13 - Subcontractor Certified Cost or Pricing Data-Modifications.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Cost or Pricing Data-Modifications. 52.215-13 Section 52.215-13 Federal Acquisition Regulations System... Text of Provisions and Clauses 52.215-13 Subcontractor Certified Cost or Pricing Data—Modifications. As prescribed in 15.408(e), insert the following clause: Subcontractor Certified Cost or Pricing Data...

48 CFR 252.243-7001 - Pricing of contract modifications.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Pricing of contract... of Provisions And Clauses 252.243-7001 Pricing of contract modifications. As prescribed in 243.205-70, use the following clause: Pricing of Contract Modifications (DEC 1991) When costs are a factor in any...

48 CFR 22.404-6 - Modifications of wage determinations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Modifications of wage... Involving Construction 22.404-6 Modifications of wage determinations. (a) General. (1) The Department of Labor may modify a wage determination to make it current by specifying only the items being changed or...

48 CFR 1322.404-6 - Modification of wage determination.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Modification of wage... Involving Construction 1322.404-6 Modification of wage determination. The designee authorized to request an extension beyond 90 days after bid opening from the Department of Labor Administrator, Wage and Hour...

Final Rule for Control of Air Pollution From Motor Vehicles and New Motor Vehicle Engines; Modification of Federal Onboard Diagnostic Regulations for Light-Duty Vehicles and Light-Duty Trucks; Extension of Acceptance of California OBD

EPA Pesticide Factsheets

This action finalizes modifications to the federal on-board diagnostics regulations, including: harmonizing the emission levels above which a component or system is considered malfunctioning with those of the California Air Resources Board (CARB).

The recognition and modification sites for the bacterial type I restriction systems KpnAI, StySEAI, StySENI and StySGI

PubMed Central

Kasarjian, Julie K. A.; Hidaka, Masumi; Horiuchi, Takashi; Iida, Masatake; Ryu, Junichi

2004-01-01

Using an in vivo plasmid transformation method, we have determined the DNA sequences recognized by the KpnAI, StySEAI, StySENI and StySGI R-M systems from Klebsiella oxytoca strain M5a1, Salmonella eastbourne, Salmonella enteritidis and Salmonella gelsenkirchen, respectively. These type I restriction-modification systems were originally identified using traditional phage assay, and described here is the plasmid transformation test and computer program used to determine their DNA recognition sequences. For this test, we constructed two sets of plasmids, pL and pE, that contain phage lambda and Escherichia coli K-12 chromosomal DNA fragments, respectively. Further, using the methylation sensitivities of various known type II restriction enzymes, we identified the target adenines for methylation (listed in bold italics below as A or T in case of the complementary strand). The recognition sequence and methylation sites are GAA(6N)TGCC (KpnAI), ACA(6N)TYCA (StySEAI), CGA(6N)TACC (StySENI) and TAAC(7N)RTCG (StySGI). These DNA recognition sequences all have a typical type I bipartite pattern and represent three novel specificities and one isoschizomer (StySENI). For confirmation, oligonucleotides containing each of the predicted sequences were synthesized, cloned into plasmid pMECA and transformed into each strain, resulting in a large reduction in efficiency of transformation (EOT). PMID:15199175

Resilience of biochemical activity in protein domains in the face of structural divergence.

PubMed

Zhang, Dapeng; Iyer, Lakshminarayan M; Burroughs, A Maxwell; Aravind, L

2014-06-01

Recent studies point to the prevalence of the evolutionary phenomenon of drastic structural transformation of protein domains while continuing to preserve their basic biochemical function. These transformations span a wide spectrum, including simple domains incorporated into larger structural scaffolds, changes in the structural core, major active site shifts, topological rewiring and extensive structural transmogrifications. Proteins from biological conflict systems, such as toxin-antitoxin, restriction-modification, CRISPR/Cas, polymorphic toxin and secondary metabolism systems commonly display such transformations. These include endoDNases, metal-independent RNases, deaminases, ADP ribosyltransferases, immunity proteins, kinases and E1-like enzymes. In eukaryotes such transformations are seen in domains involved in chromatin-related peptide recognition and protein/DNA-modification. Intense selective pressures from 'arms-race'-like situations in conflict and macromolecular modification systems could favor drastic structural divergence while preserving function. Published by Elsevier Ltd.

From Agrobacterium to viral vectors: genome modification of plant cells by rare cutting restriction enzymes.

PubMed

Marton, Ira; Honig, Arik; Omid, Ayelet; De Costa, Noam; Marhevka, Elena; Cohen, Barry; Zuker, Amir; Vainstein, Alexander

2013-01-01

Researchers and biotechnologists require methods to accurately modify the genome of higher eukaryotic cells. Such modifications include, but are not limited to, site-specific mutagenesis, site-specific insertion of foreign DNA, and replacement and deletion of native sequences. Accurate genome modifications in plant species have been rather limited, with only a handful of plant species and genes being modified through the use of early genome-editing techniques. The development of rare-cutting restriction enzymes as a tool for the induction of site-specific genomic double-strand breaks and their introduction as a reliable tool for genome modification in animals, animal cells and human cell lines have paved the way for the adaptation of rare-cutting restriction enzymes to genome editing in plant cells. Indeed, the number of plant species and genes which have been successfully edited using zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and engineered homing endonucleases is on the rise. In our review, we discuss the basics of rare-cutting restriction enzyme-mediated genome-editing technology with an emphasis on its application in plant species.

Type II restriction modification system methylation subunit of Alicyclobacillus acidocaldarius

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

Lee, Brady D.; Newby, Deborah T.; Lacey, Jeffrey A.

2018-02-13

Isolated and/or purified polypeptides and nucleic acid sequences encoding polypeptides from Alicyclobacillus acidocaldarius are provided. Further provided are methods for modulating or altering recombination inside or outside of a cell using isolated and/or purified polypeptides and/or nucleic acid sequences from Alicyclobacillus acidocaldarius.

Type II restriction-modification system methylation subunit of Alicyclobacillus acidocaldarius

DOEpatents

Lee, Brady D; Newby, Deborah T; Lacey, Jeffrey A; Thompson, David N; Thompson, Vicki S; Apel, William A; Roberto, Francisco F; Reed, David W

2013-10-29

Isolated and/or purified polypeptides and nucleic acid sequences encoding polypeptides from Alicyclobacillus acidocaldarius are provided. Further provided are methods for modulating or altering recombination inside or outside of a cell using isolated and/or purified polypeptides and/or nucleic acid sequences from Alicyclobacillus acidocaldarius.

Type II restriction-modification system methylation subunit of Alicyclobacillus acidocaldarius

DOEpatents

Lee, Brady D; Newby, Deborah T; Lacey, Jeffrey A; Thompson, David N; Thompson, Vicki S; Apel, William A; Roberto, Francisco F; Reed, David W

2015-05-12

Isolated and/or purified polypeptides and nucleic acid sequences encoding polypeptides from Alicyclobacillus acidocaldarius are provided. Further provided are methods for modulating or altering recombination inside or outside of a cell using isolated and/or purified polypeptides and/or nucleic acid sequences from Alicyclobacillus acidocaldarius.

Type II restriction modification system methylation subunit of Alicyclobacillus acidocaldarius

DOEpatents

Lee, Brady D.; Newby, Deborah T.; Lacey, Jeffrey A.; Thompson, David N.; Thompson, Vicki S.; Apel, William A.; Roberto, Francisco F.; Reed, David W.

2017-02-14

Isolated and/or purified polypeptides and nucleic acid sequences encoding polypeptides from Alicyclobacillus acidocaldarius are provided. Further provided are methods for modulating or altering recombination inside or outside of a cell using isolated and/or purified polypeptides and/or nucleic acid sequences from Alicyclobacillus acidocaldarius.

Epigenetics in women's health care.

PubMed

Pozharny, Yevgeniya; Lambertini, Luca; Clunie, Garfield; Ferrara, Lauren; Lee, Men-Jean

2010-01-01

Epigenetics refers to structural modifications to genes that do not change the nucleotide sequence itself but instead control and regulate gene expression. DNA methylation, histone modification, and RNA regulation are some of the mechanisms involved in epigenetic modification. Epigenetic changes are believed to be a result of changes in an organism's environment that result in fixed and permanent changes in most differentiated cells. Some environmental changes that have been linked to epigenetic changes include starvation, folic acid, and various chemical exposures. There are periods in an organism's life cycle in which the organism is particularly susceptible to epigenetic influences; these include fertilization, gametogenesis, and early embryo development. These are also windows of opportunity for interventions during the reproductive life cycle of women to improve maternal-child health. New data suggest that epigenetic influences might be involved in the regulation of fetal development and the pathophysiology of adult diseases such as cancer, diabetes, obesity, and neurodevelopmental disorders. Various epigenetic mechanisms may also be involved in the pathogenesis of preeclampsia and intrauterine growth restriction. Additionally, environmental exposures are being held responsible for causing epigenetic changes that lead to a disease process. Exposure to heavy metals, bioflavonoids, and endocrine disruptors, such as bisphenol A and phthalates, has been shown to affect the epigenetic memory of an organism. Their long-term effects are unclear at this point, but many ongoing studies are attempting to elucidate the pathophysiological effects of such gene-environment interactions. (c) 2010 Mount Sinai School of Medicine.

48 CFR 252.225-7011 - Restriction on acquisition of supercomputers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... of supercomputers. 252.225-7011 Section 252.225-7011 Federal Acquisition Regulations System DEFENSE... CLAUSES Text of Provisions And Clauses 252.225-7011 Restriction on acquisition of supercomputers. As prescribed in 225.7012-3, use the following clause: Restriction on Acquisition of Supercomputers (JUN 2005...

48 CFR 252.225-7011 - Restriction on acquisition of supercomputers.

Code of Federal Regulations, 2014 CFR

2014-10-01

... of supercomputers. 252.225-7011 Section 252.225-7011 Federal Acquisition Regulations System DEFENSE... CLAUSES Text of Provisions And Clauses 252.225-7011 Restriction on acquisition of supercomputers. As prescribed in 225.7012-3, use the following clause: Restriction on Acquisition of Supercomputers (JUN 2005...

48 CFR 252.225-7011 - Restriction on acquisition of supercomputers.

Code of Federal Regulations, 2012 CFR

2012-10-01

... of supercomputers. 252.225-7011 Section 252.225-7011 Federal Acquisition Regulations System DEFENSE... CLAUSES Text of Provisions And Clauses 252.225-7011 Restriction on acquisition of supercomputers. As prescribed in 225.7012-3, use the following clause: Restriction on Acquisition of Supercomputers (JUN 2005...

48 CFR 252.225-7011 - Restriction on acquisition of supercomputers.

Code of Federal Regulations, 2013 CFR

2013-10-01

... of supercomputers. 252.225-7011 Section 252.225-7011 Federal Acquisition Regulations System DEFENSE... CLAUSES Text of Provisions And Clauses 252.225-7011 Restriction on acquisition of supercomputers. As prescribed in 225.7012-3, use the following clause: Restriction on Acquisition of Supercomputers (JUN 2005...

48 CFR 252.225-7011 - Restriction on acquisition of supercomputers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... of supercomputers. 252.225-7011 Section 252.225-7011 Federal Acquisition Regulations System DEFENSE... CLAUSES Text of Provisions And Clauses 252.225-7011 Restriction on acquisition of supercomputers. As prescribed in 225.7012-3, use the following clause: Restriction on Acquisition of Supercomputers (JUN 2005...

48 CFR 1852.227-19 - Commercial computer software-Restricted rights.

Code of Federal Regulations, 2013 CFR

2013-10-01

... software-Restricted rights. 1852.227-19 Section 1852.227-19 Federal Acquisition Regulations System NATIONAL... Provisions and Clauses 1852.227-19 Commercial computer software—Restricted rights. (a) As prescribed in 1827... regarding any computer software delivered under this contract/purchase order, the NASA Contracting Officer...

48 CFR 1852.227-19 - Commercial computer software-Restricted rights.

Code of Federal Regulations, 2010 CFR

2010-10-01

... software-Restricted rights. 1852.227-19 Section 1852.227-19 Federal Acquisition Regulations System NATIONAL... Provisions and Clauses 1852.227-19 Commercial computer software—Restricted rights. (a) As prescribed in 1827... regarding any computer software delivered under this contract/purchase order, the NASA Contracting Officer...

48 CFR 1852.227-19 - Commercial computer software-Restricted rights.

Code of Federal Regulations, 2011 CFR

2011-10-01

... software-Restricted rights. 1852.227-19 Section 1852.227-19 Federal Acquisition Regulations System NATIONAL... Provisions and Clauses 1852.227-19 Commercial computer software—Restricted rights. (a) As prescribed in 1827... regarding any computer software delivered under this contract/purchase order, the NASA Contracting Officer...

48 CFR 1852.227-19 - Commercial computer software-Restricted rights.

Code of Federal Regulations, 2012 CFR

2012-10-01

... software-Restricted rights. 1852.227-19 Section 1852.227-19 Federal Acquisition Regulations System NATIONAL... Provisions and Clauses 1852.227-19 Commercial computer software—Restricted rights. (a) As prescribed in 1827... regarding any computer software delivered under this contract/purchase order, the NASA Contracting Officer...

48 CFR 1852.227-19 - Commercial computer software-Restricted rights.

Code of Federal Regulations, 2014 CFR

2014-10-01

... software-Restricted rights. 1852.227-19 Section 1852.227-19 Federal Acquisition Regulations System NATIONAL... Provisions and Clauses 1852.227-19 Commercial computer software—Restricted rights. (a) As prescribed in 1827... regarding any computer software delivered under this contract/purchase order, the NASA Contracting Officer...

Highlights of the DNA cutters: a short history of the restriction enzymes

PubMed Central

Loenen, Wil A. M.; Dryden, David T. F.; Raleigh, Elisabeth A.; Wilson, Geoffrey G.; Murray, Noreen E.

2014-01-01

In the early 1950’s, ‘host-controlled variation in bacterial viruses’ was reported as a non-hereditary phenomenon: one cycle of viral growth on certain bacterial hosts affected the ability of progeny virus to grow on other hosts by either restricting or enlarging their host range. Unlike mutation, this change was reversible, and one cycle of growth in the previous host returned the virus to its original form. These simple observations heralded the discovery of the endonuclease and methyltransferase activities of what are now termed Type I, II, III and IV DNA restriction-modification systems. The Type II restriction enzymes (e.g. EcoRI) gave rise to recombinant DNA technology that has transformed molecular biology and medicine. This review traces the discovery of restriction enzymes and their continuing impact on molecular biology and medicine. PMID:24141096

Highlights of the DNA cutters: a short history of the restriction enzymes.

PubMed

Loenen, Wil A M; Dryden, David T F; Raleigh, Elisabeth A; Wilson, Geoffrey G; Murray, Noreen E

2014-01-01

In the early 1950's, 'host-controlled variation in bacterial viruses' was reported as a non-hereditary phenomenon: one cycle of viral growth on certain bacterial hosts affected the ability of progeny virus to grow on other hosts by either restricting or enlarging their host range. Unlike mutation, this change was reversible, and one cycle of growth in the previous host returned the virus to its original form. These simple observations heralded the discovery of the endonuclease and methyltransferase activities of what are now termed Type I, II, III and IV DNA restriction-modification systems. The Type II restriction enzymes (e.g. EcoRI) gave rise to recombinant DNA technology that has transformed molecular biology and medicine. This review traces the discovery of restriction enzymes and their continuing impact on molecular biology and medicine.

GENETIC CONTROL OF RESTRICTION AND MODIFICATION IN ESCHERICHIA COLI1

PubMed Central

Boyer, Herbert

1964-01-01

Boyer, Herbert (Yale University, New Haven, Conn.). Genetic control of restriction and modification in Escherichia coli. J. Bacteriol. 88:1652–1660. 1964.—Bacterial crosses with K-12 strains of Escherichia coli as Hfr donors (Hfr Hayes, Hfr Cavalli, and Hfr P4X-6) and B/r strains of E. coli as F− recipients were found to differ from crosses between K-12 Hfr donors and K-12 F− recipients in two ways: (i) recombinants (leu, pro, lac, and gal) did not appear at discrete time intervals but did appear simultaneously 30 min after matings were initiated, and (ii) the linkage of unselected markers to selected markers was reduced. Integration of a genetic region linked to the threonine locus of K-12 into the B/r genome resulted in a hybrid which no longer gave anomalous results in conjugation experiments. A similar region of the B strain was introduced into the K-12 strain, which then behaved as a typical B F− recipient. These observations are interpreted as the manifestation of host-controlled modification and restriction on the E. coli chromosome. This was verified by experiments on the restriction and modification of the bacteriophage lambda, F-lac, F-gal, and sex-factor, F1. It was found that the genetic region that controlled the mating responses of the K-12 and B/r strains also controlled the modification and restriction properties of these two strains. The genes responsible for the restricting and modifying properties of the K-12 and B strains of E. coli were found to be allelic, linked to each other, and linked to the threonine locus. PMID:14240953

[Epigenome: what we learned from Rett syndrome, a neurological disease caused by mutation of a methyl-CpG binding protein].

PubMed

Kubota, Takeo

2013-01-01

Epigenome is defined as DNA and histone modification-dependent gene regulation system. Abnormalities in this system are known to cause various neuro-developmental diseases. We recently reported that neurological symptoms of Rett syndrome, which is an autistic disorder caused by mutations in methyl-CpG binding protein 2 (MeCP2), was associated with failure of epigenomic gene regulation in neuronal cells, and that clinical differences in the identical twins with Rett syndrome in the differences in DNA methylation in neuronal genes, but not caused by DNA sequence differences. Since central nervus system requires precise gene regulation, neurological diseases including Alzheimer and Parkinson diseases may be caused by acquired DNA modification (epigenomic) changes that results in aberrant gene regulation as well as DNA sequence changes congenitally occurred (mutation).

cuRRBS: simple and robust evaluation of enzyme combinations for reduced representation approaches.

PubMed

Martin-Herranz, Daniel E; Ribeiro, António J M; Krueger, Felix; Thornton, Janet M; Reik, Wolf; Stubbs, Thomas M

2017-11-16

DNA methylation is an important epigenetic modification in many species that is critical for development, and implicated in ageing and many complex diseases, such as cancer. Many cost-effective genome-wide analyses of DNA modifications rely on restriction enzymes capable of digesting genomic DNA at defined sequence motifs. There are hundreds of restriction enzyme families but few are used to date, because no tool is available for the systematic evaluation of restriction enzyme combinations that can enrich for certain sites of interest in a genome. Herein, we present customised Reduced Representation Bisulfite Sequencing (cuRRBS), a novel and easy-to-use computational method that solves this problem. By computing the optimal enzymatic digestions and size selection steps required, cuRRBS generalises the traditional MspI-based Reduced Representation Bisulfite Sequencing (RRBS) protocol to all restriction enzyme combinations. In addition, cuRRBS estimates the fold-reduction in sequencing costs and provides a robustness value for the personalised RRBS protocol, allowing users to tailor the protocol to their experimental needs. Moreover, we show in silico that cuRRBS-defined restriction enzymes consistently out-perform MspI digestion in many biological systems, considering both CpG and CHG contexts. Finally, we have validated the accuracy of cuRRBS predictions for single and double enzyme digestions using two independent experimental datasets. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

48 CFR 225.7016 - Restriction on Ballistic Missile Defense research, development, test, and evaluation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Restriction on Ballistic Missile Defense research, development, test, and evaluation. 225.7016 Section 225.7016 Federal Acquisition... Acquisition 225.7016 Restriction on Ballistic Missile Defense research, development, test, and evaluation. [68...

48 CFR 227.7107-3 - Approval of restricted designs.

Code of Federal Regulations, 2011 CFR

2011-10-01

... designs. 227.7107-3 Section 227.7107-3 Federal Acquisition Regulations System DEFENSE ACQUISITION... Rights in Technical Data 227.7107-3 Approval of restricted designs. The clause at 252.227-7024, Notice and Approval of Restricted Designs, may be included in architect-engineer contracts to permit the...

48 CFR 14.404-4 - Restrictions on disclosure of descriptive literature.

Code of Federal Regulations, 2012 CFR

2012-10-01

... of descriptive literature. 14.404-4 Section 14.404-4 Federal Acquisition Regulations System FEDERAL... Contract 14.404-4 Restrictions on disclosure of descriptive literature. When a bid is accompanied by descriptive literature (as defined in 2.101), and the bidder imposes a restriction that prevents the public...

48 CFR 14.404-4 - Restrictions on disclosure of descriptive literature.

Code of Federal Regulations, 2013 CFR

2013-10-01

... of descriptive literature. 14.404-4 Section 14.404-4 Federal Acquisition Regulations System FEDERAL... Contract 14.404-4 Restrictions on disclosure of descriptive literature. When a bid is accompanied by descriptive literature (as defined in 2.101), and the bidder imposes a restriction that prevents the public...

48 CFR 14.404-4 - Restrictions on disclosure of descriptive literature.

Code of Federal Regulations, 2014 CFR

2014-10-01

... of descriptive literature. 14.404-4 Section 14.404-4 Federal Acquisition Regulations System FEDERAL... Contract 14.404-4 Restrictions on disclosure of descriptive literature. When a bid is accompanied by descriptive literature (as defined in 2.101), and the bidder imposes a restriction that prevents the public...

48 CFR 14.404-4 - Restrictions on disclosure of descriptive literature.

Code of Federal Regulations, 2011 CFR

2011-10-01

... of descriptive literature. 14.404-4 Section 14.404-4 Federal Acquisition Regulations System FEDERAL... Contract 14.404-4 Restrictions on disclosure of descriptive literature. When a bid is accompanied by descriptive literature (as defined in 2.101), and the bidder imposes a restriction that prevents the public...

36 CFR 13.1120 - Bartlett Cove Developed Area closures and restrictions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... closures and restrictions. 13.1120 Section 13.1120 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve Bartlett Cove § 13.1120 Bartlett Cove Developed Area closures and restrictions...

36 CFR 13.1120 - Bartlett Cove Developed Area closures and restrictions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... closures and restrictions. 13.1120 Section 13.1120 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve Bartlett Cove § 13.1120 Bartlett Cove Developed Area closures and restrictions...

36 CFR 13.1120 - Bartlett Cove Developed Area closures and restrictions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... closures and restrictions. 13.1120 Section 13.1120 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve Bartlett Cove § 13.1120 Bartlett Cove Developed Area closures and restrictions...

48 CFR 14.404-4 - Restrictions on disclosure of descriptive literature.

Code of Federal Regulations, 2010 CFR

2010-10-01

... of descriptive literature. 14.404-4 Section 14.404-4 Federal Acquisition Regulations System FEDERAL... Contract 14.404-4 Restrictions on disclosure of descriptive literature. When a bid is accompanied by descriptive literature (as defined in 2.101), and the bidder imposes a restriction that prevents the public...

48 CFR 252.225-7025 - Restriction on acquisition of forgings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... of forgings. 252.225-7025 Section 252.225-7025 Federal Acquisition Regulations System DEFENSE... CLAUSES Text of Provisions And Clauses 252.225-7025 Restriction on acquisition of forgings. As prescribed in 225.7102-4, use the following clause: Restriction on Acquisition of Forgings (DEC 2009) (a...

Gametocidal chromosomes enhancing chromosome aberration in common wheat induced by 5-azacytidine.

PubMed

Su, W-Y; Cong, W-W; Shu, Y-J; Wang, D; Xu, G-H; Guo, C-H

2013-07-08

The gametocidal (Gc) chromosome from Aegilops spp induces chromosome mutation, which is introduced into common wheat as a tool of chromosome manipulation for genetic improvement. The Gc chromosome functions similar to a restriction-modification system in bacteria, in which DNA methylation is an important regulator. We treated root tips of wheat carrying Gc chromosomes with the hypomethylation agent 5-azacytidine; chromosome breakage and micronuclei were observed in these root tips. The frequency of aberrations differed in wheat containing different Gc chromosomes, suggesting different functions inducing chromosome breakage. Gc chromosome 3C caused the greatest degree of chromosome aberration, while Gc chromosome 3C(SAT) and 2C caused only slight chromosome aberration. Gc chromosome 3C induced different degrees of chromosome aberration in wheat varieties Triticum aestivum var. Chinese Spring and Norin 26, demonstrating an inhibition function in common wheat.

A Type 3 prophage of “Candidatus Liberibacter asiaticus” carrying a restriction-modification system

USDA-ARS?s Scientific Manuscript database

Prophages, the lysogenic form of bacterial phages, are important genetic entities of “Candidatus Liberibacter asiaticus” (CLas), a non-culturable alfa-proteobacterium associated with citrus Huanglongbing (HLB). Two different CLas prophages are currently known, SC1 (Type 1) that has a lytic cycle and...

An Investigation of Privately Financed Renewable Energy Projects for Army Installations

DTIC Science & Technology

1990-09-01

PURPA ) restrictions, current Internal Revenue Service (IRS) rulings, and the expiration of Federal tax credits were identified. Task 3: Innovative...palatable to the policymakers. Existing legislation, including Federal acquisition regulations, PURPA restrictions, and existing tax laws, while not...discourage the application of renewable energy systems. The PURPA rules are undergoing evaluation. Although the effect of the FederalEnergy Regulating

Quantitative proteomic characterization of redox-dependent post-translational modifications on protein cysteines

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

Duan, Jicheng; Gaffrey, Matthew J.; Qian, Wei-Jun

Protein cysteine thiols play a crucial role in redox signaling, regulation of enzymatic activity and protein function, and maintaining redox homeostasis in living systems. The unique chemical reactivity of thiol groups makes cysteine susceptible to oxidative modifications by reactive oxygen and nitrogen species to form a broad array of reversible and irreversible protein post-translational modifications (PTMs). The reversible modifications in particular are one of the major components of redox signaling and are involved in regulation of various cellular processes under physiological and pathological conditions. The biological significance of these redox PTMs in health and diseases has been increasingly recognized. Herein,more » we review the recent advances of quantitative proteomic approaches for investigating redox PTMs in complex biological systems, including the general considerations of sample processing, various chemical or affinity enrichment strategies, and quantitative approaches. We also highlight a number of redox proteomic approaches that enable effective profiling of redox PTMs for addressing specific biological questions. Although some technological limitations remain, redox proteomics is paving the way towards a better understanding of redox signaling and regulation in human health and diseases.« less

EXTRA-EMBRYONIC-SPECIFIC IMPRINTED EXPRESSION IS RESTRICTED TO DEFINED LINEAGES IN THE POST-IMPLANTATION EMBRYO

PubMed Central

Hudson, Quanah J.; Seidl, Christine I.M.; Kulinski, Tomasz M.; Huang, Ru; Warczok, Katarzyna E.; Bittner, Romana; Bartolomei, Marisa S.; Barlow, Denise P.

