Host factor I, Hfq, binds to Escherichia coli ompA mRNA in a growth rate-dependent fashion and regulates its stability

DEFF Research Database (Denmark)

Vytvytska, O; Jakobsen, J S; Balcunaite, G

1998-01-01

RNA. In hfq mutant cells with a deficient Hfq gene product, the RNA-binding activity is missing, and analysis of the ompA mRNA showed that the growth-rate dependence of degradation is lost. Furthermore, the half-life of the ompA mRNA is prolonged in the mutant cells, irrespective of growth rate. Hfq has...

Expression, crystallization and preliminary crystallographic analysis of RNA-binding protein Hfq (YmaH) from Bacillus subtilis in complex with an RNA aptamer.

Science.gov (United States)

Baba, Seiki; Someya, Tatsuhiko; Kawai, Gota; Nakamura, Kouji; Kumasaka, Takashi

2010-05-01

The Hfq protein is a hexameric RNA-binding protein which regulates gene expression by binding to RNA under the influence of diverse environmental stresses. Its ring structure binds various types of RNA, including mRNA and sRNA. RNA-bound structures of Hfq from Escherichia coli and Staphylococcus aureus have been revealed to have poly(A) RNA at the distal site and U-rich RNA at the proximal site, respectively. Here, crystals of a complex of the Bacillus subtilis Hfq protein with an A/G-repeat 7-mer RNA (Hfq-RNA) that were prepared using the hanging-drop vapour-diffusion technique are reported. The type 1 Hfq-RNA crystals belonged to space group I422, with unit-cell parameters a = b = 123.70, c = 119.13 A, while the type 2 Hfq-RNA crystals belonged to space group F222, with unit-cell parameters a = 91.92, b = 92.50, c = 114.92 A. Diffraction data were collected to a resolution of 2.20 A from both crystal forms. The hexameric structure of the Hfq protein was clearly shown by self-rotation analysis.

Cyanobacteria contain a structural homologue of the Hfq protein with altered RNA binding properties

DEFF Research Database (Denmark)

Bøggild, Andreas; Overgaard, Martin; Valentin-Hansen, Poul

2009-01-01

Hfq proteins are common in many species of enterobacteria, where they participate in RNA folding and translational regulation through pairing of small RNAs and messenger RNAs. Hfq proteins share the distinctive Sm fold, and form ring-shaped structures similar to those of the Sm/Lsm proteins...... proteins from the cyanobacteria Synechocystis sp. PCC 6803 and Anabaena PCC 7120 at 1.3 and 2.3 A resolution, respectively, and show that they retain the classic Sm fold despite low sequence conservation. In addition, the intersubunit contacts and RNA-binding site are divergent, and we show biochemically...

Cyanobacteria contain a structural homologue of the Hfq protein with altered RNA-binding properties

DEFF Research Database (Denmark)

Bøggild, Andreas; Overgaard, Martin; Valentin-Hansen, Poul

2009-01-01

Hfq proteins are common in many species of enterobacteria, where they participate in RNA folding and translational regulation through pairing of small RNAs and messenger RNAs. Hfq proteins share the distinctive Sm fold, and form ring-shaped structures similar to those of the Sm/Lsm proteins...... proteins from the cyanobacteria Synechocystis sp. PCC 6803 and Anabaena PCC 7120 at 1.3 and 2.3 A resolution, respectively, and show that they retain the classic Sm fold despite low sequence conservation. In addition, the intersubunit contacts and RNA-binding site are divergent, and we show biochemically...

Global Systems-Level Analysis of Hfq and SmpB Deletion Mutants in Salmonella: Implications for Virulence and Global Protein Translation

Energy Technology Data Exchange (ETDEWEB)

Ansong, Charles; Yoon, Hyunjin; Porwollik, Steffen; Mottaz-Brewer, Heather; Petritis, Brianne O.; Jaitly, Navdeep; Adkins, Joshua N.; Mcclelland, Michael; Heffron, Fred; Smith, Richard D.

2009-03-11

In recent years the profound importance of sRNA-mediated translational/post-transcriptional regulation has been increasingly appreciated. However, the global role played by translational regulation in control of gene expression has never been elucidated in any organism for the simple reason that global proteomics methods required to accurately characterize post-transcriptional processes and the knowledge of translational control mechanisms have only become available within the last few years. The proteins Hfq and SmpB are essential for the biological activity of a range of regulatory sRNAs and thus provide a means to identify potential targets of sRNA regulation. We performed a sample-matched global proteomics and transcriptional analysis to examine the role of Hfq and SmpB in global protein translation and virulence using the Salmonella typhimurium model system. Samples were analyzed from bacteria grown under four different conditions; two laboratory conditions and two that are thought to mimic the intracellular environment. We show that mutants of hfq and smpB directly or indirectly modulate at least 20% and 4% of all Salmonella proteins, respectively, with limited correlation between transcription and protein expression. This is the first report suggesting that SmpB could be a general translational regulator. The broad spectrum of proteins modulated by Hfq was also surprising including central metabolism, LPS biosynthesis, two-component regulatory systems, quorum sensing, SP1-TTSS, oxidative stress, fatty acid metabolism, nucleoside and nucleotide metabolism, envelope stress, aminoacyl-tRNA synthetases, amino acid biosynthesis, peptide transport, and motility.. The extent of global regulation of translation by Hfq is unexpected, with profound effects in all stages of Salmonella’s life cycle. Our results represent the first global systems-level analysis of translational regulation; the elucidated potential targets of sRNA regulation from our analysis will

Structural characterization of the RNA chaperone Hfq from the nitrogen-fixing bacterium Herbaspirillum seropedicae SmR1.

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Kadowaki, Marco Antonio Seiki; Iulek, Jorge; Barbosa, João Alexandre Ribeiro Gonçalves; Pedrosa, Fábio de Oliveira; de Souza, Emanuel Maltempi; Chubatsu, Leda Satie; Monteiro, Rose Adele; de Oliveira, Marco Aurélio Schüler; Steffens, Maria Berenice Reynaud

2012-02-01

The RNA chaperone Hfq is a homohexamer protein identified as an E. coli host factor involved in phage Qβ replication and it is an important posttranscriptional regulator of several types of RNA, affecting a plethora of bacterial functions. Although twenty Hfq crystal structures have already been reported in the Protein Data Bank (PDB), new insights into these protein structures can still be discussed. In this work, the structure of Hfq from the β-proteobacterium Herbaspirillum seropedicae, a diazotroph associated with economically important agricultural crops, was determined by X-ray crystallography and small-angle X-ray scattering (SAXS). Biochemical assays such as exclusion chromatography and RNA-binding by the electrophoretic shift assay (EMSA) confirmed that the purified protein is homogeneous and active. The crystal structure revealed a conserved Sm topology, composed of one N-terminal α-helix followed by five twisted β-strands, and a novel π-π stacking intra-subunit interaction of two histidine residues, absent in other Hfq proteins. Moreover, the calculated ab initio envelope based on small-angle X-ray scattering (SAXS) data agreed with the Hfq crystal structure, suggesting that the protein has the same folding structure in solution. Copyright © 2011 Elsevier B.V. All rights reserved.

Reduced heme levels underlie the exponential growth defect of the Shewanella oneidensis hfq mutant.

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Christopher M Brennan

Full Text Available The RNA chaperone Hfq fulfills important roles in small regulatory RNA (sRNA function in many bacteria. Loss of Hfq in the dissimilatory metal reducing bacterium Shewanella oneidensis strain MR-1 results in slow exponential phase growth and a reduced terminal cell density at stationary phase. We have found that the exponential phase growth defect of the hfq mutant in LB is the result of reduced heme levels. Both heme levels and exponential phase growth of the hfq mutant can be completely restored by supplementing LB medium with 5-aminolevulinic acid (5-ALA, the first committed intermediate synthesized during heme synthesis. Increasing expression of gtrA, which encodes the enzyme that catalyzes the first step in heme biosynthesis, also restores heme levels and exponential phase growth of the hfq mutant. Taken together, our data indicate that reduced heme levels are responsible for the exponential growth defect of the S. oneidensis hfq mutant in LB medium and suggest that the S. oneidensis hfq mutant is deficient in heme production at the 5-ALA synthesis step.

A role for the RNA chaperone Hfq in controlling adherent-invasive Escherichia coli colonization and virulence.

Directory of Open Access Journals (Sweden)

Karina T Simonsen

Full Text Available Adherent-invasive Escherichia coli (AIEC has been linked with the onset and perpetuation of inflammatory bowel diseases. The AIEC strain LF82 was originally isolated from an ileal biopsy from a patient with Crohn's disease. The pathogenesis of LF82 results from its abnormal adherence to and subsequent invasion of the intestinal epithelium coupled with its ability to survive phagocytosis by macrophages once it has crossed the intestinal barrier. To gain further insight into AIEC pathogenesis we employed the nematode Caenorhabditis elegans as an in vivo infection model. We demonstrate that AIEC strain LF82 forms a persistent infection in C. elegans, thereby reducing the host lifespan significantly. This host killing phenotype was associated with massive bacterial colonization of the nematode intestine and damage to the intestinal epithelial surface. C. elegans killing was independent of known LF82 virulence determinants but was abolished by deletion of the LF82 hfq gene, which encodes an RNA chaperone involved in mediating posttranscriptional gene regulation by small non-coding RNAs. This finding reveals that important aspects of LF82 pathogenesis are controlled at the posttranscriptional level by riboregulation. The role of Hfq in LF82 virulence was independent of its function in regulating RpoS and RpoE activity. Further, LF82Δhfq mutants were non-motile, impaired in cell invasion and highly sensitive to various chemical stress conditions, reinforcing the multifaceted function of Hfq in mediating bacterial adaptation. This study highlights the usefulness of simple non-mammalian infection systems for the identification and analysis of bacterial virulence factors.

Bacillus subtilis Hfq: A role in chemotaxis and motility

Indian Academy of Sciences (India)

2016-07-16

Jul 16, 2016 ... motility, thus assigning a new function for Hfq in B. subtilis. 1. Introduction. Hfq in ... to play a role in pathogenecity in mice, tolerance to osmotic and ethanol stress ...... in B. subtilis is characterized by events like surfactin pro- duction .... SM Cutting (New York: John Wiley and Sons Inc) pp 442–444. Nicolas P ...

Structural and biochemical studies on ATP binding and hydrolysis by the Escherichia coli RNA chaperone Hfq.

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Hermann Hämmerle

Full Text Available In Escherichia coli the RNA chaperone Hfq is involved in riboregulation by assisting base-pairing between small regulatory RNAs (sRNAs and mRNA targets. Several structural and biochemical studies revealed RNA binding sites on either surface of the donut shaped Hfq-hexamer. Whereas sRNAs are believed to contact preferentially the YKH motifs present on the proximal site, poly(A(15 and ADP were shown to bind to tripartite binding motifs (ARE circularly positioned on the distal site. Hfq has been reported to bind and to hydrolyze ATP. Here, we present the crystal structure of a C-terminally truncated variant of E. coli Hfq (Hfq(65 in complex with ATP, showing that it binds to the distal R-sites. In addition, we revisited the reported ATPase activity of full length Hfq purified to homogeneity. At variance with previous reports, no ATPase activity was observed for Hfq. In addition, FRET assays neither indicated an impact of ATP on annealing of two model oligoribonucleotides nor did the presence of ATP induce strand displacement. Moreover, ATP did not lead to destabilization of binary and ternary Hfq-RNA complexes, unless a vast stoichiometric excess of ATP was used. Taken together, these studies strongly suggest that ATP is dispensable for and does not interfere with Hfq-mediated RNA transactions.

Cross-regulation by CrcZ RNA controls anoxic biofilm formation in Pseudomonas aeruginosa

Science.gov (United States)

Pusic, Petra; Tata, Muralidhar; Wolfinger, Michael T.; Sonnleitner, Elisabeth; Häussler, Susanne; Bläsi, Udo

2016-12-01

Pseudomonas aeruginosa (PA) can thrive in anaerobic biofilms in the lungs of cystic fibrosis (CF) patients. Here, we show that CrcZ is the most abundant PA14 RNA bound to the global regulator Hfq in anoxic biofilms grown in cystic fibrosis sputum medium. Hfq was crucial for anoxic biofilm formation. This observation complied with an RNAseq based transcriptome analysis and follow up studies that implicated Hfq in regulation of a central step preceding denitrification. CrcZ is known to act as a decoy that sequesters Hfq during relief of carbon catabolite repression, which in turn alleviates Hfq-mediated translational repression of catabolic genes. We therefore inferred that CrcZ indirectly impacts on biofilm formation by competing for Hfq. This hypothesis was supported by the findings that over-production of CrcZ mirrored the biofilm phenotype of the hfq deletion mutant, and that deletion of the crcZ gene augmented biofilm formation. To our knowledge, this is the first example where competition for Hfq by CrcZ cross-regulates an Hfq-dependent physiological process unrelated to carbon metabolism.

Expression, crystallization and preliminary crystallographic analysis of RNA-binding protein Hfq (YmaH) from Bacillus subtilis in complex with an RNA aptamer

International Nuclear Information System (INIS)

Baba, Seiki; Someya, Tatsuhiko; Kawai, Gota; Nakamura, Kouji; Kumasaka, Takashi

2010-01-01

The RNA-binding protein Hfq from B. subtilis was crystallized using the hanging-drop vapour-diffusion method in two crystal forms that belonged to space groups I422 and F222; diffraction data were collected to 2.2 Å resolution from both forms. The Hfq protein is a hexameric RNA-binding protein which regulates gene expression by binding to RNA under the influence of diverse environmental stresses. Its ring structure binds various types of RNA, including mRNA and sRNA. RNA-bound structures of Hfq from Escherichia coli and Staphylococcus aureus have been revealed to have poly(A) RNA at the distal site and U-rich RNA at the proximal site, respectively. Here, crystals of a complex of the Bacillus subtilis Hfq protein with an A/G-repeat 7-mer RNA (Hfq–RNA) that were prepared using the hanging-drop vapour-diffusion technique are reported. The type 1 Hfq–RNA crystals belonged to space group I422, with unit-cell parameters a = b = 123.70, c = 119.13 Å, while the type 2 Hfq–RNA crystals belonged to space group F222, with unit-cell parameters a = 91.92, b = 92.50, c = 114.92 Å. Diffraction data were collected to a resolution of 2.20 Å from both crystal forms. The hexameric structure of the Hfq protein was clearly shown by self-rotation analysis

Fluorescence reporters for Hfq oligomerization and RNA annealing

Science.gov (United States)

Panja, Subrata; Woodson, Sarah A.

2015-01-01

Fluorescence spectroscopy is a sensitive technique for detecting protein-protein, protein-RNA and RNA-RNA interactions, requiring only nanomolar concentrations of labeled components. Fluorescence anisotropy provides information about the assembly of multi-subunit proteins, while molecular beacons provide a sensitive and quantitative reporter for base pairing between complementary RNAs. Here we present a detailed protocol for labeling Hfq protein with cyanine 3-maleimide and dansyl chloride to study the protein oligomerization and RNA binding by semi-native polyacrylamide gel electrophoresis (PAGE) and fluorescence anisotropy. We also present a detailed protocol for measuring the rate of annealing between a molecular beacon and a target RNA in the presence of Hfq using a stopped-flow spectrometer. PMID:25579597

Effect of Crc and Hfq proteins on the transcription, processing, and stability of the Pseudomonas putida CrcZ sRNA.

Science.gov (United States)

Hernández-Arranz, Sofía; Sánchez-Hevia, Dione; Rojo, Fernando; Moreno, Renata

2016-12-01

In Pseudomonas putida, the Hfq and Crc proteins regulate the expression of many genes in response to nutritional and environmental cues, by binding to mRNAs that bear specific target motifs and inhibiting their translation. The effect of these two proteins is antagonized by the CrcZ and CrcY small RNAs (sRNAs), the levels of which vary greatly according to growth conditions. The crcZ and crcY genes are transcribed from promoters PcrcZ and PcrcY, respectively, a process that relies on the CbrB transcriptional activator and the RpoN σ factor. Here we show that crcZ can also be transcribed from the promoter of the immediate upstream gene, cbrB, a weak constitutive promoter. The cbrB-crcZ transcript was processed to render a sRNA very similar in size to the CrcZ produced from promoter PcrcZ The processed sRNA, termed CrcZ*, was able to antagonize Hfq/Crc because, when provided in trans, it relieved the deregulated Hfq/Crc-dependent hyperrepressing phenotype of a ΔcrcZΔcrcY strain. CrcZ* may help in attaining basal levels of CrcZ/CrcZ* that are sufficient to protect the cell from an excessive Hfq/Crc-dependent repression. Since a functional sRNA can be produced from PcrcZ, an inducible strong promoter, or by cleavage of the cbrB-crcZ mRNA, crcZ can be considered a 3'-untranslated region of the cbrB-crcZ mRNA. In the absence of Hfq, the processed form of CrcZ was not observed. In addition, we show that Crc and Hfq increase CrcZ stability, which supports the idea that these proteins can form a complex with CrcZ and protect it from degradation by RNases. © 2016 Hernández-Arranz et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Glucose uptake in Azotobacter vinelandii occurs through a GluP transporter that is under the control of the CbrA/CbrB and Hfq-Crc systems.

Science.gov (United States)

Quiroz-Rocha, Elva; Moreno, Renata; Hernández-Ortíz, Armando; Fragoso-Jiménez, Juan Carlos; Muriel-Millán, Luis Felipe; Guzmán, Josefina; Espín, Guadalupe; Rojo, Fernando; Núñez, Cinthia

2017-04-12

Azotobacter vinelandii, a strict aerobic, nitrogen fixing bacterium in the Pseudomonadaceae family, exhibits a preferential use of acetate over glucose as a carbon source. In this study, we show that GluP (Avin04150), annotated as an H + -coupled glucose-galactose symporter, is the glucose transporter in A. vinelandii. This protein, which is widely distributed in bacteria and archaea, is uncommon in Pseudomonas species. We found that expression of gluP was under catabolite repression control thorugh the CbrA/CbrB and Crc/Hfq regulatory systems, which were functionally conserved between A. vinelandii and Pseudomonas species. While the histidine kinase CbrA was essential for glucose utilization, over-expression of the Crc protein arrested cell growth when glucose was the sole carbon source. Crc and Hfq proteins from either A. vinelandii or P. putida could form a stable complex with an RNA A-rich Hfq-binding motif present in the leader region of gluP mRNA. Moreover, in P. putida, the gluP A-rich Hfq-binding motif was functional and promoted translational inhibition of a lacZ reporter gene. The fact that gluP is not widely distributed in the Pseudomonas genus but is under control of the CbrA/CbrB and Crc/Hfq systems demonstrates the relevance of these systems in regulating metabolism in the Pseudomonadaceae family.

Characterization of an Hfq dependent antisense sRNA in the Gram-positive human pathogen Listeria monocytogenes

DEFF Research Database (Denmark)

Nielsen, Jesper Sejrup; Lei Kristensen, Lisbeth; Hanghøj Chrisitansen, Mie

between sRNA and target mRNA rely on the RNA chaperone Hfq. Hfq is a ubiquitous protein found in almost all genres of bacterial life. However, so far its role as an RNA chaperone has only been described in Gram-negative species such as Escherichia coli and Salmonella (Vogel, J. 2009). We previously...... identified several Hfq-binding sRNAs in the Gram-positive human pathogen L. monocytogenes (Christiansen et al 2006). Through bioinformatics, we have identified a number of candidate targets for one of these sRNAs (LhrA). Here, we present the characterization of one of these targets. Our results suggest...

Structural and dynamic properties of the C-terminal region of the Escherichia coli RNA chaperone Hfq: integrative experimental and computational studies.

Science.gov (United States)

Wen, Bin; Wang, Weiwei; Zhang, Jiahai; Gong, Qingguo; Shi, Yunyu; Wu, Jihui; Zhang, Zhiyong

2017-08-09

In Escherichia coli, hexameric Hfq is an important RNA chaperone that facilitates small RNA-mediated post-transcriptional regulation. The Hfq monomer consists of an evolutionarily conserved Sm domain (residues 1-65) and a flexible C-terminal region (residues 66-102). It has been recognized that the existence of the C-terminal region is important for the function of Hfq, but its detailed structural and dynamic properties remain elusive due to its disordered nature. In this work, using integrative experimental techniques, such as nuclear magnetic resonance spectroscopy and small-angle X-ray scattering, as well as multi-scale computational simulations, new insights into the structure and dynamics of the C-terminal region in the context of the Hfq hexamer are provided. Although the C-terminal region is intrinsically disordered, some residues (83-86) are motionally restricted. The hexameric core may affect the secondary structure propensity of the C-terminal region, due to transient interactions between them. The residues at the rim and the proximal side of the core have significantly more transient contacts with the C-terminal region than those residues at the distal side, which may facilitate the function of the C-terminal region in the release of double-stranded RNAs and the cycling of small non-coding RNAs. Structure ensembles constructed by fitting the experimental data also support that the C-terminal region prefers to locate at the proximal side. From multi-scale simulations, we propose that the C-terminal region may play a dual role of steric effect (especially at the proximal side) and recruitment (at the both sides) in the binding process of RNA substrates. Interestingly, we have found that these motionally restricted residues may serve as important binding sites for the incoming RNAs that is probably driven by favorable electrostatic interactions. These integrative studies may aid in our understanding of the functional role of the C-terminal region of Hfq.

The stationary phase sigma factor, RpoS, regulates the production of a carbapenem antibiotic, a bioactive prodigiosin and virulence in the enterobacterial pathogen Serratia sp. ATCC 39006.

Science.gov (United States)

Wilf, Nabil M; Salmond, George P C

2012-03-01

Serratia sp. ATCC 39006 (S39006) is a Gram-negative bacterium that is virulent in plant (potato) and invertebrate animal (Caenorhabditis elegans) models. It produces two secondary metabolite antibiotics, a prodigiosin and a carbapenem, and the exoenzymes pectate lyase and cellulase. We showed previously that deletion of the RNA chaperone Hfq abolished antibiotic production and attenuated virulence in both animal and plant hosts. Hfq and dependent small RNAs (sRNAs) are known to regulate the post-transcriptional expression of rpoS, which encodes σ(S), the stationary phase sigma factor subunit of RNA polymerase. An S39006 hfq deletion mutant showed decreased transcript levels of rpoS. Therefore, in this study we investigated whether the phenotypes regulated by Hfq were mediated through its control of rpoS. Whereas loss of Hfq abolished prodigiosin and carbapenem production and attenuated virulence in both C. elegans and potato, characterization of an S39006 rpoS mutant showed unexpectedly elevated prodigiosin and carbapenem production. Furthermore, the rpoS mutant exhibited attenuated animal pathogenesis, but not plant pathogenesis. Additionally, a homologue of the Hfq-dependent sRNA, RprA, was identified and shown to regulate prodigiosin production in a manner consistent with its role in positively regulating translation of rpoS mRNA. Combined, these results demonstrate that Hfq regulation of secondary metabolism and plant pathogenesis is independent of RpoS and establishes RpoS and RprA as regulators of antibiotic production.

Multiple Hfq-Crc target sites are required to impose catabolite repression on (methyl)phenol metabolism in Pseudomonas putida CF600.

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Wirebrand, Lisa; Madhushani, Anjana W K; Irie, Yasuhiko; Shingler, Victoria

2018-01-01

The dmp-system encoded on the IncP-2 pVI150 plasmid of Pseudomonas putida CF600 confers the ability to assimilate (methyl)phenols. Regulation of the dmp-genes is subject to sophisticated control, which includes global regulatory input to subvert expression of the pathway in the presence of preferred carbon sources. Previously we have shown that in P. putida, translational inhibition exerted by the carbon repression control protein Crc operates hand-in-hand with the RNA chaperon protein Hfq to reduce translation of the DmpR regulator of the Dmp-pathway. Here, we show that Crc and Hfq co-target four additional sites to form riboprotein complexes within the proximity of the translational initiation sites of genes encoding the first two steps of the Dmp-pathway to mediate two-layered control in the face of selection of preferred substrates. Furthermore, we present evidence that Crc plays a hitherto unsuspected role in maintaining the pVI150 plasmid within a bacterial population, which has implications for (methyl)phenol degradation and a wide variety of other physiological processes encoded by the IncP-2 group of Pseudomonas-specific mega-plasmids. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Investigation of interfacial heat transfer mechanism for 7075-T6 aluminum alloy in HFQ hot forming process

International Nuclear Information System (INIS)

Ying, Liang; Gao, Tianhan; Dai, Minghua; Hu, Ping

2017-01-01

Highlights: • The transient IHTC between 7075 alloy and die in HFQ process is investigated. • The accuracy of IHTC calculated by Beck and heat balance method is compared. • The relationship between IHTC and process parameter of 7075 alloy is studied. • The transient IHTC law is verified by U-type HFQ forming experiment. - Abstract: The IHTC (Interfacial-Heat-Transfer-Coefficient) between aluminum alloy and die during HFQ (Heat-Forming-Quenching) process is an important thermal parameter to reflect the heat transfer efficiency. In the present work, the instantaneous heat transfer law for high strength 7075-T6 alloy during HFQ process based on cylindrical-die model was investigated. The accuracy of IHTC calculated by Beck’s non-linear estimation method (Beck’s method) and heat balance method (HBM) were compared, and instantaneous IHTC of 7075-T6 alloy was acquired in experiment and analyzed in consideration of different contact pressure, surface roughness and lubricate conditions. Furthermore, the obtained IHTC was applied to the simulation process of typical U-type experimental model in order to validate the universality of heat transfer law. The result shows that the average IHTC goes near to 3300 W/m"2·K when pressure is above 80 MPa; Surface roughness can also affect the IHTC in HFQ process, but the effect mechanism is different from the boron steel in hot stamping process. The average IHTC decreases sharply when surface roughness increases in the range of 0.570–0.836 μm, the value is from 3453 W/m"2·K to 2001 W/m"2·K under 80 MPa. Furthermore, surface lubrication can promote heat transfer efficiency and increase IHTC value when contact pressure is relatively high.

The Crc protein participates in down-regulation of the Lon gene to promote rhamnolipid production and rhl quorum sensing in Pseudomonas aeruginosa.

Science.gov (United States)

Yang, Nana; Ding, Shuting; Chen, Feifei; Zhang, Xue; Xia, Yongjie; Di, Hongxia; Cao, Qiao; Deng, Xin; Wu, Min; Wong, Catherine C L; Tian, Xiao-Xu; Yang, Cai-Guang; Zhao, Jing; Lan, Lefu

2015-05-01

Rhamnolipid acts as a virulence factor during Pseudomonas aeruginosa infection. Here, we show that deletion of the catabolite repression control (crc) gene in P. aeruginosa leads to a rhamnolipid-negative phenotype. This effect is mediated by the down-regulation of rhl quorum sensing (QS). We discover that a disruption of the gene encoding the Lon protease entirely offsets the effect of crc deletion on the production of both rhamnolipid and rhl QS signal C4-HSL. Crc is unable to bind lon mRNA in vitro in the absence of the RNA chaperon Hfq, while Crc contributes to Hfq-mediated repression of the lon gene expression at a posttranscriptional level. Deletion of crc, which results in up-regulation of lon, significantly reduces the in vivo stability and abundance of the RhlI protein that synthesizes C4-HSL, causing the attenuation of rhl QS. Lon is also capable of degrading the RhlI protein in vitro. In addition, constitutive expression of rhlI suppresses the defects of the crc deletion mutant in rhamnolipid, C4-HSL and virulence on lettuce leaves. This study therefore uncovers a novel posttranscriptional regulatory cascade, Crc-Hfq/Lon/RhlI, for the regulation of rhamnolipid production and rhl QS in P. aeruginosa. © 2015 John Wiley & Sons Ltd.

Deep sequencing of Salmonella RNA associated with heterologous Hfq proteins in vivo reveals small RNAs as a major target class and identifies RNA processing phenotypes.

Science.gov (United States)

Sittka, Alexandra; Sharma, Cynthia M; Rolle, Katarzyna; Vogel, Jörg

2009-01-01

The bacterial Sm-like protein, Hfq, is a key factor for the stability and function of small non-coding RNAs (sRNAs) in Escherichia coli. Homologues of this protein have been predicted in many distantly related organisms yet their functional conservation as sRNA-binding proteins has not entirely been clear. To address this, we expressed in Salmonella the Hfq proteins of two eubacteria (Neisseria meningitides, Aquifex aeolicus) and an archaeon (Methanocaldococcus jannaschii), and analyzed the associated RNA by deep sequencing. This in vivo approach identified endogenous Salmonella sRNAs as a major target of the foreign Hfq proteins. New Salmonella sRNA species were also identified, and some of these accumulated specifically in the presence of a foreign Hfq protein. In addition, we observed specific RNA processing defects, e.g., suppression of precursor processing of SraH sRNA by Methanocaldococcus Hfq, or aberrant accumulation of extracytoplasmic target mRNAs of the Salmonella GcvB, MicA or RybB sRNAs. Taken together, our study provides evidence of a conserved inherent sRNA-binding property of Hfq, which may facilitate the lateral transmission of regulatory sRNAs among distantly related species. It also suggests that the expression of heterologous RNA-binding proteins combined with deep sequencing analysis of RNA ligands can be used as a molecular tool to dissect individual steps of RNA metabolism in vivo.

The RNA Chaperone Hfq Is Required for Virulence of Bordetella pertussis

Czech Academy of Sciences Publication Activity Database

Bíbová, Ilona; Škopová, Karolína; Mašín, Jiří; Černý, Ondřej; Hot, D.; Šebo, Peter; Večerek, Branislav

2013-01-01

Roč. 81, č. 11 (2013), s. 4081-4090 ISSN 0019-9567 R&D Projects: GA ČR(CZ) GAP302/11/1940; GA ČR GAP302/12/0460 Institutional support: RVO:61388971 Keywords : ADENYLATE-CYCLASE TOXIN * ISLET-ACTIVATING PROTEIN * ESCHERICHIA-COLI HFQ Subject RIV: EC - Immunology Impact factor: 4.156, year: 2013

Lack of the RNA chaperone Hfq attenuates pathogenicity of several Escherichia coli pathotypes towards Caenorhabditis elegans

DEFF Research Database (Denmark)

Bojer, Martin Saxtorph; Jakobsen, Henrik; Struve, Carsten

2012-01-01

as a model for virulence characterization and screening for novel antimicrobial entities. Several E. coli human pathotypes are also pathogenic towards C. elegans, and we show here that lack of the RNA chaperone Hfq significantly reduces pathogenicity of VTEC, EAEC, and UPEC in the nematode model. Thus, Hfq...... is intrinsically essential to pathogenic E. coli for survival and virulence exerted in the C. elegans host.......Escherichia coli is an important agent of Gram-negative bacterial infections worldwide, being one of the leading causes of diarrhoea and urinary tract infections. Strategies to understand pathogenesis and develop therapeutic compounds include the use of the nematode Caenorhabditis elegans...

An Hfq-like protein in archaea: crystal structure and functional characterization of the Sm protein from Methanococcus jannaschii

DEFF Research Database (Denmark)

Nielsen, Jesper S; Bøggild, Andreas; Andersen, Christian B F

2007-01-01

The Sm and Sm-like proteins are conserved in all three domains of life and have emerged as important players in many different RNA-processing reactions. Their proposed role is to mediate RNA-RNA and/or RNA-protein interactions. In marked contrast to eukaryotes, bacteria appear to contain only one...... diameter of the archaeal Hfq hexamer is significantly smaller than its bacterial counterparts. Functional analysis reveals that Escherichia coli and M. jannaschii Hfqs display very similar biochemical and biological properties. It thus appears that the archaeal and bacterial Hfq proteins are largely...

Overexpression of an Outer Membrane Protein Associated with Decreased Susceptibility to Carbapenems in Proteus mirabilis

Science.gov (United States)

Tsai, Yi-Lin; Wang, Min-Cheng; Hsueh, Po-Ren; Liu, Ming-Che; Hu, Rouh-Mei; Wu, Yue-Jin; Liaw, Shwu-Jen

2015-01-01

Proteus mirabilis isolates commonly have decreased susceptibility to imipenem. Previously, we found P. mirabilis hfq mutant was more resistant to imipenem and an outer membrane protein (OMP) could be involved. Therefore, we investigated the role of this OMP in carbapenem susceptibility. By SDS-PAGE we found this OMP (named ImpR) was increased in hfq mutant and LC-MS/MS revealed it to be the homologue of Salmonella YbfM, which is a porin for chitobiose and subject to MicM (a small RNA) regulation. We demonstrated that ImpR overexpression resulted in increased carbapenem MICs in the laboratory strain and clinical isolates. Chitobiose induced expression of chb (a chitobiose utilization operon). Real-time RT-PCR and SDS-PAGE were performed to elucidate the relationship of hfq, impR, chb and MicM in P. mirabilis. We found MicM RNA was decreased in hfq mutant and chbBC-intergenic region (chbBC-IGR) overexpression strain (chbIGRov), while impR mRNA was increased in hfq mutant, micM mutant and chbIGRov strain. In addition, mutation of hfq or micM and overexpression of chbBC-IGR increased ImpR protein level. Accordingly, chitobiose made wild-type have higher levels of ImpR protein and are more resistant to carbapenems. Hfq- and MicM-complemented strains restored wild-type MICs. Mutation of both impR and hfq eliminated the increase in carbapenem MICs observed in hfq mutant and ImpR-complementation of hfq/impR double mutant resulted in MICs as hfq mutant, indicating that the ImpR-dependent decreased carbapenem susceptibility of hfq mutant. These indicate MicM was antisense to impR mRNA and was negatively-regulated by chbBC-IGR. Together, overexpression of ImpR contributed to the decreased carbapenem susceptibility in P. mirabilis. PMID:25756370

An Hfq-like protein in archaea: structural and functional characterization of the Sm protein from Methanococcus jannaschii

DEFF Research Database (Denmark)

Nielsen, Jesper Sejrup; Andreas, Bøggild; Nielsen, Gorm

The Sm and Sm-like proteins are conserved in all three domains of life and has emerged as important players in many RNA-processing events. Their proposed role is to mediate RNA-RNA and/or RNA-protein interactions. In marked contrast to eukaryotes, bacteria appear to harbour only a single distinct......-helix the overall diameter of the archaeal Hfq is significantly smaller than its bacterial counterparts. Functional analysis reveals that E. coli and M. jannaschii Hfqs display very similar biochemical and biological properties. It thus appears that the archaeal and bacterial Hfq proteins are largely functionally...

Low Fluid Shear Culture of Staphylococcus Aureus Represses hfq Expression and Induces an Attachment-Independent Biofilm Phenotype

Science.gov (United States)

Ott, C. Mark; Castro, S. L.; Nickerson, C. A.; Nelman-Gonzalez, M.

2011-01-01

Background: The opportunistic pathogen, Staphylococcus aureus, experiences fluctuations in fluid shear during infection and colonization of a human host. Colonization frequently occurs at mucus membrane sites such as in the gastrointestinal tract where the bacterium may experience low levels of fluid shear. The response of S. aureus to low fluid shear remains unclear. Methods: S. aureus was cultured to stationary phase using Rotating-Wall Vessel (RWV) bioreactors which produce a physiologically relevant low fluid shear environment. The bacterial aggregates that developed in the RWV were evaluated by electron microscopy as well as for antibiotic resistance and other virulence-associated stressors. Genetic expression profiles for the low-shear cultured S. aureus were determined by microarray analysis and quantitative real-time PCR. Results: Planktonic S. aureus cultures in the low-shear environment formed aggregates completely encased in high amounts of extracellular polymeric substances. In addition, these aggregates demonstrated increased antibiotic resistance indicating attachment-independent biofilm formation. Carotenoid production in the low-shear cultured S. aureus was significantly decreased, and these cultures displayed an increased susceptibility to oxidative stress and killing by whole blood. The hfq gene, associated with low-shear growth in Gram negative organisms, was also found to be down-regulated in S. aureus. Conclusions: Collectively, this data suggests that S. aureus decreases virulence characteristics in favor of a biofilm-dwelling colonization phenotype in response to a low fluid shear environment. Furthermore, the identification of an Hfq response to low-shear culture in S. aureus, in addition to the previously reported responses in Gram negative organisms, strongly suggests an evolutionarily conserved response to mechanical stimuli among structurally diverse prokaryotes.

Quick change: post-transcriptional regulation in Pseudomonas.

Science.gov (United States)

Grenga, Lucia; Little, Richard H; Malone, Jacob G

2017-08-01

Pseudomonas species have evolved dynamic and intricate regulatory networks to fine-tune gene expression, with complex regulation occurring at every stage in the processing of genetic information. This approach enables Pseudomonas to generate precise individual responses to the environment in order to improve their fitness and resource economy. The weak correlations we observe between RNA and protein abundance highlight the significant regulatory contribution of a series of intersecting post-transcriptional pathways, influencing mRNA stability, translational activity and ribosome function, to Pseudomonas environmental responses. This review examines our current understanding of three major post-transcriptional regulatory systems in Pseudomonas spp.; Gac/Rsm, Hfq and RimK, and presents an overview of new research frontiers, emerging genome-wide methodologies, and their potential for the study of global regulatory responses in Pseudomonas. © FEMS 2017.

Transcriptional profiling of Bordetella pertussis reveals requirement of RNA chaperone Hfq for Type III secretion system functionality

Czech Academy of Sciences Publication Activity Database

Bíbová, Ilona; Hot, D.; Keidel, Kristina; Amman, F.; Slupek, S.; Černý, Ondřej; Gross, R.; Večerek, Branislav

2015-01-01

Roč. 12, č. 2 (2015), s. 175-185 ISSN 1547-6286 R&D Projects: GA ČR(CZ) GAP302/11/1940; GA MŠk(CZ) EE2.3.20.0055; GA MŠk(CZ) EE2.3.30.0003; GA MŠk(CZ) 7AMB14AR028; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61388971 Keywords : Bsp22 * Hfq * infection Subject RIV: CE - Biochemistry Impact factor: 4.076, year: 2015

Translational regulation of gene expression by an anaerobically induced small non-coding RNA in Escherichia coli

DEFF Research Database (Denmark)

Boysen, Anders; Møller-Jensen, Jakob; Kallipolitis, Birgitte H.

2010-01-01

Small non-coding RNAs (sRNA) have emerged as important elements of gene regulatory circuits. In enterobacteria such as Escherichia coli and Salmonella many of these sRNAs interact with the Hfq protein, an RNA chaperone similar to mammalian Sm-like proteins and act in the post...... that adaptation to anaerobic growth involves the action of a small regulatory RNA....... of at least one sRNA regulator. Here, we extend this view by the identification and characterization of a highly conserved, anaerobically induced small sRNA in E. coli, whose expression is strictly dependent on the anaerobic transcriptional fumarate and nitrate reductase regulator (FNR). The sRNA, named Fnr...

An attenuated Shigella mutant lacking the RNA-binding protein Hfq provides cross-protection against Shigella strains of broad serotype.

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Mitobe, Jiro; Sinha, Ritam; Mitra, Soma; Nag, Dhrubajyoti; Saito, Noriko; Shimuta, Ken; Koizumi, Nobuo; Koley, Hemanta

2017-07-01

Few live attenuated vaccines protect against multiple serotypes of bacterial pathogen because host serotype-specific immune responses are limited to the serotype present in the vaccine strain. Here, immunization with a mutant of Shigella flexneri 2a protected guinea pigs against subsequent infection by S. dysenteriae type 1 and S. sonnei strains. This deletion mutant lacked the RNA-binding protein Hfq leading to increased expression of the type III secretion system via loss of regulation, resulting in attenuation of cell viability through repression of stress response sigma factors. Such increased antigen production and simultaneous attenuation were expected to elicit protective immunity against Shigella strains of heterologous serotypes. Thus, the vaccine potential of this mutant was tested in two guinea pig models of shigellosis. Animals vaccinated in the left eye showed fewer symptoms upon subsequent challenge via the right eye, and even survived subsequent intestinal challenge. In addition, oral vaccination effectively induced production of immunoglobulins without severe side effects, again protecting all animals against subsequent intestinal challenge with S. dysenteriae type 1 or S. sonnei strains. Antibodies against common virulence proteins and the O-antigen of S. flexneri 2a were detected by immunofluorescence microscopy. Reaction of antibodies with various strains, including enteroinvasive Escherichia coli, suggested that common virulence proteins induced protective immunity against a range of serotypes. Therefore, vaccination is expected to cover not only the most prevalent serotypes of S. sonnei and S. flexneri 2a, but also various Shigella strains, including S. dysenteriae type 1, which produces Shiga toxin.

An attenuated Shigella mutant lacking the RNA-binding protein Hfq provides cross-protection against Shigella strains of broad serotype.

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Jiro Mitobe

2017-07-01

Full Text Available Few live attenuated vaccines protect against multiple serotypes of bacterial pathogen because host serotype-specific immune responses are limited to the serotype present in the vaccine strain. Here, immunization with a mutant of Shigella flexneri 2a protected guinea pigs against subsequent infection by S. dysenteriae type 1 and S. sonnei strains. This deletion mutant lacked the RNA-binding protein Hfq leading to increased expression of the type III secretion system via loss of regulation, resulting in attenuation of cell viability through repression of stress response sigma factors. Such increased antigen production and simultaneous attenuation were expected to elicit protective immunity against Shigella strains of heterologous serotypes. Thus, the vaccine potential of this mutant was tested in two guinea pig models of shigellosis. Animals vaccinated in the left eye showed fewer symptoms upon subsequent challenge via the right eye, and even survived subsequent intestinal challenge. In addition, oral vaccination effectively induced production of immunoglobulins without severe side effects, again protecting all animals against subsequent intestinal challenge with S. dysenteriae type 1 or S. sonnei strains. Antibodies against common virulence proteins and the O-antigen of S. flexneri 2a were detected by immunofluorescence microscopy. Reaction of antibodies with various strains, including enteroinvasive Escherichia coli, suggested that common virulence proteins induced protective immunity against a range of serotypes. Therefore, vaccination is expected to cover not only the most prevalent serotypes of S. sonnei and S. flexneri 2a, but also various Shigella strains, including S. dysenteriae type 1, which produces Shiga toxin.

sRNA-Mediated Regulation of P-Fimbriae Phase Variation in Uropathogenic Escherichia coli

DEFF Research Database (Denmark)

Khandige, Surabhi; Kronborg, Tina; Uhlin, Bernt Eric

2015-01-01

Uropathogenic Escherichia coli (UPEC) are capable of occupying physiologically distinct intracellular and extracellular niches within the urinary tract. This feat requires the timely regulation of gene expression and small RNAs (sRNAs) are known to mediate such rapid adjustments in response to ch...... to changing environmental cues. This study aimed to uncover sRNA-mediated gene regulation in the UPEC strain UTI89, during infection of bladder epithelial cells. Hfq is an RNA chaperone known to facilitate and stabilize sRNA and target mRNA interactions with bacterial cells. The co...... to the discovery of a novel virulence-associated trans-acting sRNA-PapR. Deletion of papR was found to enhance adhesion of UTI89 to both bladder and kidney cell lines in a manner independent of type-1 fimbriae. We demonstrate PapR mediated posttranscriptional repression of the P-fimbriae phase regulator gene pap...

Influence of the Crc regulator on the hierarchical use of carbon sources from a complete medium in Pseudomonas.

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La Rosa, Ruggero; Behrends, Volker; Williams, Huw D; Bundy, Jacob G; Rojo, Fernando

2016-03-01

The Crc protein, together with the Hfq protein, participates in catabolite repression in pseudomonads, helping to coordinate metabolism. Little is known about how Crc affects the hierarchy of metabolite assimilation from complex mixtures. Using proton Nuclear Magnetic Resonance (NMR) spectroscopy, we carried out comprehensive metabolite profiling of culture supernatants (metabolic footprinting) over the course of growth of both Pseudomonas putida and P. aeruginosa, and compared the wild-type strains with deletion mutants for crc. A complex metabolite consumption hierarchy was observed, which was broadly similar between the two species, although with some important differences, for example in sugar utilization. The order of metabolite utilization changed upon inactivation of the crc gene, but even in the Crc-null strains some compounds were completely consumed before late metabolites were taken up. This suggests the presence of additional regulatory elements that determine the time and order of consumption of compounds. Unexpectedly, the loss of Crc led both species to excrete acetate and pyruvate as a result of unbalanced growth during exponential phase, compounds that were later consumed in stationary phase. This loss of carbon during growth helps to explain the contribution of the Crc/Hfq regulatory system to evolutionary fitness of pseudomonads. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

Effective regulation under conditions of scientific uncertainty: how collaborative networks contribute to occupational health and safety regulation for nanomaterials

NARCIS (Netherlands)

Reichow, Aline

2015-01-01

This thesis seeks to understand, and evaluate, the contribution of business associations within the United States (US) and German chemical sector, to the effective regulation of nanomaterials. In the effective regulation of new technologies characterized by high scientific uncertainty, with

The Mechanisms of Virulence Regulation by Small Noncoding RNAs in Low GC Gram-Positive Pathogens

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Stephanie Pitman

2015-12-01

Full Text Available The discovery of small noncoding regulatory RNAs (sRNAs in bacteria has grown tremendously recently, giving new insights into gene regulation. The implementation of computational analysis and RNA sequencing has provided new tools to discover and analyze potential sRNAs. Small regulatory RNAs that act by base-pairing to target mRNAs have been found to be ubiquitous and are the most abundant class of post-transcriptional regulators in bacteria. The majority of sRNA studies has been limited to E. coli and other gram-negative bacteria. However, examples of sRNAs in gram-positive bacteria are still plentiful although the detailed gene regulation mechanisms behind them are not as well understood. Strict virulence control is critical for a pathogen’s survival and many sRNAs have been found to be involved in that process. This review outlines the targets and currently known mechanisms of trans-acting sRNAs involved in virulence regulation in various gram-positive pathogens. In addition, their shared characteristics such as CU interaction motifs, the role of Hfq, and involvement in two-component regulators, riboswitches, quorum sensing, or toxin/antitoxin systems are described.

Discovery of Salmonella Virulence Factors Translocated via Outer Membrane Vesicles to Murine Macrophages.

Energy Technology Data Exchange (ETDEWEB)

Yoon, Hyunjin; Ansong, Charles; Adkins, Joshua N.; Heffron, Fred

2011-06-01

We have previously shown that the regulators SpvR, FruR, IHF, PhoP/PhoQ, SsrA/SsrB, SlyA, Hnr, RpoE, SmpB, CsrA, RpoS, Crp, OmpR/EnvZ, and Hfq are essential for Salmonella Typhimurium virulence in mice. Here we use quantitative LC-MS-based proteomics profiling of in-frame deletion mutants of these 14 regulators to identify proteins that are coordinately regulated by these virulence regulators and are thus presumably novel factors contributing to Salmonella pathogenesis. Putative candidate proteins from proteomics analysis were determined, which exhibited similar abundance profiles to those of Salmonella pathogenicity island (SPI)-2 type III secretion system (TTSS) proteins. A subset of 5 proteins including STM0082, STM1548, PdgL, STM1633, and STM3595 was selected for further analysis. All 5 proteins were expressed inside macrophage cells and STM0082 (SrfN) was secreted into host cytoplasm. Furthermore, deletion of STM0082 attenuated virulence in mice when administered intraperitoneally as determined by competitive index. srfN transcription was positively regulated by SsrAB, however, secretion was independent of SPI-2 TTSS as well as SPI-1 TTSS and flagella. Proteins including PagK and STM2585A, which are positively regulated by PhoP/PhoQ, have sec signal peptides as predicted for SrfN and were secreted into macrophage cytoplasm regardless of SPI-2 TTSS. Isolation of outer membrane vesicles (OMVs) revealed the presence of SrfN, PagK, and STM2585A inside vesicle compartments. This result is the first case showing delivery of virulence effectors via OMVs in S. Typhimurium. Moreover, Hfq regulation of SrfN translation suggests that small non-coding RNAs may be responsible for regulating effector protein expression.

RNA-binding proteins involved in post-transcriptional regulation in bacteria

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Elke eVan Assche

2015-03-01

Full Text Available Post-transcriptional regulation is a very important mechanism to control gene expression in changing environments. In the past decade, a lot of interest has been directed towards the role of small RNAs in bacterial post-transcriptional regulation. However, small RNAs are not the only molecules controlling gene expression at this level, RNA-binding proteins play an important role as well. CsrA and Hfq are the two best studied bacterial proteins of this type, but recently, additional proteins involved in post-transcriptional control have been identified. This review focuses on the general working mechanisms of post-transcriptionally active RNA-binding proteins, which include (i adaptation of the susceptibility of mRNAs and sRNAs to RNases, (ii modulating the accessibility of the ribosome binding site of mRNAs, (iii recruiting and assisting in the interaction of mRNAs with other molecules and (iv regulating transcription terminator / antiterminator formation, and gives an overview of both the well-studied and the newly identified proteins that are involved in post-transcriptional regulatory processes. Additionally, the post-transcriptional mechanisms by which the expression or the activity of these proteins is regulated, are described. For many of the newly identified proteins, however, mechanistic questions remain. Most likely, more post-transcriptionally active proteins will be identified in the future.

The contribution of bank regulation and fair value accounting to procyclical leverage

OpenAIRE

Amel-Zadeh; Barth, ME; Landsman, WR

2017-01-01

Our analytical description of how banks’ responses to asset price changes can result in procyclical leverage reveals that for banks with a binding regulatory leverage constraint, absent differences in regulatory risk weights across assets, procyclical leverage does not occur. For banks without a binding constraint, fair value and bank regulation both can contribute to procyclical leverage. Empirical findings based on a large sample of US commercial banks reveal that bank regulation explains p...

Serotonergic contribution to boys' behavioral regulation.

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Amélie Nantel-Vivier

Full Text Available Animal and human adult studies reveal a contribution of serotonin to behavior regulation. Whether these findings apply to children is unclear. The present study investigated serotonergic functioning in boys with a history of behavior regulation difficulties through a double-blind, acute tryptophan supplementation procedure.Participants were 23 boys (age 10 years with a history of elevated physical aggression, recruited from a community sample. Eleven were given a chocolate milkshake supplemented with 500 mg tryptophan, and 12 received a chocolate milkshake without tryptophan. Boys engaged in a competitive reaction time game against a fictitious opponent, which assessed response to provocation, impulsivity, perspective taking, and sharing. Impulsivity was further assessed through a Go/No-Go paradigm. A computerized emotion recognition task and a staged instrumental help incident were also administered.Boys, regardless of group, responded similarly to high provocation by the fictitious opponent. However, boys in the tryptophan group adjusted their level of responding optimally as a function of the level of provocation, whereas boys in the control group significantly decreased their level of responding towards the end of the competition. Boys in the tryptophan group tended to show greater perspective taking, tended to better distinguish facial expressions of fear and happiness, and tended to provide greater instrumental help to the experimenter.The present study provides initial evidence for the feasibility of acute tryptophan supplementation in children and some effect of tryptophan supplementation on children's behaviors. Further studies are warranted to explore the potential impact of increased serotonergic functioning on boys' dominant and affiliative behaviors.

Serotonergic contribution to boys' behavioral regulation.

Science.gov (United States)

Nantel-Vivier, Amélie; Pihl, Robert O; Young, Simon N; Parent, Sophie; Bélanger, Stacey Ageranioti; Sutton, Rachel; Dubois, Marie-Eve; Tremblay, Richard E; Séguin, Jean R

2011-01-01

Animal and human adult studies reveal a contribution of serotonin to behavior regulation. Whether these findings apply to children is unclear. The present study investigated serotonergic functioning in boys with a history of behavior regulation difficulties through a double-blind, acute tryptophan supplementation procedure. Participants were 23 boys (age 10 years) with a history of elevated physical aggression, recruited from a community sample. Eleven were given a chocolate milkshake supplemented with 500 mg tryptophan, and 12 received a chocolate milkshake without tryptophan. Boys engaged in a competitive reaction time game against a fictitious opponent, which assessed response to provocation, impulsivity, perspective taking, and sharing. Impulsivity was further assessed through a Go/No-Go paradigm. A computerized emotion recognition task and a staged instrumental help incident were also administered. Boys, regardless of group, responded similarly to high provocation by the fictitious opponent. However, boys in the tryptophan group adjusted their level of responding optimally as a function of the level of provocation, whereas boys in the control group significantly decreased their level of responding towards the end of the competition. Boys in the tryptophan group tended to show greater perspective taking, tended to better distinguish facial expressions of fear and happiness, and tended to provide greater instrumental help to the experimenter. The present study provides initial evidence for the feasibility of acute tryptophan supplementation in children and some effect of tryptophan supplementation on children's behaviors. Further studies are warranted to explore the potential impact of increased serotonergic functioning on boys' dominant and affiliative behaviors.

The Regulation of Fear: The Contribution of Inhibition and Emotion Socialisation

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Root, Amy E.; Byrne, Rachel; Watson, S. Michelle

2015-01-01

In this study, we investigated the contribution of inhibition and maternal socialisation of children's fear to observed emotion regulation during a fear induction. Fifty-three parent-child dyads (M[subscript age]?=?3.76 years) participated. Parents completed a series of questionnaires, and parent-child dyads were observed during a fear…

Distinct contributions of the dorsolateral prefrontal and orbitofrontal cortex during emotion regulation.

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Armita Golkar

Full Text Available The lateral prefrontal and orbitofrontal cortices have both been implicated in emotion regulation, but their distinct roles in regulation of negative emotion remain poorly understood. To address this issue we enrolled 58 participants in an fMRI study in which participants were instructed to reappraise both negative and neutral stimuli. This design allowed us to separately study activations reflecting cognitive processes associated with reappraisal in general and activations specifically related to reappraisal of negative emotion. Our results confirmed that both the dorsolateral prefrontal cortex (DLPFC and the lateral orbitofrontal cortex (OFC contribute to emotion regulation through reappraisal. However, activity in the DLPFC was related to reappraisal independently of whether negative or neutral stimuli were reappraised, whereas the lateral OFC was uniquely related to reappraisal of negative stimuli. We suggest that relative to the lateral OFC, the DLPFC serves a more general role in emotion regulation, perhaps by reflecting the cognitive demand that is inherent to the regulation task.

Serotonin 2A receptors contribute to the regulation of risk-averse decisions

DEFF Research Database (Denmark)

Macoveanu, Julian; Rowe, James B; Hornboll, Bettina

2013-01-01

Pharmacological studies point to a role of the neurotransmitter serotonin (5-HT) in regulating the preference for risky decisions, yet the functional contribution of specific 5-HT receptors remains to be clarified. We used pharmacological fMRI to investigate the role of the 5-HT2A receptors...... in processing negative outcomes and regulating risk-averse behavior. During fMRI, twenty healthy volunteers performed a gambling task under two conditions: with or without blocking the 5-HT2A receptors. The volunteers repeatedly chose between small, likely rewards and large, unlikely rewards. Choices were...

Relative contributions of self-efficacy, self-regulation, and self-handicapping in predicting student procrastination.

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Strunk, Kamden K; Steele, Misty R

2011-12-01

The relative contributions of self-efficacy, self-regulation, and self-handicapping student procrastination were explored. College undergraduate participants (N = 138; 40 men, 97 women, one not reporting sex) filled out the Procrastination Scale, the Self-Handicapping Scale-Short Form, and the Self-regulation and Self-handicapping scales of the Motivated Strategies for Learning Questionnaire. A hierarchical regression of the above measures indicated that self-efficacy, self-regulation, and self-handicapping all predicted scores on the Procrastination Scale, but self-regulation fully accounted for the predictive power of self-efficacy. The results suggested self-regulation and self-handicapping predict procrastination independently. These findings are discussed in relation to the literature on the concept of "self-efficacy for self-regulation" and its use in the field of procrastination research.

Down-regulation of outer membrane proteins by noncoding RNAs: unraveling the cAMP-CRP- and sigmaE-dependent CyaR-ompX regulatory case

DEFF Research Database (Denmark)

Johansen, Jesper; Eriksen, Maiken; Kallipolitis, Birgitte

2008-01-01

is sufficient to trigger the envelope stress response. Recent work indicates that small Hfq-binding RNAs play a major role in maintaining envelope homeostasis and, so far, two sigma(E)-dependent small noncoding RNAs (sRNAs), MicA and RybB, have been shown to facilitate rapid removal of multiple omp transcripts......The sigma(E) (extracytoplasmic stress response sigma factor in Escherichia coli) signaling system of Gram-negative bacteria plays an essential role in the maintenance of the extracytoplasmic compartment. Upon induction of this system, approximately 100 genes are up-regulated. The majority...... is also up-regulated, directly or indirectly, by sigma(E). In addition, this work identified MicA as a factor that cooperates in the negative control of ompX expression. The conservation of CyaR, MicA, RybB, and their targets suggests that the omp mRNA-sRNA regulatory network is an integral part...

A small RNA controls expression of the chitinase ChiA in Listeria monocytogenes

DEFF Research Database (Denmark)

Nielsen, Jesper S; Larsen, Marianne Halberg; Lillebæk, Eva Maria Sternkopf

2011-01-01

role of LhrA in L. monocytogenes. To this end, we determined the effects of LhrA on global-wide gene expression. We observed that nearly 300 genes in L. monocytogenes are either positively or negatively affected by LhrA. Among these genes, we identified lmo0302 and chiA as direct targets of LhrA, thus...... establishing LhrA as a multiple target regulator. Lmo0302 encodes a hypothetical protein with no known function, whereas chiA encodes one of two chitinases present in L. monocytogenes. We show here that LhrA acts as a post-transcriptional regulator of lmo0302 and chiA by interfering with ribosome recruitment......, and we provide evidence that both LhrA and Hfq act to down-regulate the expression of lmo0302 and chiA. Furthermore, in vitro binding experiments show that Hfq stimulates the base pairing of LhrA to chiA mRNA. Finally, we demonstrate that LhrA has a negative effect on the chitinolytic activity of L...

RpoS induces expression of the Vibrio anguillarum quorum-sensing regulator VanT.

Science.gov (United States)

Weber, Barbara; Croxatto, Antony; Chen, Chang; Milton, Debra L

2008-03-01

In vibrios, regulation of the Vibrio harveyi-like LuxR transcriptional activators occurs post-transcriptionally via small regulatory RNAs (sRNAs) that destabilize the luxR mRNA at a low cell population, eliminating expression of LuxR. Expression of the sRNAs is modulated by the vibrio quorum-sensing phosphorelay systems. However, vanT mRNA, which encodes a LuxR homologue in Vibrio anguillarum, is abundant at low and high cell density, indicating that VanT expression may be regulated via additional mechanisms. In this study, Western analyses showed that VanT was expressed throughout growth with a peak of expression during late exponential growth. VanO induced partial destabilization of vanT mRNA via activation of at least one Qrr sRNA. Interestingly, the sigma factor RpoS significantly stabilized vanT mRNA and induced VanT expression during late exponential growth. This induction was in part due to RpoS repressing expression of Hfq, an RNA chaperone. RpoS is not part of the quorum-sensing regulatory cascade since RpoS did not regulate expression or activity of VanO, and RpoS was not regulated by VanO or VanT. VanT and RpoS were needed for survival following UV irradiation and for pigment and metalloprotease production, suggesting that RpoS works with the quorum-sensing systems to modulate expression of VanT, which regulates survival and stress responses.

A conserved small RNA promotes silencing of the outer membrane protein YbfM

DEFF Research Database (Denmark)

Rasmussen, Anders Aamann; Johansen, Jesper; Nielsen, Jesper S

2009-01-01

important physiological role of regulatory RNA molecules in Gram-negative bacteria is to modulate the cell surface and/or to prevent accumulation of OMPs in the envelope. Here, we extend the OMP-sRNA network by showing that the expression of the outer membrane protein YbfM is silenced by a conserved sRNA......In the past few years an increasing number of small non-coding RNAs (sRNAs) in enterobacteria have been found to negatively regulate the expression of outer membrane proteins (OMPs) at the post-transcriptional level. These RNAs act under various growth and stress conditions, suggesting that one......, designated MicM (also known as RybC/SroB). The regulation is strictly dependent on the RNA chaperone Hfq, and mutational analysis indicates that MicM sequesters the ribosome binding site of ybfM mRNA by an antisense mechanism. Furthermore, we provide evidence that Hfq strongly enhances the on-rate of duplex...

Strong contribution of immigration to local population regulation: evidence from a migratory passerine.

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Schaub, Michael; Jakober, Hans; Stauber, Wolfgang

2013-08-01

A mechanistic understanding of the dynamics of populations requires knowledge about the variation of the underlying demographic rates and about the reasons for their variability. In geographically open populations, immigration is often necessary to prevent declines, but little is known about whether immigration can contribute to its regulation. We studied the dynamics of a Red-backed Shrike population (Lanius collurio) over 36 years in Germany with a Bayesian integrated population model. We estimated mean and temporal variability of population sizes, productivity, apparent survival, and immigration. We assessed how strongly the demographic rates were correlated with population growth to understand the demographic reasons of population change and how strongly the demographic rates were correlated with population size to identify possible density-dependent mechanisms. The shrike population varied between 35 and 74 breeding pairs but did not show a significant trend in population size over time (growth rate 1.002 +/- 0.001 [mean +/- SD]). Apparent survival of females (juveniles 0.06 +/- 0.01; adults 0.37 +/- 0.03) was lower than that of males (juveniles 0.10 +/- 0.01; adults 0.44 +/- 0.02). Immigration rates were substantial and higher in females (0.56 +/- 0.02) than in males (0.43 +/- 0.02), and average productivity was 2.76 +/- 0.14. Without immigration, the Red-backed Shrike population would have declined strongly. Immigration was the strongest driver for the number of females while local recruitment was the most important driver for the number of males. Immigration of both sexes and productivity, but not local recruitment and survival, were subject to density dependence. Density-dependent productivity was not effectively regulating the local population but may have contributed to regulate shrike populations at larger spatial scales. These findings suggest that immigration is not only an important component to prevent a geographically open population from decline

Evolutionary Dynamics of Small RNAs in 27 Escherichia coli and Shigella Genomes

Science.gov (United States)

Skippington, Elizabeth; Ragan, Mark A.

