ClpE from Lactococcus lactis promotes repression of CtsR-dependent gene expression

DEFF Research Database (Denmark)

Varmanen, P.; Vogensen, F.K.; Hammer, Karin

2003-01-01

ATPase (ClpE) in Lactococcus lactis is required for such a decrease in expression of a gene negatively regulated by the heat shock regulator (CtsR). Northern blot analysis showed that while a shift to a high temperature in wild-type cells resulted in a temporal increase followed by a decrease...

Analysis of Linear Hybrid Systems in CLP

DEFF Research Database (Denmark)

Banda, Gourinath; Gallagher, John Patrick

2009-01-01

In this paper we present a procedure for representing the semantics of linear hybrid automata (LHAs) as constraint logic programs (CLP); flexible and accurate analysis and verification of LHAs can then be performed using generic CLP analysis and transformation tools. LHAs provide an expressive...

Preparation of 99Tcm-CLP imaging probe of lung carcinoma

International Nuclear Information System (INIS)

Qiang Yonggang; Liao Yonghua

2004-01-01

The process of preparing an imaging micro-probe 99 Tc m -CLP from bovine nose cartilage is described in detail. Both labeled rate and radiochemical purity of 99 Tc m -CLP are greater than 90%, and KA is 1.12 x 10 9 L/mol in vitro. After the Balb/c nu/nu mice with lung cancer were intravenously injected by the 99 Tc m -CLP, the radioactivity was found to be well concentrated at the lung-cancer region, which suggests that the 99 Tc m -CLP micro-probe can be used in imaging study of lung carcinoma. (authors)

The putative cellodextrin transporter-like protein CLP1 is involved in cellulase induction in Neurospora crassa.

Science.gov (United States)

Cai, Pengli; Wang, Bang; Ji, Jingxiao; Jiang, Yongsheng; Wan, Li; Tian, Chaoguang; Ma, Yanhe

2015-01-09

Neurospora crassa recently has become a novel system to investigate cellulase induction. Here, we discovered a novel membrane protein, cellodextrin transporter-like protein 1 (CLP1; NCU05853), a putative cellodextrin transporter-like protein that is a critical component of the cellulase induction pathway in N. crassa. Although CLP1 protein cannot transport cellodextrin, the suppression of cellulase induction by this protein was discovered on both cellobiose and Avicel. The co-disruption of the cellodextrin transporters cdt2 and clp1 in strain Δ3βG formed strain CPL7. With induction by cellobiose, cellulase production was enhanced 6.9-fold in CPL7 compared with Δ3βG. We also showed that the suppression of cellulase expression by CLP1 occurred by repressing the expression of cellodextrin transporters, particularly cdt1 expression. Transcriptome analysis of the hypercellulase-producing strain CPL7 showed that the cellulase expression machinery was dramatically stimulated, as were the cellulase enzyme genes including the inducer transporters and the major transcriptional regulators. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

The Putative Cellodextrin Transporter-like Protein CLP1 Is Involved in Cellulase Induction in Neurospora crassa*

Science.gov (United States)

Cai, Pengli; Wang, Bang; Ji, Jingxiao; Jiang, Yongsheng; Wan, Li; Tian, Chaoguang; Ma, Yanhe

2015-01-01

Neurospora crassa recently has become a novel system to investigate cellulase induction. Here, we discovered a novel membrane protein, cellodextrin transporter-like protein 1 (CLP1; NCU05853), a putative cellodextrin transporter-like protein that is a critical component of the cellulase induction pathway in N. crassa. Although CLP1 protein cannot transport cellodextrin, the suppression of cellulase induction by this protein was discovered on both cellobiose and Avicel. The co-disruption of the cellodextrin transporters cdt2 and clp1 in strain Δ3βG formed strain CPL7. With induction by cellobiose, cellulase production was enhanced 6.9-fold in CPL7 compared with Δ3βG. We also showed that the suppression of cellulase expression by CLP1 occurred by repressing the expression of cellodextrin transporters, particularly cdt1 expression. Transcriptome analysis of the hypercellulase-producing strain CPL7 showed that the cellulase expression machinery was dramatically stimulated, as were the cellulase enzyme genes including the inducer transporters and the major transcriptional regulators. PMID:25398875

The Mitochondrial Unfoldase-Peptidase Complex ClpXP Controls Bioenergetics Stress and Metastasis.

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Jae Ho Seo

2016-07-01

Full Text Available Mitochondria must buffer the risk of proteotoxic stress to preserve bioenergetics, but the role of these mechanisms in disease is poorly understood. Using a proteomics screen, we now show that the mitochondrial unfoldase-peptidase complex ClpXP associates with the oncoprotein survivin and the respiratory chain Complex II subunit succinate dehydrogenase B (SDHB in mitochondria of tumor cells. Knockdown of ClpXP subunits ClpP or ClpX induces the accumulation of misfolded SDHB, impairing oxidative phosphorylation and ATP production while activating "stress" signals of 5' adenosine monophosphate-activated protein kinase (AMPK phosphorylation and autophagy. Deregulated mitochondrial respiration induced by ClpXP targeting causes oxidative stress, which in turn reduces tumor cell proliferation, suppresses cell motility, and abolishes metastatic dissemination in vivo. ClpP is universally overexpressed in primary and metastatic human cancer, correlating with shortened patient survival. Therefore, tumors exploit ClpXP-directed proteostasis to maintain mitochondrial bioenergetics, buffer oxidative stress, and enable metastatic competence. This pathway may provide a "drugable" therapeutic target in cancer.

Implementation of CLP4NET in Bulgaria

International Nuclear Information System (INIS)

Naydenova, I.; Pironkov, L.; Filipov, A.; Petrova, T.; Tsochev, G.; Ganev, I.

2016-01-01

Full text: Networking solutions (networks of excellence, communities of practice, knowledge portals, etc.) are recognized as effective tools for nuclear training and education services, transfer of good practices, knowledge and programmes, and knowledge management. In addition, the e-learning is recommended as a state of the art and cost effective approach for supplementing the traditional face to face training and education programmes. Thus, the Cyber Learning Platform for Nuclear Education and Training (CLP4NET) was implemented into the Kozloduy Nuclear Power Plant (KNPP) Training System. Based on the experience of KNPP, the CLP4NET was implemented also at the College of Energy and Electronics (CEE), Technical University of Sofia (TU-Sofia), providing an appropriate tool for further establishment of a National Nuclear Network of Competency. The current study is focused mainly on specific issues and lessons learned during the installation of CLP4NET at the CEE, TU-Sofia. (author

Role of the disaggregase ClpB in processing of proteins aggregated as inclusion bodies.

Science.gov (United States)

Zblewska, Kamila; Krajewska, Joanna; Zolkiewski, Michal; Kędzierska-Mieszkowska, Sabina

2014-08-01

Overproduction of heterologous proteins in bacterial systems often results in the formation of insoluble inclusion bodies (IBs), which is a major impediment in biochemical research and biotechnology. In principle, the activity of molecular chaperones could be employed to gain control over the IB formation and to improve the recombinant protein yields, but the potential of each of the major bacterial chaperones (DnaK/J, GroEL/ES, and ClpB) to process IBs has not been fully established yet. We investigated the formation of inclusion bodies (IBs) of two aggregation-prone proteins, VP1LAC and VP1GFP, overproduced in Escherichiacoli in the presence and absence of the chaperone ClpB. We found that both ClpB isoforms, ClpB95 and ClpB80 accumulated in E. coli cells during the production of IBs. The amount of IB proteins increased in the absence of ClpB. ClpB supported the resolubilization and reactivation of the aggregated VP1LAC and VP1GFP in E. coli cells. The IB disaggregation was optimal in the presence of both ClpB95 and ClpB80. Our results indicate an essential role of ClpB in controlling protein aggregation and inclusion body formation in bacteria. Copyright © 2014 Elsevier Inc. All rights reserved.

Cooperation between two ClpB isoforms enhances the recovery of the recombinant {beta}-galactosidase from inclusion bodies

Energy Technology Data Exchange (ETDEWEB)

Guenther, Izabela [Department of Biochemistry, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk (Poland); Zolkiewski, Michal [Department of Biochemistry, Kansas State University, Manhattan, KS 66506 (United States); Kedzierska-Mieszkowska, Sabina, E-mail: kedzie@biotech.ug.gda.pl [Department of Biochemistry, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk (Poland)

2012-10-05

Highlights: Black-Right-Pointing-Pointer An important role of synergistic cooperation between the two ClpB isoforms. Black-Right-Pointing-Pointer Both ClpB isoforms are associated with IBs of {beta}-galactosidase. Black-Right-Pointing-Pointer ClpB is a key chaperone in IB protein release. -- Abstract: Bacterial ClpB is a molecular chaperone that solubilizes and reactivates aggregated proteins in cooperation with the DnaK chaperone system. The mechanism of protein disaggregation mediated by ClpB is linked to translocation of substrates through the central channel within the ring-hexameric structure of ClpB. Two isoforms of ClpB are produced in vivo: the full-length ClpB95 and the truncated ClpB80 (ClpB{Delta}N), which does not contain the N-terminal domain. The functional specificity of the two ClpB isoforms and the biological role of the N-terminal domain are still not fully understood. Recently, it has been demonstrated that ClpB may achieve its full potential as an aggregate-reactivating chaperone through the functional interaction and synergistic cooperation of its two isoforms. It has been found that the most efficient resolubilization and reactivation of stress-aggregated proteins occurred in the presence of both ClpB95 and ClpB80. In this work, we asked if the two ClpB isoforms functionally cooperate in the solubilization and reactivation of proteins from insoluble inclusion bodies (IBs) in Escherichia coli cells. Using the model {beta}-galactosidase fusion protein (VP1LAC), we found that solubilization and reactivation of enzymes entrapped in IBs occurred more efficiently in the presence of ClpB95 with ClpB80 than with either ClpB95 or ClpB80 alone. The two isoforms of ClpB chaperone acting together enhanced the solubility and enzymatic activity of {beta}-galactosidase sequestered into IBs. Both ClpB isoforms were associated with IBs of {beta}-galactosidase, what demonstrates their affinity to this type of aggregates. These results demonstrate a synergistic

Immunoreactivity of the AAA+ chaperone ClpB from Leptospira interrogans with sera from Leptospira-infected animals.