2011-01-01

A subset of imprinted genes in the mouse have been reported to show imprinted expression that is restricted to the placenta, a short-lived extra-embryonic organ. Notably these so-called 'placental-specific' imprinted genes are expressed from both parental alleles in embryo and adult tissues. The placenta is an embryonic-derived organ that is closely associated with maternal tissue and as a consequence, maternal contamination can be mistaken for maternal-specific imprinted expression. The complexity of the placenta, which arises from multiple embryonic lineages, poses additional problems in accurately assessing allele-specific repressive epigenetic modifications in genes that also show lineage-specific silencing in this organ. These problems require that extra evidence be obtained to support the imprinted status of genes whose imprinted expression is restricted to the placenta. We show here that the extra-embryonic visceral yolk sac (VYS), a nutritive membrane surrounding the developing embryo, shows a similar 'extra-embryonic-lineage-specific' pattern of imprinted expression. We present an improved enzymatic technique for separating the bilaminar VYS and show that this pattern of imprinted expression is restricted to the endoderm layer. Finally, we show that VYS 'extra-embryonic-lineage-specific' imprinted expression is regulated by DNA methylation in a similar manner as shown for genes showing multi-lineage imprinted expression in extra-embryonic, embryonic and adult tissues. These results show that the VYS is an improved model for studying the epigenetic mechanisms regulating extra-embryonic-lineage-specific imprinted expression. PMID:21354127

Arabidopsis TCH4, regulated by hormones and the environment, encodes a xyloglucan endotransglycosylase

NASA Technical Reports Server (NTRS)

Xu, W.; Purugganan, M. M.; Polisensky, D. H.; Antosiewicz, D. M.; Fry, S. C.; Braam, J.

1995-01-01

Adaptation of plants to environmental conditions requires that sensing of external stimuli be linked to mechanisms of morphogenesis. The Arabidopsis TCH (for touch) genes are rapidly upregulated in expression in response to environmental stimuli, but a connection between this molecular response and developmental alterations has not been established. We identified TCH4 as a xyloglucan endotransglycosylase by sequence similarity and enzyme activity. Xyloglucan endotransglycosylases most likely modify cell walls, a fundamental determinant of plant form. We determined that TCH4 expression is regulated by auxin and brassinosteroids, by environmental stimuli, and during development, by a 1-kb region. Expression was restricted to expanding tissues and organs that undergo cell wall modification. Regulation of genes encoding cell wall-modifying enzymes, such as TCH4, may underlie plant morphogenetic responses to the environment.

Akt kinase C-terminal modifications control activation loop dephosphorylation and enhance insulin response.

PubMed

Chan, Tung O; Zhang, Jin; Tiegs, Brian C; Blumhof, Brian; Yan, Linda; Keny, Nikhil; Penny, Morgan; Li, Xue; Pascal, John M; Armen, Roger S; Rodeck, Ulrich; Penn, Raymond B

2015-10-01

The Akt protein kinase, also known as protein kinase B, plays key roles in insulin receptor signalling and regulates cell growth, survival and metabolism. Recently, we described a mechanism to enhance Akt phosphorylation that restricts access of cellular phosphatases to the Akt activation loop (Thr(308) in Akt1 or protein kinase B isoform alpha) in an ATP-dependent manner. In the present paper, we describe a distinct mechanism to control Thr(308) dephosphorylation and thus Akt deactivation that depends on intramolecular interactions of Akt C-terminal sequences with its kinase domain. Modifications of amino acids surrounding the Akt1 C-terminal mTORC2 (mammalian target of rapamycin complex 2) phosphorylation site (Ser(473)) increased phosphatase resistance of the phosphorylated activation loop (pThr(308)) and amplified Akt phosphorylation. Furthermore, the phosphatase-resistant Akt was refractory to ceramide-dependent dephosphorylation and amplified insulin-dependent Thr(308) phosphorylation in a regulated fashion. Collectively, these results suggest that the Akt C-terminal hydrophobic groove is a target for the development of agents that enhance Akt phosphorylation by insulin. © 2015 Authors; published by Portland Press Limited.

Akt kinase C-terminal modifications control activation loop dephosphorylation and enhance insulin response

PubMed Central

Chan, Tung O.; Zhang, Jin; Tiegs, Brian C.; Blumhof, Brian; Yan, Linda; Keny, Nikhil; Penny, Morgan; Li, Xue; Pascal, John M.; Armen, Roger S.; Rodeck, Ulrich; Penn, Raymond B.

2015-01-01

The Akt protein kinase, also known as protein kinase B, plays key roles in insulin receptor signalling and regulates cell growth, survival and metabolism. Recently, we described a mechanism to enhance Akt phosphorylation that restricts access of cellular phosphatases to the Akt activation loop (Thr308 in Akt1 or protein kinase B isoform alpha) in an ATP-dependent manner. In the present paper, we describe a distinct mechanism to control Thr308 dephosphorylation and thus Akt deactivation that depends on intramolecular interactions of Akt C-terminal sequences with its kinase domain. Modifications of amino acids surrounding the Akt1 C-terminal mTORC2 (mammalian target of rapamycin complex 2) phosphorylation site (Ser473) increased phosphatase resistance of the phosphorylated activation loop (pThr308) and amplified Akt phosphorylation. Furthermore, the phosphatase-resistant Akt was refractory to ceramide-dependent dephosphorylation and amplified insulin-dependent Thr308 phosphorylation in a regulated fashion. Collectively, these results suggest that the Akt C-terminal hydrophobic groove is a target for the development of agents that enhance Akt phosphorylation by insulin. PMID:26201515

76 FR 17736 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-30

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System Pursuant to Title 49 Code of Federal Regulations (CFR) Part 235 and 49 U.S.C. 20502(a), the following railroad has petitioned the Federal Railroad...

48 CFR 1443.205 - Contract clauses.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract clauses. 1443.205 Section 1443.205 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 1443.205 Contract clauses. BPCs may establish procedures, when...

48 CFR 1443.205 - Contract clauses.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Contract clauses. 1443.205 Section 1443.205 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 1443.205 Contract clauses. BPCs may establish procedures, when...

The Modification of Biocellular Chemical Reactions by Environmental Physicochemicals

NASA Astrophysics Data System (ADS)

Ishido, M.

Environmental risk factors affect human biological system to different extent from modification of biochemical reaction to cellular catastrophe. There are considerable public concerns about electromagnetic fields and endocrine disruptors. Their risk assessments have not been fully achieved because of their scientific uncertainty: electromagnetic fields just modify the bioreaction in the restricted cells and endocrine disruptors are quite unique in that their expression is dependent on the exposure periods throughout a life. Thus, we here describe their molecular characterization to establish the new risk assessments for environmental physicochemicals.

48 CFR 1246.705 - Limitations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Limitations. 1246.705 Section 1246.705 Federal Acquisition Regulations System DEPARTMENT OF TRANSPORTATION CONTRACT MANAGEMENT QUALITY ASSURANCE Warranties 1246.705 Limitations. (a) The following restrictions are applicable to DOT...

48 CFR 225.7016-2 - Restriction.

Code of Federal Regulations, 2010 CFR

2010-10-01

... the Ballistic Missile Defense Program. [68 FR 15627, Mar. 31, 2003. Redesignated at 74 FR 53413, Oct... Section 225.7016-2 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Authorization Acts, Appropriations Acts, and...

Array automated assembly task, phase 2. Low cost silicon solar array project

NASA Technical Reports Server (NTRS)

Rhee, S. S.; Jones, G. T.; Allison, K. T.

1978-01-01

Several modifications instituted in the wafer surface preparation process served to significantly reduce the process cost to 1.55 cents per peak watt in 1975 cents. Performance verification tests of a laser scanning system showed a limited capability to detect hidden cracks or defects, but with potential equipment modifications this cost effective system could be rendered suitable for applications. Installation of electroless nickel plating system was completed along with an optimization of the wafer plating process. The solder coating and flux removal process verification test was completed. An optimum temperature range of 500-550 C was found to produce uniform solder coating with the restriction that a modified dipping procedure is utilized. Finally, the construction of the spray-on dopant equipment was completed.

Development of an air flow thermal balance calorimeter

NASA Technical Reports Server (NTRS)

Sherfey, J. M.

1972-01-01

An air flow calorimeter, based on the idea of balancing an unknown rate of heat evolution with a known rate of heat evolution, was developed. Under restricted conditions, the prototype system is capable of measuring thermal wattages from 10 milliwatts to 1 watt, with an error no greater than 1 percent. Data were obtained which reveal system weaknesses and point to modifications which would effect significant improvements.

Reduced state feedback gain computation. [optimization and control theory for aircraft control

NASA Technical Reports Server (NTRS)

Kaufman, H.

1976-01-01

Because application of conventional optimal linear regulator theory to flight controller design requires the capability of measuring and/or estimating the entire state vector, it is of interest to consider procedures for computing controls which are restricted to be linear feedback functions of a lower dimensional output vector and which take into account the presence of measurement noise and process uncertainty. Therefore, a stochastic linear model that was developed is presented which accounts for aircraft parameter and initial uncertainty, measurement noise, turbulence, pilot command and a restricted number of measurable outputs. Optimization with respect to the corresponding output feedback gains was performed for both finite and infinite time performance indices without gradient computation by using Zangwill's modification of a procedure originally proposed by Powell. Results using a seventh order process show the proposed procedures to be very effective.

The absence of ion-regulatory suppression in the gills of the aquatic air-breathing fish Trichogaster lalius during oxygen stress.

PubMed

Huang, Chun-Yen; Lin, Hsueh-Hsi; Lin, Cheng-Huang; Lin, Hui-Chen

2015-01-01

The strategy for most teleost to survive in hypoxic or anoxic conditions is to conserve energy expenditure, which can be achieved by suppressing energy-consuming activities such as ion regulation. However, an air-breathing fish can cope with hypoxic stress using a similar adjustment or by enhancing gas exchange ability, both behaviorally and physiologically. This study examined Trichogaster lalius, an air-breathing fish without apparent gill modification, for their gill ion-regulatory abilities and glycogen utilization under a hypoxic treatment. We recorded air-breathing frequency, branchial morphology, and the expression of ion-regulatory proteins (Na(+)/K(+)-ATPase and vacuolar-type H(+)-ATPase) in the 1(st) and 4(th) gills and labyrinth organ (LO), and the expression of glycogen utilization (GP, glycogen phosphorylase protein expression and glycogen content) and other protein responses (catalase, CAT; carbonic anhydrase II, CAII; heat shock protein 70, HSP70; hypoxia-inducible factor-1α, HIF-1α; proliferating cell nuclear antigen, PCNA; superoxidase dismutase, SOD) in the gills of T. lalius after 3 days in hypoxic and restricted conditions. No morphological modification of the 1(st) and 4(th) gills was observed. The air-breathing behavior of the fish and CAII protein expression both increased under hypoxia. Ion-regulatory abilities were not suppressed in the hypoxic or restricted groups, but glycogen utilization was enhanced within the groups. The expression of HIF-1α, HSP70 and PCNA did not vary among the treatments. Regarding the antioxidant system, decreased CAT enzyme activity was observed among the groups. In conclusion, during hypoxic stress, T. lalius did not significantly reduce energy consumption but enhanced gas exchange ability and glycogen expenditure. Copyright © 2014 Elsevier Inc. All rights reserved.

48 CFR 3452.215-70 - Release of restricted data.

Code of Federal Regulations, 2010 CFR

2010-10-01

... regardless of their use of the legend set forth in FAR 52.215-12, Restriction on Disclosure and Use of Data... the data may be exempted from disclosure under the Freedom of Information Act. In accordance with... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Release of restricted data...

48 CFR 352.270-6 - Restriction on use of human subjects.

Code of Federal Regulations, 2013 CFR

2013-10-01

... human subjects. 352.270-6 Section 352.270-6 Federal Acquisition Regulations System HEALTH AND HUMAN....270-6 Restriction on use of human subjects. As prescribed in 370-304(b), the Contracting Officer shall insert the following clause: Restriction on Use of Human Subjects (January 2006) Pursuant to 45 CFR part...

48 CFR 352.270-6 - Restriction on use of human subjects.

Code of Federal Regulations, 2010 CFR

2010-10-01

... human subjects. 352.270-6 Section 352.270-6 Federal Acquisition Regulations System HEALTH AND HUMAN....270-6 Restriction on use of human subjects. As prescribed in 370-304(b), the Contracting Officer shall insert the following clause: Restriction on Use of Human Subjects (January 2006) Pursuant to 45 CFR part...

48 CFR 352.270-6 - Restriction on use of human subjects.

Code of Federal Regulations, 2014 CFR

2014-10-01

... human subjects. 352.270-6 Section 352.270-6 Federal Acquisition Regulations System HEALTH AND HUMAN....270-6 Restriction on use of human subjects. As prescribed in 370-304(b), the Contracting Officer shall insert the following clause: Restriction on Use of Human Subjects (January 2006) Pursuant to 45 CFR part...

48 CFR 352.270-6 - Restriction on use of human subjects.

Code of Federal Regulations, 2011 CFR

2011-10-01

... human subjects. 352.270-6 Section 352.270-6 Federal Acquisition Regulations System HEALTH AND HUMAN....270-6 Restriction on use of human subjects. As prescribed in 370-304(b), the Contracting Officer shall insert the following clause: Restriction on Use of Human Subjects (January 2006) Pursuant to 45 CFR part...

48 CFR 352.270-6 - Restriction on use of human subjects.

Code of Federal Regulations, 2012 CFR

2012-10-01

... human subjects. 352.270-6 Section 352.270-6 Federal Acquisition Regulations System HEALTH AND HUMAN....270-6 Restriction on use of human subjects. As prescribed in 370-304(b), the Contracting Officer shall insert the following clause: Restriction on Use of Human Subjects (January 2006) Pursuant to 45 CFR part...

36 CFR 13.1174 - Whale water restrictions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false Whale water restrictions. 13.1174 Section 13.1174 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve Vessel Operating Restrictions § 13.1174 Whale...

36 CFR 13.1174 - Whale water restrictions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false Whale water restrictions. 13.1174 Section 13.1174 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve Vessel Operating Restrictions § 13.1174 Whale...

The structure of the KlcA and ArdB proteins reveals a novel fold and antirestriction activity against Type I DNA restriction systems in vivo but not in vitro

PubMed Central

Serfiotis-Mitsa, Dimitra; Herbert, Andrew P.; Roberts, Gareth A.; Soares, Dinesh C.; White, John H.; Blakely, Garry W.; Uhrín, Dušan; Dryden, David T. F.

2010-01-01

Plasmids, conjugative transposons and phage frequently encode anti-restriction proteins to enhance their chances of entering a new bacterial host that is highly likely to contain a Type I DNA restriction and modification (RM) system. The RM system usually destroys the invading DNA. Some of the anti-restriction proteins are DNA mimics and bind to the RM enzyme to prevent it binding to DNA. In this article, we characterize ArdB anti-restriction proteins and their close homologues, the KlcA proteins from a range of mobile genetic elements; including an ArdB encoded on a pathogenicity island from uropathogenic Escherichia coli and a KlcA from an IncP-1b plasmid, pBP136 isolated from Bordetella pertussis. We show that all the ArdB and KlcA act as anti-restriction proteins and inhibit the four main families of Type I RM systems in vivo, but fail to block the restriction endonuclease activity of the archetypal Type I RM enzyme, EcoKI, in vitro indicating that the action of ArdB is indirect and very different from that of the DNA mimics. We also present the structure determined by NMR spectroscopy of the pBP136 KlcA protein. The structure shows a novel protein fold and it is clearly not a DNA structural mimic. PMID:20007596

48 CFR 2943.205 - Contract clauses.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Contract clauses. 2943.205 Section 2943.205 Federal Acquisition Regulations System DEPARTMENT OF LABOR CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 2943.205 Contract clauses. HCAs may establish procedures, or office policies, when...

48 CFR 2943.205 - Contract clauses.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 7 2011-10-01 2011-10-01 false Contract clauses. 2943.205 Section 2943.205 Federal Acquisition Regulations System DEPARTMENT OF LABOR CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 2943.205 Contract clauses. HCAs may establish procedures, or office policies, when...

New Insights Into Roles of Ubiquitin Modification in Regulating Plastids and Other Endosymbiotic Organelles.

PubMed

Broad, W; Ling, Q; Jarvis, P

2016-01-01

Recent findings have revealed important and diverse roles for the ubiquitin modification of proteins in the regulation of endosymbiotic organelles, which include the primary plastids of plants as well as complex plastids: the secondary endosymbiotic organelles of cryptophytes, alveolates, stramenopiles, and haptophytes. Ubiquitin modifications have a variety of potential consequences, both to the modified protein itself and to cellular regulation. The ubiquitin-proteasome system (UPS) can target individual proteins for selective degradation by the cytosolic 26S proteasome. Ubiquitin modifications can also signal the removal of whole endosymbiotic organelles, for example, via autophagy as has been well characterized in mitochondria. As plastids must import over 90% of their proteins from the cytosol, the observation that the UPS selectively targets the plastid protein import machinery is particularly significant. In this way, the UPS may influence the development and interconversions of different plastid types, as well as plastid responses to stress, by reconfiguring the organellar proteome. In complex plastids, the Symbiont-derived ERAD-Like Machinery (SELMA) has coopted the protein transport capabilities of the ER-Associated Degradation (ERAD) system, whereby misfolded proteins are retrotranslocated from ER for proteasomal degradation, uncoupling them from proteolysis: SELMA components have been retargeted to the second outermost plastid membrane to mediate protein import. In spite of this wealth of new information, there still remain a large number of unanswered questions and a need to define the roles of ubiquitin modification further in the regulation of plastids. Copyright © 2016 Elsevier Inc. All rights reserved.

Genetic Control of the Secondary Modification of Deoxyribonucleic Acid in Escherichia coli1

PubMed Central

Mamelak, Linda; Boyer, Herbert W.

1970-01-01

The wild-type restriction and modification alleles of Escherichia coli K-12 and B were found to have no measurable effect on the patterns of methylated bases in the deoxyribonucleic acid (DNA) of these strains. The genetic region controlling the methylation of cytosine in E. coli K-12 was mapped close to his, and the presence or absence of this gene in E. coli B or E. coli K had no effect on the restriction and modification properties of these strains. Thus, only a few of the methylated bases in the DNA of these strains are involved in host modification, and the biological role of the remainder remains obscure. PMID:4919756

Regulations which govern the availability of therapeutic drugs in Australia.

PubMed

Shaw, J

1988-10-01

This article looks at the history and development of drug regulation in Australia, concentrating on the changes that have occurred in the last few years. It touches briefly on the system by which many drugs are subsidized and examines the way in which a de facto "restricted" list became less restricted. It deals with clinical trial approval procedures as these have changed markedly and turns to consider advertising and promotion of drugs. In concluding, it discusses the advantages and some of the shortcomings of the system.

Health Benefits of Fasting and Caloric Restriction.

PubMed

Golbidi, Saeid; Daiber, Andreas; Korac, Bato; Li, Huige; Essop, M Faadiel; Laher, Ismail

2017-10-23

Obesity and obesity-related diseases, largely resulting from urbanization and behavioral changes, are now of global importance. Energy restriction, though, is associated with health improvements and increased longevity. We review some important mechanisms related to calorie limitation aimed at controlling of metabolic diseases, particularly diabetes. Calorie restriction triggers a complex series of intricate events, including activation of cellular stress response elements, improved autophagy, modification of apoptosis, and alteration in hormonal balance. Intermittent fasting is not only more acceptable to patients, but it also prevents some of the adverse effects of chronic calorie restriction, especially malnutrition. There are many somatic and potentially psychologic benefits of fasting or intermittent calorie restriction. However, some behavioral modifications related to abstinence of binge eating following a fasting period are crucial in maintaining the desired favorable outcomes.

75 FR 76069 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-07

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration Docket Number FRA-2010-0154 Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System Pursuant to Title 49 Code of Federal Regulations (CFR) part 235 and 49 U.S.C. 20502(a), the following railroad has...

Gene Loss and Lineage-Specific Restriction-Modification Systems Associated with Niche Differentiation in the Campylobacter jejuni Sequence Type 403 Clonal Complex

PubMed Central

Morley, Laura; McNally, Alan; Paszkiewicz, Konrad; Corander, Jukka; Méric, Guillaume; Sheppard, Samuel K.; Blom, Jochen

2015-01-01

Campylobacter jejuni is a highly diverse species of bacteria commonly associated with infectious intestinal disease of humans and zoonotic carriage in poultry, cattle, pigs, and other animals. The species contains a large number of distinct clonal complexes that vary from host generalist lineages commonly found in poultry, livestock, and human disease cases to host-adapted specialized lineages primarily associated with livestock or poultry. Here, we present novel data on the ST403 clonal complex of C. jejuni, a lineage that has not been reported in avian hosts. Our data show that the lineage exhibits a distinctive pattern of intralineage recombination that is accompanied by the presence of lineage-specific restriction-modification systems. Furthermore, we show that the ST403 complex has undergone gene decay at a number of loci. Our data provide a putative link between the lack of association with avian hosts of C. jejuni ST403 and both gene gain and gene loss through nonsense mutations in coding sequences of genes, resulting in pseudogene formation. PMID:25795671

48 CFR 801.602-81 - Documents required for business clearance reviews.

Code of Federal Regulations, 2010 CFR

2010-10-01

... business clearance reviews. 801.602-81 Section 801.602-81 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL DEPARTMENT OF VETERANS AFFAIRS ACQUISITION REGULATION SYSTEM Career... reviews. When a bid or offer, proposed contract modification, or proposed lease requires a business...

48 CFR 917.7403 - Application.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Application. 917.7403 Section 917.7403 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CONTRACTING METHODS AND... Application. The clause at 48 CFR 952.217-70 shall be included in contracts or modifications where contractor...

48 CFR 537.270 - Contract clause.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Contract clause. 537.270 Section 537.270 Federal Acquisition Regulations System GENERAL SERVICES ADMINISTRATION SPECIAL CATEGORIES... the clause at 552.237-73, Restriction on Disclosure of Information, in solicitations and contracts for...

48 CFR 537.270 - Contract clause.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Contract clause. 537.270 Section 537.270 Federal Acquisition Regulations System GENERAL SERVICES ADMINISTRATION SPECIAL CATEGORIES... the clause at 552.237-73, Restriction on Disclosure of Information, in solicitations and contracts for...

48 CFR 3452.215-70 - Release of restricted data.

Code of Federal Regulations, 2014 CFR

2014-10-01

... regardless of their use of the legend set forth in FAR 52.215-1(e), Restriction on Disclosure and Use of Data... and whether the data may be exempted from disclosure under FOIA. In accordance with Executive Order... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false Release of restricted data...

48 CFR 3452.215-70 - Release of restricted data.

Code of Federal Regulations, 2011 CFR

2011-10-01

... regardless of their use of the legend set forth in FAR 52.215-1(e), Restriction on Disclosure and Use of Data... and whether the data may be exempted from disclosure under FOIA. In accordance with Executive Order... 48 Federal Acquisition Regulations System 7 2011-10-01 2011-10-01 false Release of restricted data...

48 CFR 3452.215-70 - Release of restricted data.

Code of Federal Regulations, 2013 CFR

2013-10-01

... regardless of their use of the legend set forth in FAR 52.215-1(e), Restriction on Disclosure and Use of Data... and whether the data may be exempted from disclosure under FOIA. In accordance with Executive Order... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Release of restricted data...

48 CFR 3452.215-70 - Release of restricted data.

Code of Federal Regulations, 2012 CFR

2012-10-01

... regardless of their use of the legend set forth in FAR 52.215-1(e), Restriction on Disclosure and Use of Data... and whether the data may be exempted from disclosure under FOIA. In accordance with Executive Order... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Release of restricted data...

New restriction enzymes discovered from Escherichia coli clinical strains using a plasmid transformation method

PubMed Central

Kasarjian, Julie K. A.; Iida, Masatake; Ryu, Junichi

2003-01-01

The presence of restriction enzymes in bacterial cells has been predicted by either classical phage restriction-modification (R-M) tests, direct in vitro enzyme assays or more recently from bacterial genome sequence analysis. We have applied phage R-M test principles to the transformation of plasmid DNA and established a plasmid R-M test. To validate this test, six plasmids that contain BamHI fragments of phage lambda DNA were constructed and transformed into Escherichia coli strains containing known R-M systems including: type I (EcoBI, EcoAI, Eco124I), type II (HindIII) and type III (EcoP1I). Plasmid DNA with a single recognition site showed a reduction of relative efficiency of transformation (EOT = 10–1–10–2). When multiple recognition sites were present, greater reductions in EOT values were observed. Once established in the cell, the plasmids were subjected to modification (EOT = 1.0). We applied this test to screen E.coli clinical strains and detected the presence of restriction enzymes in 93% (14/15) of cells. Using additional subclones and the computer program, RM Search, we identified four new restriction enzymes, Eco377I, Eco585I, Eco646I and Eco777I, along with their recognition sequences, GGA(8N)ATGC, GCC(6N)TGCG, CCA(7N)CTTC, and GGA(6N)TATC, respectively. Eco1158I, an isoschizomer of EcoBI, was also found in this study. PMID:12595571

48 CFR 1843.205-70 - NASA contract clauses.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false NASA contract clauses. 1843.205-70 Section 1843.205-70 Federal Acquisition Regulations System NATIONAL AERONAUTICS AND SPACE ADMINISTRATION CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 1843.205-70 NASA contract clauses. (a)(1...

48 CFR 1843.205-70 - NASA contract clauses.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false NASA contract clauses. 1843.205-70 Section 1843.205-70 Federal Acquisition Regulations System NATIONAL AERONAUTICS AND SPACE ADMINISTRATION CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 1843.205-70 NASA contract clauses. (a)(1...

48 CFR 1843.205-70 - NASA contract clauses.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true NASA contract clauses. 1843.205-70 Section 1843.205-70 Federal Acquisition Regulations System NATIONAL AERONAUTICS AND SPACE ADMINISTRATION CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 1843.205-70 NASA contract clauses. (a)(1...

48 CFR 1843.205-70 - NASA contract clauses.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false NASA contract clauses. 1843.205-70 Section 1843.205-70 Federal Acquisition Regulations System NATIONAL AERONAUTICS AND SPACE ADMINISTRATION CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 1843.205-70 NASA contract clauses. (a)(1...

48 CFR 1843.205-70 - NASA contract clauses.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false NASA contract clauses. 1843.205-70 Section 1843.205-70 Federal Acquisition Regulations System NATIONAL AERONAUTICS AND SPACE ADMINISTRATION CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 1843.205-70 NASA contract clauses. (a)(1...

48 CFR 2143.101 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Section 2143.101 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT, FEDERAL EMPLOYEES GROUP LIFE INSURANCE FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT CONTRACT MODIFICATIONS General..., except to the extent that the definition conflicts with LIFAR 2101.370. ...