2012-01-01

Small RNAs (sRNAs) are widespread in bacteria and play critical roles in regulating physiological processes. They are best characterized in Escherichia coli K-12 MG1655, where 83 sRNAs constitute nearly 2% of the gene complement. Most sRNAs act by base pairing with a target mRNA, modulating its translation and/or stability; many of these RNAs share only limited complementarity to their mRNA target, and require the chaperone Hfq to facilitate base pairing. Little is known about the evolutionary dynamics of bacterial sRNAs. Here, we apply phylogenetic and network analyses to investigate the evolutionary processes and principles that govern sRNA gene distribution in 27 E. coli and Shigella genomes. We identify core (encoded in all 27 genomes) and variable sRNAs; more than two-thirds of the E. coli K-12 MG1655 sRNAs are core, whereas the others show patterns of presence and absence that are principally due to genetic loss, not duplication or lateral genetic transfer. We present evidence that variable sRNAs are less tightly integrated into cellular genetic regulatory networks than are the core sRNAs, and that Hfq facilitates posttranscriptional cross talk between the E. coli–Shigella core and variable genomes. Finally, we present evidence that more than 80% of genes targeted by Hfq-associated core sRNAs have been transferred within the E. coli–Shigella clade, and that most of these genes have been transferred intact. These results suggest that Hfq and sRNAs help integrate laterally acquired genes into established regulatory networks. PMID:22223756

The phosphotransferase VanU represses expression of four qrr genes antagonizing VanO-mediated quorum-sensing regulation in Vibrio anguillarum.

Science.gov (United States)

Weber, Barbara; Lindell, Kristoffer; El Qaidi, Samir; Hjerde, Erik; Willassen, Nils-Peder; Milton, Debra L

2011-12-01

Vibrio anguillarum utilizes quorum sensing to regulate stress responses required for survival in the aquatic environment. Like other Vibrio species, V. anguillarum contains the gene qrr1, which encodes the ancestral quorum regulatory RNA Qrr1, and phosphorelay quorum-sensing systems that modulate the expression of small regulatory RNAs (sRNAs) that destabilize mRNA encoding the transcriptional regulator VanT. In this study, three additional Qrr sRNAs were identified. All four sRNAs were positively regulated by σ(54) and the σ(54)-dependent response regulator VanO, and showed a redundant activity. The Qrr sRNAs, together with the RNA chaperone Hfq, destabilized vanT mRNA and modulated expression of VanT-regulated genes. Unexpectedly, expression of all four qrr genes peaked at high cell density, and exogenously added N-acylhomoserine lactone molecules induced expression of the qrr genes at low cell density. The phosphotransferase VanU, which phosphorylates and activates VanO, repressed expression of the Qrr sRNAs and stabilized vanT mRNA. A model is presented proposing that VanU acts as a branch point, aiding cross-regulation between two independent phosphorelay systems that activate or repress expression of the Qrr sRNAs, giving flexibility and precision in modulating VanT expression and inducing a quorum-sensing response to stresses found in a constantly changing aquatic environment.

dRYBP contributes to the negative regulation of the Drosophila Imd pathway.

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Ricardo Aparicio

Full Text Available The Drosophila humoral innate immune response fights infection by producing antimicrobial peptides (AMPs through the microbe-specific activation of the Toll or the Imd signaling pathway. Upon systemic infection, the production of AMPs is both positively and negatively regulated to reach a balanced immune response required for survival. Here, we report the function of the dRYBP (drosophila Ring and YY1 Binding Protein protein, which contains a ubiquitin-binding domain, in the Imd pathway. We have found that dRYBP contributes to the negative regulation of AMP production: upon systemic infection with Gram-negative bacteria, Diptericin expression is up-regulated in the absence of dRYBP and down-regulated in the presence of high levels of dRYBP. Epistatic analyses using gain and loss of function alleles of imd, Relish, or skpA and dRYBP suggest that dRYBP functions upstream or together with SKPA, a member of the SCF-E3-ubiquitin ligase complex, to repress the Imd signaling cascade. We propose that the role of dRYBP in the regulation of the Imd signaling pathway is to function as a ubiquitin adaptor protein together with SKPA to promote SCF-dependent proteasomal degradation of Relish. Beyond the identification of dRYBP as a novel component of Imd pathway regulation, our results also suggest that the evolutionarily conserved RYBP protein may be involved in the human innate immune response.

Metacognition, Motivation and Emotions: Contribution of Self-Regulated Learning to Solving Mathematical Problems

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Meirav Tzohar-Rozen

2014-11-01

Full Text Available Mathematical problem solving is among the most valuable aspects of mathematics education. It is also the hardest for elementary school students (Verschaffel, Greer & De Corte, 2000. Students experience cognitive and metacognitive difficulties in this area and develop negative emotions and poor motivation which hamper their efforts (Kramarski, Weiss, & Kololshi-Minsker, 2010. 9–11 seems the critical stage for developing attitudes and emotional reactions towards mathematics (Artino, 2009. These metacognitive and motivational-emotional factors are fundamental components of Self-Regulated Learning (SRL, a non-innate process requiring systematic, explicit student training (Pintrich, 2000; Zimmerman, 2000. Most self-regulation studies relating to problem-solving focus on metacognition. Few explore the motivational-emotional component. This study aimed to develop, examine, and compare two SRL interventions dealing with two additional components of self-regulation: metacognitive regulation (MC and motivational-emotional regulation (ME. It also sought to examine the significance of these components and their contribution to learners' problem-solving achievements and self-regulation. The study examined 118 fifth grade students, randomly assigned to two groups. Pre- and post-intervention, the two groups completed self-regulation questionnaires relating to metacognition, motivation, and emotion. They also solved arithmetic series problems presented in two ways (verbal form and numeric form. After intervention we also examined a novel transfer problem. The intervention consisted of 10 hours for 5 weeks. Following the intervention the groups exhibited similar improvements across all the problems. The MC group performed best in metacognitive self-regulation and the ME group performed best in certain motivational-emotional aspects of self-regulation. Research implications are discussed.

Improvement of Weldment Properties by Hot Forming Quenching of Friction Stir Welded TWB Sheet

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Dae-Hoon Ko

2014-04-01

Full Text Available The purpose of this study is to improve the mechanical properties and formability of friction stir welded tailor-welded blanks (TWBs of Al6061 alloy with a new forming method called hot forming quenching (HFQ in which solid-solution heat-treated aluminum sheets are formed at elevated temperature. Forming and quenching during HFQ are simultaneously performed with the forming die for the solid-solution heat-treated sheet. In this study, specimens of aluminum TWBs were prepared by friction stir welding (FSW with a butt joint. The effectiveness of FSW joining was evaluated by observation of the macrostructure for different sheet thicknesses. In order to evaluate the formability of TWBs by HFQ, a hemisphere dome stretching test of the limit dome height achieved without specimen failure was performed with various tool temperatures. A Vickers test was also performed to measure weldment hardness as a function of position. The formability and mechanical properties of products formed by HFQ are compared with those formed by conventional forming methods, demonstrating the suitability of HFQ for sheet metal forming of friction stir welded TWBs.

Circulating Blood eNOS Contributes to the Regulation of Systemic Blood Pressure and Nitrite Homeostasis

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Wood, Katherine C.; Cortese-Krott, Miriam M.; Kovacic, Jason C.; Noguchi, Audrey; Liu, Virginia B.; Wang, Xunde; Raghavachari, Nalini; Boehm, Manfred; Kato, Gregory J.; Kelm, Malte; Gladwin, Mark T.

2013-01-01

Objective Mice genetically deficient in endothelial nitric oxide synthase (eNOS−/−) are hypertensive with lower circulating nitrite levels, indicating the importance of constitutively produced nitric oxide (NO•) to blood pressure regulation and vascular homeostasis. While the current paradigm holds that this bioactivity derives specifically from expression of eNOS in endothelium, circulating blood cells also express eNOS protein. A functional red cell eNOS that modulates vascular NO• signaling has been proposed. Approach and Results To test the hypothesis that blood cells contribute to mammalian blood pressure regulation via eNOS-dependent NO• generation, we cross-transplanted WT and eNOS−/− mice, producing chimeras competent or deficient for eNOS expression in circulating blood cells. Surprisingly, we observed a significant contribution of both endothelial and circulating blood cell eNOS to blood pressure and systemic nitrite levels, the latter being a major component of the circulating NO• reservoir. These effects were abolished by the NOS inhibitor L-NAME and repristinated by the NOS substrate L-Arginine, and were independent of platelet or leukocyte depletion. Mouse erythrocytes were also found to carry an eNOS protein and convert 14C-Arginine into 14C-Citrulline in a NOS-dependent fashion. Conclusions These are the first studies to definitively establish a role for a blood borne eNOS, using cross transplant chimera models, that contributes to the regulation of blood pressure and nitrite homeostasis. This work provides evidence suggesting that erythrocyte eNOS may mediate this effect. PMID:23702660

Calculating the capital contribution required for regulation of incentives in the energy sector; Bestimmung des Eigenkapitalzinssatzes fuer eine Anreizregulierung des Energiesektors

Energy Technology Data Exchange (ETDEWEB)

Schaeffner, D. [WIK GmbH, Wissenschaftliches Inst. fuer Infrastruktur und Kommunikationsdienste, Bad Honnef (Germany)

2006-12-15

On 30 June 2006, the Federal Regulatory Agency (BNetzA) published its final report on the introduction of regulation by incentives according to Section 21a EnWG. The new regulation regime is to start on 1 January 2008. By this date, a starting value must be defined for the initial cost level and grid use reimbursements. Further, the interest rate for the capital contribution must be redefined (currently: 6.5 percent for the electricity sector and 7.8 percent for the gas sector). The contribution presents a regulation-economic method which takes account of individual parameteres in defining the capital contribution interest rate and of tax parameters and links these to current legal boundary conditions. As an example, the well-known CAPM is presented. (orig.)

Biotechnology regulation: limiting or contributing to biotech development?

DEFF Research Database (Denmark)

Hansen, Anne Grethe

2001-01-01

to the European arena, their role and extension are still an issue. In this paper, the often anticipated innovation-inhibiting effects of regulation are questioned by giving an account of regulations and debates in Denmark. An account which includes the shifting positions of industry, the research community......Modern biotechnology has been characterized by being surrounded by scientific and public debate and by interest conflicts. An early Danish debate and regulation has been criticized for inhibiting or retarding development and thus growth. Though much regulation and debate have been transferred...

Identification and Characterization of 5′ Untranslated Regions (5′UTRs in Zymomonas mobilis as Regulatory Biological Parts

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Seung Hee Cho

2017-12-01

Full Text Available Regulatory RNA regions within a transcript, particularly in the 5′ untranslated region (5′UTR, have been shown in a variety of organisms to control the expression levels of these mRNAs in response to various metabolites or environmental conditions. Considering the unique tolerance of Zymomonas mobilis to ethanol and the growing interest in engineering microbial strains with enhanced tolerance to industrial inhibitors, we searched natural cis-regulatory regions in this microorganism using transcriptomic data and bioinformatics analysis. Potential regulatory 5′UTRs were identified and filtered based on length, gene function, relative gene counts, and conservation in other organisms. An in vivo fluorescence-based screening system was developed to confirm the responsiveness of 36 5′UTR candidates to ethanol, acetate, and xylose stresses. UTR_ZMO0347 (5′UTR of gene ZMO0347 encoding the RNA binding protein Hfq was found to down-regulate downstream gene expression under ethanol stress. Genomic deletion of UTR_ZMO0347 led to a general decrease of hfq expression at the transcript level and increased sensitivity for observed changes in Hfq expression at the protein level. The role of UTR_ZMO0347 and other 5′UTRs gives us insight into the regulatory network of Z. mobilis in response to stress and unlocks new strategies for engineering robust industrial strains as well as for harvesting novel responsive regulatory biological parts for controllable gene expression platforms in this organism.

Small RNA-based feedforward loop with AND-gate logic regulates extrachromosomal DNA transfer in Salmonella.

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Papenfort, Kai; Espinosa, Elena; Casadesús, Josep; Vogel, Jörg

2015-08-25

Horizontal gene transfer via plasmid conjugation is a major driving force in microbial evolution but constitutes a complex process that requires synchronization with the physiological state of the host bacteria. Although several host transcription factors are known to regulate plasmid-borne transfer genes, RNA-based regulatory circuits for host-plasmid communication remain unknown. We describe a posttranscriptional mechanism whereby the Hfq-dependent small RNA, RprA, inhibits transfer of pSLT, the virulence plasmid of Salmonella enterica. RprA employs two separate seed-pairing domains to activate the mRNAs of both the sigma-factor σ(S) and the RicI protein, a previously uncharacterized membrane protein here shown to inhibit conjugation. Transcription of ricI requires σ(S) and, together, RprA and σ(S) orchestrate a coherent feedforward loop with AND-gate logic to tightly control the activation of RicI synthesis. RicI interacts with the conjugation apparatus protein TraV and limits plasmid transfer under membrane-damaging conditions. To our knowledge, this study reports the first small RNA-controlled feedforward loop relying on posttranscriptional activation of two independent targets and an unexpected role of the conserved RprA small RNA in controlling extrachromosomal DNA transfer.

Fatherhood contributes to increased hippocampal spine density and anxiety regulation in California mice.

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Glasper, Erica R; Hyer, Molly M; Katakam, Jhansi; Harper, Robyn; Ameri, Cyrus; Wolz, Thomas

2016-01-01

Parenting alters the hippocampus, an area of the brain that undergoes significant experience-induced plasticity and contributes to emotional regulation. While the relationship between maternal care and hippocampal neuroplasticity has been characterized, the extent to which fatherhood alters the structure and function of the hippocampus is far less understood. Here, we investigated to what extent fatherhood altered anxiety regulation and dendritic morphology of the hippocampus using the highly paternal California mouse (Peromyscus californicus). Fathers spent significantly more time on the open arms of the elevated plus maze, compared to non-fathers. Total distance traveled in the EPM was not changed by paternal experience, which suggests that the increased time spent on the open arms of the maze indicates decreased anxiety-like behavior. Fatherhood also increased dendritic spine density of granule cells in the dentate gyrus and basal dendrites of pyramidal cells in area CA1 of the hippocampus. These findings parallel those observed in maternal rodents, suggesting that the hippocampus of fathers and mothers respond similarly to offspring.

48 CFR 31.205-8 - Contributions or donations.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Contributions or donations. 31.205-8 Section 31.205-8 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... Organizations 31.205-8 Contributions or donations. Contributions or donations, including cash, property and...

MicroRNA regulation in Ames dwarf mouse liver may contribute to delayed aging.

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Bates, David J; Li, Na; Liang, Ruqiang; Sarojini, Harshini; An, Jin; Masternak, Michal M; Bartke, Andrzej; Wang, Eugenia

2010-02-01

The Ames dwarf mouse is well known for its remarkable propensity to delay the onset of aging. Although significant advances have been made demonstrating that this aging phenotype results primarily from an endocrine imbalance, the post-transcriptional regulation of gene expression and its impact on longevity remains to be explored. Towards this end, we present the first comprehensive study by microRNA (miRNA) microarray screening to identify dwarf-specific lead miRNAs, and investigate their roles as pivotal molecular regulators directing the long-lived phenotype. Mapping the signature miRNAs to the inversely expressed putative target genes, followed by in situ immunohistochemical staining and in vitro correlation assays, reveals that dwarf mice post-transcriptionally regulate key proteins of intermediate metabolism, most importantly the biosynthetic pathway involving ornithine decarboxylase and spermidine synthase. Functional assays using 3'-untranslated region reporter constructs in co-transfection experiments confirm that miRNA-27a indeed suppresses the expression of both of these proteins, marking them as probable targets of this miRNA in vivo. Moreover, the putative repressed action of this miRNA on ornithine decarboxylase is identified in dwarf mouse liver as early as 2 months of age. Taken together, our results show that among the altered aspects of intermediate metabolism detected in the dwarf mouse liver--glutathione metabolism, the urea cycle and polyamine biosynthesis--miRNA-27a is a key post-transcriptional control. Furthermore, compared to its normal siblings, the dwarf mouse exhibits a head start in regulating these pathways to control their normality, which may ultimately contribute to its extended health-span and longevity.

Increasing T-type calcium channel activity by β-adrenergic stimulation contributes to β-adrenergic regulation of heart rates.

Science.gov (United States)

Li, Yingxin; Zhang, Xiaoxiao; Zhang, Chen; Zhang, Xiaoying; Li, Ying; Qi, Zhao; Szeto, Christopher; Tang, Mingxin; Peng, Yizhi; Molkentin, Jeffery D; Houser, Steven R; Xie, Mingxing; Chen, Xiongwen

2018-04-01

Cav3.1 T-type Ca 2+ channel current (I Ca-T ) contributes to heart rate genesis but is not known to contribute to heart rate regulation by the sympathetic/β-adrenergic system (SAS). We show that the loss of Cav3.1 makes the beating rates of the heart in vivo and perfused hearts ex vivo, as well as sinoatrial node cells, less sensitive to β-adrenergic stimulation; it also renders less conduction acceleration through the atrioventricular node by β-adrenergic stimulation. Increasing Cav3.1 in cardiomyocytes has the opposite effects. I Ca-T in sinoatrial nodal cells can be upregulated by β-adrenergic stimulation. The results of the present study add a new contribution to heart rate regulation by the SAS system and provide potential new mechanisms for the dysregulation of heart rate and conduction by the SAS in the heart. T-type Ca 2+ channel can be a target for heart disease treatments that aim to slow down the heart rate ABSTRACT: Cav3.1 (α 1G ) T-type Ca 2+ channel (TTCC) is expressed in mouse sinoatrial node cells (SANCs) and atrioventricular (AV) nodal cells and contributes to heart rate (HR) genesis and AV conduction. However, its role in HR regulation and AV conduction acceleration by the β-adrenergic system (SAS) is unclear. In the present study, L- (I Ca-L ) and T-type (I Ca-T ) Ca 2+ currents were recorded in SANCs from Cav3.1 transgenic (TG) and knockout (KO), and control mice. I Ca-T was absent in KO SANCs but enhanced in TG SANCs. In anaesthetized animals, different doses of isoproterenol (ISO) were infused via the jugular vein and the HR was recorded. The EC 50 of the HR response to ISO was lower in TG mice but higher in KO mice, and the maximal percentage of HR increase by ISO was greater in TG mice but less in KO mice. In Langendorff-perfused hearts, ISO increased HR and shortened PR intervals to a greater extent in TG but to a less extent in KO hearts. KO SANCs had significantly slower spontaneous beating rates than control SANCs before and after

Contribution of Hfe expression in macrophages to the regulation of hepatic hepcidin levels and iron loading

OpenAIRE

Makui, Hortence; Soares, Ricardo J.; Jiang, Wenlei; Constante, Marco; Santos, Manuela M.

2005-01-01

Hereditary hemochromatosis (HH), an iron overload disease associated with mutations in the HFE gene, is characterized by increased intestinal iron absorption and consequent deposition of excess iron, primarily in the liver. Patients with HH and Hfe-deficient (Hfe−/−) mice manifest inappropriate expression of the iron absorption regulator hepcidin, a peptide hormone produced by the liver in response to iron loading. In this study, we investigated the contribution of Hfe expression in macrophag...

Overexpressed DNA polymerase iota regulated by JNK/c-Jun contributes to hypermutagenesis in bladder cancer.

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Yuan, Fang; Xu, Zhigang; Yang, Mingzhen; Wei, Quanfang; Zhang, Yi; Yu, Jin; Zhi, Yi; Liu, Yang; Chen, Zhiwen; Yang, Jin

2013-01-01

Human DNA polymerase iota (pol ι) possesses high error-prone DNA replication features and performs translesion DNA synthesis. It may be specialized and strictly regulated in normal mammalian cells. Dysregulation of pol ι may contribute to the acquisition of a mutator phenotype. However, there are few reports describing the transcription regulatory mechanism of pol ι, and there is controversy regarding its role in carcinogenesis. In this study, we performed the deletion and point-mutation experiment, EMSA, ChIP, RNA interference and western blot assay to prove that c-Jun activated by c-Jun N-terminal kinase (JNK) regulates the transcription of pol ι in normal and cancer cells. Xeroderma pigmentosum group C protein (XPC) and ataxia-telangiectasia mutated related protein (ATR) promote early JNK activation in response to DNA damage and consequently enhance the expression of pol ι, indicating that the novel role of JNK signal pathway is involved in DNA damage response. Furthermore, associated with elevated c-Jun activity, the overexpression of pol ι is positively correlated with the clinical tumor grade in 97 bladder cancer samples and may contribute to the hypermutagenesis. The overexpressed pol ι-involved mutagenesis is dependent on JNK/c-Jun pathway in bladder cancer cells identifying by the special mutation spectra. Our results support the conclusion that dysregulation of pol ι by JNK/c-Jun is involved in carcinogenesis and offer a novel understanding of the role of pol ι or c-Jun in mutagenesis.

Optimal Control and Operation Strategy for Wind Turbines Contributing to Grid Primary Frequency Regulation

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Mun-Kyeom Kim

2017-09-01

Full Text Available This study introduces a frequency regulation strategy to enable the participation of wind turbines with permanent magnet synchronous generators (PMSGs. The optimal strategy focuses on developing the frequency support capability of PMSGs connected to the power system. Active power control is performed using maximum power point tracking (MPPT and de-loaded control to supply the required power reserve following a disturbance. A kinetic energy (KE reserve control is developed to enhance the frequency regulation capability of wind turbines. The coordination with the de-loaded control prevents instability in the PMSG wind system due to excessive KE discharge. A KE optimization method that maximizes the sum of the KE reserves at wind farms is also adopted to determine the de-loaded power reference for each PMSG wind turbine using the particle swarm optimization (PSO algorithm. To validate the effectiveness of the proposed optimal control and operation strategy, three different case studies are conducted using the PSCAD/EMTDC simulation tool. The results demonstrate that the optimal strategy enhances the frequency support contribution from PMSG wind turbines.

Contributions of the Hippocampus and Medial Prefrontal Cortex to Energy and Body Weight Regulation

Science.gov (United States)

Davidson, T. L.; Chan, Kinho; Jarrard, Leonard E.; Kanoski, Scott E.; Clegg, Deborah J.; Benoit, Stephen C.

2008-01-01

The effects of selective ibotenate lesions of the complete hippocampus (CHip), the hippocampal ventral pole (VP), or the medial prefrontal cortex (mPFC) in male rats were assessed on several measures related to energy regulation (i.e., body weight gain, food intake, body adiposity, metabolic activity general behavioral activity, conditioned appetitive responding). The testing conditions were designed to minimize the nonspecific debilitating effects of these surgeries on intake and body weight. Rats with CHip and VP lesions exhibited significantly greater weight gain and food intake compared to controls. Furthermore, CHip-lesioned rats, but not rats with VP lesions, showed elevated metabolic activity, general activity in the dark phase of the light-dark cycle, and greater conditioned appetitive behavior, compared to control rats without these brain lesions. In contrast, rats with mPFC lesions were not different from controls on any of these measures. These results indicate that hippocampal damage interferes with energy and body weight regulation, perhaps by disrupting higher-order learning and memory processes that contribute to the control of appetitive and consummatory behavior. PMID:18831000

Riboregulation of the bacterial actin-homolog MreB by DsrA small noncoding RNA.

Science.gov (United States)

Cayrol, Bastien; Fortas, Emilie; Martret, Claire; Cech, Grzegorz; Kloska, Anna; Caulet, Stephane; Barbet, Marion; Trépout, Sylvain; Marco, Sergio; Taghbalout, Aziz; Busi, Florent; Wegrzyn, Grzegorz; Arluison, Véronique

2015-01-01

The bacterial actin-homolog MreB is a key player in bacterial cell-wall biosynthesis and is required for the maintenance of the rod-like morphology of Escherichia coli. However, how MreB cellular levels are adjusted to growth conditions is poorly understood. Here, we show that DsrA, an E. coli small noncoding RNA (sRNA), is involved in the post-transcriptional regulation of mreB. DsrA is required for the downregulation of MreB cellular concentration during environmentally induced slow growth-rates, mainly growth at low temperature and during the stationary phase. DsrA interacts in an Hfq-dependent manner with the 5' region of mreB mRNA, which contains signals for translation initiation and thereby affects mreB translation and stability. Moreover, as DsrA is also involved in the regulation of two transcriptional regulators, σ(S) and the nucleoid associated protein H-NS, which negatively regulate mreB transcription, it also indirectly contributes to mreB transcriptional down-regulation. By using quantitative analyses, our results evidence the complexity of this regulation and the tangled interplay between transcriptional and post-transcriptional control. As transcription factors and sRNA-mediated post-transcriptional regulators use different timescales, we propose that the sRNA pathway helps to adapt to changes in temperature, but also indirectly mediates long-term regulation of MreB concentration. The tight regulation and fine-tuning of mreB gene expression in response to cellular stresses is discussed in regard to the effect of the MreB protein on cell elongation.

TGFβ1-induced down-regulation of microRNA-138 contributes to epithelial-mesenchymal transition in primary lung cancer cells.

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Zhang, Fang; Li, Tiepeng; Han, Lu; Qin, Peng; Wu, Zhao; Xu, Benling; Gao, Quanli; Song, Yongping

2018-02-19

The existence of cancer stem cells within the tumor could lead to cancer therapy resistance. TGFβ1 is considered as one of the most powerful players in the generation of CSCs through induction of epithelial-mesenchymal transition in different types of cancer including lung cancer, however, the detailed mechanisms by which TGFβ1 contribute to EMT induction and CSC maintenance remains unclear. Here, we showed primary lung cancer cells treated by TGFβ1 exhibit mesenchymal features, including morphology and expression of mesenchymal marker in a time-dependent manner. We also observed long-term TGFβ1 exposure leads to an enrichment of a sub-population of CD44 + CD90 + cells which represent CSCs in lung cancer cells. Moreover, the differential expression microRNAs between CSCs and non-CSCs were identified using next-generation sequencing to screen key miRNAs which might contribute to TGFβ1-induced EMT and CSCs generation. Among those differentially expressed miRNAs, the expression of microRNA-138 was time-dependently down-regulated by TGFβ1 treatment. We further demonstrated primary lung cancer cells, in which we knockdown the expression of miR-138, exhibit mesenchymal phenotypes and stem cell properties. Taken together, these findings indicate TGFβ1-induced down-regulation of microRNA-138 contributes to EMT in primary lung cancer cells, and suggest that miR-138 might serve as a potential therapeutic target. Copyright © 2018 Elsevier Inc. All rights reserved.

Down-regulation of SFRP1 as a putative tumor suppressor gene can contribute to human hepatocellular carcinoma

International Nuclear Information System (INIS)

Huang, Jian; Zhang, Yun-Li; Teng, Xiao-Mei; Lin, Yun; Zheng, Da-Li; Yang, Peng-Yuan; Han, Ze-Guang

2007-01-01

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. SFRP1 (the secreted frizzled-related protein 1), a putative tumor suppressor gene mapped onto chromosome 8p12-p11.1, the frequent loss of heterozygosity (LOH) region in human HCC, encodes a Wingless-type (Wnt) signaling antagonist and is frequently inactivated by promoter methylation in many human cancers. However, whether the down-regulation of SFRP1 can contribute to hepatocarcinogenesis still remains unclear. We investigated the expression of SFRP1 through real time RT-PCR and immunohistochemistry staining. The cell growth and colony formation were observed as the overexpression and knockdown of SFRP1. The DNA methylation status within SFRP1 promoter was analyzed through methylation-specific PCR or bisulphate-treated DNA sequencing assays. Loss of heterozygosity was here detected with microsatellite markers. SFRP1 was significantly down-regulated in 76.1% (35/46) HCC specimens at mRNA level and in 30% (30/100) HCCs indicated by immunohistochemistry staining, as compared to adjacent non-cancerous livers. The overexpression of SFRP1 can significantly inhibit the cell growth and colony formation of YY-8103, SMMC7721, and Hep3B cells. The RNA interference against the constitutional SFRP1 in the offspring SMMC7721 cells, which were stably transfected by ectopic SFRP1, can markedly promote cell growth of these cells. LOH of both microsatellite markers D8S532 and D8SAC016868 flanking the gene locus was found in 13% (6 of 46 HCCs) and 6.5% (3 of 46 HCCs) of the informative cases, respectively, where 5 of 8 HCC specimens with LOH showed the down-regulation of SFRP1. DNA hypermethylation within SFRP1 promoter was identified in two of three HCC specimens without SFRP1 expression. Moreover, the DNA methylation of SFRP1 promoter was significantly reduced, along with the re-expression of the gene, in those HCC cell lines, Bel7404, QGY7701, and MHCC-H, as treated by DAC. Our data suggested that the

Untangling the Contributions of Sex-Specific Gene Regulation and X-Chromosome Dosage to Sex-Biased Gene Expression in Caenorhabditis elegans

Science.gov (United States)

Kramer, Maxwell; Rao, Prashant; Ercan, Sevinc

2016-01-01

Dosage compensation mechanisms equalize the level of X chromosome expression between sexes. Yet the X chromosome is often enriched for genes exhibiting sex-biased, i.e., imbalanced expression. The relationship between X chromosome dosage compensation and sex-biased gene expression remains largely unexplored. Most studies determine sex-biased gene expression without distinguishing between contributions from X chromosome copy number (dose) and the animal’s sex. Here, we uncoupled X chromosome dose from sex-specific gene regulation in Caenorhabditis elegans to determine the effect of each on X expression. In early embryogenesis, when dosage compensation is not yet fully active, X chromosome dose drives the hermaphrodite-biased expression of many X-linked genes, including several genes that were shown to be responsible for hermaphrodite fate. A similar effect is seen in the C. elegans germline, where X chromosome dose contributes to higher hermaphrodite X expression, suggesting that lack of dosage compensation in the germline may have a role in supporting higher expression of X chromosomal genes with female-biased functions in the gonad. In the soma, dosage compensation effectively balances X expression between the sexes. As a result, somatic sex-biased expression is almost entirely due to sex-specific gene regulation. These results suggest that lack of dosage compensation in different tissues and developmental stages allow X chromosome copy number to contribute to sex-biased gene expression and function. PMID:27356611

Conservation of σ28-Dependent Non-Coding RNA Paralogs and Predicted σ54-Dependent Targets in Thermophilic Campylobacter Species.

Directory of Open Access Journals (Sweden)

My Thanh Le

Full Text Available Assembly of flagella requires strict hierarchical and temporal control via flagellar sigma and anti-sigma factors, regulatory proteins and the assembly complex itself, but to date non-coding RNAs (ncRNAs have not been described to regulate genes directly involved in flagellar assembly. In this study we have investigated the possible role of two ncRNA paralogs (CjNC1, CjNC4 in flagellar assembly and gene regulation of the diarrhoeal pathogen Campylobacter jejuni. CjNC1 and CjNC4 are 37/44 nt identical and predicted to target the 5' untranslated region (5' UTR of genes transcribed from the flagellar sigma factor σ54. Orthologs of the σ54-dependent 5' UTRs and ncRNAs are present in the genomes of other thermophilic Campylobacter species, and transcription of CjNC1 and CNC4 is dependent on the flagellar sigma factor σ28. Surprisingly, inactivation and overexpression of CjNC1 and CjNC4 did not affect growth, motility or flagella-associated phenotypes such as autoagglutination. However, CjNC1 and CjNC4 were able to mediate sequence-dependent, but Hfq-independent, partial repression of fluorescence of predicted target 5' UTRs in an Escherichia coli-based GFP reporter gene system. This hints towards a subtle role for the CjNC1 and CjNC4 ncRNAs in post-transcriptional gene regulation in thermophilic Campylobacter species, and suggests that the currently used phenotypic methodologies are insufficiently sensitive to detect such subtle phenotypes. The lack of a role of Hfq in the E. coli GFP-based system indicates that the CjNC1 and CjNC4 ncRNAs may mediate post-transcriptional gene regulation in ways that do not conform to the paradigms obtained from the Enterobacteriaceae.

Conservation of σ28-Dependent Non-Coding RNA Paralogs and Predicted σ54-Dependent Targets in Thermophilic Campylobacter Species

Science.gov (United States)

Le, My Thanh; van Veldhuizen, Mart; Porcelli, Ida; Bongaerts, Roy J.; Gaskin, Duncan J. H.; Pearson, Bruce M.; van Vliet, Arnoud H. M.

2015-01-01

Assembly of flagella requires strict hierarchical and temporal control via flagellar sigma and anti-sigma factors, regulatory proteins and the assembly complex itself, but to date non-coding RNAs (ncRNAs) have not been described to regulate genes directly involved in flagellar assembly. In this study we have investigated the possible role of two ncRNA paralogs (CjNC1, CjNC4) in flagellar assembly and gene regulation of the diarrhoeal pathogen Campylobacter jejuni. CjNC1 and CjNC4 are 37/44 nt identical and predicted to target the 5' untranslated region (5' UTR) of genes transcribed from the flagellar sigma factor σ54. Orthologs of the σ54-dependent 5' UTRs and ncRNAs are present in the genomes of other thermophilic Campylobacter species, and transcription of CjNC1 and CNC4 is dependent on the flagellar sigma factor σ28. Surprisingly, inactivation and overexpression of CjNC1 and CjNC4 did not affect growth, motility or flagella-associated phenotypes such as autoagglutination. However, CjNC1 and CjNC4 were able to mediate sequence-dependent, but Hfq-independent, partial repression of fluorescence of predicted target 5' UTRs in an Escherichia coli-based GFP reporter gene system. This hints towards a subtle role for the CjNC1 and CjNC4 ncRNAs in post-transcriptional gene regulation in thermophilic Campylobacter species, and suggests that the currently used phenotypic methodologies are insufficiently sensitive to detect such subtle phenotypes. The lack of a role of Hfq in the E. coli GFP-based system indicates that the CjNC1 and CjNC4 ncRNAs may mediate post-transcriptional gene regulation in ways that do not conform to the paradigms obtained from the Enterobacteriaceae. PMID:26512728

Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration

Energy Technology Data Exchange (ETDEWEB)

Zhu, Zhong Xin [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Sun, Cong Cong [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wenzhou People' s Hospital, Wenzhou, Zhejiang (China); Ting Zhu, Yu; Wang, Ying; Wang, Tao; Chi, Li Sha; Cai, Wan Hui [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Zheng, Jia Yong [Wenzhou People' s Hospital, Wenzhou, Zhejiang (China); Zhou, Xuan [Ningbo First Hospital, Ningbo, Zhejiang (China); Cong, Wei Tao [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Li, Xiao Kun, E-mail: proflxk@163.com [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Jin, Li Tai, E-mail: jin_litai@126.com [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China)

2017-06-15

Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Western blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hh signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.

Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration

International Nuclear Information System (INIS)

Zhu, Zhong Xin; Sun, Cong Cong; Ting Zhu, Yu; Wang, Ying; Wang, Tao; Chi, Li Sha; Cai, Wan Hui; Zheng, Jia Yong; Zhou, Xuan; Cong, Wei Tao; Li, Xiao Kun; Jin, Li Tai

2017-01-01

Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Western blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hh signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.

Cystic fibrosis transmembrane conductance regulator contributes to reacidification of alkalinized lysosomes in RPE cells.

Science.gov (United States)

Liu, Ji; Lu, Wennan; Guha, Sonia; Baltazar, Gabriel C; Coffey, Erin E; Laties, Alan M; Rubenstein, Ronald C; Reenstra, William W; Mitchell, Claire H

2012-07-15

The role of the cystic fibrosis transmembrane conductance regulator (CFTR) in lysosomal acidification has been difficult to determine. We demonstrate here that CFTR contributes more to the reacidification of lysosomes from an elevated pH than to baseline pH maintenance. Lysosomal alkalinization is increasingly recognized as a factor in diseases of accumulation, and we previously showed that cAMP reacidified alkalinized lysosomes in retinal pigmented epithelial (RPE) cells. As the influx of anions to electrically balance proton accumulation may enhance lysosomal acidification, the contribution of the cAMP-activated anion channel CFTR to lysosomal reacidification was probed. The antagonist CFTR(inh)-172 had little effect on baseline levels of lysosomal pH in cultured human RPE cells but substantially reduced the reacidification of compromised lysosomes by cAMP. Likewise, CFTR activators had a bigger impact on cells whose lysosomes had been alkalinized. Knockdown of CFTR with small interfering RNA had a larger effect on alkalinized lysosomes than on baseline levels. Inhibition of CFTR in isolated lysosomes altered pH. While CFTR and Lamp1 were colocalized, treatment with cAMP did not increase targeting of CFTR to the lysosome. The inhibition of CFTR slowed lysosomal degradation of photoreceptor outer segments while activation of CFTR enhanced their clearance from compromised lysosomes. Activation of CFTR acidified RPE lysosomes from the ABCA4(-/-) mouse model of recessive Stargardt's disease, whose lysosomes are considerably alkalinized. In summary, CFTR contributes more to reducing lysosomal pH from alkalinized levels than to maintaining baseline pH. Treatment to activate CFTR may thus be of benefit in disorders of accumulation associated with lysosomal alkalinization.

The contribution of emotion regulation difficulties to risky sexual behavior within a sample of patients in residential substance abuse treatment.

Science.gov (United States)

Tull, Matthew T; Weiss, Nicole H; Adams, Claire E; Gratz, Kim L

2012-10-01

The present study examined the unique contribution of emotion regulation difficulties to past-year risky sexual behavior (RSB) among substance use disorder (SUD) patients (above and beyond other known RSB risk factors). A sample of 177 SUD patients completed a series of questionnaires. At the zero-order level, emotion regulation difficulties, were significantly positively associated with the number of commercial sexual (i.e., the exchange of sex for drugs or money) partners with which penetrative sex occurred and significantly negatively associated with the likelihood of using a condom when having sex with a commercial partner under the influence of drugs. Emotion regulation difficulties also significantly predicted these RSB indices above and beyond other RSB risk factors, including demographics, depression, sensation seeking, traumatic exposure, and substance use severity. The specific emotion regulation difficulty of lack of emotional clarity emerged as a unique predictor of RSB. The implications of these findings for understanding motivations for RSB and developing targeted interventions for RSB among SUD patients are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

A possible contribution of retinoids to regulation of fetal B lymphopoiesis.

Science.gov (United States)

Chen, Xinrong; Welner, Robert S; Kincade, Paul W

2009-09-01

We recently found that all trans retinoic acid (ATRA) accelerated B lymphocyte formation. In the current study, we address the question whether retinoids account for the rapid lymphopoiesis that is characteristic of fetal progenitors. Surprisingly, addition of ATRA to fetal liver cultures actually reduced B lymphopoiesis. A pan-retinoid receptor antagonist selectively suppressed lymphocyte formation from fetal and adult progenitors, suggesting some normal contribution of retinoids to this process. Consistent with this role, B lymphopoiesis was compromised in the marrow of mice with prolonged vitamin A deficiency. Recently identified B1 progenitors from adult marrow were similar to adult B2 progenitors in that their differentiation was stimulated by ATRA. The inhibitory response observed with fetal cells was seen when adult progenitors were exposed to high doses in culture or when adult mice were treated with ATRA for 2 wk. In addition to explosive lymphocyte generation, fetal progenitors tend to be less IL-7 dependent than their adult counterparts, but ATRA did not make fetal progenitors IL-7 independent. We conclude that all known categories of B lineage progenitors are responsive to retinoids and probably regulated by these compounds under physiological conditions. Retinoids may account in part for rapid differentiation in fetal life, but not all unique features of fetal progenitors.

Carbon storage regulator A contributes to the virulence of Haemophilus ducreyi in humans by multiple mechanisms.

Science.gov (United States)

Gangaiah, Dharanesh; Li, Wei; Fortney, Kate R; Janowicz, Diane M; Ellinger, Sheila; Zwickl, Beth; Katz, Barry P; Spinola, Stanley M

2013-02-01

The carbon storage regulator A (CsrA) controls a wide variety of bacterial processes, including metabolism, adherence, stress responses, and virulence. Haemophilus ducreyi, the causative agent of chancroid, harbors a homolog of csrA. Here, we generated an unmarked, in-frame deletion mutant of csrA to assess its contribution to H. ducreyi pathogenesis. In human inoculation experiments, the csrA mutant was partially attenuated for pustule formation compared to its parent. Deletion of csrA resulted in decreased adherence of H. ducreyi to human foreskin fibroblasts (HFF); Flp1 and Flp2, the determinants of H. ducreyi adherence to HFF cells, were downregulated in the csrA mutant. Compared to its parent, the csrA mutant had a significantly reduced ability to tolerate oxidative stress and heat shock. The enhanced sensitivity of the mutant to oxidative stress was more pronounced in bacteria grown to stationary phase compared to that in bacteria grown to mid-log phase. The csrA mutant also had a significant survival defect within human macrophages when the bacteria were grown to stationary phase but not to mid-log phase. Complementation in trans partially or fully restored the mutant phenotypes. These data suggest that CsrA contributes to virulence by multiple mechanisms and that these contributions may be more profound in bacterial cell populations that are not rapidly dividing in the human host.

Regulation of galactolipid biosynthesis by overexpression of the rice MGD gene contributes to enhanced aluminum tolerance in tobacco

Directory of Open Access Journals (Sweden)

Meijuan eZhang

2016-03-01

Full Text Available Membrane lipid alterations affect Al tolerance in plants, but little is known about the regulation of membrane lipid metabolism in response to Al stress. Transgenic tobacco (Nicotiana tabacum overexpressing rice monogalactosyldiacylglycerol (MGDG synthase (OsMGD gene and wild-type tobacco plants were exposed to AlCl3, and the impact of Al toxicity on root growth, Al accumulation, plasma membrane integrity, lipid peroxidation and membrane lipid composition were investigated. Compared with the wild type, the transgenic plants exhibited rapid regrowth of roots after removal of Al and less damage to membrane integrity and lipid peroxidation under Al stress, meanwhile, the Al accumulation showed no difference between wild-type and transgenic plants. Lipid analysis showed that Al treatment dramatically decreased the content of MGDG and the ratio of MGDG to digalactosyldiacylglycerol (DGDG in wild-type plants, while it was unchanged in transgenic plants. The stable of MGDG level and the ratio of MGDG/DGDG contribute to maintain the membrane stability and permeability. Moreover, Al caused a significant increase in phospholipids in wild-type plants, resulting in a high proportion of phospholipids and low proportion of galactolipids, but these proportions were unaffected in transgenic plants. The high proportion of phospholipids could contribute to a higher rate of Al3+ binding in the membrane and thereby leads to more membrane perturbation and damage. These results show that the regulation of galactolipid biosynthesis could play an important role in maintaining membrane structure and function under Al stress.

Contribution of VSC-HVDC to Frequency Regulation of Power Systems With Offshore Wind Generation

DEFF Research Database (Denmark)

Liu, Hongzhi; Chen, Zhe

2015-01-01

to the onshore system grid through voltage-source converter-based–high voltage direct current (VSC-HVdc) transmission systems. Due to the decoupling of VSC-HVdc and signal transmission delay, offshore wind farms may not be able to respond to the onshore grid frequency excursion in time and, consequently......, the stability and security of the power system will be put at risk, especially for those with high wind penetration. This paper proposes a coordinated control scheme to allow VSC-HVdc link to contribute to the system frequency regulation by adjusting its dc-link voltage. By means of this approach, the dc...... capacitors of VSC-HVdc are controlled to absorb or release energy so as to provide frequency support. To further enhance the system frequency response, the frequency support from VSC-HVdc is also finely coordinated with that from offshore wind farm according to the latency of offshore wind farm responding...

Environmental compatible design of power operated products. Contribution of the ecological design regulation to the energy efficiency targets of the EU; Umweltgerechte Gestaltung energiebetriebener Produkte. Der Beitrag der Oekodesign-Richtlinie zu den Energieeffizienzzielen der EU

Energy Technology Data Exchange (ETDEWEB)

Oehme, Ines; Halatsch, Andreas; Schuberth, Jens; Mordziol, Christoph

2009-07-15

The ecological design regulation and its further arrangement are a central component of the climatic protection politics and the policy of the European Union according to the sustainability in production and consumption. This regulation is to contribute to reduce the environmental impacts caused by power operated products. In the contribution under consideration, the Federal Office for Environment Protection (Dessau-Rosslau, Federal Republic of Germany) reports on the ecological design regulation and answers the following questions: (a) Which goals pursues the ecological design regulation and which processes lead to their arrangement?; (b) Which contribution does the regulation perform to the energy saving?; (c) Which challenges and chances exist for the manufacturers?; (d) What are the effects of the ecological design regulation for the consumers?; (e) What mean the ecological design requirements concretely for the individual products? The ecological design requirements not only reduce the environmental impacts but also contribute to the climate protection and reduce the energy costs in the phase of utilization. The consumers receive comprehensive information on the technical characteristics of the products as well as their quality and environmental fairness. Parallel to the conversion of the ecological design regulation, the European Union updates the marking of the energy consumption for numerous products. The ecological design requirements refer to technical characteristics. They do not forbid products or techniques as such.

Trigeminal nerve injury-induced thrombospondin-4 up-regulation contributes to orofacial neuropathic pain states in a rat model.

Science.gov (United States)

Li, K-W; Kim, D-S; Zaucke, F; Luo, Z D

2014-04-01

Injury to the trigeminal nerve often results in the development of chronic pain states including tactile allodynia, or hypersensitivity to light touch, in orofacial area, but its underlying mechanisms are poorly understood. Peripheral nerve injury has been shown to cause up-regulation of thrombospondin-4 (TSP4) in dorsal spinal cord that correlates with neuropathic pain development. In this study, we examined whether injury-induced TSP4 is critical in mediating orofacial pain development in a rat model of chronic constriction injury to the infraorbital nerve. Orofacial sensitivity to mechanical stimulation was examined in a unilateral infraorbital nerve ligation rat model. The levels of TSP4 in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 spinal cord (Vc/C2) from injured rats were examined at time points correlating with the initiation and peak orofacial hypersensitivity. TSP4 antisense and mismatch oligodeoxynucleotides were intrathecally injected into injured rats to see if antisense oligodeoxynucleotide treatment could reverse injury-induced TSP4 up-regulation and orofacial behavioural hypersensitivity. Our data indicated that trigeminal nerve injury induced TSP4 up-regulation in Vc/C2 at a time point correlated with orofacial tactile allodynia. In addition, intrathecal treatment with TSP4 antisense, but not mismatch, oligodeoxynucleotides blocked both injury-induced TSP4 up-regulation in Vc/C2 and behavioural hypersensitivity. Our data support that infraorbital nerve injury leads to TSP4 up-regulation in trigeminal spinal complex that contributes to orofacial neuropathic pain states. Blocking this pathway may provide an alternative approach in management of orofacial neuropathic pain states. © 2013 European Pain Federation - EFIC®

Chemicals regulation and the Porter Hypothesis:a critical review of the new European chemicals regulation

OpenAIRE

Frohwein, T. (Torsten); Hansjürgens, B. (Bernd)

2005-01-01

In this contribution, discussions about the Porter Hypothesis and the pros and cons of the new European chemicals regulation system REACH are tied together. The contribution seeks to apply the Porter Hypothesis to the field of European chemicals regulation. Porter’s claim of positive effects of regulation on innovations seems especially important for the chemicals sector pursuing differentiation. But, understanding Porter’s concept of strategic management indicates that certain segments of th...

Relative contributions of norspermidine synthesis and signaling pathways to the regulation of Vibrio cholerae biofilm formation.

Directory of Open Access Journals (Sweden)

Caitlin K Wotanis

Full Text Available The polyamine norspermidine is one of the major polyamines synthesized by Vibrionales and has also been found in various aquatic organisms. Norspermidine is among the environmental signals that positively regulate Vibrio cholerae biofilm formation. The NspS/MbaA signaling complex detects extracellular norspermidine and mediates the response to this polyamine. Norspermidine binding to the NspS periplasmic binding protein is thought to inhibit the phosphodiesterase activity of MbaA, increasing levels of the biofilm-promoting second messenger cyclic diguanylate monophosphate, thus enhancing biofilm formation. V. cholerae can also synthesize norspermidine using the enzyme NspC as well as import it from the environment. Deletion of the nspC gene was shown to reduce accumulation of bacteria in biofilms, leading to the conclusion that intracellular norspermidine is also a positive regulator of biofilm formation. Because V. cholerae uses norspermidine to synthesize the siderophore vibriobactin it is possible that intracellular norspermidine is required to obtain sufficient amounts of iron, which is also necessary for robust biofilm formation. The objective of this study was to assess the relative contributions of intracellular and extracellular norspermidine to the regulation of biofilm formation in V. cholerae. We show the biofilm defect of norspermidine synthesis mutants does not result from an inability to produce vibriobactin as vibriobactin synthesis mutants do not have diminished biofilm forming abilities. Furthermore, our work shows that extracellular, but not intracellular norspermidine, is mainly responsible for promoting biofilm formation. We establish that the NspS/MbaA signaling complex is the dominant mediator of biofilm formation in response to extracellular norspermidine, rather than norspermidine synthesized by NspC or imported into the cell.

MicroRNA-mediated down-regulation of NKG2D ligands contributes to glioma immune escape.

Science.gov (United States)

Codo, Paula; Weller, Michael; Meister, Gunter; Szabo, Emese; Steinle, Alexander; Wolter, Marietta; Reifenberger, Guido; Roth, Patrick

2014-09-15

Malignant gliomas are intrinsic brain tumors with a dismal prognosis. They are well-adapted to hypoxic conditions and poorly immunogenic. NKG2D is one of the major activating receptors of natural killer (NK) cells and binds to several ligands (NKG2DL). Here we evaluated the impact of miRNA on the expression of NKG2DL in glioma cells including stem-like glioma cells. Three of the candidate miRNA predicted to target NKG2DL were expressed in various glioma cell lines as well as in glioblastomas in vivo: miR-20a, miR-93 and miR-106b. LNA inhibitor-mediated miRNA silencing up-regulated cell surface NKG2DL expression, which translated into increased susceptibility to NK cell-mediated lysis. This effect was reversed by neutralizing NKG2D antibodies, confirming that enhanced lysis upon miRNA silencing was mediated through the NKG2D system. Hypoxia, a hallmark of glioblastomas in vivo, down-regulated the expression of NKG2DL on glioma cells, associated with reduced susceptibility to NK cell-mediated lysis. This process, however, was not mediated through any of the examined miRNA. Accordingly, both hypoxia and the expression of miRNA targeting NKG2DL may contribute to the immune evasion of glioma cells at the level of the NKG2D recognition pathway. Targeting miRNA may therefore represent a novel approach to increase the immunogenicity of glioblastoma.

Epigenetic regulation – contribution to herbicide resistance in weeds?

Czech Academy of Sciences Publication Activity Database

Markus, C.; Pečinka, Aleš; Karan, R.; Barney, J. N.; Merotto, A.

2018-01-01

Roč. 74, č. 2 (2018), s. 275-281 ISSN 1526-498X Institutional support: RVO:61389030 Keywords : DNA methylation * epigenetic s * gene expression * gene regulation * herbicide detoxification * plant stress response Subject RIV: EF - Botanics OBOR OECD: Plant sciences, botany Impact factor: 3.253, year: 2016

ER-plasma membrane contact sites contribute to autophagosome biogenesis by regulation of local PI3P synthesis.

Science.gov (United States)

Nascimbeni, Anna Chiara; Giordano, Francesca; Dupont, Nicolas; Grasso, Daniel; Vaccaro, Maria I; Codogno, Patrice; Morel, Etienne

2017-07-14

The double-membrane-bound autophagosome is formed by the closure of a structure called the phagophore, origin of which is still unclear. The endoplasmic reticulum (ER) is clearly implicated in autophagosome biogenesis due to the presence of the omegasome subdomain positive for DFCP1, a phosphatidyl-inositol-3-phosphate (PI3P) binding protein. Contribution of other membrane sources, like the plasma membrane (PM), is still difficult to integrate in a global picture. Here we show that ER-plasma membrane contact sites are mobilized for autophagosome biogenesis, by direct implication of the tethering extended synaptotagmins (E-Syts) proteins. Imaging data revealed that early autophagic markers are recruited to E-Syt-containing domains during autophagy and that inhibition of E-Syts expression leads to a reduction in autophagosome biogenesis. Furthermore, we demonstrate that E-Syts are essential for autophagy-associated PI3P synthesis at the cortical ER membrane via the recruitment of VMP1, the stabilizing ER partner of the PI3KC3 complex. These results highlight the contribution of ER-plasma membrane tethers to autophagosome biogenesis regulation and support the importance of membrane contact sites in autophagy. © 2017 The Authors.

The vital role of industry in contributing to the IAEA transport regulations

International Nuclear Information System (INIS)

Owen, G.

2004-01-01

Industry has taken a key role in the development of radioactive transport regulation for many years. There are two main parties that need consideration in the regulatory process: the 'public and worker' interest, this responsibility is represented by the regulators: the 'industry' interest, these parties by their nature, give priority to representing their own interests. Any amendment or review of the regulations benefits greatly from the industry perspective. The opposite ends of the 'spectrum of opinion' suggests that insufficient industry involvement may lead to uneconomic transport, whereas, insufficient Competent Authority involvement may lead to unsafe transport. These seemingly polarised views are considered and discussed, but it becomes clear that the two parties complement each other, both ensuring each remains grounded. The basis for a regulation that compares the costs directly with the benefit in terms of reduced risk to the public or employees is at the heart of successful regulation. This balance is fragile and sensitive and underlines the importance of a harmonised approach by both Industry and Competent Authorities

The vital role of industry in contributing to the IAEA transport regulations

Energy Technology Data Exchange (ETDEWEB)

Owen, G. [BNFL (United Kingdom)

2004-07-01

Industry has taken a key role in the development of radioactive transport regulation for many years. There are two main parties that need consideration in the regulatory process: the 'public and worker' interest, this responsibility is represented by the regulators: the 'industry' interest, these parties by their nature, give priority to representing their own interests. Any amendment or review of the regulations benefits greatly from the industry perspective. The opposite ends of the 'spectrum of opinion' suggests that insufficient industry involvement may lead to uneconomic transport, whereas, insufficient Competent Authority involvement may lead to unsafe transport. These seemingly polarised views are considered and discussed, but it becomes clear that the two parties complement each other, both ensuring each remains grounded. The basis for a regulation that compares the costs directly with the benefit in terms of reduced risk to the public or employees is at the heart of successful regulation. This balance is fragile and sensitive and underlines the importance of a harmonised approach by both Industry and Competent Authorities.

BCL11B is up-regulated by EWS/FLI and contributes to the transformed phenotype in Ewing sarcoma.

Directory of Open Access Journals (Sweden)

Elizabeth T Wiles

Full Text Available The EWS/FLI translocation product is the causative oncogene in Ewing sarcoma and acts as an aberrant transcription factor. EWS/FLI dysregulates gene expression during tumorigenesis by abnormally activating or repressing genes. The expression levels of thousands of genes are affected in Ewing sarcoma, however, it is unknown which of these genes contribute to the transformed phenotype. Here we characterize BCL11B as an up-regulated EWS/FLI target that is necessary for the maintenance of transformation in patient derived Ewing sarcoma cells lines. BCL11B, a zinc finger transcription factor, acts as a transcriptional repressor in Ewing's sarcoma and contributes to the EWS/FLI repressed gene signature. BCL11B repressive activity is mediated by the NuRD co-repressor complex. We further demonstrate that re-expression of SPRY1, a repressed target of BCL11B, limits the transformation capacity of Ewing sarcoma cells. These data define a new pathway downstream of EWS/FLI required for oncogenic maintenance in Ewing sarcoma.

Contributions of metacognitive and self-regulated learning theories to investigations of calibration of comprehension

Directory of Open Access Journals (Sweden)

Stephanie Stolp

2009-10-01

Full Text Available In this paper we examine the contributions of metacognitive and self-regulated learning theories to research on students' calibration of comprehension. Historically, cognitive psychologists have studied calibration of comprehension within a purely metacognitive framework, with an emphasis on the role of text and task factors but little consideration of factors of self. There has been a recent trend, however, towards incorporating a social cognitive perspective to the study of calibration of comprehension, with factors of self such as motivation and affect being examined more often. Among the factors of self that have been examined, self-efficacy has played a major role as it may be all but impossible to disentangle its influence on students' calibration of comprehension. Other variables of self that have been examined include ability, familiarity, ego and goal-orientation, goal setting, personality traits and susceptibility to social and cultural influences. Broadening the context in which calibration of comprehension is assessed allows a more complete examination of the rich set of interrelated processes that affect students' performance.

Small RNA-Controlled Gene Regulatory Networks in Pseudomonas putida

DEFF Research Database (Denmark)

Bojanovic, Klara

evolved numerous mechanisms to controlgene expression in response to specific environmental signals. In addition to two-component systems, small regulatory RNAs (sRNAs) have emerged as major regulators of gene expression. The majority of sRNAs bind to mRNA and regulate their expression. They often have...... multiple targets and are incorporated into large regulatory networks and the RNA chaper one Hfq in many cases facilitates interactions between sRNAs and their targets. Some sRNAs also act by binding to protein targets and sequestering their function. In this PhD thesis we investigated the transcriptional....... Detailed insights into the mechanisms through which P. putida responds to different stress conditions and increased understanding of bacterial adaptation in natural and industrial settings were gained. Additionally, we identified genome-wide transcription start sites, andmany regulatory RNA elements...

Maternal Self-Regulation, Relationship Adjustment, and Home Chaos: Contributions to Infant Negative Emotionality

Science.gov (United States)

Bridgett, David J.; Burt, Nicole M.; Laake, Lauren M.; Oddi, Kate B.

2013-01-01

There has been increasing interest in the direct and indirect effects of parental self-regulation on children’s outcomes. In the present investigation, the effects of maternal self-regulation, home chaos, and inter-parental relationship adjustment on broad and specific indicators of infant negative emotionality (NE) were examined. A sample of maternal caregivers and their 4-month-old infants (N = 85) from a rural community participated. Results demonstrated that better maternal self-regulation was associated with lower infant NE broadly, as well as with lower infant sadness and distress to limitations/frustration and better falling reactivity (i.e. emotion regulation), specifically. Maternal self-regulation also predicted less chaotic home environments and better maternal inter-parental relationship adjustment. Findings also supported the indirect effects of maternal self-regulation on broad and specific indicators of infant NE through home chaos and maternal relationship adjustment. Some differential effects were also identified. Elevated home chaos appeared to specifically affect infant frustration/distress to limitations whereas maternal relationship adjustment affected broad infant NE, as well as several specific indicators of infant NE: frustration/distress to limitations, sadness, and falling reactivity. In conjunction with other recent investigations that have reported the effects of maternal self-regulation on parenting, the findings in the present investigation suggest that parental self-regulation may influence children’s outcomes through several proximal environmental pathways. PMID:23748168

Homeostatic and Circadian Contribution to EEG and Molecular State Variables of Sleep Regulation

Science.gov (United States)

Curie, Thomas; Mongrain, Valérie; Dorsaz, Stéphane; Mang, Géraldine M.; Emmenegger, Yann; Franken, Paul

2013-01-01

Study Objectives: Besides their well-established role in circadian rhythms, our findings that the forebrain expression of the clock-genes Per2 and Dbp increases and decreases, respectively, in relation to time spent awake suggest they also play a role in the homeostatic aspect of sleep regulation. Here, we determined whether time of day modulates the effects of elevated sleep pressure on clock-gene expression. Time of day effects were assessed also for recognized electrophysiological (EEG delta power) and molecular (Homer1a) markers of sleep homeostasis. Design: EEG and qPCR data were obtained for baseline and recovery from 6-h sleep deprivation starting at ZT0, -6, -12, or -18. Setting: Mouse sleep laboratory. Participants: Male mice. Interventions: Sleep deprivation. Results: The sleep-deprivation induced changes in Per2 and Dbp expression importantly varied with time of day, such that Per2 could even decrease during sleep deprivations occurring at the decreasing phase in baseline. Dbp showed similar, albeit opposite dynamics. These unexpected results could be reliably predicted assuming that these transcripts behave according to a driven damped harmonic oscillator. As expected, the sleep-wake distribution accounted for a large degree of the changes in EEG delta power and Homer1a. Nevertheless, the sleep deprivation-induced increase in delta power varied also with time of day with higher than expected levels when recovery sleep started at dark onset. Conclusions: Per2 and delta power are widely used as exclusive state variables of the circadian and homeostatic process, respectively. Our findings demonstrate a considerable cross-talk between these two processes. As Per2 in the brain responds to both sleep loss and time of day, this molecule is well positioned to keep track of and to anticipate homeostatic sleep need. Citation: Curie T; Mongrain V; Dorsaz S; Mang GM; Emmenegger Y; Franken P. Homeostatic and circadian contribution to EEG and molecular state

Homeostatic and circadian contribution to EEG and molecular state variables of sleep regulation.

Science.gov (United States)

Curie, Thomas; Mongrain, Valérie; Dorsaz, Stéphane; Mang, Géraldine M; Emmenegger, Yann; Franken, Paul

2013-03-01

Besides their well-established role in circadian rhythms, our findings that the forebrain expression of the clock-genes Per2 and Dbp increases and decreases, respectively, in relation to time spent awake suggest they also play a role in the homeostatic aspect of sleep regulation. Here, we determined whether time of day modulates the effects of elevated sleep pressure on clock-gene expression. Time of day effects were assessed also for recognized electrophysiological (EEG delta power) and molecular (Homer1a) markers of sleep homeostasis. EEG and qPCR data were obtained for baseline and recovery from 6-h sleep deprivation starting at ZT0, -6, -12, or -18. Mouse sleep laboratory. Male mice. Sleep deprivation. The sleep-deprivation induced changes in Per2 and Dbp expression importantly varied with time of day, such that Per2 could even decrease during sleep deprivations occurring at the decreasing phase in baseline. Dbp showed similar, albeit opposite dynamics. These unexpected results could be reliably predicted assuming that these transcripts behave according to a driven damped harmonic oscillator. As expected, the sleep-wake distribution accounted for a large degree of the changes in EEG delta power and Homer1a. Nevertheless, the sleep deprivation-induced increase in delta power varied also with time of day with higher than expected levels when recovery sleep started at dark onset. Per2 and delta power are widely used as exclusive state variables of the circadian and homeostatic process, respectively. Our findings demonstrate a considerable cross-talk between these two processes. As Per2 in the brain responds to both sleep loss and time of day, this molecule is well positioned to keep track of and to anticipate homeostatic sleep need. Curie T; Mongrain V; Dorsaz S; Mang GM; Emmenegger Y; Franken P. Homeostatic and circadian contribution to EEG and molecular state variables of sleep regulation. SLEEP 2013;36(3):311-323.