Science.gov (United States)

Krajewska, Joanna; Arent, Zbigniew; Więckowski, Daniel; Zolkiewski, Michal; Kędzierska-Mieszkowska, Sabina

2016-07-16

Leptospira interrogans is a spirochaete responsible for leptospirosis in mammals. The molecular mechanisms of the Leptospira virulence remain mostly unknown. Recently, it has been demonstrated that L. interrogans ClpB (ClpBLi) is essential for bacterial survival under stressful conditions and also during infection. The aim of this study was to provide further insight into the role of ClpB in L. interrogans and answer the question whether ClpBLi as a potential virulence factor may be a target of the humoral immune response during leptospiral infections in mammals. ClpBLi consists of 860 amino acid residues with a predicted molecular mass of 96.3 kDa and shows multi-domain organization similar to that of the well-characterized ClpB from Escherichia coli. The amino acid sequence identity between ClpBLi and E. coli ClpB is 52 %. The coding sequence of the clpB Li gene was cloned and expressed in E. coli BL21(DE3) strain. Immunoreactivity of the recombinant ClpBLi protein was assessed with the sera collected from Leptospira-infected animals and uninfected healthy controls. Western blotting and ELISA analysis demonstrated that ClpBLi activates the host immune system, as evidenced by an increased level of antibodies against ClpBLi in the sera from infected animals, as compared to the control group. Additionally, ClpBLi was found in kidney tissues of Leptospira-infected hamsters. ClpBLi is both synthesized and immunogenic during the infectious process, further supporting its involvement in the pathogenicity of Leptospira. In addition, the immunological properties of ClpBLi point to its potential value as a diagnostic antigen for the detection of leptospirosis.

Substrate Discrimination by ClpB and Hsp104

Directory of Open Access Journals (Sweden)

Danielle M. Johnston

2017-05-01

Full Text Available ClpB of E. coli and yeast Hsp104 are homologous molecular chaperones and members of the AAA+ (ATPases Associated with various cellular Activities superfamily of ATPases. They are required for thermotolerance and function in disaggregation and reactivation of aggregated proteins that form during severe stress conditions. ClpB and Hsp104 collaborate with the DnaK or Hsp70 chaperone system, respectively, to dissolve protein aggregates both in vivo and in vitro. In yeast, the propagation of prions depends upon Hsp104. Since protein aggregation and amyloid formation are associated with many diseases, including neurodegenerative diseases and cancer, understanding how disaggregases function is important. In this study, we have explored the innate substrate preferences of ClpB and Hsp104 in the absence of the DnaK and Hsp70 chaperone system. The results suggest that substrate specificity is determined by nucleotide binding domain-1.

Chance, destiny, and the inner workings of ClpXP.

Science.gov (United States)

Russell, Rick; Matouschek, Andreas

2014-07-31

AAA+ proteases are responsible for protein degradation in all branches of life. Using single-molecule and ensemble assays, Cordova et al. investigate how the bacterial protease ClpXP steps through a substrate's polypeptide chain and construct a quantitative kinetic model that recapitulates the interplay between stochastic and deterministic behaviors of ClpXP. Copyright © 2014 Elsevier Inc. All rights reserved.

Structural dynamics of the MecA-ClpC complex: a type II AAA+ protein unfolding machine.

Science.gov (United States)

Liu, Jing; Mei, Ziqing; Li, Ningning; Qi, Yutao; Xu, Yanji; Shi, Yigong; Wang, Feng; Lei, Jianlin; Gao, Ning

2013-06-14

The MecA-ClpC complex is a bacterial type II AAA(+) molecular machine responsible for regulated unfolding of substrates, such as transcription factors ComK and ComS, and targeting them to ClpP for degradation. The six subunits of the MecA-ClpC complex form a closed barrel-like structure, featured with three stacked rings and a hollow passage, where substrates are threaded and translocated through successive pores. Although the general concepts of how polypeptides are unfolded and translocated by internal pore loops of AAA(+) proteins have long been conceived, the detailed mechanistic model remains elusive. With cryoelectron microscopy, we captured four different structures of the MecA-ClpC complexes. These complexes differ in the nucleotide binding states of the two AAA(+) rings and therefore might presumably reflect distinctive, representative snapshots from a dynamic unfolding cycle of this hexameric complex. Structural analysis reveals that nucleotide binding and hydrolysis modulate the hexameric complex in a number of ways, including the opening of the N-terminal ring, the axial and radial positions of pore loops, the compactness of the C-terminal ring, as well as the relative rotation between the two nucleotide-binding domain rings. More importantly, our structural and biochemical data indicate there is an active allosteric communication between the two AAA(+) rings and suggest that concerted actions of the two AAA(+) rings are required for the efficiency of the substrate unfolding and translocation. These findings provide important mechanistic insights into the dynamic cycle of the MecA-ClpC unfoldase and especially lay a foundation toward the complete understanding of the structural dynamics of the general type II AAA(+) hexamers.

Increased expression of clp genes in Lactobacillus delbrueckii UFV H2b20 exposed to acid stress and bile salts.

Science.gov (United States)

Ferreira, A B; De Oliveira, M N V; Freitas, F S; Alfenas-Zerbini, P; Da Silva, D F; De Queiroz, M V; Borges, A C; De Moraes, C A

2013-12-01

The ability to survive in harsh environments is an important criterion to select potential probiotics strains. The objective of this study was to identify and carry out phylogenetic and expression analysis by quantitative real-time PCR of the clpP, clpE, clpL and clpX genes in the probiotic strain Lactobacillus delbrueckii UFV H2b20 exposed to the conditions prevailing in the gastrointestinal tract (GIT). Phylogenetic trees reconstructed by Bayesian inference showed that the L. delbrueckii UFV H2b20 clpP, clpL and clpE genes and the ones from L. delbrueckii ATCC 11842 were grouped. The exposure of cells to MRS broth of pH 3.5 for 30 and 60 min resulted in an increased expression of the four genes. Exposure of the L. delbrueckii UFV H2b20 cells for 30 and 60 min to MRS broth containing 0.1% bile salts increased the expression of the clpP and clpE genes, while the expression level of the clpL and clpX genes increased only after 30 min of exposure. The involvement of the studied genes in the responses to acid stress and bile salts suggests a possible central role of these genes in the survival of L. delbrueckii UFV H2b20 during the passage through the GIT, a characteristic necessary for probiotic strains.

The Symbiotic Performance of Chickpea Rhizobia Can Be Improved by Additional Copies of the clpB Chaperone Gene.

Science.gov (United States)

Paço, Ana; Brígido, Clarisse; Alexandre, Ana; Mateos, Pedro F; Oliveira, Solange

2016-01-01

The ClpB chaperone is known to be involved in bacterial stress response. Moreover, recent studies suggest that this protein has also a role in the chickpea-rhizobia symbiosis. In order to improve both stress tolerance and symbiotic performance of a chickpea microsymbiont, the Mesorhizobium mediterraneum UPM-Ca36T strain was genetically transformed with pPHU231 containing an extra-copy of the clpB gene. To investigate if the clpB-transformed strain displays an improved stress tolerance, bacterial growth was evaluated under heat and acid stress conditions. In addition, the effect of the extra-copies of the clpB gene in the symbiotic performance was evaluated using plant growth assays (hydroponic and pot trials). The clpB-transformed strain is more tolerant to heat shock than the strain transformed with pPHU231, supporting the involvement of ClpB in rhizobia heat shock tolerance. Both plant growth assays showed that ClpB has an important role in chickpea-rhizobia symbiosis. The nodulation kinetics analysis showed a higher rate of nodule appearance with the clpB-transformed strain. This strain also induced a greater number of nodules and, more notably, its symbiotic effectiveness increased ~60% at pH5 and 83% at pH7, compared to the wild-type strain. Furthermore, a higher frequency of root hair curling was also observed in plants inoculated with the clpB-transformed strain, compared to the wild-type strain. The superior root hair curling induction, nodulation ability and symbiotic effectiveness of the clpB-transformed strain may be explained by an increased expression of symbiosis genes. Indeed, higher transcript levels of the nodulation genes nodA and nodC (~3 folds) were detected in the clpB-transformed strain. The improvement of rhizobia by addition of extra-copies of the clpB gene may be a promising strategy to obtain strains with enhanced stress tolerance and symbiotic effectiveness, thus contributing to their success as crop inoculants, particularly under

The Symbiotic Performance of Chickpea Rhizobia Can Be Improved by Additional Copies of the clpB Chaperone Gene.