48 CFR 3006.303-270 - Content.

Code of Federal Regulations, 2010 CFR

2017-10-01

... 48 Federal Acquisition Regulations System 7 2017-10-01 2017-10-01 false Content. 3006.303-270 Section 3006.303-270 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND... Open Competition 3006.303-270 Content. (a)(9)(iv) For a proposed contract subject to the restrictions...

Npas4 Is a Critical Regulator of Learning-Induced Plasticity at Mossy Fiber-CA3 Synapses during Contextual Memory Formation.

PubMed

Weng, Feng-Ju; Garcia, Rodrigo I; Lutzu, Stefano; Alviña, Karina; Zhang, Yuxiang; Dushko, Margaret; Ku, Taeyun; Zemoura, Khaled; Rich, David; Garcia-Dominguez, Dario; Hung, Matthew; Yelhekar, Tushar D; Sørensen, Andreas Toft; Xu, Weifeng; Chung, Kwanghun; Castillo, Pablo E; Lin, Yingxi

2018-03-07

Synaptic connections between hippocampal mossy fibers (MFs) and CA3 pyramidal neurons are essential for contextual memory encoding, but the molecular mechanisms regulating MF-CA3 synapses during memory formation and the exact nature of this regulation are poorly understood. Here we report that the activity-dependent transcription factor Npas4 selectively regulates the structure and strength of MF-CA3 synapses by restricting the number of their functional synaptic contacts without affecting the other synaptic inputs onto CA3 pyramidal neurons. Using an activity-dependent reporter, we identified CA3 pyramidal cells that were activated by contextual learning and found that MF inputs on these cells were selectively strengthened. Deletion of Npas4 prevented both contextual memory formation and this learning-induced synaptic modification. We further show that Npas4 regulates MF-CA3 synapses by controlling the expression of the polo-like kinase Plk2. Thus, Npas4 is a critical regulator of experience-dependent, structural, and functional plasticity at MF-CA3 synapses during contextual memory formation. Copyright © 2018 Elsevier Inc. All rights reserved.

48 CFR 31.103 - Contracts with commercial organizations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Contracts with commercial... with commercial organizations. This category includes all contracts and contract modifications for... modifications with commercial organizations whenever cost analysis is performed as required by 15.404-1(c). (b...

48 CFR 227.7103-3 - Early identification of technical data to be furnished to the Government with restrictions on use...

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Early identification of technical data to be furnished to the Government with restrictions on use, reproduction or disclosure. 227... 227.7103-3 Early identification of technical data to be furnished to the Government with restrictions...

48 CFR 227.7103-3 - Early identification of technical data to be furnished to the Government with restrictions on use...

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Early identification of technical data to be furnished to the Government with restrictions on use, reproduction or disclosure. 227... 227.7103-3 Early identification of technical data to be furnished to the Government with restrictions...

Complex transcriptional and post-transcriptional regulation of an enzyme for Lipopolysaccharide modification

PubMed Central

Moon, Kyung; Six, David A.; Lee, Hyun-Jung; Raetz, Christian R.H.; Gottesman, Susan

2013-01-01

Summary The PhoQ/PhoP two-component system activates many genes for lipopolysaccharide (LPS) modification when cells are grown at low Mg2+ concentrations. An additional target of PhoQ and PhoP is MgrR, an Hfq-dependent small RNA that negatively regulates expression of eptB, also encoding a protein that carries out LPS modification. Examination of LPS confirmed that MgrR effectively silences EptB; the phosphoethanolamine modification associated with EptB is found in ΔmgrR::kan but not mgrR+ cells. Sigma E has been reported to positively regulate eptB, although the eptB promoter does not have the expected Sigma E recognition motifs. The effects of Sigma E and deletion of mgrR on levels of eptB mRNA were independent, and the same 5′ end was found in both cases. In vitro transcription and the behavior of transcriptional and translational fusions demonstrate that Sigma E acts directly at the level of transcription initiation for eptB, from the same start point as Sigma 70. The results suggest that when Sigma E is active, synthesis of eptB transcript outstrips MgrR-dependent degradation; presumably the modification of LPS is important under these conditions. Adding to the complexity of eptB regulation is a second sRNA, ArcZ, which also directly and negatively regulates eptB. PMID:23659637

Restricted and disrupted sleep: effects on autonomic function, neuroendocrine stress systems and stress responsivity.

PubMed

Meerlo, Peter; Sgoifo, Andrea; Suchecki, Deborah

2008-06-01

Frequently disrupted and restricted sleep is a common problem for many people in our modern around-the-clock society. In this context, it is an important question how sleep loss affects the stress systems in our bodies since these systems enable us to deal with everyday challenges. Altered activity and reactivity of these systems following insufficient sleep might have serious repercussions for health and well-being. Studies on both humans and rodents have shown that sleep deprivation and sleep restriction are conditions often associated with mild, temporary increases in the activity of the major neuroendocrine stress systems, i.e., the autonomic sympatho-adrenal system and the hypothalamic-pituitary-adrenal axis. Sleep deprivation may not only have a direct activating effect by itself but, in the long run, it may also affect the reactivity of these systems to other stressors and challenges. Although the first signs of alterations in the way people deal with challenges under conditions of restricted sleep appear to be on the level of emotional perception, chronic sleep restriction may ultimately change the fundamental properties of neuroendocrine stress systems as well. Understandably, few controlled studies in humans have been devoted to this topic. Yet, experimental studies in rodents show that chronic sleep restriction may gradually alter neuroendocrine stress responses as well as the central mechanisms involved in the regulation of these responses. Importantly, the available data from studies in laboratory animals suggest that sleep restriction may gradually change certain brain systems and neuroendocrine systems in a manner that is similar to what is seen in stress-related disorders such as depression (e.g., reduced serotonin receptor sensitivity and altered regulation of the hypothalamic-pituitary-adrenal axis). Such data support the view that insufficient sleep, by acting on stress systems, may sensitize individuals to stress-related disorders. Indeed, epidemiological studies suggest that sleep complaints and sleep restriction may be important risk factors for a variety of diseases that are often linked to stress, including cardiovascular diseases and mood disorders.

48 CFR 2913.301 - Governmentwide commercial purchase card.

Code of Federal Regulations, 2013 CFR

2013-10-01

... other methods of purchasing. However, the same legal restrictions apply to credit card purchases that.../Agency Purchase/Credit Card Program procedures. A number of the more common restrictions which... purchase card. 2913.301 Section 2913.301 Federal Acquisition Regulations System DEPARTMENT OF LABOR...

48 CFR 2913.301 - Governmentwide commercial purchase card.

Code of Federal Regulations, 2014 CFR

2014-10-01

... other methods of purchasing. However, the same legal restrictions apply to credit card purchases that.../Agency Purchase/Credit Card Program procedures. A number of the more common restrictions which... purchase card. 2913.301 Section 2913.301 Federal Acquisition Regulations System DEPARTMENT OF LABOR...

48 CFR 2913.301 - Governmentwide commercial purchase card.

Code of Federal Regulations, 2011 CFR

2011-10-01

... other methods of purchasing. However, the same legal restrictions apply to credit card purchases that.../Agency Purchase/Credit Card Program procedures. A number of the more common restrictions which... purchase card. 2913.301 Section 2913.301 Federal Acquisition Regulations System DEPARTMENT OF LABOR...

48 CFR 2052.204-70 - Security.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Security. 2052.204-70... SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 2052.204-70 Security. As prescribed... National Security information, restricted data, formerly restricted data, and other classified data...

48 CFR 2052.204-70 - Security.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Security. 2052.204-70... SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 2052.204-70 Security. As prescribed... National Security information, restricted data, formerly restricted data, and other classified data...

48 CFR 2052.204-70 - Security.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Security. 2052.204-70... SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 2052.204-70 Security. As prescribed... National Security information, restricted data, formerly restricted data, and other classified data...

48 CFR 2052.204-70 - Security.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Security. 2052.204-70... SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 2052.204-70 Security. As prescribed... National Security information, restricted data, formerly restricted data, and other classified data...

Open-type ferry safety system design for using LNG fuel

NASA Astrophysics Data System (ADS)

Pagonis, D. N.; Livanos, G.; Theotokatos, G.; Peppa, S.; Themelis, N.

2016-12-01

In this feasibility study, we investigate the viability of using Liquefied Natural Gas (LNG) fuel in an open type Ro-Ro passenger ferry and the associated potential challenges with regard to the vessel safety systems. We recommend an appropriate methodology for converting existing ships to run on LNG fuel, discuss all the necessary modifications to the ship's safety systems, and also evaluate the relevant ship evacuation procedures. We outline the basic requirements with which the ship already complies for each safety system and analyze the additional restrictions that must be taken into consideration for the use of LNG fuel. Appropriate actions are recommended. Furthermore, we carry out a hazard identification study. Overall, we clearly demonstrate the technical feasibility of the investigated scenario. Minimal modifications to the ship's safety systems are required to comply with existing safety rules for this specific type of ship.

The Predator becomes the Prey: Regulating the Ubiquitin System by Ubiquitylation and Degradation

PubMed Central

Weissman, Allan M.; Shabek, Nitzan; Ciechanover, Aaron

2012-01-01

Ubiquitylation (also known as ubiquitination) regulates essentially all intracellular processes in eukaryotes through highly specific, and often tightly spatially and temporally regulated, modification of numerous cellular proteins. Although most often associated with proteasomal degradation, ubiquitylation frequently serves non-proteolytic functions. In light of its central roles in cellular regulation, it has not been surprising to find that many of the components of the ubiquitin system itself are regulated by ubiquitylation. This observation has broad implications for pathophysiology. PMID:21860393

Comparative analyses of Xanthomonas and Xylella complete genomes.

PubMed

Moreira, Leandro M; De Souza, Robson F; Digiampietri, Luciano A; Da Silva, Ana C R; Setubal, João C

2005-01-01

Computational analyses of four bacterial genomes of the Xanthomonadaceae family reveal new unique genes that may be involved in adaptation, pathogenicity, and host specificity. The Xanthomonas genus presents 3636 unique genes distributed in 1470 families, while Xylella genus presents 1026 unique genes distributed in 375 families. Among Xanthomonas-specific genes, we highlight a large number of cell wall degrading enzymes, proteases, and iron receptors, a set of energy metabolism genes, second copy of the type II secretion system, type III secretion system, flagella and chemotactic machinery, and the xanthomonadin synthesis gene cluster. Important genes unique to the Xylella genus are an additional copy of a type IV pili gene cluster and the complete machinery of colicin V synthesis and secretion. Intersections of gene sets from both genera reveal a cluster of genes homologous to Salmonella's SPI-7 island in Xanthomonas axonopodis pv citri and Xylella fastidiosa 9a5c, which might be involved in host specificity. Each genome also presents important unique genes, such as an HMS cluster, the kdgT gene, and O-antigen in Xanthomonas axonopodis pv citri; a number of avrBS genes and a distinct O-antigen in Xanthomonas campestris pv campestris, a type I restriction-modification system and a nickase gene in Xylella fastidiosa 9a5c, and a type II restriction-modification system and two genes related to peptidoglycan biosynthesis in Xylella fastidiosa temecula 1. All these differences imply a considerable number of gene gains and losses during the divergence of the four lineages, and are associated with structural genome modifications that may have a direct relation with the mode of transmission, adaptation to specific environments and pathogenicity of each organism.

48 CFR 1545.309 - Providing Government production and research property under special restrictions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... improvements necessary for installing special tooling, special test equipment, or plant equipment, shall not be... production and research property under special restrictions. 1545.309 Section 1545.309 Federal Acquisition Regulations System ENVIRONMENTAL PROTECTION AGENCY CONTRACT MANAGEMENT GOVERNMENT PROPERTY Providing...

14 CFR 1310.9 - Restrictions on lobbying.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Restrictions on lobbying. 1310.9 Section 1310.9 Aeronautics and Space AIR TRANSPORTATION SYSTEM STABILIZATION AIR TRANSPORTATION STABILIZATION BOARD AIR CARRIER GUARANTEE LOAN PROGRAM ADMINISTRATIVE REGULATIONS AND AMENDMENT OR WAIVER OF A TERM OR...

Cloning and Characterization of the Lactococcal Plasmid-Encoded Type II Restriction/Modification System, LlaDII

PubMed Central

Madsen, Annette; Josephsen, Jytte

1998-01-01

The LlaDII restriction/modification (R/M) system was found on the naturally occurring 8.9-kb plasmid pHW393 in Lactococcus lactis subsp. cremoris W39. A 2.4-kb PstI-EcoRI fragment inserted into the Escherichia coli-L. lactis shuttle vector pCI3340 conferred to L. lactis LM2301 and L. lactis SMQ86 resistance against representatives of the three most common lactococcal phage species: 936, P335, and c2. The LlaDII endonuclease was partially purified and found to recognize and cleave the sequence 5′-GC↓NGC-3′, where the arrow indicates the cleavage site. It is thus an isoschizomer of the commercially available restriction endonuclease Fnu4HI. Sequencing of the 2.4-kb PstI-EcoRI fragment revealed two open reading frames arranged tandemly and separated by a 105-bp intergenic region. The endonuclease gene of 543 bp preceded the methylase gene of 954 bp. The deduced amino acid sequence of the LlaDII R/M system showed high homology to that of its only sequenced isoschizomer, Bsp6I from Bacillus sp. strain RFL6, with 41% identity between the endonucleases and 60% identity between the methylases. The genetic organizations of the LlaDII and Bsp6I R/M systems are identical. Both methylases have two recognition sites (5′-GCGGC-3′ and 5′-GCCGC-3′) forming a putative stem-loop structure spanning part of the presumed −35 sequence and part of the intervening region between the −35 and −10 sequences. Alignment of the LlaDII and Bsp6I methylases with other m5C methylases showed that the protein primary structures possessed the same organization. PMID:9647810

O-Fucosylation of Thrombospondin Type 1 Repeats Restricts Epithelial to Mesenchymal Transition (EMT) and Maintains Epiblast Pluripotency During Mouse Gastrulation

PubMed Central

Du, Jianguang; Takeuchi, Hideyuki; Leonhard-Melief, Christina; Shroyer, Kenneth R.; Dlugosz, Malgosia; Haltiwanger, Robert S.; Holdener, Bernadette C.

2010-01-01

Thrombospondin type 1 repeat (TSR) superfamily members regulate diverse biological activities ranging from cell motility to inhibition of angiogenesis. In this study, we verified that mouse protein O-fucosyltransferase-2 (POFUT2) specifically adds O-fucose to TSRs. Using two Pofut2 gene trap lines, we demonstrated that O-fucosylation of TSRs was essential for restricting epithelial to mesenchymal transition in the primitive streak, correct patterning of mesoderm, and localization of the definitive endoderm. Although Pofut2 mutant embryos established anterior/posterior polarity, they underwent extensive mesoderm differentiation at the expense of maintaining epiblast pluripotency. Moreover, mesoderm differentiation was biased towards the vascular endothelial cell lineage. Localization of Foxa2 and Cer1 expressing cells within the interior of Pofut2 mutant embryos suggested that POFUT2 activity was also required for the displacement of the primitive endoderm by definitive endoderm. Notably, Nodal, BMP4, Fgf8, and Wnt3 expression were markedly elevated and expanded in Pofut2 mutants, providing evidence that O-fucose modification of TSRs was essential for modulation of growth factor signaling during gastrulation. The ability of Pofut2 mutant embryos to form teratomas comprised of tissues from all three germ layer origins suggested that defects in Pofut2 mutant embryos resulted from abnormalities in the extracellular environment. This prediction is consistent with the observation that POFUT2 targets are constitutive components of the extracellular matrix (ECM) or associate with the ECM. For this reason, the Pofut2 mutants represent a valuable tool for studying the role of O-fucosylation in ECM synthesis and remodeling, and will be a valuable model to study how post-translational modification of ECM components regulates the formation of tissue boundaries, cell movements, and signaling. PMID:20637190

48 CFR 215.408 - Solicitation provisions and contract clauses.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CONTRACTING METHODS AND CONTRACT TYPES CONTRACTING BY....215-11, Price Reduction for Defective Cost or Pricing Data—Modifications; (ii) FAR 52.215-12, Subcontractor Cost or Pricing Data; or (iii) FAR 52.215-13, Subcontractor Cost or Pricing Data—Modifications. (2...

Discovery of a novel restriction endonuclease by genome comparison and application of a wheat-germ-based cell-free translation assay: PabI (5'-GTA/C) from the hyperthermophilic archaeon Pyrococcus abyssi.

PubMed

Ishikawa, Ken; Watanabe, Miki; Kuroita, Toshihiro; Uchiyama, Ikuo; Bujnicki, Janusz M; Kawakami, Bunsei; Tanokura, Masaru; Kobayashi, Ichizo

2005-07-21

To search for restriction endonucleases, we used a novel plant-based cell-free translation procedure that bypasses the toxicity of these enzymes. To identify candidate genes, the related genomes of the hyperthermophilic archaea Pyrococcus abyssi and Pyrococcus horikoshii were compared. In line with the selfish mobile gene hypothesis for restriction-modification systems, apparent genome rearrangement around putative restriction genes served as a selecting criterion. Several candidate restriction genes were identified and then amplified in such a way that they were removed from their own translation signal. During their cloning into a plasmid, the genes became connected with a plant translation signal. After in vitro transcription by T7 RNA polymerase, the mRNAs were separated from the template DNA and translated in a wheat-germ-based cell-free protein synthesis system. The resulting solution could be directly assayed for restriction activity. We identified two deoxyribonucleases. The novel enzyme was denoted as PabI, purified and found to recognize 5'-GTAC and leave a 3'-TA overhang (5'-GTA/C), a novel restriction enzyme-generated terminus. PabI is active up to 90 degrees C and optimally active at a pH of around 6 and in NaCl concentrations ranging from 100 to 200 mM. We predict that it has a novel 3D structure.

Glutamine methylation in histone H2A is an RNA-polymerase-I-dedicated modification

NASA Astrophysics Data System (ADS)

Tessarz, Peter; Santos-Rosa, Helena; Robson, Sam C.; Sylvestersen, Kathrine B.; Nelson, Christopher J.; Nielsen, Michael L.; Kouzarides, Tony

2014-01-01

Nucleosomes are decorated with numerous post-translational modifications capable of influencing many DNA processes. Here we describe a new class of histone modification, methylation of glutamine, occurring on yeast histone H2A at position 105 (Q105) and human H2A at Q104. We identify Nop1 as the methyltransferase in yeast and demonstrate that fibrillarin is the orthologue enzyme in human cells. Glutamine methylation of H2A is restricted to the nucleolus. Global analysis in yeast, using an H2AQ105me-specific antibody, shows that this modification is exclusively enriched over the 35S ribosomal DNA transcriptional unit. We show that the Q105 residue is part of the binding site for the histone chaperone FACT (facilitator of chromatin transcription) complex. Methylation of Q105 or its substitution to alanine disrupts binding to FACT in vitro. A yeast strain mutated at Q105 shows reduced histone incorporation and increased transcription at the ribosomal DNA locus. These features are phenocopied by mutations in FACT complex components. Together these data identify glutamine methylation of H2A as the first histone epigenetic mark dedicated to a specific RNA polymerase and define its function as a regulator of FACT interaction with nucleosomes.

41 CFR 105-53.132 - GSA Board of Contract Appeals.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Management Regulations System (Continued) GENERAL SERVICES ADMINISTRATION 53-STATEMENT OF ORGANIZATION AND... employment restrictions pursuant to the Ethics in Govenment Act of 1978. Additionally, the Board hears...) Regulations. Regulations pertaining to GSBCA programs are published in 41 CFR part 5A-60. Information on...

41 CFR 105-53.132 - GSA Board of Contract Appeals.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Management Regulations System (Continued) GENERAL SERVICES ADMINISTRATION 53-STATEMENT OF ORGANIZATION AND... employment restrictions pursuant to the Ethics in Govenment Act of 1978. Additionally, the Board hears...) Regulations. Regulations pertaining to GSBCA programs are published in 41 CFR part 5A-60. Information on...

Smoking Norms and the Regulation of E-Cigarettes

PubMed Central

2015-01-01

Electronic nicotine delivery systems (ENDS)—commonly called e-cigarettes—are at the center of a polarized debate. How should they be regulated? Central to this debate is the concern that e-cigarettes could lead to the renormalization of smoking and that the regulation of ENDS should therefore be modeled on the regulation of conventional cigarettes. I argue that arguments based on the renormalization of smoking can lend support to restrictions on marketing of ENDS, but that such arguments are problematic when used to justify restrictions on where ENDS can be used. The debate has been insufficiently sensitive to the ethical complexities of attempts to manipulate social norms to change health behaviors; these complexities must also inform the debate about ENDS and their regulation. PMID:26270285

36 CFR 13.1242 - BCDA closures and restrictions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false BCDA closures and restrictions. 13.1242 Section 13.1242 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Katmai National Park and...

36 CFR 13.1182 - Noise restrictions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false Noise restrictions. 13.1182 Section 13.1182 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve Vessel...

36 CFR 13.1176 - Speed restrictions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false Speed restrictions. 13.1176 Section 13.1176 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve Vessel...

36 CFR 13.1182 - Noise restrictions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false Noise restrictions. 13.1182 Section 13.1182 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve Vessel...

36 CFR 13.1182 - Noise restrictions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false Noise restrictions. 13.1182 Section 13.1182 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve Vessel...

36 CFR 13.1176 - Speed restrictions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false Speed restrictions. 13.1176 Section 13.1176 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve Vessel...

36 CFR 13.1176 - Speed restrictions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false Speed restrictions. 13.1176 Section 13.1176 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve Vessel...

48 CFR 43.201 - General.

Code of Federal Regulations, 2010 CFR

2010-10-01

....201 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 43.201 General. (a) Generally, Government contracts contain a changes clause that permits the contracting officer to make unilateral changes, in designated areas, within the general scope...

48 CFR 43.204 - Administration.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Section 43.204 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 43.204 Administration. (a) Change order documentation. When change orders are not forward priced, they require two documents: the change order and a supplemental agreement...

48 CFR 43.201 - General.

Code of Federal Regulations, 2011 CFR

2011-10-01

....201 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 43.201 General. (a) Generally, Government contracts contain a changes clause that permits the contracting officer to make unilateral changes, in designated areas, within the general scope...

Posttranslational Modifications Regulate the Postsynaptic Localization of PSD-95.

PubMed

Vallejo, Daniela; Codocedo, Juan F; Inestrosa, Nibaldo C

2017-04-01

The postsynaptic density (PSD) consists of a lattice-like array of interacting proteins that organizes and stabilizes synaptic receptors, ion channels, structural proteins, and signaling molecules required for normal synaptic transmission and synaptic function. The scaffolding and hub protein postsynaptic density protein-95 (PSD-95) is a major element of central chemical synapses and interacts with glutamate receptors, cell adhesion molecules, and cytoskeletal elements. In fact, PSD-95 can regulate basal synaptic stability as well as the activity-dependent structural plasticity of the PSD and, therefore, of the excitatory chemical synapse. Several studies have shown that PSD-95 is highly enriched at excitatory synapses and have identified multiple protein structural domains and protein-protein interactions that mediate PSD-95 function and trafficking to the postsynaptic region. PSD-95 is also a target of several signaling pathways that induce posttranslational modifications, including palmitoylation, phosphorylation, ubiquitination, nitrosylation, and neddylation; these modifications determine the synaptic stability and function of PSD-95 and thus regulate the fates of individual dendritic spines in the nervous system. In the present work, we review the posttranslational modifications that regulate the synaptic localization of PSD-95 and describe their functional consequences. We also explore the signaling pathways that induce such changes.

Epitranscriptomics: A New Regulatory Mechanism of Brain Development and Function

PubMed Central

Noack, Florian; Calegari, Federico

2018-01-01

Epigenetic modifications of DNA and chromatin are long known to control stem cell differentiation and organ function but the role of similar modifications at the level or regulatory RNAs is just beginning to emerge. Over 160 RNA modifications have been identified but their abundance, distribution and functional significance are not known. The few available maps of RNA modifications indicated their dynamic regulation during somatic stem cell differentiation, brain development and function in adulthood suggesting a hitherto unsuspected layer of regulation both at the level of RNA metabolism and post-transcriptional control of gene expression. The advent of programmable, RNA-specific CRISPR-Cas editing platforms together with the identification of RNA modifying enzymes now offers the opportunity to investigate the functional role of these elusive epitranscriptome changes. Here, we discuss recent insights in studying the most abundant modifications in functional mRNAs and lncRNAs, N6-methyladenosine and 5-(hydroxy-)methylcytosine, and their role in regulating somatic stem cell differentiation with particular attention to neural stem cells during mammalian corticogenesis. An outlook on novel CRISPR-Cas based systems that allow stem cell reprogramming by epitranscriptome-editing will also be discussed. PMID:29515357

Description, validation, and modification of the Guyton model for space-flight applications. Part A. Guyton model of circulatory, fluid and electrolyte control. Part B. Modification of the Guyton model for circulatory, fluid and electrolyte control

NASA Technical Reports Server (NTRS)

Leonard, J. I.

1985-01-01

The mathematical model that has been a cornerstone for the systems analysis of space-flight physiological studies is the Guyton model describing circulatory, fluid and electrolyte regulation. The model and the modifications that are made to permit simulation and analysis of the stress of weightlessness are described.

36 CFR 13.1910 - KNHL and developed area closures and restrictions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false KNHL and developed area closures and restrictions. 13.1910 Section 13.1910 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Wrangell-St...

36 CFR 13.1184 - Other restrictions on vessels.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false Other restrictions on vessels. 13.1184 Section 13.1184 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve...

36 CFR 13.1328 - EGDA closures and restrictions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false EGDA closures and restrictions. 13.1328 Section 13.1328 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Kenai Fjords National Park Exit...

36 CFR 13.1184 - Other restrictions on vessels.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false Other restrictions on vessels. 13.1184 Section 13.1184 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve...

46 CFR 121.202 - Restrictions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SYSTEMS AND EQUIPMENT Cooking and Heating § 121.202 Restrictions. (a) The use of gasoline for cooking... gases as cooking fuels by 46 Code of Federal Regulations (CFR) part 147 must meet the requirements of § 121.240. The use of these fuels for cooking, heating, and lighting on ferry vessels is prohibited by...

36 CFR 13.1120 - Bartlett Cove Developed Area closures and restrictions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false Bartlett Cove Developed Area closures and restrictions. 13.1120 Section 13.1120 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay...

36 CFR 13.1120 - Bartlett Cove Developed Area closures and restrictions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Bartlett Cove Developed Area closures and restrictions. 13.1120 Section 13.1120 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay...

36 CFR 13.1184 - Other restrictions on vessels.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false Other restrictions on vessels. 13.1184 Section 13.1184 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve...

36 CFR 13.1184 - Other restrictions on vessels.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Other restrictions on vessels. 13.1184 Section 13.1184 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve...