Construction of new synthetic biology tools for the control of gene expression in the cyanobacterium Synechococcus sp. strain PCC 7002.

Science.gov (United States)

Zess, Erin K; Begemann, Matthew B; Pfleger, Brian F

2016-02-01

Predictive control of gene expression is an essential tool for developing synthetic biological systems. The current toolbox for controlling gene expression in cyanobacteria is a barrier to more in-depth genetic analysis and manipulation. Towards relieving this bottleneck, this work describes the use of synthetic biology to construct an anhydrotetracycline-based induction system and adapt a trans-acting small RNA (sRNA) system for use in the cyanobacterium Synechococcus sp. strain PCC 7002. An anhydrotetracycline-inducible promoter was developed to maximize intrinsic strength and dynamic range. The resulting construct, PEZtet , exhibited tight repression and a maximum 32-fold induction upon addition of anhydrotetracycline. Additionally, a sRNA system based on the Escherichia coli IS10 RNA-IN/OUT regulator was adapted for use in Synechococcus sp. strain PCC 7002. This system exhibited 70% attenuation of target gene expression, providing a demonstration of the use of sRNAs for differential gene expression in cyanobacteria. These systems were combined to produce an inducible sRNA system, which demonstrated 59% attenuation of target gene expression. Lastly, the role of Hfq, a critical component of sRNA systems in E. coli, was investigated. Genetic studies showed that the Hfq homolog in Synechococcus sp. strain PCC 7002 did not impact repression by the engineered sRNA system. In summary, this work describes new synthetic biology tools that can be applied to physiological studies, metabolic engineering, or sRNA platforms in Synechococcus sp. strain PCC 7002. © 2015 Wiley Periodicals, Inc.

Distinct Residues Contribute to Motility Repression and Autoregulation in the Proteus mirabilis Fimbria-Associated Transcriptional Regulator AtfJ.

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Bode, Nadine J; Chan, Kun-Wei; Kong, Xiang-Peng; Pearson, Melanie M

2016-08-01

Proteus mirabilis contributes to a significant number of catheter-associated urinary tract infections, where coordinated regulation of adherence and motility is critical for ascending disease progression. Previously, the mannose-resistant Proteus-like (MR/P) fimbria-associated transcriptional regulator MrpJ has been shown to both repress motility and directly induce the transcription of its own operon; in addition, it affects the expression of a wide range of cellular processes. Interestingly, 14 additional mrpJ paralogs are included in the P. mirabilis genome. Looking at a selection of MrpJ paralogs, we discovered that these proteins, which consistently repress motility, also have nonidentical functions that include cross-regulation of fimbrial operons. A subset of paralogs, including AtfJ (encoded by the ambient temperature fimbrial operon), Fim8J, and MrpJ, are capable of autoinduction. We identified an element of the atf promoter extending from 487 to 655 nucleotides upstream of the transcriptional start site that is responsive to AtfJ, and we found that AtfJ directly binds this fragment. Mutational analysis of AtfJ revealed that its two identified functions, autoregulation and motility repression, are not invariably linked. Residues within the DNA-binding helix-turn-helix domain are required for motility repression but not necessarily autoregulation. Likewise, the C-terminal domain is dispensable for motility repression but is essential for autoregulation. Supported by a three-dimensional (3D) structural model, we hypothesize that the C-terminal domain confers unique regulatory capacities on the AtfJ family of regulators. Balancing adherence with motility is essential for uropathogens to successfully establish a foothold in their host. Proteus mirabilis uses a fimbria-associated transcriptional regulator to switch between these antagonistic processes by increasing fimbrial adherence while simultaneously downregulating flagella. The discovery of multiple

Autoinducer-2 Quorum Sensing Contributes to Regulation of Microcin PDI in Escherichia coli

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Shao-Yeh Lu

2017-12-01

Full Text Available The Escherichia coli quorum sensing (QS signal molecule, autoinducer-2 (AI-2, reaches its maximum concentration during mid-to-late growth phase after which it quickly degrades during stationary phase. This pattern of AI-2 concentration coincides with the up- then down-regulation of a recently described microcin PDI (mccPDI effector protein (McpM. To determine if there is a functional relationship between these systems, a prototypical mccPDI-expressing strain of E. coli 25 was used to generate ΔluxS, ΔlsrACDBFG (Δlsr, and ΔlsrR mutant strains that are deficient in AI-2 production, transportation, and AI-2 transport regulation, respectively. Trans-complementation, RT-qPCR, and western blot assays were used to detect changes of microcin expression and synthesis under co-culture and monoculture conditions. Compared to the wild-type strain, the AI-2-deficient strain (ΔluxS and -uptake negative strain (Δlsr were >1,000-fold less inhibitory to susceptible bacteria (P < 0.05. With in trans complementation of luxS, the AI-2 deficient mutant reduced the susceptible E. coli population by 4-log, which was within 1-log of the wild-type phenotype. RT-qPCR and western blot results for the AI-2 deficient E. coli 25 showed a 5-fold reduction in mcpM transcription with an average 2-h delay in McpM synthesis. Furthermore, overexpression of sRNA micC and micF (both involved in porin protein regulation was correlated with mcpM regulation, consistent with a possible link between QS and mcpM regulation. This is the direct first evidence that microcin regulation can be linked to quorum sensing in a Gram-negative bacterium.

Ca²⁺ signal contributing to the synthesis and emission of monoterpenes regulated by light intensity in Lilium 'siberia'.

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Hu, Zenghui; Li, Tianjiao; Zheng, Jian; Yang, Kai; He, Xiangfeng; Leng, Pingsheng

2015-06-01

The floral scent is an important part of plant volatile compounds, and is influenced by environmental factors. The emission of monoterpenes of Lilium 'siberia' is regulated by light intensity, but the mechanism is large unknown. In this study, the expression of Li-mTPS, a monoterpene synthase gene in the tepals of Lilium 'siberia', and net Ca(2+) flux were investigated after exposure to different levels of light intensity (0, 100, 300, 600, 1000, and 1500 μmol m(-2) s(-1)). Moreover the effect of LaCl3 and ethylene glycol-bis-(2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA) on the Li-mTPS expression, monoterpene emission, and net Ca(2+) flux were examined at 600 μmol m(-2) s(-1). The results showed that along with the enhancement of light intensity, the expression level of Li-mTPS increased gradually, and the net Ca(2+) influx was also enhanced showing a similar pattern. It was found that LaCl3 and EGTA effectively inhibited the increase in expression of Li-mTPS and the net Ca(2+) influx induced by light treatment. Moreover, the release amounts of monoterpenes decreased significantly after treatment with LaCl3 and EGTA. So it can be concluded that Ca(2+) signal contributed to the biosynthesis and emission of monoterpenes regulated by light intensity in Lilium 'siberia' tepals. The increased light intensity firstly triggered the Ca(2+) influx to cytoplasm, and then the gene expression of monoterpene synthases downstream was activated to regulate the biosynthesis and emission of monoterpenes. But in the signaling pathway other mechanisms were thought to be involved in the emission of monoterpenes regulated by light intensity, which need to be investigated in future research. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Post-translational regulation enables robust p53 regulation.

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Shin, Yong-Jun; Chen, Kai-Yuan; Sayed, Ali H; Hencey, Brandon; Shen, Xiling

2013-08-30

The tumor suppressor protein p53 plays important roles in DNA damage repair, cell cycle arrest and apoptosis. Due to its critical functions, the level of p53 is tightly regulated by a negative feedback mechanism to increase its tolerance towards fluctuations and disturbances. Interestingly, the p53 level is controlled by post-translational regulation rather than transcriptional regulation in this feedback mechanism. We analyzed the dynamics of this feedback to understand whether post-translational regulation provides any advantages over transcriptional regulation in regard to disturbance rejection. When a disturbance happens, even though negative feedback reduces the steady-state error, it can cause a system to become less stable and transiently overshoots, which may erroneously trigger downstream reactions. Therefore, the system needs to balance the trade-off between steady-state and transient errors. Feedback control and adaptive estimation theories revealed that post-translational regulation achieves a better trade-off than transcriptional regulation, contributing to a more steady level of p53 under the influence of noise and disturbances. Furthermore, post-translational regulation enables cells to respond more promptly to stress conditions with consistent amplitude. However, for better disturbance rejection, the p53- Mdm2 negative feedback has to pay a price of higher stochastic noise. Our analyses suggest that the p53-Mdm2 feedback favors regulatory mechanisms that provide the optimal trade-offs for dynamic control.

76 FR 65965 - Contributions to the Telecommunications Relay Services Fund

Science.gov (United States)

2011-10-25

...] Contributions to the Telecommunications Relay Services Fund AGENCY: Federal Communications Commission. ACTION... Telecommunications Relay Services (TRS) Fund in a manner prescribed by regulation that is consistent with and... . SUPPLEMENTARY INFORMATION: This is a summary of the Commission's Contributions to the Telecommunications Relay...

Contributions of citrate in redox potential maintenance and ATP production: metabolic pathways and their regulation in Lactobacillus panis PM1.

Science.gov (United States)

Kang, Tae Sun; Korber, Darren R; Tanaka, Takuji

2013-10-01

Lactobacillus panis PM1 belongs to the group III heterofermentative lactobacilli and can utilize various NADH-reoxidizing routes (e.g., citrate, glycerol, and oxygen) according to environmental conditions. In this study, we investigated the ability of L. panis PM1 to produce succinate, acetate, and lactate via citrate utilization. Possible pathways, as well as regulation, for citrate metabolism were examined on the basis of the genome sequence data and metabolic profiles of L. panis PM1. The presence of citrate led to the up-regulation, at the transcriptional level, of the genes encoding for citrate lyase, malate dehydrogenase, and malic enzyme of the citrate pathways by 10- to 120-fold. The transcriptional regulator of the dha operon coding for glycerol dehydratase of L. panis PM1 repressed the expression of the citrate lyase gene (10-fold). Metabolite analyses indicated that the transcriptional enhancement by citrate stimulated succinate yield. Citrate metabolism contributed to energy production by providing a major alternate pathway for NAD(+) regeneration and allowed acetyl phosphate to yield acetate/ATP instead of ethanol/NAD(+). Additionally, a branching pathway from oxaloacetate to pyruvate increased the pool of lactate, which was then used to produce ATP during stationary phase. However, the redirection of NADH-to-citrate utilization resulted in stress caused by end-products (i.e., succinate and acetate). This stress reduced succinate production by up to 50 % but did not cause significant changes at transcriptional level. Overall, citrate utilization was beneficial for the growth of L. panis PM1 by providing a NAD(+) regeneration route and producing extra ATP.

Federal Gasoline Regulations

Science.gov (United States)

The Clean Air Act requires EPA to regulate fuels and fuel additives for use in mobile sources if such fuel, fuel additive or any emission products causes or contributes to air or water pollution that may endanger the public health or welfare.

The Regulation of Medicines in Croatia - a Contribution to Public Health

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Ilić Martinac, A

2010-07-01

Full Text Available The regulatory system for medicinal products includes the existence of a legislative framework and a medicines agency as the regulatory body. The legislative framework for medicinal products has been amended several times so as to align it with the EU acquis communautaire, where medicinal products represent one of the best regulated and aligned areas. For the purpose of regulating the Croatian medicines market, the Agency for Medicinal Products and Medical Devices was established in 2003 to implement the procedure of granting marketing authorisation for medicinal products, to supervise the adverse reactions of medicinal products, to conduct laboratory tests of the quality of medicines and vaccines sampled from the market, to issue licences for the manufacture and distribution of medicinal products, to monitor medicine consumption, and to inform about medicines and promote their rational use. Medical devices are regulated under a special act, and the Agency conducts entries into the register in that field and carries out vigilance over medical devices. In this way, products intended for health care on the Croatian market are of the appropriate quality, safety and efficacy, and are under the constant supervision of the competent body that assesses their risk-to-benefit ratio. Upon accession of the Republic of Croatia to full membership in the European Union, the Agency will be included in the European authorisation procedures for medicines, such as the centralised procedure in the European Medicines Agency (EMA, and above all, the mutual recognition procedure and decentralised procedure in which the role of the agencies of EU Member States is greater. This article gives an overview of the most important regulatory activities in the field of medicinal products, and the readiness of the Agency to function in the future integrated European regulatory area.

USP37 deubiquitinates Cdt1 and contributes to regulate DNA replication.

Science.gov (United States)

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

2016-10-01

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

Mindful Emotion Regulation: Exploring the Neurocognitive Mechanisms behind Mindfulness

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Alessandro Grecucci

2015-01-01

Full Text Available The purpose of this paper is to review some of the psychological and neural mechanisms behind mindfulness practice in order to explore the unique factors that account for its positive impact on emotional regulation and health. After reviewing the mechanisms of mindfulness and its effects on clinical populations we will consider how the practice of mindfulness contributes to the regulation of emotions. We argue that mindfulness has achieved effective outcomes in the treatment of anxiety, depression, and other psychopathologies through the contribution of mindfulness to emotional regulation. We consider the unique factors that mindfulness meditation brings to the process of emotion regulation that may account for its effectiveness. We review experimental evidence that points towards the unique effects of mindfulness specifically operating over and above the regulatory effects of cognitive reappraisal mechanisms. A neuroanatomical circuit that leads to mindful emotion regulation is also suggested. This paper thereby aims to contribute to proposed models of mindfulness for research and theory building by proposing a specific model for the unique psychological and neural processes involved in mindful detachment that account for the effects of mindfulness over and above the effects accounted for by other well-established emotional regulation processes such as cognitive reappraisal.

STIGLER’S INFLUENTIAL CONTRIBUTION TO ECONOMIC THOUGHT

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Artidiatun Adji

2017-01-01

Full Text Available This paper analyzes George J. Stigler’s influential contributions to economic ideas, specifically on industrial structures, the functioning of markets, the causes and effects of public regulation, the economics of information, and on the development of economic thought. Stigler’s most influential contribution to economic thought came in his work on information theory. Treating information as a valuable commodity, he explained why prices differ for identical goods. From his work, many other theories have been built to explain economic behavior. A considerable number of works on decision making under uncertainty could not have progressed without an understanding of the role of information. His swing of the pendulum in economic regulation constitutes a great turnabout. He started research, known as public choice, which assumes that government policymakers are driven by self-interest rather than pure concern for the public’s welfare. His views have now become those of the mainstream.

The complex contribution of NOS interneurons in the physiology of cerebrovascular regulation

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Sonia eDuchemin

2012-08-01

Full Text Available Following the discovery of the vasorelaxant properties of nitric oxide (NO by Furchgott and Ignarro, the finding by Bredt and coll. of a constitutively expressed NO synthase in neurons (nNOS led to the presumption that neuronal NO may control cerebrovascular functions. Consequently, numerous studies have sought to determine whether neuraly-derived NO is involved in the regulation of cerebral blood flow. Anatomically, axons, dendrites or somata of NO neurons have been found to contact the basement membrane of blood vessels or perivascular astrocytes in all segments of the cortical microcirculation. Functionally, various experimental approaches support a role of neuronal NO in the maintenance of resting cerebral blood flow as well as in the vascular response to neuronal activity. Since decades, it has been assumed that neuronal NO simply diffuses to the local blood vessels and produce vasodilation through a cGMP-PKG dependent mechanism. However, NO is not the sole mediator of vasodilation in the cerebral microcirculation and is known to interact with a myriad of signaling pathways also involved in vascular control. In addition, cerebrovascular regulation is the result of a complex orchestration between all components of the neurovascular unit (i.e. neuronal, glial and vascular cells also known to produce NO. In this review article, the role of NO interneuron in the regulation of cortical microcirculation will be discussed in the context of the neurovascular unit.

Designing Next Generation Telecom Regulation

DEFF Research Database (Denmark)

Henten, Anders; Samarajiva, Rohan; Melody, William H.

2003-01-01

This article critically examines the multiple rationales for telecom, IT, media convergence regulation, on the one hand, and multisector utility regulation, on the other, and the practical questions of implementation they pose, with a view to contributing to informed policy and regulatory decisions...... to the regulatory process such as scarcity of regulatory resources and safeguards for regulatory independence, are examined. It is concluded that ICT and media convergence issues are primarily about improving the efficiency of market economies, and how changes in regulation can facilitate this process. Multi...

MicroRNA regulation of Autophagy

DEFF Research Database (Denmark)

Frankel, Lisa B; Lund, Anders H

2012-01-01

recently contributed to our understanding of the molecular mechanisms of the autophagy machinery, yet several gaps remain in our knowledge of this process. The discovery of microRNAs (miRNAs) established a new paradigm of post-transcriptional gene regulation and during the past decade these small non......RNAs to regulation of the autophagy pathway. This regulation occurs both through specific core pathway components as well as through less well-defined mechanisms. Although this field is still in its infancy, we are beginning to understand the potential implications of these initial findings, both from a pathological...

Implementation of an Electric Vehicle Test Bed Controlled by a Virtual Power Plant for Contributing to Regulating Power Reserves

DEFF Research Database (Denmark)

Marra, Francesco; Sacchetti, Dario; Pedersen, Anders Bro

2012-01-01

and communication interfaces, is able to respond in real-time to smart grid control signals. The EV test bed is equipped with a Lithium-ion battery pack, a Battery Management System (BMS), a charger and a Vehicle-to-Grid (V2G) unit for feeding power back to the grid. The designed solution serves......With the increased focus on Electric Vehicles (EV) research and the potential benefits they bring for smart grid applications, there is a growing need for an evaluation platform connected to the electricity grid. This paper addresses the design of an EV test bed, which using real EV components...... requests from the Danish TSO are used as a proof-of-concept, to demonstrate the EV test bed power response. Test results have proven the capability to respond to frequent power control requests and they reveal the potential EV ability for contributing to regulating power reserves....

What Makes a Good Student? How Emotions, Self-Regulated Learning, and Motivation Contribute to Academic Achievement

Science.gov (United States)

Mega, Carolina; Ronconi, Lucia; De Beni, Rossana

2014-01-01

The authors propose a theoretical model linking emotions, self-regulated learning, and motivation to academic achievement. This model was tested with 5,805 undergraduate students. They completed the Self-Regulated Learning, Emotions, and Motivation Computerized Battery (LEM-B) composed of 3 self-report questionnaires: the Self-Regulated Learning…

The significance of translation regulation in the stress response

Science.gov (United States)

2013-01-01

Background The stress response in bacteria involves the multistage control of gene expression but is not entirely understood. To identify the translational response of bacteria in stress conditions and assess its contribution to the regulation of gene expression, the translational states of all mRNAs were compared under optimal growth condition and during nutrient (isoleucine) starvation. Results A genome-scale study of the translational response to nutritional limitation was performed in the model bacterium Lactococcus lactis. Two measures were used to assess the translational status of each individual mRNA: the fraction engaged in translation (ribosome occupancy) and ribosome density (number of ribosomes per 100 nucleotides). Under isoleucine starvation, half of the mRNAs considered were translationally down-regulated mainly due to decreased ribosome density. This pattern concerned genes involved in growth-related functions such as translation, transcription, and the metabolism of fatty acids, phospholipids and bases, contributing to the slowdown of growth. Only 4% of the mRNAs were translationally up-regulated, mostly related to prophagic expression in response to stress. The remaining genes exhibited antagonistic regulations of the two markers of translation. Ribosome occupancy increased significantly for all the genes involved in the biosynthesis of isoleucine, although their ribosome density had decreased. The results revealed complex translational regulation of this pathway, essential to cope with isoleucine starvation. To elucidate the regulation of global gene expression more generally, translational regulation was compared to transcriptional regulation under isoleucine starvation and to other post-transcriptional regulations related to mRNA degradation and mRNA dilution by growth. Translational regulation appeared to accentuate the effects of transcriptional changes for down-regulated growth-related functions under isoleucine starvation although m

Triceps surae short latency stretch reflexes contribute to ankle stiffness regulation during human running.

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Neil J Cronin

Full Text Available During human running, short latency stretch reflexes (SLRs are elicited in the triceps surae muscles, but the function of these responses is still a matter of controversy. As the SLR is primarily mediated by Ia afferent nerve fibres, various methods have been used to examine SLR function by selectively blocking the Ia pathway in seated, standing and walking paradigms, but stretch reflex function has not been examined in detail during running. The purpose of this study was to examine triceps surae SLR function at different running speeds using Achilles tendon vibration to modify SLR size. Ten healthy participants ran on an instrumented treadmill at speeds between 7 and 15 km/h under 2 Achilles tendon vibration conditions: no vibration and 90 Hz vibration. Surface EMG from the triceps surae and tibialis anterior muscles, and 3D lower limb kinematics and ground reaction forces were simultaneously collected. In response to vibration, the SLR was depressed in the triceps surae muscles at all speeds. This coincided with short-lasting yielding at the ankle joint at speeds between 7 and 12 km/h, suggesting that the SLR contributes to muscle stiffness regulation by minimising ankle yielding during the early contact phase of running. Furthermore, at the fastest speed of 15 km/h, the SLR was still depressed by vibration in all muscles but yielding was no longer evident. This finding suggests that the SLR has greater functional importance at slow to intermediate running speeds than at faster speeds.

Information, Interests, and Environmental Regulation

DEFF Research Database (Denmark)

Winter, Søren; May, Peter J.

2002-01-01

This study contributes to the understanding of informational approaches to bringing about compliance with environmental regulations with particular attention to differences in the influence of information provided by different information sources. Based on theorizing from a combination of informa......This study contributes to the understanding of informational approaches to bringing about compliance with environmental regulations with particular attention to differences in the influence of information provided by different information sources. Based on theorizing from a combination...... of information processing and interest group literatures, we develop hypotheses about regulatees' reliance upon and the influence of different sources of information. We test these hypotheses for Danish farmers’ compliance with agro-environmental rules. Our findings show that information plays a role in bringing...

The cyclophilin D/Drp1 axis regulates mitochondrial fission contributing to oxidative stress-induced mitochondrial dysfunctions in SH-SY5Y cells

International Nuclear Information System (INIS)

Xiao, Anqi; Gan, Xueqi; Chen, Ruiqi; Ren, Yanming; Yu, Haiyang; You, Chao

2017-01-01

Oxidative stress plays a central role in the pathogenesis of various neurodegenerative diseases. Increasing evidences have demonstrated that structural abnormalities in mitochondria are involved in oxidative stress related nerve cell damage. And Drp1 plays a critical role in mitochondrial dynamic imbalance insulted by oxidative stress-derived mitochondria. However, the status of mitochondrial fusion and fission pathway and its relationship with mitochondrial properties such as mitochondrial membrane permeability transition pore (mPTP) have not been fully elucidated. Here, we demonstrated for the first time the role of Cyclophilin D (CypD), a crucial component for mPTP formation, in the regulation of mitochondrial dynamics in oxidative stress treated nerve cell. We observed that CypD-mediated phosphorylation of Drp1 and subsequently augmented Drp1 recruitment to mitochondria and shifts mitochondrial dynamics toward excessive fission, which contributes to the mitochondrial structural and functional dysfunctions in oxidative stress-treated nerve cells. CypD depletion or over expression accompanies mitochondrial dynamics/functions recovery or aggravation separately. We also demonstrated first time the link between the CypD to mitochondrial dynamics. Our data offer new insights into the mechanism of mitochondrial dynamics which contribute to the mitochondrial dysfunctions, specifically the role of CypD in Drp1-mediated mitochondrial fission. The protective effect of CsA, or other molecules affecting the function of CypD hold promise as a potential novel therapeutic strategy for governing oxidative stress pathology via mitochondrial pathways. - Highlights: • Demonstrated first time the link between the mPTP to mitochondrial dynamics. • The role of Cyclophilin D in the regulation of Drp1-mediated mitochondrial fission. • CsA as a potential target for governing oxidative stress related neuropathology.

Quercetin enhances adiponectin secretion by a PPAR-gamma independent mechanism

DEFF Research Database (Denmark)

Wein, Silvia; Behm, Norma; Petersen, Rasmus Koefoed

2010-01-01

To study possible insulin sensitizing, anti-inflammatory and anti-oxidative effects of the flavonol quercetin, rats were fed a high-fat diet (19%, w/w) with (HFQ) or without (HF) 0.03% quercetin or a flavonoid-poor low-fat (5%, w/w) maintenance diet (LF) over 4 weeks. Body weight was measured...... and WAT mRNA levels of adiponectin were elevated compared with the HF group, however, PPAR-gamma mRNA concentration in WAT was decreased (HFQ vs. HF). Compared to both other groups quercetin feeding significantly reduced oxidative stress, measured by plasma 8-iso-PGF(2alpha), while body weight gain, body...... composition and plasma leptin levels were not affected. Neither quercetin nor its metabolites induced PPAR-gamma-mediated transactivation in vitro. Adiponectin stimulating effects of quercetin are PPAR-gamma-independent and prevent impairment of insulin sensitivity without affecting body weight...

[Aging and metabolism: changes and regulation].

Science.gov (United States)

Ortiz, Genaro Gabriel; Arias-Merino, Elva D; Velázquez-Brizuela, Irma E; Pacheco-Moisés, Fermín P; Flores-Alvarado, Luis J; Torres-Sánchez, Erandis D; Cortés-Enríquez, Fernando; González-Renovato, Erika D; Ortiz-Velázquez, Irma G

2012-09-01

Studies about the effects of aging in the physiology and metabolism are increasingly, one of its objectives is to help implement programs to improve the quality of life and prevent disability in elderly. It is relevant to mention that, during aging, there is a natural metabolic deceleration, a series of changes in the regulation of energy are produced, which contributes to loss of weight and fat; the changes in the regulation of caloric intake contribute to increase the susceptibility to energy imbalance both positive and negative, which is associated with a deterioration in health. However, to grow old, is not a death sentence for metabolism, on the other hand, it can be controlled by maintaining an active lifestyle, coupled with this, research has shown that the metabolism'can be regulated by a synchronized clock (circadian rhythms), which is mediated by regulatory proteins, this relationship ensures the proper functioning of the cells and therefore good health. The aim of this review is to provide updated information on the energy- metabolism-regulation and its relationship with the great variety of components involved in energy expenditure that accompany aging, to analyze the regulation of this system to improve the quality of life and maintenance of health in old age.

Duplex formation between the sRNA DsrA and rpoS mRNA is not sufficient for efficient RpoS synthesis at low temperature

Czech Academy of Sciences Publication Activity Database

Hämmerle, H.; Večerek, Branislav; Resch, A.; Bläsi, U.

2013-01-01

Roč. 10, č. 12 (2013), s. 1834-1841 ISSN 1547-6286 Institutional support: RVO:61388971 Keywords : DsrA * Hfq * Riboregulation Subject RIV: EE - Microbiology, Virology Impact factor: 5.377, year: 2013 http://www.ncbi.nlm.nih.gov/pubmed/24448230

Contextualized Contribution of Kindness to Favorable Goal- and Circumstantial-Driven Neuropsychological Regulation

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Nayara Mota

2017-09-01

Full Text Available Kindness involves care and non-judgmental understanding toward someone. As a prosocial inclination, kindness would increase the possibility of favorable interaction with the environment, with a successful adjustment of one's response in novel or challenging circumstances, taking into account rules or goals. This adjustment ability is commonly referred to as executive functions, dependent on the prefrontal and parietal functioning, still under development during late adolescence. This study aimed to investigate if kindness would relate with the executive functions. If so, it would correlate more with measures of self-regulation, mainly dependent on the medial prefrontal corticosubcortical circuits. Also, among self-regulating processes, kindness would be more associated with autonomic responses—choices guided by one's understanding/intention - than with adaptive responses—changes on one's choices triggered by unfavorable circumstances. A sample of 46 (31 female; 18 to 21 years-old healthy college students from the University of the State of Rio de Janeiro attended a clinical interview and a comprehensive neuropsychological assessment. Kindness was measured by the Compassion Scale subscore. Generalized non-linear models for each neuropsychological variable were executed on R, followed by an estimation of weighted parameters for each factor. Significant models which included kindness (weighted parameter Pc > 74 and all of their psychosocial or sociodemographic factors on their maximum expression (Pc > 74 were identified. In a contextualized joint influence with other psychosocial and sociodemographic factors, kindness fits equally goal- and circumstantial- self-regulation, as well as integrative organization of information. Kindness is a principle that optimizes a refreshing and prosocial interaction with the environment. As it anticipates sharing and cooperation behaviors, it might have a primordial function on individual and social

75 FR 41017 - Political Contributions by Certain Investment Advisers

Science.gov (United States)

2010-07-14

... enterprise corruption and State securities fraud for selling access to management of public funds in return... Part IV Securities and Exchange Commission 17 CFR Part 275 Political Contributions by Certain... and Regulations#0;#0; [[Page 41018

Electromyogram refinement using muscle synergy based regulation of uncertain information.

Science.gov (United States)

Min, Kyuengbo; Shin, Duk; Lee, Jongho; Kakei, Shinji

2018-04-27

Electromyogram signal (EMG) measurement frequently experiences uncertainty attributed to issues caused by technical constraints such as cross talk and maximum voluntary contraction. Due to these problems, individual EMGs exhibit uncertainty in representing their corresponding muscle activations. To regulate this uncertainty, we proposed an EMG refinement, which refines EMGs with regulating the contribution redundancy of the signals from EMGs to approximating torques through EMG-driven torque estimation (EDTE) using the muscular skeletal forward dynamic model. To regulate this redundancy, we must consider the synergistic contribution redundancy of muscles, including "unmeasured" muscles, to approximating torques, which primarily causes redundancy of EDTE. To suppress this redundancy, we used the concept of muscle synergy, which is a key concept of analyzing the neurophysiological regulation of contribution redundancy of muscles to exerting torques. Based on this concept, we designed a muscle-synergy-based EDTE as a framework for EMG refinement, which regulates the abovementioned uncertainty of individual EMGs in consideration of unmeasured muscles. In achieving the proposed EMG refinement, the most considerable point is to suppress a large change such as overestimation attributed to enhancement of the contribution of particular muscles to estimating torques. Therefore it is reasonable to refine EMGs by minimizing the change in EMGs. To evaluate this model, we used a Bland-Altman plot, which quantitatively evaluates the proportional bias of refined signals to EMGs. Through this evaluation, we showed that the proposed EDTE minimizes the bias while approximating torques. Therefore this minimization optimally regulates the uncertainty of EMGs and thereby leads to optimal EMG refinement. Copyright © 2018 Elsevier Ltd. All rights reserved.

Structured association analysis leads to insight into Saccharomyces cerevisiae gene regulation by finding multiple contributing eQTL hotspots associated with functional gene modules.

Science.gov (United States)

Curtis, Ross E; Kim, Seyoung; Woolford, John L; Xu, Wenjie; Xing, Eric P

2013-03-21

Association analysis using genome-wide expression quantitative trait locus (eQTL) data investigates the effect that genetic variation has on cellular pathways and leads to the discovery of candidate regulators. Traditional analysis of eQTL data via pairwise statistical significance tests or linear regression does not leverage the availability of the structural information of the transcriptome, such as presence of gene networks that reveal correlation and potentially regulatory relationships among the study genes. We employ a new eQTL mapping algorithm, GFlasso, which we have previously developed for sparse structured regression, to reanalyze a genome-wide yeast dataset. GFlasso fully takes into account the dependencies among expression traits to suppress false positives and to enhance the signal/noise ratio. Thus, GFlasso leverages the gene-interaction network to discover the pleiotropic effects of genetic loci that perturb the expression level of multiple (rather than individual) genes, which enables us to gain more power in detecting previously neglected signals that are marginally weak but pleiotropically significant. While eQTL hotspots in yeast have been reported previously as genomic regions controlling multiple genes, our analysis reveals additional novel eQTL hotspots and, more interestingly, uncovers groups of multiple contributing eQTL hotspots that affect the expression level of functional gene modules. To our knowledge, our study is the first to report this type of gene regulation stemming from multiple eQTL hotspots. Additionally, we report the results from in-depth bioinformatics analysis for three groups of these eQTL hotspots: ribosome biogenesis, telomere silencing, and retrotransposon biology. We suggest candidate regulators for the functional gene modules that map to each group of hotspots. Not only do we find that many of these candidate regulators contain mutations in the promoter and coding regions of the genes, in the case of the Ribi group

A thermodynamic and theoretical view for enzyme regulation.

Science.gov (United States)

Zhao, Qinyi

2015-01-01

Precise regulation is fundamental to the proper functioning of enzymes in a cell. Current opinions about this, such as allosteric regulation and dynamic contribution to enzyme regulation, are experimental models and substantially empirical. Here we proposed a theoretical and thermodynamic model of enzyme regulation. The main idea is that enzyme regulation is processed via the regulation of abundance of active conformation in the reaction buffer. The theoretical foundation, experimental evidence, and experimental criteria to test our model are discussed and reviewed. We conclude that basic principles of enzyme regulation are laws of protein thermodynamics and it can be analyzed using the concept of distribution curve of active conformations of enzymes.

7 CFR 3015.51 - Acceptable contributions and costs.

Science.gov (United States)

2010-01-01

.... This includes allowable costs supported by non-Federal grants or by cash donations from non-Federal... 7 Agriculture 15 2010-01-01 2010-01-01 false Acceptable contributions and costs. 3015.51 Section... FINANCIAL OFFICER, DEPARTMENT OF AGRICULTURE UNIFORM FEDERAL ASSISTANCE REGULATIONS Cost-Sharing or Matching...

Dual Diathesis-Stressor Model of Emotional and Linguistic Contributions to Developmental Stuttering

Science.gov (United States)

Walden, Tedra A.; Frankel, Carl B.; Buhr, Anthony P.; Johnson, Kia N.; Conture, Edward G.; Karrass, Jan M.

2012-01-01

This study assessed emotional and speech-language contributions to childhood stuttering. A dual diathesis-stressor framework guided this study, in which both linguistic requirements and skills, and emotion and its regulation, are hypothesized to contribute to stuttering. The language diathesis consists of expressive and receptive language skills.…

Chemical regulators of plant hormones and their applications in basic research and agriculture.

Science.gov (United States)

Jiang, Kai; Asami, Tadao

2018-04-20

Plant hormones are small molecules that play versatile roles in regulating plant growth, development, and responses to the environment. Classic methodologies, including genetics, analytic chemistry, biochemistry, and molecular biology, have contributed to the progress in plant hormone studies. In addition, chemical regulators of plant hormone functions have been important in such studies. Today, synthetic chemicals, including plant growth regulators, are used to study and manipulate biological systems, collectively referred to as chemical biology. Here, we summarize the available chemical regulators and their contributions to plant hormone studies. We also pose questions that remain to be addressed in plant hormone studies and that might be solved with the help of chemical regulators.

Regulation of Autophagy by Glucose in Mammalian Cells

OpenAIRE

Moruno, Félix; Pérez-Jiménez, Eva; Knecht, Erwin

2012-01-01

Autophagy is an evolutionarily conserved process that contributes to maintain cell homeostasis. Although it is strongly regulated by many extracellular factors, induction of autophagy is mainly produced by starvation of nutrients. In mammalian cells, the regulation of autophagy by amino acids, and also by the hormone insulin, has been extensively investigated, but knowledge about the effects of other autophagy regulators, including another nutrient, glucose, is more limited. Here we will focu...

New Directions for Self-Regulation of Learning in Postsecondary Education

Science.gov (United States)

Bembenutty, Hefer

2011-01-01

This chapter highlights the major contributions of this volume on self-regulation of learning and provides new directions for cutting-edge theoretical and empirical work that could serve to facilitate self-regulation of learning in postsecondary education. "Self-regulation of learning" refers to learners' beliefs about their ability to engage in…

Massive contribution of transposable elements to mammalian regulatory sequences.

Science.gov (United States)

Rayan, Nirmala Arul; Del Rosario, Ricardo C H; Prabhakar, Shyam

2016-09-01

Barbara McClintock discovered the existence of transposable elements (TEs) in the late 1940s and initially proposed that they contributed to the gene regulatory program of higher organisms. This controversial idea gained acceptance only much later in the 1990s, when the first examples of TE-derived promoter sequences were uncovered. It is now known that half of the human genome is recognizably derived from TEs. It is thus important to understand the scope and nature of their contribution to gene regulation. Here, we provide a timeline of major discoveries in this area and discuss how transposons have revolutionized our understanding of mammalian genomes, with a special emphasis on the massive contribution of TEs to primate evolution. Our analysis of primate-specific functional elements supports a simple model for the rate at which new functional elements arise in unique and TE-derived DNA. Finally, we discuss some of the challenges and unresolved questions in the field, which need to be addressed in order to fully characterize the impact of TEs on gene regulation, evolution and disease processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Attentional and sensory contributions to postural sway in children with autism spectrum disorder

NARCIS (Netherlands)

Stins, J.F.; Emck, C.; de Vries, E.M.; Doop, S.; Beek, P.J.

2015-01-01

Postural control is known to depend on sensory and cognitive factors. Little is known about how children with autism spectrum disorder (ASD) regulate static balance, and to what extent vision and cognition contribute to the regulation of balance in this group. We compared a group of children with

EU Energy Market and Regulation enter a new Framework: Energy Union

International Nuclear Information System (INIS)

Sencar, M.

2015-01-01

Energy Union provides a new framework for market and regulation. This contribution discusses its main elements (dimensions), in particular energy market functioning. Energy Union adds some new focal points to its development, e.g. research and innovation, in addition to sustainability. Energy Union also aims at improving customers position on the market, and paves the way for efficiency enhancements in regulation and market monitoring at European level. Three aspects of potential future improvements are discussed how the existing Agency for the Cooperation of Energy Regulators may further contribute to the efficient market functioning and implementation of planned infrastructure investment. (author).

Epigenetic regulation of macrophage function

NARCIS (Netherlands)

Hoeksema, M.A.

2016-01-01

Atherosclerosis is a lipid-driven chronic inflammatory disorder with a key role for macrophages in all disease stages. Macrophages are involved as scavengers of lipids, regulate inflammation, attract other immune cells and contribute to the resolution of inflammation, fibrosis and plaque stability.

Regulations in radiation protection

International Nuclear Information System (INIS)

1986-01-01

On the occasion of the twenty fifth anniversary of the Dutch Society for Radiation Protection, a symposium was held about Regulations in Radiation Protection. The program consisted of six contributions of which four are included in this publication. The posters presented are published in NVS-nieuws, 1985, vol. 11(5). (G.J.P.)

Emotional Regulation in Young Adults with Internet Gaming Disorder

Directory of Open Access Journals (Sweden)

Ju-Yu Yen

2017-12-01

Full Text Available People diagnosed with Internet gaming disorder (IGD have been frequently reported to experience depression, anxiety, and hostility. Emotional regulation contributes to these mood symptoms. This study evaluated emotional regulation in subjects with IGD and examined relationships between emotional regulation, depression, anxiety, and hostility in young adults with IGD. We recruited 87 people with IGD and a control group of 87 people without a history of IGD. All participants underwent a diagnostic interview based on the IGD criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and they completed a questionnaire on emotional regulation, depression, anxiety, and hostility. We found that subjects with IGD were less likely to practice cognitive reappraisal and were more likely to suppress their emotions. Linear regression revealed the higher cognitive reappraisal and lower expressive suppression associated with depression, anxiety, and hostility among subjects with IGD. The emotional regulation strategies that characterize those with IGD could be contributing factors to the depression and hostility tendencies of these people. When treating patients with IGD, in addition to providing appropriate interventions to relieve depression and hostility, practitioners should effectively assess emotional regulation strategies and provide emotional regulation therapy to prevent a vicious cycle of negative emotions.

Emotional Regulation in Young Adults with Internet Gaming Disorder.

Science.gov (United States)

Yen, Ju-Yu; Yeh, Yi-Chun; Wang, Peng-Wei; Liu, Tai-Ling; Chen, Yun-Yu; Ko, Chih-Hung

2017-12-25

People diagnosed with Internet gaming disorder (IGD) have been frequently reported to experience depression, anxiety, and hostility. Emotional regulation contributes to these mood symptoms. This study evaluated emotional regulation in subjects with IGD and examined relationships between emotional regulation, depression, anxiety, and hostility in young adults with IGD. We recruited 87 people with IGD and a control group of 87 people without a history of IGD. All participants underwent a diagnostic interview based on the IGD criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and they completed a questionnaire on emotional regulation, depression, anxiety, and hostility. We found that subjects with IGD were less likely to practice cognitive reappraisal and were more likely to suppress their emotions. Linear regression revealed the higher cognitive reappraisal and lower expressive suppression associated with depression, anxiety, and hostility among subjects with IGD. The emotional regulation strategies that characterize those with IGD could be contributing factors to the depression and hostility tendencies of these people. When treating patients with IGD, in addition to providing appropriate interventions to relieve depression and hostility, practitioners should effectively assess emotional regulation strategies and provide emotional regulation therapy to prevent a vicious cycle of negative emotions.

Nuclear translocation contributes to regulation of DNA excision repair activities

DEFF Research Database (Denmark)

Knudsen, Nina Østergaard; Andersen, Sofie Dabros; Lützen, Anne

2009-01-01

for regulation of nuclear import that is necessary for proper localization of the repair proteins. This review summarizes the current knowledge on nuclear import mechanisms of DNA excision repair proteins and provides a model that categorizes the import by different mechanisms, including classical nuclear import......DNA mutations are circumvented by dedicated specialized excision repair systems, such as the base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR) pathways. Although the individual repair pathways have distinct roles in suppressing changes in the nuclear DNA......, it is evident that proteins from the different DNA repair pathways interact [Y. Wang, D. Cortez, P. Yazdi, N. Neff, S.J. Elledge, J. Qin, BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures, Genes Dev. 14 (2000) 927-939; M. Christmann, M...

Volume regulated anion channel currents of rat hippocampal neurons and their contribution to oxygen-and-glucose deprivation induced neuronal death.

Directory of Open Access Journals (Sweden)

Huaqiu Zhang

2011-02-01

Full Text Available Volume-regulated anion channels (VRAC are widely expressed chloride channels that are critical for the cell volume regulation. In the mammalian central nervous system, the physiological expression of neuronal VRAC and its role in cerebral ischemia are issues largely unknown. We show that hypoosmotic medium induce an outwardly rectifying chloride conductance in CA1 pyramidal neurons in rat hippocampal slices. The induced chloride conductance was sensitive to some of the VRAC inhibitors, namely, IAA-94 (300 µM and NPPB (100 µM, but not to tamoxifen (10 µM. Using oxygen-and-glucose deprivation (OGD to simulate ischemic conditions in slices, VRAC activation appeared after OGD induced anoxic depolarization (AD that showed a progressive increase in current amplitude over the period of post-OGD reperfusion. The OGD induced VRAC currents were significantly inhibited by inhibitors for glutamate AMPA (30 µM NBQX and NMDA (40 µM AP-5 receptors in the OGD solution, supporting the view that induction of AD requires an excessive Na(+-loading via these receptors that in turn to activate neuronal VRAC. In the presence of NPPB and DCPIB in the post-OGD reperfusion solution, the OGD induced CA1 pyramidal neuron death, as measured by TO-PRO-3-I staining, was significantly reduced, although DCPIB did not appear to be an effective neuronal VRAC blocker. Altogether, we show that rat hippocampal pyramidal neurons express functional VRAC, and ischemic conditions can initial neuronal VRAC activation that may contribute to ischemic neuronal damage.

Unique contributions of emotion regulation and executive functions in predicting the quality of parent-child interaction behaviors.

Science.gov (United States)

Shaffer, Anne; Obradović, Jelena

2017-03-01

Parenting is a cognitive, emotional, and behavioral endeavor, yet limited research investigates parents' executive functions and emotion regulation as predictors of how parents interact with their children. The current study is a multimethod investigation of parental self-regulation in relation to the quality of parenting behavior and parent-child interactions in a diverse sample of parents and kindergarten-age children. Using path analyses, we tested how parent executive functions (inhibitory control) and lack of emotion regulation strategies uniquely relate to both sensitive/responsive behaviors and positive/collaborative behaviors during observed interaction tasks. In our analyses, we accounted for parent education, financial stress, and social support as socioeconomic factors that likely relate to parent executive function and emotion regulation skills. In a diverse sample of primary caregivers (N = 102), we found that direct assessment of parent inhibitory control was positively associated with sensitive/responsive behaviors, whereas parent self-reported difficulties in using emotion regulation strategies were associated with lower levels of positive and collaborative dyadic behaviors. Parent education and financial stress predicted inhibitory control, and social support predicted emotion regulation difficulties; parent education was also a significant predictor of sensitive/responsive behaviors. Greater inhibitory control skills and fewer difficulties identifying effective emotion regulation strategies were not significantly related in our final path model. We discuss our findings in the context of current and emerging parenting interventions. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

How do different components of Effortful Control contribute to children's mathematics achievement?

Science.gov (United States)

Sánchez-Pérez, Noelia; Fuentes, Luis J; Pina, Violeta; López-López, Jose A; González-Salinas, Carmen

2015-01-01

This work sought to investigate the specific contribution of two different components of Effortful Control (EC) -attentional focusing (AF) and inhibitory control- to children's mathematics achievement. The sample was composed of 142 children aged 9-12 year-old. EC components were measured through the Temperament in Middle Childhood Questionnaire (TMCQ; parent's report); math achievement was measured via teacher's report and through the standard Woodcock-Johnson test. Additionally, the contribution of other cognitive and socio-emotional processes was taken into account. Our results showed that only AF significantly contributed to the variance of children's mathematics achievement; interestingly, mediational models showed that the relationship between effortful attentional self-regulation and mathematics achievement was mediated by academic peer popularity, as well as by intelligence and study skills. Results are discussed in the light of the current theories on the role of children's self-regulation abilities in the context of school.

Sex Differences and Emotion Regulation: An Event-Related Potential Study

OpenAIRE

Gardener, Elyse K. T.; Carr, Andrea R.; MacGregor, Amy; Felmingham, Kim L.

2013-01-01

Difficulties in emotion regulation have been implicated as a potential mechanism underlying anxiety and mood disorders. It is possible that sex differences in emotion regulation may contribute towards the heightened female prevalence for these disorders. Previous fMRI studies of sex differences in emotion regulation have shown mixed results, possibly due to difficulties in discriminating the component processes of early emotional reactivity and emotion regulation. The present study used event...

Seminar for Master's Thesis Projects: Promoting Students' Self-Regulation

Science.gov (United States)

Miedijensky, Shirley; Lichtinger, Einat

2016-01-01

This study presents a thesis seminar model aimed at promoting students' self-regulation. Students' perceptions regarding the contribution of the seminar to their learning process were characterized and the seminar's effect upon their self-regulation expressions was examined. Data was collected using questionnaires and analyzed thematically. The…

Phosphatidyl inositol 3-kinase signaling in hypothalamic proopiomelanocortin neurons contributes to the regulation of glucose homeostasis.

Science.gov (United States)

Hill, Jennifer W; Xu, Yong; Preitner, Frederic; Fukuda, Makota; Cho, You-Ree; Luo, Ji; Balthasar, Nina; Coppari, Roberto; Cantley, Lewis C; Kahn, Barbara B; Zhao, Jean J; Elmquist, Joel K

2009-11-01

Recent studies demonstrated a role for hypothalamic insulin and leptin action in the regulation of glucose homeostasis. This regulation involves proopiomelanocortin (POMC) neurons because suppression of phosphatidyl inositol 3-kinase (PI3K) signaling in these neurons blunts the acute effects of insulin and leptin on POMC neuronal activity. In the current study, we investigated whether disruption of PI3K signaling in POMC neurons alters normal glucose homeostasis using mouse models designed to both increase and decrease PI3K-mediated signaling in these neurons. We found that deleting p85alpha alone induced resistance to diet-induced obesity. In contrast, deletion of the p110alpha catalytic subunit of PI3K led to increased weight gain and adipose tissue along with reduced energy expenditure. Independent of these effects, increased PI3K activity in POMC neurons improved insulin sensitivity, whereas decreased PI3K signaling resulted in impaired glucose regulation. These studies show that activity of the PI3K pathway in POMC neurons is involved in not only normal energy regulation but also glucose homeostasis.

Risk-informed regulation

International Nuclear Information System (INIS)

Hoffman, D.R.

2003-01-01

In assessing safety for nuclear facilities, regulators have traditionally used a deterministic approach. New techniques for assessing nuclear or radiological risks make it possible for regulators to incorporate risk insights into their regulations. By 'risk-informing' the regulatory processes, independent bodies tasked with protecting the health and safety of the public can focus on those design and operational issues most important to safety. Such an approach is a move away from prescriptive regulations that were based on conservative engineering judgments toward regulations focused on issues that contribute significantly to safety. Despite the availability of probabilistic risk assessment (PRA) tools, organisations often struggle with how to best use this capability. Most international regulations are still based largely on deterministic analyses that were developed without the benefit of quantitative or measurable estimates of risk. PRA considers issues of risk in a more comprehensive manner by examining a wider spectrum of initiating events and their frequency, and considers the likelihood of events in a rigorous and comprehensive manner. In some countries, nuclear regulators are actively moving toward increasing the use of risk insights in a variety of strategic arenas, including risk-informed technical specifications (operating limits and conditions), in-service inspection and testing, programs, and assessment and enforcement actions. A risk-informed approach enhances the traditional deterministic approach by explicitly considering a broader range of safety challenges, focusing resources on the basis of risk significance, considering a broader range of counter measures to mitigate challenges, and explicitly identifying and quantifying uncertainties in analyses. (author)

Procedural problems in phase-out regulations in nuclear law

International Nuclear Information System (INIS)

Kloepfer, Michael

2012-01-01

The contribution discusses the legal regulations accompanying German nuclear policy during the past twelve years. There were several radical changes in 2002, 2010, and 2011 which reflect the opinions of the then German governments; some of these regulations, according to the author, were not compatible with German constitutional law.

How do different components of Effortful Control contribute to children's mathematics achievement?

Directory of Open Access Journals (Sweden)

Noelia eSánchez-Pérez

2015-09-01

Full Text Available This work sought to investigate the specific contribution of two different components of Effortful Control -attentional focusing and inhibitory control- to children’s mathematics achievement. The sample was composed of 142 children aged 9 to 12 years old. Effortful Control components were measured through the Temperament in Middle Childhood Questionnaire (TMCQ; parent´s report; math achievement was measured via teacher’s report and through the standard Woodcock-Johnson test. Additionally, the contribution of other cognitive and socio-emotional processes was taken into account. Our results showed that only attentional focusing significantly contributed to the variance of children’s mathematics achievement; interestingly, mediational models showed that the relationship between effortful attentional self-regulation and mathematics achievement was mediated by academic peer popularity, as well as by intelligence and study skills. Results are discussed in the light of the current theories on the role of children’ self-regulation abilities in the context of school.

Linking Maternal Warmth and Responsiveness to Children's Self-Regulation

Science.gov (United States)

von Suchodoletz, Antje; Trommsdorff, Gisela; Heikamp, Tobias

2011-01-01

The present study demonstrated that a more differentiated view of positive parenting practices is necessary in the study of children's acquisition of self-regulation. Here, the unique contributions of maternal warmth and responsiveness to distress to children's self-regulation were tested in a sample of 102 German mothers and their kindergarten…

The Root Hair Specific SYP123 Regulates the Localization of Cell Wall Components and Contributes to Rizhobacterial Priming of Induced Systemic Resistance

Directory of Open Access Journals (Sweden)

Cecilia Rodriguez-Furlán

2016-07-01

Full Text Available Root hairs are important for nutrient and water uptake and are also critically involved the interaction with soil inhabiting microbiota. Root hairs are tubular-shaped outgrowths that emerge from trichoblasts. This polarized elongation is maintained and regulated by a robust mechanism involving the endomembrane secretory and endocytic system. Members of the syntaxin family of SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptor in plants (SYP, have been implicated in regulation of the fusion of vesicles with the target membranes in both exocytic and endocytic pathways. One member of this family, SYP123, is expressed specifically in the root hairs and accumulated in the growing tip region. This study shows evidence of the SYP123 role in polarized trafficking using knockout insertional mutant plants. We were able to observe defects in the deposition of cell wall proline rich protein PRP3 and cell wall polysaccharides. In a complementary strategy, similar results were obtained using a plant expressing a dominant negative soluble version of SYP123 (SP2 fragment lacking the transmembrane domain. The evidence presented indicates that SYP123 is also regulating PRP3 protein distribution by recycling by endocytosis. We also present evidence that indicates that SYP123 is necessary for the response of roots to plant growth promoting rhizobacterium (PGPR in order to trigger trigger induced systemic response (ISR. Plants with a defective SYP123 function were unable to mount a systemic acquired resistance (SAR in response to bacterial pathogen infection and induced systemic resistance (ISR upon interaction with rhizobacteria. These results indicated that SYP123 was involved in the polarized localization of protein and polysaccharides in growing root hairs and that this activity also contributed to the establishment of effective plant defense responses. Root hairs represent very plastic structures were many biotic and abiotic factors

Entry: direct control or regulation?

NARCIS (Netherlands)

Perotti, E.; Vorage, M.

2009-01-01

We model a setting in which citizens form coalitions to seek preferential entry to a given market. The lower entry the higher firm profits and political contributions, but the lower social welfare. Politicians choose to either control entry directly and be illegally bribed, or regulate entry using a

Contribution of Neuroepigenetics to Huntington?s Disease

OpenAIRE

Francelle, Laetitia; Lotz, Caroline; Outeiro, Tiago; Brouillet, Emmanuel; Merienne, Karine

2017-01-01

Unbalanced epigenetic regulation is thought to contribute to the progression of several neurodegenerative diseases, including Huntington’s disease (HD), a genetic disorder considered as a paradigm of epigenetic dysregulation. In this review, we attempt to address open questions regarding the role of epigenetic changes in HD, in the light of recent advances in neuroepigenetics. We particularly discuss studies using genome-wide scale approaches that provide insights into the rela...

Emotion regulation and psychological problems among Indian college youth

Directory of Open Access Journals (Sweden)

T P Lavanya

2017-01-01

Full Text Available Background: Study of emotion regulation strategies used by youth becomes necessary in the background of the high prevalence of emotional disorders in this population. This study examined emotion regulation and psychological problems among college youth as well as the relationship between the two. Methodology: Four hundred and nineteen students, who were divided into two groups (older adolescents, aged 16-17 years - group 1, n = 217; young adults aged 18-25 years - group 2, n = 202 participated in this exploratory study. Results: Predominantly positive emotion regulation strategies were used by group 1 (positive refocusing, refocus on planning, and positive reappraisal, respectively. The sample as a whole used more positive strategies (positive refocusing: 82% and 64% and refocus on planning: 93% and 87% in groups 1 and 2, respectively. Significant correlations between emotion regulation strategies (CERQ and psychological problems (YSR/YASR were found, thereby indicating that negative emotion regulation strategies were associated with psychological problems and vice versa. Females were found to have more of anxiety problems as opposed to males with more of conduct problems. However with increase in age, increase in the percentage of psychological problems and usage of negative emotion regulation strategies was observed. Conclusion: The findings of the present study contribute to understanding the patterns of emotion regulation in various emotional disorders. Findings could also contribute to developing an intervention program to help students having difficulty in regulation of their emotions.

Effects of regulation on drug launch and pricing in interdependent markets.

Science.gov (United States)

Danzon, Patricia M; Epstein, Andrew J

2012-01-01

This study examines the effect of price regulation and competition on launch timing and pricing of new drugs. Our data cover launch experience in 15 countries from 1992 to 2003 for drugs in 12 major therapeutic classes. We estimate a two-equation model of launch hazard and launch price of new drugs. We find that launch timing and prices of new drugs are related to a country's average prices of established products in a class. Thus to the extent that price regulation reduces price levels, such regulation directly contributes to launch delay in the regulating country. Regulation by external referencing, whereby high-price countries reference low-price countries, also has indirect or spillover effects, contributing to launch delay and higher launch prices in low-price referenced countries. Referencing policies adopted in high-price countries indirectly impose welfare loss on low-price countries. These findings have implications for US proposals to constrain pharmaceutical prices through external referencing and drug importation.

Corporate Governance Convergence : Evidence from Takeover Regulation Reforms in Europe

NARCIS (Netherlands)

Goergen, M.; Martynova, M.; Renneboog, L.D.R.

2005-01-01

This paper contributes to the research on corporate governance by predicting the effects of European takeover regulation.In particular, we investigate whether the recent reforms of takeover regulation in Europe are leading to a harmonization of the national legislations.With the help of 150

Serine racemase is expressed in islets and contributes to the regulation of glucose homeostasis.

Science.gov (United States)

Lockridge, Amber D; Baumann, Daniel C; Akhaphong, Brian; Abrenica, Alleah; Miller, Robert F; Alejandro, Emilyn U

2016-11-01

NMDA receptors (NMDARs) have recently been discovered as functional regulators of pancreatic β-cell insulin secretion. While these excitatory receptor channels have been extensively studied in the brain for their role in synaptic plasticity and development, little is known about how they work in β-cells. In neuronal cells, NMDAR activation requires the simultaneous binding of glutamate and a rate-limiting co-agonist, such as D-serine. D-serine levels and availability in most of the brain rely on endogenous synthesis by the enzyme serine racemase (Srr). Srr transcripts have been reported in human and mouse islets but it is not clear whether Srr is functionally expressed in β-cells or what its role in the pancreas might be. In this investigation, we reveal that Srr protein is highly expressed in primary human and mouse β-cells. Mice with whole body deletion of Srr (Srr KO) show improved glucose tolerance through enhanced insulin secretory capacity, possibly through Srr-mediated alterations in islet NMDAR expression and function. We observed elevated insulin sensitivity in some animals, suggesting Srr metabolic regulation in other peripheral organs as well. Srr expression in neonatal and embryonic islets, and adult deficits in Srr KO pancreas weight and islet insulin content, point toward a potential role for Srr in pancreatic development. These data reveal the first evidence that Srr may regulate glucose homeostasis in peripheral tissues and provide circumstantial evidence that D-serine may be an endogenous islet NMDAR co-agonist in β-cells.

78 FR 22036 - Proposed Collection; Comment Request for Regulation Project

Science.gov (United States)

2013-04-12

... fair market value of the underlying property before and after the donation and (2) the conservation... qualified conservation contributions (Sec. 1.170A-14). DATES: Written comments should be received on or... INFORMATION: Title: Qualified Conservation Contributions. OMB Number: 1545-0763. Regulation Project Number: TD...

Ex Post Regulation as the Method of Sectoral Regulation in Electricity Sector

Directory of Open Access Journals (Sweden)

Rafał Nagaj

2017-10-01

Full Text Available Aim/purpose - The aim of the article is to present the essence of ex post approach to sectoral regulation, to show the advantages and disadvantages of ex post regulation and to answer the question whether it is worth using in the electricity sector. Design/methodology/approach - For this purpose, a critical analysis of expert literature was made and an empirical analysis of countries that have applied ex post regulation in the electricity sector in the European Union. Two research methods were used: a case study and a comparison of changes in price and quality of services. The research period covered the period 2000-2016. Findings - It was found that ex post regulation reduces regulatory costs, does not adversely affect the quality of service and long-term rates, gives businesses the freedom of decision-making and the ability to react quickly to changes in the economy. The main disadvantages of ex post regulation are the tendency for companies to over-estimate bills for consumers, the difficulty of pursuing claims by consumers and the need to shift regulatory risk to consumers. Research implications/limitations - In the paper there was identified a research gap, i.e. the effects of ex post regulation in the electricity sector in European Union countries where such regulation was applied. Identifying the research gap will help us understand what are the advantages and disadvantages of ex post regulation and will create a model for when it is good moment to implement this in the economy. Besides identifying the research gap, further studies will be required over ex post regulation. Originality/value/contribution - The additional value of the paper is the study of ex post regulation, its essence and types. The article analyzed the effects of ex post regulation in the electricity sector and provided valuable insights into the potential risks associated with this approach to economic regulation.

Dual function of the McaS small RNA in controlling biofilm formation

DEFF Research Database (Denmark)

Jørgensen, Mikkel Girke; Thomason, Maureen K.; Havelund, Johannes

2013-01-01

, and biofilm formation. Moreover, ectopic McaS expression leads to induction of two additional CsrA-repressed genes encoding diguanylate cyclases. Collectively, our study shows that McaS is a dual-function sRNA with roles in the two major post-transcriptional regulons controlled by the RNA-binding proteins Hfq...

Structural Genomics of Bacterial Virulence Factors

Science.gov (United States)

2006-05-01

Moller, T., T. Franch , P. Hojrup, D.R. Keene, H.P. Bachinger, R.G. Brennan, and P. Valentin-Hansen. 2002. Hfq: a bacterial Sm-like protein that...level, an unre- sponsiveness to external stimuli, or an inability to obtain readily available food or water, along with any of the following accompa

20 CFR 222.42 - When employee is contributing to support.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false When employee is contributing to support. 222.42 Section 222.42 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT FAMILY RELATIONSHIPS Relationship as Parent, Grandchild, Brother or Sister § 222.42 When...

Emotion regulation in mothers and young children faced with trauma.