Directory of Open Access Journals (Sweden)

Ana Paço

Full Text Available The ClpB chaperone is known to be involved in bacterial stress response. Moreover, recent studies suggest that this protein has also a role in the chickpea-rhizobia symbiosis. In order to improve both stress tolerance and symbiotic performance of a chickpea microsymbiont, the Mesorhizobium mediterraneum UPM-Ca36T strain was genetically transformed with pPHU231 containing an extra-copy of the clpB gene. To investigate if the clpB-transformed strain displays an improved stress tolerance, bacterial growth was evaluated under heat and acid stress conditions. In addition, the effect of the extra-copies of the clpB gene in the symbiotic performance was evaluated using plant growth assays (hydroponic and pot trials. The clpB-transformed strain is more tolerant to heat shock than the strain transformed with pPHU231, supporting the involvement of ClpB in rhizobia heat shock tolerance. Both plant growth assays showed that ClpB has an important role in chickpea-rhizobia symbiosis. The nodulation kinetics analysis showed a higher rate of nodule appearance with the clpB-transformed strain. This strain also induced a greater number of nodules and, more notably, its symbiotic effectiveness increased ~60% at pH5 and 83% at pH7, compared to the wild-type strain. Furthermore, a higher frequency of root hair curling was also observed in plants inoculated with the clpB-transformed strain, compared to the wild-type strain. The superior root hair curling induction, nodulation ability and symbiotic effectiveness of the clpB-transformed strain may be explained by an increased expression of symbiosis genes. Indeed, higher transcript levels of the nodulation genes nodA and nodC (~3 folds were detected in the clpB-transformed strain. The improvement of rhizobia by addition of extra-copies of the clpB gene may be a promising strategy to obtain strains with enhanced stress tolerance and symbiotic effectiveness, thus contributing to their success as crop inoculants

GFA Taq I polymorphism and cleft lip with or without cleft palate (CL/P) risk

Science.gov (United States)

Dong, Lijia; Ma, Lian

2015-01-01

The transforming growth factor alpha (TGFA) Taq I polymorphism has been indicated to be correlated with cleft lip with or without cleft palate (CL/P) susceptibility, but study results are still debatable. Thus, a meta-analysis was conducted. We conducted a comprehensive search of Embase, Ovid, Web of Science, the Cochrane database, PubMed, the Chinese Biomedical Literature Database (CBM-disc, 1979-2014), the database of National Knowledge Infrastructure (CNKI, 1979-2014) and the full paper database of Chinese Science and Technology of Chongqing (VIP, 1989-2014) to identify suitable studies. There were 18 studies suitable for this meta-analysis, involving a total of 3135 cases and 3575 controls. Significantly increased CL/P risk was observed (OR = 1.49; 95% CI 1.17-1.89; P = 0.001). In subgroup analyses stratified by ethnicity, there was evidence in the Caucasian population for an association between this polymorphism and CL/P risk (OR = 1.52; 95% CI 1.14-2.02; P = 0.004). However, no significant association was found between this his polymorphism and CL/P risk in African and Hispanic populations. According to a specific CL/P type, increased clip lip and palate risk and clip palate risk were found (OR = 1.38; 95% CI 1.10-1.73; P = 0.005; OR = 1.29; 95% CI 1.01-1.66; P = 0.042). In conclusion, the present meta-analysis found that the TGFA Taq I polymorphism may be associated with CL/P susceptibility. PMID:26064247

In Vitro Evaluation of Dentin Tubule Occlusion for Novel Calcium Lactate Phosphate (CLP Paste

Directory of Open Access Journals (Sweden)

Jen-Chang Yang

2017-02-01

Full Text Available Introduction: The objective of this in vitro study is to evaluate the effective and long-term occlusion of dentinal tubules using a novel calcium lactate phosphate (CLP based desensitizing agent. Methods: Dentin disks (n = 9 were pre-etched using 1 M lactic acid for 30 s and individually treated with Colgate® Pro-Relief™ paste, CLP paste, and double distilled water (ddH2O by a rubber-cupped handpiece. Dentin disks were analyzed under optical micrographs for pre-treatment, directly after treatment, and 14 days post-treatment. One-way ANOVA and post-hoc Tukey’s test were used to determine whether there were any statistically significant differences in dentinal tubule diameter. Results: A significant decrease occurred in the mean tubule diameter for dentin disks treated with CLP paste. A decrease was observed from 3.52 ± 0.83 µm to 2.62 ± 0.42 µm right after treatment, further decreasing to 1.71 ± 0.45 µm after immersion in artificial saliva for 14 days (p < 0.05. Conclusions: The results suggest that the CLP based desensitizing paste has remineralization properties and provides instant and lasting effectiveness in dentinal tubule occlusion.

Roles of conserved arginines in ATP-binding domains of AAA+ chaperone ClpB from Thermus thermophilus.

Science.gov (United States)

Yamasaki, Takashi; Nakazaki, Yosuke; Yoshida, Masasuke; Watanabe, Yo-hei

2011-07-01

ClpB, a member of the expanded superfamily of ATPases associated with diverse cellular activities (AAA+), forms a ring-shaped hexamer and cooperates with the DnaK chaperone system to reactivate aggregated proteins in an ATP-dependent manner. The ClpB protomer consists of an N-terminal domain, an AAA+ module (AAA-1), a middle domain, and a second AAA+ module (AAA-2). Each AAA+ module contains highly conserved WalkerA and WalkerB motifs, and two arginines (AAA-1) or one arginine (AAA-2). Here, we investigated the roles of these arginines (Arg322, Arg323, and Arg747) of ClpB from Thermus thermophilus in the ATPase cycle and chaperone function by alanine substitution. These mutations did not affect nucleotide binding, but did inhibit the hydrolysis of the bound ATP and slow the threading of the denatured protein through the central pore of the T. thermophilus ClpB ring, which severely impaired the chaperone functions. Previously, it was demonstrated that ATP binding to the AAA-1 module induced motion of the middle domain and stabilized the ClpB hexamer. However, the arginine mutations of the AAA-1 module destabilized the ClpB hexamer, even though ATP-induced motion of the middle domain was not affected. These results indicated that the three arginines are crucial for ATP hydrolysis and chaperone activity, but not for ATP binding. In addition, the two arginines in AAA-1 and the ATP-induced motion of the middle domain independently contribute to the stabilization of the hexamer. © 2011 The Authors Journal compilation © 2011 FEBS.

The Cell Wall Polymer Lipoteichoic Acid Becomes Nonessential in Staphylococcus aureus Cells Lacking the ClpX Chaperone

DEFF Research Database (Denmark)

Baek, Kristoffer T.; Bowman, Lisa; Millership, Charlotte

2016-01-01

Lipoteichoic acid (LTA) is an important cell wall component of Gram-positive bacteria and a promising target for the development of vaccines and antimicrobial compounds against Staphylococcus aureus. Here we demonstrate that mutations in the conditionally essential ltaS (LTA synthase) gene arise...... not produce LTA, and genetic analyses confirmed that LTA becomes nonessential in the absence of the ClpX chaperone. In fact, inactivation of ltaS alleviated the severe growth defect conferred by the clpX deletion. Microscopic analyses showed that the absence of ClpX partly alleviates the septum placement...

A simple fragment of cyclic acyldepsipeptides is necessary and sufficient for ClpP activation and antibacterial activity.

Science.gov (United States)

Carney, Daniel W; Compton, Corey L; Schmitz, Karl R; Stevens, Julia P; Sauer, Robert T; Sello, Jason K

2014-10-13

The development of new antibacterial agents, particularly those with unique biological targets, is essential to keep pace with the inevitable emergence of drug resistance in pathogenic bacteria. We identified the minimal structural component of the cyclic acyldepsipeptide (ADEP) antibiotics that exhibits antibacterial activity. We found that N-acyldifluorophenylalanine fragments function via the same mechanism of action as ADEPs, as evidenced by the requirement of ClpP for the fragments' antibacterial activity, the ability of fragments to activate Bacillus subtilis ClpP in vitro, and the capacity of an N-acyldifluorophenylalanine affinity matrix to capture ClpP from B. subtilis cell lysates. N-acyldifluorophenylalanine fragments are much simpler in structure than the full ADEPs and are also highly amenable to structural diversification. Thus, the stage has been set for the development of non-peptide activators of ClpP that can be used as antibacterial agents. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biosynthesis of the antimicrobial cyclic lipopeptides nunamycin and nunapeptin by Pseudomonas fluorescens strain In5 is regulated by the LuxR-type transcriptional regulator NunF

DEFF Research Database (Denmark)

Hennessy, Rosanna Catherine; Phippen, Christopher; Nielsen, Kristian Fog

2017-01-01

-producing pseudomonads except for the border regions where putative LuxR-type regulators are located. This study focuses on understanding the regulatory role of the LuxR-type-encoding gene nunF in CLP production of P. fluorescens In5. Functional analysis of nunF coupled with liquid chromatography-high-resolution mass...... spectrometry (LC-HRMS) showed that CLP biosynthesis is regulated by nunF. Quantitative real-time PCR analysis indicated that transcription of the NRPS genes catalyzing CLP production is strongly reduced when nunF is mutated indicating that nunF is part of the nun-nup regulon. Swarming and biofilm formation...... that environmental elicitors may also influence nunF expression which upon activation regulates nunamycin and nunapeptin production required for the growth inhibition of phytopathogens....