36 CFR 13.1184 - Other restrictions on vessels.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Other restrictions on vessels. 13.1184 Section 13.1184 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve...

SHIELDING CONSIDERATIONS FOR THE SMALL ANIMAL RADIATION RESEARCH PLATFORM (SARRP)

PubMed Central

Sayler, Elaine; Dolney, Derek; Avery, Stephen; Koch, Cameron

2014-01-01

The Small Animal Radiation Research Platform (SARRP) is a commercially available platform designed to deliver conformal, image-guided radiation to small animals using a dual-anode kV x-ray source. At the University of Pennsylvania, a free-standing 2 m3 enclosure was designed to shield the SARRP according to federal code regulating cabinet x-ray systems. The initial design consisted of 4.0-mm-thick lead for all secondary barriers and proved wholly inadequate. Radiation levels outside the enclosure were 15 times higher than expected. Additionally, the leakage appeared to be distributed broadly within the enclosure, so concern arose that a subject might receive significant doses outside the intended treatment field. Thus, a detailed analysis was undertaken to identify and block all sources of leakage. Leakage sources were identified by Kodak X-OmatV (XV) film placed throughout the enclosure. Radiation inside the enclosure was quantified using Gafchromic film. Outside the enclosure, radiation was measured using a survey meter. Sources of leakage included (1) an unnecessarily broad beam exiting the tube, (2) failure of the secondary collimator to confine the primary beam entirely, (3) scatter from the secondary collimator, (4) lack of beam-stop below the treatment volume, and (5) incomplete shielding of the x-ray tube. The exit window was restricted, and a new collimator was designed to address problems (1–3). A beam-stop and additional tube shielding were installed. These modifications reduced internal scatter by more than 100-fold. Radiation outside the enclosure was reduced to levels compliant with federal regulations, provided the SARRP is operated using tube potentials of 175 kV or less. In addition, these simple and relatively inexpensive modifications eliminate the possibility of exposing a larger animal (such as a rat) to significant doses outside the treatment field. PMID:23532076

A phosphoethanolamine transferase specific for the 4'-phosphate residue of Cronobacter sakazakii lipid A.

PubMed

Liu, L; Li, Y; Wang, X; Guo, W

2016-11-01

Investigate how Cronobacter sakazakii modify their lipid A structure to avoid recognition by the host immune cells. Lipid A modification was observed in C. sakazakii BAA894 grown at pH 5·0 but not pH 7·0. Overexpression of C. sakazakii gene ESA_RS09200 in Escherichia coli W3110 caused a phosphoethanolamine (PEA) modification of lipid A; when ESA_RS09200 was deleted in C. sakazakii BAA894, this lipid A modification disappeared. Lipid A modification was observed in BAA894 grown at pH 5·0 when the 1- phosphate residue of lipid A was removed, but disappeared when the 4'- phosphate residue of lipid A was removed. When ESA_RS16430, the orthologous gene of E. coli pmrA, was deleted in C. sakazakii BAA894, this PEA modification of lipid A was still observed, suggesting that this modification was not regulated by the PmrA-PmrB system. Compared to the wild-type BAA894, ESA_RS09200 deletion mutant showed decreased resistance to cationic antimicrobial peptides (CAMP), increased recognition by TLR4/MD2, decreased ability to invade and persist in mammalian cells. ESA_RS09200 in C. sakazakii BAA894 encodes a PEA transferase that specifically adds a PEA to the 4'-phosphate residue of lipid A, but not regulated by the PmrA-PmrB system. PEA modification of lipid A reduces recognition and killing by the host innate immune system. This study showed that modification of the lipid A moiety of C. sakazakii with PEA increased resistance to CAMP and recognition of the immune response although signalling of TLR4/MD2 cascade, suggesting that the organism could not successfully evade the host innate immune system without the transference of PEA to its lipid A moiety. © 2016 The Society for Applied Microbiology.

The Campylobacter jejuni Oxidative Stress Regulator RrpB Is Associated with a Genomic Hypervariable Region and Altered Oxidative Stress Resistance.

PubMed

Gundogdu, Ozan; da Silva, Daiani T; Mohammad, Banaz; Elmi, Abdi; Wren, Brendan W; van Vliet, Arnoud H M; Dorrell, Nick

2016-01-01

Campylobacter jejuni is the leading cause of bacterial foodborne diarrhoeal disease worldwide. Despite the microaerophilic nature of the bacterium, C. jejuni can survive the atmospheric oxygen conditions in the environment. Bacteria that can survive either within a host or in the environment like C. jejuni require variable responses to survive the stresses associated with exposure to different levels of reactive oxygen species. The MarR-type transcriptional regulators RrpA and RrpB have recently been shown to play a role in controlling both the C. jejuni oxidative and aerobic stress responses. Analysis of 3,746 C. jejuni and 486 C. coli genome sequences showed that whilst rrpA is present in over 99% of C. jejuni strains, the presence of rrpB is restricted and appears to correlate with specific MLST clonal complexes (predominantly ST-21 and ST-61). C. coli strains in contrast lack both rrpA and rrpB . In C. jejuni rrpB + strains, the rrpB gene is located within a variable genomic region containing the IF subtype of the type I Restriction-Modification ( hsd ) system, whilst this variable genomic region in C. jejuni rrpB - strains contains the IAB subtype hsd system and not the rrpB gene. C. jejuni rrpB - strains exhibit greater resistance to peroxide and aerobic stress than C. jejuni rrpB + strains. Inactivation of rrpA resulted in increased sensitivity to peroxide stress in rrpB + strains, but not in rrpB - strains. Mutation of rrpA resulted in reduced killing of Galleria mellonella larvae and enhanced biofilm formation independent of rrpB status. The oxidative and aerobic stress responses of rrpB - and rrpB + strains suggest adaptation of C. jejuni within different hosts and niches that can be linked to specific MLST clonal complexes.

Ketone bodies as signaling metabolites

PubMed Central

Newman, John C.; Verdin, Eric

2014-01-01

Traditionally, the ketone body β-hydroxybutyrate (βOHB) has been looked upon as a carrier of energy from liver to peripheral tissues during fasting or exercise. However, βOHB also signals via extracellular receptors and acts as an endogenous inhibitor of histone deacetylases (HDACs). These recent findings support a model in which βOHB functions to link the environment, in this case the diet, and gene expression via chromatin modifications. Here, we review the regulation and functions of ketone bodies, the relationship between ketone bodies and calorie restriction, and the implications of HDAC inhibition by the ketone body βOHB in the modulation of metabolism, and diseases of aging. PMID:24140022

Phenotypic, fermentation characterization, and resistance mechanism analysis of bacteriophage-resistant mutants of Lactobacillus delbrueckii ssp. bulgaricus isolated from traditional Chinese dairy products.

PubMed

Deng, Kaibo; Fang, Wei; Zheng, Baodong; Miao, Song; Huo, Guicheng

2018-03-01

Bacteriophage infection is a large factor in dairy industrial production failure on the basis of pure inoculation fermentation, and developing good commercial starter cultures from wild dairy products and improving the environmental vigor of starter cultures by enhancing their phage resistance are still the most effective solutions. Here we used a spontaneous isolation method to obtain bacteriophage-resistant mutants of Lactobacillus delbrueckii ssp. bulgaricus strains that are used in traditional Chinese fermented dairy products. We analyzed their phenotypes, fermentation characteristics, and resistance mechanisms. The results showed that bacteriophage-insensitive mutants (BIM) BIM8 and BIM12 had high bacteriophage resistance while exhibiting fermentation and coagulation attributes that were as satisfying as those of their respective parent strains KLDS1.1016 and KLDS1.1028. According to the attachment receptor detection, mutants BIM8 and BIM12 exhibited reduced absorption to bacteriophage phiLdb compared with their respective bacteriophage-sensitive parent strains because of changes to the polysaccharides or teichoic acids connected to their peptidoglycan layer. Additionally, genes, including HSDR, HSDM, and HSDS, encoding 3 subunits of a type I restriction-modification system were identified in their respective parent strains. We also discovered that HSDR and HSDM were highly conserved but that HSDS was variable because it is responsible for the DNA specificity of the complex. The late lysis that occurred only in strain KLDS1.1016 and not in strain KLDS1.1028 suggests that the former and its mutant BIM8 also may have an activatable restriction-modification mechanism. We conclude that the L. bulgaricus BIM8 and BIM12 mutants have great potential in the dairy industry as starter cultures, and their phage-resistance mechanism was effective mainly due to the adsorption interference and restriction-modification system. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Alterations in expression of imprinted genes from the H19/IGF2 loci in a multigenerational model of intrauterine growth restriction (IUGR).

PubMed

Gonzalez-Rodriguez, Pablo; Cantu, Jessica; O'Neil, Derek; Seferovic, Maxim D; Goodspeed, Danielle M; Suter, Melissa A; Aagaard, Kjersti M

2016-05-01

The H19/IGF2 imprinted loci have attracted recent attention because of their role in cellular differentiation and proliferation, heritable gene regulation, and in utero or early postnatal growth and development. Expression from the imprinted H19/IGF2 locus involves a complex interplay of 3 means of epigenetic regulation: proper establishment of DNA methylation, promoter occupancy of CTCF, and expression of microRNA-675. We have demonstrated previously in a multigenerational rat model of intrauterine growth restriction the epigenetic heritability of adult metabolic syndrome in a F2 generation. We have further demonstrated abrogation of the F2 adult metabolic syndrome phenotype with essential nutrient supplementation of intermediates along the 1-carbon pathway and shown that alterations in the metabolome precede the adult onset of metabolic syndrome. The upstream molecular and epigenomic mediators underlying these observations, however, have yet to be elucidated fully. In the current study, we sought to characterize the impact of the intrauterine growth-restricted lineage and essential nutrient supplementation on both levels and molecular mediators of H19 and IGF2 gene expression in the F2 generation. F2 intrauterine growth-restricted and sham lineages were obtained by exposing P1 (grandmaternal) pregnant dams to bilateral uterine artery ligation or sham surgery at gestational day 19.5. F1 pups were allocated to the essential nutrient supplemented or control diet at postnatal day 21, and bred at 6-7 weeks of age. Hepatic tissues from the resultant F2 offspring at birth and at weaning (day 21) were obtained. Bisulfite modification and sequencing was employed for methylation analysis. H19 and IGF2 expression was measured by quantitative polymerase chain reaction. Promoter occupancy was quantified by the use of chromatin immunoprecipitation, or ChIP, against CTCF insulator proteins. Growth-restricted F2 on control diet demonstrated significant down-regulation in H19 expression compared with sham lineage (0.7831 vs 1.287; P < .05); however, essential nutrient supplementation diet abrogates this difference (4.995 vs 5.100; P > .05). Conversely, Igf2 was up-regulated by essential nutrient supplemented diet on the sham lineage (2.0 fold, P = .01), an effect that was not observed in the growth restricted offspring. A significant differential methylation was observed in the promoter region of region H19 among the intrauterine growth-restricted lineage (18% vs 25%; P < .05) on a control diet, whereas the essential nutrient supplemented diet was alternately associated with hypermethylation in both lineages (sham: 50%; intrauterine growth restriction: 84%, P < .05). Consistent with essential nutrient supplementation impacting the epigenome, a decrease of CTCF promoter occupancy was observed in CTCF4 of the growth restricted lineage (2.45% vs 0.56%; P < .05) on the control diet, an effect that was repressed with essential nutrient supplementation. Heritable growth restriction is associated with changes in H19 gene expression; these changes are reversible with diet supplementation to favorably impact adult metabolic syndrome. Copyright © 2016. Published by Elsevier Inc.

Rational approaches to the treatment of hypertension: modification of lifestyle measures.

PubMed

Sayarlioglu, Hayriye

2013-12-01

Hypertension is an important health problem. Informative counseling is required for patients to completely understand the importance of non-pharmacologic treatments. Lifestyle changes such as restriction of salt intake, exercise, restriction of alcohol intake, diet, and weight loss are included in all hypertension treatment guidelines. However, serious motivation is required from the patient and the physician to succeed in this. Although the decrease in blood pressure may be limited with these measures, lifestyle modifications should be continued.

Epigenetic Control of Cytokine Gene Expression: Regulation of the TNF/LT Locus and T Helper Cell Differentiation

PubMed Central

Falvo, James V.; Jasenosky, Luke D.; Kruidenier, Laurens; Goldfeld, Anne E.

2014-01-01

Epigenetics encompasses transient and heritable modifications to DNA and nucleosomes in the native chromatin context. For example, enzymatic addition of chemical moieties to the N-terminal “tails” of histones, particularly acetylation and methylation of lysine residues in the histone tails of H3 and H4, plays a key role in regulation of gene transcription. The modified histones, which are physically associated with gene regulatory regions that typically occur within conserved noncoding sequences, play a functional role in active, poised, or repressed gene transcription. The “histone code” defined by these modifications, along with the chromatin-binding acetylases, deacetylases, methylases, demethylases, and other enzymes that direct modifications resulting in specific patterns of histone modification, shows considerable evolutionary conservation from yeast to humans. Direct modifications at the DNA level, such as cytosine methylation at CpG motifs that represses promoter activity, are another highly conserved epigenetic mechanism of gene regulation. Furthermore, epigenetic modifications at the nucleosome or DNA level can also be coupled with higher-order intra- or interchromosomal interactions that influence the location of regulatory elements and that can place them in an environment of specific nucleoprotein complexes associated with transcription. In the mammalian immune system, epigenetic gene regulation is a crucial mechanism for a range of physiological processes, including the innate host immune response to pathogens and T cell differentiation driven by specific patterns of cytokine gene expression. Here, we will review current findings regarding epigenetic regulation of cytokine genes important in innate and/or adaptive immune responses, with a special focus upon the tumor necrosis factor/lymphotoxin locus and cytokine-driven CD4+ T cell differentiation into the Th1, Th2, and Th17 lineages. PMID:23683942

Technical prospects for commercial and residential distribution and utilization of hydrogen

NASA Technical Reports Server (NTRS)

Pangborn, J.; Scott, M.; Sharer, J.

1976-01-01

Various investigators have assumed that hydrogen will be compatible with conventional gas delivery systems and that, with minor modifications, hydrogen can be utilized in existing equipment for heating and cooking. The paper addresses some of the issues of concern in the compatibility of natural gas systems with hydrogen and hydrogen mixtures and identifies areas for which tests, research, or development are appropriate. Requirements to be met by atmospheric burners built for most commercial and residential gas appliances are discussed. Expected modifications to appliances for satisfactory operation with hydrogen are closing the primary air shutters, replacing the burners, adjusting the appliance gas regulator for proper delivery pressure, and possibly replacing the gas regulator or its vent.

Cellular architecture mediates DivIVA ultrastructure and regulates min activity in Bacillus subtilis | Center for Cancer Research

Cancer.gov

The Min system in rod-shaped bacteria restricts improper assembly of the division septum. In Escherichia coli, the Min system localizes to the cell poles, but in Bacillus subtilis, it is recruited to nascent cell division sites at mid-cell to prevent aberrant septation events immediately adjacent to a constricting septum. How does the cell spatially and temporally restrict the

Synergistic Modification Induced Specific Recognition between Histone and TRIM24 via Fluctuation Correlation Network Analysis

NASA Astrophysics Data System (ADS)

Zhang, Jinmai; Luo, Huajie; Liu, Hao; Ye, Wei; Luo, Ray; Chen, Hai-Feng

2016-04-01

Histone modification plays a key role in gene regulation and gene expression. TRIM24 as a histone reader can recognize histone modification. However the specific recognition mechanism between TRIM24 and histone modification is unsolved. Here, systems biology method of dynamics correlation network based on molecular dynamics simulation was used to answer the question. Our network analysis shows that the dynamics correlation network of H3K23ac is distinctly different from that of wild type and other modifications. A hypothesis of “synergistic modification induced recognition” is then proposed to link histone modification and TRIM24 binding. These observations were further confirmed from community analysis of networks with mutation and network perturbation. Finally, a possible recognition pathway is also identified based on the shortest path search for H3K23ac. Significant difference of recognition pathway was found among different systems due to methylation and acetylation modifications. The analysis presented here and other studies show that the dynamic network-based analysis might be a useful general strategy to study the biology of protein post-translational modification and associated recognition.

48 CFR 37.101 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., modernization, or modification of supplies, systems, or equipment. (2) Routine recurring maintenance of real... Government-owned equipment, real property, and systems. (6) Communications services. (7) Architect... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Definitions. 37.101...

Genome analysis of Listeria ivanovii strain G770 that caused a deadly aortic prosthesis infection

PubMed Central

Beye, M.; Gouriet, F.; Michelle, C.; Casalta, J.-P.; Habib, G.; Raoult, D.; Fournier, P.-E.

2016-01-01

We sequenced the genome of Listeria ivanovii strain G770, which caused a deadly infection of the thoracic aortic prosthesis of a 78-year-old man. The 2.9 Mb genome exhibited 21 specific genes among L. ivanovii strains, including five genes encoding a type I restriction modification system and one glycopeptide resistance gene. PMID:26933501

Epigenetic Modifications in Essential Hypertension

PubMed Central

Wise, Ingrid A.; Charchar, Fadi J.

2016-01-01

Essential hypertension (EH) is a complex, polygenic condition with no single causative agent. Despite advances in our understanding of the pathophysiology of EH, hypertension remains one of the world’s leading public health problems. Furthermore, there is increasing evidence that epigenetic modifications are as important as genetic predisposition in the development of EH. Indeed, a complex and interactive genetic and environmental system exists to determine an individual’s risk of EH. Epigenetics refers to all heritable changes to the regulation of gene expression as well as chromatin remodelling, without involvement of nucleotide sequence changes. Epigenetic modification is recognized as an essential process in biology, but is now being investigated for its role in the development of specific pathologic conditions, including EH. Epigenetic research will provide insights into the pathogenesis of blood pressure regulation that cannot be explained by classic Mendelian inheritance. This review concentrates on epigenetic modifications to DNA structure, including the influence of non-coding RNAs on hypertension development. PMID:27023534

48 CFR 52.225-20 - Prohibition on Conducting Restricted Business Operations in Sudan-Certification.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Prohibition on Conducting Restricted Business Operations in Sudan-Certification. 52.225-20 Section 52.225-20 Federal Acquisition... Operations in Sudan—Certification. As prescribed at 25.1103(d), insert the following provision: Prohibition...

48 CFR 252.227-7019 - Validation of asserted restrictions-Computer software.

Code of Federal Regulations, 2010 CFR

2010-10-01

... restrictions-Computer software. 252.227-7019 Section 252.227-7019 Federal Acquisition Regulations System...—Computer software. As prescribed in 227.7104(e)(3) or 227.7203-6(c), use the following clause: Validation of Asserted Restrictions—Computer Software (JUN 1995) (a) Definitions. (1) As used in this clause...

48 CFR 252.227-7019 - Validation of asserted restrictions-Computer software.

Code of Federal Regulations, 2011 CFR

2011-10-01

... restrictions-Computer software. 252.227-7019 Section 252.227-7019 Federal Acquisition Regulations System...—Computer software. As prescribed in 227.7104(e)(3) or 227.7203-6(c), use the following clause: Validation of Asserted Restrictions—Computer Software (SEP 2011) (a) Definitions. (1) As used in this clause...

48 CFR 252.227-7019 - Validation of asserted restrictions-Computer software.

Code of Federal Regulations, 2012 CFR

2012-10-01

... restrictions-Computer software. 252.227-7019 Section 252.227-7019 Federal Acquisition Regulations System...—Computer software. As prescribed in 227.7104(e)(3) or 227.7203-6(c), use the following clause: Validation of Asserted Restrictions—Computer Software (SEP 2011) (a) Definitions. (1) As used in this clause...

48 CFR 252.227-7019 - Validation of asserted restrictions-Computer software.

Code of Federal Regulations, 2014 CFR

2014-10-01

... restrictions-Computer software. 252.227-7019 Section 252.227-7019 Federal Acquisition Regulations System...—Computer software. As prescribed in 227.7104(e)(3) or 227.7203-6(c), use the following clause: Validation of Asserted Restrictions—Computer Software (SEP 2011) (a) Definitions. (1) As used in this clause...

48 CFR 252.227-7019 - Validation of asserted restrictions-Computer software.

Code of Federal Regulations, 2013 CFR

2013-10-01

... restrictions-Computer software. 252.227-7019 Section 252.227-7019 Federal Acquisition Regulations System...—Computer software. As prescribed in 227.7104(e)(3) or 227.7203-6(c), use the following clause: Validation of Asserted Restrictions—Computer Software (SEP 2011) (a) Definitions. (1) As used in this clause...

36 CFR 13.1172 - When general operating restrictions do not apply.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false When general operating restrictions do not apply. 13.1172 Section 13.1172 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park...

48 CFR 252.225-7016 - Restriction on acquisition of ball and roller bearings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... of ball and roller bearings. 252.225-7016 Section 252.225-7016 Federal Acquisition Regulations System... and roller bearings. As prescribed in 225.7009-5, use the following clause: Restriction on Acquisition of Ball and Roller Bearings (MAR 2006) (a) Definitions. As used in this clause' (1) Bearing...

36 CFR 13.1172 - When general operating restrictions do not apply.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false When general operating restrictions do not apply. 13.1172 Section 13.1172 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park...

36 CFR 13.1172 - When general operating restrictions do not apply.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false When general operating restrictions do not apply. 13.1172 Section 13.1172 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park...

36 CFR 13.1172 - When general operating restrictions do not apply.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false When general operating restrictions do not apply. 13.1172 Section 13.1172 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park...

36 CFR 13.1172 - When general operating restrictions do not apply.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false When general operating restrictions do not apply. 13.1172 Section 13.1172 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park...

48 CFR 52.215-11 - Price Reduction for Defective Certified Cost or Pricing Data-Modifications.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 2 2011-10-01 2011-10-01 false Price Reduction for... CONTRACT CLAUSES Text of Provisions and Clauses 52.215-11 Price Reduction for Defective Certified Cost or Pricing Data—Modifications. As prescribed in 15.408(c), insert the following clause: Price Reduction for...

48 CFR 43.104 - Notification of contract changes.

Code of Federal Regulations, 2010 CFR

2010-10-01

... changes. 43.104 Section 43.104 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT CONTRACT MODIFICATIONS General 43.104 Notification of contract changes. (a) When a contractor considers that the Government has effected or may effect a change in the contract that has not...

Structural basis for methylesterase CheB regulation by a phosphorylation-activated domain

PubMed Central

Djordjevic, Snezana; Goudreau, Paul N.; Xu, Qingping; Stock, Ann M.; West, Ann H.

1998-01-01

We report the x-ray crystal structure of the methylesterase CheB, a phosphorylation-activated response regulator involved in reversible modification of bacterial chemotaxis receptors. Methylesterase CheB and methyltransferase CheR modulate signaling output of the chemotaxis receptors by controlling the level of receptor methylation. The structure of CheB, which consists of an N-terminal regulatory domain and a C-terminal catalytic domain joined by a linker, was solved by molecular replacement methods using independent search models for the two domains. In unphosphorylated CheB, the N-terminal domain packs against the active site of the C-terminal domain and thus inhibits methylesterase activity by directly restricting access to the active site. We propose that phosphorylation of CheB induces a conformational change in the regulatory domain that disrupts the domain interface, resulting in a repositioning of the domains and allowing access to the active site. Structural similarity between the two companion receptor modification enzymes, CheB and CheR, suggests an evolutionary and/or functional relationship. Specifically, the phosphorylated N-terminal domain of CheB may facilitate interaction with the receptors, similar to the postulated role of the N-terminal domain of CheR. Examination of surfaces in the N-terminal regulatory domain of CheB suggests that despite a common fold throughout the response regulator family, surfaces used for protein–protein interactions differ significantly. Comparison between CheB and other response regulators indicates that analogous surfaces are used for different functions and conversely, similar functions are mediated by different molecular surfaces. PMID:9465023

Sleep Moderates the Association Between Response Inhibition and Self-Regulation in Early Childhood

PubMed Central

Schumacher, Allyson M.; Miller, Alison L.; Watamura, Sarah E.; Kurth, Salome; Lassonde, Jonathan M.; LeBourgeois, Monique K.

2017-01-01

Early childhood is a time of rapid developmental changes in sleep, cognitive control processes, and the regulation of emotion and behavior. This experimental study examined sleep-dependent effects on response inhibition and self-regulation, as well as whether acute sleep restriction moderated the association between these processes. Preschool children (N = 19; 45.6 ± 2.2 months; 11 female) followed a strict sleep schedule for at least 3 days before each of 2 morning behavior assessments: baseline (habitual nap/night sleep) and sleep restriction (missed nap/delayed bedtime). Response inhibition was evaluated via a go/no-go task. Twelve self-regulation strategies were coded from videotapes of children while attempting an unsolvable puzzle. We then created composite variables representing adaptive and maladaptive self-regulation strategies. Although we found no sleep-dependent effects on response inhibition or self-regulation measures, linear mixed-effects regression showed that acute sleep restriction moderated the relationship between these processes. At baseline, children with better response inhibition were more likely to use adaptive self-regulation strategies (e.g., self-talk, alternate strategies), and those with poorer response inhibition showed increased use of maladaptive self-regulation strategies (e.g., perseveration, fidgeting); however, response inhibition was not related to self-regulation strategies following sleep restriction. Our results showing a sleep-dependent effect on the associations between response inhibition and self-regulation strategies indicate that adequate sleep facilitates synergy between processes supporting optimal social-emotional functioning in early childhood. Although replication studies are needed, findings suggest that sleep may alter connections between maturing emotional and cognitive systems, which have important implications for understanding risk for or resilience to developmental psychopathology. PMID:27652491

Sleep Moderates the Association Between Response Inhibition and Self-Regulation in Early Childhood.

PubMed

Schumacher, Allyson M; Miller, Alison L; Watamura, Sarah E; Kurth, Salome; Lassonde, Jonathan M; LeBourgeois, Monique K

2017-01-01

Early childhood is a time of rapid developmental changes in sleep, cognitive control processes, and the regulation of emotion and behavior. This experimental study examined sleep-dependent effects on response inhibition and self-regulation, as well as whether acute sleep restriction moderated the association between these processes. Preschool children (N = 19; 45.6 ± 2.2 months; 11 female) followed a strict sleep schedule for at least 3 days before each of 2 morning behavior assessments: baseline (habitual nap/night sleep) and sleep restriction (missed nap/delayed bedtime). Response inhibition was evaluated via a go/no-go task. Twelve self-regulation strategies were coded from videotapes of children while attempting an unsolvable puzzle. We then created composite variables representing adaptive and maladaptive self-regulation strategies. Although we found no sleep-dependent effects on response inhibition or self-regulation measures, linear mixed-effects regression showed that acute sleep restriction moderated the relationship between these processes. At baseline, children with better response inhibition were more likely to use adaptive self-regulation strategies (e.g., self-talk, alternate strategies), and those with poorer response inhibition showed increased use of maladaptive self-regulation strategies (e.g., perseveration, fidgeting); however, response inhibition was not related to self-regulation strategies following sleep restriction. Our results showing a sleep-dependent effect on the associations between response inhibition and self-regulation strategies indicate that adequate sleep facilitates synergy between processes supporting optimal social-emotional functioning in early childhood. Although replication studies are needed, findings suggest that sleep may alter connections between maturing emotional and cognitive systems, which have important implications for understanding risk for or resilience to developmental psychopathology.