Science.gov (United States)

Pat-Horenczyk, Ruth; Cohen, S; Ziv, Y; Achituv, M; Asulin-Peretz, L; Blanchard, T R; Schiff, M; Brom, D

2015-01-01

The present study investigated maternal emotion regulation as mediating the association between maternal posttraumatic stress symptoms and children's emotional dysregulation in a community sample of 431 Israeli mothers and children exposed to trauma. Little is known about the specific pathways through which maternal posttraumatic symptoms and deficits in emotion regulation contribute to emotional dysregulation. Inspired by the intergenerational process of relational posttraumatic stress disorder (PTSD), in which posttraumatic distress is transmitted from mothers to children, we suggest an analogous concept of relational emotion regulation, by which maternal emotion regulation problems may contribute to child emotion regulation deficits. Child emotion regulation problems were measured using the Child Behavior Checklist-Dysregulation Profile (CBCL-DP; T.M. Achenbach & I. Rescorla, 2000), which is comprised of three subscales of the CBCL: Attention, Aggression, and Anxiety/Depression. Maternal PTSD symptoms were assessed by the Posttraumatic Diagnostic Scale (E.B. Foa, L. Cashman, L. Jaycox, & K. Perry, 1997) and maternal emotion regulation by the Difficulties in Emotion Regulation Scale (K.L. Gratz & L. Roemer, 2004). Results showed that the child's emotion regulation problems were associated with both maternal posttraumatic symptoms and maternal emotion dysregulation. Further, maternal emotion regulation mediated the association between maternal posttraumatic symptoms and the child's regulation deficits. These findings highlight the central role of mothers' emotion regulation skills in the aftermath of trauma as it relates to children's emotion regulation skills. The degree of mothers' regulatory skills in the context of posttraumatic stress symptoms reflects a key process through which the intergenerational transmission of trauma may occur. Study results have critical implications for planning and developing clinical interventions geared toward the treatment of

Contribution of organic farming to public goods in Denmark

DEFF Research Database (Denmark)

Jespersen, Lizzie Melby; Baggesen, Dorte Lau; Fog, Erik

2017-01-01

€”in particular in relation to the public goods Energy and Climate, which at present are not addressed in the EU Organic Regulation. Moreover, some organic farming requirements and practices cause dilemmas; e.g. more space per animal and outdoor access improves Animal Health and Welfare but at the same time has......The potential contribution of organic farming to the public goods, ‘Nature and Biodiversity’, ‘Environment’, ‘Energy and Climate’, ‘Human Health and Welfare’ and ‘Animal Health and Welfare’ in Denmark is guided and partly secured by the principles and specific requirements...... of the EU Organic Regulation. However, other factors, such as the production type, farm size, geographical location and—not the least—the management of the farm, also influence the contribution. Using the ban on synthetic pesticides and restricted use of antibiotics, including the requirements...

Is there a hard gluonic contribution to the first moment of g1?

International Nuclear Information System (INIS)

Bodwin, G.T.; Qiu, Jianwei

1990-01-01

We show that the size of the hard gluonic contribution to the first moment of the proton's spin-dependent structure function g 1 is entirely a matter of the convention used in defining the quark distributions. If the UV regulator for the spin-dependent quark distributions respects the gauge invariance of Green's functions (allows shifts of loop momenta) and respects the analyticity structure of the unregulated distributions, then the hard gluonic contribution to the first moment of g 1 vanishes. This is the case, for example, in dimensional regularization. By relaxing the requirement that the regulator allow shifts of loop moments, we are able to obtain a nonvanishing hard gluonic contribution to the first moment of g 1 . However, the first moments of the resulting quark distributions correspond to matrix elements that are either gauge variant or involve nonlocal operators and, hence, have no analogue in the standard operator-product expansion. 11 refs., 2 figs

How do different components of Effortful Control contribute to children’s mathematics achievement?

Science.gov (United States)

Sánchez-Pérez, Noelia; Fuentes, Luis J.; Pina, Violeta; López-López, Jose A.; González-Salinas, Carmen

2015-01-01

This work sought to investigate the specific contribution of two different components of Effortful Control (EC) -attentional focusing (AF) and inhibitory control- to children’s mathematics achievement. The sample was composed of 142 children aged 9–12 year-old. EC components were measured through the Temperament in Middle Childhood Questionnaire (TMCQ; parent’s report); math achievement was measured via teacher’s report and through the standard Woodcock–Johnson test. Additionally, the contribution of other cognitive and socio-emotional processes was taken into account. Our results showed that only AF significantly contributed to the variance of children’s mathematics achievement; interestingly, mediational models showed that the relationship between effortful attentional self-regulation and mathematics achievement was mediated by academic peer popularity, as well as by intelligence and study skills. Results are discussed in the light of the current theories on the role of children’s self-regulation abilities in the context of school. PMID:26441758

Understanding purposes of regulation: a case example in mental health.

Science.gov (United States)

Ziegenfuss, J T; Hadley, T

1980-01-01

This paper reviews the purposes of governmental regulation and how an exploration of purpose can contribute to our understanding of specific regulations. The primary regulatory purpose is defined as the achievement of quality control of a subject system, its process or its product. Quality control via regulation is achieved through one or a combination of approaches: (1) accountability, (2) organizational development, (3) protectionism. Regulatory purpose and approach is illustrated by a case example of the development of regulations for partial hospitalization mental health services.

Regulation of Membrane-Type 4 Matrix Metalloproteinase by SLUG Contributes to Hypoxia-Mediated Metastasis

Directory of Open Access Journals (Sweden)

Chi-Hung Huang

2009-12-01

Full Text Available The hypoxic tumor environment has been shown to be critical to cancer metastasis through the promotion of angiogenesis, induction of epithelial-mesenchymal transition (EMT, and acquisition of invasive potential. However, the impact of hypoxia on the expression profile of the proteolytic enzymes involved in invasiveness is relatively unknown. Membrane-type 4 matrix metalloproteinase (MT4-MMP is a glycosyl-phosphatidyl inositol-anchored protease that has been shown to be overexpressed in human cancers. However, detailed mechanisms regarding the regulation and function of MT4-MMP expression in tumor cells remain unknown. Here, we demonstrate that hypoxia or overexpression of hypoxia-inducible factor-1α (HIF-1α induced MT4-MMP expression in human cancer cells. Activation of SLUG, a transcriptional factor regulating the EMT process of human cancers, by HIF-1α was critical for the induction of MT4-MMP under hypoxia. SLUG regulated the transcription of MT4-MMP through direct binding to the E-box located in its proximal promoter. Short-interference RNA-mediated knockdown of MT4-MMP attenuated in vitro invasiveness and in vivo pulmonary colonization of tumor cells without affecting cell migratory ability. MT4-MMP promoted invasiveness and pulmonary colonization through modulation of the expression profile of MMPs and angiogenic factors. Finally, coexpression of HIF-1α and MT4-MMP in human head and neck cancer was predictive of a worse clinical outcome. These findings establish a novel signaling pathway for hypoxia-mediated metastasis and elucidate the underlying regulatory mechanism and functional significance of MT4-MMP in cancer metastasis.

Down-regulation of vascular PPAR-γ contributes to endothelial dysfunction in high-fat diet-induced obese mice exposed to chronic intermittent hypoxia.

Science.gov (United States)

Zhang, Yanan; Zhang, Chunlian; Li, Haiou; Hou, Jingdong

2017-10-14

Obstructive sleep apnea (OSA), characterized by chronic intermittent hypoxia (CIH), is associated with endothelial dysfunction. The prevalence of OSA is linked to an epidemic of obesity. CIH has recently been reported to cause endothelial dysfunction in diet-induced obese animals by exaggerating oxidative stress and inflammation, but the underlying mechanism remains unclear. PPAR-γ, a ligand-inducible transcription factor that exerts anti-oxidant and anti-inflammatory effects, is down-regulated in the peripheral tissues in diet-induce obesity. We tested the hypothesis that down-regulation of vascular PPAR-γ in diet-induced obesity enhances inflammation and oxidative stress in response to CIH, resulting in endothelial dysfunction. Male C57BL/6 mice were fed either a high-fat diet (HFD) or a low-fat diet (LFD) and simultaneously exposed to CIH or intermittent air for 6 weeks. An additional HFD group received a combination of CIH and PPAR-γ agonist pioglitazone for 6 weeks. Endothelial-dependent vasodilation was impaired only in HFD group exposed to CIH, compared with other groups, but was restored by concomitant pioglitazone treatment. Molecular studies revealed that vascular PPAR-γ expression and activity were reduced in HFD groups, compared with LFD groups, but were reversed by pioglitazone treatment. In addition, CIH elevated vascular expression of NADPH oxidase 4 and dihydroethidium fluorescence, and increased expression of proinflammatory cytokines TNF-α and IL-1β in both LFD and HFD groups, but these increases was significantly greater in HFD group, along with decreased vascular eNOS activity. Pioglitazone treatment of HFD group prevented CIH-induced changes in above molecular markers. The results suggest that HFD-induced obesity down-regulates vascular PPAR-γ, which results in exaggerated oxidative stress and inflammation in response to CIH, contributing to endothelial dysfunction. This finding may provide new insights into the mechanisms by which OSA

Down-regulation of cellular FLICE-inhibitory protein (Long Form contributes to apoptosis induced by Hsp90 inhibition in human lung cancer cells

Directory of Open Access Journals (Sweden)

Wang Qilin

2012-12-01

Full Text Available Abstract Background Cellular FLICE-Inhibitory Protein (long form, c-FLIPL is a critical negative regulator of death receptor-mediated apoptosis. Overexpression of c-FLIPL has been reported in many cancer cell lines and is associated with chemoresistance. In contrast, down-regulation of c-FLIP may drive cancer cells into cellular apoptosis. This study aims to demonstrate that inhibition of the heat shock protein 90 (Hsp90 either by inhibitors geldanamycin/17-N-Allylamino-17-demethoxygeldanamycin (GA/17-AAG or siRNA technique in human lung cancer cells induces c-FLIPL degradation and cellular apoptosis through C-terminus of Hsp70-interacting protein (CHIP-mediated mechanisms. Methods Calu-1 and H157 cell lines (including H157-c-FLIPL overexpressing c-FLIPL and control cell H157-lacZ were treated with 17-AAG and the cell lysates were prepared to detect the given proteins by Western Blot and the cell survival was assayed by SRB assay. CHIP and Hsp90 α/β proteins were knocked down by siRNA technique. CHIP and c-FLIPL plasmids were transfected into cells and immunoprecipitation experiments were performed to testify the interactions between c-FLIPL, CHIP and Hsp90. Results c-FLIPL down-regulation induced by 17-AAG can be reversed with the proteasome inhibitor MG132, which suggested that c-FLIPL degradation is mediated by a ubiquitin-proteasome system. Inhibition of Hsp90α/β reduced c-FLIPL level, whereas knocking down CHIP expression with siRNA technique inhibited c-FLIPL degradation. Furthermore, c-FLIPL and CHIP were co-precipitated in the IP complexes. In addition, overexpression of c-FLIPL can rescue cancer cells from apoptosis. When 17-AAG was combined with an anti-cancer agent celecoxib(CCB, c-FLIPL level declined further and there was a higher degree of caspase activation. Conclusion We have elucidated c-FLIPL degradation contributes to apoptosis induced by Hsp90 inhibition, suggesting c-FLIP and Hsp90 may be the promising combined targets

Vinculin contributes to Cell Invasion by Regulating Contractile Activation

Science.gov (United States)

Mierke, Claudia Tanja

2008-07-01

Vinculin is a component of the focal adhesion complex and is described as a mechano-coupling protein connecting the integrin receptor and the actin cytoskeleton. Vinculin knock-out (k.o.) cells (vin-/-) displayed increased migration on a 2-D collagen- or fibronectin-coated substrate compared to wildtype cells, but the role of vinculin in cell migration through a 3-D connective tissue is unknown. We determined the invasiveness of established tumor cell lines using a 3-D collagen invasion assay. Gene expression analysis of 4 invasive and 4 non-invasive tumor cell lines revealed that vinculin expression was significantly increased in invasive tumor cell lines. To analyze the mechanisms by which vinculin increased cell invasion in a 3-D gel, we studied mouse embryonic fibroblasts wildtype and vin-/- cells. Wildtype cells were 3-fold more invasive compared vin-/- cells. We hypothesized that the ability to generate sufficient traction forces is a prerequisite for tumor cell migration in a 3-D connective tissue matrix. Using traction microscopy, we found that wildtype exerted 3-fold higher tractions on fibronectin-coated polyacrylamide gels compared to vin-/- cells. These results show that vinculin controls two fundamental functions that lead to opposite effects on cell migration in a 2-D vs. a 3-D environment: On the one hand, vinculin stabilizes the focal adhesions (mechano-coupling function) and thereby reduces motility in 2-D. On the other hand, vinculin is also a potent activator of traction generation (mechano-regulating function) that is important for cell invasion in a 3-D environment.

Audit Risk Assessment in the Light of Current European Regulations

OpenAIRE

Ciprian-Costel Munteanu

2015-01-01

Recent European reforms on audit regulations have been motivated by efforts to increase audit quality, functioning and performance. We believe the adoption of Directive 2014/56 and Regulation 537/2014 strengthened the role of independent audit and risk committees, which will positively contribute towards audit quality. This paper aims to critically assess the status quo of audit risk assessment in current European standards and regulations, by conducting a theoretical analysis of different as...

Lymphotoxin organizes contributions to host defense and metabolic illness from innate lymphoid cells.

Science.gov (United States)

Upadhyay, Vaibhav; Fu, Yang-Xin

2014-04-01

The lymphotoxin (LT)-pathway is a unique constituent branch of the Tumor Necrosis Superfamily (TNFSF). Use of LT is a critical mechanism by which fetal innate lymphoid cells regulate lymphoid organogenesis. Within recent years, adult innate lymphoid cells have been discovered to utilize this same pathway to regulate IL-22 and IL-23 production for host defense. Notably, genetic studies have linked polymorphisms in the genes encoding LTα to several phenotypes contributing to metabolic syndrome. The role of the LT-pathway may lay the foundation for a bridge between host immune response, microbiota, and metabolic syndrome. The contribution of the LT-pathway to innate lymphoid cell function and metabolic syndrome will be visited in this review. Copyright © 2013 Elsevier Ltd. All rights reserved.

Growth Conditions Regulate the Requirements for Caulobacter Chromosome Segregation

DEFF Research Database (Denmark)

Shebelut, Conrad W.; Jensen, Rasmus Bugge; Gitai, Zemer

2009-01-01

Growth environments are important metabolic and developmental regulators. Here we demonstrate a growth environment-dependent effect on Caulobacter chromosome segregation of a small-molecule inhibitor of the MreB bacterial actin cytoskeleton. Our results also implicate ParAB as important segregation...... determinants, suggesting that multiple distinct mechanisms can mediate Caulobacter chromosome segregation and that their relative contributions can be environmentally regulated....

Alteration of Epigenetic Regulation by Long Noncoding RNAs in Cancer

Directory of Open Access Journals (Sweden)

Mariangela Morlando

2018-02-01

Full Text Available Long noncoding RNAs (lncRNAs are important regulators of the epigenetic status of the human genome. Besides their participation to normal physiology, lncRNA expression and function have been already associated to many diseases, including cancer. By interacting with epigenetic regulators and by controlling chromatin topology, their misregulation may result in an aberrant regulation of gene expression that may contribute to tumorigenesis. Here, we review the functional role and mechanisms of action of lncRNAs implicated in the aberrant epigenetic regulation that has characterized cancer development and progression.

Cosmetic Regulations: A Comparative Study.

Science.gov (United States)

Suhag, Jyoti; Dureja, Harish

2015-01-01

The regulatory framework, compliance requirement, efficacy, safety, and marketing of cosmetic products are considered the most important factors for growth of the cosmetic industry. There are different regulatory bodies across the globe that have their own insights for regulation; moreover, governments such as the United States, European Union, and Japan follow a stringent regulatory framework, whereas cosmetics are not so much strictly regulated in countries such as India, Brazil, and China. The alignment of a regulatory framework will play a significant role in the removal of barriers to trade, growth of market at an international level, innovation in the development and presentation of new products, and most importantly safety and efficacy of the marketed products. The present contribution gives insight into the important cosmetic regulations in areas of premarket approval, ingredient control, and labeling and warnings, with a special focus on the cosmetic regulatory environments in the United States, European Union, Japan, and India. Most importantly, the authors highlight the dark side of cosmetics associated with allergic reactions and even skin cancer. The importance of cosmetic regulations has been highlighted by dint of which the society can be healthier, accomplished by more stringent and harmonized regulations.

Lower expression of glutamic acid decarboxylase 67 in the prefrontal cortex in schizophrenia: contribution of altered regulation by Zif268.

Science.gov (United States)

Kimoto, Sohei; Bazmi, H Holly; Lewis, David A

2014-09-01

Cognitive deficits of schizophrenia may be due at least in part to lower expression of the 67-kDa isoform of glutamic acid decarboxylase (GAD67), a key enzyme for GABA synthesis, in the dorsolateral prefrontal cortex of individuals with schizophrenia. However, little is known about the molecular regulation of lower cortical GAD67 levels in schizophrenia. The GAD67 promoter region contains a conserved Zif268 binding site, and Zif268 activation is accompanied by increased GAD67 expression. Thus, altered expression of the immediate early gene Zif268 may contribute to lower levels of GAD67 mRNA in the dorsolateral prefrontal cortex in schizophrenia. The authors used polymerase chain reaction to quantify GAD67 and Zif268 mRNA levels in dorsolateral prefrontal cortex area 9 from 62 matched pairs of schizophrenia and healthy comparison subjects, and in situ hybridization to assess Zif268 expression at laminar and cellular levels of resolution. The effects of potentially confounding variables were assessed in human subjects, and the effects of antipsychotic treatments were tested in antipsychotic-exposed monkeys. The specificity of the Zif268 findings was assessed by quantifying mRNA levels for other immediate early genes. GAD67 and Zif268 mRNA levels were significantly lower and were positively correlated in the schizophrenia subjects. Both Zif268 mRNA-positive neuron density and Zif268 mRNA levels per neuron were significantly lower in the schizophrenia subjects. These findings were robust to the effects of the confounding variables examined and differed from other immediate early genes. Deficient Zif268 mRNA expression may contribute to lower cortical GAD67 levels in schizophrenia, suggesting a potential mechanistic basis for altered cortical GABA synthesis and impaired cognition in schizophrenia.

Epigenetic Regulation in Prostate Cancer Progression.

Science.gov (United States)

Ruggero, Katia; Farran-Matas, Sonia; Martinez-Tebar, Adrian; Aytes, Alvaro

2018-01-01

An important number of newly identified molecular alterations in prostate cancer affect gene encoding master regulators of chromatin biology epigenetic regulation. This review will provide an updated view of the key epigenetic mechanisms underlying prostate cancer progression, therapy resistance, and potential actionable mechanisms and biomarkers. Key players in chromatin biology and epigenetic master regulators has been recently described to be crucially altered in metastatic CRPC and tumors that progress to AR independency. As such, epigenetic dysregulation represents a driving mechanism in the reprograming of prostate cancer cells as they lose AR-imposed identity. Chromatin integrity and accessibility for transcriptional regulation are key features altered in cancer progression, and particularly relevant in nuclear hormone receptor-driven tumors like prostate cancer. Understanding how chromatin remodeling dictates prostate development and how its deregulation contributes to prostate cancer onset and progression may improve risk stratification and treatment selection for prostate cancer patients.

Contribution of Neuroepigenetics to Huntington's Disease.

Science.gov (United States)

Francelle, Laetitia; Lotz, Caroline; Outeiro, Tiago; Brouillet, Emmanuel; Merienne, Karine

2017-01-01

Unbalanced epigenetic regulation is thought to contribute to the progression of several neurodegenerative diseases, including Huntington's disease (HD), a genetic disorder considered as a paradigm of epigenetic dysregulation. In this review, we attempt to address open questions regarding the role of epigenetic changes in HD, in the light of recent advances in neuroepigenetics. We particularly discuss studies using genome-wide scale approaches that provide insights into the relationship between epigenetic regulations, gene expression and neuronal activity in normal and diseased neurons, including HD neurons. We propose that cell-type specific techniques and 3D-based methods will advance knowledge of epigenome in the context of brain region vulnerability in neurodegenerative diseases. A better understanding of the mechanisms underlying epigenetic changes and of their consequences in neurodegenerative diseases is required to design therapeutic strategies more effective than current strategies based on histone deacetylase (HDAC) inhibitors. Researches in HD may play a driving role in this process.

Defined contribution health benefits.

Science.gov (United States)

Fronstin, P

2001-03-01

This Issue Brief discusses the emerging issue of "defined contribution" (DC) health benefits. The term "defined contribution" is used to describe a wide variety of approaches to the provision of health benefits, all of which have in common a shift in the responsibility for payment and selection of health care services from employers to employees. DC health benefits often are mentioned in the context of enabling employers to control their outlay for health benefits by avoiding increases in health care costs. DC health benefits may also shift responsibility for choosing a health plan and the associated risks of choosing a plan from employers to employees. There are three primary reasons why some employers currently are considering some sort of DC approach. First, they are once again looking for ways to keep their health care cost increases in line with overall inflation. Second, some employers are concerned that the public "backlash" against managed care will result in new legislation, regulations, and litigation that will further increase their health care costs if they do not distance themselves from health care decisions. Third, employers have modified not only most employee benefit plans, but labor market practices in general, by giving workers more choice, control, and flexibility. DC-type health benefits have existed as cafeteria plans since the 1980s. A cafeteria plan gives each employee the opportunity to determine the allocation of his or her total compensation (within employer-defined limits) among various employee benefits (primarily retirement or health). Most types of DC health benefits currently being discussed could be provided within the existing employment-based health insurance system, with or without the use of cafeteria plans. They could also allow employees to purchase health insurance directly from insurers, or they could drive new technologies and new forms of risk pooling through which health care services are provided and financed. DC health

Transcriptional regulation of hepatic lipogenesis.

Science.gov (United States)

Wang, Yuhui; Viscarra, Jose; Kim, Sun-Joong; Sul, Hei Sook

2015-11-01

Fatty acid and fat synthesis in the liver is a highly regulated metabolic pathway that is important for very low-density lipoprotein (VLDL) production and thus energy distribution to other tissues. Having common features at their promoter regions, lipogenic genes are coordinately regulated at the transcriptional level. Transcription factors, such as upstream stimulatory factors (USFs), sterol regulatory element-binding protein 1C (SREBP1C), liver X receptors (LXRs) and carbohydrate-responsive element-binding protein (ChREBP) have crucial roles in this process. Recently, insights have been gained into the signalling pathways that regulate these transcription factors. After feeding, high blood glucose and insulin levels activate lipogenic genes through several pathways, including the DNA-dependent protein kinase (DNA-PK), atypical protein kinase C (aPKC) and AKT-mTOR pathways. These pathways control the post-translational modifications of transcription factors and co-regulators, such as phosphorylation, acetylation or ubiquitylation, that affect their function, stability and/or localization. Dysregulation of lipogenesis can contribute to hepatosteatosis, which is associated with obesity and insulin resistance.

Regulators of Slc4 bicarbonate transporter activity

Directory of Open Access Journals (Sweden)

Ian M. Thornell

2015-06-01

Full Text Available The Slc4 family of transporters is comprised of anion exchangers (AE1-4, Na-coupled bicarbonate transporters (NCBTs including electrogenic Na/bicarbonate cotransporters (NBCe1 and NBCe2, electroneutral Na/bicarbonate cotransporters (NBCn1 and NBCn2, and the electroneutral Na-driven Cl-bicarbonate exchanger (NDCBE, as well as a borate transporter (BTR1. These transporters regulate intracellular pH (pHi and contribute to steady-state pHi, but are also involved in other physiological processes including CO2 carriage by red blood cells and solute secretion/reabsorption across epithelia. Acid-base transporters function as either acid extruders or acid loaders, with the Slc4 proteins moving HCO3– either into or out of cells. According to results from both molecular and functional studies, multiple Slc4 proteins and/or associated splice variants with similar expected effects on pHi are often found in the same tissue or cell. Such apparent redundancy is likely to be physiologically important. In addition to regulating pHi, a HCO3– transporter contributes to a cell’s ability to fine tune the intracellular regulation of the cotransported/exchanged ion(s (e.g., Na+ or Cl–. In addition, functionally similar transporters or splice variants with different regulatory profiles will optimize pH physiology and solute transport under various conditions or within subcellular domains. Such optimization will depend on activated signaling pathways and transporter expression profiles. In this review, we will summarize and discuss both classical and more recently identified regulators of the Slc4 proteins. Some of these regulators include traditional second messengers, lipids, binding proteins, autoregulatory domains, and less conventional regulators. The material presented will provide insight into the diversity and physiological significance of multiple members within the Slc4 gene family.

Nuclear and Membrane Actions of Estrogen Receptor Alpha: Contribution to the Regulation of Energy and Glucose Homeostasis.

Science.gov (United States)

Guillaume, Maeva; Montagner, Alexandra; Fontaine, Coralie; Lenfant, Françoise; Arnal, Jean-François; Gourdy, Pierre

2017-01-01

Estrogen receptor alpha (ERα) has been demonstrated to play a key role in reproduction but also to exert numerous functions in nonreproductive tissues. Accordingly, ERα is now recognized as a key regulator of energy homeostasis and glucose metabolism and mediates the protective effects of estrogens against obesity and type 2 diabetes. This chapter attempts to summarize our current understanding of the mechanisms of ERα activation and their involvement in the modulation of energy balance and glucose metabolism. We first focus on the experimental studies that constitute the basis of the understanding of ERα as a nuclear receptor and more specifically on the key roles played by its two activation functions (AFs). We depict the consequences of the selective inactivation of these AFs in mouse models, which further underline the prominent role of nuclear ERα in the prevention of obesity and diabetes, as on the reproductive tract and the vascular system. Besides these nuclear actions, a fraction of ERα is associated with the plasma membrane and activates nonnuclear signaling from this site. Such rapid effects, called membrane-initiated steroid signals (MISS), have been characterized in a variety of cell lines and in particular in endothelial cells. The development of selective pharmacological tools that specifically activate MISS as well as the generation of mice expressing an ERα protein impeded for membrane localization has just begun to unravel the physiological role of MISS in vivo and their contribution to ERα-mediated metabolic protection. Finally, we discuss novel perspectives for the design of tissue-selective ER modulators.

Implicit Beliefs about Emotion Regulation and Their Relations with Emotional Experiences among Chinese Adolescents

Science.gov (United States)

Deng, Xinmei; Sang, Biao; Chen, Xinyin

2017-01-01

There is growing interest in understanding how beliefs about emotion regulation are related to individual emotional experiences. Extant studies have mainly focused on explicit beliefs about emotion regulation among individuals in Western societies. The current study examined implicit emotion regulation and explored their contributions to emotional…

Differential contribution of CBP:CREB binding to corticotropin-releasing hormone expression in the infant and adult hypothalamus

NARCIS (Netherlands)

Cope, J.L.; Regev, L.; Chen, Y.; Korosi, A.; Rice, C.J.; Ji, S.; Rogge, G.A.; Wood, M.A.; Baram, T.Z.

2014-01-01

Corticotropin-releasing hormone (CRH) contributes crucially to the regulation of central and peripheral responses to stress. Because of the importance of a finely-tuned stress system, CRH expression is tightly regulated in an organ- and brain region-specific manner. Thus, in hypothalamus, CRH is

Layers of Self- and Co-Regulation: Teachers Working Collaboratively to Support Adolescents' Self-Regulated Learning through Reading

Directory of Open Access Journals (Sweden)

Deborah L. Butler

2013-01-01

Full Text Available This paper reports findings from a longitudinal project in which secondary teachers were working collaboratively to support adolescents' self-regulated learning through reading (LTR in subject-area classrooms. We build from prior research to “connect the dots” between teachers' engagement in self- and co-regulated inquiry, associated shifts in classroom practice, and student self-regulation. More specifically, we investigated whether and how teachers working within a community of inquiry were mobilizing research to shape classroom practice and advance student learning. Drawing on evidence from 18 teachers and their respective classrooms, we describe findings related to the following research questions: (1 While engaged in self- and co-regulated inquiry, what types of practices did teachers enact to support LTR in their subject-area classrooms? (2 How did teachers draw on research-based resources to inform practice development? (3 What kinds of practices could be associated with gains in students' self-regulated LTR? In our discussion, we highlight contributions to understanding how teachers can be supported to situate research in authentic classroom environments and about qualities of practices supportive of students' self-regulated LTR. We also identify limitations of this work and important future directions.

Emotion regulation deficits in regular marijuana users.

Science.gov (United States)

Zimmermann, Kaeli; Walz, Christina; Derckx, Raissa T; Kendrick, Keith M; Weber, Bernd; Dore, Bruce; Ochsner, Kevin N; Hurlemann, René; Becker, Benjamin

2017-08-01

Effective regulation of negative affective states has been associated with mental health. Impaired regulation of negative affect represents a risk factor for dysfunctional coping mechanisms such as drug use and thus could contribute to the initiation and development of problematic substance use. This study investigated behavioral and neural indices of emotion regulation in regular marijuana users (n = 23) and demographically matched nonusing controls (n = 20) by means of an fMRI cognitive emotion regulation (reappraisal) paradigm. Relative to nonusing controls, marijuana users demonstrated increased neural activity in a bilateral frontal network comprising precentral, middle cingulate, and supplementary motor regions during reappraisal of negative affect (P marijuana users relative to controls. Together, the present findings could reflect an unsuccessful attempt of compensatory recruitment of additional neural resources in the context of disrupted amygdala-prefrontal interaction during volitional emotion regulation in marijuana users. As such, impaired volitional regulation of negative affect might represent a consequence of, or risk factor for, regular marijuana use. Hum Brain Mapp 38:4270-4279, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Personality and self-regulation: trait and information-processing perspectives.

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Hoyle, Rick H

2006-12-01

This article introduces the special issue of Journal of Personality on personality and self-regulation. The goal of the issue is to illustrate and inspire research that integrates personality and process-oriented accounts of self-regulation. The article begins by discussing the trait perspective on self-regulation--distinguishing between temperament and personality accounts--and the information-processing perspective. Three approaches to integrating these perspectives are then presented. These range from methodological approaches, in which constructs representing the two perspectives are examined in integrated statistical models, to conceptual approaches, in which the two perspectives are unified in a holistic theoretical model of self-regulation. The article concludes with an overview of the special issue contributions, which are organized in four sections: broad, integrative models of personality and self-regulation; models that examine the developmental origins of self-regulation and self-regulatory styles; focused programs of research that concern specific aspects or applications of self-regulation; and strategies for increasing the efficiency and effectiveness of self-regulation.

The contribution of p53 and Y chromosome long arm genes to regulation of apoptosis in mouse testis.

Science.gov (United States)

Lech, Tomasz; Styrna, Józefa; Kotarska, Katarzyna

2018-03-01

Apoptosis of excessive or defective germ cells is a natural process occurring in mammalian testes. Tumour suppressor protein p53 is involved in this process both in developing and adult male gonads. Its contribution to testicular physiology is known to be modified by genetic background. The aim of this study was to evaluate the combined influence of the p53 and Y chromosome long arm genes on male germ cell apoptosis. Knockout of the transformation related protein 53 (Trp53) gene was introduced into congenic strains: B10.BR (intact Y chromosome) and B10.BR-Ydel (Y chromosome with a deletion in the long arm). The level of apoptosis in the testes of 19-day-old and 3-month-old male mice was determined using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick-end labelling (TUNEL) method. The study revealed that although p53 is involved in germ cell apoptosis in peripubertal testes, this process can also be mediated by p53-independent mechanisms. However, activation of p53-independent apoptotic pathways in the absence of the p53 protein requires engagement of the multicopy Yq genes and was not observed in gonads of B10.BR-Ydel-p53-/- males. The role of Yq genes in the regulation of testicular apoptosis seems to be restricted to the initial wave of spermatogenesis and is not evident in adult gonads. The study confirmed, instead, that p53 does participate in spontaneous apoptosis in mature testes.

Contribution of Neuroinflammation to the Pathogenesis of Cancer Cachexia.

Science.gov (United States)

Molfino, Alessio; Gioia, Gianfranco; Rossi Fanelli, Filippo; Laviano, Alessandro

2015-01-01

Inflammation characterizes the course of acute and chronic diseases and is largely responsible for the metabolic and behavioral changes occurring during the clinical journey of patients. Robust data indicate that, during cancer, functional modifications within brain areas regulating energy homeostasis contribute to the onset of anorexia, reduced food intake, and increased catabolism of muscle mass and adipose tissue. In particular, functional changes are associated with increased hypothalamic concentration of proinflammatory cytokines, which suggests that neuroinflammation may represent the adaptive response of the brain to peripheral challenges, including tumor growth. Within this conceptual framework, the vagus nerve appears to be involved in conveying alert signals to the hypothalamus, whereas hypothalamic serotonin appears to contribute to triggering catabolic signals.

Self trust, a major challenge for nuclear regulators

Energy Technology Data Exchange (ETDEWEB)

Eibenschutz, J. [National Nuclear Safety and Safeguards Commission (CNSN), Mexico City (Mexico)

2014-07-01

Self trust. The nuclear community and particularly nuclear regulators overreact to accidents, this has been the case with the three NPP major accidents. Lowering admissible radiation levels, for example, conveys the wrong message to politicians and the general public, and contributes to enhance mistrust towards nuclear. Industry as well as regulators should mature and act with self respect, since the scientific bases of regulation are very solid and should be trusted. Lessons learned should be seriously pursued in spite of the 'uneven playing field'. Obviously safety continues as the main priority, but paranoid reactions from the nuclear professionals could destroy the future of nuclear power. (author)

Self trust, a major challenge for nuclear regulators

International Nuclear Information System (INIS)

Eibenschutz, J.

2014-01-01

Self trust. The nuclear community and particularly nuclear regulators overreact to accidents, this has been the case with the three NPP major accidents. Lowering admissible radiation levels, for example, conveys the wrong message to politicians and the general public, and contributes to enhance mistrust towards nuclear. Industry as well as regulators should mature and act with self respect, since the scientific bases of regulation are very solid and should be trusted. Lessons learned should be seriously pursued in spite of the 'uneven playing field'. Obviously safety continues as the main priority, but paranoid reactions from the nuclear professionals could destroy the future of nuclear power. (author)

Differential cytokine contributions of perivascular haematopoietic stem cell niches.

Science.gov (United States)

Asada, Noboru; Kunisaki, Yuya; Pierce, Halley; Wang, Zichen; Fernandez, Nicolas F; Birbrair, Alexander; Ma'ayan, Avi; Frenette, Paul S

2017-03-01

Arterioles and sinusoids of the bone marrow (BM) are accompanied by stromal cells that express nerve/glial antigen 2 (NG2) and leptin receptor (LepR), and constitute specialized niches that regulate quiescence and proliferation of haematopoietic stem cells (HSCs). However, how niche cells differentially regulate HSC functions remains unknown. Here, we show that the effects of cytokines regulating HSC functions are dependent on the producing cell sources. Deletion of chemokine C-X-C motif ligand 12 (Cxcl12) or stem cell factor (Scf) from all perivascular cells marked by nestin-GFP dramatically depleted BM HSCs. Selective Cxcl12 deletion from arteriolar NG2 + cells, but not from sinusoidal LepR + cells, caused HSC reductions and altered HSC localization in BM. By contrast, deletion of Scf in LepR + cells, but not NG2 + cells, led to reductions in BM HSC numbers. These results uncover distinct contributions of cytokines derived from perivascular cells in separate vascular niches to HSC maintenance.

Down-regulated miR-448 relieves spinal cord ischemia/reperfusion injury by up-regulating SIRT1

Directory of Open Access Journals (Sweden)

Yun Wang

2018-03-01

Full Text Available MicroRNAs play a crucial role in the progression of spinal cord ischemia/reperfusion injury (SCII. The role of miR-448 and SIRT1 in SCII was investigated in this study, to provide further insights into prevention and improvement of this disorder. In this study, expressions of miR-448 and SIRT1 protein were determined by qRT-PCR and western blot, respectively. Flow cytometry was used to analyze cell apoptosis. The endogenous expression of genes was modulated by recombinant plasmids and cell transfection. Dual-luciferase reporter assay was performed to determine the interaction between miR-448 and SIRT1. The Basso, Beattie, and Bresnahan score was used to measure the hind-limb function of rat. The spinal cord ischemia reperfusion injury model of adult rats was developed by abdominal aorta clamping, and the nerve function evaluation was completed by motor deficit index score. In SCII tissues and cells treated with hypoxia, miR-448 was up-regulated while SIRT1 was down-regulated. Hypoxia treatment reduced the expression of SIRT1 through up-regulating miR-448 in nerve cells. Up-regulation of miR-448 induced by hypoxia promoted apoptosis of nerve cells through down-regulating SIRT1. Down-regulated miR-448 improved neurological function and hind-limb motor function of rats with SCII by up-regulating SIRT1. Down-regulated miR-448 inhibited apoptosis of nerve cells and improved neurological function by up-regulating SIRT1, which contributes to relieving SCII.

"Do as I say!" : parenting and the biology of child self-regulation

NARCIS (Netherlands)

Kok, Rianne

2013-01-01

The development of self-regulation is one of the major challenges of a child’s healthy development. In the current thesis, the contribution and interplay of parental and biological factors in the development of self-regulation in preschoolers are studied in a large population-based cohort, the

Regulations by the DFTCE concerning the Fund for the decommissioning of nuclear installations

International Nuclear Information System (INIS)

1985-02-01

These Regulations were made by the Federal Ministry of Transport, Communications and Energy in implementation of the Ordinance of 5 December 1983 establishing a fund for the decommissioning of nuclear installations. They specify the way in which nuclear operators must contribute to the fund and the method for calculating the contributions. The costs of decommissioning also include dismantling and disposal of the resulting waste. The Regulations entered into force retroactively, on 1 January 1984, on the same date as the 1983 Ordinance. (NEA) [fr

Fibroblast Growth Factor 21 Mediates Glycemic Regulation by Hepatic JNK

Directory of Open Access Journals (Sweden)

Santiago Vernia

2016-03-01

Full Text Available The cJun NH2-terminal kinase (JNK-signaling pathway is implicated in metabolic syndrome, including dysregulated blood glucose concentration and insulin resistance. Fibroblast growth factor 21 (FGF21 is a target of the hepatic JNK-signaling pathway and may contribute to the regulation of glycemia. To test the role of FGF21, we established mice with selective ablation of the Fgf21 gene in hepatocytes. FGF21 deficiency in the liver caused marked loss of FGF21 protein circulating in the blood. Moreover, the protective effects of hepatic JNK deficiency to suppress metabolic syndrome in high-fat diet-fed mice were not observed in mice with hepatocyte-specific FGF21 deficiency, including reduced blood glucose concentration and reduced intolerance to glucose and insulin. Furthermore, we show that JNK contributes to the regulation of hepatic FGF21 expression during fasting/feeding cycles. These data demonstrate that the hepatokine FGF21 is a key mediator of JNK-regulated metabolic syndrome.

Computer simulation studies in fluid and calcium regulation and orthostatic intolerance

Science.gov (United States)

1985-01-01

The systems analysis approach to physiological research uses mathematical models and computer simulation. Major areas of concern during prolonged space flight discussed include fluid and blood volume regulation; cardiovascular response during shuttle reentry; countermeasures for orthostatic intolerance; and calcium regulation and bone atrophy. Potential contributions of physiologic math models to future flight experiments are examined.

Circadian Regulation of Glutamate Transporters

Directory of Open Access Journals (Sweden)

Donají Chi-Castañeda

2018-06-01

Full Text Available L-glutamate is the major excitatory amino acid in the mammalian central nervous system (CNS. This neurotransmitter is essential for higher brain functions such as learning, cognition and memory. A tight regulation of extra-synaptic glutamate levels is needed to prevent a neurotoxic insult. Glutamate removal from the synaptic cleft is carried out by a family of sodium-dependent high-affinity transporters, collectively known as excitatory amino acid transporters. Dysfunction of glutamate transporters is generally involved in acute neuronal injury and neurodegenerative diseases, so characterizing and understanding the mechanisms that lead to the development of these disorders is an important goal in the design of novel treatments for the neurodegenerative diseases. Increasing evidence indicates glutamate transporters are controlled by the circadian system in direct and indirect manners, so in this contribution we focus on the mechanisms of circadian regulation (transcriptional, translational, post-translational and post-transcriptional regulation of glutamate transport in neuronal and glial cells, and their consequence in brain function.

Regulation of Membrane-Type 4 Matrix Metalloproteinase by SLUG Contributes to Hypoxia-Mediated Metastasis12

Science.gov (United States)

Huang, Chi-Hung; Yang, Wen-Hao; Chang, Shyue-Yih; Tai, Shyh-Kuan; Tzeng, Cheng-Hwei; Kao, Jung-Yie; Wu, Kou-Juey; Yang, Muh-Hwa

2009-01-01

The hypoxic tumor environment has been shown to be critical to cancer metastasis through the promotion of angiogenesis, induction of epithelial-mesenchymal transition (EMT), and acquisition of invasive potential. However, the impact of hypoxia on the expression profile of the proteolytic enzymes involved in invasiveness is relatively unknown. Membrane-type 4 matrix metalloproteinase (MT4-MMP) is a glycosyl-phosphatidyl inositol-anchored protease that has been shown to be overexpressed in human cancers. However, detailed mechanisms regarding the regulation and function of MT4-MMP expression in tumor cells remain unknown. Here, we demonstrate that hypoxia or overexpression of hypoxia-inducible factor-1α (HIF-1α) induced MT4-MMP expression in human cancer cells. Activation of SLUG, a transcriptional factor regulating the EMT process of human cancers, by HIF-1α was critical for the induction of MT4-MMP under hypoxia. SLUG regulated the transcription of MT4-MMP through direct binding to the E-box located in its proximal promoter. Short-interference RNA-mediated knockdown of MT4-MMP attenuated in vitro invasiveness and in vivo pulmonary colonization of tumor cells without affecting cell migratory ability. MT4-MMP promoted invasiveness and pulmonary colonization through modulation of the expression profile of MMPs and angiogenic factors. Finally, coexpression of HIF-1α and MT4-MMP in human head and neck cancer was predictive of a worse clinical outcome. These findings establish a novel signaling pathway for hypoxia-mediated metastasis and elucidate the underlying regulatory mechanism and functional significance of MT4-MMP in cancer metastasis. PMID:20019845

White book for the conference of experts on the climate-energy contribution

International Nuclear Information System (INIS)

2009-01-01

This publication discusses the main questions raised by the creation of a climate-energy contribution which aims at better taking into account the costs generated by degradations of the environment. It discusses the stakes and justifications of this contribution within the frame of emission reduction objectives and of the Emission Trading Scheme, and outlines the benefit of economic tools with respect to regulation. It discusses how to implement this contribution, how to define its base, whether existing taxes on fossil energies will have the expected effects and how to hinge these existing taxes on the climate-energy contribution. It discusses what would be the scope of application of the contribution, what should be its level and how it should change in time, how to support it and make it more efficient. It discusses its macro-economical consequences, notably by referring to the Swedish example

Risk-based regulation: A regulatory perspective

International Nuclear Information System (INIS)

Scarborough, J.C.

1993-01-01

In the early development of regulations for nuclear power plants, risk was implicitly considered through qualitative assessments and engineering reliability principles and practices. Examples included worst case analysis, defense in depth, and the single failure criterion. However, the contributions of various systems, structures, components and operator actions to plant safety were not explicitly assessed since a methodology for this purpose had not been developed. As a consequence of the TMI accident, the use of more quantitative risk methodology and information in regulation such as probabilistic risk analysis (PRA) increased. The use of both qualitative and quantitative consideration of risk in regulation has been a set of regulations and regulatory guides and practices that ensure adequate protection of public health and safety. Presently, the development of PRA techniques has developed to the point that safety goals, expressed in terms of risk, have been established to help guide further regulatory decision making. This paper presents the personal opinions of the author as regards the use of risk today in nuclear power plant regulation, areas of further information needs, and necessary plans for moving toward a more systematic use of risk-based information in regulatory initiatives in the future

[Membrane-bound cytokine and feedforward regulation].

Science.gov (United States)

Wu, Ke-Fu; Zheng, Guo-Guang; Ma, Xiao-Tong; Song, Yu-Hua

2013-10-01

Feedback and feedforward widely exist in life system, both of them are the basic processes of control system. While the concept of feedback has been widely used in life science, feedforward regulation was systematically studied in neurophysiology, awaiting further evidence and mechanism in molecular biology and cell biology. The authors put forward a hypothesis about the feedforward regulation of membrane bound macrophage colony stimulation factor (mM-CSF) on the basis of their previous work. This hypothesis might provide a new direction for the study on the biological effects of mM-CSF on leukemia and solid tumors, and contribute to the study on other membrane bound cytokines.

Lanthanide-Dependent Regulation of Methanol Oxidation Systems in Methylobacterium extorquens AM1 and Their Contribution to Methanol Growth.

Science.gov (United States)

Vu, Huong N; Subuyuj, Gabriel A; Vijayakumar, Srividhya; Good, Nathan M; Martinez-Gomez, N Cecilia; Skovran, Elizabeth

2016-04-01

Methylobacterium extorquens AM1 has two distinct types of methanol dehydrogenase (MeDH) enzymes that catalyze the oxidation of methanol to formaldehyde. MxaFI-MeDH requires pyrroloquinoline quinone (PQQ) and Ca in its active site, while XoxF-MeDH requires PQQ and lanthanides, such as Ce and La. Using MeDH mutant strains to conduct growth analysis and MeDH activity assays, we demonstrate that M. extorquens AM1 has at least one additional lanthanide-dependent methanol oxidation system contributing to methanol growth. Additionally, the abilities of different lanthanides to support growth were tested and strongly suggest that both XoxF and the unknown methanol oxidation system are able to use La, Ce, Pr, Nd, and, to some extent, Sm. Further, growth analysis using increasing La concentrations showed that maximum growth rate and yield were achieved at and above 1 μM La, while concentrations as low as 2.5 nM allowed growth at a reduced rate. Contrary to published data, we show that addition of exogenous lanthanides results in differential expression from the xox1 and mxa promoters, upregulating genes in the xox1 operon and repressing genes in the mxa operon. Using transcriptional reporter fusions, intermediate expression from both the mxa and xox1 promoters was detected when 50 to 100 nM La was added to the growth medium, suggesting that a condition may exist under which M. extorquens AM1 is able to utilize both enzymes simultaneously. Together, these results suggest that M. extorquens AM1 actively senses and responds to lanthanide availability, preferentially utilizing the lanthanide-dependent MeDHs when possible. The biological role of lanthanides is a nascent field of study with tremendous potential to impact many areas in biology. Our studies demonstrate that there is at least one additional lanthanide-dependent methanol oxidation system, distinct from the MxaFI and XoxF MeDHs, that may aid in classifying additional environmental organisms as methylotrophs. Further

Immune regulation by microbiome metabolites.

Science.gov (United States)

Kim, Chang H

2018-03-22

Commensal microbes and the host immune system have been co-evolved for mutual regulation. Microbes regulate the host immune system, in part, by producing metabolites. A mounting body of evidence indicates that diverse microbial metabolites profoundly regulate the immune system via host receptors and other target molecules. Immune cells express metabolite-specific receptors such as P2X 7 , GPR41, GPR43, GPR109A, aryl hydrocarbon receptor precursor (AhR), pregnane X receptor (PXR), farnesoid X receptor (FXR), TGR5 and other molecular targets. Microbial metabolites and their receptors form an extensive array of signals to respond to changes in nutrition, health and immunological status. As a consequence, microbial metabolite signals contribute to nutrient harvest from diet, and regulate host metabolism and the immune system. Importantly, microbial metabolites bidirectionally function to promote both tolerance and immunity to effectively fight infection without developing inflammatory diseases. In pathogenic conditions, adverse effects of microbial metabolites have been observed as well. Key immune-regulatory functions of the metabolites, generated from carbohydrates, proteins and bile acids, are reviewed in this article. © 2018 John Wiley & Sons Ltd.

Impaired Voluntary Control in PTSD: Probing Self-Regulation of the ACC With Real-Time fMRI

Directory of Open Access Journals (Sweden)

Jana Zweerings

2018-05-01

Full Text Available Background: Post-traumatic stress disorder (PTSD is characterized by deficits in the self-regulation of cognitions and emotions. Neural networks of emotion regulation may exhibit reduced control mediated by the anterior cingulate cortex (ACC, contributing to aberrant limbic responses in PTSD.Methods: Real-time fMRI neurofeedback (rt-fMRI NF assessed self-regulation of the ACC in nine patients with PTSD after single trauma exposure and nine matched healthy controls. All participants were instructed to train ACC upregulation on three training days.Results: Both groups achieved regulation, which was associated with wide-spread brain activation encompassing the ACC. Compared to the controls, regulation amplitude and learning rate was lower in patients, correlating with symptom severity. In addition, a frontopolar activation cluster was associated with self-regulation efforts in patients.Conclusions: For the first time, we tested self-regulation of the ACC in patients with PTSD. The observed impairment supports models of ACC-mediated regulation deficits that may contribute to the psychopathology of PTSD. Controlled trials in a larger sample are needed to confirm our findings and to directly investigate whether training of central regulation mechanisms improves emotion regulation in PTSD.

Contribution of Neuroepigenetics to Huntington’s Disease

Science.gov (United States)

Francelle, Laetitia; Lotz, Caroline; Outeiro, Tiago; Brouillet, Emmanuel; Merienne, Karine

2017-01-01

Unbalanced epigenetic regulation is thought to contribute to the progression of several neurodegenerative diseases, including Huntington’s disease (HD), a genetic disorder considered as a paradigm of epigenetic dysregulation. In this review, we attempt to address open questions regarding the role of epigenetic changes in HD, in the light of recent advances in neuroepigenetics. We particularly discuss studies using genome-wide scale approaches that provide insights into the relationship between epigenetic regulations, gene expression and neuronal activity in normal and diseased neurons, including HD neurons. We propose that cell-type specific techniques and 3D-based methods will advance knowledge of epigenome in the context of brain region vulnerability in neurodegenerative diseases. A better understanding of the mechanisms underlying epigenetic changes and of their consequences in neurodegenerative diseases is required to design therapeutic strategies more effective than current strategies based on histone deacetylase (HDAC) inhibitors. Researches in HD may play a driving role in this process. PMID:28194101

Self-Entrustment: How Trainees' Self-Regulated Learning Supports Participation in the Workplace

Science.gov (United States)

Sagasser, Margaretha H.; Kramer, Anneke W. M.; Fluit, Cornelia R. M. G.; van Weel, Chris; van der Vleuten, Cees P. M.

2017-01-01

Clinical workplaces offer postgraduate trainees a wealth of opportunities to learn from experience. To promote deliberate and meaningful learning self-regulated learning skills are foundational. We explored trainees' learning activities related to patient encounters to better understand what aspects of self-regulated learning contribute to…

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to L-tyrosine and contribution to normal synthesis of dopamine pursuant to Article 13(5) of Regulation (EC) No 1924/2006

DEFF Research Database (Denmark)

Tetens, Inge

Following an application from Vitabiotics Ltd. pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of the United Kingdom, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver an opinion on the scientific substantiation of a health claim...... relationship has been established between the consumption of L-tyrosine in a protein adequate diet and contribution to normal synthesis of dopamine. However, no evidence has been provided that the protein supply in the diet of the European population is not sufficient to fulfil this function of the amino acid....... The following wording reflects the scientific evidence: “L-tyrosine contributes to normal synthesis of dopamine”. In order to bear the claim a food should be at least a source of protein as per Annex to Regulation (EC) No 1924/2006. Such amounts can be easily consumed as part of a balanced diet. The target...

THE FRENCH REGULATION SCHOOL: A CRITICAL REVISION

Directory of Open Access Journals (Sweden)

Natalia, Gajst

2010-01-01

Full Text Available The French regulation school sets out to carry out an analysis of Capitalism and its transformations, with the purpose of understanding the periods of stable growth and the moments of structural change. The object of this paper consists of carrying out a critical revision of the contributions of this school, concentrating on the conceptual framework that it has developed. For this, in the first place the influences that marked the regulation approach will be reviewed, with special attention on its recovery from the Marxist tradition. Secondly, the ontological and methodological differences between the regulation approach and the neoclassic economy theory will be highlighted. Thirdly, the fundamental concepts of the regulation school will be examined. In fourth place, it will be seen how, from these concepts, the crisis at the beginning of the 1970s was interpreted. In fifth place, how the regulation approach is thought as to the relation between economy and policy. In sixth place, the question of the international dimension will be examined. Finally, the main objections that have been presented to the regulation approach, will be shown and will be evaluated critically.

The Development of Prosocial Behaviour in Early Childhood: Contributions of Early Parenting and Self-Regulation

Science.gov (United States)

Williams, Kate E.; Berthelsen, Donna

2017-01-01

This research considers the role of parenting practices and early self-regulation, on children's prosocial behaviour when they begin school. Data for 4007 children were drawn from "Growing Up in Australia: The Longitudinal Study of Australian Children" (LSAC). The analyses explored relations between self-reported parenting practices for…

FOXO3-mediated up-regulation of Bim contributes to rhein-induced cancer cell apoptosis.

Science.gov (United States)

Wang, Jiao; Liu, Shu; Yin, Yancun; Li, Mingjin; Wang, Bo; Yang, Li; Jiang, Yangfu

2015-03-01

The anthraquinone compound rhein is a natural agent in the traditional Chinese medicine rhubarb. Preclinical studies demonstrate that rhein has anticancer activity. Treatment of a variety of cancer cells with rhein may induce apoptosis. Here, we report that rhein induces atypical unfolded protein response in breast cancer MCF-7 cells and hepatoma HepG2 cells. Rhein induces CHOP expression, eIF2α phosphorylation and caspase cleavage, while it does not induce glucose-regulated protein 78 (GRP78) expression in both MCF-7 and HepG2 cells. Meanwhile, rhein inhibits thapsigargin-induced GRP78 expression and X box-binding protein 1 splicing. In addition, rhein inhibits Akt phosphorylation and stimulates FOXO transactivation activity. Rhein induces Bim expression in MCF-7 and HepG2 cells, which can be abrogated by FOXO3a knockdown. Knockdown of FOXO3a or Bim abrogates rhein-induced caspase cleavage and apoptosis. The chemical chaperone 4-phenylbutyrate acid antagonizes the induction of FOXO activation, Bim expression and caspase cleavage by rhein, indicating that protein misfolding may be involved in triggering these deleterious effects. We conclude that FOXO3a-mediated up-regulation of Bim is a key mechanism underlying rhein-induced cancer cells apoptosis.

Contribution of Neuroinflammation to the Pathogenesis of Cancer Cachexia

Directory of Open Access Journals (Sweden)

Alessio Molfino

2015-01-01

Full Text Available Inflammation characterizes the course of acute and chronic diseases and is largely responsible for the metabolic and behavioral changes occurring during the clinical journey of patients. Robust data indicate that, during cancer, functional modifications within brain areas regulating energy homeostasis contribute to the onset of anorexia, reduced food intake, and increased catabolism of muscle mass and adipose tissue. In particular, functional changes are associated with increased hypothalamic concentration of proinflammatory cytokines, which suggests that neuroinflammation may represent the adaptive response of the brain to peripheral challenges, including tumor growth. Within this conceptual framework, the vagus nerve appears to be involved in conveying alert signals to the hypothalamus, whereas hypothalamic serotonin appears to contribute to triggering catabolic signals.

NRC safety research in support of regulation. Selected highlights

International Nuclear Information System (INIS)

1986-05-01

The report presents selected highlights of how research has contributed to the regulatory effort. It explains the research role of the NRC and nuclear safety research contributions in the areas of: pressure vessel integrity, piping, small- and large-break loss-of-coolant accidents, hydrogen and containment, source term analysis, seismic hazards and high-level waste management. The report also provides a summary of current and future research directions in support of regulation

Predicting heavy episodic drinking using an extended temporal self-regulation theory.

Science.gov (United States)

Black, Nicola; Mullan, Barbara; Sharpe, Louise

2017-10-01

Alcohol consumption contributes significantly to the global burden from disease and injury, and specific patterns of heavy episodic drinking contribute uniquely to this burden. Temporal self-regulation theory and the dual-process model describe similar theoretical constructs that might predict heavy episodic drinking. The aims of this study were to test the utility of temporal self-regulation theory in predicting heavy episodic drinking, and examine whether the theoretical relationships suggested by the dual-process model significantly extend temporal self-regulation theory. This was a predictive study with 149 Australian adults. Measures were questionnaires (self-report habit index, cues to action scale, purpose-made intention questionnaire, timeline follow-back questionnaire) and executive function tasks (Stroop, Tower of London, operation span). Participants completed measures of theoretical constructs at baseline and reported their alcohol consumption two weeks later. Data were analysed using hierarchical multiple linear regression. Temporal self-regulation theory significantly predicted heavy episodic drinking (R 2 =48.0-54.8%, ptheory and the extended temporal self-regulation theory provide good prediction of heavy episodic drinking. Intention, behavioural prepotency, planning ability and inhibitory control may be good targets for interventions designed to decrease heavy episodic drinking. Copyright © 2017 Elsevier Ltd. All rights reserved.

P38/TRHr-Dependent Regulation of TPO in Thyroid Cells Contributes to the Hypothyroidism of Triclosan-Treated Rats

Directory of Open Access Journals (Sweden)

Pei Zhang

2018-02-01

Full Text Available Background/Aims: Triclosan, as an antimicrobial agent and a potential endocrine disruptor, has been used extensively in diverse products, resulting in widespread human exposure. In recent years, studies suggest that triclosan could disturb thyroid functions and decline thyroid hormones (THs. Methods: To verify our hypothesis that the MAPK pathway may function significantly in triclosan-induced hypothyroidism, Sprague-Dawley rats were gavaged with triclosan for 31 consecutive days; Nthy-ori 3-1 cells were treated with triclosan in the presence/absence of NAC, inhibitors (SB203580 and SB202474, or TRHr siRNA. Tissues and/or cells were analyzed by several techniques including transmission electron microscopy, confocal laser scanning microscopy, gene silencing, western blot, and real-time PCR. Results: Triclosan led to histopathologic changes in the thyroid and decreases in triiodothyronine (T3 and thyroxine (T4. Triclosan stimulated ROS production and oxidative stress occurrence, thereby activating the p38 pathway in vivo and in vitro. Thyrotropin releasing hormone receptor (TRHr was induced when the p38 pathway was activated, and was suppressed when that pathway was inhibited. Moreover, thyroid peroxidase (TPO was restrained and modulated by the p38/TRHr pathway after triclosan treatment. Furthermore, deiodinase 3 (D3 and hepatic enzymes (Ugt2b1, CYP1a1, CYP1a2, CYP2b1, CYP3a1, and Sult1e1 were also induced by triclosan. Conclusion: Taken together, p38/TRHr-dependent regulation of TPO in thyroid cells contributes to the hypothyroidism of triclosan-treated rats.

Deep sequencing analysis of small noncoding RNA and mRNA targets of the global post-transcriptional regulator, Hfq

DEFF Research Database (Denmark)

Sittka, A; Lucchini, S; Papenfort, K

2008-01-01

would be rescued by overexpression of HilD and FlhDC, and we proved this to be correct. The combination of epitope-tagging and HTPS of immunoprecipitated RNA detected the expression of many intergenic chromosomal regions of Salmonella. Our approach overcomes the limited availability of high...

A study for good regulation of the CANDU's in Korea

Energy Technology Data Exchange (ETDEWEB)

Oh, Se Ki; Shin, Y. K.; Joe, S. K.; Kim, J. S.; Yu, Y. J.; Lee, Y. J. [Ajou Univ., Suwon (Korea, Republic of)

2002-03-15

The objective of project is to derive the policy recommendations to improve the efficiency of CANDU plants regulation. These policy recommendations will eventually contribute to the upgrading of Korean nuclear regulatory system and safety enhancement. During the second phase of this 2 years study, following research activities were done. Review the technical basis and framework of the new Canadian Regulation System and IAEA. Analysis on the interview of Wolsung operation staffs to identify important safety issues and regulation problems experienced at operation. Providing a plan of CANDU regulation system enhancement program.

Contribution of ecosystem services to air quality and climate change mitigation policies: the case of urban forests in Barcelona, Spain.

Science.gov (United States)

Baró, Francesc; Chaparro, Lydia; Gómez-Baggethun, Erik; Langemeyer, Johannes; Nowak, David J; Terradas, Jaume

2014-05-01

Mounting research highlights the contribution of ecosystem services provided by urban forests to quality of life in cities, yet these services are rarely explicitly considered in environmental policy targets. We quantify regulating services provided by urban forests and evaluate their contribution to comply with policy targets of air quality and climate change mitigation in the municipality of Barcelona, Spain. We apply the i-Tree Eco model to quantify in biophysical and monetary terms the ecosystem services "air purification," "global climate regulation," and the ecosystem disservice "air pollution" associated with biogenic emissions. Our results show that the contribution of urban forests regulating services to abate pollution is substantial in absolute terms, yet modest when compared to overall city levels of air pollution and GHG emissions. We conclude that in order to be effective, green infrastructure-based efforts to offset urban pollution at the municipal level have to be coordinated with territorial policies at broader spatial scales.

31 CFR 370.40 - Can I be held accountable if my negligence contributes to a forged signature?

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Can I be held accountable if my negligence contributes to a forged signature? 370.40 Section 370.40 Money and Finance: Treasury Regulations... if my negligence contributes to a forged signature? (a) General. If your failure to exercise ordinary...

Regulation of H+ Extrusion and Cytoplasmic pH in Maize Root Tips Acclimated to a Low-Oxygen Environment.

Science.gov (United States)

Xia, J. H.; Roberts, JKM.

1996-05-01

We tested the hypothesis that H+ extrusion contributes to cytoplasmic pH regulation and tolerance of anoxia in maize (Zea mays) root tips. We studied root tips of whole seedlings that were acclimated to a low-oxygen environment by pretreatment in 3% (v/v) O2. Acclimated root tips characteristically regulate cytoplasmic pH near neutrality and survive prolonged anoxia, whereas nonacclimated tips undergo severe cytoplasmic acidosis and die much more quickly. We show that the plasma membrane H+-ATPase can operate under anoxia and that net H+ extrusion increases when cytoplasmic pH falls. However, at an external pH near 6.0, H+ extrusion contributes little to cytoplasmic pH regulation. At more acidic external pH values, net H+ flux into root tips increases dramatically, leading to a decrease in cytoplasmic pH and reduced tolerance of anoxia. We present evidence that, under these conditions, H+ pumps are activated to partly offset acidosis due to H+ influx and, thereby, contribute to cytoplasmic pH regulation and tolerance of anoxia. The regulation of H+ extrusion under anoxia is discussed with respect to the acclimation response and mechanisms of intracellular pH regulation in aerobic plant cells.