Biosynthesis of the antimicrobial cyclic lipopeptides nunamycin and nunapeptin by Pseudomonas fluorescens strain In5 is regulated by the LuxR-type transcriptional regulator NunF

DEFF Research Database (Denmark)

Hennessy, Rosanna Catherine; Phippen, Christopher; Nielsen, Kristian Fog

2017-01-01

-producing pseudomonads except for the border regions where putative LuxR-type regulators are located. This study focuses on understanding the regulatory role of the LuxR-type-encoding gene nunF in CLP production of P. fluorescens In5. Functional analysis of nunF coupled with liquid chromatography-high-resolution mass......Nunamycin and nunapeptin are two antimicrobial cyclic lipopeptides (CLPs) produced by Pseudomonas fluorescens In5 and synthesized by nonribosomal synthetases (NRPS) located on two gene clusters designated the nun-nup regulon. Organization of the regulon is similar to clusters found in other CLP...... spectrometry (LC-HRMS) showed that CLP biosynthesis is regulated by nunF. Quantitative real-time PCR analysis indicated that transcription of the NRPS genes catalyzing CLP production is strongly reduced when nunF is mutated indicating that nunF is part of the nun-nup regulon. Swarming and biofilm formation...

Activated ClpP kills persisters and eradicates a chronic biofilm infection.

Energy Technology Data Exchange (ETDEWEB)

Conlon, Brian P.; Nakayasu, Ernesto S.; Fleck, Laura E.; LaFleur, Michael D.; Isabella, Vincent M.; Coleman, K.; Leonard, Steve N.; Smith, Richard D.; Adkins, Joshua N.; Lewis, Kim

2013-11-21

The current antibiotic crisis stems from two distinct phenomena-drug resistance, and drug tolerance. Resistance mechanisms such as drug efflux or modification prevent antibiotics from binding to their targets 1, allowing pathogens to grow. Antibiotic tolerance is the property of persister cells, phenotypic variants of regular bacteria 2. Antibiotics kill by corrupting targets, but these are inactive in dormant persisters, leading to tolerance. Persisters were first identified by Joseph Bigger in 1944, when he discovered a surviving sub-population of Staphylococcus following treatment with penicillin3. Persisters are largely responsible for recalcitrance of chronic diseases such as tuberculosis, and various infections associated with biofilms - endocarditis, osteomyelitis, infections of catheters and indwelling devices, and deep-seated infections of soft tissues 4. There are a number of redundant pathways involved in persister formation5,6 precluding development of drugs inhibiting their formation. The acyldepsipeptide antibiotic (ADEP 4) has been shown to activate the ClpP protease resulting in death of growing cells 7. Here we show that ADEP4 activated ClpP becomes a fairly non-specific protease and kills persister cells by degradation of over 400 intracellular targets. clpP mutants are resistant to ADEP4 7, but we find that they display increased susceptibility to killing by a range of conventional antibiotics. Combining ADEP4 with rifampicin leads to eradication of persisters, stationary and biofilm populations of Staphylococcus aureus in vitro and in a deep-seated murine infection. Target corruption/activation provides an approach to killing persisters and eradicating chronic infections.

Labelling of electronic cigarettes: regulations and current practice.

Science.gov (United States)

Buonocore, Federico; Marques Gomes, Ana C N; Nabhani-Gebara, Shereen; Barton, Stephen J; Calabrese, Gianpiero

2017-01-01

Over the past decade e-cigarettes have established themselves in the global market. E-cigarettes triggered much interest in relation to their content and efficacy as smoking cessation tools, but less attention has been paid to users and environmental safety warnings and guidance. Several regulations have been introduced to promote their safe handling and disposal. From May 2016, liquids and cartridges will be regulated by European Community Directives (ECDs) 2001/83/EC and 93/42/EEC, or 2014/40/EU if marketed as tobacco-related products. Currently, manufacturers and distributors must abide by the Chemical (Hazard Information and Packaging for Supply) Regulations 2009 (CHIP) or Classification, Labelling and Packaging Regulations (CLP), the latter replacing CHIP in June 2015. In this work, the compliance of marketed e-liquids and e-cigarettes with current European Union and UK legislations is assessed. E-liquids and e-cigarettes (21 and 9 brands, respectively) were evaluated. Evidence of non-compliance was found in relation to the CHIP/CLP toxic (13%) and environmental (37%) pictograms, tactile warning (23%), nominal amount of solution (30%), supplier contact telephone number and address (40%). None of the evaluated e-cigarettes displayed information on the correct disposal/recycling of batteries in line with the ECD 2006/66/EC. More stringent enforcement of regulations is needed to ensure not only the user's safety and awareness, but also the safeguarding of the environment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Theoretical insight into the heat shock response (HSR) regulation in Lactobacillus casei and L. rhamnosus.

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Rossi, Franca; Zotta, Teresa; Iacumin, Lucilla; Reale, Anna

2016-08-07

The understanding of the heat shock response (HSR) in lactobacilli from a regulatory point of view is still limited, though an increased knowledge on the regulation of this central stress response can lead to improvements in the exploitation of these health promoting microorganisms. Therefore the aim of this in silico study, that is the first to be carried out for members of the Lactobacillus genus, was predicting how HSR influences cell functions in the food associated and probiotic species Lactobacillus casei and Lactobacillus rhamnosus. To this purpose, thirteen whole genomes of these bacteria were analyzed to identify which genes involved in HSR are present. It was found that all the genomes share 25 HSR related genes, including those encoding protein repair systems, HSR repressors, HrcA and CtsR, and the positive regulators of HSR, alternative σ factors σ(32) and σ(24). Two genes encoding a σ(70)/σ(24) factor and a Lon protease, respectively, were found only in some genomes. The localization of the HSR regulators binding sites in genomes was analyzed in order to identify regulatory relationships driving HSR in these lactobacilli. It was observed that the binding site for the HrcA repressor is found upstream of the hrcA-grpE-dnaK-dnaJ and groES-groEL gene clusters, of two hsp genes, clpE, clpL and clpP, while the CtsR repressor binding site precedes the ctsR-clpC operon, clpB, clpE and clpP. Therefore the ClpE-ClpP protease complex is dually regulated by HrcA and CtsR. Consensus sequences for the promoters recognized by the HSR alternative σ factors were defined for L. casei and L. rhamnosus and were used in whole genome searches to identify the genes that are possibly regulated by these transcription factors and whose expression level is expected to increases in HSR. The results were validated by applying the same procedure of promoter consensus generation and whole genome search to an additional 11 species representative of the main Lactobacillus

Um modelo híbrido (CLP-MILP para scheduling de operações em polidutos

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Leandro Magatão

2008-12-01

Full Text Available A eficácia na transferência de derivados de petróleo através de dutos motiva a execução deste trabalho. O objetivo principal é a modelagem do scheduling de um poliduto, isto é, um sistema de dutos que transporta diferentes derivados de petróleo. O poliduto em estudo com 93,5 km de extensão conecta uma refinaria a um terminal portuário. Foi desenvolvido um modelo de otimização baseado na união de Constraint Logic Programming (CLP e Mixed Integer Linear Programming (MILP. O modelo utiliza uma abordagem de decomposição do problema, com representação temporal contínua e calcula janelas de tempo (restrições temporais que devem ser respeitadas. A abordagem híbrida CLP-MILP proporcionou a solução de cenários reais em tempo computacional da ordem de segundos. A resolução computacional do modelo proposto evidenciou novos pontos de operação para o poliduto, proporcionando ganhos operacionais significativos. O modelo implementado configura uma ferramenta de auxílio para tomada de decisões operacionais no cenário estudado.This work is motivated by the need of optimization in the pipeline-oil distribution scenario. The considered problem involves the short-term scheduling of activities in a specific pipeline. The pipeline is 93.5 km in length, and it connects refinery and harbor tankfarms, conveying different types of commodities (gasoline, diesel, kerosene, etc. An optimization model was developed to determine the pipeline scheduling with improved efficiency. Such model combines Constraint Logic Programming (CLP and Mixed Integer Linear Programming (MILP in an integrated CLP-MILP framework. The proposed model uses decomposition strategies, continuous time representation, and intervals that represent time constraints (time windows. Real cases were solved in a reduced computational time (order of seconds. The computational results have demonstrated that the model is able to define new operational points to the pipeline

Stepwise decrease in daptomycin susceptibility in clinical Staphylococcus aureus isolates associated with an initial mutation in rpoB and a compensatory inactivation of the clpX gene

DEFF Research Database (Denmark)

Bæk, Kristoffer Torbjørn; Thøgersen, Louise; Mogensen, René G.

2015-01-01

, reduced expression of virulence traits, induced expression of the stress-associated transcriptional regulator, Spx, and slow growth. A subsequent acquired loss-of-function mutation in clpX partly alleviated the growth defect conferred by the rpoB mutation without changing antibiotic susceptibility...

Biosynthesis of the antimicrobial cyclic lipopeptides nunamycin and nunapeptin by Pseudomonas fluorescens strain In5 is regulated by the LuxR-type transcriptional regulator NunF.