Pseudouridine and N6-methyladenosine modifications weaken PUF protein/RNA interactions

PubMed Central

AlSadhan, Ishraq; Merriman, Dawn K.; Al-Hashimi, Hashim M.; Herschlag, Daniel

2017-01-01

RNA modifications are ubiquitous in biology, with over 100 distinct modifications. While the vast majority were identified and characterized on abundant noncoding RNA such as tRNA and rRNA, the advent of sensitive sequencing-based approaches has led to the discovery of extensive and regulated modification of eukaryotic messenger RNAs as well. The two most abundant mRNA modifications—pseudouridine (Ψ) and N6-methyladenosine (m6A)—affect diverse cellular processes including mRNA splicing, localization, translation, and decay and modulate RNA structure. Here, we test the hypothesis that RNA modifications directly affect interactions between RNA-binding proteins and target RNA. We show that Ψ and m6A weaken the binding of the human single-stranded RNA binding protein Pumilio 2 (hPUM2) to its consensus motif, with individual modifications having effects up to approximately threefold and multiple modifications giving larger effects. While there are likely to be some cases where RNA modifications essentially fully ablate protein binding, here we see modest responses that may be more common. Such modest effects could nevertheless profoundly alter the complex landscape of RNA:protein interactions, and the quantitative rather than qualitative nature of these effects underscores the need for quantitative, systems-level accounting of RNA:protein interactions to understand post-transcriptional regulation. PMID:28138061

Viral Mimicry to Usurp Ubiquitin and SUMO Host Pathways

PubMed Central

Wimmer, Peter; Schreiner, Sabrina

2015-01-01

Posttranslational modifications (PTMs) of proteins include enzymatic changes by covalent addition of cellular regulatory determinants such as ubiquitin (Ub) and small ubiquitin-like modifier (SUMO) moieties. These modifications are widely used by eukaryotic cells to control the functional repertoire of proteins. Over the last decade, it became apparent that the repertoire of ubiquitiylation and SUMOylation regulating various biological functions is not restricted to eukaryotic cells, but is also a feature of human virus families, used to extensively exploit complex host-cell networks and homeostasis. Intriguingly, besides binding to host SUMO/Ub control proteins and interfering with the respective enzymatic cascade, many viral proteins mimic key regulatory factors to usurp this host machinery and promote efficient viral outcomes. Advanced detection methods and functional studies of ubiquitiylation and SUMOylation during virus-host interplay have revealed that human viruses have evolved a large arsenal of strategies to exploit these specific PTM processes. In this review, we highlight the known viral analogs orchestrating ubiquitin and SUMO conjugation events to subvert and utilize basic enzymatic pathways. PMID:26343706

Pull-down Assay to Characterize Ca2+/Calmodulin Binding to Plant Receptor Kinases.

PubMed

Kaufmann, Christine; Sauter, Margret

2017-01-01

Plant receptor-like kinases (RLKs) are regulated by posttranscriptional modification and by interaction with regulatory proteins. A common modification of RLKs is (auto)phosphorylation, and a common regulatory protein is the calcium sensor calmodulin (CaM). We have developed protocols to detect the interaction of an RLK with CaM. The interaction with CaM was shown by bimolecular fluorescence complementation (BiFC) (see Chapter 14) and pull-down assay (this chapter). Both methods offer unique advantages. BiFC is useful in showing interaction of soluble as well as of membrane-bound proteins in planta. Pull-down assays are restricted to soluble proteins and provide in vitro data. The pull-down assay provides the advantage that proteins can be modified prior to binding and that experimental conditions such as the concentration of Ca 2+ or other divalent cations can be controlled. This chapter provides a pull-down protocol to study RLK-CaM interaction with optional steps to investigate the impact of RLK phosphorylation or of Ca 2+ .

7 CFR 301.81 - Restrictions on interstate movement of regulated articles.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Restrictions on interstate movement of regulated articles. 301.81 Section 301.81 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL... Fire Ant Quarantine and Regulations § 301.81 Restrictions on interstate movement of regulated articles...

7 CFR 301.50 - Restrictions on interstate movement of regulated articles.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Restrictions on interstate movement of regulated articles. 301.50 Section 301.50 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL... Beetle § 301.50 Restrictions on interstate movement of regulated articles. Regulated articles may be...

The Regulation of Carcinogenic Hazards.

ERIC Educational Resources Information Center

Gori, Gio Batta

1980-01-01

It is suggested that a system of relative standards be formulated which would compare utility of substances to their relative risk as carcinogens. This would define a range of use restrictions. Substances intended for specific uses would then be regulated according to these standards. (Author/RE)

Differential expression of cocaine- and amphetamine-regulated transcript and agouti related-protein in chronically food-restricted sheep.

PubMed

Henry, B A; Rao, A; Ikenasio, B A; Mountjoy, K G; Tilbrook, A J; Clarke, I J

2001-11-09

Recently, much attention has focused on the role of the melanocortin system in the regulation of energy homeostasis, especially the satiety effects of the pro-opiomelanocortin (POMC)-derived peptide alpha-melanocyte stimulating hormone (alpha-MSH). We have found that POMC mRNA levels are similar in fat and thin sheep and the current study sought to further characterize the effects of nutritional status on the melanocortin system. To this end, we studied the expression of agouti-related peptide (AGRP) (an endogenous antagonist of alpha-MSH) and cocaine- and amphetamine-regulated transcript (CART), which is co-localized within POMC cells of the arcuate nucleus (ARC) in rodents. Twelve ovariectomized ewes were randomly divided into two groups and fed a maintenance (n=6) or restricted diet (n=6). At the time of experimentation, the animals had significantly (P<0.0001) different bodyweights (53.4+/-2.2 kg, ad libitum vs. 30.4+/-1.2 kg, food-restricted), which was largely due to altered body fat deposits. In situ hybridization was used to study the expression of POMC, AGRP and CART. The expression of POMC in the ARC was similar in ad libitum and food-restricted animals but the expression of AGRP was profoundly increased in the food-restricted group. The expression of CART was abundant throughout the hypothalamus but was not found in the ARC. In food-restricted animals, the expression of CART was lower in the retrochiasmatic nucleus (P<0.01), paraventricular nucleus (P<0.001), the dorsomedial nucleus and the lateral hypothalamic area (P<0.05), but was higher (P<0.01) in the posterior hypothalamic area. Thus, long-term changes in nutritional status have profound effects on the expression of AGRP and CART in the hypothalamus.

The story so far: post-translational regulation of peroxisome proliferator-activated receptors by ubiquitination and SUMOylation

PubMed Central

Wadosky, Kristine M.

2012-01-01

Many studies have implicated the peroxisome proliferator-activated receptor (PPAR) family of nuclear receptor transcription factors in regulating cardiac substrate metabolism and ATP generation. Recently, evidence from a variety of cell culture and organ systems has implicated ubiquitin and small ubiquitin-like modifier (SUMO) conjugation as post-translational modifications that regulate the activity of PPAR transcription factors and their coreceptors/coactivators. Here we introduce the ubiquitin and SUMO conjugation systems and extensively review how they have been shown to regulate all three PPAR isoforms (PPARα, PPARβ/δ, and PPARγ) in addition to the retinoid X receptor and PPARγ coactivator-1α subunits of the larger PPAR transcription factor complex. We then present how the specific ubiquitin (E3) ligases have been implicated and review emerging evidence that post-translational modifications of PPARs with ubiquitin and/or SUMO may play a role in cardiac disease. Because PPAR activity is perturbed in a variety of forms of heart disease and specific proteins regulate this process (E3 ligases), this may be a fruitful area of investigation with respect to finding new therapeutic targets. PMID:22037188

Influences of thermal environment on fish growth.

PubMed

Boltaña, Sebastián; Sanhueza, Nataly; Aguilar, Andrea; Gallardo-Escarate, Cristian; Arriagada, Gabriel; Valdes, Juan Antonio; Soto, Doris; Quiñones, Renato A

2017-09-01

Thermoregulation in ectothermic animals is influenced by the ability to effectively respond to thermal variations. While it is known that ectotherms are affected by thermal changes, it remains unknown whether physiological and/or metabolic traits are impacted by modifications to the thermal environment. Our research provides key evidence that fish ectotherms are highly influenced by thermal variability during development, which leads to important modifications at several metabolic levels (e.g., growth trajectories, microstructural alterations, muscle injuries, and molecular mechanisms). In Atlantic salmon ( Salmo salar ), a wide thermal range (Δ T 6.4°C) during development (posthatch larvae to juveniles) was associated with increases in key thermal performance measures for survival and growth trajectory. Other metabolic traits were also significantly influenced, such as size, muscle cellularity, and molecular growth regulators possibly affected by adaptive processes. In contrast, a restricted thermal range (Δ T 1.4°C) was detrimental to growth, survival, and cellular microstructure as muscle growth could not keep pace with increased metabolic demands. These findings provide a possible basic explanation for the effects of thermal environment during growth. In conclusion, our results highlight the key role of thermal range amplitude on survival and on interactions with major metabolism-regulating processes that have positive adaptive effects for organisms.

Effects of photoperiod and food restriction on the reproductive physiology of female California mice

PubMed Central

Steinman, Michael Q.; Knight, Jennifer A.; Trainor, Brian C.

2012-01-01

Many temperate-zone animals use changes in photoperiod to time breeding. Shorter term cues, like food availability, are integrated with photoperiod to adjust reproductive timing under unexpected conditions. Many mice of the genus Peromyscus breed in the summer. California mice (Peromyscus californicus), however, can breed year round, but tend to begin breeding in the winter. Glial cells may be involved in transduction of environmental signals that regulate gonadotrophin releasing hormone (GnRH) activity. We examined the effects of diet and photoperiod on reproduction in female California mice. Mice placed on either short days (8L:16D) or long days (16L:8D) were food restricted (80% of normal intake) or fed ad libitum. Short day-food restricted mice showed significant regression of the reproductive system. GnRH-immunoreactivity was increased in the tuberal hypothalamus of long day-food restricted mice. This may be associated with the sparing effect long days have when mice are food restricted. The number of GFAP-immunoreactive fibers in proximity to GnRH nerve terminals correlated negatively with uterine size in ad libitum but not food restricted mice, suggesting diet may alter glial regulation of the reproductive axis. There was a trend towards food restriction increasing uterine expression of c-fos mRNA, an estrogen dependent gene. Similar to other seasonally breeding rodents, short days render the reproductive system of female California mice more susceptible to effects of food restriction. This may be vestigial, or it may have evolved to mitigate consequences of unexpectedly poor winter food supplies. PMID:22245263

48 CFR 47.303-17 - Contractor-prepaid commercial bills of lading, small package shipments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT TRANSPORTATION Transportation in Supply... advantageous to the Government, the contracting officer may authorize the contractor to ship supplies, which... subsection, do not require a contract modification. Unless otherwise provided in the contract, the supplies...

41 CFR 101-39.100 - General.

Code of Federal Regulations, 2010 CFR

2010-07-01

... FEDERAL PROPERTY MANAGEMENT REGULATIONS AVIATION, TRANSPORTATION, AND MOTOR VEHICLES 39-INTERAGENCY FLEET MANAGEMENT SYSTEMS 39.1-Establishment, Modification, and Discontinuance of Interagency Fleet Management... fleet management systems. (a) Based on these studies, the Administrator of General Services, with the...

Modulation of Immune Function by Polyphenols: Possible Contribution of Epigenetic Factors

PubMed Central

Cuevas, Alejandro; Saavedra, Nicolás; Salazar, Luis A.; Abdalla, Dulcineia S. P.

2013-01-01

Several biological activities have been described for polyphenolic compounds, including a modulator effect on the immune system. The effects of these biologically active compounds on the immune system are associated to processes as differentiation and activation of immune cells. Among the mechanisms associated to immune regulation are epigenetic modifications as DNA methylation of regulatory sequences, histone modifications and posttranscriptional repression by microRNAs that influences the gene expression of key players involved in the immune response. Considering that polyphenols are able to regulate the immune function and has been also demonstrated an effect on epigenetic mechanisms, it is possible to hypothesize that there exists a mediator role of epigenetic mechanisms in the modulation of the immune response by polyphenols. PMID:23812304

The Serine Protease Inhibitor Neuroserpin Is Required for Normal Synaptic Plasticity and Regulates Learning and Social Behavior

ERIC Educational Resources Information Center

Reumann, Rebecca; Vierk, Ricardo; Zhou, Lepu; Gries, Frederice; Kraus, Vanessa; Mienert, Julia; Romswinkel, Eva; Morellini, Fabio; Ferrer, Isidre; Nicolini, Chiara; Fahnestock, Margaret; Rune, Gabriele; Glatzel, Markus; Galliciotti, Giovanna

2017-01-01

The serine protease inhibitor neuroserpin regulates the activity of tissue-type plasminogen activator (tPA) in the nervous system. Neuroserpin expression is particularly prominent at late stages of neuronal development in most regions of the central nervous system (CNS), whereas it is restricted to regions related to learning and memory in the…

48 CFR 252.225-7019 - Restriction on acquisition of anchor and mooring chain.

Code of Federal Regulations, 2012 CFR

2012-10-01

... of anchor and mooring chain. 252.225-7019 Section 252.225-7019 Federal Acquisition Regulations System... and mooring chain. As prescribed in 225.7007-3, use the following clause: Restriction on Acquisition of Anchor and Mooring Chain (DEC 2009)) (a) Definition. “Component,” as used in this clause, means an...

48 CFR 252.225-7019 - Restriction on acquisition of anchor and mooring chain.

Code of Federal Regulations, 2013 CFR

2013-10-01

... of anchor and mooring chain. 252.225-7019 Section 252.225-7019 Federal Acquisition Regulations System... and mooring chain. As prescribed in 225.7007-3, use the following clause: Restriction on Acquisition of Anchor and Mooring Chain (DEC 2009)) (a) Definition. “Component,” as used in this clause, means an...

48 CFR 252.225-7019 - Restriction on acquisition of anchor and mooring chain.

Code of Federal Regulations, 2014 CFR

2014-10-01

... of anchor and mooring chain. 252.225-7019 Section 252.225-7019 Federal Acquisition Regulations System... and mooring chain. As prescribed in 225.7007-3, use the following clause: Restriction on Acquisition of Anchor and Mooring Chain (DEC 2009)) (a) Definition. “Component,” as used in this clause, means an...

48 CFR 252.225-7019 - Restriction on acquisition of anchor and mooring chain.

Code of Federal Regulations, 2011 CFR

2011-10-01

... of anchor and mooring chain. 252.225-7019 Section 252.225-7019 Federal Acquisition Regulations System... and mooring chain. As prescribed in 225.7007-3, use the following clause: Restriction on Acquisition of Anchor and Mooring Chain (DEC 2009)) (a) Definition. “Component,” as used in this clause, means an...

48 CFR 252.225-7019 - Restriction on acquisition of anchor and mooring chain.

Code of Federal Regulations, 2010 CFR

2010-10-01

... of anchor and mooring chain. 252.225-7019 Section 252.225-7019 Federal Acquisition Regulations System... and mooring chain. As prescribed in 225.7007-3, use the following clause: Restriction on Acquisition of Anchor and Mooring Chain (DEC 2009)) (a) Definition. “Component,” as used in this clause, means an...

Solar energy plant as a complement to a conventional heating system: Measurement of the storage and consumption of solar energy

NASA Astrophysics Data System (ADS)

Doering, E.; Lippe, W.

1982-08-01

The technical and economic performances of a complementary solar heating installation for a new swimming pool added to a two-floor dwelling were examined after measurements were taken over a period of 12 months and analyzed. In particular, the heat absorption and utilization were measured and modifications were carried out to improve pipe insulation and regulation of mixer valve motor running and volume flow. The collector system efficiency was evaluated at 15.4%, the proportion of solar energy of the total consumption being 6.1%. The solar plant and the measuring instruments are described and recommendations are made for improved design and performance, including enlargement of the collector surface area, further modification of the regulation system, utilization of temperature stratification in the storage tanks and avoiding mutual overshadowing of the collectors.

75 FR 1269 - Vegetable Import Regulations; Modification of Potato Import Regulations; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-11

... C] Vegetable Import Regulations; Modification of Potato Import Regulations; Correction AGENCY... modified the import regulations for Irish potatoes and made minor administrative changes to the potato...

MCM: one ring to rule them all.

PubMed

Deegan, Tom D; Diffley, John F X

2016-04-01

Precise replication of the eukaryotic genome is achieved primarily through strict regulation of the enzyme responsible for DNA unwinding, the replicative helicase. The motor of this helicase is a hexameric AAA+ ATPase called MCM. The loading of MCM onto DNA and its subsequent activation and disassembly are each restricted to separate cell cycle phases; this ensures that a functional replisome is only built once at any replication origin. In recent years, biochemical and structural studies have shown that distinct conformational changes in MCM, each requiring post-translational modifications and/or the activity of other replication proteins, define the various stages of the chromosome replication cycle. Here, we review recent progress in this area. Copyright © 2016. Published by Elsevier Ltd.

Reproductive medicine and the law: egg donation in Germany, Spain and other European countries.

PubMed

Romeo Casabona, Carlos María; Paslack, Rainer; Simon, Jörgen W

2013-01-01

This paper analyzes the key legal issues raised by Reproductive Medicine practiced in Europe, with special attention to the rules prevailing in countries such as Germany and Spain. Thus, the paper involves a detailed study of the regulation in force in those countries, comparing their solutions with the rules adopted in other EU countries. It also highlights the high risk of com-modification in oocyte donation. In light of this, the differences between the laws of EU countries -some of them, very restrictive with prohibitions or requirements for recipient women and others more permissive with the use of reproductive technologies- can lead to a "reproductive tourism" between countries, as indeed is happening nowadays.

Situation Selection and Modification for Emotion Regulation in Younger and Older Adults.

PubMed

Livingstone, Kimberly M; Isaacowitz, Derek M

2015-11-01

This research investigated age differences in use and effectiveness of situation selection and situation modification for emotion regulation. Socioemotional selectivity theory suggests stronger emotional well-being goals in older age; emotion regulation may support this goal. Younger and older adults assigned to an emotion regulation or "just view" condition first freely chose to engage with negative, neutral, or positive material (situation selection), then chose to view or skip negative and positive material (situation modification), rating affect after each experience. In both tasks, older adults in both goal conditions demonstrated pro-hedonic emotion regulation, spending less time with negative material compared to younger adults. Younger adults in the regulate condition also engaged in pro-hedonic situation selection, but not modification. Whereas situation selection was related to affect, modification of negative material was not. This research supports more frequent pro-hedonic motivation in older age, as well as age differences in use of early-stage emotion regulation.

7 CFR 301.55 - Restrictions on interstate movement of regulated articles.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Restrictions on interstate movement of regulated articles. 301.55 Section 301.55 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL... American Cactus Moth § 301.55 Restrictions on interstate movement of regulated articles. No person may move...

7 CFR 301.74 - Restrictions on interstate movement of regulated articles.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Restrictions on interstate movement of regulated articles. 301.74 Section 301.74 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL... § 301.74 Restrictions on interstate movement of regulated articles. No person may move interstate from...

7 CFR 301.86 - Restrictions on interstate movement of regulated articles.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Restrictions on interstate movement of regulated articles. 301.86 Section 301.86 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL... Nematode § 301.86 Restrictions on interstate movement of regulated articles. No person may move interstate...

Evaluation of exercise-respiratory system modifications and integration schemes for physiological systems

NASA Technical Reports Server (NTRS)

Gallagher, R. R.

1974-01-01

Exercise subroutine modifications are implemented in an exercise-respiratory system model yielding improvement of system response to exercise forcings. A more physiologically desirable respiratory ventilation rate in addition to an improved regulation of arterial gas tensions and cerebral blood flow is observed. A respiratory frequency expression is proposed which would be appropriate as an interfacing element of the respiratory-pulsatile cardiovascular system. Presentation of a circulatory-respiratory system integration scheme along with its computer program listing is given. The integrated system responds to exercise stimulation for both nonstressed and stressed physiological states. Other integration possibilities are discussed with respect to the respiratory, pulsatile cardiovascular, thermoregulatory, and the long-term circulatory systems.

An Efficient and Versatile System for Visualization and Genetic Modification of Dopaminergic Neurons in Transgenic Mice

PubMed Central

Kramer, Edgar R.

2015-01-01

Background & Aims The brain dopaminergic (DA) system is involved in fine tuning many behaviors and several human diseases are associated with pathological alterations of the DA system such as Parkinson’s disease (PD) and drug addiction. Because of its complex network integration, detailed analyses of physiological and pathophysiological conditions are only possible in a whole organism with a sophisticated tool box for visualization and functional modification. Methods & Results Here, we have generated transgenic mice expressing the tetracycline-regulated transactivator (tTA) or the reverse tetracycline-regulated transactivator (rtTA) under control of the tyrosine hydroxylase (TH) promoter, TH-tTA (tet-OFF) and TH-rtTA (tet-ON) mice, to visualize and genetically modify DA neurons. We show their tight regulation and efficient use to overexpress proteins under the control of tet-responsive elements or to delete genes of interest with tet-responsive Cre. In combination with mice encoding tet-responsive luciferase, we visualized the DA system in living mice progressively over time. Conclusion These experiments establish TH-tTA and TH-rtTA mice as a powerful tool to generate and monitor mouse models for DA system diseases. PMID:26291828

Understanding the Role of O-GlcNAc Modifications in Plant Development

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

Olszewski, Neil, E.

2011-06-16

This project has contributed towards understanding the role of O-GlcNAc (O-linked N-acetylglucosamine) transferases (OGTs) in plants. Through analyses of single and double mutants, we have investigated the unique and overlapping functions of SECRET AGENT (SEC) and SPINDLY (SPY), the arabidopsis OGTs. This work showed that SEC functions as negative regulators of the long-day flowering pathway. SEC also has a positive role in regulation of rosette. An E. coli co-expression system that allows potential substrates to be co-expressed with and O-GlcNAc modified by SEC was developed. We showed that SEC is a bona fide OGT that modifies itself with single O-linkedmore » GlcNAc(s). Using this system, we tested a number of proteins that were hypothesized to be substrates of SEC and identified a number of substrates include GIGANTEA (GI), a component of the long day flowering pathway. The hypothesis that O-GlcNAc modification controls GI activity was tested by first mapping where E. coli-expressed SEC modifies GI and then assessing the activity of a non-modifiable mutant form of GI. The activity of the mutant form of GI was indistinguishable from that of wild type suggesting that either O-GlcNAc does not regulate GI activity or that additional modification sites exist on GI. In collaboration with Dr. Juan Antonio Garcia at Universidad Autónoma de Madrid the role of O-GlcNAc modification of the plum pox virus coat protein (PPV-CP) was investigated. SEC was shown to O-GlcNAc modify PPV-CP and the modification was shown to facilitate the infection process. E. coli-expressed SEC was shown to modify the same PPV-CP sites that are modified in plants. SEC has a large protein interaction domain called the TPR domain that has been hypothesized to have a role in determining the substrate specificity of the enzyme and/or to regulate its activity. A mutational analysis of the TPR domain did not find evidence for a role in substrate specificity but did obtain evidence that the domain regulates enzyme activity.« less

76 FR 27271 - TSCA Inventory Update Reporting Modifications; Submission Period Suspension

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-11

... TSCA Inventory Update Reporting Modifications; Submission Period Suspension AGENCY: Environmental... proposed modifications to the IUR regulations. EPA is suspending the next submission period to allow additional time to finalize the proposed modifications to the IUR regulations, and to avoid finalizing...

48 CFR 952.204-72 - Disclosure of information.

Code of Federal Regulations, 2011 CFR

2011-10-01

.... 952.204-72 Section 952.204-72 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND... information except in accordance with the Atomic Energy Act 1954, as amended, Executive Order 12356, and DOE's regulations or requirements. (c) The term Restricted Data as used in this article means all data concerning...

48 CFR 952.204-72 - Disclosure of information.

Code of Federal Regulations, 2010 CFR

2010-10-01

.... 952.204-72 Section 952.204-72 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND... information except in accordance with the Atomic Energy Act 1954, as amended, Executive Order 12356, and DOE's regulations or requirements. (c) The term Restricted Data as used in this article means all data concerning...

41 CFR 102-117.155 - Where do I go for further information about coastwise laws?

Code of Federal Regulations, 2010 CFR

2010-07-01

... Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION TRANSPORTATION 117-TRANSPORTATION MANAGEMENT Restrictions That Affect International Transportation of Freight and... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Where do I go for...

Comparison of Intracellular "Ca. Endomicrobium Trichonymphae" Genomovars Illuminates the Requirement and Decay of Defense Systems against Foreign DNA.

PubMed

Izawa, Kazuki; Kuwahara, Hirokazu; Kihara, Kumiko; Yuki, Masahiro; Lo, Nathan; Itoh, Takehiko; Ohkuma, Moriya; Hongoh, Yuichi

2016-10-13

"Candidatus Endomicrobium trichonymphae" (Bacteria; Elusimicrobia) is an obligate intracellular symbiont of the cellulolytic protist genus Trichonympha in the termite gut. A previous genome analysis of "Ca Endomicrobium trichonymphae" phylotype Rs-D17 (genomovar Ri2008), obtained from a Trichonympha agilis cell in the gut of the termite Reticulitermes speratus, revealed that its genome is small (1.1 Mb) and contains many pseudogenes; it is in the course of reductive genome evolution. Here we report the complete genome sequence of another Rs-D17 genomovar, Ti2015, obtained from a different T. agilis cell present in an R. speratus gut. These two genomovars share most intact protein-coding genes and pseudogenes, showing 98.6% chromosome sequence similarity. However, characteristic differences were found in their defense systems, which comprised restriction-modification and CRISPR/Cas systems. The repertoire of intact restriction-modification systems differed between the genomovars, and two of the three CRISPR/Cas loci in genomovar Ri2008 are pseudogenized or missing in genomovar Ti2015. These results suggest relaxed selection pressure for maintaining these defense systems. Nevertheless, the remaining CRISPR/Cas system in each genomovar appears to be active; none of the "spacer" sequences (112 in Ri2008 and 128 in Ti2015) were shared whereas the "repeat" sequences were identical. Furthermore, we obtained draft genomes of three additional endosymbiotic Endomicrobium phylotypes from different host protist species, and discovered multiple, intact CRISPR/Cas systems in each genome. Collectively, unlike bacteriome endosymbionts in insects, the Endomicrobium endosymbionts of termite-gut protists appear to require defense against foreign DNA, although the required level of defense has likely been reduced during their intracellular lives. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Proyecto de Ley por el Cual se Dicta el Estatuto General de Educacion y Pliego de Modificaciones Propuesto (Bill Establishing a General Statute for Education and Explanation of Proposed Modifications).