Phosphorylation-dependent regulation of plant chromatin and chromatin-associated proteins

KAUST Repository

Bigeard, Jean; Rayapuram, Naganand; Pflieger, Delphine; Hirt, Heribert

2014-01-01

In eukaryotes, most of the DNA is located in the nucleus where it is organized with histone proteins in a higher order structure as chromatin. Chromatin and chromatin-associated proteins contribute to DNA-related processes such as replication and transcription as well as epigenetic regulation. Protein functions are often regulated by PTMs among which phosphorylation is one of the most abundant PTM. Phosphorylation of proteins affects important properties, such as enzyme activity, protein stability, or subcellular localization. We here describe the main specificities of protein phosphorylation in plants and review the current knowledge on phosphorylation-dependent regulation of plant chromatin and chromatin-associated proteins. We also outline some future challenges to further elucidate protein phosphorylation and chromatin regulation.

Phosphorylation-dependent regulation of plant chromatin and chromatin-associated proteins

KAUST Repository

Bigeard, Jean

2014-07-10

In eukaryotes, most of the DNA is located in the nucleus where it is organized with histone proteins in a higher order structure as chromatin. Chromatin and chromatin-associated proteins contribute to DNA-related processes such as replication and transcription as well as epigenetic regulation. Protein functions are often regulated by PTMs among which phosphorylation is one of the most abundant PTM. Phosphorylation of proteins affects important properties, such as enzyme activity, protein stability, or subcellular localization. We here describe the main specificities of protein phosphorylation in plants and review the current knowledge on phosphorylation-dependent regulation of plant chromatin and chromatin-associated proteins. We also outline some future challenges to further elucidate protein phosphorylation and chromatin regulation.

Interaction Analysis for Supporting Students' Self-Regulation during Blog-Based CSCL Activities

Science.gov (United States)

Michailidis, Nikolaos; Kapravelos, Efstathios; Tsiatsos, Thrasyvoulos

2018-01-01

Self-regulated learning is an important means of supporting students' self-awareness and self-regulation level so as to enhance their motivation and engagement. Interaction Analysis (IA) contributes to this end, and its use in studying learning dynamics involved in asynchronous Computer-Supported Collaborative Learning (CSCL) activities has…

European Communities (Drinking water) Regulations, 2000

International Nuclear Information System (INIS)

2000-12-01

These Regulations were adopted as Statutory Instrument No. 439 of 2000 on 18 December 2000 and come in to operation on 1 January 2004. The regulations give effect to provisions of EU Council Directive 98/83/EC on the quality of water intended for human consumption.. They prescribe quality standards to be applied in relation to certain supplies of drinking water. S.I. 439 of 2000 stipulates that the radiation dose arising from one year's consumption of drinking water should not exceed 0.1 mSv. It further stipulates that the dose calculation should include contributions from all natural and artificial radionuclides with the exception of tritium, potassium-40, radon and radon decay products

Deleted in breast cancer 1 (DBC1) protein regulates hepatic gluconeogenesis.

Science.gov (United States)

Nin, Veronica; Chini, Claudia C S; Escande, Carlos; Capellini, Verena; Chini, Eduardo N

2014-02-28

Liver gluconeogenesis is essential to provide energy to glycolytic tissues during fasting periods. However, aberrant up-regulation of this metabolic pathway contributes to the progression of glucose intolerance in individuals with diabetes. Phosphoenolpyruvate carboxykinase (PEPCK) expression plays a critical role in the modulation of gluconeogenesis. Several pathways contribute to the regulation of PEPCK, including the nuclear receptor Rev-erbα and the histone deacetylase SIRT1. Deleted in breast cancer 1 (DBC1) is a nuclear protein that binds to and regulates both Rev-erbα and SIRT1 and, therefore, is a candidate to participate in the regulation of PEPCK. In this work, we provide evidence that DBC1 regulates glucose metabolism and the expression of PEPCK. We show that DBC1 levels decrease early in the fasting state. Also, DBC1 KO mice display higher gluconeogenesis in a normal and a high-fat diet. DBC1 absence leads to an increase in PEPCK mRNA and protein expression. Conversely, overexpression of DBC1 results in a decrease in PEPCK mRNA and protein levels. DBC1 regulates the levels of Rev-erbα, and manipulation of Rev-erbα activity or levels prevents the effect of DBC1 on PEPCK. In addition, Rev-erbα levels decrease in the first hours of fasting. Finally, knockdown of the deacetylase SIRT1 eliminates the effect of DBC1 knockdown on Rev-erbα levels and PEPCK expression, suggesting that the mechanism of PEPCK regulation is, at least in part, dependent on the activity of this enzyme. Our results point to DBC1 as a novel regulator of gluconeogenesis.

Ghrelin receptor regulates appetite and satiety during aging in mice by regulating meal frequency and portion size but not total food intake

Science.gov (United States)

Aging is often associated with overweight and obesity. There exists a long-standing debate about whether meal pattern also contributes to the development of obesity. The orexigenic hormone ghrelin regulates appetite and satiety by activating its receptor, growth hormone secretagogue receptor (GHS-R)...

Social Regulation of Leukocyte Homeostasis: The Role of Glucocorticoid Sensitivity

Science.gov (United States)

Cole, Steve W.

2010-01-01

Recent small-scale genomics analyses suggest that physiologic regulation of pro-inflammatory gene expression by endogenous glucocorticoids may be compromised in individuals who experience chronic social isolation. This could potentially contribute to the elevated prevalence of inflammation-related disease previously observed in social isolates. The present study assessed the relationship between leukocyte distributional sensitivity to glucocorticoid regulation and subjective social isolation in a large population-based sample of older adults. Initial analyses confirmed that circulating neutrophil percentages were elevated, and circulating lymphocyte and monocyte percentages were suppressed, in direct proportion to circulating cortisol levels. However, leukocyte distributional sensitivity to endogenous glucocorticoids was abrogated in individuals reporting either occasional or frequent experiences of subjective social isolation. This finding held in both nonparametric univariate analyses and in multivariate linear models controlling for a variety of biological, social, behavioral, and psychological confounders. The present results suggest that social factors may alter immune cell sensitivity to physiologic regulation by the hypothalamic-pituitary-adrenal axis in ways that could ultimately contribute to the increased physical health risks associated with social isolation. PMID:18394861

Up-regulation of miR-146a contributes to the inhibition of invasion of pancreatic cancer cells

Science.gov (United States)

Li, Yiwei; VandenBoom, Timothy G.; Wang, Zhiwei; Kong, Dejuan; Ali, Shadan; Philip, Philip A.; Sarkar, Fazlul H.

2009-01-01

Pancreatic cancer (PC) is an aggressive malignancy with high mortality and is believed to be in part due to its highly invasive and metastatic behavior, which is associated with over-expression of EGFR and activation of NF-κB. Emerging evidence also suggest critical roles of microRNAs (miRNAs) in the regulation of various pathobiological processes including metastasis in PC and in other human malignancies. In the present study, we found lower expression of miR-146a in PC cells compared to normal human pancreatic duct epithelial (HPDE) cells. Interestingly, re-expression of miR-146a inhibited the invasive capacity of Colo357 and Panc-1 PC cells with concomitant down-regulation of EGFR and IRAK-1. Mechanistic studies including miR-146a re-expression, anti-miR-146 transfection, and EGFR knock-down experiment showed that there was a crosstalk between EGFR, MTA-2, IRAK-1, IκBα and NF-κB. Most importantly, we found that the treatment of PC cells with “natural agents” [3,3′-diinodolylmethane (DIM) or isoflavone] led to an increase in the expression of miR-146a and consequently down-regulated the expression of EGFR, MTA-2, IRAK-1 and NF-κB, resulting in the inhibition of invasion of Colo357 and Panc-1 cells. These results provide experimental evidence in support of the role of DIM and isoflavone as potential non-toxic agents as regulators of miRNA, which could be useful for the inhibition of cancer cell invasion and metastasis, and further suggesting that these agents could be important for designing novel targeted strategy for the treatment of PC. PMID:25242818

Deregulation of epidermal stem cell niche contributes to pathogenesis of non-healing venous ulcers

Science.gov (United States)

Nusbaum, Aron G.; Vukelic, Sasa; Krzyzanowska, Agata; Tomic-Canic, Marjana

2014-01-01

The epidermis is maintained by epidermal stem cells (ESC) that reside in distinct niches and contribute to homeostasis and wound closure. Keratinocytes at the non-healing edges of venous ulcers (VUs) are healing-incompetent, hyper-proliferative and non-migratory suggesting deregulation of ESCs. To date genes which regulate ESC niches have been studied in mice only. Utilizing microarray analysis of VU non-healing edges, we identified changes in expression of genes harboring regulation of ESCs and their fate. In a prospective clinical study of ten VUs, we confirmed suppression of the bone morphogenetic protein receptor and GATA binding protein3 as well as inhibitors of DNA-binding proteins 2 and 4. We also found decreased levels of phosphorylated glycogen synthase kinase 3, nuclear presence of ß-catenin and overexpression of its transcriptional target, c-myc indicating activation of the Wnt pathway. Additionally, we found down-regulation of leucine-rich repeats and immunoglobulin-like domains protein 1, a gene important for maintaining ESCs in a quiescent state, and absence of keratin 15, a marker of the basal stem cell compartment suggesting local depletion of ESCs. Our study shows that loss of genes important for regulation of ESCs and their fate along with activation of ß-catenin and c-myc in the VU may contribute to ESC deprivation and a hyper-proliferative, non-migratory, healing incapable wound edge. PMID:24635172

Endosomal protein sorting and autophagy genes contribute to the regulation of yeast life span.

Science.gov (United States)

Longo, Valter D; Nislow, Corey; Fabrizio, Paola

2010-11-01

Accumulating evidence from various organisms points to a role for autophagy in the regulation of life span. By performing a genome-wide screen to identify novel life span determinants in Saccharomyces cerevisiae, we have obtained further insights into the autophagy-related and -unrelated degradation processes that may be important for preventing cellular senescence. The generation of multivesicular bodies and their fusion with the vacuole in the endosomal pathway emerged as novel cell functions involved in yeast chronological survival and longevity extension.

The role of guilt and pride in consumers’ self-regulation: an exploration on sustainability and ethical consumption

OpenAIRE

Antonetti, Paolo

2012-01-01

Researchers are interested in understanding the individual processes that favour consumers’ self-regulation since they can contribute to the achievement of personal and collective long-term goals in many areas. Sustainable and ethical consumption represents one such context; self-regulation can be a key driver for the solution of environmental and social sustainability challenges. In a series of three studies, this thesis investigates how guilt and pride contribute to consum...

Regulation of SFRP-1 expression in the rat dental follicle.

Science.gov (United States)

Liu, Dawen; Yao, Shaomian; Wise, Gary E

2012-01-01

Tooth eruption requires osteoclastogenesis and subsequent bone resorption. Secreted frizzled-related protein-1 (SFRP-1) negatively regulates osteoclastogenesis. Our previous studies indicated that SFRP-1 is expressed in the rat dental follicle (DF), with reduced expression at days 3 and 9 close to the times for the major and minor bursts of osteoclastogenesis, respectively; but it remains unclear as to what molecules contribute to its reduced expression at these critical times. Thus, it was the aim of this study to determine which molecules regulate the expression of SFRP-1 in the DF. To that end, the DF cells were treated with cytokines that are maximally expressed at days 3 or 9, and SFRP-1 expression was determined. Our study indicated that colony-stimulating factor-1 (CSF-1), a molecule maximally expressed in the DF at day 3, down-regulated SFRP-1 expression. As to endothelial monocyte-activating polypeptide II (EMAP-II), a highly expressed molecule in the DF at day 3, it had no effect on the expression of SFRP-1. However, when EMAP-II was knocked down by siRNA, the expression of SFRP-1 was elevated, and this elevated SFRP-1 expression could be reduced by adding recombinant EMAP-II protein. This suggests that EMAP-II maintained a lower level of SFRP-1 in the DF. TNF-α is a molecule maximally expressed at day 9, and this study indicated that it also down-regulated the expression of SFRP-1 in the DF cells. In conclusion, CSF-1 and EMAP-II may contribute to the reduced SFRP-1 expression seen on day 3, while TNF-α may contribute to the reduced SFRP-1 expression at day 9.

Study on institutionalization of risk-informed performance-based regulation

Energy Technology Data Exchange (ETDEWEB)

Kim, M. G.; Hong, S. Y.; Seo, M. R. [Korea Electric Power Research Institute, Taejon (Korea, Republic of)

2003-02-15

In this study, for the institutionalization of risk informed and performance based regulation in Korea, the latest technical movements of overseas countries are examined and reviewed. And the issues that was found when license change petition using risk information was submitted in Korean regulatory body are reviewed. Based on these review, the applicable areas to domestic situation will be found and proposed. This study can contribute to setting up the proper direction for the institutionalization of risk informed and performance based regulation.

Maternal emotion socialization differentially predicts third-grade children's emotion regulation and lability.

Science.gov (United States)

Rogers, Megan L; Halberstadt, Amy G; Castro, Vanessa L; MacCormack, Jennifer K; Garrett-Peters, Patricia

2016-03-01

Numerous parental emotion socialization factors have been implicated as direct and indirect contributors to the development of children's emotional competence. To date, however, no study has combined parents' emotion-related beliefs, behaviors, and regulation strategies in one model to assess their cumulative-as well as unique-contributions to children's emotion regulation. We considered the 2 components that have recently been distinguished: emotion regulation and emotional lability. We predicted that mothers' beliefs about the value of and contempt for children's emotions, mothers' supportive and nonsupportive reactions to their children's emotions, as well as mothers' use of cognitive reappraisal and suppression of their own emotions would each contribute unique variance to their children's emotion regulation and lability, as assessed by children's teachers. The study sample consisted of an ethnically and socioeconomically diverse group of 165 mothers and their third-grade children. Different patterns emerged for regulation and lability: Controlling for family income, child gender, and ethnicity, only mothers' lack of suppression as a regulatory strategy predicted greater emotion regulation in children, whereas mothers' valuing of children's emotions, mothers' lack of contempt for children's emotions, mothers' use of cognitive reappraisal to reinterpret events, and mothers' lack of emotional suppression predicted less lability in children. These findings support the divergence of emotion regulation and lability as constructs and indicate that, during middle childhood, children's lability may be substantially and uniquely affected by multiple forms of parental socialization. (c) 2016 APA, all rights reserved).

Adjustments to financial benefits and contributions with effect from 1 January 2011

CERN Multimedia

HR Department

2011-01-01

In accordance with recommendations made by the Finance Committee and decisions taken by Council in December 2010, certain financial benefits and contributions impacting salaries and stipends have been adjusted with effect from 1 January 2011. 1) Annual adjustments An increase of 0.35% to the scale of basic salaries paid to Staff Members and the scale of stipends paid to Fellows (Annexes R A 5 and R A 6 of the Staff Regulations). No adjustments to the subsistence allowances of Paid Associates and Students (Annex R A 7 of the Staff Regulations). No modifications to the following social benefits: Family, child and infant allowances (Annex R A 3 of the Staff Regulations) Payment ceilings of education fees (Annex R A 4 of the Staff Regulations). 2) Five-yearly review 2010, financial elements: Adjustment of basic salaries: An increase of 1% for Career Path D. An increase of 2% for Career Paths E to G. Technical adjustment of th...

Contemplative Practices in Early Childhood: Implications for Self-Regulation Skills and School Readiness

Science.gov (United States)

Willis, Elizabeth; Dinehart, Laura H.

2014-01-01

This article examines the development of self-regulation skills in early childhood and the possibilities of children's contemplative practices as a viable tool to facilitate this development. Current research indicates that self-regulation skills in early childhood education make a significant contribution to school readiness, and long-term…

Proceedings of the 8. Brazilian congress on energy: energy policy, regulation and sustainable development. v. 1: energy, environment and energy sector regulation

International Nuclear Information System (INIS)

1999-01-01

The theme energy policy, regulation and sustainable development chosen for the 8. Brazilian congress on energy to be held in Rio de Janeiro from 30 November of 1999 to 02 December of 1999, specifically means the contribution of energy to a satisfactory quality of life for everyone. Within such a context, the congress technical programme theme has been structured around six different divisions: energy, environment and development; energy sector regulation; energy policy and planning; technology innovation; energy conservation; and renewable energy sources and rural areas energy supply

Targeting self-regulation to promote health behaviors in children.

Science.gov (United States)

Miller, Alison L; Gearhardt, Ashley N; Fredericks, Emily M; Katz, Benjamin; Shapiro, Lilly Fink; Holden, Kelsie; Kaciroti, Niko; Gonzalez, Richard; Hunter, Christine; Lumeng, Julie C

2018-02-01

Poor self-regulation (i.e., inability to harness cognitive, emotional, motivational resources to achieve goals) is hypothesized to contribute to unhealthy behaviors across the lifespan. Enhancing early self-regulation may increase positive health outcomes. Obesity is a major public health concern with early-emerging precursors related to self-regulation; it is therefore a good model for understanding self-regulation and health behavior. Preadolescence is a transition when children increase autonomy in health behaviors (e.g., eating, exercise habits), many of which involve self-regulation. This paper presents the scientific rationale for examining self-regulation mechanisms that are hypothesized to relate to health behaviors, specifically obesogenic eating, that have not been examined in children. We describe novel intervention protocols designed to enhance self-regulation skills, specifically executive functioning, emotion regulation, future-oriented thinking, and approach bias. Interventions are delivered via home visits. Assays of self-regulation and obesogenic eating behaviors using behavioral tasks and self-reports are implemented and evaluated to determine feasibility and psychometrics and to test intervention effects. Participants are low-income 9-12 year-old children who have been phenotyped for self-regulation, stress, eating behavior and adiposity through early childhood. Study goals are to examine intervention effects on self-regulation and whether change in self-regulation improves obesogenic eating. Copyright © 2017 Elsevier Ltd. All rights reserved.

DC microgrids providing frequency regulation in electrical power system - imperfect communication issues

DEFF Research Database (Denmark)

Bašić, Hrvoje; Dragicevic, Tomislav; Pandžić, Hrvoje

2017-01-01

This paper presents a model of multiple DC microgrids with battery energy storage systems and demand response capability, taking part in primary frequency regulation of electrical power system. Although DC microgrids can contribute to stability and efficiency of frequency regulation, these complex...... systems may cause serious stability issues due to the imperfect communication. This work presents possible scenarios of unstable primary frequency regulation in a simplified model of electrical power system with DC microgrids, which are controlled through communication network....

MicroRNAs That Contribute to Coordinating the Immune Response in Drosophila melanogaster.

Science.gov (United States)

Atilano, Magda L; Glittenberg, Marcus; Monteiro, Annabel; Copley, Richard R; Ligoxygakis, Petros

2017-09-01

Small noncoding RNAs called microRNAs (miRNAs) have emerged as post-transcriptional regulators of gene expression related to host defenses. Here, we have used Drosophila melanogaster to explore the contribution of individual or clusters of miRNAs in countering systemic Candida albicans infection. From a total of 72 tested, we identify 6 miRNA allelic mutant backgrounds that modulate the survival response to infection and the ability to control pathogen number. These mutants also exhibit dysregulation of the Toll pathway target transcripts Drosomycin ( Drs ) and Immune-Induced Molecule 1 ( IM1 ). These are characteristics of defects in Toll signaling, and consistent with this, we demonstrate dependency for one of the miRNA mutants on the NF-κΒ homolog Dif. We also quantify changes in the miRNA expression profile over time in response to three pathogen types, and identify 13 mature miRNA forms affected by pathogens that stimulate Toll signaling. To complement this, we provide a genome-wide map of potential NF-κB sites in proximity to miRNA genes. Finally, we demonstrate that systemic C. albicans infection contributes to a reduction in the total amount of branch-chained amino acids, which is miRNA-regulated. Overall, our data reveal a new layer of miRNA complexity regulating the fly response to systemic fungal infection. Copyright © 2017 Atilano et al.

Reflections on Competition, Competition Regulation and the Current Crises

DEFF Research Database (Denmark)

Buch-Hansen, Hubert; Wigger, Angela

2013-01-01

competition came to enjoy such an exalted status in Europe and then challenges conventional wisdom by bringing into focus the downsides of competition. It argues that excessive competition and neoliberal competition regulation have contributed to intensify the economic, political, social and environmental...

Commodification of Sexual Labor: The Contribution of Internet Communities to Prostitution Reform

Science.gov (United States)

Young, Jeffrey R.

2009-01-01

This is an ethnographic study of a self-regulated Internet site that facilitates illegal female prostitution in South Florida. The purpose is to identify the social and economic characteristics of the site that can contribute to acceptable prostitution reform. The members of the site appear to sustain an orderly and mutually respectful exchange of…

Genetic and environmental influences on individual differences in emotion regulation and its relation to working memory in toddlerhood.

Science.gov (United States)

Wang, Manjie; Saudino, Kimberly J

2013-12-01

This is the first study to explore genetic and environmental contributions to individual differences in emotion regulation in toddlers, and the first to examine the genetic and environmental etiology underlying the association between emotion regulation and working memory. In a sample of 304 same-sex twin pairs (140 MZ, 164 DZ) at age 3, emotion regulation was assessed using the Behavior Rating Scale of the Bayley Scales of Infant Development (BRS; Bayley, 1993), and working memory was measured by the visually cued recall (VCR) task (Zelazo, Jacques, Burack, & Frye, 2002) and several memory tasks from the Mental Scale of the BSID. Based on model-fitting analyses, both emotion regulation and working memory were significantly influenced by genetic and nonshared environmental factors. Shared environmental effects were significant for working memory, but not for emotion regulation. Only genetic factors significantly contributed to the covariation between emotion regulation and working memory.

Government regulation as an impetus for innovation: Evidence from energy performance regulation in the Dutch residential building sector

International Nuclear Information System (INIS)

Beerepoot, Milou; Beerepoot, Niels

2007-01-01

The recent implementation of energy performance policy as a way to tackle energy consumption in the building sector in Europe draws attention to the effect it has on the development and diffusion of energy-saving innovations. According to innovation system literature, government regulation through norms and standards is one of the factors stimulating innovation. This paper concentrates on the role of stricter government regulation as an incentive to innovation in the Dutch residential building sector. Innovation in this sector is predominantly a process of applying incremental modifications to comply with new and stricter government regulations and standards. Energy performance policy in its current shape will therefore not contribute to the diffusion of really new innovation in energy techniques for residential buildings in the Netherlands. If diffusion of really new innovation is an explicit aim of energy performance policy then the European wide introduction of this scheme needs reconsideration

Dual diathesis-stressor model of emotional and linguistic contributions to developmental stuttering.

Science.gov (United States)

Walden, Tedra A; Frankel, Carl B; Buhr, Anthony P; Johnson, Kia N; Conture, Edward G; Karrass, Jan M

2012-05-01

This study assessed emotional and speech-language contributions to childhood stuttering. A dual diathesis-stressor framework guided this study, in which both linguistic requirements and skills, and emotion and its regulation, are hypothesized to contribute to stuttering. The language diathesis consists of expressive and receptive language skills. The emotion diathesis consists of proclivities to emotional reactivity and regulation of emotion, and the emotion stressor consists of experimentally manipulated emotional inductions prior to narrative speaking tasks. Preschool-age children who do and do not stutter were exposed to three emotion-producing overheard conversations-neutral, positive, and angry. Emotion and emotion-regulatory behaviors were coded while participants listened to each conversation and while telling a story after each overheard conversation. Instances of stuttering during each story were counted. Although there was no main effect of conversation type, results indicated that stuttering in preschool-age children is influenced by emotion and language diatheses, as well as coping strategies and situational emotional stressors. Findings support the dual diathesis-stressor model of stuttering.

Biphasic regulation of intracellular calcium by gemfibrozil contributes to inhibiting L6 myoblast differentiation: implications for clinical myotoxicity.

Science.gov (United States)

Liu, Aiming; Yang, Julin; Gonzalez, Frank J; Cheng, Gary Q; Dai, Renke

2011-02-18

Gemfibrozil is the most myotoxic fibrate drug commonly used for dyslipidemia, but the mechanism is poorly understood. The current study revealed that gemfibrozil inhibits myoblast differentiation through the regulation of intracellular calcium ([Ca(2+)]i) as revealed in L6 myoblasts by use of laser scan confocal microscopy and flow cytometry using Fluo-4 AM as a probe. Gemfibrozil at 20-400 μM, could regulate [Ca(2+)]i in L6 cells in a biphasic manner, and sustained reduction was observed when the concentration reached 200 μM. Inhibition of L6 differentiation by gemfibrozil was concentration-dependent with maximal effect noted between 200 and 400 μM, as indicated by creatine kinase activities and the differentiation index, respectively. In differentiating L6 myoblasts, gemfibrozil at concentrations below 400 μM led to no significant signs of apoptosis or cytotoxicity, whereas differentiation, inhibited by 200 μM gemfibrozil, was only partially recovered. A good correlation was noted between gemfibrozil concentrations that regulate [Ca(2+)]i and inhibit L6 myoblasts differentiation, and both are within the range of total serum concentrations found in the clinic. These data suggest a potential pharmacodynamic effect of gemfibrozil on myogenesis as a warning sign, in addition to the complex pharmacokinetic interactions. It is also noteworthy that mobilization of [Ca(2+)]i by gemfibrozil may trigger complex biological responses besides myocyte differentiation. Information revealed in this study explores the mechanism of gemfibrozil-induced myotoxicity through the regulation of intracellular calcium.

Factors contribution to the reduction of occupational exposures at Dukovany NPP

International Nuclear Information System (INIS)

Petrova, K.; Urbancik, L.; Fuchsova, D.; Kulich, V.

2008-01-01

This paper describes the causes of achieving such low collective doses and the ways used for a further optimization process reducing occupational exposure at the Dukovany NPP from the beginning of operation up to now. The objective of this contribution is to explain the approaches leading to reduced occupational radiation exposure, measures which have been implemented and what is needed for the maintenance of excellent results in the future. It is possible to identify three main areas and eight main sources affecting collective dose values. There are one objective and two specific causes for low exposures: 1. Objective cause: - General arrangement; - Structural materials; - Fuel integrity. 2. Specific cause influenced by the state regulation: - Legislative support; - Operational safety culture; - Well-though tout system of radiological monitoring; - Effective radiological event feedback; - Effective education and training. 3. Specific cause uninfluenced by the state regulation: - Modified water chemistry of the primary circuit adopted by the licensee; - Licensee's system of radiation work debriefing. All the items specified above contribute to a unique concurrence of circumstances leading to the constantly low occupational exposures at the Czech nuclear power plants. The paper discusses all factors involved in these good results. (authors)

The New Intergovernmentalism in Financial Regulation and European Banking Union

OpenAIRE

Howarth, David; Quaglia, Lucia

2015-01-01

This contribution asks whether a new type of intergovernmentalism has emerged in financial services regulation and Banking Union. Since financial services are a key area of the single market, the chapter concludes by reflecting on whether the governance trends in the financial sector can be generalised to other areas of the single market. It is argued that the single market for financial services, which encompasses financial regulation and the plan for Banking Union, provides an interesting m...

Commission de regulation de l'energie. Activity Report 2009

International Nuclear Information System (INIS)

2010-01-01

CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2009 activity report of CRE. Content: A - How the CRE works and the activity of the CoRDiS; B - Implementation of the third energy package will strengthen regulation in this sector; C - The regulator contributes to the correct operation of the infrastructures, the interconnection of European grids and security of supplies; D - Regulation: serving investment and quality; E - Renewable energy, advanced metering systems and the grids of the future are all priority means of delivering sustainable development; F - The CRE is contributing to the smooth operation of electricity and gas markets to the benefit of consumers; G - Appendices: 1. Summary of the principal deliberations of the CRE; 2. European and international calendar for 2009; 3. Council of European Energy Regulators (CEER); 4. Glossary; 5. Acronyms; 6. Units and conversions; 7. Index; 8. List of boxes, figures and tables

Down-regulation of CatSper1 channel in epididymal spermatozoa contributes to the pathogenesis of asthenozoospermia, whereas up-regulation of the channel by Sheng-Jing-San treatment improves the sperm motility of asthenozoospermia in rats.

Science.gov (United States)

Wang, Ya-Nan; Wang, Bo; Liang, Ming; Han, Cai-Yan; Zhang, Bin; Cai, Jie; Sun, Wei; Xing, Guo-Gang

2013-02-01

To determine the expression of CatSper1 channel in epididymal spermatozoa in a rat model of asthenozoospermia, induced by cyclophosphamide (CP), and further examine the effects of soluble granules of Sheng-Jing-San (SJS), a traditional Chinese medicine recipe, on CatSper1 expression and sperm motility in the CP-induced asthenozoospermic rats. Placebo-controlled, randomized trial. Neuroscience Research Institute, Peking University, China. Sexually mature male Sprague-Dawley rats (n = 60). In the CP group, CP at the dose of 35 mg/kg intraperitoneally injected into rats once a day for 7 days; in the normal saline (NS) group, 0.9% saline solution was injected as control. Sperm motility and count were evaluated by computer-assisted sperm assay (CASA); protein and mRNA expression of CatSper1 channel in epididymal spermatozoa was determined by Western blotting and quantitative real-time RT-PCR, respectively. The rats were randomly divided into five groups with 12 rats in each group: CP, normal saline (NS), CP + SJS, CP + NS, and treatment naïve. In the CP + SJS group, after the last injection of CP, SJS at a dose of 30 mg/kg was intragastrically administrated to rats once a day for 14 days; in CP + NS group, saline solution instead of SJS was administrated as control. In the treatment naïve group, rats were normally fed for 21 days as controls. We found a statistically significant reduction of the CatSper1 channel, which is associated with an impairment of sperm motility in the epididymal spermatozoa of CP-induced asthenozoospermic rats. Soluble granules of SJS could dramatically restore the CP-induced down-regulation of CatSper1 in epididymal spermatozoa, which greatly improved the sperm motility in the asthenozoospermic rats. Down-regulation of the CatSper1 channel in epididymal spermatozoa likely contributes to the pathogenesis of asthenozoospermia, whereas up-regulation of the channel by SJS improves sperm motility and thus can be used as an effective therapeutic

RNA polymerase III transcription - regulated by chromatin structure and regulator of nuclear chromatin organization.

Science.gov (United States)

Pascali, Chiara; Teichmann, Martin

2013-01-01

RNA polymerase III (Pol III) transcription is regulated by modifications of the chromatin. DNA methylation and post-translational modifications of histones, such as acetylation, phosphorylation and methylation have been linked to Pol III transcriptional activity. In addition to being regulated by modifications of DNA and histones, Pol III genes and its transcription factors have been implicated in the organization of nuclear chromatin in several organisms. In yeast, the ability of the Pol III transcription system to contribute to nuclear organization seems to be dependent on direct interactions of Pol III genes and/or its transcription factors TFIIIC and TFIIIB with the structural maintenance of chromatin (SMC) protein-containing complexes cohesin and condensin. In human cells, Pol III genes and transcription factors have also been shown to colocalize with cohesin and the transcription regulator and genome organizer CCCTC-binding factor (CTCF). Furthermore, chromosomal sites have been identified in yeast and humans that are bound by partial Pol III machineries (extra TFIIIC sites - ETC; chromosome organizing clamps - COC). These ETCs/COC as well as Pol III genes possess the ability to act as boundary elements that restrict spreading of heterochromatin.

Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling

Directory of Open Access Journals (Sweden)

Neha S. Dole

2017-11-01

Full Text Available Poor bone quality contributes to bone fragility in diabetes, aging, and osteogenesis imperfecta. However, the mechanisms controlling bone quality are not well understood, contributing to the current lack of strategies to diagnose or treat bone quality deficits. Transforming growth factor beta (TGF-β signaling is a crucial mechanism known to regulate the material quality of bone, but its cellular target in this regulation is unknown. Studies showing that osteocytes directly remodel their perilacunar/canalicular matrix led us to hypothesize that TGF-β controls bone quality through perilacunar/canalicular remodeling (PLR. Using inhibitors and mice with an osteocyte-intrinsic defect in TGF-β signaling (TβRIIocy−/−, we show that TGF-β regulates PLR in a cell-intrinsic manner to control bone quality. Altogether, this study emphasizes that osteocytes are key in executing the biological control of bone quality through PLR, thereby highlighting the fundamental role of osteocyte-mediated PLR in bone homeostasis and fragility.

Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling.

Science.gov (United States)

Dole, Neha S; Mazur, Courtney M; Acevedo, Claire; Lopez, Justin P; Monteiro, David A; Fowler, Tristan W; Gludovatz, Bernd; Walsh, Flynn; Regan, Jenna N; Messina, Sara; Evans, Daniel S; Lang, Thomas F; Zhang, Bin; Ritchie, Robert O; Mohammad, Khalid S; Alliston, Tamara

2017-11-28

Poor bone quality contributes to bone fragility in diabetes, aging, and osteogenesis imperfecta. However, the mechanisms controlling bone quality are not well understood, contributing to the current lack of strategies to diagnose or treat bone quality deficits. Transforming growth factor beta (TGF-β) signaling is a crucial mechanism known to regulate the material quality of bone, but its cellular target in this regulation is unknown. Studies showing that osteocytes directly remodel their perilacunar/canalicular matrix led us to hypothesize that TGF-β controls bone quality through perilacunar/canalicular remodeling (PLR). Using inhibitors and mice with an osteocyte-intrinsic defect in TGF-β signaling (TβRII ocy-/- ), we show that TGF-β regulates PLR in a cell-intrinsic manner to control bone quality. Altogether, this study emphasizes that osteocytes are key in executing the biological control of bone quality through PLR, thereby highlighting the fundamental role of osteocyte-mediated PLR in bone homeostasis and fragility. Published by Elsevier Inc.

Developmental regulation of aromatase activity in the rat hypothalamus

International Nuclear Information System (INIS)

Lephart, E.D.

1989-01-01

The brain of all mammalian species studied thus far contain an enzymatic activity (aromatase) that catalyzes the conversion of androgens to estrogens. The activity is highest during prenatal development and contributes to the establishment of sex differences which determine adult gonadotropin secretion patterns and reproductive behavior. The studies presented in this dissertation represent a systematic effort to elucidate the mechanism(s) that control the initiation of and contribute to maintaining rat hypothalamic aromatase activity during pre- and postnatal development. Aromatase enzyme activity was measured by the 3 H 2 O release assay or by traditional estrogen product isolation. Brain aromatase mRNA was detected by hybridization to a cDNA encoding rat aromatase cytochrome P-450. In both males and females the time of puberty was associated with a decline in hypothalamic aromatase activity. This decline may represent a factor underlying the peri-pubertal decrease in the sensitivity to gonadal steroid feedback that accompanies completion of puberty. The results also indicate that androgens regulate brain aromatase levels during both the prepubertal and peri-pubertal stages of sexual development and that this regulation is transiently lost in young adults. Utilizing a hypothalamic organotypic culture system, aromatase activity in vitro was maintained for as long as two days. The results of studies of a variety of hormonal and metabolic regulators suggest that prenatal aromatase activity is regulated by factor(s) that function independently from the classical cyclic AMP and protein kinase C trans-membrane signaling pathways

e-Research and Learning Theory: What Do Sequence and Process Mining Methods Contribute?

Science.gov (United States)

Reimann, Peter; Markauskaite, Lina; Bannert, Maria

2014-01-01

This paper discusses the fundamental question of how data-intensive e-research methods could contribute to the development of learning theories. Using methodological developments in research on self-regulated learning as an example, it argues that current applications of data-driven analytical techniques, such as educational data mining and its…

Measuring strategies for learning regulation in medical education: scale reliability and dimensionality in a Swedish sample.

Science.gov (United States)

Edelbring, Samuel

2012-08-15

The degree of learners' self-regulated learning and dependence on external regulation influence learning processes in higher education. These regulation strategies are commonly measured by questionnaires developed in other settings than in which they are being used, thereby requiring renewed validation. The aim of this study was to psychometrically evaluate the learning regulation strategy scales from the Inventory of Learning Styles with Swedish medical students (N = 206). The regulation scales were evaluated regarding their reliability, scale dimensionality and interrelations. The primary evaluation focused on dimensionality and was performed with Mokken scale analysis. To assist future scale refinement, additional item analysis, such as item-to-scale correlations, was performed. Scale scores in the Swedish sample displayed good reliability in relation to published results: Cronbach's alpha: 0.82, 0.72, and 0.65 for self-regulation, external regulation and lack of regulation scales respectively. The dimensionalities in scales were adequate for self-regulation and its subscales, whereas external regulation and lack of regulation displayed less unidimensionality. The established theoretical scales were largely replicated in the exploratory analysis. The item analysis identified two items that contributed little to their respective scales. The results indicate that these scales have an adequate capacity for detecting the three theoretically proposed learning regulation strategies in the medical education sample. Further construct validity should be sought by interpreting scale scores in relation to specific learning activities. Using established scales for measuring students' regulation strategies enables a broad empirical base for increasing knowledge on regulation strategies in relation to different disciplinary settings and contributes to theoretical development.

Lipids in the cell: organisation regulates function.

Science.gov (United States)

Santos, Ana L; Preta, Giulio

2018-06-01

Lipids are fundamental building blocks of all cells and play important roles in the pathogenesis of different diseases, including inflammation, autoimmune disease, cancer, and neurodegeneration. The lipid composition of different organelles can vary substantially from cell to cell, but increasing evidence demonstrates that lipids become organised specifically in each compartment, and this organisation is essential for regulating cell function. For example, lipid microdomains in the plasma membrane, known as lipid rafts, are platforms for concentrating protein receptors and can influence intra-cellular signalling. Lipid organisation is tightly regulated and can be observed across different model organisms, including bacteria, yeast, Drosophila, and Caenorhabditis elegans, suggesting that lipid organisation is evolutionarily conserved. In this review, we summarise the importance and function of specific lipid domains in main cellular organelles and discuss recent advances that investigate how these specific and highly regulated structures contribute to diverse biological processes.

Microenvironmental regulation of hematopoietic stem cells and its implications in leukemogenesis.

Science.gov (United States)

Seshadri, Madhav; Qu, Cheng-Kui

2016-07-01

Hematopoietic stem cells (HSCs) are a population of cells in the bone marrow which can self-renew, differentiate into late lineage progenitors, or remain quiescent. HSCs exist alongside several cell types in the bone marrow microenvironment that comprise the stem cell niche. These cells regulate HSC function and can contribute to leukemogenesis. In this review we will discuss recent advances in this field. In the vascular niche, arteriolar and sinusoidal zones appear to play distinct roles in HSC function. Endothelial cells modulate HSC function via Notch and other signaling pathways. In the endosteal niche multiple cell types regulate HSCs. Osteoblasts promote HSC quiescence via secreted factors and possibly physical interactions, whereas adipocytes may oppose HSC quiescence. The balance of these opposing factors depends on metabolic cues. Feedback from HSC-derived cells, including macrophages and megakaryocytes also appears to regulate HSC quiescence. Dysfunction of the bone marrow microenvironment, including mesenchymal stem cell-derived stromal cells and the sympathetic nervous system can induce or alter the progression of hematologic malignancies. Many cell types in the bone marrow microenvironment affect HSC function and contribute to malignancy. Further understanding how HSCs are regulated by the microenvironment has clinical implications for stem cell transplantation and other therapies for hematologic malignancies.

Regulations as a Tool to Increase Consumer Protection on the European Retail Payment Market

Directory of Open Access Journals (Sweden)

Janina Harasim

2018-03-01

Full Text Available Aim/purpose - The purpose of the paper is to identify the main areas of customers' threats concerning using financial services and the in-depth review of European industry- -specific consumer regulations concerning current accounts and payments. Design/methodology/approach - Desk research including in-depth analysis of industry- specific consumer regulations referring to current accounts and payment services having the character of EU directives and regulations, European Commission reports, and documents. Findings - The paper shows that consumers' interests are threatened even when they use basic financial services as current account and combined payment instruments. The analysis based on of desk resources has revealed that the regulations give effect to customer protection only if they strictly correspond to defined areas of threats and particular types of risks. Research implications/limitations - The experience of the recent financial crisis proved that the asymmetry of knowledge and information was one of the crucial reasons disrupting customers' position on financial markets. Research findings will help to identify gaps in regulations and develop the quality of further initiatives aimed on informing customers about the implementation of regulations and improving their financial literacy level. Originality/value/contribution - The payment products are rarely discussed in the literature in the context of consumers' protection and financial regulations. This paper contributes to the debate by providing an overview of financial consumer protection issues concerning retail payments.(original abstract

Deleted in breast cancer-1 regulates SIRT1 activity and contributes to high-fat diet-induced liver steatosis in mice.

NARCIS (Netherlands)

Escande, C.; Chini, C.C.; Nin, V.; Dykhouse, K.M.; Novak, C.M.; Levine, J.; Deursen, J.M.A. van; Gores, G.J.; Chen, J.; Lou, Z.; Chini, E.N.

2010-01-01

The enzyme sirtuin 1 (SIRT1) is a critical regulator of many cellular functions, including energy metabolism. However, the precise mechanisms that modulate SIRT1 activity remain unknown. As SIRT1 activity in vitro was recently found to be negatively regulated by interaction with the deleted in

Hypothalamic inflammation and food intake regulation during chronic illness

NARCIS (Netherlands)

Dwarkasing, J.T.; Marks, D.L.; Witkamp, R.F.; Norren, van K.

2016-01-01

Anorexia is a common symptom in chronic illness. It contributes to malnutrition and strongly affects survival and quality of life. A common denominator of many chronic diseases is an elevated inflammatory status, which is considered to play a pivotal role in the failure of food-intake regulating

A study on the safety regulation of byproduct material (II)

Energy Technology Data Exchange (ETDEWEB)

Song, Jong Sun; Song, Yang Su [Chosun Univ., Gwangju (Korea, Republic of)

2000-03-15

The scope of this study consists of : in relating to the domestic license of byproduct material, a survey of technical criteria and status of regulation in U.S.A., a determination of range of application and contents of byproduct material, a tentative suggestion of related technical criteria and regulatory system. A study was performed about the above topics to establish the safe regulation of byproduct material institutionally, and this can be contributed in establishing the proper domestic technical criteria related.

Blood pressure regulation in diabetic autonomic neuropathy

DEFF Research Database (Denmark)

Hilsted, J

1985-01-01

Defective blood pressure responses to standing, exercise and epinephrine infusions have been demonstrated in diabetic patients with autonomic neuropathy. The circulatory mechanisms underlying blood pressure responses to exercise and standing up in these patients are well characterized: In both...... which may contribute to exercise hypotension in these patients. During hypoglycemia, blood pressure regulation seems intact in patients with autonomic neuropathy. This is probably due to release of substantial amounts of catecholamines during these experiments. During epinephrine infusions a substantial...... blood pressure fall ensues in patients with autonomic neuropathy, probably due to excessive muscular vasodilation. It is unresolved why blood pressure regulation is intact during hypoglycemia and severely impaired--at similar catecholamine concentrations--during epinephrine infusions....

Posttranscriptional regulation of adrenal TH gene expression contributes to the maladaptive responses triggered by insulin-induced recurrent hypoglycemia.

Science.gov (United States)

Kudrick, Necla; Chan, Owen; La Gamma, Edmund F; Kim, Juhye Lena; Tank, Arnold William; Sterling, Carol; Nankova, Bistra B

2015-02-01

Acute metabolic stress such as insulin-induced hypoglycemia triggers a counterregulatory response during which the release of catecholamines (epinephrine), the activation of tyrosine hydroxylase (TH) enzyme and subsequent compensatory catecholamine biosynthesis occur in the adrenal medulla. However, recurrent exposure to hypoglycemia (RH), a consequence of tight glycemic control in individuals with type 1 and type 2 diabetes compromises this physiological response. The molecular mechanisms underlying the maladaptive response to repeated glucose deprivation are incompletely understood. We hypothesize that impaired epinephrine release following RH reflects altered regulation of adrenal catecholamine biosynthesis. To test this hypothesis, we compared the effect of single daily (RH) and twice-daily episodes of insulin-induced hypoglycemia (2RH) on adrenal epinephrine release and production in normal rats. Control animals received saline injections under similar conditions (RS and 2RS, respectively). Following 3 days of treatment, we assessed the counterregulatory hormonal responses during a hypoglycemic clamp. Changes in adrenal TH gene expression were also analyzed. The counterregulatory responses, relative TH transcription and TH mRNA levels and Ser40-TH phosphorylation (marker for enzyme activation) were induced to a similar extent in RS, 2RS, and RH groups. In contrast, epinephrine and glucagon responses were attenuated in the 2RH group and this was associated with a limited elevation of adrenal TH mRNA, rapid inactivation of TH enzyme and no significant changes in TH protein. Our results suggest that novel posttranscriptional mechanisms controlling TH mRNA and activated TH enzyme turnover contribute to the impaired epinephrine responses and may provide new therapeutic targets to prevent HAAF. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Professional Self-Regulation and the Public Interest in Canada

Directory of Open Access Journals (Sweden)

Tracey L. Adams

2016-09-01

Full Text Available The regulation of professional groups has often been justified as being in the public interest. In recent decades, policymakers in Anglo-American countries have questioned whether self-regulating professions have truly served the public interest, or whether they have merely acted in their own interests. This paper draws on legislative records and policy reports to explore meanings attached to professional self-regulation and the public interest in Canada by state actors over the past 150 years. The findings point to a shift in the definition of the public interest away from service quality and professional interests, towards efficiency, human rights, consumer choice, and in some contexts business interests. Changing views of the public interest contribute to regulatory change.

Ethanol activation of protein kinase A regulates GABA-A receptor subunit expression in the cerebral cortex and contributes to ethanol-induced hypnosis

Directory of Open Access Journals (Sweden)

Sandeep eKumar

2012-04-01

Full Text Available Protein kinases are implicated in neuronal cell functions such as modulation of ion channel function, trafficking and synaptic excitability. Both protein kinase C (PKC and A (PKA are involved in regulation of γ-aminobutyric acid type A (GABA-A receptors through phosphorylation. However, the role of PKA in regulating GABA-A receptors following acute ethanol exposure is not known. The present study investigated the role of PKA in ethanol effects on GABA-A receptor α1 subunit expression in the P2 synaptosomal fraction of the rat cerebral cortex. Additionally, GABA-related behaviors were also examined. Rats were administered ethanol (2.0 – 3.5 g/kg or saline and PKC, PKA and GABA-A receptor α1 subunit levels were measured by Western blot analysis. Ethanol (3.5 g/kg transiently increased GABA-A receptor α1 subunit expression and PKA RIIβ subunit expression at similar time points whereas PKA RIIα was increased at later time points. In contrast, PKC isoform expression remained unchanged. Notably, the moderate ethanol dose (2.0g/kg had no effect on GABA-A α1 subunit levels although PKA RIIα and RIIβ were increased at 10 and 60 minutes, when PKC isozymes are also known to be elevated. To determine if PKA activation was responsible for the ethanol-induced elevation of GABA-A α1 subunits, the PKA antagonist H89 was administered to rats prior to ethanol exposure. H89 administration prevented ethanol-induced increases in GABA-A receptor α1 subunit expression. Moreover, increasing PKA activity intracerebroventricularly with Sp-cAMP prior to a hypnotic dose of ethanol increased ethanol-induced loss of righting reflex duration. This effect appears to be mediated in part by GABA-A receptors as increasing PKA activity also increased the duration of muscimol-induced loss of righting reflex. Overall these data suggest that PKA mediates ethanol-induced GABA-A receptor expression and contributes to ethanol behavioral effects involving GABA-A receptors.

An action plan for radioactive substances regulation

International Nuclear Information System (INIS)

1998-01-01

This document sets out an action plan for the Agency's Radioactive Substances Regulation function. Our vision is to secure continuous improvement in the protection of the public and the environment from the harmful effects of radioactive substances. Radioactive Substances Regulation will work with others to realise this vision and contribute to the Agency's role in achieving sustainable development. We will also work to ensure that the Agency achieves its objectives in an efficient, consistent and integrated way. The main elements of our Action Plan are as follows: establishing indicators of sustainability and the means and methods of monitoring them; establishing performance indicators and a programme of targets and objectives to be achieved; establishing a database of all premises subject to RSA93 and to use it for work planning, resource targeting, and improvement to radioactive waste management; provision of systems of procedures and technical guidance to ensure nationally consistent and cost- effective regulation; establishing systems to audit the implementation of the procedures and guidance; ensuring quality of regulation by defining technical competencies of inspectors and the training programmes to secure them; an R and D programme targeted on improving radioactive waste management and radioactive substances regulation; and full and effective participation in development of national policy

ELF4 Regulates GIGANTEA Chromatin Access through Subnuclear Sequestration

Directory of Open Access Journals (Sweden)

Yumi Kim

2013-03-01

Full Text Available Many organisms, including plants, use the circadian clock to measure the duration of day and night. Daily rhythms in the plant circadian system are generated by multiple interlocked transcriptional/translational loops and also by spatial regulations such as nuclear translocation. GIGANTEA (GI, one of the key clock components in Arabidopsis, makes distinctive nuclear bodies like other nuclear-localized circadian regulators. However, little is known about the dynamics or roles of GI subnuclear localization. Here, we characterize GI subnuclear compartmentalization and identify unexpected dynamic changes under diurnal conditions. We further identify EARLY FLOWERING 4 (ELF4 as a regulator of GI nuclear distribution through a physical interaction. ELF4 sequesters GI from the nucleoplasm, where GI binds the promoter of CONSTANS (CO, to discrete nuclear bodies. We suggest that the subnuclear compartmentalization of GI by ELF4 contributes to the regulation of photoperiodic flowering.

Carbohydrate solutions and contribute to the improvement of physical performance during a high-intensity and long-lasting physical exercise: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006

DEFF Research Database (Denmark)

Sjödin, Anders Mikael

2018-01-01

Following an application from Specialised Nutrition Europe (SNE), submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of France, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver...... an opinion on the scientific substantiation of a health claim related to carbohydrate solutions and contribute to the improvement of physical performance during a high‐intensity and long‐lasting physical exercise. The scope of the application was proposed to fall under a health claim based on newly developed...... effect. The claimed effect proposed by the applicant is ‘contribute to the improvement of physical performance during a high‐intensity and long‐lasting physical exercise’, which is considered by the Panel as a beneficial physiological effect. The Panel concludes that a cause and effect relationship has...

Solar wind heat flux regulation by the whistler instability

International Nuclear Information System (INIS)

Gary, S.P.; Feldman, W.C.

1977-01-01

This paper studies the role of the whistler instability in the regulation of the solar wind heat flux near 1 AU. A comparison of linear and second-order theory with experimental results provides strong evidence that the whistler may at times contribute to the limitation of this heat flux

Commission for Energy regulation (CRE) - Activity report june 2008; Commission de regulation de l'energie (CRE) - Rapport d'activite juin 2008

Energy Technology Data Exchange (ETDEWEB)

NONE

2008-07-01

CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2008 activity report of CRE. Content: A - How CRE works: CRE regulatory authority and organisation: Powers, Organisation; Budget resources; Personnel; B - The Standing Committee for Dispute Settlement and Sanctions (CoRDiS) activity: Admissibility, Authority; C - Building a single European energy market: Overview; Organisation and coordination of the main European regulators (Work carried out collectively by European regulators, Regulator organisation and development, CRE's relations with European Community institutions, Development of CEER activities outside the European Union); CRE's European activities (The contribution of European regulators to the Third Energy Package, Integration of gas markets, Integration of electricity markets, Operation of the European interconnected electricity grid and security of supply, Opening up markets to benefit consumers); European Community activities (The European Commission's proposals for the internal energy market: the Third Energy Package, The European Commission's proposals for fighting climate change: the Climate Package, Infringement

Early Behavioral Self-Regulation, Academic Achievement, and Gender: Longitudinal Findings from France, Germany, and Iceland

Science.gov (United States)

Gestsdottir, Steinunn; von Suchodoletz, Antje; Wanless, Shannon B.; Hubert, Blandine; Guimard, Philippe; Birgisdottir, Freyja; Gunzenhauser, Catherine; McClelland, Megan

2014-01-01

Research suggests that behavioral self-regulation skills are critical for early school success, but few studies have explored such links among young children in Europe. This study examined the contribution of early self-regulation to academic achievement gains among children in France, Germany, and Iceland. Gender differences in behavioral…

Eight paths of ERK1/2 signalling pathway regulating hepatocyte ...

Indian Academy of Sciences (India)

2011-12-05

Dec 5, 2011 ... This study aims at exploring which paths of ERK1/2 signalling pathway participate in the regulation of rat .... total RNA was used to synthesize the first strand of cDNA. ..... stem cells contribute to regeneration of injured liver.

Enhancer-derived lncRNAs regulate genome architecture: fact or fiction?

CSIR Research Space (South Africa)

Fanucchi, Stephanie

2017-06-01

Full Text Available How does the non-coding portion of the genome contribute to the regulation of genome architecture? A recent paper by Tan et al. focuses on the relationship between cis-acting complex-trait-associated lincRNAs and the formation of chromosomal...

Measuring strategies for learning regulation in medical education: Scale reliability and dimensionality in a Swedish sample

Directory of Open Access Journals (Sweden)

Edelbring Samuel

2012-08-01

Full Text Available Abstract Background The degree of learners’ self-regulated learning and dependence on external regulation influence learning processes in higher education. These regulation strategies are commonly measured by questionnaires developed in other settings than in which they are being used, thereby requiring renewed validation. The aim of this study was to psychometrically evaluate the learning regulation strategy scales from the Inventory of Learning Styles with Swedish medical students (N = 206. Methods The regulation scales were evaluated regarding their reliability, scale dimensionality and interrelations. The primary evaluation focused on dimensionality and was performed with Mokken scale analysis. To assist future scale refinement, additional item analysis, such as item-to-scale correlations, was performed. Results Scale scores in the Swedish sample displayed good reliability in relation to published results: Cronbach’s alpha: 0.82, 0.72, and 0.65 for self-regulation, external regulation and lack of regulation scales respectively. The dimensionalities in scales were adequate for self-regulation and its subscales, whereas external regulation and lack of regulation displayed less unidimensionality. The established theoretical scales were largely replicated in the exploratory analysis. The item analysis identified two items that contributed little to their respective scales. Discussion The results indicate that these scales have an adequate capacity for detecting the three theoretically proposed learning regulation strategies in the medical education sample. Further construct validity should be sought by interpreting scale scores in relation to specific learning activities. Using established scales for measuring students’ regulation strategies enables a broad empirical base for increasing knowledge on regulation strategies in relation to different disciplinary settings and contributes to theoretical development.

Medial prefrontal cortex and the adaptive regulation of reinforcement learning parameters.

Science.gov (United States)

Khamassi, Mehdi; Enel, Pierre; Dominey, Peter Ford; Procyk, Emmanuel

2013-01-01

Converging evidence suggest that the medial prefrontal cortex (MPFC) is involved in feedback categorization, performance monitoring, and task monitoring, and may contribute to the online regulation of reinforcement learning (RL) parameters that would affect decision-making processes in the lateral prefrontal cortex (LPFC). Previous neurophysiological experiments have shown MPFC activities encoding error likelihood, uncertainty, reward volatility, as well as neural responses categorizing different types of feedback, for instance, distinguishing between choice errors and execution errors. Rushworth and colleagues have proposed that the involvement of MPFC in tracking the volatility of the task could contribute to the regulation of one of RL parameters called the learning rate. We extend this hypothesis by proposing that MPFC could contribute to the regulation of other RL parameters such as the exploration rate and default action values in case of task shifts. Here, we analyze the sensitivity to RL parameters of behavioral performance in two monkey decision-making tasks, one with a deterministic reward schedule and the other with a stochastic one. We show that there exist optimal parameter values specific to each of these tasks, that need to be found for optimal performance and that are usually hand-tuned in computational models. In contrast, automatic online regulation of these parameters using some heuristics can help producing a good, although non-optimal, behavioral performance in each task. We finally describe our computational model of MPFC-LPFC interaction used for online regulation of the exploration rate and its application to a human-robot interaction scenario. There, unexpected uncertainties are produced by the human introducing cued task changes or by cheating. The model enables the robot to autonomously learn to reset exploration in response to such uncertain cues and events. The combined results provide concrete evidence specifying how prefrontal

Regulation of Autophagy by Glucose in Mammalian Cells

Directory of Open Access Journals (Sweden)

Erwin Knecht

2012-07-01

Full Text Available Autophagy is an evolutionarily conserved process that contributes to maintain cell homeostasis. Although it is strongly regulated by many extracellular factors, induction of autophagy is mainly produced by starvation of nutrients. In mammalian cells, the regulation of autophagy by amino acids, and also by the hormone insulin, has been extensively investigated, but knowledge about the effects of other autophagy regulators, including another nutrient, glucose, is more limited. Here we will focus on the signalling pathways by which environmental glucose directly, i.e., independently of insulin and glucagon, regulates autophagy in mammalian cells, but we will also briefly mention some data in yeast. Although glucose deprivation mainly induces autophagy via AMPK activation and the subsequent inhibition of mTORC1, we will also comment other signalling pathways, as well as evidences indicating that, under certain conditions, autophagy can be activated by glucose. A better understanding on how glucose regulates autophagy not only will expand our basic knowledge of this important cell process, but it will be also relevant to understand common human disorders, such as cancer and diabetes, in which glucose levels play an important role.

Systemic risk in the energy sector—Is there need for financial regulation?

International Nuclear Information System (INIS)

Kerste, Marco; Gerritsen, Matthijs; Weda, Jarst; Tieben, Bert

2015-01-01

The credit crisis points at serious systemic risks in Over The Counter derivative trading. This has resulted in new financial regulation, covering both the financial sector and non-financial sectors. The actual extent to which non-financial companies trading on OTC markets contribute to systemic risk has hardly been the subject of research. This paper investigates the need for financial regulation in the energy sector, which shows a high use of OTC derivatives, by modeling systemic risk measured by the expected fraction of additional failing firms (EAF). Contagion risk within the energy sector and from the energy sector towards the banking sector is compared with that in other non-financial sectors. This paper adds to existing systemic risk literature by specifically looking at financial interdependence between a non-financial sector showing a high usage of OTC commodity derivatives and the banking sector, while contributing to the discussion on energy sector regulation with technical systemic risk analysis. Results indicate that contagion risk from the energy towards the banking sector is not relatively high compared to other non-financial sectors. Our results provide a first indication to question the need for generalized regulation of OTC derivative transactions, as recently introduced by the European Market Infrastructure Regulation (EMIR). - Highlights: • We assess the need for regulating OTC energy commodity derivatives under EMIR. • We present a methodology to model systemic risk in non-financial sectors. • We analyse direct and indirect channels for contagion giving rise to systemic risk. • Contagion risk from the energy towards the banking sector is not relatively high. • New EU regulation for energy OTC trading not supported by analysis of systemic risk

Towards transparent, proportionate and deliverable regulation for geological disposal

International Nuclear Information System (INIS)

2010-01-01

As part of its activities, the Regulators' Forum of the NEA Radioactive Waste Management Committee has been examining the regulatory criteria for the long-term performance of geological disposal. In this context, it organised a workshop entitled 'Towards Transparent, Proportionate and Deliverable Regulation for Geological Disposal', which served to verify current status and needs. Participants included regulators, implementers, policy makers, R and D specialists and academics. Themes addressed included duties to future generations, timescales for regulation, stepwise decision making, roles of optimisation and best available techniques (BAT), multiple lines of reasoning, safety and performance indicators, recognition of uncertainties and the importance of stakeholder interactions. The workshop highlighted the significant amount of work accomplished over the past decade, but also identified important differences between national regulations even if these are not in contradiction with international guidance. Also highlighted was the importance of R and D carried out on behalf of the regulator. In addition to the contributed papers, these proceedings trace the numerous discussions that formed an integral part of the workshop. They constitute an important and unique documentary basis for researchers and radioactive waste management specialists

Hypoxic regulation of the noncoding genome and NEAT1

Science.gov (United States)

Choudhry, Hani

2016-01-01

Activation of hypoxia pathways is both associated with and contributes to an aggressive phenotype across multiple types of solid cancers. The regulation of gene transcription by hypoxia-inducible factor (HIF) is a key element in this response. HIF directly upregulates the expression of many hundreds of protein-coding genes, which act to both improve oxygen delivery and to reduce oxygen demand. However, it is now becoming apparent that many classes of noncoding RNAs are also regulated by hypoxia, with several (e.g. micro RNAs, long noncoding RNAs and antisense RNAs) under direct transcriptional regulation by HIF. These hypoxia-regulated, noncoding RNAs may act as effectors of the indirect response to HIF by acting on specific coding transcripts or by affecting generic RNA-processing pathways. In addition, noncoding RNAs may also act as modulators of the HIF pathway, either by integrating other physiological responses or, in the case of HIF-regulated, noncoding RNAs, by providing negative or positive feedback and feedforward loops that affect upstream or downstream components of the HIF cascade. These hypoxia-regulated, noncoding transcripts play important roles in the aggressive hypoxic phenotype observed in cancer. PMID:26590207

Threatened biodiversity, the nema eia regulations and cultivation of ...

African Journals Online (AJOL)

Until such listing, unresolved legal questions that inhibited the effective consideration of biodiversity in agricultural decision-making prior to the promulgation of the NEMA EIA regulations are likely to persist—to the detriment of a globally imperilled biodiversity. This contribution sets out to identify some of the key issues that ...