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Hennessy, Rosanna C; Phippen, Christopher B W; Nielsen, Kristian F; Olsson, Stefan; Stougaard, Peter

2017-12-01

Nunamycin and nunapeptin are two antimicrobial cyclic lipopeptides (CLPs) produced by Pseudomonas fluorescens In5 and synthesized by nonribosomal synthetases (NRPS) located on two gene clusters designated the nun-nup regulon. Organization of the regulon is similar to clusters found in other CLP-producing pseudomonads except for the border regions where putative LuxR-type regulators are located. This study focuses on understanding the regulatory role of the LuxR-type-encoding gene nunF in CLP production of P. fluorescens In5. Functional analysis of nunF coupled with liquid chromatography-high-resolution mass spectrometry (LC-HRMS) showed that CLP biosynthesis is regulated by nunF. Quantitative real-time PCR analysis indicated that transcription of the NRPS genes catalyzing CLP production is strongly reduced when nunF is mutated indicating that nunF is part of the nun-nup regulon. Swarming and biofilm formation was reduced in a nunF knockout mutant suggesting that these CLPs may also play a role in these phenomena as observed in other pseudomonads. Fusion of the nunF promoter region to mCherry showed that nunF is strongly upregulated in response to carbon sources indicating the presence of a fungus suggesting that environmental elicitors may also influence nunF expression which upon activation regulates nunamycin and nunapeptin production required for the growth inhibition of phytopathogens. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

13 CFR 120.441 - How does a Lender become a CLP Lender?

Science.gov (United States)

2010-01-01

... consider whether the Lender: (1) Has the ability to process, close, service and liquidate loans; (2) Has a... application packages; (3) Has an acceptable SBA purchase rate; and (4) Has shown the ability to work well with... Lender may appeal to the D/FA, whose decision will be final. If SBA grants CLP status, it applies only in...

Analysis of the cooperative ATPase cycle of the AAA+ chaperone ClpB from Thermus thermophilus by using ordered heterohexamers with an alternating subunit arrangement.

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Yamasaki, Takashi; Oohata, Yukiko; Nakamura, Toshiki; Watanabe, Yo-hei

2015-04-10

The ClpB/Hsp104 chaperone solubilizes and reactivates protein aggregates in cooperation with DnaK/Hsp70 and its cofactors. The ClpB/Hsp104 protomer has two AAA+ modules, AAA-1 and AAA-2, and forms a homohexamer. In the hexamer, these modules form a two-tiered ring in which each tier consists of homotypic AAA+ modules. By ATP binding and its hydrolysis at these AAA+ modules, ClpB/Hsp104 exerts the mechanical power required for protein disaggregation. Although ATPase cycle of this chaperone has been studied by several groups, an integrated understanding of this cycle has not been obtained because of the complexity of the mechanism and differences between species. To improve our understanding of the ATPase cycle, we prepared many ordered heterohexamers of ClpB from Thermus thermophilus, in which two subunits having different mutations were cross-linked to each other and arranged alternately and measured their nucleotide binding, ATP hydrolysis, and disaggregation abilities. The results indicated that the ATPase cycle of ClpB proceeded as follows: (i) the 12 AAA+ modules randomly bound ATP, (ii) the binding of four or more ATP to one AAA+ ring was sensed by a conserved Arg residue and converted another AAA+ ring into the ATPase-active form, and (iii) ATP hydrolysis occurred cooperatively in each ring. We also found that cooperative ATP hydrolysis in at least one ring was needed for the disaggregation activity of ClpB. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

GSK-3β Inhibition Attenuates CLP-Induced Liver Injury by Reducing Inflammation and Hepatic Cell Apoptosis

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Hui Zhang

2014-01-01

Full Text Available Liver dysfunction has been known to occur frequently in cases of sepsis. Excessive inflammation and apoptosis are pathological features of acute liver failure. Recent studies suggest that activation of glycogen synthase kinase- (GSK- 3β is involved in inflammation and apoptosis. We aimed to investigate the protective effects of GSK-3β inhibition on polymicrobial sepsis-induced liver injury and to explore the possible mechanisms. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP, and SB216763 was used to inhibit GSK-3β in C57BL/6 mice. GSK-3β was activated following CLP. Administration of SB216763 decreased mortality, ameliorated liver injury, and reduced hepatic apoptosis. The inhibition of GSK-3β also reduced leukocyte infiltration and hepatic inflammatory cytokine expression and release. Moreover, GSK-3β inhibition suppressed the transcriptional activity of nuclear factor-kappa B (NF-κB but enhanced the transcriptional activity of cAMP response element binding protein (CREB in the liver. In in vitro studies, GSK-3β inhibition reduced inflammatory cytokine production via modulation of NF-κB and CREB signaling pathways in lipopolysaccharide-stimulated macrophages. In conclusion, these findings suggest that GSK-3β blockade protects against CLP-induced liver via inhibition of inflammation by modulating NF-κB and CREB activity and suppression of hepatic apoptosis.

75 FR 75904 - Global Terrorism Sanctions Regulations; Terrorism Sanctions Regulations; Foreign Terrorist...

Science.gov (United States)

2010-12-07

... Terrorism Sanctions Regulations; Terrorism Sanctions Regulations; Foreign Terrorist Organizations Sanctions... Foreign Assets Control (``OFAC'') of the U.S. Department of the Treasury is amending the Global Terrorism Sanctions Regulations (``GTSR'') and the Terrorism Sanctions Regulations (``TSR'') to expand the scope of...

USA IN THE EMERGING SYSTEM OF GLOBAL FINANCIAL REGULATION

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V. K. Kulakova

2016-01-01

Full Text Available In the globalizing world of fi nancial and economic interdependence, a polycentric, multi-level, and hierarchical system of global financial regulation is emerging. The article highlights two vectors of recent development in international fi nancial regulation: the rise of cooperation through the mechanisms of the Group of Twenty (G-20 on the one hand, and the efforts to maintain the US leading role in global fi nance, on the other hand. In the circumstances of the global fi nancial crisis of 2008, the G-20 countries initiated an international reform of fi nancial regulation. According to G-20 decisions, international standardsetting organizations developed transnational regulatory regimes in the fi elds of banking, derivatives and bankruptcy resolution, and the states now implement these regimes in their jurisdictions. The so-called “soft law system”, which is not legally binding, allows the states to sustain national sovereignty in their fi nancial policy. The United States play a leading role in the international fi nancial reform, as well as in the shaping of the global fi nancial regulation system. The American regulators push for extraterritorial application of the US norms and take other unilateral actions on the international arena. The article also touches upon legitimacy problems of the emerging system of global fi nancial regulation. The most important constrains are the excessive infl uence of the fi nancial industry (“regulatory capture”, the weakness of civil society participation, and also the fact that for the rest of the world the American norms lack legitimacy, as they are adopted by regulators assigned by offi cials elected by population of a foreign territory.

Whole-gene positive selection, elevated synonymous substitution rates, duplication, and indel evolution of the chloroplast clpP1 gene.

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Per Erixon

Full Text Available BACKGROUND: Synonymous DNA substitution rates in the plant chloroplast genome are generally relatively slow and lineage dependent. Non-synonymous rates are usually even slower due to purifying selection acting on the genes. Positive selection is expected to speed up non-synonymous substitution rates, whereas synonymous rates are expected to be unaffected. Until recently, positive selection has seldom been observed in chloroplast genes, and large-scale structural rearrangements leading to gene duplications are hitherto supposed to be rare. METHODOLOGY/PRINCIPLE FINDINGS: We found high substitution rates in the exons of the plastid clpP1 gene in Oenothera (the Evening Primrose family and three separate lineages in the tribe Sileneae (Caryophyllaceae, the Carnation family. Introns have been lost in some of the lineages, but where present, the intron sequences have substitution rates similar to those found in other introns of their genomes. The elevated substitution rates of clpP1 are associated with statistically significant whole-gene positive selection in three branches of the phylogeny. In two of the lineages we found multiple copies of the gene. Neighboring genes present in the duplicated fragments do not show signs of elevated substitution rates or positive selection. Although non-synonymous substitutions account for most of the increase in substitution rates, synonymous rates are also markedly elevated in some lineages. Whereas plant clpP1 genes experiencing negative (purifying selection are characterized by having very conserved lengths, genes under positive selection often have large insertions of more or less repetitive amino acid sequence motifs. CONCLUSIONS/SIGNIFICANCE: We found positive selection of the clpP1 gene in various plant lineages to correlated with repeated duplication of the clpP1 gene and surrounding regions, repetitive amino acid sequences, and increase in synonymous substitution rates. The present study sheds light on the

Dissecting specific and global transcriptional regulation of bacterial gene expression

NARCIS (Netherlands)

Gerosa, Luca; Kochanowski, Karl; Heinemann, Matthias; Sauer, Uwe

Gene expression is regulated by specific transcriptional circuits but also by the global expression machinery as a function of growth. Simultaneous specific and global regulation thus constitutes an additional-but often neglected-layer of complexity in gene expression. Here, we develop an

Intrinsic limits to gene regulation by global crosstalk

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Friedlander, Tamar; Prizak, Roshan; Guet, Călin C.; Barton, Nicholas H.; Tkačik, Gašper

2016-01-01

Gene regulation relies on the specificity of transcription factor (TF)–DNA interactions. Limited specificity may lead to crosstalk: a regulatory state in which a gene is either incorrectly activated due to noncognate TF–DNA interactions or remains erroneously inactive. As each TF can have numerous interactions with noncognate cis-regulatory elements, crosstalk is inherently a global problem, yet has previously not been studied as such. We construct a theoretical framework to analyse the effects of global crosstalk on gene regulation. We find that crosstalk presents a significant challenge for organisms with low-specificity TFs, such as metazoans. Crosstalk is not easily mitigated by known regulatory schemes acting at equilibrium, including variants of cooperativity and combinatorial regulation. Our results suggest that crosstalk imposes a previously unexplored global constraint on the functioning and evolution of regulatory networks, which is qualitatively distinct from the known constraints that act at the level of individual gene regulatory elements. PMID:27489144