ERIC Educational Resources Information Center

Suarez Villa, Diego

This document contains the 1971 Colombian education bill and suggested bill modifications. The bill states educational objectives and establishes the structure of the national education system, the organization for educational administration, financing procedures, regulations for educational personnel, and the means for implementing the…

Redox regulation of plant S-nitrosoglutathione reductase activity through post-translational modifications of cysteine residues.

PubMed

Tichá, Tereza; Lochman, Jan; Činčalová, Lucie; Luhová, Lenka; Petřivalský, Marek

2017-12-09

Nitric oxide (NO) is considered as a signalling molecule involved in a variety of important physiological and pathological processes in plant and animal systems. The major pathway of NO reactions in vivo represents S-nitrosation of thiols to form S-nitrosothiols. S-nitrosoglutathione reductase (GSNOR) is the key enzyme in the degradation pathway of S-nitrosoglutathione (GSNO), a low-molecular weight adduct of NO and glutathione. GSNOR indirectly regulates the level of protein S-nitrosothiol in the cells. This study was focused on the dynamic regulation of the activity of plant GSNORs through reversible S-nitrosation and/or oxidative modifications of target cysteine residues. Pre-incubation with NO/NO - donors or hydrogen peroxide resulted in a decreased reductase and dehydrogenase activity of all studied plant GSNORs. Incubation with thiol reducing agent completely reversed inhibitory effects of nitrosative modifications and partially also oxidative inhibition. In biotin-labelled samples, S-nitrosation of plant GSNORs was confirmed after immunodetection and using mass spectrometry S-nitrosation of conserved Cys271 was identified in tomato GSNOR. Negative regulation of constitutive GSNOR activity in vivo by nitrosative or oxidative modifications might present an important mechanism to control GSNO levels, a critical mediator of the downstream signalling effects of NO, as well as for formaldehyde detoxification in dehydrogenase reaction mode. Copyright © 2017. Published by Elsevier Inc.

Impact of sleep restriction versus idealized sleep on emotional experience, reactivity and regulation in healthy adolescents.

PubMed

Reddy, Radhika; Palmer, Cara A; Jackson, Christine; Farris, Samantha G; Alfano, Candice A

2017-08-01

Sleep loss is associated with affective disturbances and disorders; however, there is limited understanding of specific mechanisms underlying these links, especially in adolescence. The current study tested the effects of sleep restriction versus idealized sleep on adolescents' emotional experience, reactivity and regulation (specifically cognitive reappraisal). Following 1 week of sleep monitoring, healthy adolescents (n = 42; ages 13-17 years) were randomized to 1 night of sleep restriction (4 h) or idealized sleep (9.5 h). The following day, adolescents provided self-reports of affect and anxiety and completed a laboratory-based task to assess: (1) emotional reactivity in response to positive, negative, and neutral images from the International Affective Picture System (IAPS); and (2) ability to use cognitive reappraisal to decrease negative emotional responses. Large effects were observed for the adverse impact of sleep restriction on positive affect and anxiety as well as a medium-sized effect for negative affect, compared to the idealized sleep condition. Subjective reactivity to positive and neutral images did not differ between the groups, but a moderate effect was detected for reactivity to negative images whereby sleep-restricted teens reported greater reactivity. Across both sleep conditions, use of cognitive reappraisal down-regulated negative emotion effectively; however, sleep restriction did not impact upon adolescents' ability to use this strategy. These findings add to a growing body of literature demonstrating the deleterious effects of sleep restriction on aspects of emotion and highlight directions for future research in adolescents. © 2016 European Sleep Research Society.

Cost-effectiveness of a complex workplace dietary intervention: an economic evaluation of the Food Choice at Work study

PubMed Central

Fitzgerald, Sarah; Murphy, Aileen; Kirby, Ann; Geaney, Fiona; Perry, Ivan J

2018-01-01

Objective To evaluate the costs, benefits and cost-effectiveness of complex workplace dietary interventions, involving nutrition education and system-level dietary modification, from the perspective of healthcare providers and employers. Design Single-study economic evaluation of a cluster-controlled trial (Food Choice at Work (FCW) study) with 1-year follow-up. Setting Four multinational manufacturing workplaces in Cork, Ireland. Participants 517 randomly selected employees (18–65 years) from four workplaces. Interventions Cost data were obtained from the FCW study. Nutrition education included individual nutrition consultations, nutrition information (traffic light menu labelling, posters, leaflets and emails) and presentations. System-level dietary modification included menu modification (restriction of fat, sugar and salt), increase in fibre, fruit discounts, strategic positioning of healthier alternatives and portion size control. The combined intervention included nutrition education and system-level dietary modification. No intervention was implemented in the control. Outcomes The primary outcome was an improvement in health-related quality of life, measured using the EuroQoL 5 Dimensions 5 Levels questionnaire. The secondary outcome measure was reduction in absenteeism, which is measured in monetary amounts. Probabilistic sensitivity analysis (Monte Carlo simulation) assessed parameter uncertainty. Results The system-level intervention dominated the education and combined interventions. When compared with the control, the incremental cost-effectiveness ratio (€101.37/quality-adjusted life-year) is less than the nationally accepted ceiling ratio, so the system-level intervention can be considered cost-effective. The cost-effectiveness acceptability curve indicates there is some decision uncertainty surrounding this, arising from uncertainty surrounding the differences in effectiveness. These results are reiterated when the secondary outcome measure is considered in a cost–benefit analysis, whereby the system-level intervention yields the highest net benefit (€56.56 per employee). Conclusions System-level dietary modification alone offers the most value per improving employee health-related quality of life and generating net benefit for employers by reducing absenteeism. While system-level dietary modification strategies are potentially sustainable obesity prevention interventions, future research should include long-term outcomes to determine if improvements in outcomes persist. Trial registration number ISRCTN35108237; Post-results. PMID:29502090

76 FR 23225 - Modification of Regulations Regarding the Practice of Accepting Bonds During the Provisional...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-26

... online at http://www.Regulations.gov and on the Department's Web site at http://www.trade.gov/ia/ . Any questions concerning file formatting, document conversion, access on the Internet, or other electronic... system, for the provisional measure period an estimated antidumping or countervailing duty rate is...

78 FR 60800 - Airworthiness Directives; Bombardier Inc., Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-02

... from fuel system reviews conducted by the manufacturer. This proposed AD would require accomplishing modifications to the fuel system. We are proposing this AD to prevent the potential of ignition sources inside... regulations, and existing maintenance practices for fuel tank systems. As a result of those findings, we...

48 CFR 43.203 - Change order accounting procedures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Change order accounting... CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 43.203 Change order accounting procedures. (a) Contractors' accounting systems are seldom designed to segregate the costs of performing changed work...

Histone modifications and chromatin dynamics: a focus on filamentous fungi

PubMed Central

Brosch, Gerald; Loidl, Peter; Graessle, Stefan

2008-01-01

The readout of the genetic information of eukaryotic organisms is significantly regulated by modifications of DNA and chromatin proteins. Chromatin alterations induce genome-wide and local changes in gene expression and affect a variety of processes in response to internal and external signals during growth, differentiation, development, in metabolic processes, diseases, and abiotic and biotic stresses. This review aims at summarizing the roles of histone H1 and the acetylation and methylation of histones in filamentous fungi and links this knowledge to the huge body of data from other systems. Filamentous fungi show a wide range of morphologies and have developed a complex network of genes that enables them to use a great variety of substrates. This fact, together with the possibility of simple and quick genetic manipulation, highlights these organisms as model systems for the investigation of gene regulation. However, little is still known about regulation at the chromatin level in filamentous fungi. Understanding the role of chromatin in transcriptional regulation would be of utmost importance with respect to the impact of filamentous fungi in human diseases and agriculture. The synthesis of compounds (antibiotics, immunosuppressants, toxins, and compounds with adverse effects) is also likely to be regulated at the chromatin level. PMID:18221488

Resident perceptions of the impact of duty hour restrictions on resident-attending interactions: an exploratory study.

PubMed

Gerjevic, Kristen A; Rosenbaum, Marcy E; Suneja, Manish

2017-07-18

The institution of duty hour reforms by the Accreditation Council for Graduate Medical Education in 2003 has created a learning environment where residents are consistently looking for input from attending physicians with regards to balancing duty hour regulations and providing quality patient care. There is a paucity of literature regarding resident perceptions of attending physician actions or attitudes towards work hour restrictions. The purpose of this study was to identify attending physician behaviors that residents perceived as supportive or unsupportive of their compliance with duty hour regulations. Focus group interviews were conducted with residents exploring their perceptions of how duty hour regulations impact their interactions with attending physicians. Qualitative analysis identified key themes in residents' experiences interacting with faculty in regard to duty hour regulations. Forty residents from five departments in two hospital systems participated. Discussion of these interactions highlighted that attending physicians demonstrate behaviors that explicitly or implicitly either lend their support and understanding of residents' need to comply with these regulations or imply a lack of support and understanding. Three major themes that contributed to the ease or difficulty in addressing duty hour regulations included attending physicians' explicit communication of expectations, implicit non-verbal and verbal cues and the program's organizational culture. Resident physicians' perception of attending physicians' explicit and implicit communication and residency programs organization culture has an impact on residents' experience with duty hour restrictions. Residency faculty and programs could benefit from explicitly addressing and supporting the challenges that residents perceive in complying with duty hour restrictions.

Identification of the lipopolysaccharide modifications controlled by the Salmonella PmrA/PmrB system mediating resistance to Fe(III) and Al(III)

PubMed Central

Nishino, Kunihiko; Hsu, Fong-Fu; Turk, John; Cromie, Michael J; Wösten, Marc M S M; Groisman, Eduardo A

2006-01-01

Iron is an essential metal but can be toxic in excess. While several homeostatic mechanisms prevent oxygen-dependent killing promoted by Fe(II), little is known about how cells cope with Fe(III), which kills by oxygen-independent means. Several Gram-negative bacterial species harbour a regulatory system – termed PmrA/PmrB – that is activated by and required for resistance to Fe(III). We now report the identification of the PmrA-regulated determinants mediating resistance to Fe(III) and Al(III) in Salmonella enterica serovar Typhimurium. We establish that these determinants remodel two regions of the lipopolysaccharide, decreasing the negative charge of this major constituent of the outer membrane. Remodelling entails the covalent modification of the two phosphates in the lipid A region with phosphoethanolamine and 4-aminoarabinose, which has been previously implicated in resistance to polymyxin B, as well as dephosphorylation of the Hep(II) phosphate in the core region by the PmrG protein. A mutant lacking the PmrA-regulated Fe(III) resistance genes bound more Fe(III) than the wild-type strain and was defective for survival in soil, suggesting that these PmrA-regulated lipopolysaccharide modifications aid Salmonella's survival and spread in non-host environments. PMID:16803591

Situation Selection and Modification for Emotion Regulation in Younger and Older Adults

PubMed Central

Livingstone, Kimberly M.; Isaacowitz, Derek M.

2016-01-01

This research investigated age differences in use and effectiveness of situation selection and situation modification for emotion regulation. Socioemotional selectivity theory suggests stronger emotional well-being goals in older age; emotion regulation may support this goal. Younger and older adults assigned to an emotion regulation or “just view” condition first freely chose to engage with negative, neutral, or positive material (situation selection), then chose to view or skip negative and positive material (situation modification), rating affect after each experience. In both tasks, older adults in both goal conditions demonstrated pro-hedonic emotion regulation, spending less time with negative material compared to younger adults. Younger adults in the regulate condition also engaged in pro-hedonic situation selection, but not modification. Whereas situation selection was related to affect, modification of negative material was not. This research supports more frequent pro-hedonic motivation in older age, as well as age differences in use of early-stage emotion regulation. PMID:26998196

The methylome and virulence of bovine respiratory disease bacterial pathogens

USDA-ARS?s Scientific Manuscript database

With the advent of single molecule, real-time (SMRT®) sequencing, it is now possible to study complete microbial epigenomes. It has been known for decades that methylation and other types of epigenetic modifications in bacteria are responsible for much more than restriction-modification mechanics, b...

Development of at-line assay to monitor charge variants of MAbs during production.

PubMed

St Amand, M M; Ogunnaike, B A; Robinson, A S

2014-01-01

One major challenge currently facing the biopharmaceutical industry is to understand how MAb microheterogeneity affects therapeutic efficacy, potency, immunogenicity, and clearance. MAb micro-heterogeneity can result from post-translational modifications such as sialylation, galactosylation, C-terminal lysine cleavage, glycine amidation, and tryptophan oxidation, each of which can generate MAb charge variants; such heterogeneity can affect pharmacokinetics (PK) considerably. Implementation of appropriate on-line quality control strategies may help to regulate bioprocesses, thus enabling more homogenous material with desired post-translational modifications and PK behavior. However, one major restriction to implementation of quality control strategies is the availability of techniques for obtaining on-line or at-line measurements of these attributes. In this work, we describe the development of an at-line assay to separate MAb charge variants in near real-time, which could ultimately be used to implement on-line quality control strategies for MAb production. The assay consists of a 2D-HPLC method with sequential in-line Protein A and WCX-10 HPLC column steps. To perform the 2D-HPLC assay at-line, the two columns steps were integrated into a single method using a novel system configuration that allowed parallel flow over column 1 or column 2 or sequential flow from column 1 to column 2. A bioreactor system was also developed such that media samples could be removed automatically from bioreactor vessels during production and delivered to the 2D-HPLC for analysis. With this at-line HPLC assay, we have demonstrated that MAb microheterogeneity occurs throughout the cell cycle whether the host cell line is grown under different or the same nominal culture conditions. © 2013 American Institute of Chemical Engineers.

Role of ND10 nuclear bodies in the chromatin repression of HSV-1.

PubMed

Gu, Haidong; Zheng, Yi

2016-04-05

Herpes simplex virus (HSV) is a neurotropic virus that establishes lifelong latent infection in human ganglion sensory neurons. This unique life cycle necessitates an intimate relation between the host defenses and virus counteractions over the long course of infection. Two important aspects of host anti-viral defense, nuclear substructure restriction and epigenetic chromatin regulation, have been intensively studied in the recent years. Upon viral DNA entering the nucleus, components of discrete nuclear bodies termed nuclear domain 10 (ND10), converge at viral DNA and place restrictions on viral gene expression. Meanwhile the infected cell mobilizes its histones and histone-associated repressors to force the viral DNA into nucleosome-like structures and also represses viral transcription. Both anti-viral strategies are negated by various HSV countermeasures. One HSV gene transactivator, infected cell protein 0 (ICP0), is a key player in antagonizing both the ND10 restriction and chromatin repression. On one hand, ICP0 uses its E3 ubiquitin ligase activity to target major ND10 components for proteasome-dependent degradation and thereafter disrupts the ND10 nuclear bodies. On the other hand, ICP0 participates in de-repressing the HSV chromatin by changing histone composition or modification and therefore activates viral transcription. Involvement of a single viral protein in two seemingly different pathways suggests that there is coordination in host anti-viral defense mechanisms and also cooperation in viral counteraction strategies. In this review, we summarize recent advances in understanding the role of chromatin regulation and ND10 dynamics in both lytic and latent HSV infection. We focus on the new observations showing that ND10 nuclear bodies play a critical role in cellular chromatin regulation. We intend to find the connections between the two major anti-viral defense pathways, chromatin remodeling and ND10 structure, in order to achieve a better understanding of how host orchestrates a concerted defense and how HSV adapts with and overcomes the host immunity.

Genetic modification of hematopoietic stem cells with nonviral systems: past progress and future prospects.

PubMed

Papapetrou, E P; Zoumbos, N C; Athanassiadou, A

2005-10-01

Serious unwanted complications provoked by retroviral gene transfer into hematopoietic stem cells (HSCs) have recently raised the need for the development and assessment of alternative gene transfer vectors. Within this context, nonviral gene transfer systems are attracting increasing interest. Their main advantages include low cost, ease of handling and large-scale production, large packaging capacity and, most importantly, biosafety. While nonviral gene transfer into HSCs has been restricted in the past by poor transfection efficiency and transient maintenance, in recent years, biotechnological developments are converting nonviral transfer into a realistic approach for genetic modification of cells of hematopoietic origin. Herein we provide an overview of past accomplishments in the field of nonviral gene transfer into hematopoietic progenitor/stem cells and we point at future challenges. We argue that episomally maintained self-replicating vectors combined with physical methods of delivery show the greatest promise among nonviral gene transfer strategies for the treatment of disorders of the hematopoietic system.

Nucleic Acid Immunity.

PubMed

Hartmann, G

2017-01-01

Organisms throughout biology need to maintain the integrity of their genome. From bacteria to vertebrates, life has established sophisticated mechanisms to detect and eliminate foreign genetic material or to restrict its function and replication. Tremendous progress has been made in the understanding of these mechanisms which keep foreign or unwanted nucleic acids from viruses or phages in check. Mechanisms reach from restriction-modification systems and CRISPR/Cas in bacteria and archaea to RNA interference and immune sensing of nucleic acids, altogether integral parts of a system which is now appreciated as nucleic acid immunity. With inherited receptors and acquired sequence information, nucleic acid immunity comprises innate and adaptive components. Effector functions include diverse nuclease systems, intrinsic activities to directly restrict the function of foreign nucleic acids (e.g., PKR, ADAR1, IFIT1), and extrinsic pathways to alert the immune system and to elicit cytotoxic immune responses. These effects act in concert to restrict viral replication and to eliminate virus-infected cells. The principles of nucleic acid immunity are highly relevant for human disease. Besides its essential contribution to antiviral defense and restriction of endogenous retroelements, dysregulation of nucleic acid immunity can also lead to erroneous detection and response to self nucleic acids then causing sterile inflammation and autoimmunity. Even mechanisms of nucleic acid immunity which are not established in vertebrates are relevant for human disease when they are present in pathogens such as bacteria, parasites, or helminths or in pathogen-transmitting organisms such as insects. This review aims to provide an overview of the diverse mechanisms of nucleic acid immunity which mostly have been looked at separately in the past and to integrate them under the framework nucleic acid immunity as a basic principle of life, the understanding of which has great potential to advance medicine. © 2017 Elsevier Inc. All rights reserved.

Comparative proteomic analysis of Bombyx mori hemolymph and fat body after calorie restriction.

PubMed

Chen, Huiqing; Li, Yijia; Chen, Keping; Yao, Qin; Li, Guohui; Wang, Lin

2010-01-01

Calorie restriction (CR) is known to extend life span from yeast to mammals. To gain an insight into the effects of CR on growth and development of the silkworm Bombyx mori at protein level, we employed comparative proteomic approach to investigate proteomic differences of hemolymph and fat body of the silkworm larvae subjected to CR. Thirty-nine differentially expressed proteins were identified by MALDI TOF/TOF MS. Among them, 19 were from the hemolymph and 20 from the fat body. The hemolymph of the CR group contained two down-regulated and 17 up-regulated proteins, whereas the fat body contained 15 down-regulated and five up-regulated ones. These proteins belonged to those functioning in immune system, in signal transduction and apoptosis, in regulation of growth and development, and in energy metabolism. Our results suggest that CR can alter the expression of proteins related to the above four aspects, implying that these proteins may regulate life span of the silkworm through CR.

Reduced volatile organic compound (VOC) ammunition coatings. Progress report, October 1994-September 1995

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

Duncan, J.L.

1996-05-01

Production requirements and film thickness limitations typically require that ammunition coating systems consist of a single film. This single film must provide the corrosion resistance of a primer plus such properties as color, gloss, and solvent resistance that are required of a topcoat, a compromise at best. Federal and local regulations resulting from the Clean Air Act and its amendments restrict the amount of VOC emitted during the application of protective coatings, and regulations on worker safety restrict exposure to hazardous materials such as chromates. These materials also generate hazardous wastes and the associated high disposal costs. This report summarizesmore » progress in developing ammunition coatings that perform as well as or better than current systems, but at reduced VOC levels with chromate-free pigmentation.« less

Children's Self-Regulation and School Achievement in Cultural Contexts: The Role of Maternal Restrictive Control

PubMed Central

Weis, Mirjam; Trommsdorff, Gisela; Muñoz, Lorena

2016-01-01

Self-regulation can be developed through parent-child interactions and has been related to developmental outcomes, e.g., such as educational achievement. This study examined cross-cultural differences and similarities in maternal restrictive control, self-regulation (i.e., behavior and emotion regulation) and school achievement and relations among these variables in Germany and Chile. Seventy-six German and 167 Chilean fourth graders, their mothers, and their teachers participated. Mothers and teachers rated children's behavior regulation with a subscale of the Strengths and Difficulties Questionnaire. Children reported their use of emotion regulation strategies on the Questionnaire for the Measurement of Stress and Coping. Mothers rated maternal restrictive control by answering the Parenting Practice Questionnaire. School achievement was assessed by grades for language and mathematics. Results showed higher behavior regulation of German children in comparison to Chilean children and a higher preference of restrictive parental control in Chilean mothers than in German mothers. Regression analyses revealed positive relations between children's behavior regulation and school achievement in Germany and in Chile. Further, in both cultural contexts, maternal restrictive control was related negatively to behavior regulation and positively to anger-oriented emotion regulation. In sum, the study showed the central function of behavior regulation for school achievement underlining negative relations of maternal restrictive control with children's self-regulation and school achievement in diverse cultural contexts. Culturally adapted interventions related to parenting practices to promote children's behavior regulation may assist in also promoting children's school achievement. PMID:27303318

Overly Regulated Thinking and Autism Revisited.

PubMed

Cashin, Andrew; Yorke, James

2016-08-01

Humans exist within a socially mediated dynamical system. Frequent demands are experienced to respond to change in the environment to adapt and flourish. People with autism have impaired behavioral and thinking flexibility and experience high levels of anxiety, as change and adaptation do not come naturally. The disability inherent in autism is by definition the impaired social and occupational functioning that results from lack of adaptation. The point of the behavioral triad of restricted and repetitive interests, activities, and behaviors has received relatively little attention as compared to the other two points of the triad. A review of the literature related to restricted and repetitive interests and activities and behaviors and autism was conducted to inform this theoretical review. This paper considers the overly regulated thought and behavior inherent in autism spectrum disorders through the lens of dynamical systems, and an explanatory model is generated. The mathematical tools applied to understand dynamical systems may be a fruitful basis of further research to enable the movement from a theoretical concept of overly regulated thinking and behavior in autism to an empirically derived understanding. © 2016 Wiley Periodicals, Inc.

Pharmacovigilance in China: current situation, successes and challenges.

PubMed

Zhang, Li; Wong, Lisa Y L; He, Ying; Wong, Ian C K

2014-10-01

With the integration of the global pharmaceutical economy and the gradual transformation of the healthcare insurance system in China, the legislative framework for a comprehensive regulatory system monitoring the whole process including drug development, manufacture, distribution and use has been established by the China Food and Drug Administration (CFDA) to ensure the safety and effectiveness of medication use. China has established a relatively comprehensive pharmacovigilance system covering regulation, organisation and technology from 1989 to 2014. As of 2013, one national centre, 34 provincial centres and more than 400 municipal centres for adverse drug reaction (ADR) monitoring were included in the four-level pharmacovigilance network (national, provincial, municipal and county) with more than 200,000 grassroot organisation users. The China Adverse Drug Reaction Monitoring System (CADRMS) is an online spontaneous reporting system which connects the four-level pharmacovigilance network. By 2013, CADRMS had received over 6.6 million ADR case reports. After integrating and analysing pharmacovigilance data, the National Centre for ADR Monitoring (NCADRM) publishes medication safety information by releasing ADR bulletins, National ADR Annual Reports and International Pharmacovigilance Newsletters. The NCADRM also routinely provides CADRMS data feedback to manufacturers. The CFDA implemented risk management through several approaches, including arranging 'manufacturer communication meetings', modification of medication package inserts, and restriction, suspension or withdrawal of marketing authorisations. Seamless information exchange with overseas regulatory authorities and organisations remains an area for improvement. Further development of the China pharmacovigilance system in terms of signal generation, post-marketing pharmacoepidemiology research and education is also needed.

50 CFR 648.140 - Catch quotas and other restrictions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... specification process, provided that new information does not require a modification to the multiple-year quotas, to determine the allowable levels of fishing and other restrictions necessary to result in a target... target exploitation rate specified in paragraph (a) of this section is not exceeded: (1) Research quota...

Identification of histone modifications in biomedical text for supporting epigenomic research

PubMed Central

Kolářik, Corinna; Klinger, Roman; Hofmann-Apitius, Martin

2009-01-01

Background Posttranslational modifications of histones influence the structure of chromatine and in such a way take part in the regulation of gene expression. Certain histone modification patterns, distributed over the genome, are connected to cell as well as tissue differentiation and to the adaption of organisms to their environment. Abnormal changes instead influence the development of disease states like cancer. The regulation mechanisms for modifying histones and its functionalities are the subject of epigenomics investigation and are still not completely understood. Text provides a rich resource of knowledge on epigenomics and modifications of histones in particular. It contains information about experimental studies, the conditions used, and results. To our knowledge, no approach has been published so far for identifying histone modifications in text. Results We have developed an approach for identifying histone modifications in biomedical literature with Conditional Random Fields (CRF) and for resolving the recognized histone modification term variants by term standardization. For the term identification F1 measures of 0.84 by 10-fold cross-validation on the training corpus and 0.81 on an independent test corpus have been obtained. The standardization enabled the correct transformation of 96% of the terms from training and 98% from test the corpus. Due to the lack of terminologies exhaustively covering specific histone modification types, we developed a histone modification term hierarchy for use in a semantic text retrieval system. Conclusion The developed approach highly improves the retrieval of articles describing histone modifications. Since text contains context information about performed studies and experiments, the identification of histone modifications is the basis for supporting literature-based knowledge discovery and hypothesis generation to accelerate epigenomic research. PMID:19208128

Identification of histone modifications in biomedical text for supporting epigenomic research.