Negative regulation of NOD1 mediated angiogenesis by PPARγ-regulated miR-125a

International Nuclear Information System (INIS)

Kang, Hyesoo; Park, Youngsook; Lee, Aram; Seo, Hyemin; Kim, Min Jung; Choi, Jihea; Jo, Ha-neul; Jeong, Ha-neul; Cho, Jin Gu; Chang, Woochul; Lee, Myeong-Sok; Jeon, Raok; Kim, Jongmin

2017-01-01

Infection with pathogens activates the endothelial cell and its sustained activation may result in impaired endothelial function. Endothelial dysfunction contributes to the pathologic angiogenesis that is characteristic of infection-induced inflammatory pathway activation. Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a protein receptor which recognizes bacterial molecules and stimulates an immune reaction in various cells; however, the underlying molecular mechanisms in the regulation of inflammation-triggered angiogenesis are not fully understood. Here we report that peroxisome proliferator-activated receptor gamma (PPARγ)-mediated miR-125a serves as an important regulator of NOD1 agonist-mediated angiogenesis in endothelial cells by directly targeting NOD1. Treatment of human umbilical vein endothelial cells with natural PPARγ ligand, 15-Deoxy-Delta12,14-prostaglandin J2, led to inhibition of NOD1 expression; contrarily, protein levels of NOD1 were significantly increased by PPARγ knockdown. We report that PPARγ regulation of NOD1 expression is a novel microRNA-mediated regulation in endothelial cells. MiR-125a expression was markedly decreased in human umbilical vein endothelial cells subjected to PPARγ knockdown while 15-Deoxy-Delta12,14-prostaglandin J2 treatment increased the level of miR-125a. In addition, NOD1 is closely regulated by miR-125a, which directly targets the 3′ untranslated region of NOD1. Moreover, both overexpression of miR-125a and PPARγ activation led to inhibition of NOD1 agonist-induced tube formation in endothelial cells. Finally, NOD1 agonist increased the formation of cranial and subintestinal vessel plexus in zebrafish, and this effect was abrogated by concurrent PPARγ activation. Overall, these findings identify a PPARγ-miR-125a-NOD1 signaling axis in endothelial cells that is critical in the regulation of inflammation-mediated angiogenesis. - Highlights: • Expression of NOD1 is regulated by

The radioprotection of the patient in the Italian regulation

International Nuclear Information System (INIS)

Russo, A. A.; Delia, R.; Moccaldi, A.; Campanella, F.

2002-01-01

The regulation in order to the radioprotection of the patient was firstly issued in Italy in the 1995. This regulation was a specific part of a more general law on the radiation protection of the workers, public and environment. After, in the year 2000, a specific law regulates the use of ionizing radiation in the medical field, in relation to patient's protection and safety. This law is based on the main principles of the justification and of the optimization of the exposure. The application of the law involves many different professional roles, which all together provide to ensure the respect of the previous principles and the radioprotection of the patients. The above professional figures are: the manager of the medical laboratory, the person in charge of the section, the specialist medical doctor (responsible of the radiological practice), the health physicist and the radiological technician. In the present paper, the Authors show the basic rules of the radioprotection regulation, focusing the attention on the different roles of all involved people, in the all kinds of the radiological practices. The proper application of the law allows the respect of the principle of the dose limitation, through either technical, or physical or medical methodologies. The examination of the Italian experience in this field could be an useful contribution to the improvement of the problem of the patient's radiation protection, taken also into account that the absorbed doses from the patients, for medical purposes, are those ones, which mainly contribute to the computation of the mean level of the dose in every Country

Insights into the post-transcriptional regulation of the mitochondrial electron transport chain.

Science.gov (United States)

Sirey, Tamara M; Ponting, Chris P

2016-10-15

The regulation of the mitochondrial electron transport chain is central to the control of cellular homeostasis. There are significant gaps in our understanding of how the expression of the mitochondrial and nuclear genome-encoded components of the electron transport chain are co-ordinated, and how the assembly of the protein complexes that constitute the electron transport chain are regulated. Furthermore, the role post-transcriptional gene regulation may play in modulating these processes needs to be clarified. This review summarizes the current knowledge regarding the post-transcriptional gene regulation of the electron transport chain and highlights how noncoding RNAs may contribute significantly both to complex electron transport chain regulatory networks and to mitochondrial dysfunction. © 2016 The Author(s).

Contribution of ecosystem services to air quality and climate change mitigation policies: The case of urban forests in Barcelona, Spain

Science.gov (United States)

Francesc Baró; Lydia Chaparro; Erik Gómez-Baggethun; Johannes Langemeyer; David J. Nowak; Jaume. Terradas

2014-01-01

Mounting research highlights the contribution of ecosystem services provided by urban forests to quality of life in cities, yet these services are rarely explicitly considered in environmental policy targets. We quantify regulating services provided by urban forests and evaluate their contribution to comply with policy targets of air quality and climate change...

Olivocochlear efferent vs. middle-ear contributions to the alteration of otoacoustic emissions by contralateral noise

NARCIS (Netherlands)

Buki, B; Wit, HP; Avan, P

2000-01-01

The medial olivocochlear efferent bundle is the key element of a bilateral efferent reflex activated by sound in either ear and acting directly on cochlear outer hair cells (OHC) via numerous cholinegic synapses. It probably contributes to regulating the mechanical activity of the cochlea

HNF-4α regulated miR-122 contributes to development of gluconeogenesis and lipid metabolism disorders in Type 2 diabetic mice and in palmitate-treated HepG2 cells.

Science.gov (United States)

Wei, Shengnan; Zhang, Ming; Yu, Yang; Xue, Huan; Lan, Xiaoxin; Liu, Shuping; Hatch, Grant; Chen, Li

2016-11-15

Hepatocyte Nuclear Factor-4α (HNF-4α) is a key nuclear receptor protein required for liver development. miR-122 is a predominant microRNA expressed in liver and is involved in the regulation of cholesterol and fatty acid metabolism. HNF-4α is know to regulate expression of miR-122 in liver. We examined how HNF-4α regulated gluconeogenesis and lipid metabolism through miR-122 in vivo and in vitro. Expression of miR-122, HNF-4α, phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), sterol response elementary binding protein-1 (SREBP-1), fatty acid synthase-1 (FAS-1), carnitine palmitoyltransferase-1 (CPT-1) and acetyl Coenzyme A carboxylase alpha (ACCα) were determined in livers of Type 2 diabetic mice and in insulin resistant palmitate-treated HepG2 cells. CPT-1 and phosphorylated ACCα expression were significantly decreased in livers of Type 2 diabetic mice and in palmitate-treated HepG2 cells compared to controls. In contrast, expression of miR-122, HNF-4α, PEPCK, G6Pase, SREBP-1, FAS-1 and ACCα were significantly elevated in liver of Type 2 diabetic mice and in palmitate-treated HepG2 cells compared to controls. Expression of HNF-4α increased whereas siRNA knockdown of HNF-4α decreased miR-122 levels in HepG2 cells compared to controls. In addition, expression of HNF-4α in HepG2 cells increased PEPCK, G6Pase, SREBP-1, FAS-1, ACCα mRNA and protein expression and decreased CPT-1 and p-ACCα mRNA and protein expression compared to controls. Addition of miR-122 inhibitors attenuated the HNF-4α mediated effect on expression of these gluconeogenic and lipid metabolism proteins. The results indicate that HNF-4α regulated miR-122 contributes to development of the gluconeogenic and lipid metabolism alterations observed in Type 2 diabetic mice and in palmitate-treated HepG2 cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Independent and Collaborative Contributions of the Cerebral Hemispheres to Emotional Processing

Science.gov (United States)

Shobe, Elizabeth R.

2014-01-01

Presented is a model suggesting that the right hemisphere (RH) directly mediates the identification and comprehension of positive and negative emotional stimuli, whereas the left hemisphere (LH) contributes to higher level processing of emotional information that has been shared via the corpus callosum. RH subcortical connections provide initial processing of emotional stimuli, and their innervation to cortical structures provides a secondary pathway by which the hemispheres process emotional information more fully. It is suggested that the LH contribution to emotion processing is in emotional regulation, social well-being, and adaptation, and transforming the RH emotional experience into propositional and verbal codes. Lastly, it is proposed that the LH has little ability at the level of emotion identification, having a default positive bias and no ability to identify a stimulus as negative. Instead, the LH must rely on the transfer of emotional information from the RH to engage higher-order emotional processing. As such, either hemisphere can identify positive emotions, but they must collaborate for complete processing of negative emotions. Evidence presented draws from behavioral, neurological, and clinical research, including discussions of subcortical and cortical pathways, callosal agenesis, commissurotomy, emotion regulation, mood disorders, interpersonal interaction, language, and handedness. Directions for future research are offered. PMID:24795597

An Approach to Regulation on Financial Derivatives in the Spanish Law

Directory of Open Access Journals (Sweden)

Pablo Sanz Bayón

2013-07-01

Full Text Available This review examines the major reforms implemented in the regulations governing the trading of financial derivatives in Spain. This new regulation is intended to harmonize the treatment of derivative products with the legal standards of international markets in the European area as well as improving their competitiveness by enhancing the trading of new products and business lines in the Spanish markets while reducing the systemic risk associated to the clearing and settlement of derivatives contracts. Including measures regarding the conversion of OTC derivatives into assets quoted on organized markets into Spanish law has made an important contribution to a better regulation, security and transparency of the financial system.

Drone and Worker Brood Microclimates Are Regulated Differentially in Honey Bees, Apis mellifera.

Science.gov (United States)

Li, Zhiyong; Huang, Zachary Y; Sharma, Dhruv B; Xue, Yunbo; Wang, Zhi; Ren, Bingzhong

2016-01-01

Honey bee (Apis mellifera) drones and workers show differences in morphology, physiology, and behavior. Because the functions of drones are more related to colony reproduction, and those of workers relate to both survival and reproduction, we hypothesize that the microclimate for worker brood is more precisely regulated than that of drone brood. We assessed temperature and relative humidity (RH) inside honey bee colonies for both drone and worker brood throughout the three-stage development period, using digital HOBO® Data Loggers. The major findings of this study are that 1) both drone and worker castes show the highest temperature for eggs, followed by larvae and then pupae; 2) temperature in drones are maintained at higher precision (smaller variance) in drone eggs and larvae, but at a lower precision in pupae than the corresponding stages of workers; 3) RH regulation showed higher variance in drone than workers across all brood stages; and 4) RH regulation seems largely due to regulation by workers, as the contribution from empty honey combs are much smaller compared to that from adult workers. We conclude that honey bee colonies maintain both temperature and humidity actively; that the microclimate for sealed drone brood is less precisely regulated than worker brood; and that combs with honey contribute very little to the increase of RH in honey bee colonies. These findings increase our understanding of microclimate regulation in honey bees and may have implications for beekeeping practices.

Balancing Public and Private Regulation

Directory of Open Access Journals (Sweden)

Martijn Scheltema

2016-01-01

Full Text Available Voluntary Sustainability Standards (VSS might develop into a viable alternative to public regulation. However, it turns on the (regulatory circumstances whether that holds true in practice. If public regulation on CSR topics is lacking, governments are unable to agree upon certain topics on a global level or diverging public regulation exists, VSS can be helpful to set global standards. Obviously, private standards will especially be helpful if they are commensurate with local public legislation (and e.g. treaties and/or are accepted by local governments. If one neglects this, numerous domestic structures might exist that frustrate VSS. Furthermore, governments have to remain vigilant as to whether these private regimes do not result in market disruption, consumer detriment or hamper trade. VSS might also compete with public arrangements which might limit the uptake of VSS. However, if public regulation exists VSS might be a viable alternative if compliance with not too compelling public norms by market participants is rather poor and the public policymaker is aiming to incentivize the better performing part of the market to embark on higher standards and thus only desires to regulate the less performing part of the market. However, of paramount importance is the effectiveness of VSS in order to be a viable alternative to public regulation. The effectiveness of VSS should be assessed using an integrated multi-disciplinary (comparative approach entailing legal, impact-assessment, legitimacy, governance and behavioural aspects. Only effective VSS in the aforementioned sense are a true alternative to public regulation.Beyond that, the legal perspective in connection with (the effectiveness of VSS is discussed, featuring FSC and UTZ Certified as an example. It is important from this perspective that VSS have a clear and sufficiently selective objective and sufficiently specific norms, are regularly evaluated, entail ‘conflict of law rules’ and

Adjustment of interbank lending in pre- and post-regulation periods: Empirical analysis of Vietnamese commercial banks

Directory of Open Access Journals (Sweden)

Ho Thanh Tung

2017-10-01

Full Text Available This article aims to analyze the interbank lending adjustment during the period when Vietnamese commercial banks are compliant with some parts of the Basel regulation framework. A pilot regulation period has started in 2011 and full application will be effective by the end of 2018. Partial adjustment models and variance decomposition are used for the analyses. In the analysis of the quarterly released financial statements of Vietnamese commercial banks in the period from 2008/Q1 to 2015/Q4, the empirical evidence showed that throughout the period, lending to non-bank and high liquidity assets contributed to the adjustment in both long run and short run with a negative association. In addition, the loan loss allowance contributed to the adjustment in the post-regulation period only with a positive association. These highly contributing factors also show a potential shock after the adjustment of the interbank lending. The results imply there is a need for interbank lending portfolio report and an efficient control over the IRB of Vietnamese commercial banks.

Homologue Pairing in Flies and Mammals: Gene Regulation When Two Are Involved

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Manasi S. Apte

2012-01-01

Full Text Available Chromosome pairing is usually discussed in the context of meiosis. Association of homologues in germ cells enables chromosome segregation and is necessary for fertility. A few organisms, such as flies, also pair their entire genomes in somatic cells. Most others, including mammals, display little homologue pairing outside of the germline. Experimental evidence from both flies and mammals suggests that communication between homologues contributes to normal genome regulation. This paper will contrast the role of pairing in transmitting information between homologues in flies and mammals. In mammals, somatic homologue pairing is tightly regulated, occurring at specific loci and in a developmentally regulated fashion. Inappropriate pairing, or loss of normal pairing, is associated with gene misregulation in some disease states. While homologue pairing in flies is capable of influencing gene expression, the significance of this for normal expression remains unknown. The sex chromosomes pose a particularly interesting situation, as females are able to pair X chromosomes, but males cannot. The contribution of homologue pairing to the biology of the X chromosome will also be discussed.

A study on the safety regulation of byproduct material

Energy Technology Data Exchange (ETDEWEB)

Song, Jong Soon; Song, Yang Su [Chosun Univ., Gwangju (Korea, Republic of)

1999-04-15

The objective of this study is to develop the technical criteria and regulatory system for establishing the safe regulation of byproduct material institutionally. Up to this point, domestically, though many byproduct materials are distributed and used already, it seems that there are no related technical criteria and regulatory system and it becomes an obstacle in the development of relating industry. Since this kind of situation may give negative impact on the proper recognizance of the radiation to public, it is very urgent to establish the safe regulation of byproduct material. In relating to the domestic license of byproduct material, a survey of technical criteria and status of regulation in U.S.A. A determination of range of application and contents of byproduct material. A tentative suggestion of related technical criteria and regulatory system. A study was performed about the above topics to establish the safe regulation of byproduct material institutionally, and this can be contributed in establishing the proper domestic technical criteria related.

Security of supply and regulation of energy networks

International Nuclear Information System (INIS)

Jamasb, Tooraj; Pollitt, Michael

2008-01-01

In recent years, the security of energy supplies has re-emerged as a central issue in the energy policy arena in the UK and elsewhere. This re-emergence takes place against a backdrop of increased liberalisation of the energy markets, so that security of supply needs to be revisited within this context. Security of supply is multifaceted, but is often discussed in terms of physical availability of energy sources and their commodity price risk. This paper discusses the relationship between security of supply and network regulation - that is, how the energy networks, and appropriate regulation of them, can contribute to security of supply in liberalised energy sectors. Energy networks are predominantly natural monopolies and as a result are generally subject to regulatory oversight. We discuss a range of issues and trends that pose challenges and opportunities to network regulation and which call for new and innovative measures. The paper identifies a number of areas where network regulation can play a significant role in increasing the security of supply of future energy systems. (author)

Slow dissolving of emotional distress contributes to hyperarousal.

Science.gov (United States)

Wassing, Rick; Benjamins, Jeroen S; Dekker, Kim; Moens, Sarah; Spiegelhalder, Kai; Feige, Bernd; Riemann, Dieter; van der Sluis, Sophie; Van Der Werf, Ysbrand D; Talamini, Lucia M; Walker, Matthew P; Schalkwijk, Frans; Van Someren, Eus J W

2016-03-01

The mechanisms underlying hyperarousal, the key symptom of insomnia, have remained elusive, hampering cause-targeted treatment. Recently, restless rapid-eye-movement (REM) sleep emerged as a robust signature of sleep in insomnia. Given the role of REM sleep in emotion regulation, we hypothesized that restless REM sleep could interfere with the overnight resolution of emotional distress, thus contributing to accumulation of arousal. Participants (n = 1,199) completed questionnaires on insomnia severity, hyperarousal, self-conscious emotional distress, and thought-like nocturnal mentation that was validated to be a specific proxy for restless REM sleep (selective fragmentation: R = 0.57, P insomnia severity (β = 0.29, P Insomnia severity was associated with hyperarousal (β = 0.47, P insomnia was mediated specifically by reduced overnight resolution of emotional distress. The model outperformed all alternative mediation pathways. The findings suggest that restless REM sleep reflects a process that interferes with the overnight resolution of distress. Its accumulation may promote the development of chronic hyperarousal, giving clinical relevance to the role of REM sleep in emotion regulation in insomnia, depression, and posttraumatic stress disorder.

Up-Regulation of P21 Inhibits TRAIL-Mediated Extrinsic Apoptosis, Contributing Resistance to SAHA in Acute Myeloid Leukemia Cells

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Xing Wu

2014-08-01

Full Text Available Background/Aim: P21, a multifunctional cell cycle-regulatory molecule, regulates apoptotic cell death. In this study we examined the effect of altered p21 expression on the sensitivity of acute myeloid leukemia cells in response to HDAC inhibitor SAHA treatment and investigated the underlying mechanism. Methods: Stably transfected HL60 cell lines were established in RPMI-1640 with supplementation of G-418. Cell viability was measured by MTT assay. Western blot was applied to assess the protein expression levels of target genes. Cell apoptosis was monitored by AnnexinV-PE/7AAD assay. Results: We showed HL60 cells that that didn't up-regulate p21 expression were more sensitive to SAHA-mediated apoptosis than NB4 and U937 cells that had increased p21 level. Enforced expression of p21 in HL60 cells reduced sensitivity to SAHA and blocked TRAIL-mediated apoptosis. Conversely, p21 silencing in NB4 cells enhanced SAHA-mediated apoptosis and lethality. Finally, we found that combined treatment with SAHA and rapamycin down-regulated p21 and enhanced apoptosis in AML cells. Conclusion: We conclude that up-regulated p21 expression mediates resistance to SAHA via inhibition of TRAIL apoptotic pathway. P21 may serve as a candidate biomarker to predict responsiveness or resistance to SAHA-based therapy in AML patients. In addition, rapamycin may be an effective agent to override p21-mediated resistance to SAHA in AML patients.

Wind/PV Generation for Frequency Regulation and Oscillation Damping in the Eastern Interconnection

Energy Technology Data Exchange (ETDEWEB)

Liu, Yong [Univ. of Tennessee, Knoxville, TN (United States); Gracia, Jose R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Hadley, Stanton W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Liu, Yilu [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2013-12-01

This report presents the control of renewable energy sources, including the variable-speed wind generators and solar photovoltaic (PV) generators, for frequency regulation and inter-area oscillation damping in the U.S. Eastern Interconnection (EI). In this report, based on the user-defined wind/PV generator electrical control model and the 16,000-bus Eastern Interconnection dynamic model, the additional controllers for frequency regulation and inter-area oscillation damping are developed and incorporated and the potential contributions of renewable energy sources to the EI system frequency regulation and inter-area oscillation damping are evaluated.

Emotion Regulation and Emotion Work: Two Sides of the Same Coin?

Science.gov (United States)

von Scheve, Christian

2012-01-01

This contribution links psychological models of emotion regulation to sociological accounts of emotion work to demonstrate the extent to which emotion regulation is systematically shaped by culture and society. I first discuss a well-established two-factor process model of emotion regulation and argue that a substantial proportion of emotion regulatory goals are derived from emotion norms. In contrast to universal emotion values and hedonic preferences, emotion norms are highly specific to social situations and institutional contexts. This specificity is determined by social cognitive processes of categorization and guided by framing rules. Second, I argue that the possibilities for antecedent-focused regulation, in particular situation selection and modification, are not arbitrarily available to individuals. Instead, they depend on economic, cultural, and social resources. I suggest that the systematic and unequal distribution of these resources in society leads to discernible patterns of emotion and emotion regulation across groups of individuals. PMID:23181041

Leucine zipper, down regulated in cancer-1 gene expression in prostate cancer

OpenAIRE

Salemi, Michele; Barone, Nunziata; La Vignera, Sandro; Condorelli, Rosita A.; Recupero, Domenico; Galia, Antonio; Fraggetta, Filippo; Aiello, Anna Maria; Pepe, Pietro; Castiglione, Roberto; Vicari, Enzo; Calogero, Aldo E.

2016-01-01

Numerous genetic alterations have been implicated in the development of prostate cancer (PCa). DNA and protein microarrays have enabled the identification of genes associated with apoptosis, which is important in PCa development. Despite the molecular mechanisms are not entirely understood, inhibition of apoptosis is a critical pathophysiological factor that contributes to the onset and progression of PCa. Leucine zipper, down-regulated in cancer 1 (LDOC-1) is a known regulator of the nuclear...

Two Salt Bridges Differentially Contribute to the Maintenance of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Channel Function*

Science.gov (United States)

Cui, Guiying; Freeman, Cody S.; Knotts, Taylor; Prince, Chengyu Z.; Kuang, Christopher; McCarty, Nael A.

2013-01-01

Previous studies have identified two salt bridges in human CFTR chloride ion channels, Arg352-Asp993 and Arg347-Asp924, that are required for normal channel function. In the present study, we determined how the two salt bridges cooperate to maintain the open pore architecture of CFTR. Our data suggest that Arg347 not only interacts with Asp924 but also interacts with Asp993. The tripartite interaction Arg347-Asp924-Asp993 mainly contributes to maintaining a stable s2 open subconductance state. The Arg352-Asp993 salt bridge, in contrast, is involved in stabilizing both the s2 and full (f) open conductance states, with the main contribution being to the f state. The s1 subconductance state does not require either salt bridge. In confirmation of the role of Arg352 and Asp993, channels bearing cysteines at these sites could be latched into a full open state using the bifunctional cross-linker 1,2-ethanediyl bismethanethiosulfonate, but only when applied in the open state. Channels remained latched open even after washout of ATP. The results suggest that these interacting residues contribute differently to stabilizing the open pore in different phases of the gating cycle. PMID:23709221

An analytical approach to separate climate and human contributions to basin streamflow variability

Science.gov (United States)

Li, Changbin; Wang, Liuming; Wanrui, Wang; Qi, Jiaguo; Linshan, Yang; Zhang, Yuan; Lei, Wu; Cui, Xia; Wang, Peng

2018-04-01

Climate variability and anthropogenic regulations are two interwoven factors in the ecohydrologic system across large basins. Understanding the roles that these two factors play under various hydrologic conditions is of great significance for basin hydrology and sustainable water utilization. In this study, we present an analytical approach based on coupling water balance method and Budyko hypothesis to derive effectiveness coefficients (ECs) of climate change, as a way to disentangle contributions of it and human activities to the variability of river discharges under different hydro-transitional situations. The climate dominated streamflow change (ΔQc) by EC approach was compared with those deduced by the elasticity method and sensitivity index. The results suggest that the EC approach is valid and applicable for hydrologic study at large basin scale. Analyses of various scenarios revealed that contributions of climate change and human activities to river discharge variation differed among the regions of the study area. Over the past several decades, climate change dominated hydro-transitions from dry to wet, while human activities played key roles in the reduction of streamflow during wet to dry periods. Remarkable decline of discharge in upstream was mainly due to human interventions, although climate contributed more to runoff increasing during dry periods in the semi-arid downstream. Induced effectiveness on streamflow changes indicated a contribution ratio of 49% for climate and 51% for human activities at the basin scale from 1956 to 2015. The mathematic derivation based simple approach, together with the case example of temporal segmentation and spatial zoning, could help people understand variation of river discharge with more details at a large basin scale under the background of climate change and human regulations.

Yeast aquaporin regulation by 4-hydroxynonenal is implicated in oxidative stress response.

Science.gov (United States)

Rodrigues, Claudia; Tartaro Bujak, Ivana; Mihaljević, Branka; Soveral, Graça; Cipak Gasparovic, Ana

2017-05-01

Reactive oxygen species, especially hydrogen peroxide (H 2 O 2 ), contribute to functional molecular impairment and cellular damage, but also are necessary in normal cellular metabolism, and in low doses play stimulatory role in cell proliferation and stress resistance. In parallel, reactive aldehydes such as 4-hydroxynonenal (HNE), are lipid peroxidation breakdown products which also contribute to regulation of numerous cellular processes. Recently, channeling of H 2 O 2 by some mammalian aquaporin isoforms has been reported and suggested to contribute to aquaporin involvement in cancer malignancies, although the mechanism by which these membrane water channels are implicated in oxidative stress is not clear. In this study, two yeast models with increased levels of membrane polyunsaturated fatty acids (PUFAs) and aquaporin AQY1 overexpression, respectively, were used to evaluate their interplay in cell's oxidative status. In particular, the aim of the study was to investigate if HNE accumulation could affect aquaporin function with an outcome in oxidative stress response. The data showed that induction of aquaporin expression by PUFAs results in increased water permeability in yeast membranes and that AQY1 activity is impaired by HNE. Moreover, AQY1 expression increases cellular sensitivity to oxidative stress by facilitating H 2 O 2 influx. On the other hand, AQY1 expression has no influence on the cellular antioxidant GSH levels and catalase activity. These results strongly suggest that aquaporins are important players in oxidative stress response and could contribute to regulation of cellular processes by regulation of H 2 O 2 influx. © 2017 IUBMB Life, 69(5):355-362, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Colonization of fish skin is vital for Vibrio anguillarum to cause disease.

Science.gov (United States)

Weber, Barbara; Chen, Chang; Milton, Debra L

2010-02-01

Vibrio anguillarum causes a fatal haemorrhagic septicaemia in marine fish. During initial stages of infection, host surfaces are colonized; however, few virulence factors required for colonization of the host are identified. In this study, in vivo bioluminescent imaging was used to analyse directly the colonization of the whole rainbow trout animal by V. anguillarum. The wild type rapidly colonized both the skin and the intestines by 24 h; however, the bacterial numbers on the skin were significantly higher than in the intestines indicating that skin colonization may be important for disease to occur. Mutants defective for the anguibactin iron uptake system, exopolysaccharide transport, or Hfq, an RNA chaperone, were attenuated for virulence, did not colonize the skin, and penetrated skin mucus less efficiently than the wild type. These mutants, however, did colonize the intestines and were as resistant to 2% bile salts as is the wild type. Moreover, exopolysaccharide mutants were significantly more sensitive to lysozyme and antimicrobial peptides, while the Hfq and anguibactin mutants were sensitive to lysozyme compared with the wild type. Vibrio anguillarum encodes several mechanisms to protect against antimicrobial components of skin mucus enabling an amazingly abundant growth on the skin enhancing its disease opportunities. © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.

Regulations Relating to Foodstuffs for Infants and Young Children

African Journals Online (AJOL)

RV

2010-11-22

Nov 22, 2010 ... published regulations1 in terms of section 15(1) of the Foodstuffs, Cosmetics and. Disinfectants Act.2 .... and support of appropriate and timely complementary feeding (weaning) practices with the use of local ... aim of the Code is "to contribute to the provision of safe and adequate nutrition for infants, by the ...

Commission for Energy regulation (CRE) - Activity report june 2008

International Nuclear Information System (INIS)

2008-01-01

CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2008 activity report of CRE. Content: A - How CRE works: CRE regulatory authority and organisation: Powers, Organisation; Budget resources; Personnel; B - The Standing Committee for Dispute Settlement and Sanctions (CoRDiS) activity: Admissibility, Authority; C - Building a single European energy market: Overview; Organisation and coordination of the main European regulators (Work carried out collectively by European regulators, Regulator organisation and development, CRE's relations with European Community institutions, Development of CEER activities outside the European Union); CRE's European activities (The contribution of European regulators to the Third Energy Package, Integration of gas markets, Integration of electricity markets, Operation of the European interconnected electricity grid and security of supply, Opening up markets to benefit consumers); European Community activities (The European Commission's proposals for the internal energy market: the Third Energy Package, The European Commission's proposals for fighting climate change: the Climate Package, Infringement

Integration of AI-2 Based Cell-Cell Signaling with Metabolic Cues in Escherichia coli.

Directory of Open Access Journals (Sweden)

Arindam Mitra

Full Text Available The quorum sensing molecule Autoinducer-2 (AI-2 is generated as a byproduct of activated methyl cycle by the action of LuxS in Escherichia coli. AI-2 is synthesized, released and later internalized in a cell-density dependent manner. Here, by mutational analysis of the genes, uvrY and csrA, we describe a regulatory circuit of accumulation and uptake of AI-2. We constructed a single-copy chromosomal luxS-lacZ fusion in a luxS + merodiploid strain and evaluated its relative expression in uvrY and csrA mutants. At the entry of stationary phase, the expression of the fusion and AI-2 accumulation was positively regulated by uvrY and negatively regulated by csrA respectively. A deletion of csrA altered message stability of the luxS transcript and CsrA protein exhibited weak binding to 5' luxS regulatory region. DNA protein interaction and chromatin immunoprecipitation analysis confirmed direct interaction of UvrY with the luxS promoter. Additionally, reduced expression of the fusion in hfq deletion mutant suggested involvement of small RNA interactions in luxS regulation. In contrast, the expression of lsrA operon involved in AI-2 uptake, is negatively regulated by uvrY and positively by csrA in a cell-density dependent manner. The dual role of csrA in AI-2 synthesis and uptake suggested a regulatory crosstalk of cell signaling with carbon regulation in Escherichia coli. We found that the cAMP-CRP mediated catabolite repression of luxS expression was uvrY dependent. This study suggests that luxS expression is complex and regulated at the level of transcription and translation. The multifactorial regulation supports the notion that cell-cell communication requires interaction and integration of multiple metabolic signals.

Regulation of the Contribution of Integrin to Cell Attachment on Poly(2-Methoxyethyl Acrylate (PMEA Analogous Polymers for Attachment-Based Cell Enrichment.

Directory of Open Access Journals (Sweden)

Takashi Hoshiba

Full Text Available Cell enrichment is currently in high demand in medical engineering. We have reported that non-blood cells can attach to a blood-compatible poly(2-methoxyethyl acrylate (PMEA substrate through integrin-dependent and integrin-independent mechanisms because the PMEA substrate suppresses protein adsorption. Therefore, we assumed that PMEA analogous polymers can change the contribution of integrin to cell attachment through the regulation of protein adsorption. In the present study, we investigated protein adsorption, cell attachment profiles, and attachment mechanisms on PMEA analogous polymer substrates. Additionally, we demonstrated the possibility of attachment-based cell enrichment on PMEA analogous polymer substrates. HT-1080 and MDA-MB-231 cells started to attach to poly(butyl acrylate (PBA and poly(tetrahydrofurfuryl acrylate (PTHFA, on which proteins could adsorb well, within 1 h. HepG2 cells started to attach after 1 h. HT-1080, MDA-MB-231, and HepG2 cells started to attach within 30 min to PMEA, poly(2-(2-methoxyethoxy ethyl acrylate-co-butyl acrylate (30:70 mol%, PMe2A and poly(2-(2-methoxyethoxy ethoxy ethyl acrylate-co-butyl acrylate (30:70 mol%, PMe3A, which suppress protein adsorption. Moreover, the ratio of attached cells from a cell mixture can be changed on PMEA analogous polymers. These findings suggested that PMEA analogous polymers can be used for attachment-based cell enrichment.

Roles of Transcriptional and Translational Control Mechanisms in Regulation of Ribosomal Protein Synthesis in Escherichia coli.

Science.gov (United States)

Burgos, Hector L; O'Connor, Kevin; Sanchez-Vazquez, Patricia; Gourse, Richard L

2017-11-01

Bacterial ribosome biogenesis is tightly regulated to match nutritional conditions and to prevent formation of defective ribosomal particles. In Escherichia coli , most ribosomal protein (r-protein) synthesis is coordinated with rRNA synthesis by a translational feedback mechanism: when r-proteins exceed rRNAs, specific r-proteins bind to their own mRNAs and inhibit expression of the operon. It was recently discovered that the second messenger nucleotide guanosine tetra and pentaphosphate (ppGpp), which directly regulates rRNA promoters, is also capable of regulating many r-protein promoters. To examine the relative contributions of the translational and transcriptional control mechanisms to the regulation of r-protein synthesis, we devised a reporter system that enabled us to genetically separate the cis -acting sequences responsible for the two mechanisms and to quantify their relative contributions to regulation under the same conditions. We show that the synthesis of r-proteins from the S20 and S10 operons is regulated by ppGpp following shifts in nutritional conditions, but most of the effect of ppGpp required the 5' region of the r-protein mRNA containing the target site for translational feedback regulation and not the promoter. These results suggest that most regulation of the S20 and S10 operons by ppGpp following nutritional shifts is indirect and occurs in response to changes in rRNA synthesis. In contrast, we found that the promoters for the S20 operon were regulated during outgrowth, likely in response to increasing nucleoside triphosphate (NTP) levels. Thus, r-protein synthesis is dynamic, with different mechanisms acting at different times. IMPORTANCE Bacterial cells have evolved complex and seemingly redundant strategies to regulate many high-energy-consuming processes. In E. coli , synthesis of ribosomal components is tightly regulated with respect to nutritional conditions by mechanisms that act at both the transcription and translation steps. In

Commission for Energy regulation (CRE) - Activity report june 2008; Commission de regulation de l'energie (CRE) - Rapport d'activite juin 2008

Energy Technology Data Exchange (ETDEWEB)

NONE

2008-07-01

CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2008 activity report of CRE. Content: A - How CRE works: CRE regulatory authority and organisation: Powers, Organisation; Budget resources; Personnel; B - The Standing Committee for Dispute Settlement and Sanctions (CoRDiS) activity: Admissibility, Authority; C - Building a single European energy market: Overview; Organisation and coordination of the main European regulators (Work carried out collectively by European regulators, Regulator organisation and development, CRE's relations with European Community institutions, Development of CEER activities outside the European Union); CRE's European activities (The contribution of European regulators to the Third Energy Package, Integration of gas markets, Integration of electricity markets, Operation of the European interconnected electricity grid and security of supply, Opening up markets to benefit consumers); European Community activities (The European Commission's proposals for the internal energy market: the Third Energy Package, The European Commission's proposals for fighting climate change: the Climate

Mid-embryo patterning and precision in Drosophila segmentation: Krüppel dual regulation of hunchback.

Directory of Open Access Journals (Sweden)

David M Holloway

Full Text Available In early development, genes are expressed in spatial patterns which later define cellular identities and tissue locations. The mechanisms of such pattern formation have been studied extensively in early Drosophila (fruit fly embryos. The gap gene hunchback (hb is one of the earliest genes to be expressed in anterior-posterior (AP body segmentation. As a transcriptional regulator for a number of downstream genes, the spatial precision of hb expression can have significant effects in the development of the body plan. To investigate the factors contributing to hb precision, we used fine spatial and temporal resolution data to develop a quantitative model for the regulation of hb expression in the mid-embryo. In particular, modelling hb pattern refinement in mid nuclear cleavage cycle 14 (NC14 reveals some of the regulatory contributions of simultaneously-expressed gap genes. Matching the model to recent data from wild-type (WT embryos and mutants of the gap gene Krüppel (Kr indicates that a mid-embryo Hb concentration peak important in thoracic development (at parasegment 4, PS4 is regulated in a dual manner by Kr, with low Kr concentration activating hb and high Kr concentration repressing hb. The processes of gene expression (transcription, translation, transport are intrinsically random. We used stochastic simulations to characterize the noise generated in hb expression. We find that Kr regulation can limit the positional variability of the Hb mid-embryo border. This has been recently corroborated in experimental comparisons of WT and Kr- mutant embryos. Further, Kr regulation can decrease uncertainty in mid-embryo hb expression (i.e. contribute to a smooth Hb boundary and decrease between-copy transcriptional variability within nuclei. Since many tissue boundaries are first established by interactions between neighbouring gene expression domains, these properties of Hb-Kr dynamics to diminish the effects of intrinsic expression noise may

Emotion regulation predicts symptoms of depression over five years.

Science.gov (United States)

Berking, Matthias; Wirtz, Carolin M; Svaldi, Jennifer; Hofmann, Stefan G

2014-06-01

Deficits in emotion regulation have been identified as an important risk and maintaining factor for depression. The aim of this study was to examine the long-term effects of emotion regulation on symptoms of depression. Moreover, we investigated which specific emotion regulation skills were associated with subsequent symptoms of depression. Participants were 116 individuals (78% women, average age 35.2 years) who registered for an online-based assessment of depression and its risk-factors and reported at least some symptoms of depression. Successful application of emotion regulation skills and depressive symptom severity were assessed twice over a 5-year period. We utilized cross-lagged panel analyses to assess whether successful skills application would be negatively associated with subsequent depressive symptom severity. Cross-lagged panel analyses identified successful skills application as a significant predictor for depressive symptom severity even when controlling for the effects of initial symptoms of depression. A comparison of the effect sizes for different emotion regulation skills on subsequent depressive symptoms suggests that most of the skills included have similar predictive value. These findings provide preliminary evidence for the hypotheses that deficits in emotion regulation may contribute to the development of depression and that interventions systematically enhancing adaptive emotion regulation skills may help prevent and treat depressive symptoms. Copyright © 2014 Elsevier Ltd. All rights reserved.

29 CFR 2509.94-3 - Interpretive bulletin relating to in-kind contributions to employee benefit plans.

Science.gov (United States)

2010-07-01

... employee benefit plans. 2509.94-3 Section 2509.94-3 Labor Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS SECURITY ADMINISTRATION, DEPARTMENT OF LABOR GENERAL INTERPRETIVE BULLETINS RELATING TO...-kind contributions to employee benefit plans. (a) General. This bulletin sets forth the views of the...

Lipid metabolism in the heart. Contribution of BMIPP to the diseased heart

Energy Technology Data Exchange (ETDEWEB)

Nohara, Ryuji [Tazuke Kofukai Medical Research Inst., Osaka (Japan). Kitano Hospital

2001-10-01

Lipid contributes greatly in cardiac metabolism to produce high energy ATPs, and is suggested to be related to the progression and deterioration of heart disease. It is fortunate that the I-123-betamethyliodophenylpentadecanoic acid (BMIPP) imaging technique is now available in determining heart condition, but we must be cautious about the interpretation of images obtained with new tracer. From the uptake of BMIPP into the cell to breakdown and catabolism of it, there exist so many critical enzymatical pathways relating to the modification of BMIPP imaging. In clinical evaluation, the image will be translated as the integral effects of these pathways. In order words, we must be aware of these critical pathways regulating lipid metabolism and modifying factors in order to correctly understand BMIPP imaging. Lipid transport is affected by the albumin/FFA ratio in the blood, and extraction with membrane transporter proteins. Fatty acid binding protein (FABP) in the cytosole will play an important role in regulating lipid flux and following metabolism. Lipid will be utilized either for oxidation, triglyceride or phospholipid formation. For oxidation, carnitine palmitoil transferase is the key enzyme for the entrance of lipid into mitochondria, and oxidative enzymes such as acyl CoA dehydrogenase (MCAD, LCAD, HAD) will determine lipid use for the TCA cycle. ATPs produced in the mitochondria again limit the TG store. It is well known that BMIPP imaging completely changes in the ischemic condition, and is also shown that lipid metabolical regulation completely differs from normal in the very early phase of cardiac hypertrophy. In the process of deteriorating heart failure, metabolical switching of lipid with glucose will take place. In such a different heart disease conditions, it is clear that lipid metabolical regulation, including many lipid enzymes, works differently from in the healthy condition. These lipid enzymes are regulated by nuclear factor peroxisome

Emotion regulation and emotion work: Two sides of the same coin?

Directory of Open Access Journals (Sweden)

Christian evon Scheve

2012-11-01

Full Text Available This contribution links psychological models of emotion regulation to sociological accounts of emotion work to demonstrate the extent to which emotion regulation is systematically shaped by culture and society. I first discuss a well-established two-factor process model of emotion regulation and argue that a substantial proportion of emotion regulatory goals are derived from emotion norms. In contrast to universal emotion values and hedonic preferences, emotion norms are highly specific to social situations and institutional contexts. This specificity is determined by social cognitive processes of categorization and guided by framing rules. Second, I argue that the possibilities for antecedent-focused regulation, in particular situation selection and modification, are not arbitrarily available to individuals. Instead, they depend on economic, cultural, and social resources. I suggest that the systematic and unequal distribution of these resources in society leads to discernible patterns of emotion and emotion regulation across groups of individuals.

A 3' UTR-Derived Small RNA Provides the Regulatory Noncoding Arm of the Inner Membrane Stress Response.

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Chao, Yanjie; Vogel, Jörg

2016-02-04

Small RNAs (sRNAs) from conserved noncoding genes are crucial regulators in bacterial signaling pathways but have remained elusive in the Cpx response to inner membrane stress. Here we report that an alternative biogenesis pathway releasing the conserved mRNA 3' UTR of stress chaperone CpxP as an ∼60-nt sRNA provides the noncoding arm of the Cpx response. This so-called CpxQ sRNA, generated by general mRNA decay through RNase E, acts as an Hfq-dependent repressor of multiple mRNAs encoding extracytoplasmic proteins. Both CpxQ and the Cpx pathway are required for cell survival under conditions of dissipation of membrane potential. Our discovery of CpxQ illustrates how the conversion of a transcribed 3' UTR into an sRNA doubles the output of a single mRNA to produce two factors with spatially segregated functions during inner membrane stress: a chaperone that targets problematic proteins in the periplasm and a regulatory RNA that dampens their synthesis in the cytosol. Copyright © 2016 Elsevier Inc. All rights reserved.

Cell Cycle Regulation of Stem Cells by MicroRNAs.

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Mens, Michelle M J; Ghanbari, Mohsen

2018-06-01

MicroRNAs (miRNAs) are a class of small non-coding RNA molecules involved in the regulation of gene expression. They are involved in the fine-tuning of fundamental biological processes such as proliferation, differentiation, survival and apoptosis in many cell types. Emerging evidence suggests that miRNAs regulate critical pathways involved in stem cell function. Several miRNAs have been suggested to target transcripts that directly or indirectly coordinate the cell cycle progression of stem cells. Moreover, previous studies have shown that altered expression levels of miRNAs can contribute to pathological conditions, such as cancer, due to the loss of cell cycle regulation. However, the precise mechanism underlying miRNA-mediated regulation of cell cycle in stem cells is still incompletely understood. In this review, we discuss current knowledge of miRNAs regulatory role in cell cycle progression of stem cells. We describe how specific miRNAs may control cell cycle associated molecules and checkpoints in embryonic, somatic and cancer stem cells. We further outline how these miRNAs could be regulated to influence cell cycle progression in stem cells as a potential clinical application.

Associations of Child and Adolescent Mastery Motivation and Self-Regulation With Adult Outcomes: A Longitudinal Study of Individuals With Down Syndrome.

Science.gov (United States)

Gilmore, Linda; Cuskelly, Monica

2017-05-01

This 20-year prospective longitudinal study focuses on the contribution of mastery motivation and self-regulation to adult outcomes for individuals with Down syndrome. In earlier phases of the research, 25 participants completed measures of cognitive ability, mastery motivation and self-regulation in childhood (4 to 6 years) and adolescence (11 to 15 years). In the adult phase reported here, self-determination and adaptive behavior were assessed in 21 of the original participants at age 23 to 26 years. Mastery motivation and self-regulation made unique contributions to adult outcomes, over and above the effects of cognitive ability. The findings provide powerful evidence about the important role of child and adolescent mastery motivation and self-regulation for the adult lives of individuals with Down syndrome.

Beyond the medial regions of prefrontal cortex in the regulation of fear and anxiety

Directory of Open Access Journals (Sweden)

Yoshiro eShiba

2016-02-01

Full Text Available Fear and anxiety are adaptive responses but if left unregulated, or inappropriately regulated, they become biologically and socially maladaptive. Dysregulated emotions are manifest in a wide variety of psychiatric and neurological conditions but the external expression gives little indication of the underlying causes, which are inevitably multi-determined. To go beyond the overt phenotype and begin to understand the causal mechanisms leading to conditions characterized by anxiety and disorders of mood, it is necessary to identify the base psychological processes that have become dysregulated, and map them on to their associated neural substrates. So far, attention has been focused primarily on the medial regions of prefrontal cortex (PFC and in particular their contribution to the expression and extinction of conditioned fear. However, functional neuroimaging studies have shown that the sphere of influence within the PFC is not restricted to its medial regions, but extends into dorsal, ventrolateral (vlPFC and orbitofrontal (OFC regions too; although the causal role of these other areas in the regulation of fear and anxiety remains to be determined and in the case of the OFC, existing findings are conflicting. Here we review the evidence for the contribution of these other regions in negative emotion regulation in rodents and old world and new world monkeys. We consider a variety of different contexts, including conditioned and innate fear, learned and unlearned anxiety and cost-benefit decision-making, and a range of physiological and behavioral measures of emotion. It is proposed that both the OFC and vlPFC contribute to emotion regulation via their involvement, respectively, in the prediction of future outcomes and higher-order attentional control. The fractionation of these neurocognitive and neurobehavioral systems that regulate fear and anxiety opens up new opportunities for diagnostic stratification and personalized treatment strategies.

Regulation of UDP glucuronosyltransferases in the gastrointestinal tract

International Nuclear Information System (INIS)

Gregory, Philip A.; Lewinsky, Rikke H.; Gardner-Stephen, Dione A.; Mackenzie, Peter I.

2004-01-01

The UDP glucuronosyltransferases (UGT) of the gastrointestinal (GI) tract have a crucial role in protection against the toxic effects of lipophilic chemicals in the environment. UGTs such as UGT1A7, UGT1A8, and UGT1A10 are exclusively expressed in gastrointestinal tissues, each with a unique tissue distribution pattern that is subject to interindividual variation. The factors regulating this tissue-specific expression and that contribute to variability are beginning to be elucidated. Studies on the UGT1A7, 1A8, 1A9, and 1A10 gene promoters in Caco-2 cells, an in vitro model of enterocytes of the gastrointestinal tract, have identified the caudal homeodomain transcription factor, Cdx2, as an important regulator of the UGT1A8 and 1A10 gene proximal promoters. This transcription factor is found exclusively in the small intestine and colon: it is absent in the gastric epithelium and the esophagus. Cdx2 regulates the UGT1A8 and 1A10 promoters in cooperation with hepatocyte nuclear factor 1α (HNF1α). It is noteworthy that UGT1A7 is not expressed in gastrointestinal tissue distal to the gastric mucosa and does not contain a Cdx2 binding site in its proximal promoter. Transcription factors, including Sp1, which differentially bind to the initiator regions of the UGT1A8, 1A9, and 1A10 promoters, also contribute to the differences in expression of these UGTs in Caco-2 cells. The identification of important regulatory regions of UGT genes expressed in the gastrointestinal tract, and the transcription factors that bind to these regions, will aid in the elucidation of factors that contribute to interindividual differences in gastrointestinal UGT expression. In turn, this will lead to further understanding of interindividual variation in the capacity of the GI tract to metabolize lipophilic chemicals and to act as a barrier to dietary toxins and orally administered drugs

Acute regulation of IGF-I by alterations in post-exercise macronutrients

Science.gov (United States)

This investigation sought to examine the contributions of exercise and nutrient replenishment on in vivo regulation of the insulin-like growth factor-I (IGF-I) axis components. Eight college-aged males completed three high-intensity interval training (HIIT) protocols followed by three post-exercise ...

Mycotoxins: Risks, regulations and European co-operation

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Van Egmond Hans P.

2013-01-01

Full Text Available Mycotoxins and mycotoxicises have been problems of the past and the present, but scientific attention for mycotoxins did not start until the early 1960’s. Nowa­days, many mycotoxins are known, and their occurrence in food and animal feed may cause various adverse effects on human and animal health, including carcinogenic, hepatotoxic, immunotoxic, nephrotoxic, neurotoxic, oestrogenic and teratogenic effects. Some important mycotoxins include the aflatoxins, ochratoxin A, the fumonisins and the trichothecenes, and their significance is briefly described. To protect human and animal health, many countries have enacted specific regulations for mycotoxins in food and animal feed. Risk assessment is a major factor for scientific underpinning of regulations, but other factors such as availability of adequate sampling and analysis procedures also play an important a role in the establishment of mycotoxin regulations. In addition, socio-economic factors such as cost-benefit considerations, trade issues and sufficiency of food supply are equally important in the decision-taking process to come to meaningful regulations. Nowadays, more than 100 countries have formal mycotoxin regulations for food and feed. The mycotoxin regulations are the most stringent in the EU, where various organizations and pan-European networks contribute to combat the mycotoxin problem. It is to be expected that mycotoxins will stay with us in the future and climate change might have a negative influence in this respect. Several possibilities exist to mitigate the problems caused by mycotoxins. In particular prevention of mould growth and mycotoxin formation is key to the control of mycotoxins.

The heterogeneity of attention-deficit/hyperactivity disorder symptoms and conduct problems: Cognitive inhibition, emotion regulation, emotionality, and disorganized attachment.

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Forslund, Tommie; Brocki, Karin C; Bohlin, Gunilla; Granqvist, Pehr; Eninger, Lilianne

2016-09-01

This study examined the contributions of several important domains of functioning to attention-deficit/hyperactivity disorder (ADHD) symptoms and conduct problems. Specifically, we investigated whether cognitive inhibition, emotion regulation, emotionality, and disorganized attachment made independent and specific contributions to these externalizing behaviour problems from a multiple pathways perspective. The study included laboratory measures of cognitive inhibition and disorganized attachment in 184 typically developing children (M age = 6 years, 10 months, SD = 1.7). Parental ratings provided measures of emotion regulation, emotionality, and externalizing behaviour problems. Results revealed that cognitive inhibition, regulation of positive emotion, and positive emotionality were independently and specifically related to ADHD symptoms. Disorganized attachment and negative emotionality formed independent and specific relations to conduct problems. Our findings support the multiple pathways perspective on ADHD, with poor regulation of positive emotion and high positive emotionality making distinct contributions to ADHD symptoms. More specifically, our results support the proposal of a temperamentally based pathway to ADHD symptoms. The findings also indicate that disorganized attachment and negative emotionality constitute pathways specific to conduct problems rather than to ADHD symptoms. © 2016 The British Psychological Society.

Acrolein contributes to TRPA1 up-regulation in peripheral and central sensory hypersensitivity following spinal cord injury.

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Park, Jonghyuck; Zheng, Lingxing; Acosta, Glen; Vega-Alvarez, Sasha; Chen, Zhe; Muratori, Breanne; Cao, Peng; Shi, Riyi

2015-12-01

Acrolein, an endogenous aldehyde, has been shown to be involved in sensory hypersensitivity after rat spinal cord injury (SCI), for which the pathogenesis is unclear. Acrolein can directly activate a pro-algesic transient receptor protein ankyrin 1 (TRPA1) channel that exists in sensory neurons. Both acrolein and TRPA1 mRNA are elevated post SCI, which contributes to the activation of TRPA1 by acrolein and consequently, neuropathic pain. In the current study, we further showed that, post-SCI elevation of TRPA1 mRNA exists not only in dorsal root ganglias but also in both peripheral (paw skin) and central endings of primary afferent nerves (dorsal horn of spinal cord). This is the first indication that pain signaling can be over-amplified in the peripheral skin by elevated expressions of TRPA1 following SCI, in addition over-amplification previously seen in the spinal cord and dorsal root ganglia. Furthermore, we show that acrolein alone, in the absence of physical trauma, could lead to the elevation of TRPA1 mRNA at various locations when injected to the spinal cord. In addition, post-SCI elevation of TRPA1 mRNA could be mitigated using acrolein scavengers. Both of these attributes support the critical role of acrolein in elevating TRPA1 expression through gene regulation. Taken together, these data indicate that acrolein is likely a critical causal factor in heightening pain sensation post-SCI, through both the direct binding of TRPA1 receptor, and also by boosting the expression of TRPA1. Finally, our data also further support the notion that acrolein scavenging may be an effective therapeutic approach to alleviate neuropathic pain after SCI. We propose that the trauma-mediated elevation of acrolein causes neuropathic pain through at least two mechanisms: acrolein stimulates the production of transient receptor protein ankyrin 1 (TRPA1) in both central and peripheral locations, and it activates TRPA1 channels directly. Therefore, acrolein appears to be a critical

Regulation of intestinal protein metabolism by amino acids.

Science.gov (United States)

Bertrand, Julien; Goichon, Alexis; Déchelotte, Pierre; Coëffier, Moïse

2013-09-01

Gut homeostasis plays a major role in health and may be regulated by quantitative and qualitative food intake. In the intestinal mucosa, an intense renewal of proteins occurs, at approximately 50% per day in humans. In some pathophysiological conditions, protein turnover is altered and may contribute to intestinal or systemic diseases. Amino acids are key effectors of gut protein turnover, both as constituents of proteins and as regulatory molecules limiting intestinal injury and maintaining intestinal functions. Many studies have focused on two amino acids: glutamine, known as the preferential substrate of rapidly dividing cells, and arginine, another conditionally essential amino acid. The effects of glutamine and arginine on protein synthesis appear to be model and condition dependent, as are the involved signaling pathways. The regulation of gut protein degradation by amino acids has been minimally documented until now. This review will examine recent data, helping to better understand how amino acids regulate intestinal protein metabolism, and will explore perspectives for future studies.

Transcriptional and posttranscriptional regulation of cyanobacterial photosynthesis.

Science.gov (United States)

Wilde, Annegret; Hihara, Yukako

2016-03-01

Cyanobacteria are well established model organisms for the study of oxygenic photosynthesis, nitrogen metabolism, toxin biosynthesis, and salt acclimation. However, in comparison to other model bacteria little is known about regulatory networks, which allow cyanobacteria to acclimate to changing environmental conditions. The current work has begun to illuminate how transcription factors modulate expression of different photosynthetic regulons. During the past few years, the research on other regulatory principles like RNA-based regulation showed the importance of non-protein regulators for bacterial lifestyle. Investigations on modulation of photosynthetic components should elucidate the contributions of all factors within the context of a larger regulatory network. Here, we focus on regulation of photosynthetic processes including transcriptional and posttranscriptional mechanisms, citing examples from a limited number of cyanobacterial species. Though, the general idea holds true for most species, important differences exist between various organisms, illustrating diversity of acclimation strategies in the very heterogeneous cyanobacterial clade. This article is part of a Special Issue entitled Organization and dynamics of bioenergetic systems in bacteria, edited by Prof Conrad Mullineaux. Copyright © 2015 Elsevier B.V. All rights reserved.

Cognitive emotion regulation strategies In women abuse

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Vanesa Galego Carrillo

2016-06-01

Full Text Available Emotional regulation through cognitions is directly linked to human life and help people to maintain control on their emotions, both during and after experimenting an stressful event.  Exposition to gender violence cause serious health problems related to stress that need the activation of cognitive and behavioral processes to cope with it. WHOWorld Health Organization states that women in maltreatment situation have limitations on self-autonomy (autonomy and independent behavior. For this reason, self-regulation, understood as a mechanic of self-management through cognitions, emotions, mood, impulsive control and executive task may be affected. The main objective of this research is, to know the impact that gender-based violence may result in the use of cognitive emotion regulation strategies. It was an observational cross-over design of two non-equivalent women's groups/samples. A total of 116 women completed adapted versions to Spanish of "Cognitive Emotion Regulation Questionnaire (CERQ”. Of these, 51 were in a situation of abuse. Results show that the greatest differences between being affected or not by abuse reside in “Rumination”, “Acceptance”, “Catastrophizing and blaming others”. These findings contribute to the empirical evidence in the field of gender-based violence and provide key elements for intervention.

Regulation of Cellular Redox Signaling by Matricellular Proteins in Vascular Biology, Immunology, and Cancer.

Science.gov (United States)

Roberts, David D; Kaur, Sukhbir; Isenberg, Jeffrey S

2017-10-20

In contrast to structural elements of the extracellular matrix, matricellular proteins appear transiently during development and injury responses, but their sustained expression can contribute to chronic disease. Through interactions with other matrix components and specific cell surface receptors, matricellular proteins regulate multiple signaling pathways, including those mediated by reactive oxygen and nitrogen species and H 2 S. Dysregulation of matricellular proteins contributes to the pathogenesis of vascular diseases and cancer. Defining the molecular mechanisms and receptors involved is revealing new therapeutic opportunities. Recent Advances: Thrombospondin-1 (TSP1) regulates NO, H 2 S, and superoxide production and signaling in several cell types. The TSP1 receptor CD47 plays a central role in inhibition of NO signaling, but other TSP1 receptors also modulate redox signaling. The matricellular protein CCN1 engages some of the same receptors to regulate redox signaling, and ADAMTS1 regulates NO signaling in Marfan syndrome. In addition to mediating matricellular protein signaling, redox signaling is emerging as an important pathway that controls the expression of several matricellular proteins. Redox signaling remains unexplored for many matricellular proteins. Their interactions with multiple cellular receptors remains an obstacle to defining signaling mechanisms, but improved transgenic models could overcome this barrier. Therapeutics targeting the TSP1 receptor CD47 may have beneficial effects for treating cardiovascular disease and cancer and have recently entered clinical trials. Biomarkers are needed to assess their effects on redox signaling in patients and to evaluate how these contribute to their therapeutic efficacy and potential side effects. Antioxid. Redox Signal. 27, 874-911.

A Longitudinal Study of Emotion Regulation, Emotion Lability-Negativity, and Internalizing Symptomatology in Maltreated and Nonmaltreated Children

Science.gov (United States)

Kim-Spoon, Jungmeen; Cicchetti, Dante; Rogosch, Fred A.

2013-01-01

The longitudinal contributions of emotion regulation and emotion lability-negativity to internalizing symptomatology were examined in a low-income sample (171 maltreated and 151 nonmaltreated children, from age 7 to 10 years). Latent difference score models indicated that for both maltreated and nonmaltreated children, emotion regulation was a…

Moving to the Beat: Using Music, Rhythm, and Movement to Enhance Self-Regulation in Early Childhood Classrooms

Science.gov (United States)

Williams, Kate E.

2018-01-01

Differences in early self-regulation skills contribute to disparities in success in early learning and school transition, as well as in childhood well-being. Self-regulation refers to managing emotional, cognitive, and behavioral processes that are conducive to positive adjustment and social relationships. Researchers have identified that various…

Children’s Self-Regulation in Cultural Contexts: The Role of Parental Socialization Theories, Goals, and Practices

Science.gov (United States)

Jaramillo, Jorge M.; Rendón, María I.; Muñoz, Lorena; Weis, Mirjam; Trommsdorff, Gisela

2017-01-01

Self-regulation is a complex multidimensional construct which has been approached mainly in Western cultural contexts. The present contribution examines the importance of considering the culture-sensitive nature of self-regulation by reviewing theory and research on the development of children’s self-regulation in different cultural contexts. This review of theory and research allows to suggest that widely shared values in a cultural group influence parental socialization theories, goals, and practices, which in turn have an impact on how children learn to self-regulate, the forms of self-regulation they develop, and the goals associated with self-regulation. Thus, this article concludes that more specific research is required to relate both the developmental and the cultural aspects of children’s self-regulation. PMID:28634460

Assessing Self-Regulation of Learning Dimensions in a Stand-alone MOOC Platform

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Daniel Friday Owoichoche Onah

2017-06-01

Full Text Available A capacity for self-regulated learning (SRL has long been recognised as an important factor in successful studies. Although educational researchers have started to investigate the concept of SRL in the context of online education, very little is yet known about SRL in relation to massive open online courses (MOOCs or of appropriate strategies to foster SRL skills in MOOC learners. Self-regulation is particularly important in a MOOC-based study, which demands effective independent learning, and where widely acknowledged high dropout rates are observed. This study reports an investigation and assessment of the concept of SRL using a novel MOOC platform (eLDa by providing study options (either via a self-directed learning or instructor-led learning using a novel learning tool. In view of this, the research presents general description of self-regulated learning and explored the various existing dimensions used to expose the learners SRL skills. Drawing comparison of the online tool, the results and findings of the data were analysed. The study dis¬cusses how the various dimensions contributed to the knowledge representation of the self-regulated learning abilities shown by the learners. We present how these SRL dimensions captured using the measuring instrument contributes to our growing understanding of the distinctive features of the individual learner’s self-regulated learning. MOOCs success required a high performance of self-regulated learning abilities which at the moment very little has shown these degree of supporting SRL skills. This paper presents preliminary evaluation of a novel e-learning tool known, as ‘eLDa’ developed to implement this investi¬gation of self-regulation of learning. The research applied a modified online self-regulated learning questionnaire (OSLQ as the instrument to measure the SRL skills. The modified questionnaire known as MOOC OSLQ (MOSLQ was developed with a 19-item scale questions that exposes the six

Innovation in regulation of rapidly changing health markets.

Science.gov (United States)

Bloom, Gerald; Henson, Spencer; Peters, David H

2014-06-24

The rapid evolution and spread of health markets across low and middle-income countries (LMICs) has contributed to a significant increase in the availability of health-related goods and services around the world. The support institutions needed to regulate these markets have lagged behind, with regulatory systems that are weak and under-resourced. This paper explores the key issues associated with regulation of health markets in LMICs, and the different goals of regulation, namely quality and safety of care, value for money, social agreement over fair access and financing, and accountability. Licensing, price controls, and other traditional approaches to the regulation of markets for health products and services have played an important role, but they have been of questionable effectiveness in ensuring safety and efficacy at the point of the user in LMICs. The paper proposes a health market systems conceptual framework, using the value chain for the production, distribution and retail of health goods and services, to examine regulation of health markets in the LMIC context. We conclude by exploring the changing context going forwards, laying out implications for future heath market regulation. We argue that the case for new approaches to the regulation of markets for health products and services in LMICs is compelling. Although traditional "command and control" approaches will have a place in the toolkit of regulators, a broader bundle of approaches is needed that is adapted to the national and market-level context of particular LMICs. The implication is that it is not possible to apply standard or single interventions across countries, as approaches proven to work well in one context will not necessarily work well elsewhere.