Global approaches to regulating electronic cigarettes

Science.gov (United States)

Kennedy, Ryan David; Awopegba, Ayodeji; De León, Elaine; Cohen, Joanna E

2017-01-01

Objectives Classify and describe the policy approaches used by countries to regulate e-cigarettes. Methods National policies regulating e-cigarettes were identified by (1) conducting web searches on Ministry of Health websites, and (2) broad web searches. The mechanisms used to regulate e-cigarettes were classified as new/amended laws, or existing laws. The policy domains identified include restrictions or prohibitions on product: sale, manufacturing, importation, distribution, use, product design including e-liquid ingredients, advertising/promotion/sponsorship, trademarks, and regulation requiring: taxation, health warning labels and child-safety standards. The classification of the policy was reviewed by a country expert. Results The search identified 68 countries that regulate e-cigarettes: 22 countries regulate e-cigarettes using existing regulations; 25 countries enacted new policies to regulate e-cigarettes; 7 countries made amendments to existing legislation; 14 countries use a combination of new/amended and existing regulation. Common policies include a minimum-age-of-purchase, indoor-use (vape-free public places) bans and marketing restrictions. Few countries are applying a tax to e-cigarettes. Conclusions A range of regulatory approaches are being applied to e-cigarettes globally; many countries regulate e-cigarettes using legislation not written for e-cigarettes. PMID:27903958

The ClpS-like N-domain is essential for the functioning of Ubr11, an N-recognin in Schizosaccharomyces pombe.

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Kitamura, Kenji

2014-01-01

Several Ubr ubiquitin ligases recognize the N-terminal amino acid of substrate proteins and promote their degradation via the Arg/N-end rule pathway. The primary destabilizing N-terminal amino acids in yeast are classified into type 1 (Arg, Lys, and His) and type 2 (Phe, Trp, Tyr, Leu, Ile, and Met-Ф) residues. The type 1 and type 2 residues bind to the UBR box and the ClpS/N-domain, respectively, in canonical Ubr ubiquitin ligases that act as N-recognins. In this study, the requirement for type 1 and type 2 amino acid recognition by Schizosaccharomyces pombe Ubr11 was examined in vivo. Consistent with the results of previous studies, the ubr11∆ null mutant was found to be defective in oligopeptide uptake and resistant to ergosterol synthesis inhibitors. Furthermore, the ubr11∆ mutant was also less sensitive to some protein synthesis inhibitors. A ubr11 ClpS/N-domain mutant, which retained ubiquitin ligase activity but could not recognize type 2 amino acids, phenocopied all known defects of the ubr11∆ mutant. However, the recognition of type 1 residues by Ubr11 was not required for its functioning, and no severe physiological abnormalities were observed in a ubr11 mutant defective in the recognition of type 1 residues. These results reinforce the fundamental importance of the ClpS/N-domain for the functioning of the N-recognin, Ubr11.

Differential regulation of tissue thiol-disulfide redox status in a murine model of peritonitis

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Benton Shana M

2012-10-01

Full Text Available Abstract Background Glutathione (GSH/glutathione disulfide (GSSG and cysteine (Cys/cystine (CySS are major redox pools with important roles in cytoprotection. We determined the impact of septic peritonitis on thiol-disulfide redox status in mice. Methods FVB/N mice (6–12 week old; 8/group underwent laparotomy with cecal ligation and puncture (CLP or laparotomy alone (control. Sections of ileum, colon, lung and liver were obtained and GSH, GSSG, Cys and CySS concentrations determined by HPLC 24 h after laparotomy. Redox potential [Eh in millivolts (mV] of the GSH/GSSG and Cys/CySS pools was calculated using the Nernst equation. Data were analyzed by ANOVA (mean ± SE. Results GSH/GSSG Eh in ileum, colon, and liver was significantly oxidized in septic mice versus control mice (ileum: septic −202±4 versus control −228±2 mV; colon: -195±8 versus −214±1 mV; and liver: -194±3 vs. -210±1 mV, all Ph was unchanged with CLP, while liver and lung Cys/CySS Eh became significantly more reducing (liver: septic = −103±3 versus control −90±2 mV; lung: -101±5 versus −81±1 mV, each P Conclusions Septic peritonitis induced by CLP oxidizes ileal and colonic GSH/GSSG redox but Cys/CySS Eh remains unchanged in these intestinal tissues. In liver, CLP oxidizes the GSH/GSSG redox pool and CyS/CySS Eh becomes more reducing; in lung, CLP does not alter GSH/GSSG Eh, and Cys/CySS Eh is less oxidized. CLP-induced infection/inflammation differentially regulates major thiol-disulfide redox pools in this murine model.

Global pharmaceutical regulation: the challenge of integration for developing states.

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Pezzola, Anthony; Sweet, Cassandra M

2016-12-20

This paper has set out to map the state of pharmaceutical regulation in the developing world through the construction of cross-national indices drawing from World Health Organization data. The last two decades have been characterized by deep changes for the pharmaceutical sector, including the complete transformation of intellectual property systems at the behest of the World Trade Organization and the consolidation of global active ingredient suppliers in China and India. Although the rules for ownership of medicine have been set and globally implemented, we know surprisingly little about how the standards for market entrance and regulation of pharmaceutical products have changed at the national level. How standardized are national pharmaceutical market systems? Do we find homogeneity or variation across the developing world? Are their patterns for understanding why some countries have moved closer to one global norm for pharmaceutical regulation and others have developed hybrid models for oversight of this sector? Access to medicine is a core tool in public health. This paper gauges the levels of standards in public and private generics markets for developing countries building on national-level pharmaceutical market surveys for 78 countries to offer three indicators of market oversight: State Regulatory Infrastructure, Monitoring the Private Market and Public Quality Control. Identifying the different variables that affect a state's institutional capacity and current standard level offers new insights to the state of pharmaceuticals in the developing world. It is notable that there are very few (none at the time of this paper) studies that map out the new global terrain for pharmaceutical regulation in the post-TRIPS context. This paper uses item response theory to develop original indicators of pharmaceutical regulation. We find remarkable resistance to the implementation of global pharmaceutical norms for quality standards in developing states and in

Local and global responses in complex gene regulation networks

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Tsuchiya, Masa; Selvarajoo, Kumar; Piras, Vincent; Tomita, Masaru; Giuliani, Alessandro

2009-04-01

An exacerbated sensitivity to apparently minor stimuli and a general resilience of the entire system stay together side-by-side in biological systems. This apparent paradox can be explained by the consideration of biological systems as very strongly interconnected network systems. Some nodes of these networks, thanks to their peculiar location in the network architecture, are responsible for the sensitivity aspects, while the large degree of interconnection is at the basis of the resilience properties of the system. One relevant feature of the high degree of connectivity of gene regulation networks is the emergence of collective ordered phenomena influencing the entire genome and not only a specific portion of transcripts. The great majority of existing gene regulation models give the impression of purely local ‘hard-wired’ mechanisms disregarding the emergence of global ordered behavior encompassing thousands of genes while the general, genome wide, aspects are less known. Here we address, on a data analysis perspective, the discrimination between local and global scale regulations, this goal was achieved by means of the examination of two biological systems: innate immune response in macrophages and oscillating growth dynamics in yeast. Our aim was to reconcile the ‘hard-wired’ local view of gene regulation with a global continuous and scalable one borrowed from statistical physics. This reconciliation is based on the network paradigm in which the local ‘hard-wired’ activities correspond to the activation of specific crucial nodes in the regulation network, while the scalable continuous responses can be equated to the collective oscillations of the network after a perturbation.

Aflatoxin regulations and global pistachio trade: insights from social network analysis.

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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.

Down-regulation of E protein activity augments an ILC2 differentiation program in the thymus

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Innate lymphoid cells (ILCs) are important regulators in various immune responses. Current paradigm states that all newly-made ILCs originate from common lymphoid progenitors (CLP) in the bone marrow. Id2, an inhibitor of E protein transcription factors, is indispensable for ILC differentiation. Une...

Global health security and the International Health Regulations

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Oliva Otavio

2010-12-01

Full Text Available Abstract Global nuclear proliferation, bioterrorism, and emerging infections have challenged national capacities to achieve and maintain global security. Over the last century, emerging infectious disease threats resulted in the development of the preliminary versions of the International Health Regulations (IHR of the World Health Organization (WHO. The current HR(2005 contain major differences compared to earlier versions, including: substantial shifts from containment at the border to containment at the source of the event; shifts from a rather small disease list (smallpox, plague, cholera, and yellow fever required to be reported, to all public health threats; and shifts from preset measures to tailored responses with more flexibility to deal with the local situations on the ground. The new IHR(2005 call for accountability. They also call for strengthened national capacity for surveillance and control; prevention, alert, and response to international public health emergencies beyond the traditional short list of required reporting; global partnership and collaboration; and human rights, obligations, accountability, and procedures of monitoring. Under these evolved regulations, as well as other measures, such as the Revolving Fund for vaccine procurement of the Pan American Health Organization (PAHO, global health security could be maintained in the response to urban yellow fever in Paraguay in 2008 and the influenza (H1N1 pandemic of 2009-2010.

In the shadow of the Cosmetic Directive — Inconsistencies in EU environmental hazard classification requirements for UV-filters

International Nuclear Information System (INIS)

Sobek, A.; Bejgarn, S.; Rudén, C.; Molander, L.; Breitholtz, M.