PubMed

Kolárik, Corinna; Klinger, Roman; Hofmann-Apitius, Martin

2009-01-30

Posttranslational modifications of histones influence the structure of chromatine and in such a way take part in the regulation of gene expression. Certain histone modification patterns, distributed over the genome, are connected to cell as well as tissue differentiation and to the adaption of organisms to their environment. Abnormal changes instead influence the development of disease states like cancer. The regulation mechanisms for modifying histones and its functionalities are the subject of epigenomics investigation and are still not completely understood. Text provides a rich resource of knowledge on epigenomics and modifications of histones in particular. It contains information about experimental studies, the conditions used, and results. To our knowledge, no approach has been published so far for identifying histone modifications in text. We have developed an approach for identifying histone modifications in biomedical literature with Conditional Random Fields (CRF) and for resolving the recognized histone modification term variants by term standardization. For the term identification F1 measures of 0.84 by 10-fold cross-validation on the training corpus and 0.81 on an independent test corpus have been obtained. The standardization enabled the correct transformation of 96% of the terms from training and 98% from test the corpus. Due to the lack of terminologies exhaustively covering specific histone modification types, we developed a histone modification term hierarchy for use in a semantic text retrieval system. The developed approach highly improves the retrieval of articles describing histone modifications. Since text contains context information about performed studies and experiments, the identification of histone modifications is the basis for supporting literature-based knowledge discovery and hypothesis generation to accelerate epigenomic research.

77 FR 2679 - Defense Federal Acquisition Regulation Supplement: Order of Application for Modifications

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-19

... following methods: [cir] Regulations.gov : http://www.regulations.gov . Submit comments via the Federal e... contract. In order to determine the sequence of modifications to a contract or order, a method for... the numeric order of the modifications to a contract is not the order in which the changes to the...

Epigenetic regulation of oligodendrocyte identity

PubMed Central

Liu, Jia; Casaccia, Patrizia

2010-01-01

The interplay of transcription factors and epigenetic modifiers, including histone modifications, DNA methylation and microRNAs during development is essential for the acquisition of specific cell fates. Here we review the epigenetic “programming” of stem cells into oligodendrocytes, by analyzing three sequential stages of lineage progression. The first transition from pluripotent stem cell to neural precursor is characterized by repression of pluripotency genes and restriction of the lineage potential to the neural fate. The second transition from multipotential precursor to oligodendrocyte progenitor is associated with the progressive loss of plasticity and the repression of neuronal and astrocytic genes. The last step of differentiation of oligodendrocyte progenitors into myelin-forming cells is defined by a model of de-repression of myelin genes. PMID:20227775

Identification of zinc finger transcription factor EGR2 as a novel acetylated protein.

PubMed

Noritsugu, Kota; Ito, Akihiro; Nakao, Yoichi; Yoshida, Minoru

2017-08-05

EGR2 is a zinc finger transcription factor that regulates myelination in the peripheral nervous system and T cell anergy. The transcriptional activity of EGR2 is known to be regulated by its co-activators and/or co-repressors. Although the activity of transcription factors is generally regulated not only by interactions with co-regulators but also posttranslational modifications including acetylation, little is known about posttranslational modifications of EGR2. Here we show that EGR2 is a novel acetylated protein. Through immunoblotting analyses using an antibody that specifically recognizes the acetylated form of EGR2, CBP and p300 were identified as acetyltransferases, while HDAC6, 10 and SIRT1 were identified as deacetylases of EGR2. Although the NuRD complex containing HDAC1 and HDAC2 is known to associate with EGR2, the present study suggests that acetylation of EGR2 is regulated independently of NuRD. Copyright © 2017 Elsevier Inc. All rights reserved.

The diversity of regulation and public financing of IVF in Europe and its impact on utilization.

PubMed

Berg Brigham, K; Cadier, B; Chevreul, K

2013-03-01

How do the different forms of regulation and public financing of IVF affect utilization in otherwise similar European welfare state systems? Countries with more liberal social eligibility regulations had higher levels of IVF utilization, which diminished as the countries' policies became more restrictive. Europe is a world leader in the development and utilization of IVF, yet surveillance reveals significant differences in uptake among countries which have adopted different approaches to the regulation and and public financing of IVF. A descriptive and comparative analysis of legal restrictions on access to IVF in 13 of the EU15 countries that affirmatively regulate and publicly finance IVF. Using 2009 data from the European Society of Human Reproduction and Embryology study of regulatory frameworks in Europe and additional legislative research, we examined and described restrictions on access to IVF in terms of general eligibility, public financing and the scope of available services. Multiple correspondence analysis was used to identify patterns of regulation and groups of countries with similar regulatory patterns and to explore the effects on utilization of IVF, using data from the most recent European and international IVF monitoring reports. Regulations based on social characteristics of treatment seekers who are not applicable to other medical treatments, including relationship status and sexual orientation, appear to have the greatest impact on utilization. Countries with the most generous public financing schemes tend to restrict access to covered IVF to a greater degree. However, no link could be established between IVF utilization and the manner in which coverage was regulated or the level of public financing. Owing to the lack of data regarding the actual level of public versus private financing of IVF it is impossible to draw conclusions regarding equity of access. Moreover, the regulatory and utilization data were not completely temporally matched in what can be a quickly changing regulatory landscape. Whether motivated by cost, eligility restrictions or the availability of particular services, cross-border treatment seeking is driven by regulatory policies, underscoring the extra-territorial implications of in-country political decisions regarding access to IVF. There was no funding source for this study. The authors have no conflicts of interest to declare.

Identification of methyllysine peptides binding to chromobox protein homolog 6 chromodomain in the human proteome.

PubMed

Li, Nan; Stein, Richard S L; He, Wei; Komives, Elizabeth; Wang, Wei

2013-10-01

Methylation is one of the important post-translational modifications that play critical roles in regulating protein functions. Proteomic identification of this post-translational modification and understanding how it affects protein activity remain great challenges. We tackled this problem from the aspect of methylation mediating protein-protein interaction. Using the chromodomain of human chromobox protein homolog 6 as a model system, we developed a systematic approach that integrates structure modeling, bioinformatics analysis, and peptide microarray experiments to identify lysine residues that are methylated and recognized by the chromodomain in the human proteome. Given the important role of chromobox protein homolog 6 as a reader of histone modifications, it was interesting to find that the majority of its interacting partners identified via this approach function in chromatin remodeling and transcriptional regulation. Our study not only illustrates a novel angle for identifying methyllysines on a proteome-wide scale and elucidating their potential roles in regulating protein function, but also suggests possible strategies for engineering the chromodomain-peptide interface to enhance the recognition of and manipulate the signal transduction mediated by such interactions.

48 CFR 243.205-72 - Unpriced change orders.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 243.205-72 Unpriced change orders. See the clause prescriptions at 217.7406 for all unpriced change orders with an... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Unpriced change orders...

48 CFR 243.205-72 - Unpriced change orders.

Code of Federal Regulations, 2011 CFR

2011-10-01

... SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 243.205-72 Unpriced change orders. See the clause prescriptions at 217.7406 for all unpriced change orders with an... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Unpriced change orders...

GPS-Lipid: a robust tool for the prediction of multiple lipid modification sites.

PubMed

Xie, Yubin; Zheng, Yueyuan; Li, Hongyu; Luo, Xiaotong; He, Zhihao; Cao, Shuo; Shi, Yi; Zhao, Qi; Xue, Yu; Zuo, Zhixiang; Ren, Jian

2016-06-16

As one of the most common post-translational modifications in eukaryotic cells, lipid modification is an important mechanism for the regulation of variety aspects of protein function. Over the last decades, three classes of lipid modifications have been increasingly studied. The co-regulation of these different lipid modifications is beginning to be noticed. However, due to the lack of integrated bioinformatics resources, the studies of co-regulatory mechanisms are still very limited. In this work, we developed a tool called GPS-Lipid for the prediction of four classes of lipid modifications by integrating the Particle Swarm Optimization with an aging leader and challengers (ALC-PSO) algorithm. GPS-Lipid was proven to be evidently superior to other similar tools. To facilitate the research of lipid modification, we hosted a publicly available web server at http://lipid.biocuckoo.org with not only the implementation of GPS-Lipid, but also an integrative database and visualization tool. We performed a systematic analysis of the co-regulatory mechanism between different lipid modifications with GPS-Lipid. The results demonstrated that the proximal dual-lipid modifications among palmitoylation, myristoylation and prenylation are key mechanism for regulating various protein functions. In conclusion, GPS-lipid is expected to serve as useful resource for the research on lipid modifications, especially on their co-regulation.

Methyltransferases acquired by lactococcal 936-type phage provide protection against restriction endonuclease activity.

PubMed

Murphy, James; Klumpp, Jochen; Mahony, Jennifer; O'Connell-Motherway, Mary; Nauta, Arjen; van Sinderen, Douwe

2014-10-01

So-called 936-type phages are among the most frequently isolated phages in dairy facilities utilising Lactococcus lactis starter cultures. Despite extensive efforts to control phage proliferation and decades of research, these phages continue to negatively impact cheese production in terms of the final product quality and consequently, monetary return. Whole genome sequencing and in silico analysis of three 936-type phage genomes identified several putative (orphan) methyltransferase (MTase)-encoding genes located within the packaging and replication regions of the genome. Utilising SMRT sequencing, methylome analysis was performed on all three phages, allowing the identification of adenine modifications consistent with N-6 methyladenine sequence methylation, which in some cases could be attributed to these phage-encoded MTases. Heterologous gene expression revealed that M.Phi145I/M.Phi93I and M.Phi93DAM, encoded by genes located within the packaging module, provide protection against the restriction enzymes HphI and DpnII, respectively, representing the first functional MTases identified in members of 936-type phages. SMRT sequencing technology enabled the identification of the target motifs of MTases encoded by the genomes of three lytic 936-type phages and these MTases represent the first functional MTases identified in this species of phage. The presence of these MTase-encoding genes on 936-type phage genomes is assumed to represent an adaptive response to circumvent host encoded restriction-modification systems thereby increasing the fitness of the phages in a dynamic dairy environment.

Addendum to the Closure Report for Corrective Action Unit 271: Areas 25, 26, and 27 Septic Systems Nevada Test Site, Nevada, Revision 0

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

Lynn Kidman

This document constitutes an addendum to the August 2004, Closure Report for Corrective Action Unit 271, Areas 25, 26, and 27 Septic Systems as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. The approval of the UR Modification document constituted approval of each of the recommended UR modifications. In conformance with the UR Modification document, this addendum consistsmore » of: • This cover page that refers the reader to the UR Modification document for additional information • The cover and signature pages of the UR Modification document • The NDEP approval letter • The corresponding section of the UR Modification document This addendum provides the documentation justifying the modification of the UR for CAS 27-05-02, Leachfield. This UR was established as part of a Federal Facility Agreement and Consent Order (FFACO) corrective action and is based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996; as amended August 2006). Since this UR was established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, this UR was re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006c). This re-evaluation consisted of comparing the original data (used to define the need for the UR) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to modify the UR to an administrative UR. Administrative URs differ from standard URs in that they do not require onsite postings (i.e., signs) or other physical barriers (e.g., fencing, monuments), and they do not require periodic inspections (see Section 6.2 of the Industrial Sites Project Establishment of Final Action Levels [NNSA/NSO, 2006c]). This Administrative UR was based on an “Occasional Use Area” future land use scenario that was used to calculate the FAL. The administrative UR will protect workers from an exposure exceeding that used in the calculation of the FAL (i.e., 400 total work hours). Any proposed activity within this use restricted area that would potentially cause an exposure exceeding this exposure limit would require approval from the Nevada Division of Environmental Protection (NDEP). Requirements for inspecting and maintaining postings at this UR will be canceled, and the postings and signage at this site will be removed. Fencing and posting may be present at this site that are unrelated to the FFACO UR such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004f). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at this site.« less

Stem cells. m6A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation.

PubMed

Geula, Shay; Moshitch-Moshkovitz, Sharon; Dominissini, Dan; Mansour, Abed AlFatah; Kol, Nitzan; Salmon-Divon, Mali; Hershkovitz, Vera; Peer, Eyal; Mor, Nofar; Manor, Yair S; Ben-Haim, Moshe Shay; Eyal, Eran; Yunger, Sharon; Pinto, Yishay; Jaitin, Diego Adhemar; Viukov, Sergey; Rais, Yoach; Krupalnik, Vladislav; Chomsky, Elad; Zerbib, Mirie; Maza, Itay; Rechavi, Yoav; Massarwa, Rada; Hanna, Suhair; Amit, Ido; Levanon, Erez Y; Amariglio, Ninette; Stern-Ginossar, Noam; Novershtern, Noa; Rechavi, Gideon; Hanna, Jacob H

2015-02-27

Naïve and primed pluripotent states retain distinct molecular properties, yet limited knowledge exists on how their state transitions are regulated. Here, we identify Mettl3, an N(6)-methyladenosine (m(6)A) transferase, as a regulator for terminating murine naïve pluripotency. Mettl3 knockout preimplantation epiblasts and naïve embryonic stem cells are depleted for m(6)A in mRNAs, yet are viable. However, they fail to adequately terminate their naïve state and, subsequently, undergo aberrant and restricted lineage priming at the postimplantation stage, which leads to early embryonic lethality. m(6)A predominantly and directly reduces mRNA stability, including that of key naïve pluripotency-promoting transcripts. This study highlights a critical role for an mRNA epigenetic modification in vivo and identifies regulatory modules that functionally influence naïve and primed pluripotency in an opposing manner. Copyright © 2015, American Association for the Advancement of Science.

Insights into inner ear-specific gene regulation: epigenetics and non-coding RNAs in inner ear development and regeneration

PubMed Central

Avraham, Karen B.

2016-01-01

The vertebrate inner ear houses highly specialized sensory organs, tuned to detect and encode sound, head motion and gravity. Gene expression programs under the control of transcription factors orchestrate the formation and specialization of the non-sensory inner ear labyrinth and its sensory constituents. More recently, epigenetic factors and non-coding RNAs emerged as an additional layer of gene regulation, both in inner ear development and disease. In this review, we provide an overview on how epigenetic modifications and non-coding RNAs, in particular microRNAs (miRNAs), influence gene expression and summarize recent discoveries that highlight their critical role in the proper formation of the inner ear labyrinth and its sensory organs. In contrast to non-mammalian vertebrates, adult mammals lack the ability to regenerate inner ear mechano-sensory hair cells. Finally, we discuss recent insights into how epigenetic factors and miRNAs may facilitate, or in the case of mammals, restrict sensory hair cell regeneration. PMID:27836639

Controlling hormone signaling is a plant and pathogen challenge for growth and survival.

PubMed

López, Miguel Angel; Bannenberg, Gerard; Castresana, Carmen

2008-08-01

Plants and pathogens have continuously confronted each other during evolution in a battle for growth and survival. New advances in the field have provided fascinating insights into the mechanisms that have co-evolved to gain a competitive advantage in this battle. When plants encounter an invading pathogen, not only responses signaled by defense hormones are activated to restrict pathogen invasion, but also the modulation of additional hormone pathways is required to serve other purposes, which are equally important for plant survival, such as re-allocation of resources, control of cell death, regulation of water stress, and modification of plant architecture. Notably, pathogens can counteract both types of responses as a strategy to enhance virulence. Pathogens regulate production and signaling responses of plant hormones during infection, and also produce phytohormones themselves to modulate plant responses. These results indicate that hormone signaling is a relevant component in plant-pathogen interactions, and that the ability to dictate hormonal directionality is critical to the outcome of an interaction.

78 FR 69286 - Electric System Construction Policies and Procedures

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-19

... DEPARTMENT OF AGRICULTURE Rural Utilities Service 7 CFR Part 1726 Electric System Construction Policies and Procedures CFR Correction In Title 7 of the Code of Federal Regulations, Parts 1600 to 1759, revised as of January 1, 2013, on page 246, in Sec. 1726.14, the second definition of Minor modification...

Defining the SUMO System in Maize: SUMOylation Is Up-Regulated during Endosperm Development and Rapidly Induced by Stress1[OPEN

PubMed Central

Augustine, Robert C.; Rytz, Thérèse C.

2016-01-01

In response to abiotic and biotic challenges, plants rapidly attach small ubiquitin-related modifier (SUMO) to a large collection of nuclear proteins, with studies in Arabidopsis (Arabidopsis thaliana) linking SUMOylation to stress tolerance via its modification of factors involved in chromatin and RNA dynamics. Despite this importance, little is known about SUMOylation in crop species. Here, we describe the plant SUMO system at the phylogenetic, biochemical, and transcriptional levels with a focus on maize (Zea mays). In addition to canonical SUMOs, land plants encode a loosely constrained noncanonical isoform and a variant containing a long extension upstream of the signature β-grasp fold, with cereals also expressing a novel diSUMO polypeptide bearing two SUMO β-grasp domains in tandem. Maize and other cereals also synthesize a unique SUMO-conjugating enzyme variant with more restricted expression patterns that is enzymatically active despite a distinct electrostatic surface. Maize SUMOylation primarily impacts nuclear substrates, is strongly induced by high temperatures, and displays a memory that suppresses subsequent conjugation. Both in-depth transcript and conjugate profiles in various maize organs point to tissue/cell-specific functions for SUMOylation, with potentially significant roles during embryo and endosperm maturation. Collectively, these studies define the organization of the maize SUMO system and imply important functions during seed development and stress defense. PMID:27208252

Short term effects of energy restriction and dietary fat sub-type on weight loss and disease risk factors.

PubMed

Tapsell, L; Batterham, M; Huang, X F; Tan, S-Y; Teuss, G; Charlton, K; Oshea, J; Warensjö, E

2010-06-01

Decreasing energy intake relative to energy expenditure is the indisputable tenet of weight loss. In addition to caloric restriction modification of the type of dietary fat may provide further benefits. The aim of the present study was to examine the effect of energy restriction alone and with dietary fat modification on weight loss and adiposity, as well as on risk factors for obesity related disease. One-hundred and fifty overweight men and women were randomized into a 3month controlled trial with four low fat (30% energy) dietary arms: (1) isocaloric (LF); (2) isocaloric with 10% polyunsaturated fatty acids (LF-PUFA); (3) low calorie (LF-LC) (-2MJ); (4) low calorie with 10% PUFA (LF-PUFA-LC). Primary outcomes were changes in body weight and body fat and secondary outcomes were changes in fasting levels of leptin, insulin, glucose, lipids and erythrocyte fatty acids. Changes in dietary intake were assessed using 3day food records. One-hundred and twenty-two participants entered the study and 95 completed the study. All groups lost weight and body fat (P<0.0001 time effect for both), but the LC groups lost more weight (P=0.026 for diet effect). All groups reduced total cholesterol levels (P<0.0001 time effect and P=0.017 intervention effect), but the LC and PUFA groups were better at reducing triacylglycerol levels (P=0.056 diet effect). HDL increased with LF-LC and LF-PUFA but not with LF-PUFA-LC (0.042 diet effect). The LF and LF-LC groups reported greater dietary fat reductions than the two PUFA groups (P=0.043). Energy restriction has the most potent effect on weight loss and lipids, but fat modification is also beneficial when energy restriction is more modest.

Plasma functionalization of polycarbonaturethane to improve endothelialization--Effect of shear stress as a critical factor for biocompatibility control.

PubMed

Lukas, Karin; Thomas, Ulrich; Gessner, André; Wehner, Daniel; Schmid, Thomas; Schmid, Christof; Lehle, Karla

2016-04-01

Medical devices made of polycarbonaturethane (PCU) combine excellent mechanical properties and little biological degradation, but restricted hemocompatibility. Modifications of PCU might reduce platelet adhesion and promote stable endothelialization. PCU was modified using gas plasma treatment, binding of hydrogels, and coupling of cell-active molecules (modified heparin, anti-thrombin III (ATIII), argatroban, fibronectin, laminin-nonapeptide, peptides with integrin-binding arginine-glycine-aspartic acid (RGD) motif). Biocompatibility was verified with static and dynamic cell culture techniques. Blinded analysis focused on improvement in endothelial cell (EC) adhesion/proliferation, anti-thrombogenicity, reproducible manufacturing process, and shear stress tolerance of ECs. EC adhesion and antithrombogenicity were achieved with 9/35 modifications. Additionally, 6/9 stimulated EC proliferation and 3/6 modification processes were highly reproducible for endothelialization. The latter modifications comprised immobilization of ATIII (A), polyethyleneglycole-diamine-hydrogel (E) and polyethylenimine-hydrogel connected with modified heparin (IH). Under sheer stress, only the IH modification improved EC adhesion within the graft. However, ECs did not arrange in flow direction and cell anchorage was restricted. Despite large variation in surface modification chemistry and improved EC adhesion under static culture conditions, additional introduction of shear stress foiled promising preliminary data. Therefore, biocompatibility testing required not only static tests but also usage of physiological conditions such as shear stress in the case of vascular grafts. © The Author(s) 2016.

Redox Signaling Mediated by Thioredoxin and Glutathione Systems in the Central Nervous System.

PubMed

Ren, Xiaoyuan; Zou, Lili; Zhang, Xu; Branco, Vasco; Wang, Jun; Carvalho, Cristina; Holmgren, Arne; Lu, Jun

2017-11-01

The thioredoxin (Trx) and glutathione (GSH) systems play important roles in maintaining the redox balance in the brain, a tissue that is prone to oxidative stress due to its high-energy demand. These two disulfide reductase systems are active in various areas of the brain and are considered to be critical antioxidant systems in the central nervous system (CNS). Various neuronal disorders have been characterized to have imbalanced redox homeostasis. Recent Advances: In addition to their detrimental effects, recent studies have highlighted that reactive oxygen species/reactive nitrogen species (ROS/RNS) act as critical signaling molecules by modifying thiols in proteins. The Trx and GSH systems, which reversibly regulate thiol modifications, regulate redox signaling involved in various biological events in the CNS. In this review, we focus on the following: (i) how ROS/RNS are produced and mediate signaling in CNS; (ii) how Trx and GSH systems regulate redox signaling by catalyzing reversible thiol modifications; (iii) how dysfunction of the Trx and GSH systems causes alterations of cellular redox signaling in human neuronal diseases; and (iv) the effects of certain small molecules that target thiol-based signaling pathways in the CNS. Further study on the roles of thiol-dependent redox systems in the CNS will improve our understanding of the pathogenesis of many human neuronal disorders and also help to develop novel protective and therapeutic strategies against neuronal diseases. Antioxid. Redox Signal. 27, 989-1010.

Modeling and performance improvement of the constant power regulator systems in variable displacement axial piston pump.

PubMed

Park, Sung Hwan; Lee, Ji Min; Kim, Jong Shik

2013-01-01

An irregular performance of a mechanical-type constant power regulator is considered. In order to find the cause of an irregular discharge flow at the cut-off pressure area, modeling and numerical simulations are performed to observe dynamic behavior of internal parts of the constant power regulator system for a swashplate-type axial piston pump. The commercial numerical simulation software AMESim is applied to model the mechanical-type regulator with hydraulic pump and simulate the performance of it. The validity of the simulation model of the constant power regulator system is verified by comparing simulation results with experiments. In order to find the cause of the irregular performance of the mechanical-type constant power regulator system, the behavior of main components such as the spool, sleeve, and counterbalance piston is investigated using computer simulation. The shape modification of the counterbalance piston is proposed to improve the undesirable performance of the mechanical-type constant power regulator. The performance improvement is verified by computer simulation using AMESim software.

Regulation of T cell receptor complex-mediated signaling by ubiquitin and ubiquitin-like modifications.

PubMed

Friend, Samantha F; Deason-Towne, Francina; Peterson, Lisa K; Berger, Allison J; Dragone, Leonard L

2014-01-01

Post-translational protein modifications are a dynamic method of regulating protein function in response to environmental signals. As with any cellular process, T cell receptor (TCR) complex-mediated signaling is highly regulated, since the strength and duration of TCR-generated signals governs T cell development and activation. While regulation of TCR complex-mediated signaling by phosphorylation has been well studied, regulation by ubiquitin and ubiquitin-like modifiers is still an emerging area of investigation. This review will examine how ubiquitin, E3 ubiquitin ligases, and other ubiquitin-like modifications such as SUMO and NEDD8 regulate TCR complex-mediated signaling.

Regulation of T cell receptor complex-mediated signaling by ubiquitin and ubiquitin-like modifications

PubMed Central

Friend, Samantha F; Deason-Towne, Francina; Peterson, Lisa K; Berger, Allison J; Dragone, Leonard L

2014-01-01

Post-translational protein modifications are a dynamic method of regulating protein function in response to environmental signals. As with any cellular process, T cell receptor (TCR) complex-mediated signaling is highly regulated, since the strength and duration of TCR-generated signals governs T cell development and activation. While regulation of TCR complex-mediated signaling by phosphorylation has been well studied, regulation by ubiquitin and ubiquitin-like modifiers is still an emerging area of investigation. This review will examine how ubiquitin, E3 ubiquitin ligases, and other ubiquitin-like modifications such as SUMO and NEDD8 regulate TCR complex-mediated signaling. PMID:25628960

An overview of safety assessment, regulation, and control of hazardous material use at NREL

NASA Astrophysics Data System (ADS)

Nelson, B. P.; Crandall, R. S.; Moskowitz, P. D.; Fthenakis, V. M.

1992-12-01

This paper summarizes the methodology we use to ensure the safe use of hazardous materials at the National Renewable Energy Laboratory (NREL). First, we analyze the processes and the materials used in those processes to identify the hazards presented. Then we study federal, state, and local regulations and apply the relevant requirements to our operations. When necessary, we generate internal safety documents to consolidate this information. We design research operations and support systems to conform to these requirements. Before we construct the systems, we perform a semiquantitative risk analysis on likely accident scenarios. All scenarios presenting an unacceptable risk require system or procedural modifications to reduce the risk. Following these modifications, we repeat the risk analysis to ensure that the respective accident scenarios present an acceptable risk. Once all risks are acceptable, we conduct an operational readiness review (ORR). A management-appointed panel performs the ORR ensuring compliance with all relevant requirements. After successful completion of the ORR, operations can begin.

Heterochromatin influences the secondary metabolite profile in the plant pathogen Fusarium graminearum

PubMed Central

Reyes-Dominguez, Yazmid; Boedi, Stefan; Sulyok, Michael; Wiesenberger, Gerlinde; Stoppacher, Norbert; Krska, Rudolf; Strauss, Joseph

2012-01-01

Chromatin modifications and heterochromatic marks have been shown to be involved in the regulation of secondary metabolism gene clusters in the fungal model system Aspergillus nidulans. We examine here the role of HEP1, the heterochromatin protein homolog of Fusarium graminearum, for the production of secondary metabolites. Deletion of Hep1 in a PH-1 background strongly influences expression of genes required for the production of aurofusarin and the main tricothecene metabolite DON. In the Hep1 deletion strains AUR genes are highly up-regulated and aurofusarin production is greatly enhanced suggesting a repressive role for heterochromatin on gene expression of this cluster. Unexpectedly, gene expression and metabolites are lower for the trichothecene cluster suggesting a positive function of Hep1 for DON biosynthesis. However, analysis of histone modifications in chromatin of AUR and DON gene promoters reveals that in both gene clusters the H3K9me3 heterochromatic mark is strongly reduced in the Hep1 deletion strain. This, and the finding that a DON-cluster flanking gene is up-regulated, suggests that the DON biosynthetic cluster is repressed by HEP1 directly and indirectly. Results from this study point to a conserved mode of secondary metabolite (SM) biosynthesis regulation in fungi by chromatin modifications and the formation of facultative heterochromatin. PMID:22100541

77 FR 74631 - General Services Administration Acquisition Regulation: Modifications (Multiple Award Schedules...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-17

...-0001; Sequence 21] General Services Administration Acquisition Regulation: Modifications (Multiple... Modifications (Multiple Award Schedule). DATES: Submit comments on or before: February 15, 2013. FOR FURTHER INFORMATION CONTACT: Ms. Dana Munson, General Services Acquisition Policy Division, GSA, (202) 357-9652 or...