Positive Emotion Regulation and Psychopathology: A Transdiagnostic Cultural Neuroscience Approach

Science.gov (United States)

Hechtman, Lisa A.; Raila, Hannah; Chiao, Joan Y.; Gruber, June

2013-01-01

There is burgeoning interest in the study of positive emotion regulation and psychopathology. Given the significant public health costs and the tremendous variance in national prevalence rates associated with many disorders of positive emotion, it is critical to reach an understanding of how cultural factors, along with biological factors, mutually influence positive emotion regulation. Progress in this domain has been relatively unexplored, however, underscoring the need for an integrative review and empirical roadmap for investigating the cultural neuroscientific contributions to positive emotion disturbance for both affective and clinical science domains. The present paper thus provides a multidisciplinary, cultural neuroscience approach to better understand positive emotion regulation and psychopathology. We conclude with a future roadmap for researchers aimed at harnessing positive emotion and alleviating the burden of mental illness cross-culturally. PMID:24812583

INTRINSIC REGULATION OF HEMOGLOBIN EXPRESSION BY VARIABLE SUBUNIT INTERFACE STRENGTHS

Science.gov (United States)

Manning, James M.; Popowicz, Anthony M.; Padovan, Julio C.; Chait, Brian T.; Manning, Lois R.

2012-01-01

SUMMARY The expression of the six types of human hemoglobin subunits over time is currently considered to be regulated mainly by transcription factors that bind to upstream control regions of the gene (the “extrinsic” component of regulation). Here we describe how subunit pairing and further assembly to tetramers in the liganded state is influenced by the affinity of subunits for one another (the “intrinsic” component of regulation). The adult hemoglobin dimers have the strongest subunit interfaces and the embryonic hemoglobins are the weakest with fetal hemoglobins of intermediate strength, corresponding to the temporal order of their expression. These variable subunit binding strengths and the attenuating effects of acetylation contribute to the differences with which these hemoglobin types form functional O2-binding tetramers consistent with gene switching. PMID:22129306

Rictor/mTORC2 facilitates central regulation of energy and glucose homeostasis

OpenAIRE

Kocalis, Heidi E.; Hagan, Scott L.; George, Leena; Turney, Maxine K.; Siuta, Michael A.; Laryea, Gloria N.; Morris, Lindsey C.; Muglia, Louis J.; Printz, Richard L.; Stanwood, Gregg D.; Niswender, Kevin D.

2014-01-01

Insulin signaling in the central nervous system (CNS) regulates energy balance and peripheral glucose homeostasis. Rictor is a key regulatory/structural subunit of the mTORC2 complex and is required for hydrophobic motif site phosphorylation of Akt at serine 473. To examine the contribution of neuronal Rictor/mTORC2 signaling to CNS regulation of energy and glucose homeostasis, we utilized Cre-LoxP technology to generate mice lacking Rictor in all neurons, or in either POMC or AgRP expressing...

A quorum sensing-mediated switch contributes to natural transformation of Vibrio cholerae

OpenAIRE

Blokesch Melanie

2013-01-01

There is a fundamental gap in our understanding of how horizontal gene transfer contributes to the enormous range of genetic variations that are observed among bacteria. The objective of our study was to better understand how the acquisition of genetic material by natural transformation is regulated within a population of Vibrio cholerae cells. V. cholerae is an aquatic bacterium and a facultative human pathogen. It acquires natural competence for transformation in response to changing enviro...

Up-regulation of ROS by mitochondria-dependent bystander signaling contributes to genotoxicity of bystander effects

International Nuclear Information System (INIS)

Chen Shaopeng; Zhao Ye; Zhao Guoping; Han Wei; Bao Lingzhi; Yu, K.N.; Wu Lijun

2009-01-01

Genomic instability can be observed in bystander cells. However, the underlying mechanism(s) is still relatively unclear. In a previous study, we found that irradiated cells released mitochondria-dependent intracellular factor(s) which could lead to bystander γ-H2AX induction. In this paper, we used normal (ρ + ) and mtDNA-depleted (ρ 0 ) human-hamster hybrid cells to investigate mitochondrial effects on the genotoxicity in bystander effect through medium transfer experiments. Through the detection of DNA double-strand breaks with γ-H2AX, we found that the fraction of γ-H2AX positive cells changed with time when irradiation conditioned cell medium (ICCM) were harvested. ICCM harvested from irradiated ρ + cells at 10 min post-irradiation (ρ + ICCM 10min ) caused larger increases of bystander γ-H2AX induction comparing to ρ 0 ICCM 10min , which only caused a slight increase of bystander γ-H2AX induction. The ρ + ICCM 10min could also result in the up-regulation of ROS production (increased by 35% at 10 min), while there was no significant increase in cells treated with ρ 0 ICCM 10min . We treated cells with dimethyl sulfoxide (DMSO), the scavenger of ROS, and quenched γ-H2AX induction by ρ + ICCM. Furthermore, after the medium had been transferred and the cells were continuously cultured for 7 days, we found significantly increased CD59 - gene loci mutation (increased by 45.9%) and delayed cell death in the progeny of ρ + ICCM-treated bystander cells. In conclusion, the work presented here suggested that up-regulation of the mitochondria-dependent ROS might be very important in mediating genotoxicity of bystander effects.

Identification of IbeR as a Stationary-Phase Regulator in Meningitic Escherichia coli K1 that Carries a Loss-of-Function Mutation in rpoS

Directory of Open Access Journals (Sweden)

Feng Chi

2009-01-01

Full Text Available IbeR is a regulator present in meningitic Escherichia coli strain E44 that carries a loss-of-function mutation in the stationary-phase (SP regulatory gene rpoS. In order to determine whether IbeR is an SP regulator in E44, two-dimensional gel electrophoresis and LC-MS were used to compare the proteomes of a noninvasive ibeR deletion mutant BR2 and its parent strain E44 in the SP. Four up-regulated (TufB, GapA, OmpA, AhpC and three down-regulated (LpdA, TnaA, OpmC proteins in BR2 were identified when compared to E44. All these proteins contribute to energy metabolism or stress resistance, which is related to SP regulation. One of the down-regulated proteins, tryptophanase (TnaA, which is regulated by RpoS in other E. coli strains, is associated with SP regulation via production of a signal molecule indole. Our studies demonstrated that TnaA was required for E44 invasion, and that indole was able to restore the noninvasive phenotype of the tnaA mutant. The production of indole was significantly reduced in BR2, indicating that ibeR is required for the indole production via tnaA. Survival studies under different stress conditions indicated that IbeR contributed to bacteria stress resistance in the SP. Taken together, IbeR is a novel regulator contributing to the SP regulation.

Work Programme 2010. Nordic Energy Regulators (NordREG)

Energy Technology Data Exchange (ETDEWEB)

2010-02-15

The Nordic regulators' cooperation through NordREG is based on a strong consensus and common understanding of the Nordic market. Through mutual efforts and contributions NordREG members identify areas of work that can create added value for the Nordic electricity market. NordREG works by exchanging information and views, mapping and analysing energy market issues and by delivering statements and reports for harmonisation and improvement. In this, the regulators aim at identifying areas where NordREG can take joint action to influence Nordic or European electricity market development. NordREGs key focus in 2010 is the work towards a common Nordic retail market and the emphasis is on promoting a legal and institutional framework that supports this goal

Expectancies for Social Support and Negative Mood Regulation Mediate the Relationship between Childhood Maltreatment and Self-Injury

Directory of Open Access Journals (Sweden)

Fiona Tresno

2016-07-01

Full Text Available Nonsuicidal self-injury (NSSI is common among young people. A majority of individuals who injure themselves do so to alleviate negative affect, as most self-injurers report difficulties with mood regulation. Trauma in childhood is an important risk factor that may cause individuals to develop poor interpersonal relations and impaired emotion-regulation, leading to the use of non-adaptive coping strategies such as NSSI. This study examined factors contributing to self-injury, focusing on the link from childhood maltreatment, through mood regulation expectancies and expectancies for social support (father, mother, and friends, to self-injury. Understanding how these variables relate to NSSI is crucial for early identification of individuals at risk of NSSI. Participants were 377 Japanese university students. Lifetime prevalence of self-injury was 20% among the sample. Results showed childhood maltreatment is a strong predictor that increases the risk for NSSI. However, expectancies for social support and mood regulation seem to be potential protective factors. Mood regulation expectancies mediate the relationship between childhood maltreatment and self-injury. In addition, expectancies for social support were indirectly linked with NSSI through negative mood regulation expectancies. It appears that perceived support from father and friends increases one's confidence in regulating difficult emotions, which in turn reduces risk for NSSI. Results suggest that strong expectancies for social support, especially from friends, increase one's confidence in regulating emotion, which contributes as a protective factor against self-injury.

The Behavioural Law and Economics of the Precautionary Principle in the EU and Its Impact on Internal Market Regulation

NARCIS (Netherlands)

Purnhagen, K.

2014-01-01

The precautionary principle contributes to “the social” of internal market regulation as it counterbalances the loss aversion and availability bias of regulators who may too hastily endorse measures based to further the fundamental freedoms instead of fundamental rights and environmental protection.

[Performance based regulation: a strategy to increase breastfeeding rates].

Science.gov (United States)

Cobo-Armijo, Fernanda; Charvel, Sofía; Hernández-Ávila, Mauricio

2017-01-01

The decreasing breastfeeding rate in México is of public health concern. In this paper we discus an innovative regulatory approach -Performance Based Regulation- and its application to improve breastfeeding rates. This approach, forces industry to take responsibility for the lack of breastfeeding and its consequences. Failure to comply with this targets results in financial penalties. Applying performance based regulation as a strategy to improve breastfeeding is feasible because: the breastmilk substitutes market is an oligopoly, hence it is easy to identify the contribution of each market participant; the regulation's target population is clearly defined; it has a clear regulatory standard which can be easily evaluated, and sanctions to infringement can be defined under objective parameters. modify public policy, celebrate concertation agreements with the industry, create persuasive sanctions, strengthen enforcement activities and coordinate every action with the International Code of Marketing of Breast-milk Substitutes.

VMAT2-mediated neurotransmission from midbrain leptin receptor neurons in feeding regulation

Science.gov (United States)

Leptin receptors (LepRs) expressed in the midbrain contribute to the action of leptin on feeding regulation. The midbrain neurons release a variety of neurotransmitters including dopamine (DA), glutamate and GABA. However, which neurotransmitter mediates midbrain leptin action on feeding remains unc...

The Regulation of Immunological Processes by Peripheral Neurons in Homeostasis and Disease.

Science.gov (United States)

Ordovas-Montanes, Jose; Rakoff-Nahoum, Seth; Huang, Siyi; Riol-Blanco, Lorena; Barreiro, Olga; von Andrian, Ulrich H

2015-10-01

The nervous system and the immune system are the principal sensory interfaces between the internal and external environment. They are responsible for recognizing, integrating, and responding to varied stimuli, and have the capacity to form memories of these encounters leading to learned or 'adaptive' future responses. We review current understanding of the cross-regulation between these systems. The autonomic and somatosensory nervous systems regulate both the development and deployment of immune cells, with broad functions that impact on hematopoiesis as well as on priming, migration, and cytokine production. In turn, specific immune cell subsets contribute to homeostatic neural circuits such as those controlling metabolism, hypertension, and the inflammatory reflex. We examine the contribution of the somatosensory system to autoimmune, autoinflammatory, allergic, and infectious processes in barrier tissues and, in this context, discuss opportunities for therapeutic manipulation of neuro-immune interactions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rapamycin down-regulates LDL-receptor expression independently of SREBP-2

International Nuclear Information System (INIS)

Sharpe, Laura J.; Brown, Andrew J.

2008-01-01

As a key regulator of cholesterol homeostasis, sterol-regulatory element binding protein-2 (SREBP-2) up-regulates expression of genes involved in cholesterol synthesis (e.g., 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) Reductase) and uptake (the low density lipoprotein (LDL)-receptor). Previously, we showed that Akt, a critical kinase in cell growth and proliferation, contributes to SREBP-2 activation. However, the specific Akt target involved is unknown. A potential candidate is the mammalian target of rapamycin, mTOR. Rapamycin can cause hyperlipidaemia clinically, and we hypothesised that this may be mediated via an effect of mTOR on SREBP-2. Herein, we found that SREBP-2 activation and HMG-CoA Reductase gene expression were unaffected by rapamycin treatment. However, LDL-receptor gene expression was decreased by rapamycin, suggesting that this may contribute to the hyperlipidaemia observed in rapamycin-treated patients. Rapamycin did not affect mRNA stability, so the decrease in LDL-receptor gene expression is likely to be occurring at the transcriptional level, although independently of SREBP-2

Rab proteins: The key regulators of intracellular vesicle transport

International Nuclear Information System (INIS)

Bhuin, Tanmay; Roy, Jagat Kumar

2014-01-01

Vesicular/membrane trafficking essentially regulates the compartmentalization and abundance of proteins within the cells and contributes in many signalling pathways. This membrane transport in eukaryotic cells is a complex process regulated by a large and diverse array of proteins. A large group of monomeric small GTPases; the Rabs are essential components of this membrane trafficking route. Most of the Rabs are ubiquitously expressed proteins and have been implicated in vesicle formation, vesicle motility/delivery along cytoskeleton elements and docking/fusion at target membranes through the recruitment of effectors. Functional impairments of Rabs affecting transport pathways manifest different diseases. Rab functions are accompanied by cyclical activation and inactivation of GTP-bound and GDP-bound forms between the cytosol and membranes which is regulated by upstream regulators. Rab proteins are characterized by their distinct sub-cellular localization and regulate a wide variety of endocytic, transcytic and exocytic transport pathways. Mutations of Rabs affect cell growth, motility and other biological processes. - Highlights: • Rab proteins regulate different signalling pathways. • Deregulation of Rabs is the fundamental causes of a variety of human diseases. • This paper gives potential directions in developing therapeutic targets. • This paper also gives ample directions for modulating pathways central to normal physiology. • These are the huge challenges for drug discovery and delivery in near future

Rab proteins: The key regulators of intracellular vesicle transport

Energy Technology Data Exchange (ETDEWEB)

Bhuin, Tanmay [Cell and Developmental Biology Unit, Department of Zoology, The University of Burdwan, Golapbag 713104 (India); Roy, Jagat Kumar, E-mail: jkroy@bhu.ac.in [Cytogenetics Laboratory, Department of Zoology, Banaras Hindu University, Varanasi 221005 (India)

2014-10-15

Vesicular/membrane trafficking essentially regulates the compartmentalization and abundance of proteins within the cells and contributes in many signalling pathways. This membrane transport in eukaryotic cells is a complex process regulated by a large and diverse array of proteins. A large group of monomeric small GTPases; the Rabs are essential components of this membrane trafficking route. Most of the Rabs are ubiquitously expressed proteins and have been implicated in vesicle formation, vesicle motility/delivery along cytoskeleton elements and docking/fusion at target membranes through the recruitment of effectors. Functional impairments of Rabs affecting transport pathways manifest different diseases. Rab functions are accompanied by cyclical activation and inactivation of GTP-bound and GDP-bound forms between the cytosol and membranes which is regulated by upstream regulators. Rab proteins are characterized by their distinct sub-cellular localization and regulate a wide variety of endocytic, transcytic and exocytic transport pathways. Mutations of Rabs affect cell growth, motility and other biological processes. - Highlights: • Rab proteins regulate different signalling pathways. • Deregulation of Rabs is the fundamental causes of a variety of human diseases. • This paper gives potential directions in developing therapeutic targets. • This paper also gives ample directions for modulating pathways central to normal physiology. • These are the huge challenges for drug discovery and delivery in near future.

Regulated degradation of the APC coactivator Cdc20

Directory of Open Access Journals (Sweden)

Robbins Jonathan A

2010-09-01

Full Text Available Abstract Background Cdc20 is a highly conserved activator of the anaphase-promoting complex (APC, promoting cell-cycle-regulated ubiquitination and proteolysis of a number of critical cell-cycle-regulatory targets including securin and mitotic cyclins. APC-Cdc20 activity is tightly regulated, and this regulation is likely important for accurate cell cycle control. One significant component of Cdc20 regulation is thought to be Cdc20 proteolysis. However, published literature suggests different mechanisms and requirements for Cdc20 proteolysis. The degree to which Cdc20 proteolysis is cell-cycle regulated, the dependence of Cdc20 proteolysis on Cdc20 destruction boxes (recognition sequences for APC-mediated ubiqutination, either by Cdc20 or by the related Cdh1 APC activator, and the need for APC itself for Cdc20 proteolysis all have been disputed to varying extents. In animals, Cdc20 proteolysis is thought to be mediated by Cdh1, contributing an intrinsic order of APC activation by Cdc20 and then by Cdh1. One report suggests a Cdh1 requirement for Cdc20 proteolysis in budding yeast; this idea has not been tested further. Results We characterized Cdc20 proteolysis using Cdc20 expressed from its endogenous locus; previous studies generally employed strongly overexpressed Cdc20, which can cause significant artifacts. We analyzed Cdc20 proteolysis with or without mutations in previously identified destruction box sequences, using varying methods of cell cycle synchronization, and in the presence or absence of Cdh1. Cdc20 instability is only partially dependent on destruction boxes. A much stronger dependence on Cdh1 for Cdc20 proteolysis was observed, but Cdh1-independent proteolysis was also clearly observed. Cdc20 proteolysis independent of both destruction boxes and Cdh1 was especially detectable around the G1/S transition; Cdh1-dependent proteolysis was most notable in late mitosis and G1. Conclusions Cdc20 proteolysis is under complex control

In vivo labelling of functional ribosomes reveals spatial regulation during starvation in Podospora anserina

Directory of Open Access Journals (Sweden)

Silar Philippe

2000-11-01

Full Text Available Abstract Background To date, in eukaryotes, ribosomal protein expression is known to be regulated at the transcriptional and/or translational levels. But other forms of regulation may be possible. Results Here, we report the successful tagging of functional ribosomal particles with a S7-GFP chimaeric protein, making it possible to observe in vivo ribosome dynamics in the filamentous fungus Podospora anserina. Microscopic observations revealed a novel kind of ribosomal protein regulation during the passage between cell growth and stationary phases, with a transient accumulation of ribosomal proteins and/or ribosome subunits in the nucleus, possibly the nucleolus, being observed at the beginning of stationary phase. Conclusion Nuclear sequestration can be another level of ribosomal protein regulation in eukaryotic cells.This may contribute to the regulation of cell growth and division.

In vivo labelling of functional ribosomes reveals spatial regulation during starvation in Podospora anserina

Science.gov (United States)

Lalucque, Hervé; Silar, Philippe

2000-01-01

Background To date, in eukaryotes, ribosomal protein expression is known to be regulated at the transcriptional and/or translational levels. But other forms of regulation may be possible. Results Here, we report the successful tagging of functional ribosomal particles with a S7-GFP chimaeric protein, making it possible to observe in vivo ribosome dynamics in the filamentous fungus Podospora anserina. Microscopic observations revealed a novel kind of ribosomal protein regulation during the passage between cell growth and stationary phases, with a transient accumulation of ribosomal proteins and/or ribosome subunits in the nucleus, possibly the nucleolus, being observed at the beginning of stationary phase. Conclusion Nuclear sequestration can be another level of ribosomal protein regulation in eukaryotic cells.This may contribute to the regulation of cell growth and division. PMID:11112985

Food Safety Regulation and Firm Productivity: Evidence from the French Food Industry

OpenAIRE

Requillart, Vincent; Nauges, Celine; Simioni, Michel; Bontemps, Christophe

2012-01-01

The purpose of this article is to assess whether food safety regulations imposed by the European Union in the 2000s may have induced a slow-down in the productivity of firms in the food processing sector. The impact of regulations on costs and productivity has seldom been studied. This article contributes to the literature by measuring productivity change using a panel of French food processing firms for the years 1996 to 2006. To do so, we develop an original iterative testing procedure b...

Regulation of pH in human skeletal muscle: adaptations to physical activity

DEFF Research Database (Denmark)

Juel, C

2008-01-01

-transport) and describes the contribution of each transport system in pH regulation at rest and during muscle activity. It is reported that the mechanisms involved in pH regulation can undergo adaptational changes in association with physical activity and that these changes are of functional importance....... resonance technique to exercise experiments including blood sampling and muscle biopsies. The present review characterizes the cellular buffering system as well as the most important membrane transport systems involved (Na(+)/H(+) exchange, Na-bicarbonate co-transport and lactate/H(+) co...

Facebook: selvfremstilling, small-talk og social regulering

DEFF Research Database (Denmark)

Sørensen, Anne Scott

2012-01-01

In this paper, I will document the use of Facebook in a Danish context, taking a mediatisation perspective focused on the network sociality in question (Jensen, 2009; Tække, 2010a/b) and the communication (Miller, 2008) of social media. This discussion is based on a qualitative study from 2010......, consisting of participants recruited from a survey study. The study explores three dilemmas resulting from network media’s communicative paradox, involving the premises of self-representation, use of status updates, and social regulation. These dilemmas are contextualised by recent theories of genre......, such research has not previously been documented (or refined) in a Danish context. The paper’s most important contributions, however, consist of its identification of the three communicative dilemmas, its tentative genre classification of the status update, and its discussion of implicit social regulation...

Chromatin regulators, phenotypic robustness and autism risk

Directory of Open Access Journals (Sweden)

Reut eSuliman

2014-04-01

Full Text Available Though extensively characterized clinically, the causes of autism spectrum disorder (ASD remain a mystery. ASD is known to have a strong genetic basis, but it is genetically very heterogeneous. Recent studies have estimated that de novo disruptive mutations in hundreds of genes may contribute to ASD. However, it is unclear how it is possible for mutations in so many different genes to contribute to ASD. Recent findings suggest that many of the mutations disrupt genes involved in transcription regulation that are expressed prenatally in the developing brain. De novo disruptive mutations are also more frequent in girls with ASD, despite the fact that ASD is more prevalent in boys. In this paper, we hypothesize that loss of robustness may contribute to ASD. Loss of phenotypic robustness may be caused by mutations that disrupt capacitors that operate in the developing brain. This may lead to the release of cryptic genetic variation that contributes to ASD. Reduced robustness is consistent with the observed variability in expressivity and incomplete penetrance. It is also consistent with the hypothesis that the development of the female brain is more robust, and it may explain the higher rate and severity of disruptive de novo mutations in girls with ASD.

Contralesional Hemisphere Regulation of Transcranial Magnetic Stimulation-Induced Kinetic Coupling in the Poststroke Lower Limb

OpenAIRE

Tan, Andrew Q.; Dhaher, Yasin Y.

2017-01-01

Background The neural constraints underlying hemiparetic gait dysfunction are associated with abnormal kinetic outflow and altered muscle synergy structure. Recent evidence from our lab implicates the lesioned hemisphere in mediating the expression of abnormally coupled hip adduction and knee extension synergy, suggesting a role of cortical networks in the regulation of lower limb motor outflow poststroke. The potential contribution of contralesional hemisphere (CON-H) in regulating pareti...

The Heterogeneity of ADHD Symptoms and Conduct Problems : Cognitive Inhibition, Emotion Regulation, Emotionality and Disorganized Attachment

OpenAIRE

Forslund, Tommie; Brocki, Karin; Bohlin, Gunilla; Granqvist, Pehr; Eninger, Lilianne

2016-01-01

This study examined the contributions of several important domains of functioning to attention-deficit/hyperactivity disorder (ADHD) symptoms and conduct problems. Specifically, we investigated whether cognitive inhibition, emotion regulation, emotionality, and disorganized attachment made independent and specific contributions to these externalizing behaviour problems from a multiple pathways perspective. The study included laboratory measures of cognitive inhibition and disorganized attachm...

Microorganisms having enhanced tolerance to inhibitors and stress

Energy Technology Data Exchange (ETDEWEB)

Brown, Steven D.; Yang, Shihui

2014-07-29

The present invention provides genetically modified strains of microorganisms that display enhanced tolerance to stress and/or inhibitors such as sodium acetate and vanillin. The enhanced tolerance can be achieved by increasing the expression of a protein of the Sm-like superfamily such as a bacterial Hfq protein and a fungal Sm or Lsm protein. Further, the present invention provides methods of producing alcohol from biomass materials by using the genetically modified microorganisms of the present invention.

Regulation and competition issues in Thai electricity sector

International Nuclear Information System (INIS)

Wisuttisak, Pornchai

2012-01-01

This paper explores the issues related to regulatory reform and liberalisation leading toward competition in the Thai electricity sector, which is still under the monopoly control of state-owned enterprises (SOEs). Following an overview of the current market structure of the Thai electricity sector, the process of liberalisation and deregulation that contributes to the uncompetitive market structure under SOEs’ control is examined. The author asserts that there are problems within the Energy Commission and the Energy Industry Act BE 2550 (2007) that contribute to the continuance of an uncompetitive electricity supply. Possible reforms to the Thai electricity regulation are proposed with the aim of creating market competition and efficiency in the Thai electricity sector. - Highlights: ► Author studies on the regulatory reform and a development of liberalisation plans on Thai electricity sector. ► The paper presents that the liberalisation plan was affected by the government implementation on electricity corporatisation. ► The paper asserts that the current energy regulation will not lead to market reform and competition in electricity. ► The paper also discusses on the current monopoly structure of Thai electricity sector under state owned enterprises. ► The paper concludes that Thailand needs an appropriate regulatory reform for building competition in electricity sector.

Support for the revision of regulation on CO2 emissions from light commercial vehicles

Energy Technology Data Exchange (ETDEWEB)

Smokers, R.; Fraga, F.; Verbeek, M.; Willems, F.; Massink, R.; Spreen, J. [TNO, Delft (Netherlands); Norris, J.; Martinez, C. [AEA Technology plc, London (United Kingdom); Kampman, B.; Brinke, L.; Van Essen, H. [CE Delft, Delft (Netherlands); Schilling, S.; Gruhlke, A.; Sander, K. [Institut fuer Oekologie und Politik Oekopol, Hamburg (Netherlands); Breemersch, T.; De Ceuster, G.; Vanherle, K.; Heyndrickx, C. [Transport and Mobility Leuven TML, Leuven (Belgium); Wrigley, S.; O' Brien, S.; Johnson, A. [Ricardo UK, Shoreham-by-Sea, West Sussex (United Kingdom); Buttigieg, D.; Sima, L.; Pagnac, J.; Dhaene, G. [IHS Global Insight, Nijmegen (Netherlands)

2012-04-15

Road vehicles make a major contribution to transport sector CO2 emissions and the European Union has several policies in place to reduce their emissions. One of these is the regulation to reduce the CO2 emissions of light commercial vehicles (LCVs or vans), Regulation (EU) 510/2011, often referred to as the vans regulation. This contains a number of review clauses, which require the European Commission to carry out an impact assessment on the 2020 target of 147 gCO2/km, and to assess a number of further issues. The ensuing study addresses a wide range of topics relating to this regulation, and includes the development of cost curves for different LCV segments, the evaluation of different utility parameters, a comparison with the effort needed to reduce the CO2 emissions of passenger cars, an assessment of the impact of electric vehicle penetration and calculation of the effects on the total cost of ownership and the societal abatement costs associated with the 2020 target. CE Delft contributed to this study by developing scenarios for the market uptake of electric vehicles in this vehicle segment, and by providing support to the Commission regarding the economic aspects of the Impact Analysis.

Up-regulation of ROS by mitochondria-dependent bystander signaling contributes to genotoxicity of bystander effects

Energy Technology Data Exchange (ETDEWEB)

Chen Shaopeng [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Zhao Ye; Zhao Guoping [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Han Wei [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Bao Lingzhi [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Yu, K.N., E-mail: peter.yu@cityu.edu.hk [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Wu Lijun, E-mail: ljw@ipp.ac.cn [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China)

2009-06-18

Genomic instability can be observed in bystander cells. However, the underlying mechanism(s) is still relatively unclear. In a previous study, we found that irradiated cells released mitochondria-dependent intracellular factor(s) which could lead to bystander {gamma}-H2AX induction. In this paper, we used normal ({rho}{sup +}) and mtDNA-depleted ({rho}{sup 0}) human-hamster hybrid cells to investigate mitochondrial effects on the genotoxicity in bystander effect through medium transfer experiments. Through the detection of DNA double-strand breaks with {gamma}-H2AX, we found that the fraction of {gamma}-H2AX positive cells changed with time when irradiation conditioned cell medium (ICCM) were harvested. ICCM harvested from irradiated {rho}{sup +} cells at 10 min post-irradiation ({rho}{sup +} ICCM{sub 10min}) caused larger increases of bystander {gamma}-H2AX induction comparing to {rho}{sup 0} ICCM{sub 10min}, which only caused a slight increase of bystander {gamma}-H2AX induction. The {rho}{sup +} ICCM{sub 10min} could also result in the up-regulation of ROS production (increased by 35% at 10 min), while there was no significant increase in cells treated with {rho}{sup 0} ICCM{sub 10min}. We treated cells with dimethyl sulfoxide (DMSO), the scavenger of ROS, and quenched {gamma}-H2AX induction by {rho}{sup +} ICCM. Furthermore, after the medium had been transferred and the cells were continuously cultured for 7 days, we found significantly increased CD59{sup -} gene loci mutation (increased by 45.9%) and delayed cell death in the progeny of {rho}{sup +} ICCM-treated bystander cells. In conclusion, the work presented here suggested that up-regulation of the mitochondria-dependent ROS might be very important in mediating genotoxicity of bystander effects.

Regulative environmental policy. Regulative Umweltpolitik

Energy Technology Data Exchange (ETDEWEB)

Goerlitz, A; Voigt, R [Universitaet der Bundeswehr Muenchen, Neubiberg (Germany, F.R.). Fakultaet fuer Sozialwissenschaften; eds.

1991-01-01

Regulative policy means those governmental attempts to steer the course of things which can fall back on a certain repertoire of instruments for actions in order to warrant the causal and temporal connection between the making available and the employment of means. The fact that environmental protection needs regulative policy is substantiated by the thesis that the market has failed; consequently only government can manage the public goods 'environment' in a suitable way, and it is a matter of fact that environmental protection at present is operated preferably via regulative policy. The problems of regulative enviromental policy are manifold. Its implementation often miscarries because of limited administrative resources on the one hand - making sufficient control impossible for instance -, and because of poor quality regulative instruments on the other hand. One way out would be to increase the efficiency of regulative policy by sophisticating judicial techniques. Other ways out point to the executing level and aim at improving implementation strategies or are concerned with post-regulative law. The latter refers to a new legal quality which demonstrates itself already in corporatistical crisis regulation or in induction programs such as pollution limits. A final way out favours deregulation strategies which includes the introduction of environmental levies or the allocation of environmental licences. An interdisciplinary discourse is to find out what would happen if these ways were taken. Pointers to solutions from varying scientific disciplines resulting from this discourse are to be found in this volume. (orig./HSCH).

Federal Act on Protection against Nuisances (BImSchG) and supplementing regulations. 11. ed.

International Nuclear Information System (INIS)

Hansmann, K.

1993-01-01

This handy booklet contains the BImSchG and related implementing regulations as well as the Technical Codes Clean Air and Noise Abatement. The contribution on the BImSchG explains the origin of the Act, the scope of application, its concept and principles. The contents of the Act is portrayed by emphasizing subject-related connections. Dealt with are also regulations for installations requiring licensing, the measurement of airborne pollution, stipulations concerning the area of installations and transport, as well as the regulation concerning the monitoring of airborne pollution in the Federal Republic of Germany. (orig.) [de

Federal Act on Protection against Nuisances (BImSchG) and supplementing regulations. 9. ed.

International Nuclear Information System (INIS)

Hansmann, K.

1992-01-01

This handy booklet contains the BImSchG and related implementing regulations as well as the Technical Codes Clean Air and Noise Abatement. The contribution on the BImSchG explains the origin of the Act, the scope of application, its concept and principles. The contents of the Act is portrayed by emphasizing subject-related connections. Dealt with are also regulations for installations requiring licensing, the measurement of airborne pollution, stipulations concerning the area of installations and transport, as well as the regulation concerning the monitoring of airborne pollution in the Federal Republic of Germany. (orig.) [de

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to acetyl-L-carnitine and contribution to normal cognitive function (ID 1432) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

DEFF Research Database (Denmark)

Tetens, Inge

claims in relation to acetyl-L-carnitine and contribution to normal cognitive function. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims and references that EFSA has received from Member States or directly from......Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006. This opinion addresses the scientific substantiation of health...... be drawn for the scientific substantiation of the claim. On the basis of the data presented, the Panel concludes that a cause and effect relationship has not been established between the consumption of acetyl-L-carnitine and contribution to normal cognitive function....

Systemic risk in the energy sector: is there need for financial regulation?

NARCIS (Netherlands)

Kerste, M.; Gerritsen, M.; Weda, J.; Tieben, B.

2015-01-01

The credit crisis points at serious systemic risks in Over The Counter derivative trading. This has resulted in new financial regulation, covering both the financial sector and non-financial sectors. The actual extent to which non-financial companies trading on OTC markets contribute to systemic

The transcription factor VvMYB5b contributes to the regulation of anthocyanin and proanthocyanidin biosynthesis in developing grape berries.

Science.gov (United States)

Deluc, Laurent; Bogs, Jochen; Walker, Amanda R; Ferrier, Thilia; Decendit, Alain; Merillon, Jean-Michel; Robinson, Simon P; Barrieu, François

2008-08-01

Among the dramatic changes occurring during grape berry (Vitis vinifera) development, those affecting the flavonoid pathway have provoked a number of investigations in the last 10 years. In addition to producing several compounds involved in the protection of the berry and the dissemination of the seeds, final products of this pathway also play a critical role in berry and wine quality. In this article, we describe the cloning and functional characterization of VvMYB5b, a cDNA isolated from a grape berry (V. vinifera 'Cabernet Sauvignon') library. VvMYB5b encodes a protein belonging to the R2R3-MYB family of transcription factors and displays significant similarity with VvMYB5a, another MYB factor recently shown to regulate flavonoid synthesis in grapevine. The ability of VvMYB5a and VvMYB5b to activate the grapevine promoters of several structural genes of the flavonoid pathway was confirmed by transient expression of the corresponding cDNAs in grape cells. Overexpression of VvMYB5b in tobacco (Nicotiana tabacum) leads to an up-regulation of genes encoding enzymes of the flavonoid pathway and results in the accumulation of anthocyanin- and proanthocyanidin-derived compounds. The ability of VvMYB5b to regulate particularly the anthocyanin and the proanthocyanidin pathways is discussed in relation to other recently characterized MYB transcription factors in grapevine. Taken together, data presented in this article give insight into the transcriptional mechanisms associated with the regulation of the flavonoid pathway throughout grape berry development.

Masculine Discrepancy Stress, Emotion-Regulation Difficulties, and Intimate Partner Violence.

Science.gov (United States)

Berke, Danielle S; Reidy, Dennis E; Gentile, Brittany; Zeichner, Amos

2016-05-24

Research suggests that masculine socialization processes contribute to the perpetration of intimate partner violence (IPV) by men. Although this research has traditionally focused on men who strongly adhere to traditional gender norms, men who negatively evaluate themselves as falling short of these norms (a construct termed masculine discrepancy stress) have proven to be at increased risk of IPV perpetration. Likewise, men experiencing problems with emotion regulation, a multidimensional construct reflecting difficulties in effectively experiencing and responding to emotional states, are also at risk of IPV perpetration. In the present research, we tested the hypothesis that the link between discrepancy stress and IPV perpetration is mediated via difficulties in emotion regulation. Three hundred fifty-seven men completed online surveys assessing their experience of discrepancy stress, emotion-regulation difficulties, and history of IPV perpetration. Results indicated that discrepancy-stressed men's use of physical IPV was fully mediated by emotion-regulation difficulties. In addition, emotion-regulation difficulties partially mediated the association between discrepancy stress and sexual IPV. Findings are discussed in terms of the potential utility of emotion-focused interventions for modifying men's experience and expression of discrepancy stress and reducing perpetration of IPV. © The Author(s) 2016.

Masculine Discrepancy Stress, Emotion-Regulation Difficulties, and Intimate Partner Violence

Science.gov (United States)

Berke, Danielle S.; Reidy, Dennis E.; Gentile, Brittany; Zeichner, Amos

2018-01-01

Research suggests that masculine socialization processes contribute to the perpetration of intimate partner violence (IPV) by men. Although this research has traditionally focused on men who strongly adhere to traditional gender norms, men who negatively evaluate themselves as falling short of these norms (a construct termed masculine discrepancy stress) have proven to be at increased risk of IPV perpetration. Likewise, men experiencing problems with emotion regulation, a multidimensional construct reflecting difficulties in effectively experiencing and responding to emotional states, are also at risk of IPV perpetration. In the present research, we tested the hypothesis that the link between discrepancy stress and IPV perpetration is mediated via difficulties in emotion regulation. Three hundred fifty-seven men completed online surveys assessing their experience of discrepancy stress, emotion-regulation difficulties, and history of IPV perpetration. Results indicated that discrepancy-stressed men's use of physical IPV was fully mediated by emotion-regulation difficulties. In addition, emotion-regulation difficulties partially mediated the association between discrepancy stress and sexual IPV. Findings are discussed in terms of the potential utility of emotion-focused interventions for modifying men's experience and expression of discrepancy stress and reducing perpetration of IPV. PMID:27226013

Fronto-Limbic Brain Dysfunction during the Regulation of Emotion in Schizophrenia.

Directory of Open Access Journals (Sweden)

Shaun M Eack

Full Text Available Schizophrenia is characterized by significant and widespread impairments in the regulation of emotion. Evidence is only recently emerging regarding the neural basis of these emotion regulation impairments, and few studies have focused on the regulation of emotion during effortful cognitive processing. To examine the neural correlates of deficits in effortful emotion regulation, schizophrenia outpatients (N = 20 and age- and gender-matched healthy volunteers (N = 20 completed an emotional faces n-back task to assess the voluntary attentional control subprocess of emotion regulation during functional magnetic resonance imaging. Behavioral measures of emotional intelligence and emotion perception were administered to examine brain-behavior relationships with emotion processing outcomes. Results indicated that patients with schizophrenia demonstrated significantly greater activation in the bilateral striatum, ventromedial prefrontal, and right orbitofrontal cortices during the effortful regulation of positive emotional stimuli, and reduced activity in these same regions when regulating negative emotional information. The opposite pattern of results was observed in healthy individuals. Greater fronto-striatal response to positive emotional distractors was significantly associated with deficits in facial emotion recognition. These findings indicate that abnormalities in striatal and prefrontal cortical systems may be related to deficits in the effortful emotion regulatory process of attentional control in schizophrenia, and may significantly contribute to emotion processing deficits in the disorder.

"Genetic regulation of Mycobacterium tuberculosis in a lipid-rich environment".

Science.gov (United States)

Aguilar-Ayala, Diana A; Palomino, Juan Carlos; Vandamme, Peter; Martin, Anandi; Gonzalez-Y-Merchand, Jorge A

2017-11-01

Tuberculosis (TB) remains as one of the leading causes of morbidity and mortality among infectious diseases worldwide. Although lipids (mainly fatty acids and cholesterol) have been reported to play an important role during active and latent infection of M. tuberculosis, there are other molecular aspects of bacterial response to those substrates that are not fully understood, involving gene regulation background. This review highlights recent insights on pathogen gene expression: regulation during its active growth, during survival in presence of lipids and under variable hostile host microenvironments. We also propose several application options of this knowledge that may contribute for improved TB control. Copyright © 2016 Elsevier B.V. All rights reserved.

Regulation of homologous recombination at telomeres in budding yeast

DEFF Research Database (Denmark)

Eckert-Boulet, Nadine; Lisby, Michael

2010-01-01

Homologous recombination is suppressed at normal length telomere sequences. In contrast, telomere recombination is allowed when telomeres erode in the absence of telomerase activity or as a consequence of nucleolytic degradation or incomplete replication. Here, we review the mechanisms that contr...... that contribute to regulating mitotic homologous recombination at telomeres and the role of these mechanisms in signalling short telomeres in the budding yeast Saccharomyces cerevisiae....

Impact of Hfq on the Bacillus subtilis Transcriptome

Czech Academy of Sciences Publication Activity Database

Hämmerle, H.; Amman, F.; Večerek, Branislav; Stülke, J.; Hofacker, I.; Bläsi, U.

2014-01-01

Roč. 9, č. 6 (2014) E-ISSN 1932-6203 Institutional support: RVO:61388971 Keywords : STAPHYLOCOCCUS-AUREUS RNAIII * SMALL NONCODING RNAS * SMALL REGULATORY RNA Subject RIV: EE - Microbiology, Virology Impact factor: 3.234, year: 2014

Relative contribution of ruminal buffering systems to pH regulation in feedlot cattle fed either low- or high-forage diets.

Science.gov (United States)

Chibisa, G E; Beauchemin, K A; Penner, G B

2016-07-01

The relative contribution of ruminal short-chain fatty acid (SCFA) absorption and salivary buffering to pH regulation could potentially change under different dietary conditions. Therefore, the objective of this study was to investigate the effects of altering the ruminal supply of rapidly fermentable carbohydrate (CHO) on absorptive function and salivation in beef cattle. Eight heifers (mean BW±SD=410±14 kg) were randomly allocated to two treatments in a crossover design with 37-day periods. Dietary treatments were barley silage at 30% low forage (LF) or 70% high forage (HF) of dietary dry matter (DM), with the remainder of the diet consisting of barley grain (65% or 25% on a DM basis) and a constant level (5%) of supplement. The LF and HF diets contained 45.3% and 30.9% starch, and 4.1% and 14.0% physically effective fiber (DM basis), respectively. Ruminal pH was continuously measured from day 17 to day 23, whereas ruminal fluid was collected on day 23 to determine SCFA concentration. Ruminal liquid passage rate was determined on day 23 using Cr-ethylenediaminetetraacetic acid. Eating or resting salivation was measured by collecting masticate (days 28 and 29) or saliva samples (days 30 and 31) at the cardia, respectively. On days 30 and 31, the temporarily isolated and washed reticulo-rumen technique was used to measure total, and Cl--competitive (an indirect measure of protein-mediated transport) absorption of acetate, propionate and butyrate. As a result of the higher dietary starch content and DM intake, the ruminal supply of rapidly fermentable CHO, total ruminal SCFA concentration (118 v. 95 mM; Pruminal pH in cattle with greater rapidly fermentable CHO intake was attributed to an increase in SCFA production and decrease in salivation, which were not compensated for by an increase in epithelial permeability.

Difficulties in emotion regulation and risky driving among Lithuanian drivers.

Science.gov (United States)

Šeibokaitė, Laura; Endriulaitienė, Auksė; Sullman, Mark J M; Markšaitytė, Rasa; Žardeckaitė-Matulaitienė, Kristina

2017-10-03

Risky driving is a common cause of traffic accidents and injuries. However, there is no clear evidence of how difficulties in emotion regulation contribute to risky driving behavior, particularly in small post-Soviet countries. The present study aimed to investigate the relationship between difficulties in emotion regulation and self-reported risky driving behavior in a sample of Lithuanian drivers. A total of 246 nonprofessional Lithuanian drivers participated in a cross-sectional survey. Difficulties in emotion regulation were assessed using the Difficulties in Emotion Regulation Scale (DERS; Gratz and Roemer 2004), and risky driving behavior was assessed using the Manchester Driver Behaviour Questionnaire (DBQ; Lajunen et al. 2004). Males scored higher than females in aggressive violations and ordinary violations. Females scored higher for the nonacceptance of emotional responses, whereas males had more difficulties with emotional awareness than females. More difficulties in emotion regulation were positively correlated with driving errors, lapses, aggressive violations, and ordinary violations for both males and females. Structural equation modeling showed that difficulties in emotion regulation explained aggressive and ordinary violations more clearly than lapses and errors. When controlling for interactions among the distinct regulation difficulties, difficulties with impulse control and difficulties engaging in goal-directed behavior predicted risky driving. Furthermore, nonacceptance of emotional responses and limited access to emotion regulation strategies were related to less violations and more driving errors. Emotion regulation difficulties were associated with the self-reported risky driving behaviors of Lithuanian drivers. This provides useful hints for improving driver training programs in order to prevent traffic injuries.

A novel marRAB operon contributes to the rifampicin resistance in Mycobacterium smegmatis.

Science.gov (United States)

Zhang, Haiwei; Gao, Long; Zhang, Jiaoling; Li, Weihui; Yang, Min; Zhang, Hua; Gao, Chunhui; He, Zheng-Guo

2014-01-01

The multiple-antibiotic resistance regulator (MarR) plays an important role in modulating bacterial antibiotic resistance. However, the regulatory model of the marRAB operon in mycobacteria remains to be characterized. Here we report that a MarR, encoded by Ms6508, and its marRAB operon specifically contribute to rifampicin (RIF) resistance in Mycobacterium smegmatis. We show that the MarR recognizes a conserved 21-bp palindromic motif and negatively regulates the expression of two ABC transporters in the operon, encoded by Ms6509-6510. Unlike other known drug efflux pumps, overexpression of these two ABC transporters unexpectedly increased RIF sensitivity and deletion of these two genes increased mycobacterial resistance to the antibiotic. No change can be detected for the sensitivity of recombinant mycobacterial strains to three other anti-TB drugs. Furthermore, HPLC experiments suggested that Ms6509-Ms6510 could pump RIF into the mycobacterial cells. These findings indicated that the mycobacterial MarR functions as a repressor and constitutively inhibits the expression of the marRAB operon, which specifically contributes to RIF resistance in M. smegmatis. Therefore, our data suggest a new regulatory mechanism of RIF resistance and also provide the new insight into the regulatory model of a marRAB operon in mycobacteria.

Autonomic Regulation of Splanchnic Circulation

Directory of Open Access Journals (Sweden)

Kathleen A Fraser

1991-01-01

Full Text Available The role of the autonomic nervous system in circulatory regulation of the splanchnic organs (stomach, small intestine, colon, liver, pancreas and spleen is reviewed. In general, the sympathetic nervous system is primarily involved in vasoconstriction, while the parasympathetic contributes to vasodilation. Vasoconstriction in the splanchnic circulation appears to be mediated by alpha-2 receptors and vasodilation by activation of primary afferent nerves with subsequent release of vasodilatory peptides, or by stimulation of beta-adrenergic receptors. As well, an important function of the autonomic nervous system is to provide a mechanism by which splanchnic vascular reserve can be mobilized during stress to maintain overall cardiovascular homeostasis.

Regulation of Wnt/β-catenin signaling by posttranslational modifications

Science.gov (United States)

2014-01-01

The canonical Wnt signaling pathway (or Wnt/β-catenin pathway) plays a pivotal role in embryonic development and adult homeostasis; deregulation of the Wnt pathway contributes to the initiation and progression of human diseases including cancer. Despite its importance in human biology and disease, how regulation of the Wnt/β-catenin pathway is achieved remains largely undefined. Increasing evidence suggests that post-translational modifications (PTMs) of Wnt pathway components are essential for the activation of the Wnt/β-catenin pathway. PTMs create a highly dynamic relay system that responds to Wnt stimulation without requiring de novo protein synthesis and offer a platform for non-Wnt pathway components to be involved in the regulation of Wnt signaling, hence providing alternative opportunities for targeting the Wnt pathway. This review highlights the current status of PTM-mediated regulation of the Wnt/β-catenin pathway with a focus on factors involved in Wnt-mediated stabilization of β-catenin. PMID:24594309

Nrf2, the Master Regulator of Anti-Oxidative Responses

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Sandra Vomund

2017-12-01

Full Text Available Tight regulation of inflammation is very important to guarantee a balanced immune response without developing chronic inflammation. One of the major mediators of the resolution of inflammation is the transcription factor: the nuclear factor erythroid 2-like 2 (Nrf2. Stabilized following oxidative stress, Nrf2 induces the expression of antioxidants as well as cytoprotective genes, which provoke an anti-inflammatory expression profile, and is crucial for the initiation of healing. In view of this fundamental modulatory role, it is clear that both hyper- or hypoactivation of Nrf2 contribute to the onset of chronic diseases. Understanding the tight regulation of Nrf2 expression/activation and its interaction with signaling pathways, known to affect inflammatory processes, will facilitate development of therapeutic approaches to prevent Nrf2 dysregulation and ameliorate chronic inflammatory diseases. We discuss in this review the principle mechanisms of Nrf2 regulation with a focus on inflammation and autophagy, extending the role of dysregulated Nrf2 to chronic diseases and tumor development.

Interferon-Lambda: A Potent Regulator of Intestinal Viral Infections.

Science.gov (United States)

Lee, Sanghyun; Baldridge, Megan T

2017-01-01

Interferon-lambda (IFN-λ) is a recently described cytokine found to be of critical importance in innate immune regulation of intestinal viruses. Endogenous IFN-λ has potent antiviral effects and has been shown to control multiple intestinal viruses and may represent a factor that contributes to human variability in response to infection. Importantly, recombinant IFN-λ has therapeutic potential against enteric viral infections, many of which lack other effective treatments. In this mini-review, we describe recent advances regarding IFN-λ-mediated regulation of enteric viruses with important clinical relevance including rotavirus, reovirus, and norovirus. We also briefly discuss IFN-λ interactions with other cytokines important in the intestine, and how IFN-λ may play a role in regulation of intestinal viruses by the commensal microbiome. Finally, we indicate currently outstanding questions regarding IFN-λ control of enteric infections that remain to be explored to enhance our understanding of this important immune molecule.

Determination of sRNA expressions by RNA-seq in Yersinia pestis grown in vitro and during infection.

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Yanfeng Yan

Full Text Available BACKGROUND: Small non-coding RNAs (sRNAs facilitate host-microbe interactions. They have a central function in the post-transcriptional regulation during pathogenic lifestyles. Hfq, an RNA-binding protein that many sRNAs act in conjunction with, is required for Y. pestis pathogenesis. However, information on how Yersinia pestis modulates the expression of sRNAs during infection is largely unknown. METHODOLOGY AND PRINCIPAL FINDINGS: We used RNA-seq technology to identify the sRNA candidates expressed from Y. pestis grown in vitro and in the infected lungs of mice. A total of 104 sRNAs were found, including 26 previously annotated sRNAs, by searching against the Rfam database with 78 novel sRNA candidates. Approximately 89% (93/104 of these sRNAs from Y. pestis are shared with its ancestor Y. pseudotuberculosis. Ninety-seven percent of these sRNAs (101/104 are shared among more than 80 sequenced genomes of 135 Y. pestis strains. These 78 novel sRNAs include 62 intergenic and 16 antisense sRNAs. Fourteen sRNAs were selected for verification by independent Northern blot analysis. Results showed that nine selected sRNA transcripts were Hfq-dependent. Interestingly, three novel sRNAs were identified as new members of the transcription factor CRP regulon. Semi-quantitative analysis revealed that Y. pestis from the infected lungs induced the expressions of six sRNAs including RyhB1, RyhB2, CyaR/RyeE, 6S RNA, RybB and sR039 and repressed the expressions of four sRNAs, including CsrB, CsrC, 4.5S RNA and sR027. CONCLUSIONS AND SIGNIFICANCE: This study is the first attempt to subject RNA from Y. pestis-infected samples to direct high-throughput sequencing. Many novel sRNAs were identified and the expression patterns of relevant sRNAs in Y. pestis during in vitro growth and in vivo infection were revealed. The annotated sRNAs accounted for the most abundant sRNAs either expressed in bacteria grown in vitro or differentially expressed in the infected lungs

Epigenetic Regulation of Inflammatory Cytokines and Associated Genes in Human Malignancies

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Rehana Yasmin

2015-01-01

Full Text Available Inflammation is a multifaceted defense response of immune system against infection. Chronic inflammation has been implicated as an imminent threat for major human malignancies and is directly linked to various steps involved in tumorigenesis. Inflammatory cytokines, interleukins, interferons, transforming growth factors, chemokines, and adhesion molecules have been associated with chronic inflammation. Numerous cytokines are reported to be aberrantly regulated by different epigenetic mechanisms like DNA methylation and histone modifications in tumor tissues, contributing to pathogenesis of tumor in multiple ways. Some of these cytokines also work as epigenetic regulators of other crucial genes in tumor biology, either directly or indirectly. Such regulations are reported in lung, breast, cervical, gastric, colorectal, pancreatic, prostate, and head and neck cancers. Epigenetics of inflammatory mediators in cancer is currently subject of extensive research. These investigations may help in understanding cancer biology and to develop effective therapeutic strategies. The purpose of this paper is to have a brief view of the aberrant regulation of inflammatory cytokines in human malignancies.

YY1 regulates melanocyte development and function by cooperating with MITF.

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Juying Li

Full Text Available Studies of coat color mutants have greatly contributed to the discovery of genes that regulate melanocyte development and function. Here, we generated Yy1 conditional knockout mice in the melanocyte-lineage and observed profound melanocyte deficiency and premature gray hair, similar to the loss of melanocytes in human piebaldism and Waardenburg syndrome. Although YY1 is a ubiquitous transcription factor, YY1 interacts with M-MITF, the Waardenburg Syndrome IIA gene and a master transcriptional regulator of melanocytes. YY1 cooperates with M-MITF in regulating the expression of piebaldism gene KIT and multiple additional pigmentation genes. Moreover, ChIP-seq identified genome-wide YY1 targets in the melanocyte lineage. These studies mechanistically link genes implicated in human conditions of melanocyte deficiency and reveal how a ubiquitous factor (YY1 gains lineage-specific functions by co-regulating gene expression with a lineage-restricted factor (M-MITF-a general mechanism which may confer tissue-specific gene expression in multiple lineages.

SET protein up-regulated testosterone production in the cultured preantral follicles

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Xu Boqun

2013-02-01

Full Text Available Abstract Background We found previously that the expression of SET gene was up-regulated in polycystic ovaries. Evidences suggested that SET protein was essential for regulating both the promoter activity of CYP17A1 and the biological activity of P450c17. In this study, we explored whether SET regulated androgen production in preantral follicles. Methods The mouse preantral follicles were cultured in vitro. Testosterone secretion and expression of steroidogenic enzymes were observed in the preantral follicles treated in vitro by SET overexpression and knockdown. Results Testosterone levels in the media of the AdCMV-SET infected follicles significantly increased, and the CYP17A1 and HSD3B2 expression also significantly increased (P P  Conclusions SET played a positive role in regulating ovarian androgen biosynthesis by enhancing the transcription of steroidogenic enzymes CYP17A1 and HSD3B2, which maybe contribute to the hyperandrogenism in PCOS.

Regulation of Corticosteroidogenic Genes by MicroRNAs

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Stacy Robertson

2017-01-01

Full Text Available The loss of normal regulation of corticosteroid secretion is important in the development of cardiovascular disease. We previously showed that microRNAs regulate the terminal stages of corticosteroid biosynthesis. Here, we assess microRNA regulation across the whole corticosteroid pathway. Knockdown of microRNA using Dicer1 siRNA in H295R adrenocortical cells increased levels of CYP11A1, CYP21A1, and CYP17A1 mRNA and the secretion of cortisol, corticosterone, 11-deoxycorticosterone, 18-hydroxycorticosterone, and aldosterone. Bioinformatic analysis of genes involved in corticosteroid biosynthesis or metabolism identified many putative microRNA-binding sites, and some were selected for further study. Manipulation of individual microRNA levels demonstrated a direct effect of miR-125a-5p and miR-125b-5p on CYP11B2 and of miR-320a-3p levels on CYP11A1 and CYP17A1 mRNA. Finally, comparison of microRNA expression profiles from human aldosterone-producing adenoma and normal adrenal tissue showed levels of various microRNAs, including miR-125a-5p to be significantly different. This study demonstrates that corticosteroidogenesis is regulated at multiple points by several microRNAs and that certain of these microRNAs are differentially expressed in tumorous adrenal tissue, which may contribute to dysregulation of corticosteroid secretion. These findings provide new insights into the regulation of corticosteroid production and have implications for understanding the pathology of disease states where abnormal hormone secretion is a feature.

Local regulation between formal and informal institutions: analysis by application to the case of the town of Ksar-Hellal (Tunisia

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Makram GAALICHE

2013-06-01

Full Text Available The purpose of this paper is to detect the relevance degrees of formal and informal institutions at the level of local regulation, as well as their effects on the local companies’ productivity. Indeed, by analyzing the territory of the Ksar-Hellal town, we noted that informal institutions, apprehended by trust and collective punishment, contribute with the formal penal institutions to channel the behavior of Hilalian companies but with less effectiveness. Similarly, the strong contribution of exogenous institutions in boosting productivity compared to that of the endogenous ones states that decision makers should improve the quality of formal regulation and this at the expense of any form of regulation built by values commonly shared by the local community.

Current knowledge of microRNA-mediated regulation of drug metabolism in humans.

Science.gov (United States)

Nakano, Masataka; Nakajima, Miki

2018-05-01

Understanding the factors causing inter- and intra-individual differences in drug metabolism potencies is required for the practice of personalized or precision medicine, as well as for the promotion of efficient drug development. The expression of drug-metabolizing enzymes is controlled by transcriptional regulation by nuclear receptors and transcriptional factors, epigenetic regulation, such as DNA methylation and histone acetylation, and post-translational modification. In addition to such regulation mechanisms, recent studies revealed that microRNAs (miRNAs), endogenous ~22-nucleotide non-coding RNAs that regulate gene expression through the translational repression and degradation of mRNAs, significantly contribute to post-transcriptional regulation of drug-metabolizing enzymes. Areas covered: This review summarizes the current knowledge regarding miRNAs-dependent regulation of drug-metabolizing enzymes and transcriptional factors and its physiological and clinical significance. We also describe recent advances in miRNA-dependent regulation research, showing that the presence of pseudogenes, single-nucleotide polymorphisms, and RNA editing affects miRNA targeting. Expert opinion: It is unwavering fact that miRNAs are critical factors causing inter- and intra-individual differences in the expression of drug-metabolizing enzymes. Consideration of miRNA-dependent regulation would be a helpful tool for optimizing personalized and precision medicine.

Regulation of AMPA Receptor Trafficking by Protein Ubiquitination

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Jocelyn Widagdo

2017-10-01

Full Text Available The molecular mechanisms underlying plastic changes in the strength and connectivity of excitatory synapses have been studied extensively for the past few decades and remain the most attractive cellular models of learning and memory. One of the major mechanisms that regulate synaptic plasticity is the dynamic adjustment of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA-type glutamate receptor content on the neuronal plasma membrane. The expression of surface AMPA receptors (AMPARs is controlled by the delicate balance between the biosynthesis, dendritic transport, exocytosis, endocytosis, recycling and degradation of the receptors. These processes are dynamically regulated by AMPAR interacting proteins as well as by various post-translational modifications that occur on their cytoplasmic domains. In the last few years, protein ubiquitination has emerged as a major regulator of AMPAR intracellular trafficking. Dysregulation of AMPAR ubiquitination has also been implicated in the pathophysiology of Alzheimer’s disease. Here we review recent advances in the field and provide insights into the role of protein ubiquitination in regulating AMPAR membrane trafficking and function. We also discuss how aberrant ubiquitination of AMPARs contributes to the pathogenesis of various neurological disorders, including Alzheimer’s disease, chronic stress and epilepsy.

Ministerial regulation for double counting better biofuels; Ministeriele regeling dubbeltelling betere biobrandstoffen

Energy Technology Data Exchange (ETDEWEB)

De Waal, H.

2009-10-15

On 29 October 2009 SenterNovem organized an information meeting on the double counting regulation of biofuels and on the inspection protocol that was developed for this purpose. This is one of the presentations that were held during the meeting. The starting point of the regulation is the fact that the contribution of biofuels based on waste, residues, non food cellulose material and ligno cellulose material for the production of energy from renewable sources in all types of transport is double the volume of contributions of other biofuels. [Dutch] SenterNovem organiseerde op 29 oktober 2009 een informatiebijeenkomst over de regeling voor dubbeltelling van biobrandstoffen en over het inspectieprotocol dat daarvoor is ontwikkeld. Dit is een van de presentaties die tijdens deze bijeenkomst werden gehouden. Het uitgangspunt voor de regeling is dat de bijdrage van biobrandstoffen op basis van afval, residuen, non-food cellulosemateriaal en lignocellulosisch materiaal voor de productie van energie uit hernieuwbare bronnen in alle vervoersvormen dubbel zo groot is als die van andere biobrandstoffen.

Assessing anger regulation in middle childhood: development and validation of a behavioral observation measure

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Helena Lara Rohlf

2015-04-01

Full Text Available An observational measure of anger regulation in middle childhood was developed that facilitated the in situ assessment of five maladaptive regulation strategies in response to an anger-eliciting task. 599 children aged 6-10 years (M = 8.12, SD = 0.92 participated in the study. Construct validity of the measure was examined through correlations with parent- and self-reports of anger regulation and anger reactivity. Criterion validity was established through links with teacher-rated aggression and social rejection measured by parent-, teacher-, and self-reports. The observational measure correlated significantly with parent- and self-reports of anger reactivity, whereas it was unrelated to parent- and self-reports of anger regulation. It also made a unique contribution to predicting aggression and social rejection.

You spin me right round: Cross-relationship variability in interpersonal emotion regulation

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Karen eNiven

2012-10-01

Full Text Available Individuals use a range of interpersonal emotion regulation strategies to influence the feelings of others, e.g., friends, family members, romantic partners, work colleagues. But little is known about whether people vary their strategy use across these different relational contexts. We characterize and measure this variability as ‘spin’, i.e., the extent of dispersion in a person’s interpersonal emotion regulation strategy use across different relationships, and focus on two key questions. First, is spin adaptive or maladaptive with regard to personal well-being and relationship quality? Second, do personality traits that are considered important for interpersonal functioning (i.e., empathy, attachment style predict spin? The data used in this study is drawn from a large online survey. A key contribution of this study is to reveal that people who varied the type of strategies they used across relationships (i.e., those with high spin had lower positive mood, higher emotional exhaustion and less close relationships. A further key contribution is to show that spin was associated with low empathic concern and perspective taking and high anxious attachment style. High variability in interpersonal emotion regulation strategies across relationships therefore appears to be maladaptive both personally and socially.