2013-01-01

UV-filters are chemicals with potentially environmental hazardous properties. In the European Union (EU), UV-filters contained in sunscreen products are currently regulated by the Cosmetic Directive (from July 2013 by the Cosmetic Products Regulation). Environmental hazard classifications according to the regulation on classification, labelling and packaging of substances and mixtures (CLP) must be determined for UV-filters contained in industrial chemical products, whereas UV-filters contained in sunscreens are exempted from CLP. In this study we determined the potential environmental hazard classifications of UV-filters and sunscreen products if the CLP regulation was to be required for cosmetic products. Two sunscreen products were evaluated in accordance with the aquatic environmental hazard criteria for mixtures. The results highlight that the inconsistencies in the current EU regulation of UV filters hamper the risk management of environmental hazards of UV filters used in cosmetic products. Almost 50% of the investigated UV-filters approved for use in cosmetic products on the European market according to the current Cosmetic Directive were identified to meet the CLP classification as being hazardous to the aquatic environment. Assuming a worst-case scenario, the two examined sunscreens could both be classified as hazardous to the aquatic environment with long-lasting effects according to CLP classification criteria. Hence, if the CLP regulation was applicable to sunscreen products, both brands could potentially be labelled with the environmental hazard pictogram and associated hazard and precautionary statements. Including cosmetic products, and thereby sunscreens, in the CLP regulation would contribute to a more harmonized and transparent regulation of potentially hazardous substances on the EU market. - Highlights: • UV-filters are used in both cosmetic and industrial products/applications • UV-filters in cosmetic products are excluded from CLP • We

Fairness through regulation? Reflections on a cosmopolitan approach to global finance

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Marta Božina Beroš

2013-11-01

Full Text Available In the aftermath of the last financial crisis a strong message prevails that ‘something’ has to be changed in the manner global finance is governed. What exactly this ‘something’ entails and what could constitute the ‘common ground’ of anticipated change is more difficult to determine. Many envisage future improvements of global financial governance by evoking deliberative democracy, political equality and cosmopolitanism. As financial regulation is the main instrument through which global finance is shaped and governed nowadays, these principles should then be transmitted to regulatory arrangements. This paper focuses on a new conceptual approach to regulatory and governance issues in global finance, by employing the philosophical idea of cosmopolitanism. It argues that although as a concept, cosmopolitanism cannot mitigate all the flaws attributed to contemporary finance, its development and extension to international financial regulation that is promulgated by institutions of the global financial system, would represent a worthwhile endeavour in making global finance more accountable and just in the eyes of many.

The collectins CL-L1, CL-K1 and CL-P1, and their roles in complement and innate immunity

DEFF Research Database (Denmark)

Hansen, Soren W K; Ohtani, Katsuki; Roy, Nitai

2016-01-01

as CL-LK) and its activation of the lectin pathway via MASPs, drew new attention in the complement biology, which was further strengthened by the observed interactions between CL-P1 and CRP-C1q-factor H or properdin. Deficiency of either CL-K1 or MASP-3 has been demonstrated in 3MC syndrome patients...

Fair Trade: Social Regulation in Global Food Markets

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Raynolds, Laura T.

2012-01-01

This article analyzes the theoretical and empirical parameters of social regulation in contemporary global food markets, focusing on the rapidly expanding Fair Trade initiative. Fair Trade seeks to transform North/South relations by fostering ethical consumption, producer empowerment, and certified commodity sales. This initiative joins an array…

Lassomycin, a ribosomally synthesized cyclic peptide, kills mycobacterium tuberculosis by targeting the ATP-dependent protease ClpC1P1P2.

Science.gov (United States)

Gavrish, Ekaterina; Sit, Clarissa S; Cao, Shugeng; Kandror, Olga; Spoering, Amy; Peoples, Aaron; Ling, Losee; Fetterman, Ashley; Hughes, Dallas; Bissell, Anthony; Torrey, Heather; Akopian, Tatos; Mueller, Andreas; Epstein, Slava; Goldberg, Alfred; Clardy, Jon; Lewis, Kim

2014-04-24

Languishing antibiotic discovery and flourishing antibiotic resistance have prompted the development of alternative untapped sources for antibiotic discovery, including previously uncultured bacteria. Here, we screen extracts from uncultured species against Mycobacterium tuberculosis and identify lassomycin, an antibiotic that exhibits potent bactericidal activity against both growing and dormant mycobacteria, including drug-resistant forms of M. tuberculosis, but little activity against other bacteria or mammalian cells. Lassomycin is a highly basic, ribosomally encoded cyclic peptide with an unusual structural fold that only partially resembles that of other lasso peptides. We show that lassomycin binds to a highly acidic region of the ClpC1 ATPase complex and markedly stimulates its ATPase activity without stimulating ClpP1P2-catalyzed protein breakdown, which is essential for viability of mycobacteria. This mechanism, uncoupling ATPase from proteolytic activity, accounts for the bactericidal activity of lassomycin. Copyright © 2014 Elsevier Ltd. All rights reserved.

Intrinsic limits to gene regulation by global crosstalk

Science.gov (United States)

Friedlander, Tamar; Prizak, Roshan; Guet, Calin; Barton, Nicholas H.; Tkacik, Gasper

Gene activity is mediated by the specificity of binding interactions between special proteins, called transcription factors, and short regulatory sequences on the DNA, where different protein species preferentially bind different DNA targets. Limited interaction specificity may lead to crosstalk: a regulatory state in which a gene is either incorrectly activated due to spurious interactions or remains erroneously inactive. Since each protein can potentially interact with numerous DNA targets, crosstalk is inherently a global problem, yet has previously not been studied as such. We construct a theoretical framework to analyze the effects of global crosstalk on gene regulation, using statistical mechanics. We find that crosstalk in regulatory interactions puts fundamental limits on the reliability of gene regulation that are not easily mitigated by tuning proteins concentrations or by complex regulatory schemes proposed in the literature. Our results suggest that crosstalk imposes a previously unexplored global constraint on the functioning and evolution of regulatory networks, which is qualitatively distinct from the known constraints that act at the level of individual gene regulatory elements. The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA Grant agreement Nr. 291734 (T.F.) and ERC Grant Nr. 250152 (N.B.).

Local flow regulation and irrigation raise global human water consumption and footprint.

Science.gov (United States)

Jaramillo, Fernando; Destouni, Georgia

2015-12-04

Flow regulation and irrigation alter local freshwater conditions, but their global effects are highly uncertain. We investigated these global effects from 1901 to 2008, using hydroclimatic observations in 100 large hydrological basins. Globally, we find consistent and dominant effects of increasing relative evapotranspiration from both activities, and decreasing temporal runoff variability from flow regulation. The evapotranspiration effect increases the long-term average human consumption of fresh water by 3563 ± 979 km(3)/year from 1901-1954 to 1955-2008. This increase raises a recent estimate of the current global water footprint of humanity by around 18%, to 10,688 ± 979 km(3)/year. The results highlight the global impact of local water-use activities and call for their relevant account in Earth system modeling. Copyright © 2015, American Association for the Advancement of Science.

Elements in nucleotide sensing and hydrolysis of the AAA+ disaggregation machine ClpB: a structure-based mechanistic dissection of a molecular motor

Energy Technology Data Exchange (ETDEWEB)

Zeymer, Cathleen, E-mail: cathleen.zeymer@mpimf-heidelberg.mpg.de; Barends, Thomas R. M.; Werbeck, Nicolas D.; Schlichting, Ilme; Reinstein, Jochen, E-mail: cathleen.zeymer@mpimf-heidelberg.mpg.de [Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg (Germany)

2014-02-01

High-resolution crystal structures together with mutational analysis and transient kinetics experiments were utilized to understand nucleotide sensing and the regulation of the ATPase cycle in an AAA+ molecular motor. ATPases of the AAA+ superfamily are large oligomeric molecular machines that remodel their substrates by converting the energy from ATP hydrolysis into mechanical force. This study focuses on the molecular chaperone ClpB, the bacterial homologue of Hsp104, which reactivates aggregated proteins under cellular stress conditions. Based on high-resolution crystal structures in different nucleotide states, mutational analysis and nucleotide-binding kinetics experiments, the ATPase cycle of the C-terminal nucleotide-binding domain (NBD2), one of the motor subunits of this AAA+ disaggregation machine, is dissected mechanistically. The results provide insights into nucleotide sensing, explaining how the conserved sensor 2 motif contributes to the discrimination between ADP and ATP binding. Furthermore, the role of a conserved active-site arginine (Arg621), which controls binding of the essential Mg{sup 2+} ion, is described. Finally, a hypothesis is presented as to how the ATPase activity is regulated by a conformational switch that involves the essential Walker A lysine. In the proposed model, an unusual side-chain conformation of this highly conserved residue stabilizes a catalytically inactive state, thereby avoiding unnecessary ATP hydrolysis.