45 CFR 671.10 - Review, modification, suspension, and revocation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 3 2011-10-01 2011-10-01 false Review, modification, suspension, and revocation. 671.10 Section 671.10 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION WASTE REGULATION Permits § 671.10 Review, modification, suspension, and revocation. (a...

Trafficking and function of the cystic fibrosis transmembrane conductance regulator: a complex network of posttranslational modifications

PubMed Central

McClure, Michelle L.; Barnes, Stephen; Brodsky, Jeffrey L.

2016-01-01

Posttranslational modifications add diversity to protein function. Throughout its life cycle, the cystic fibrosis transmembrane conductance regulator (CFTR) undergoes numerous covalent posttranslational modifications (PTMs), including glycosylation, ubiquitination, sumoylation, phosphorylation, and palmitoylation. These modifications regulate key steps during protein biogenesis, such as protein folding, trafficking, stability, function, and association with protein partners and therefore may serve as targets for therapeutic manipulation. More generally, an improved understanding of molecular mechanisms that underlie CFTR PTMs may suggest novel treatment strategies for CF and perhaps other protein conformational diseases. This review provides a comprehensive summary of co- and posttranslational CFTR modifications and their significance with regard to protein biogenesis. PMID:27474090

76 FR 63612 - National Committee on Foreign Medical Education and Accreditation Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-13

..., 550 Twelfth Street, SW., Washington, DC 20202. Due to security restrictions, all attendees must pre... the Federal Register and the Code of Federal Regulations is available via the Federal Digital System...

Coordinated action of histone modification and microRNA regulations in human genome.

PubMed

Wang, Xuan; Zheng, Guantao; Dong, Dong

2015-10-10

Both histone modifications and microRNAs (miRNAs) play pivotal role in gene expression regulation. Although numerous studies have been devoted to explore the gene regulation by miRNA and epigenetic regulations, their coordinated actions have not been comprehensively examined. In this work, we systematically investigated the combinatorial relationship between miRNA and epigenetic regulation by taking advantage of recently published whole genome-wide histone modification data and high quality miRNA targeting data. The results showed that miRNA targets have distinct histone modification patterns compared with non-targets in their promoter regions. Based on this finding, we proposed a machine learning approach to fit predictive models on the task to discern whether a gene is targeted by a specific miRNA. We found a considerable advantage in both sensitivity and specificity in diverse human cell lines. Finally, we found that our predicted miRNA targets are consistently annotated with Gene Ontology terms. Our work is the first genome-wide investigation of the coordinated action of miRNA and histone modification regulations, which provide a guide to deeply understand the complexity of transcriptional regulation. Copyright © 2015 Elsevier B.V. All rights reserved.

Noachian and Hesperian modification of the original Chryse impact basin topography

NASA Technical Reports Server (NTRS)

Stockman, S. A.; Frey, H.

1995-01-01

We prospose a new center and ring assignment for the original Chryse impact basin based upon photogeologic mapping of Noachian outcrops and re-examination of the published geology using orthographic projections. While others have centered the Chryse impact on the topographic low associated with Hesperian volcanic and fluvial deposits, we suggest that the center of the Noachian-age excavation cavity was located approximately 800 km to the north, and that the basin topography was modified significantly from the Noachian into the Hesperian. Evolution of the topographic low included structural modification by a later impact centered in Acidalia, restricted volcanic deposition and loading, localized subsidence, and restricted deposition from the circum-Chryse outlfow channels.

A simple algorithm for quantifying DNA methylation levels on multiple independent CpG sites in bisulfite genomic sequencing electropherograms.

PubMed

Leakey, Tatiana I; Zielinski, Jerzy; Siegfried, Rachel N; Siegel, Eric R; Fan, Chun-Yang; Cooney, Craig A

2008-06-01

DNA methylation at cytosines is a widely studied epigenetic modification. Methylation is commonly detected using bisulfite modification of DNA followed by PCR and additional techniques such as restriction digestion or sequencing. These additional techniques are either laborious, require specialized equipment, or are not quantitative. Here we describe a simple algorithm that yields quantitative results from analysis of conventional four-dye-trace sequencing. We call this method Mquant and we compare it with the established laboratory method of combined bisulfite restriction assay (COBRA). This analysis of sequencing electropherograms provides a simple, easily applied method to quantify DNA methylation at specific CpG sites.

33 CFR 334.1030 - Oakland Inner Harbor adjacent to Alameda Facility, Naval Supply Center, Oakland; restricted area.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Alameda Facility, Naval Supply Center, Oakland; restricted area. 334.1030 Section 334.1030 Navigation and... RESTRICTED AREA REGULATIONS § 334.1030 Oakland Inner Harbor adjacent to Alameda Facility, Naval Supply Center, Oakland; restricted area. (a) The area. Within 100 feet of the Alameda Facility wharf. (b) The regulations...

33 CFR 334.1030 - Oakland Inner Harbor adjacent to Alameda Facility, Naval Supply Center, Oakland; restricted area.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Alameda Facility, Naval Supply Center, Oakland; restricted area. 334.1030 Section 334.1030 Navigation and... RESTRICTED AREA REGULATIONS § 334.1030 Oakland Inner Harbor adjacent to Alameda Facility, Naval Supply Center, Oakland; restricted area. (a) The area. Within 100 feet of the Alameda Facility wharf. (b) The regulations...

33 CFR 334.1030 - Oakland Inner Harbor adjacent to Alameda Facility, Naval Supply Center, Oakland; restricted area.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Alameda Facility, Naval Supply Center, Oakland; restricted area. 334.1030 Section 334.1030 Navigation and... RESTRICTED AREA REGULATIONS § 334.1030 Oakland Inner Harbor adjacent to Alameda Facility, Naval Supply Center, Oakland; restricted area. (a) The area. Within 100 feet of the Alameda Facility wharf. (b) The regulations...

33 CFR 334.1030 - Oakland Inner Harbor adjacent to Alameda Facility, Naval Supply Center, Oakland; restricted area.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Alameda Facility, Naval Supply Center, Oakland; restricted area. 334.1030 Section 334.1030 Navigation and... RESTRICTED AREA REGULATIONS § 334.1030 Oakland Inner Harbor adjacent to Alameda Facility, Naval Supply Center, Oakland; restricted area. (a) The area. Within 100 feet of the Alameda Facility wharf. (b) The regulations...

49 CFR 236.567 - Restrictions imposed when device fails and/or is cut out en route.

Code of Federal Regulations, 2013 CFR

2013-10-01

... cut out en route. 236.567 Section 236.567 Transportation Other Regulations Relating to Transportation... GOVERNING THE INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Train Stop, Train Control and Cab Signal Systems Rules and Instructions...

Cost-effectiveness of a complex workplace dietary intervention: an economic evaluation of the Food Choice at Work study.

PubMed

Fitzgerald, Sarah; Murphy, Aileen; Kirby, Ann; Geaney, Fiona; Perry, Ivan J

2018-03-03

To evaluate the costs, benefits and cost-effectiveness of complex workplace dietary interventions, involving nutrition education and system-level dietary modification, from the perspective of healthcare providers and employers. Single-study economic evaluation of a cluster-controlled trial (Food Choice at Work (FCW) study) with 1-year follow-up. Four multinational manufacturing workplaces in Cork, Ireland. 517 randomly selected employees (18-65 years) from four workplaces. Cost data were obtained from the FCW study. Nutrition education included individual nutrition consultations, nutrition information (traffic light menu labelling, posters, leaflets and emails) and presentations. System-level dietary modification included menu modification (restriction of fat, sugar and salt), increase in fibre, fruit discounts, strategic positioning of healthier alternatives and portion size control. The combined intervention included nutrition education and system-level dietary modification. No intervention was implemented in the control. The primary outcome was an improvement in health-related quality of life, measured using the EuroQoL 5 Dimensions 5 Levels questionnaire. The secondary outcome measure was reduction in absenteeism, which is measured in monetary amounts. Probabilistic sensitivity analysis (Monte Carlo simulation) assessed parameter uncertainty. The system-level intervention dominated the education and combined interventions. When compared with the control, the incremental cost-effectiveness ratio (€101.37/quality-adjusted life-year) is less than the nationally accepted ceiling ratio, so the system-level intervention can be considered cost-effective. The cost-effectiveness acceptability curve indicates there is some decision uncertainty surrounding this, arising from uncertainty surrounding the differences in effectiveness. These results are reiterated when the secondary outcome measure is considered in a cost-benefit analysis, whereby the system-level intervention yields the highest net benefit (€56.56 per employee). System-level dietary modification alone offers the most value per improving employee health-related quality of life and generating net benefit for employers by reducing absenteeism. While system-level dietary modification strategies are potentially sustainable obesity prevention interventions, future research should include long-term outcomes to determine if improvements in outcomes persist. ISRCTN35108237; Post-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The rational parameterization theorem for multisite post-translational modification systems.

PubMed

Thomson, Matthew; Gunawardena, Jeremy

2009-12-21

Post-translational modification of proteins plays a central role in cellular regulation but its study has been hampered by the exponential increase in substrate modification forms ("modforms") with increasing numbers of sites. We consider here biochemical networks arising from post-translational modification under mass-action kinetics, allowing for multiple substrates, having different types of modification (phosphorylation, methylation, acetylation, etc.) on multiple sites, acted upon by multiple forward and reverse enzymes (in total number L), using general enzymatic mechanisms. These assumptions are substantially more general than in previous studies. We show that the steady-state modform concentrations constitute an algebraic variety that can be parameterized by rational functions of the L free enzyme concentrations, with coefficients which are rational functions of the rate constants. The parameterization allows steady states to be calculated by solving L algebraic equations, a dramatic reduction compared to simulating an exponentially large number of differential equations. This complexity collapse enables analysis in contexts that were previously intractable and leads to biological predictions that we review. Our results lay a foundation for the systems biology of post-translational modification and suggest deeper connections between biochemical networks and algebraic geometry.

76 FR 36871 - Modification of Restricted Areas R-4401A, R-4401B, and R-4401C; Camp Shelby, MS

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-23

... National Guard (ANG) published a Final Environmental Assessment (FEA) ``Modification of CRTC-Used Airspace..., 2008. The ANG prepared the FEA and associated FONSI in compliance with their obligations under the... 404d, the FAA has independently evaluated the information contained in the FEA and is adopting the...

31 CFR 501.803 - Amendment, modification, or revocation.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Amendment, modification, or revocation. 501.803 Section 501.803 Money and Finance: Treasury Regulations Relating to Money and Finance... REGULATIONS Procedures § 501.803 Amendment, modification, or revocation. Except as otherwise provided by law...

31 CFR 501.803 - Amendment, modification, or revocation.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Amendment, modification, or revocation. 501.803 Section 501.803 Money and Finance: Treasury Regulations Relating to Money and Finance... REGULATIONS Procedures § 501.803 Amendment, modification, or revocation. Except as otherwise provided by law...

31 CFR 501.803 - Amendment, modification, or revocation.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Amendment, modification, or revocation. 501.803 Section 501.803 Money and Finance: Treasury Regulations Relating to Money and Finance... REGULATIONS Procedures § 501.803 Amendment, modification, or revocation. Except as otherwise provided by law...

31 CFR 501.803 - Amendment, modification, or revocation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Amendment, modification, or revocation. 501.803 Section 501.803 Money and Finance: Treasury Regulations Relating to Money and Finance... REGULATIONS Procedures § 501.803 Amendment, modification, or revocation. Except as otherwise provided by law...

Rescue of Notch signaling in cells incapable of GDP-L-fucose synthesis by gap junction transfer of GDP-L-fucose in Drosophila.

PubMed

Ayukawa, Tomonori; Matsumoto, Kenjiroo; Ishikawa, Hiroyuki O; Ishio, Akira; Yamakawa, Tomoko; Aoyama, Naoki; Suzuki, Takuya; Matsuno, Kenji

2012-09-18

Notch (N) is a transmembrane receptor that mediates cell-cell interactions to determine many cell-fate decisions. N contains EGF-like repeats, many of which have an O-fucose glycan modification that regulates N-ligand binding. This modification requires GDP-L-fucose as a donor of fucose. The GDP-L-fucose biosynthetic pathways are well understood, including the de novo pathway, which depends on GDP-mannose 4,6 dehydratase (Gmd) and GDP-4-keto-6-deoxy-D-mannose 3,5-epimerase/4-reductase (Gmer). However, the potential for intercellularly supplied GDP-L-fucose and the molecular basis of such transportation have not been explored in depth. To address these points, we studied the genetic effects of mutating Gmd and Gmer on fucose modifications in Drosophila. We found that these mutants functioned cell-nonautonomously, and that GDP-L-fucose was supplied intercellularly through gap junctions composed of Innexin-2. GDP-L-fucose was not supplied through body fluids from different isolated organs, indicating that the intercellular distribution of GDP-L-fucose is restricted within a given organ. Moreover, the gap junction-mediated supply of GDP-L-fucose was sufficient to support the fucosylation of N-glycans and the O-fucosylation of the N EGF-like repeats. Our results indicate that intercellular delivery is a metabolic pathway for nucleotide sugars in live animals under certain circumstances.

Chemical and Biological Tools for the Preparation of Modified Histone Proteins

PubMed Central

Howard, Cecil J.; Yu, Ruixuan R.; Gardner, Miranda L.; Shimko, John C.; Ottesen, Jennifer J.

2016-01-01

Eukaryotic chromatin is a complex and dynamic system in which the DNA double helix is organized and protected by interactions with histone proteins. This system is regulated through, a large network of dynamic post-translational modifications (PTMs) exists to ensure proper gene transcription, DNA repair, and other processes involving DNA. Homogenous protein samples with precisely characterized modification sites are necessary to better understand the functions of modified histone proteins. Here, we discuss sets of chemical and biological tools that have been developed for the preparation of modified histones, with a focus on the appropriate choice of tool for a given target. We start with genetic approaches for the creation of modified histones, including the incorporation of genetic mimics of histone modifications, chemical installation of modification analogs, and the use of the expanded genetic code to incorporate modified amino acids. Additionally, we will cover the chemical ligation techniques that have been invaluable in the generation of complex modified histones that are indistinguishable from the natural counterparts. Finally, we will end with a prospectus on future directions of synthetic chromatin in living systems. PMID:25863817

[The issues of legal support of municipal public health].

PubMed

2011-01-01

The issues of legal regulation of municipal health care system are discussed. It is demonstrated that the Federal legislation unjustifiably restricts the powers of municipal public health. This situation impacts the provision of accessible and qualified medical care to population and financing of municipal public health. The necessity of further development of legal regulation of health promotion on municipal level is postulated.

Web-Based Reading Annotation System with an Attention-Based Self-Regulated Learning Mechanism for Promoting Reading Performance

ERIC Educational Resources Information Center

Chen, Chih-Ming; Huang, Sheng-Hui

2014-01-01

Due to the rapid development of information technology, web-based learning has become a dominant trend. That is, learners can often learn anytime and anywhere without being restricted by time and space. Autonomic learning primarily occurs in web-based learning environments, and self-regulated learning (SRL) is key to autonomic learning…

78 FR 60238 - Proposed Modification and Establishment of Restricted Areas; Aberdeen Proving Ground, MD

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-01

...; Aberdeen Proving Ground, MD AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed..., within the existing restricted areas R-4001A and R- 4001B, at the U.S. Army's Aberdeen Proving Ground in... nonparticipating aircraft from a hazard to navigation in the Aberdeen Proving Ground airspace. DATES: Comments must...

Epigenetic hierarchy governing Nestin expression.

PubMed

Han, Dong Wook; Do, Jeong Tae; Araúzo-Bravo, Marcos J; Lee, Sung Ho; Meissner, Alexander; Lee, Hoon Taek; Jaenisch, Rudolf; Schöler, Hans R

2009-05-01

Nestin is an intermediate filament protein expressed specifically in neural stem cells and progenitor cells of the central nervous system. DNA demethylation and histone modifications are two types of epigenetic modifications working in a coordinate or synergistic manner to regulate the expression of various genes. This study investigated and elucidated the epigenetic regulation of Nestin gene expression during embryonic differentiation along the neural cell lineage. Nestin exhibits differential DNA methylation and histone acetylation patterns in Nestin-expressing and nonexpressing cells. In P19 embryonic carcinoma cells, activation of Nestin expression is mediated by both trichostatin A and 5-aza-2'-deoxycytidine treatment, concomitant with histone acetylation, but not with DNA demethylation. Nestin transcription is also mediated by treatment with retinoic acid, again in the absence of DNA demethylation. Thus, histone acetylation is sufficient to mediate the activation of Nestin transcription. This study proposed that the regulation of Nestin gene expression can be used as a model to study the epigenetic regulation of gene expression mediated by histone acetylation, but not by DNA demethylation.

Methylated nucleosides in tRNA and tRNA methyltransferases

PubMed Central

Hori, Hiroyuki

2014-01-01

To date, more than 90 modified nucleosides have been found in tRNA and the biosynthetic pathways of the majority of tRNA modifications include a methylation step(s). Recent studies of the biosynthetic pathways have demonstrated that the availability of methyl group donors for the methylation in tRNA is important for correct and efficient protein synthesis. In this review, I focus on the methylated nucleosides and tRNA methyltransferases. The primary functions of tRNA methylations are linked to the different steps of protein synthesis, such as the stabilization of tRNA structure, reinforcement of the codon-anticodon interaction, regulation of wobble base pairing, and prevention of frameshift errors. However, beyond these basic functions, recent studies have demonstrated that tRNA methylations are also involved in the RNA quality control system and regulation of tRNA localization in the cell. In a thermophilic eubacterium, tRNA modifications and the modification enzymes form a network that responses to temperature changes. Furthermore, several modifications are involved in genetic diseases, infections, and the immune response. Moreover, structural, biochemical, and bioinformatics studies of tRNA methyltransferases have been clarifying the details of tRNA methyltransferases and have enabled these enzymes to be classified. In the final section, the evolution of modification enzymes is discussed. PMID:24904644

Distinct 3-O-Sulfated Heparan Sulfate Modification Patterns Are Required for kal-1−Dependent Neurite Branching in a Context-Dependent Manner in Caenorhabditis elegans

PubMed Central

Tecle, Eillen; Diaz-Balzac, Carlos A.; Bülow, Hannes E.

2013-01-01

Heparan sulfate (HS) is an unbranched glycosaminoglycan exhibiting substantial molecular diversity due to multiple, nonuniformly introduced modifications, including sulfations, epimerization, and acetylation. HS modifications serve specific and instructive roles in neuronal development, leading to the hypothesis of a HS code that regulates nervous system patterning. Although the in vivo roles of many of the HS modifications have been investigated, very little is known about the function of HS 3-O-sulfation in vivo. By examining patterning of the Caenorhabditis elegans nervous system in loss of function mutants of the two 3-O-sulfotransferases, hst-3.1 and hst-3.2, we found HS 3-O-sulfation to be largely dispensable for overall neural development. However, generation of stereotypical neurite branches in hermaphroditic-specific neurons required hst-3.1, hst-3.2, as well as an extracellular cell adhesion molecule encoded by kal-1, the homolog of Kallmann Syndrome associated gene 1/anosmin-1. In contrast, kal-1−dependent neurite branching in AIY neurons required catalytic activity of hst-3.2 but not hst-3.1. The context-dependent requirement for hst-3.2 and hst-3.1 indicates that both enzymes generate distinct types of HS modification patterns in different cell types, which regulate kal-1 to promote neurite branching. We conclude that HS 3-O-sulfation does not play a general role in establishing the HS code in C. elegans but rather plays a specialized role in a context-dependent manner to establish defined aspects of neuronal circuits. PMID:23451335

Current reprogramming systems in regenerative medicine: from somatic cells to induced pluripotent stem cells.

PubMed

Hu, Chenxia; Li, Lanjuan

2016-01-01

Induced pluripotent stem cells (iPSCs) paved the way for research fields including cell therapy, drug screening, disease modeling and the mechanism of embryonic development. Although iPSC technology has been improved by various delivery systems, direct transduction and small molecule regulation, low reprogramming efficiency and genomic modification steps still inhibit its clinical use. Improvements in current vectors and the exploration of novel vectors are required to balance efficiency and genomic modification for reprogramming. Herein, we set out a comprehensive analysis of current reprogramming systems for the generation of iPSCs from somatic cells. By clarifying advantages and disadvantages of the current reprogramming systems, we are striding toward an effective route to generate clinical grade iPSCs.

The histone modifications governing TFF1 transcription mediated by estrogen receptor.

PubMed

Li, Yanyan; Sun, Luyang; Zhang, Yu; Wang, Dandan; Wang, Feng; Liang, Jing; Gui, Bin; Shang, Yongfeng

2011-04-22

Transcription regulation by histone modifications is a major contributing factor to the structural and functional diversity in biology. These modifications are encrypted as histone codes or histone languages and function to establish and maintain heritable epigenetic codes that define the identity and the fate of the cell. Despite recent advances revealing numerous histone modifications associated with transcription regulation, how such modifications dictate the process of transcription is not fully understood. Here we describe spatial and temporal analyses of the histone modifications that are introduced during estrogen receptor α (ERα)-activated transcription. We demonstrated that aborting RNA polymerase II caused a disruption of the histone modifications that are associated with transcription elongation but had a minimal effect on modifications deposited during transcription initiation. We also found that the histone H3S10 phosphorylation mark is catalyzed by mitogen- and stress-activated protein kinase 1 (MSK1) and is recognized by a 14-3-3ζ/14-3-3ε heterodimer through its interaction with H3K4 trimethyltransferase SMYD3 and the p52 subunit of TFIIH. We showed that H3S10 phosphorylation is a prerequisite for H3K4 trimethylation. In addition, we demonstrated that SET8/PR-Set7/KMT5A is required for ERα-regulated transcription and its catalyzed H4K20 monomethylation is implicated in both transcription initiation and elongation. Our experiments provide a relatively comprehensive analysis of histone modifications associated with ERα-regulated transcription and define the biological meaning of several key components of the histone code that governs ERα-regulated transcription.

Medical devices; ovarian adnexal mass assessment score test system; labeling; black box restrictions. Final rule.

PubMed

2011-12-30

The Food and Drug Administration (FDA) is amending the regulation classifying ovarian adnexal mass assessment score test systems to restrict these devices so that a prescribed warning statement that addresses a risk identified in the special controls guidance document must be in a black box and must appear in all labeling, advertising, and promotional material. The black box warning mitigates the risk to health associated with off-label use as a screening test, stand-alone diagnostic test, or as a test to determine whether or not to proceed with surgery.

75 FR 6865 - Airworthiness Directives; The Boeing Company Model 737-700 (IGW) Series Airplanes Equipped With...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-12

... deactivation or modification of PATS Aircraft, LLC, auxiliary fuel tanks. This proposed AD results from fuel... for fuel tank systems. As a result of those findings, we issued a regulation titled ``Transport Airplane Fuel Tank System Design Review, Flammability Reduction and Maintenance and Inspection Requirements...

7 CFR 301.91 - Quarantine and regulations; restrictions on interstate movement of regulated articles. 1

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 5 2012-01-01 2012-01-01 false Quarantine and regulations; restrictions on interstate... QUARANTINE NOTICES European Larch Canker Quarantine and Regulations § 301.91 Quarantine and regulations... to stop and inspect persons and means of conveyance, and to seize, quarantine, treat, apply other...

7 CFR 301.91 - Quarantine and regulations; restrictions on interstate movement of regulated articles. 1

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Quarantine and regulations; restrictions on interstate... QUARANTINE NOTICES European Larch Canker Quarantine and Regulations § 301.91 Quarantine and regulations... to stop and inspect persons and means of conveyance, and to seize, quarantine, treat, apply other...

7 CFR 301.91 - Quarantine and regulations; restrictions on interstate movement of regulated articles. 1

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 5 2014-01-01 2014-01-01 false Quarantine and regulations; restrictions on interstate... QUARANTINE NOTICES European Larch Canker Quarantine and Regulations § 301.91 Quarantine and regulations... to stop and inspect persons and means of conveyance, and to seize, quarantine, treat, apply other...

7 CFR 301.91 - Quarantine and regulations; restrictions on interstate movement of regulated articles. 1

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 5 2011-01-01 2011-01-01 false Quarantine and regulations; restrictions on interstate... QUARANTINE NOTICES European Larch Canker Quarantine and Regulations § 301.91 Quarantine and regulations... to stop and inspect persons and means of conveyance, and to seize, quarantine, treat, apply other...

7 CFR 301.91 - Quarantine and regulations; restrictions on interstate movement of regulated articles. 1

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 5 2013-01-01 2013-01-01 false Quarantine and regulations; restrictions on interstate... QUARANTINE NOTICES European Larch Canker Quarantine and Regulations § 301.91 Quarantine and regulations... to stop and inspect persons and means of conveyance, and to seize, quarantine, treat, apply other...

7 CFR 301.92-4 - Conditions governing the interstate movement of regulated, restricted, and associated articles...

Code of Federal Regulations, 2010 CFR

2010-01-01

... regulated, restricted, and associated articles, and non-host nursery stock from quarantined and regulated... associated articles, and non-host nursery stock from quarantined and regulated areas. (a) Interstate movement... movement of nursery stock from nurseries in quarantined areas—(1) Regulated articles of nursery stock and...

48 CFR 43.204 - Administration.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Administration. 43.204... CONTRACT MODIFICATIONS Change Orders 43.204 Administration. (a) Change order documentation. When change... adjusting the contract delivery schedule. (3) Contracting offices and contract administration offices, as...

48 CFR 43.204 - Administration.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Administration. 43.204... CONTRACT MODIFICATIONS Change Orders 43.204 Administration. (a) Change order documentation. When change... adjusting the contract delivery schedule. (3) Contracting offices and contract administration offices, as...

48 CFR 43.204 - Administration.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Administration. 43.204... CONTRACT MODIFICATIONS Change Orders 43.204 Administration. (a) Change order documentation. When change... adjusting the contract delivery schedule. (3) Contracting offices and contract administration offices, as...

78 FR 3367 - Modification of Regulation Regarding the Extension of Time Limits

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-16

...-2747-01] RIN 0625-AA94 Modification of Regulation Regarding the Extension of Time Limits AGENCY: Import... the extension of time limits for submissions in antidumping (AD) and countervailing duty (CVD) proceedings. The modification, if adopted, will clarify that parties may request an extension of time limits...