The rs391957 variant cis-regulating oncogene GRP78 expression contributes to the risk of hepatocellular carcinoma.

Science.gov (United States)

Zhu, Xiao; Zhang, Jinfang; Fan, Wenguo; Wang, Fang; Yao, Hong; Wang, Zifeng; Hou, Shengping; Tian, Yinghong; Fu, Weiming; Xie, Dan; Zhu, Wei; Long, Jun; Wu, Leijie; Zheng, Xuebao; Kung, Hsiangfu; Zhou, Keyuan; Lin, Marie C M; Luo, Hui; Li, Dongpei

2013-06-01

Glucose-regulated protein 78 (GRP78) is one of the most important responders to disease-related stress. We assessed the association of the promoter polymorphisms of GRP78 with risk of hepatocellular carcinoma (HCC) and GRP78 expression in a Chinese population. We examined 1007 patients undergoing diagnostic HCC and 810 unrelated healthy controls. Mechanisms by which the GRP78 promoter polymorphism modulates HCC risk and GRP78 levels were analyzed. The promoter haplotype and diplotype carrying rs391957 (-415bp) allele G and genotype GG was strongly associated with HCC risk. Luciferase reporter assays indicated that the promoter carrying rs391957 allele G (haplotype GCCd) showed increased activity in HepG2 cells and Hela cells. rs391957 was also shown to increase the affinity of the transcriptional activator Ets-2, the resistance to apoptosis, as well as cell instability in stressful microenvironment. Furthermore, compared with allele A, rs391957 allele G was associated with higher levels of GRP78 mRNA and protein in HCC tissues. These findings provided new insights into the pathogenesis of HCC and an unexpected effect of the interaction between rs391957 and Ets-2 on hepatocarcinogenesis, and especially supported the hypothesis that stress-related and evolutionarily conserved genetic variant(s) influencing transcriptional regulation could predict susceptibilities.

Audit Risk Assessment in the Light of Current European Regulations

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Ciprian-Costel Munteanu

2015-06-01

Full Text Available Recent European reforms on audit regulations have been motivated by efforts to increase audit quality, functioning and performance. We believe the adoption of Directive 2014/56 and Regulation 537/2014 strengthened the role of independent audit and risk committees, which will positively contribute towards audit quality. This paper aims to critically assess the status quo of audit risk assessment in current European standards and regulations, by conducting a theoretical analysis of different aspects of audit risk. Our main objective is to stress the importance of detecting inherent and control risk, which lead to material misstatement at the assertion level. They need to be assessed so as to determine the nature, timing and extent of further audit procedures necessary to obtain sufficient appropriate audit evidence. These pieces of evidence enable the auditor to express an opinion on the financial statements at an acceptably low level of audit risk. Therefore, we point to the fact that researchers as well as practitioners and policymakers have to be careful when using audit tools and assessing risk levels, as their conclusions continuously shape the regulations.

Cultural and gender differences in emotion regulation: relation to depression.

Science.gov (United States)

Kwon, Hoin; Yoon, K Lira; Joormann, Jutta; Kwon, Jung-Hye

2013-01-01

In the last decade, studies have shown that the use of specific emotion regulation strategies contributes to an increased risk for depression. Past research, however, has overlooked potential cultural and gender differences in emotion regulation. The present study examined the relation between the use of emotion regulation strategies and depressive symptoms among college students in two different cultures (n=380 in Seoul, Korea; n=384 in Miami, USA). Koreans, compared with American students, reported more frequent use of brooding, whereas Americans reported more anger suppression than Koreans. Women were more likely than men to use both types of rumination (i.e., reflective pondering and brooding) and anger suppression in both countries, but these gender differences disappeared once levels of depressive symptoms were controlled for. In addition, the association between the use of reappraisal and depressive symptoms was significantly stronger in the Korean compared to the US sample. In contrast, the association between anger suppression and depressive symptoms was significantly stronger in the American compared to the Korean sample. These findings highlight the importance of considering the role of culture in emotion regulation.

Insights into dynamics of mobile genetic elements in hyperthermophilic environments from five new Thermococcus plasmids.

Directory of Open Access Journals (Sweden)

Mart Krupovic

Full Text Available Mobilome of hyperthermophilic archaea dwelling in deep-sea hydrothermal vents is poorly characterized. To gain insight into genetic diversity and dynamics of mobile genetic elements in these environments we have sequenced five new plasmids from different Thermococcus strains that have been isolated from geographically remote hydrothermal vents. The plasmids were ascribed to two subfamilies, pTN2-like and pEXT9a-like. Gene content and phylogenetic analyses illuminated a robust connection between pTN2-like plasmids and Pyrococcus abyssi virus 1 (PAV1, with roughly half of the viral genome being composed of genes that have homologues in plasmids. Unexpectedly, pEXT9a-like plasmids were found to be closely related to the previously sequenced plasmid pMETVU01 from Methanocaldococcus vulcanius M7. Our data suggests that the latter observation is most compatible with an unprecedented horizontal transfer of a pEXT9a-like plasmid from Thermococcales to Methanococcales. Gene content analysis revealed that thermococcal plasmids encode Hfq-like proteins and toxin-antitoxin (TA systems of two different families, VapBC and RelBE. Notably, although abundant in archaeal genomes, to our knowledge, TA and hfq-like genes have not been previously found in archaeal plasmids or viruses. Finally, the plasmids described here might prove to be useful in developing new genetic tools for hyperthermophiles.

The Crc/CrcZ-CrcY global regulatory system helps the integration of gluconeogenic and glycolytic metabolism in Pseudomonas putida.

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La Rosa, Ruggero; Nogales, Juan; Rojo, Fernando

2015-09-01

In metabolically versatile bacteria, carbon catabolite repression (CCR) facilitates the preferential assimilation of the most efficient carbon sources, improving growth rates and fitness. In Pseudomonas putida, the Crc and Hfq proteins and the CrcZ and CrcY small RNAs, which are believed to antagonize Crc/Hfq, are key players in CCR. Unlike that seen in other bacterial species, succinate and glucose elicit weak CCR in this bacterium. In the present work, metabolic, transcriptomic and constraint-based metabolic flux analyses were combined to clarify whether P. putida prefers succinate or glucose, and to identify the role of the Crc protein in the metabolism of these compounds. When provided simultaneously, succinate was consumed faster than glucose, although both compounds were metabolized. CrcZ and CrcY levels were lower when both substrates were present than when only one was provided, suggesting a role for Crc in coordinating metabolism of these compounds. Flux distribution analysis suggested that, when both substrates are present, Crc works to organize a metabolism in which carbon compounds flow in opposite directions: from glucose to pyruvate, and from succinate to pyruvate. Thus, our results support that Crc not only favours the assimilation of preferred compounds, but balances carbon fluxes, optimizing metabolism and growth. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

EZH2: a pivotal regulator in controlling cell differentiation.

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Chen, Ya-Huey; Hung, Mien-Chie; Li, Long-Yuan

2012-01-01

Epigenetic regulation plays an important role in stem cell self-renewal, maintenance and lineage differentiation. The epigenetic profiles of stem cells are related to their transcriptional signature. Enhancer of Zeste homlog 2 (EZH2), a catalytic subunit of epigenetic regulator Polycomb repressive complex 2 (PRC2), has been shown to be a key regulator in controlling cellular differentiation. EZH2 is a histone methyltransferase that not only methylates histone H3 on Lys 27 (H3K27me3) but also interacts with and recruits DNA methyltransferases to methylate CpG at certain EZH2 target genes to establish firm repressive chromatin structures, contributing to tumor progression and the regulation of development and lineage commitment both in embryonic stem cells (ESCs) and adult stem cells. In addition to its well-recognized epigenetic gene silencing function, EZH2 also directly methylates nonhistone targets such as the cardiac transcription factor, GATA4, resulting in attenuated GATA4 transcriptional activity and gene repression. This review addresses recent progress toward the understanding of the biological functions and regulatory mechanisms of EZH2 and its targets as well as their roles in stem cell maintenance and cell differentiation.

Mib1 contributes to persistent directional cell migration by regulating the Ctnnd1-Rac1 pathway.

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Mizoguchi, Takamasa; Ikeda, Shoko; Watanabe, Saori; Sugawara, Michiko; Itoh, Motoyuki

2017-10-31

Persistent directional cell migration is involved in animal development and diseases. The small GTPase Rac1 is involved in F-actin and focal adhesion dynamics. Local Rac1 activity is required for persistent directional migration, whereas global, hyperactivated Rac1 enhances random cell migration. Therefore, precise control of Rac1 activity is important for proper directional cell migration. However, the molecular mechanism underlying the regulation of Rac1 activity in persistent directional cell migration is not fully understood. Here, we show that the ubiquitin ligase mind bomb 1 (Mib1) is involved in persistent directional cell migration. We found that knockdown of MIB1 led to an increase in random cell migration in HeLa cells in a wound-closure assay. Furthermore, we explored novel Mib1 substrates for cell migration and found that Mib1 ubiquitinates Ctnnd1. Mib1-mediated ubiquitination of Ctnnd1 K547 attenuated Rac1 activation in cultured cells. In addition, we found that posterior lateral line primordium cells in the zebrafish mib1 ta52b mutant showed increased random migration and loss of directional F-actin-based protrusion formation. Knockdown of Ctnnd1 partially rescued posterior lateral line primordium cell migration defects in the mib1 ta52b mutant. Taken together, our data suggest that Mib1 plays an important role in cell migration and that persistent directional cell migration is regulated, at least in part, by the Mib1-Ctnnd1-Rac1 pathway. Published under the PNAS license.

The Regulation of Food Science and Technology Professions in Europe

Directory of Open Access Journals (Sweden)

Rui Costa

2014-04-01

Full Text Available The regulation of a profession is justified when it improves consumer protection and public health. Higher education food science and technology (FST degrees, widely offered in many universities in Europe open to a wide range of jobs in the food sectors where the employees could cover different positions, roles and carry out diverse activities dealing with the food production and the quality and safety of the food products. This work reviews the state of the art of the FST regulated professions requiring higher education qualifications in the European countries. The research was carried out by collecting specific information on regulated professions by contacting unions, professional associations, public servant categories/professions, and by visiting national and EU websites.  The data collected for each regulated profession were: country, training/education required, date of implementation of regulation, professional training (if required, capability test (if required and acts required by law to be signed by a regulated professional. Only professions that required a higher education diploma were included in this search. Few countries were found to have a regulated profession in FST, in particular: Food Engineering (Turkey, Food Technologist (Greece, Iceland, Italy and Slovenia, and Oenologist (Italy, Portugal and Spain. FST regulated professions in Europe are thus scarce and have a rather limited history. The Food Technologist in Italy and the Food Engineer in Turkey were found to be the only completely regulated professions found in Europe. Food and professional regulation have been evolved over the years and raised the debate on the regulation of FST professions. Academia as well as other policymakers has to further contribute to this discussion to keep high the standards for quality of education and training of the qualified workforce and professionals in the food sector.

Clinical research involving minors in international and serbian regulations.

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Planojević, Nina; Zivojinović, Dragica

2013-07-01

Participation in clinical trials can be useful for the health of a person, in who it is conducted, but it does not have to be - it can even be harmful. Therefore, primary motive to accept such risk is humanity and human wish to contribute to the progress of medicine; this is expressed by personal consent. The consent, however, can be an expression of personal humanity, and for this, it is not logical that someone can give consent on behalf of someone else, as it is done by a legally authorized representative on behalf of a minor. Therefore, authors raise 3 questions: What are the reasons to consider representative's consent acceptable? How should a model of regulations look like in order to provide the most complete possible protection to a minor? Is actual regulation of minors' position within international and Serbian law, analyzed here by authors for their specific solutions, acceptable? Representative's consent is acceptable only for therapeutic research, because these can bring benefits to everyone's health, including a minor in which those are conducted - this is an acceptable (secondary) motive of participation in the research. Expression of humanity on other's behalf, typical for non-therapeutic research, is not acceptable; this makes ban of minors' participation in non-therapeutic research more appropriate regulation model. International regulations are not in accordance to results presented in the paper for allowing participation of minors both in therapeutic and non-therapeutic research. Serbian regulation is closer to the most acceptable regulation model.

RNA Helicase DDX5 Regulates MicroRNA Expression and Contributes to Cytoskeletal Reorganization in Basal Breast Cancer Cells

Energy Technology Data Exchange (ETDEWEB)

Wang, Daojing; Huang, Jing; Hu, Zhi

2011-11-15

RNA helicase DDX5 (also p68) is involved in all aspects of RNA metabolism and serves as a transcriptional co-regulator, but its functional role in breast cancer remains elusive. Here, we report an integrative biology study of DDX5 in breast cancer, encompassing quantitative proteomics, global MicroRNA profiling, and detailed biochemical characterization of cell lines and human tissues. We showed that protein expression of DDX5 increased progressively from the luminal to basal breast cancer cell lines, and correlated positively with that of CD44 in the basal subtypes. Through immunohistochemistry analyses of tissue microarrays containing over 200 invasive human ductal carcinomas, we observed that DDX5 was upregulated in the majority of malignant tissues, and its expression correlated strongly with those of Ki67 and EGFR in the triple-negative tumors. We demonstrated that DDX5 regulated a subset of MicroRNAs including miR-21 and miR-182 in basal breast cancer cells. Knockdown of DDX5 resulted in reorganization of actin cytoskeleton and reduction of cellular proliferation. The effects were accompanied by upregulation of tumor suppressor PDCD4 (a known miR-21 target); as well as upregulation of cofilin and profilin, two key proteins involved in actin polymerization and cytoskeleton maintenance, as a consequence of miR-182 downregulation. Treatment with miR-182 inhibitors resulted in morphologic phenotypes resembling those induced by DDX5 knockdown. Using bioinformatics tools for pathway and network analyses, we confirmed that the network for regulation of actin cytoskeleton was predominantly enriched for the predicted downstream targets of miR-182. Our results reveal a new functional role of DDX5 in breast cancer via the DDX5→miR-182→actin cytoskeleton pathway, and suggest the potential clinical utility of DDX5 and its downstream MicroRNAs in the theranostics of breast cancer.

Contextual Factors for Establishing Nursing Regulation in Iran: A Qualitative Content Analysis.

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Nejatian, Ahmad; Joulaei, Hassan

2018-04-01

Professional regulation is one of the strategies of the governments which protect the public's right. Nursing practice is not an exception; hence, it is regulated to protect the public against nursing services' adverse effects. Although modern nursing in Iran started from 100 years ago, documents show that there was no regulation mechanism for nursing in Iran till 2016. Hence, this study was conducted to illuminate the contextual factors affecting the nursing regulation process in Iran. To explore the contextual elements of late establishment of nursing registration as an important part of nursing regulation, we applied directed qualitative content analysis. For this purpose, all the historical events and related materials including articles published in scientific journals, gray literature, statements, news articles, and interviews in the period of 2006-2016 were reviewed and analyzed by expert panel and categorized in predetermined groups. Pooled analysis data showed four contributing elements that affected the emerging nursing regulation in Iran. These elements include 1) cultural determinants, 2) structural determinants, 3) situational determinants, and 4) international or exogenous determinants. Nursing regulation is an important health policy issue in Iran which needs to be facilitated by contextual factors. These factors are complicated and country-specific. Political willingness should be accompanied by nursing association willingness to establish and improve nursing regulation. Other researches are recommended to explore actors and process and content of nursing regulation policy in Iran.

BRAF activated non-coding RNA (BANCR) promoting gastric cancer cells proliferation via regulation of NF-κB1

International Nuclear Information System (INIS)

Zhang, Zhi-Xin; Liu, Zhi-Qiang; Jiang, Biao; Lu, Xin-Yang; Ning, Xiao-Fei; Yuan, Chuan-Tao; Wang, Ai-Liang

2015-01-01

Background and objective: Long non-coding RNA, BANCR, has been demonstrated to contribute to the proliferation and migration of tumors. However, its molecular mechanism underlying gastric cancer is still unknown. In present study, we investigated whether BANCR was involved in the development of gastric cancer cells via regulation of NF-κB1. Methods: Human gastric cancer tissues were isolated as well as human gastric cell lines MGC803 and BGC823 were cultured to investigate the role of BANCR in gastric cancer. Results: BANCR expression was significantly up-regulated in gastric tumor tissues and gastric cell lines. Down-regulation of BANCR inhibited gastric cancer cell growth and promoted cell apoptosis, and it also contributed to a significant decrease of NF-κB1 (P50/105) expression and 3′UTR of NF-κB1 activity. Overexpression of NF-κB1 reversed the effect of BANCR on cancer cell growth and apoptosis. MiroRNA-9 (miR-9) targeted NF-κB1, and miR-9 inhibitor also reversed the effects of BANCR on gastric cancer cell growth and apoptosis. Conclusion: BANCR was highly expressed both in gastric tumor tissues and in cancer cells. NF-κB1 and miR-9 were involved in the role of BANCR in gastric cancer cell growth and apoptosis. - Highlights: • BANCR up-regulated in gastric cancer (GC) tissues and cell lines MGC803 and BGC823. • Down-regulation of BANCR inhibited GC cell growth and promoted cell apoptosis. • Down-regulation of BANCR contributed to decreased 3′UTR of NF-κB1 and its expression. • Overexpressed NF-κB1 reversed the effect of BANCR on GC cell growth. • miR-9 inhibitor reversed the effect of BANCR on cancer GC cell growth

Federal Aviation Regulations - National Aviation Regulations of Russia

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Chernykh, O.; Bakiiev, M.

2018-03-01

Chinese Aerospace Engineering is currently developing cooperation with Russia on a wide-body airplane project that has directed the work towards better understanding of Russian airworthiness management system. The paper introduces national Aviation regulations of Russia, presents a comparison of them with worldwide recognized regulations, and highlights typical differences. They have been found to be: two general types of regulations used in Russia (Aviation Regulations and Federal Aviation Regulations), non-unified structure of regulations on Aircraft Operation management, various separate agencies responsible for regulation issuance instead of one national aviation authority, typical confusions in references. The paper also gives a list of effective Russian Regulations of both types.

Up-regulation of tumor suppressor genes by exogenous dhC16-Cer contributes to its anti-cancer activity in primary effusion lymphoma.

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Cao, Yueyu; Qiao, Jing; Lin, Zhen; Zabaleta, Jovanny; Dai, Lu; Qin, Zhiqiang

2017-02-28

Primary effusion lymphoma (PEL) is a rare and highly aggressive B-cell malignancy with Kaposi's sarcoma-associated herpesvirus (KSHV) infection, while lack of effective therapies. Our recent data indicated that targeting the sphingolipid metabolism by either sphingosine kinase inhibitor or exogenous ceramide species induces PEL cell apoptosis and suppresses tumor progression in vivo. However, the underlying mechanisms for these exogenous ceramides "killing" PEL cells remain largely unknown. Based on the microarray analysis, we found that exogenous dhC16-Cer treatment affected the expression of many cellular genes with important functions within PEL cells such as regulation of cell cycle, cell survival/proliferation, and apoptosis/anti-apoptosis. Interestingly, we found that a subset of tumor suppressor genes (TSGs) was up-regulated from dhC16-Cer treated PEL cells. One of these elevated TSGs, Thrombospondin-1 (THBS1) was required for dhC16-Cer induced PEL cell cycle arrest. Moreover, dhC16-Cer up-regulation of THBS1 was through the suppression of multiple KSHV microRNAs expression. Our data demonstrate that exogenous ceramides display anti-cancer activities for PEL through regulation of both host and oncogenic virus factors.

Increasing Emotional Regulation for Youths in Residential Care: Phases of Change

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Cimmarusti, Rocco A.

2011-01-01

Youths in residential care have likely experienced trauma as they have had atypical and disruptive events occur in their lives that has contributed to their out-of-home placement. For people who have been traumatized, the regulation of emotions is an important feature of their recovery. This article presents a model that traces phases from…

Brain glucose sensing in homeostatic and hedonic regulation.

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Steinbusch, Laura; Labouèbe, Gwenaël; Thorens, Bernard

2015-09-01

Glucose homeostasis as well as homeostatic and hedonic control of feeding is regulated by hormonal, neuronal, and nutrient-related cues. Glucose, besides its role as a source of metabolic energy, is an important signal controlling hormone secretion and neuronal activity, hence contributing to whole-body metabolic integration in coordination with feeding control. Brain glucose sensing plays a key, but insufficiently explored, role in these metabolic and behavioral controls, which when deregulated may contribute to the development of obesity and diabetes. The recent introduction of innovative transgenic, pharmacogenetic, and optogenetic techniques allows unprecedented analysis of the complexity of central glucose sensing at the molecular, cellular, and neuronal circuit levels, which will lead to a new understanding of the pathogenesis of metabolic diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Regulation of macrophage development and function in peripheral tissues

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Lavin, Yonit; Mortha, Arthur; Rahman, Adeeb; Merad, Miriam

2015-01-01

Macrophages are immune cells of haematopoietic origin that provide crucial innate immune defence and have tissue-specific functions in the regulation and maintenance of organ homeostasis. Recent studies of macrophage ontogeny, as well as transcriptional and epigenetic identity, have started to reveal the decisive role of the tissue stroma in the regulation of macrophage function. These findings suggest that most macrophages seed the tissues during embryonic development and functionally specialize in response to cytokines and metabolites that are released by the stroma and drive the expression of unique transcription factors. In this Review, we discuss how recent insights into macrophage ontogeny and macrophage–stroma interactions contribute to our understanding of the crosstalk that shapes macrophage function and the maintenance of organ integrity. PMID:26603899

Differential contribution of Ca2+ sources to day and night BK current activation in the circadian clock.

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Whitt, Joshua P; McNally, Beth A; Meredith, Andrea L

2018-02-05

Large conductance K + (BK) channels are expressed widely in neurons, where their activation is regulated by membrane depolarization and intracellular Ca 2+ (Ca 2+ i ). To enable this regulation, BK channels functionally couple to both voltage-gated Ca 2+ channels (VGCCs) and channels mediating Ca 2+ release from intracellular stores. However, the relationship between BK channels and their specific Ca 2+ source for particular patterns of excitability is not well understood. In neurons within the suprachiasmatic nucleus (SCN)-the brain's circadian clock-BK current, VGCC current, and Ca 2+ i are diurnally regulated, but paradoxically, BK current is greatest at night when VGCC current and Ca 2+ i are reduced. Here, to determine whether diurnal regulation of Ca 2+ is relevant for BK channel activation, we combine pharmacology with day and night patch-clamp recordings in acute slices of SCN. We find that activation of BK current depends primarily on three types of channels but that the relative contribution changes between day and night. BK current can be abrogated with nimodipine during the day but not at night, establishing that L-type Ca 2+ channels (LTCCs) are the primary daytime Ca 2+ source for BK activation. In contrast, dantrolene causes a significant decrease in BK current at night, suggesting that nighttime BK activation is driven by ryanodine receptor (RyR)-mediated Ca 2+ i release. The N- and P/Q-type Ca 2+ channel blocker ω-conotoxin MVIIC causes a smaller reduction of BK current that does not differ between day and night. Finally, inhibition of LTCCs, but not RyRs, eliminates BK inactivation, but the BK β2 subunit was not required for activation of BK current by LTCCs. These data reveal a dynamic coupling strategy between BK channels and their Ca 2+ sources in the SCN, contributing to diurnal regulation of SCN excitability. © 2018 Whitt et al.

Background for Community-Level Work on Emotional Well-Being in Adolescence: Reviewing the Literature on Contributing Factors.

Science.gov (United States)

Bridges, Lisa J.; Margie, Nancy Geyelin; Zaff, Jonathan F.

This paper reviews the research literature on factors contributing to adolescent emotional well-being, focusing on generalized mood/affective states, emotion regulation and coping, and feelings about self, including self-esteem, self-efficacy, and locus of control. Each construct is defined and evidence from research is presented to indicate the…

Contribution of glucocorticoids and glucocorticoid receptors to the regulation of neurodegenerative processes.

Science.gov (United States)

Vyas, Sheela; Maatouk, Layal

2013-12-01

Isolation of glucocorticoids (GCs) from adrenal glands followed by synthesis led rapidly to their first clinical application, about 70 years ago, for treatment of rheumatoid arthritis. To this day GCs are used in diseases that have an inflammatory component. However, their use is carefully monitored because of harmful side effects. GCs are also synonymous with stress and adaptation. In CNS, GC binds and activates high affinity mineralocorticoid receptor (MR) and low affinity glucocorticoid receptor (GR). GR, whose expression is ubiquitous, is only activated when GC levels rise as during circadian peak and in response to stress. Numerous recent studies have yielded important and new insights on the mechanisms concerning pulsatile secretory pattern of GCs as well as various processes that tightly control their synthesis via hypothalamic-pituitary-adrenal (HPA) axis involving regulated release of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) from hypothalamus and pituitary, respectively. GR modulates neuronal functions and viability through both genomic and non-genomic actions, and importantly its transcriptional regulatory activity is tightly locked with GC secretory pattern. There is increasing evidence pointing to involvement of GC-GR in neurodegenerative disorders. Patients with Alzheimer's or Parkinson's or Huntington's disease show chronically high cortisol levels suggesting changes occurring in controls of HPA axis. In experimental models of these diseases, chronic stress or GC treatment was found to exacerbate both the clinical symptoms and neurodegenerative processes. However, recent evidence also shows that GC-GR can exert neuroprotective effects. Thus, for any potential therapeutic strategies in these neurodegenerative diseases we need to understand the precise modifications both in HPA axis and in GR activity and find ways to harness their protective actions.

β-Catenin–regulated myeloid cell adhesion and migration determine wound healing

Science.gov (United States)

Amini-Nik, Saeid; Cambridge, Elizabeth; Yu, Winston; Guo, Anne; Whetstone, Heather; Nadesan, Puviindran; Poon, Raymond; Hinz, Boris; Alman, Benjamin A.

2014-01-01

A β-catenin/T cell factor–dependent transcriptional program is critical during cutaneous wound repair for the regulation of scar size; however, the relative contribution of β-catenin activity and function in specific cell types in the granulation tissue during the healing process is unknown. Here, cell lineage tracing revealed that cells in which β-catenin is transcriptionally active express a gene profile that is characteristic of the myeloid lineage. Mice harboring a macrophage-specific deletion of the gene encoding β-catenin exhibited insufficient skin wound healing due to macrophage-specific defects in migration, adhesion to fibroblasts, and ability to produce TGF-β1. In irradiated mice, only macrophages expressing β-catenin were able to rescue wound-healing deficiency. Evaluation of scar tissue collected from patients with hypertrophic and normal scars revealed a correlation between the number of macrophages within the wound, β-catenin levels, and cellularity. Our data indicate that β-catenin regulates myeloid cell motility and adhesion and that β-catenin–mediated macrophage motility contributes to the number of mesenchymal cells and ultimate scar size following cutaneous injury. PMID:24837430

EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2014. Scientific Opinion on the substantiation of a health claim related to beta-palmitate and contribution to softening of stools pursuant to Article 14 of Regulation (EC) No 1924/2006

DEFF Research Database (Denmark)

Tetens, Inge

2014-01-01

Following an application from Specialised Nutrition Europe (formerly IDACE), submitted for authorisation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of France, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked...... to deliver an opinion on the scientific substantiation of a health claim related to beta-palmitate and contribution to softening of stools. The food constituent, beta-palmitate, that is the subject of the health claim, is sufficiently characterised. Contribution to softening of stools is a beneficial...... physiological effect for infants. In weighing the evidence the Panel took into account that, out of two human intervention studies with important methodological limitations, one suggested a stool-softening effect of beta-palmitate whereas the second did not, that one animal study did not support a stool...

Kidney fibroblast growth factor 23 does not contribute to elevation of its circulating levels in uremia.

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Mace, Maria L; Gravesen, Eva; Nordholm, Anders; Hofman-Bang, Jacob; Secher, Thomas; Olgaard, Klaus; Lewin, Ewa

2017-07-01

Fibroblast growth factor 23 (FGF23) secreted by osteocytes is a circulating factor essential for phosphate homeostasis. High plasma FGF23 levels are associated with cardiovascular complications and mortality. Increases of plasma FGF23 in uremia antedate high levels of phosphate, suggesting a disrupted feedback regulatory loop or an extra-skeletal source of this phosphatonin. Since induction of FGF23 expression in injured organs has been reported we decided to examine the regulation of FGF23 gene and protein expressions in the kidney and whether kidney-derived FGF23 contributes to the high plasma levels of FGF23 in uremia. FGF23 mRNA was not detected in normal kidneys, but was clearly demonstrated in injured kidneys, already after four hours in obstructive nephropathy and at 8 weeks in the remnant kidney of 5/6 nephrectomized rats. No renal extraction was found in uremic rats in contrast to normal rats. Removal of the remnant kidney had no effect on plasma FGF23 levels. Well-known regulators of FGF23 expression in bone, such as parathyroid hormone, calcitriol, and inhibition of the FGF receptor by PD173074, had no impact on kidney expression of FGF23. Thus, the only direct contribution of the injured kidney to circulating FGF23 levels in uremia appears to be reduced renal extraction of bone-derived FGF23. Kidney-derived FGF23 does not generate high plasma FGF23 levels in uremia and is regulated differently than the corresponding regulation of FGF23 gene expression in bone. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Commission de regulation de l'energie. activity report 2015 - Reference document, 15 years of regulation

International Nuclear Information System (INIS)

2016-06-01

, Information for consumers on the retail market is still very much lacking, The end of regulated sales tariffs for businesses is a decisive step in opening up to competition); D - CRE and the networks: The CRE's work to promote non-discriminatory access to networks (Work done by the CRE defines a stable framework for network tariffs, The CRE's work to ensure independence of system operators, The CRE guarantees the transparent and non-discriminatory nature of the procedures and rates for connections, and the contracts for access to the networks, Access to storage: moving towards a regulation of revenues for French storage operators); The CRE is preparing the future of the networks (The CRE approves investments in the transmission networks, The electricity and gas networks are being modernised, The terms of access to data are yet to be defined); CRE contributes to the development of the European regulatory framework (The CRE played an active part in drafting the network codes in 2015, The rest of the CRE's work contributing to the common rules for operation of the internal energy market, The involvement of the CRE in the European Commission's consultations on 'market design'); E - CRE and the development of renewable energy sources: A new framework for the support of renewable energies defined at European level (The main conditions required of the support mechanism for renewable energies, The conditions imposed on exemptions relating to financing the aid to renewable energy applied to electro-intensive industries); In 2015 France undertook a major reform of the mechanisms to support renewable energies (A new support mechanism for renewable energy: additional remuneration, The tendering procedures used by CRE should be generalised for medium- and high-power facilities, Policy changes enacted for the development of renewable energy are resulting in increased pressure on CRE's resources); Changes in the financing of public service costs (Continued

Sex differences and emotion regulation: an event-related potential study.

Directory of Open Access Journals (Sweden)

Elyse K T Gardener

Full Text Available Difficulties in emotion regulation have been implicated as a potential mechanism underlying anxiety and mood disorders. It is possible that sex differences in emotion regulation may contribute towards the heightened female prevalence for these disorders. Previous fMRI studies of sex differences in emotion regulation have shown mixed results, possibly due to difficulties in discriminating the component processes of early emotional reactivity and emotion regulation. The present study used event-related potentials (ERPs to examine sex differences in N1 and N2 components (reflecting early emotional reactivity and P3 and LPP components (reflecting emotion regulation. N1, N2, P3, and LPP were recorded from 20 men and 23 women who were instructed to "increase," "decrease," and "maintain" their emotional response during passive viewing of negative images. Results indicated that women had significantly greater N1 and N2 amplitudes (reflecting early emotional reactivity to negative stimuli than men, supporting a female negativity bias. LPP amplitudes increased to the "increase" instruction, and women displayed greater LPP amplitudes than men to the "increase" instruction. There were no differences to the "decrease" instruction in women or men. These findings confirm predictions of the female negativity bias hypothesis and suggest that women have greater up-regulation of emotional responses to negative stimuli. This finding is highly significant in light of the female vulnerability for developing anxiety disorders.

Sex differences and emotion regulation: an event-related potential study.

Science.gov (United States)

Gardener, Elyse K T; Carr, Andrea R; Macgregor, Amy; Felmingham, Kim L

2013-01-01

Difficulties in emotion regulation have been implicated as a potential mechanism underlying anxiety and mood disorders. It is possible that sex differences in emotion regulation may contribute towards the heightened female prevalence for these disorders. Previous fMRI studies of sex differences in emotion regulation have shown mixed results, possibly due to difficulties in discriminating the component processes of early emotional reactivity and emotion regulation. The present study used event-related potentials (ERPs) to examine sex differences in N1 and N2 components (reflecting early emotional reactivity) and P3 and LPP components (reflecting emotion regulation). N1, N2, P3, and LPP were recorded from 20 men and 23 women who were instructed to "increase," "decrease," and "maintain" their emotional response during passive viewing of negative images. Results indicated that women had significantly greater N1 and N2 amplitudes (reflecting early emotional reactivity) to negative stimuli than men, supporting a female negativity bias. LPP amplitudes increased to the "increase" instruction, and women displayed greater LPP amplitudes than men to the "increase" instruction. There were no differences to the "decrease" instruction in women or men. These findings confirm predictions of the female negativity bias hypothesis and suggest that women have greater up-regulation of emotional responses to negative stimuli. This finding is highly significant in light of the female vulnerability for developing anxiety disorders.

Balancing platform control and external contribution in third-party development: the boundary resources model

DEFF Research Database (Denmark)

Ghazawneh, Ahmad; Henfridsson, Ola

2013-01-01

Prior research documents the significance of using platform boundary resources (e.g. application programming interfaces) for cultivating platform ecosystems through third-party development. However, there are few, if any, theoretical accounts of this relationship. To this end, this paper proposes......-party development: self-resourcing, regulation-based securing, diversity resourcing and sovereignty securing. Our research extends and complements existing platform literature and contributes new knowledge about an alternative form of system development...

Trojan Horse Transit Contributes to Blood-Brain Barrier Crossing of a Eukaryotic Pathogen.

Science.gov (United States)

Santiago-Tirado, Felipe H; Onken, Michael D; Cooper, John A; Klein, Robyn S; Doering, Tamara L

2017-01-31

The blood-brain barrier (BBB) protects the central nervous system (CNS) by restricting the passage of molecules and microorganisms. Despite this barrier, however, the fungal pathogen Cryptococcus neoformans invades the brain, causing a meningoencephalitis that is estimated to kill over 600,000 people annually. Cryptococcal infection begins in the lung, and experimental evidence suggests that host phagocytes play a role in subsequent dissemination, although this role remains ill defined. Additionally, the disparate experimental approaches that have been used to probe various potential routes of BBB transit make it impossible to assess their relative contributions, confounding any integrated understanding of cryptococcal brain entry. Here we used an in vitro model BBB to show that a "Trojan horse" mechanism contributes significantly to fungal barrier crossing and that host factors regulate this process independently of free fungal transit. We also, for the first time, directly imaged C. neoformans-containing phagocytes crossing the BBB, showing that they do so via transendothelial pores. Finally, we found that Trojan horse crossing enables CNS entry of fungal mutants that cannot otherwise traverse the BBB, and we demonstrate additional intercellular interactions that may contribute to brain entry. Our work elucidates the mechanism of cryptococcal brain invasion and offers approaches to study other neuropathogens. The fungal pathogen Cryptococcus neoformans invades the brain, causing a meningoencephalitis that kills hundreds of thousands of people each year. One route that has been proposed for this brain entry is a Trojan horse mechanism, whereby the fungus crosses the blood-brain barrier (BBB) as a passenger inside host phagocytes. Although indirect experimental evidence supports this intriguing mechanism, it has never been directly visualized. Here we directly image Trojan horse transit and show that it is regulated independently of free fungal entry, contributes

Yoga and Emotion Regulation in High School Students: A Randomized Controlled Trial

Directory of Open Access Journals (Sweden)

Leslie A. Daly

2015-01-01

Full Text Available Middle adolescents (15–17 years old are prone to increased risk taking and emotional instability. Emotion dysregulation contributes to a variety of psychosocial difficulties in this population. A discipline such as yoga offered during school may increase emotion regulation, but research in this area is lacking. This study was designed to evaluate the impact of a yoga intervention on the emotion regulation of high school students as compared to physical education (PE. In addition, the potential mediating effects of mindful attention, self-compassion, and body awareness on the relationship between yoga and emotion regulation were examined. High school students were randomized to participate in a 16-week yoga intervention (n=19 or regular PE (n=18. Pre-post data analyses revealed that emotion regulation increased significantly in the yoga group as compared to the PE group (F (1,32 = 7.50, p=.01, and eta2 = .19. No significant relationship was discovered between the changes in emotion regulation and the proposed mediating variables. Preliminary results suggest that yoga increases emotion regulation capacities of middle adolescents and provides benefits beyond that of PE alone.

Aflatoxin regulations and global pistachio trade: insights from social network analysis.

Science.gov (United States)

Bui-Klimke, Travis R; Guclu, Hasan; Kensler, Thomas W; Yuan, Jian-Min; Wu, Felicia

2014-01-01

Aflatoxins, carcinogenic toxins produced by Aspergillus fungi, contaminate maize, peanuts, and tree nuts in many regions of the world. Pistachios are the main source of human dietary aflatoxins from tree nuts worldwide. Over 120 countries have regulations for maximum allowable aflatoxin levels in food commodities. We developed social network models to analyze the association between nations' aflatoxin regulations and global trade patterns of pistachios from 1996-2010. The main pistachio producing countries are Iran and the United States (US), which together contribute to nearly 75% of the total global pistachio market. Over this time period, during which many nations developed or changed their aflatoxin regulations in pistachios, global pistachio trade patterns changed; with the US increasingly exporting to countries with stricter aflatoxin standards. The US pistachio crop has had consistently lower levels of aflatoxin than the Iranian crop over this same time period. As similar trading patterns have also been documented in maize, public health may be affected if countries without aflatoxin regulations, or with more relaxed regulations, continually import crops with higher aflatoxin contamination. Unlike the previous studies on maize, this analysis includes a dynamic element, examining how trade patterns change over time with introduction or adjustment of aflatoxin regulations.

Self-Regulated Workplace Learning: A Pedagogical Framework and Semantic Web-Based Environment

Science.gov (United States)

Siadaty, Melody; Gasevic, Dragan; Jovanovic, Jelena; Pata, Kai; Milikic, Nikola; Holocher-Ertl, Teresa; Jeremic, Zoran; Ali, Liaqat; Giljanovic, Aleksandar; Hatala, Marek

2012-01-01

Self-regulated learning processes have a potential to enhance the motivation of knowledge workers to take part in learning and reflection about learning, and thus contribute to the resolution of an important research challenge in workplace learning. An equally important research challenge for the successful completion of each step of a…

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to spermidine and contribution to normal hair growth (ID 1705) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

DEFF Research Database (Denmark)

Tetens, Inge

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006. This opinion addresses the scientific substantiation of health...... claims in relation to spermidine and contribution to normal hair growth. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims and references that EFSA has received from Member States or directly from stakeholders...

Deletion of the Sm1 encoding motif in the lsm gene results in distinct changes in the transcriptome and enhanced swarming activity of Haloferax cells.

Science.gov (United States)

Maier, Lisa-Katharina; Benz, Juliane; Fischer, Susan; Alstetter, Martina; Jaschinski, Katharina; Hilker, Rolf; Becker, Anke; Allers, Thorsten; Soppa, Jörg; Marchfelder, Anita

2015-10-01

Members of the Sm protein family are important for the cellular RNA metabolism in all three domains of life. The family includes archaeal and eukaryotic Lsm proteins, eukaryotic Sm proteins and archaeal and bacterial Hfq proteins. While several studies concerning the bacterial and eukaryotic family members have been published, little is known about the archaeal Lsm proteins. Although structures for several archaeal Lsm proteins have been solved already more than ten years ago, we still do not know much about their biological function, however one can confidently propose that the archaeal Lsm proteins will also be involved in RNA metabolism. Therefore, we investigated this protein in the halophilic archaeon Haloferax volcanii. The Haloferax genome encodes a single Lsm protein, the lsm gene overlaps and is co-transcribed with the gene for the ribosomal L37.eR protein. Here, we show that the reading frame of the lsm gene contains a promoter which regulates expression of the overlapping rpl37R gene. This rpl37R specific promoter ensures high expression of the rpl37R gene in exponential growth phase. To investigate the biological function of the Lsm protein we generated a lsm deletion mutant that had the coding sequence for the Sm1 motif removed but still contained the internal promoter for the downstream rpl37R gene. The transcriptome of this deletion mutant was compared to the wild type transcriptome, revealing that several genes are down-regulated and many genes are up-regulated in the deletion strain. Northern blot analyses confirmed down-regulation of two genes. In addition, the deletion strain showed a gain of function in swarming, in congruence with the up-regulation of transcripts encoding proteins required for motility. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Modelling of hydro and wind power in the regulation market

International Nuclear Information System (INIS)

Kiviluoma, J.; Holttinen, H.; Meibom, P.

2006-01-01

The amount of required regulation capacity in the power system is affected by the wind power prediction errors. A model has been developed which can evaluate the monetary effects of prediction errors. The model can be used to evaluate (1) the regulation costs of wind power, (2) regulation market prices including effects related to the participation of power producers in the regulating power market, (3) value of accurate wind forecasts and (4) the effect of decreasing the length of the spot market clearance. This article discusses the problems related to developing a realistic model of the regulating power market including the interaction between the spot market and the regulating power market. There are several issues that make things complicated. (1) How to calculate the minimum amount of needed secondary (minute) reserves. Traditionally the Nordic TSOs have used an N-1 criteria in each country to determine the required amounts of positive secondary reserve, but as installed wind power capacity grows, it will become relevant to include the wind power prediction errors in the estimation of secondary reserves. (2) Consumption forecast errors and plant outages also contribute to activation of regulating power and should have stochastic input series besides wind power. (3) Risk premiums and transaction costs in the regulating power market are difficult to estimate as well as the effects of the possible use of market power. This is especially true in the Nordic system with the high share of hydro power, since the water value and hydrological limitations make things more complex than in a thermal system. (4) The available regulation capacity is not necessarily equal to the truly available capacity. All producers don't participate in the regulation market although in principle they could. (orig.)

Contribution of kv7.4/kv7.5 heteromers to intrinsic and calcitonin gene-related Peptide-induced cerebral reactivity

DEFF Research Database (Denmark)

Chadha, Preet S; Jepps, Thomas A; Carr, Georgina

2014-01-01

Middle cerebral artery (MCA) diameter is regulated by inherent myogenic activity and the effect of potent vasodilators such as calcitonin gene-related peptide (CGRP). Previous studies showed that MCAs express KCNQ1, 4, and 5 potassium channel genes, and the expression products (Kv7 channels) part......) participate in the myogenic control of MCA diameter. The present study investigated the contribution of Kv7.4 and Kv7.5 isoforms to myogenic and CGRP regulation of MCA diameter and determined whether they were affected in hypertensive animals....

Renal intercalated cells and blood pressure regulation

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Susan M. Wall

2017-12-01

Full Text Available Type B and non-A, non-B intercalated cells are found within the connecting tubule and the cortical collecting duct. Of these cell types, type B intercalated cells are known to mediate Cl⁻ absorption and HCO₃⁻ secretion largely through pendrin-dependent Cl⁻/HCO₃⁻ exchange. This exchange is stimulated by angiotensin II administration and is also stimulated in models of metabolic alkalosis, for instance after aldosterone or NaHCO₃ administration. In some rodent models, pendrin-mediated HCO₃⁻ secretion modulates acid-base balance. However, the role of pendrin in blood pressure regulation is likely of more physiological or clinical significance. Pendrin regulates blood pressure not only by mediating aldosterone-sensitive Cl⁻ absorption, but also by modulating the aldosterone response for epithelial Na⁺ channel (ENaC-mediated Na⁺ absorption. Pendrin regulates ENaC through changes in open channel of probability, channel surface density, and channels subunit total protein abundance. Thus, aldosterone stimulates ENaC activity through both direct and indirect effects, the latter occurring through its stimulation of pendrin expression and function. Therefore, pendrin contributes to the aldosterone pressor response. Pendrin may also modulate blood pressure in part through its action in the adrenal medulla, where it modulates the release of catecholamines, or through an indirect effect on vascular contractile force. This review describes how aldosterone and angiotensin II-induced signaling regulate pendrin and the contributory role of pendrin in distal nephron function and blood pressure.

Homo sapiens exhibit a distinct pattern of CNV genes regulation: an important role of miRNAs and SNPs in expression plasticity.

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Dweep, Harsh; Kubikova, Nada; Gretz, Norbert; Voskarides, Konstantinos; Felekkis, Kyriacos

2015-07-16

Gene expression regulation is a complex and highly organized process involving a variety of genomic factors. It is widely accepted that differences in gene expression can contribute to the phenotypic variability between species, and that their interpretation can aid in the understanding of the physiologic variability. CNVs and miRNAs are two major players in the regulation of expression plasticity and may be responsible for the unique phenotypic characteristics observed in different lineages. We have previously demonstrated that a close interaction between these two genomic elements may have contributed to the regulation of gene expression during evolution. This work presents the molecular interactions between CNV and non CNV genes with miRNAs and other genomic elements in eight different species. A comprehensive analysis of these interactions indicates a unique nature of human CNV genes regulation as compared to other species. By using genes with short 3' UTR that abolish the "canonical" miRNA-dependent regulation, as a model, we demonstrate a distinct and tight regulation of human genes that might explain some of the unique features of human physiology. In addition, comparison of gene expression regulation between species indicated that there is a significant difference between humans and mice possibly questioning the effectiveness of the latest as experimental models of human diseases.

Branded prescription drug fee. Final regulations, temporary regulations, and removal of temporary regulations.

Science.gov (United States)

2014-07-28

This document contains final regulations that provide guidance on the annual fee imposed on covered entities engaged in the business of manufacturing or importing branded prescription drugs. This fee was enacted by section 9008 of the Patient Protection and Affordable Care Act, as amended by section 1404 of the Health Care and Education Reconciliation Act of 2010. This document also withdraws the Branded Prescription Drug Fee temporary regulations and contains new temporary regulations regarding the definition of controlled group that apply beginning on January 1, 2015. The final regulations and the new temporary regulations affect persons engaged in the business of manufacturing or importing certain branded prescription drugs. The text of the temporary regulations in this document also serves as the text of proposed regulations set forth in a notice of proposed rulemaking (REG-123286-14) on this subject in the Proposed Rules section in this issue of the Federal Register.

Regulation of corneal stroma extracellular matrix assembly.

Science.gov (United States)

Chen, Shoujun; Mienaltowski, Michael J; Birk, David E

2015-04-01

The transparent cornea is the major refractive element of the eye. A finely controlled assembly of the stromal extracellular matrix is critical to corneal function, as well as in establishing the appropriate mechanical stability required to maintain corneal shape and curvature. In the stroma, homogeneous, small diameter collagen fibrils, regularly packed with a highly ordered hierarchical organization, are essential for function. This review focuses on corneal stroma assembly and the regulation of collagen fibrillogenesis. Corneal collagen fibrillogenesis involves multiple molecules interacting in sequential steps, as well as interactions between keratocytes and stroma matrix components. The stroma has the highest collagen V:I ratio in the body. Collagen V regulates the nucleation of protofibril assembly, thus controlling the number of fibrils and assembly of smaller diameter fibrils in the stroma. The corneal stroma is also enriched in small leucine-rich proteoglycans (SLRPs) that cooperate in a temporal and spatial manner to regulate linear and lateral collagen fibril growth. In addition, the fibril-associated collagens (FACITs) such as collagen XII and collagen XIV have roles in the regulation of fibril packing and inter-lamellar interactions. A communicating keratocyte network contributes to the overall and long-range regulation of stromal extracellular matrix assembly, by creating micro-domains where the sequential steps in stromal matrix assembly are controlled. Keratocytes control the synthesis of extracellular matrix components, which interact with the keratocytes dynamically to coordinate the regulatory steps into a cohesive process. Mutations or deficiencies in stromal regulatory molecules result in altered interactions and deficiencies in both transparency and refraction, leading to corneal stroma pathobiology such as stromal dystrophies, cornea plana and keratoconus. Copyright © 2014 Elsevier Ltd. All rights reserved.

A family business: stem cell progeny join the niche to regulate homeostasis.

Science.gov (United States)

Hsu, Ya-Chieh; Fuchs, Elaine

2012-01-23

Stem cell niches, the discrete microenvironments in which the stem cells reside, play a dominant part in regulating stem cell activity and behaviours. Recent studies suggest that committed stem cell progeny become indispensable components of the niche in a wide range of stem cell systems. These unexpected niche inhabitants provide versatile feedback signals to their stem cell parents. Together with other heterologous cell types that constitute the niche, they contribute to the dynamics of the microenvironment. As progeny are often located in close proximity to stem cell niches, similar feedback regulations may be the underlying principles shared by different stem cell systems.

The major contributions of the worldwide gas congress CMG 2000

International Nuclear Information System (INIS)

Moncel, V.

2000-01-01

The six major contributions which took place all along the 2000 issue of the worldwide gas congress have permitted to draw out a precise status of the international opportunities and challenges that natural gas industry will have to face in order to make natural gas the first energy source of the 21 century. Despite the different national contexts, all intervening parties agreed with the undeniable stakes of natural gas which will have a promising development provided that deregulation effects are mastered and investments are maintained in new technologies R and D and in the settlement of reliable international infrastructures. This article summarizes the main content of these contributions: Gaz de France group in the new European context: opportunities and strategies of a big operator; gas industry in the US: perspectives for the millennium; leading elements of the gas industry in Europe: liberalization, regulation and technology; structural transformations of the international gas industry and its strategies: towards a worldwide gas market; the future of gas industry in Russia in the 21 century; perspectives for natural gas in Asia. (J.S.)

Evaluating Industry Self-Regulation of Food Marketing to Children.

Science.gov (United States)

Kunkel, Dale L; Castonguay, Jessica S; Filer, Christine R

2015-08-01

Concern has grown about the role of televised food advertising as a contributor to childhood obesity. In response, the food industry adopted a program of self-regulation, with participating companies pledging to limit child-targeted advertising to healthier products. The implicit promise of the industry initiative is a significant improvement in the overall nutritional quality of foods marketed to children, thereby negating the need for governmental regulation to accomplish that objective. This study assesses the efficacy of industry self-regulation by comparing advertising content on children's TV programs before and after self-regulation was implemented. A systematic content analysis of food advertisements (n=625 in 2007, n=354 in 2013) appearing in children's TV programs on the most popular cable and broadcast channels was conducted. All analyses were conducted in 2014. Findings indicated that no significant improvement in the overall nutritional quality of foods marketed to children has been achieved since industry self-regulation was adopted. In 2013, 80.5% of all foods advertised to children on TV were for products in the poorest nutritional category, and thus pose high risk for contributing to obesity. The lack of significant improvement in the nutritional quality of food marketed to children is likely a result of the weak nutritional standards for defining healthy foods employed by industry, and because a substantial proportion of child-oriented food marketers do not participate in self-regulation. The lack of success achieved by self-regulation indicates that other policy actions are needed to effectively reduce children's exposure to obesogenic food advertising. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Self-regulated learning in students of pedagogy

Directory of Open Access Journals (Sweden)

Janete Aparecida da Silva Marini

2014-12-01

Full Text Available Self-regulated learning is the process by which students plan, monitor and regulate their own learning. The aim of this study was to investigate relationships between motivation to learn, implicit theories of intelligence and self-handicapping strategies, and to examine the association of these variables in the prediction of the use of learning strategies in students of Pedagogy. The sample consisted of 107 Pedagogy students of two private universities of a city of São Paulo state. Data were collected using four Likert-type scales. Multivariate linear regression analyses revealed that participants with higher scores in the Learning Strategies Scale also presented significantly higher scores in intrinsic motivation and fewer reports of use of self-handicapping strategies. Higher scores in metacognitive strategies were significantly associated with both intrinsic an extrinsic motivation and with fewer reports of use of self-handicapping strategies. Results are discussed in terms of the contribution of Psychology to teacher education.

The significance of translation regulation in the stress response

OpenAIRE

Picard, Flora; Loubière, Pascal; Girbal, Laurence; Bousquet, Muriel

2013-01-01

Background: The stress response in bacteria involves the multistage control of gene expression but is not entirely understood. To identify the translational response of bacteria in stress conditions and assess its contribution to the regulation of gene expression, the translational states of all mRNAs were compared under optimal growth condition and during nutrient (isoleucine) starvation. Results: A genome-scale study of the translational response to nutritional limitation was performed in t...

Contributions of the model of social management to the strengthening of school council as a democratic space

Directory of Open Access Journals (Sweden)

Gislene Silva Dutra

2017-07-01

Full Text Available The paper presents a qualitative research of exploratory nature, which was developed in two phases. Initially, it has been carried out a literature review in order to discuss the contributions of the social management model for strengthening the school councils as a democratic space. Then it has been conducted a case study about the regulation of the School Council in the School System of Brumadinho, Minas Gerais. The main results showed that the model of social management has features such as dialogue, participation, democratization and empowerment, which can contribute to the strengthening of the school board as a democratic space.

The thermosensitive TRPV3 channel contributes to rapid wound healing in oral epithelia.

Science.gov (United States)

Aijima, Reona; Wang, Bing; Takao, Tomoka; Mihara, Hiroshi; Kashio, Makiko; Ohsaki, Yasuyoshi; Zhang, Jing-Qi; Mizuno, Atsuko; Suzuki, Makoto; Yamashita, Yoshio; Masuko, Sadahiko; Goto, Masaaki; Tominaga, Makoto; Kido, Mizuho A

2015-01-01

The oral cavity provides an entrance to the alimentary tract to serve as a protective barrier against harmful environmental stimuli. The oral mucosa is susceptible to injury because of its location; nonetheless, it has faster wound healing than the skin and less scar formation. However, the molecular pathways regulating this wound healing are unclear. Here, we show that transient receptor potential vanilloid 3 (TRPV3), a thermosensitive Ca(2+)-permeable channel, is more highly expressed in murine oral epithelia than in the skin by quantitative RT-PCR. We found that temperatures above 33°C activated TRPV3 and promoted oral epithelial cell proliferation. The proliferation rate in the oral epithelia of TRPV3 knockout (TRPV3KO) mice was less than that of wild-type (WT) mice. We investigated the contribution of TRPV3 to wound healing using a molar tooth extraction model and found that oral wound closure was delayed in TRPV3KO mice compared with that in WT mice. TRPV3 mRNA was up-regulated in wounded tissues, suggesting that TRPV3 may contribute to oral wound repair. We identified TRPV3 as an essential receptor in heat-induced oral epithelia proliferation and wound healing. Our findings suggest that TRPV3 activation could be a potential therapeutic target for wound healing in skin and oral mucosa. © FASEB.

The complexity of nitrogen metabolism and nitrogen-regulated gene expression in plant pathogenic fungi

NARCIS (Netherlands)

Bolton, M.D.; Thomma, B.P.H.J.

2008-01-01

Plant pathogens secrete effector molecules that contribute to the establishment of disease in their plant hosts. The identification of cellular cues that regulate effector gene expression is an important aspect of understanding the infection process. Nutritional status in the cell has been

Genetic variations in the serotoninergic system contribute to amygdala volume in humans

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Jin eLi

2015-10-01

Full Text Available The amygdala plays a critical role in emotion processing and psychiatric disorders associated with emotion dysfunction. Accumulating evidence suggests that amygdala structure is modulated by serotonin-related genes. However, there is a gap between the small contributions of single loci (less than 1% and the reported 63-65% heritability of amygdala structure. To understand the missing heritability, we systematically explored the contribution of serotonin genes on amygdala structure at the gene set level. The present study of 417 healthy Chinese volunteers examined 129 representative polymorphisms in genes from multiple biological mechanisms in the regulation of serotonin neurotransmission. A system-level approach using multiple regression analyses identified that nine SNPs collectively accounted for approximately 8% of the variance in amygdala volume. Permutation analyses showed that the probability of obtaining these findings by chance was low (p=0.043, permuted for 1000 times. Findings showed that serotonin genes contribute moderately to individual differences in amygdala volume in a healthy Chinese sample. These results indicate that the system-level approach can help us to understand the genetic basis of a complex trait such as amygdala structure.

Transcriptional regulators of Na, K-ATPase subunits

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Zhiqin eLi

2015-10-01

Full Text Available The Na,K-ATPase classically serves as an ion pump creating an electrochemical gradient across the plasma membrane that is essential for transepithelial transport, nutrient uptake and membrane potential. In addition, Na,K-ATPase also functions as a receptor, a signal transducer and a cell adhesion molecule. With such diverse roles, it is understandable that the Na,K-ATPase subunits, the catalytic alpha-subunit, the beta-subunit and the FXYD proteins, are controlled extensively during development and to accommodate physiological needs. The spatial and temporal expression of Na,K-ATPase is partially regulated at the transcriptional level. Numerous transcription factors, hormones, growth factors, lipids and extracellular stimuli modulate the transcription of the Na,K-ATPase subunits. Moreover, epigenetic mechanisms also contribute to the regulation of Na,K-ATPase expression. With the ever growing knowledge about diseases associated with the malfunction of Na,K-ATPase, this review aims at summarizing the best-characterized transcription regulators that modulate Na,K-ATPase subunit levels. As abnormal expression of Na,K-ATPase subunits have been observed in many carcinoma, we will also discuss transcription factors that are associated with epithelial-to-mesenchymal transition, a crucial step in the progression of many tumors to malignant disease.

Endogenous monitoring: a new challenge for the regulation of energy externalities

International Nuclear Information System (INIS)

Millock, K.

1999-11-01

The present article studies the problem of regulating externalities from energy use, with particular emphasis on the problem of information. A standard economics. The article shows how the optimal choice of instruments used to regulate the externalities from energy use will change with the more widespread adoption of modern monitoring technologies. We will illustrate how the application of incentive policies conditioned on monitoring can contribute to the implementation of flexible mechanisms for greenhouse gas abatement. Section 2 briefly summarises the economic framework for the regulation of externalities resulting from energy use. In Section 3, an illustrative model is presented in which the introduction of monitoring of emissions is endogenous and conditions the best type of instrument used by the regulator to internalize the externalities from energy use. Section 4 then examines the implications of this framework for the application of the flexible incentives introduced in the Kyoto Protocol. It shows how the success of project-based approaches, such as Joint Implementation and the Clean Development Mechanism, depends upon the implementation of appropriate incentives for monitoring. Section 5 concludes. (author)

The role of the regulator in promoting and evaluating safety culture. Operating experience feedback programme approach

International Nuclear Information System (INIS)

Perez, S.

2002-01-01

Promoting and Evaluating Safety Culture (S.C.) in Operating Organizations must be one of the main Nuclear Regulator goals to achieve. This can be possible only if each and every one of the regulatory activities inherently involves S.C. It can be seen throughout attitudes, values, uses and practices in both individuals and the whole regulatory organization. One among all the regulatory tools commonly used by regulators to promote and evaluate the commitment of the licensees with safety culture as a whole involves organizational factors and particular attention is directed to the operating organization. This entailed a wide range of activities, including all those related with management of safety performance. Operating Experience Feedback Programme as a tool to enhance safety operation is particularly useful for regulators in the evaluation of the role of S.C. in operating organization. Safety Culture is recognized as a subset of the wider Organizational Culture. Practices that improve organizational effectiveness can also contribute to enhance safety. An effective event investigation methodology is a specific practice, which contributes to a healthy Safety Culture. (author)

Transcriptional Regulation of Chemokine Genes: A Link to Pancreatic Islet Inflammation?

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Susan J. Burke

2015-05-01

Full Text Available Enhanced expression of chemotactic cytokines (aka chemokines within pancreatic islets likely contributes to islet inflammation by regulating the recruitment and activation of various leukocyte populations, including macrophages, neutrophils, and T-lymphocytes. Because of the powerful actions of these chemokines, precise transcriptional control is required. In this review, we highlight what is known about the signals and mechanisms that govern the transcription of genes encoding specific chemokine proteins in pancreatic islet β-cells, which include contributions from the NF-κB and STAT1 pathways. We further discuss increased chemokine expression in pancreatic islets during autoimmune-mediated and obesity-related development of diabetes.

Mechanical and IL-1β Responsive miR-365 Contributes to Osteoarthritis Development by Targeting Histone Deacetylase 4

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Xu Yang

2016-03-01

Full Text Available Mechanical stress plays an important role in the initiation and progression of osteoarthritis. Studies show that excessive mechanical stress can directly damage the cartilage extracellular matrix and shift the balance in chondrocytes to favor catabolic activity over anabolism. However, the underlying mechanism remains unknown. MicroRNAs (miRNAs are emerging as important regulators in osteoarthritis pathogenesis. We have found that mechanical loading up-regulated microRNA miR-365 in growth plate chondrocytes, which promotes chondrocyte differentiation. Here, we explored the role of the mechanical responsive microRNA miR-365 in pathogenesis of osteoarthritis (OA. We found that miR-365 was up-regulated by cyclic loading and IL-1β stimulation in articular chondrocytes through a mechanism that involved the transcription factor NF-κB. miR-365 expressed significant higher level in rat anterior cruciate ligament (ACL surgery induced OA cartilage as well as human OA cartilage from primary OA patients and traumatic OA Patients. Overexpression of miR-365 in chondrocytes increases gene expression of matrix degrading enzyme matrix metallopeptidase 13 (MMP13 and collagen type X (Col X. The increase in miR-365 expression in OA cartilage and in response to IL-1 may contribute to the abnormal gene expression pattern characteristic of OA. Inhibition of miR-365 down-regulated IL-1β induced MMP13 and Col X gene expression. We further showed histone deacetylase 4 (HDAC4 is a direct target of miR-365, which mediates mechanical stress and inflammation in OA pathogenesis. Thus, miR-365 is a critical regulator of mechanical stress and pro-inflammatory responses, which contributes cartilage catabolism. Manipulation of the expression of miR-365 in articular chondrocytes by miR-365 inhibitor may be a potent therapeutic target for the prevention and treatment of osteoarthritis.

Age-dependent regulation of ERF-VII transcription factor activity in Arabidopsis thaliana.

Science.gov (United States)