Elements in nucleotide sensing and hydrolysis of the AAA+ disaggregation machine ClpB: a structure-based mechanistic dissection of a molecular motor

International Nuclear Information System (INIS)

Zeymer, Cathleen; Barends, Thomas R. M.; Werbeck, Nicolas D.; Schlichting, Ilme; Reinstein, Jochen

2014-01-01

High-resolution crystal structures together with mutational analysis and transient kinetics experiments were utilized to understand nucleotide sensing and the regulation of the ATPase cycle in an AAA+ molecular motor. ATPases of the AAA+ superfamily are large oligomeric molecular machines that remodel their substrates by converting the energy from ATP hydrolysis into mechanical force. This study focuses on the molecular chaperone ClpB, the bacterial homologue of Hsp104, which reactivates aggregated proteins under cellular stress conditions. Based on high-resolution crystal structures in different nucleotide states, mutational analysis and nucleotide-binding kinetics experiments, the ATPase cycle of the C-terminal nucleotide-binding domain (NBD2), one of the motor subunits of this AAA+ disaggregation machine, is dissected mechanistically. The results provide insights into nucleotide sensing, explaining how the conserved sensor 2 motif contributes to the discrimination between ADP and ATP binding. Furthermore, the role of a conserved active-site arginine (Arg621), which controls binding of the essential Mg 2+ ion, is described. Finally, a hypothesis is presented as to how the ATPase activity is regulated by a conformational switch that involves the essential Walker A lysine. In the proposed model, an unusual side-chain conformation of this highly conserved residue stabilizes a catalytically inactive state, thereby avoiding unnecessary ATP hydrolysis

Structural and Molecular Mechanism of CdpR Involved in Quorum-Sensing and Bacterial Virulence in Pseudomonas aeruginosa.

Directory of Open Access Journals (Sweden)

Jingru Zhao

2016-04-01

Full Text Available Although quorum-sensing (QS systems are important regulators of virulence gene expression in the opportunistic human pathogen Pseudomonas aeruginosa, their detailed regulatory mechanisms have not been fully characterized. Here, we show that deletion of PA2588 resulted in increased production of pyocyanin and biofilm, as well as enhanced pathogenicity in a mouse model. To gain insights into the function of PA2588, we performed a ChIP-seq assay and identified 28 targets of PA2588, including the intergenic region between PA2588 and pqsH, which encodes the key synthase of Pseudomonas quinolone signal (PQS. Though the C-terminal domain was similar to DNA-binding regions of other AraC family members, structural studies revealed that PA2588 has a novel fold at the N-terminal region (NTR, and its C-terminal HTH (helix-turn-helix domain is also unique in DNA recognition. We also demonstrated that the adaptor protein ClpS, an essential regulator of ATP-dependent protease ClpAP, directly interacted with PA2588 before delivering CdpR to ClpAP for degradation. We named PA2588 as CdpR (ClpAP-degradation and pathogenicity Regulator. Moreover, deletion of clpP or clpS/clpA promotes bacterial survival in a mouse model of acute pneumonia infection. Taken together, this study uncovered that CdpR is an important QS regulator, which can interact with the ClpAS-P system to regulate the expression of virulence factors and pathogenicity.

Structural pathway of regulated substrate transfer and threading through an Hsp100 disaggregase.

Science.gov (United States)

Deville, Célia; Carroni, Marta; Franke, Kamila B; Topf, Maya; Bukau, Bernd; Mogk, Axel; Saibil, Helen R

2017-08-01

Refolding aggregated proteins is essential in combating cellular proteotoxic stress. Together with Hsp70, Hsp100 chaperones, including Escherichia coli ClpB, form a powerful disaggregation machine that threads aggregated polypeptides through the central pore of tandem adenosine triphosphatase (ATPase) rings. To visualize protein disaggregation, we determined cryo-electron microscopy structures of inactive and substrate-bound ClpB in the presence of adenosine 5'- O -(3-thiotriphosphate), revealing closed AAA+ rings with a pronounced seam. In the substrate-free state, a marked gradient of resolution, likely corresponding to mobility, spans across the AAA+ rings with a dynamic hotspot at the seam. On the seam side, the coiled-coil regulatory domains are locked in a horizontal, inactive orientation. On the opposite side, the regulatory domains are accessible for Hsp70 binding, substrate targeting, and activation. In the presence of the model substrate casein, the polypeptide threads through the entire pore channel and increased nucleotide occupancy correlates with higher ATPase activity. Substrate-induced domain displacements indicate a pathway of regulated substrate transfer from Hsp70 to the ClpB pore, inside which a spiral of loops contacts the substrate. The seam pore loops undergo marked displacements, along with ordering of the regulatory domains. These asymmetric movements suggest a mechanism for ATPase activation and substrate threading during disaggregation.

Arbitrage and Competition in Global Financial Regulation

DEFF Research Database (Denmark)

Ringe, Wolf-Georg

Regulatory arbitrage in financial markets refers to a number of strategies that market participants use to avoid the reach of regulation, in particular by virtue of shifting trading abroad or else relocating activities or operations of financial institutions to other jurisdictions. Where...... institutions’ excessive risk-taking. If such risk-taking would be judged by market discipline instead of posing a risk to global financial stability, the main downside of regulatory competition could be restrained. Within the boundaries of such a system, competition could then operate and contribute...... their standards solely to attract businesses and thereby impose externalities on the worldwide financial market by undermining financial stability as a global public good. Policymakers worldwide are experimenting with remedies to respond to the phenomenon. I introduce the importance of an effective special...

Impact of global warming on the energetics of lower tropospheric ...

Indian Academy of Sciences (India)

Two oceanic anticyclones, one over Pacific and the other over Atlantic are sources of energy ... Northward transport of sensible heat during CLP1 changes to southward during CLP2. Larger ... tion because of its impact on the regional climate.

In the shadow of the Cosmetic Directive--inconsistencies in EU environmental hazard classification requirements for UV-filters.

Science.gov (United States)

Sobek, A; Bejgarn, S; Rudén, C; Molander, L; Breitholtz, M

2013-09-01

UV-filters are chemicals with potentially environmental hazardous properties. In the European Union (EU), UV-filters contained in sunscreen products are currently regulated by the Cosmetic Directive (from July 2013 by the Cosmetic Products Regulation). Environmental hazard classifications according to the regulation on classification, labelling and packaging of substances and mixtures (CLP) must be determined for UV-filters contained in industrial chemical products, whereas UV-filters contained in sunscreens are exempted from CLP. In this study we determined the potential environmental hazard classifications of UV-filters and sunscreen products if the CLP regulation was to be required for cosmetic products. Two sunscreen products were evaluated in accordance with the aquatic environmental hazard criteria for mixtures. The results highlight that the inconsistencies in the current EU regulation of UV filters hamper the risk management of environmental hazards of UV filters used in cosmetic products. Almost 50% of the investigated UV-filters approved for use in cosmetic products on the European market according to the current Cosmetic Directive were identified to meet the CLP classification as being hazardous to the aquatic environment. Assuming a worst-case scenario, the two examined sunscreens could both be classified as hazardous to the aquatic environment with long-lasting effects according to CLP classification criteria. Hence, if the CLP regulation was applicable to sunscreen products, both brands could potentially be labelled with the environmental hazard pictogram and associated hazard and precautionary statements. Including cosmetic products, and thereby sunscreens, in the CLP regulation would contribute to a more harmonized and transparent regulation of potentially hazardous substances on the EU market. Copyright © 2013 Elsevier B.V. All rights reserved.

Role of Glycolytic Intermediates in Global Regulation and Signal Transduction. Final Report

Energy Technology Data Exchange (ETDEWEB)

Liao, J.C.

2000-05-08

The goal of this project is to determine the role of glycolytic intermediates in regulation of cell physiology. It is known that many glycolytic intermediates are involved in regulation of enzyme activities at the kinetic level. However, little is known regarding the role of these metabolites in global regulation and signal transduction. This project aims to investigate the role of glycolytic intermediates in the regulation of gene expression.

[Preliminary study on self-concept psychological feature of cleft lip and palate adolescents].

Science.gov (United States)

Liao, Rui; Zheng, Qian; Shi, Bing; Wang, Yan; Li, Ling; Dong, Rui; Shi, Jin; Yang, Chao

2006-06-01

To obtain the self-concept psychological feature of cleft lip and palate (CLP) adolescents further and accurately, and offer reasons for timely and pointed psychological intervention. Based on the procedure and criteria of development of psychological questionnaire, a psychological questionnaire for CLP adolescents was designed. 93 CLP and 88 healthy adolescents were studied by using it and their half-quantified score raging 0-9 were analyzed statistically. (1) There was no statistical difference between CLP and normal adolescents, scored 5.91 and 5.66 respectively, which demonstrated that the self-concept of CLP adolescents was at a normal level without obvious passive tendency. (2) There was no significant difference between genders, but boys were more extroversion while girls did better on being unyielding and releasing strain. (3) CLP adolescents had a higher ability of psychological regulation and could face failure more bravely. CLP patients were in a tendency of protective behavior inhibition, companied less, and maximized delight mood unconsciously to decrease harm from enviroment. (4) CLP adolescents had a good parentage. (5) A majority of patients had low expectation of life-quality. (6) Much of CLP patients considered that speech was more important than appearance. Self-concept of CLP adolescents have normal self-concept and do better in psychological regulation and dependence than normal ones.

Plate tectonic regulation of global marine animal diversity

Science.gov (United States)

Zaffos, Andrew; Finnegan, Seth; Peters, Shanan E.

2017-05-01

Valentine and Moores [Valentine JW, Moores EM (1970) Nature 228:657-659] hypothesized that plate tectonics regulates global biodiversity by changing the geographic arrangement of continental crust, but the data required to fully test the hypothesis were not available. Here, we use a global database of marine animal fossil occurrences and a paleogeographic reconstruction model to test the hypothesis that temporal patterns of continental fragmentation have impacted global Phanerozoic biodiversity. We find a positive correlation between global marine invertebrate genus richness and an independently derived quantitative index describing the fragmentation of continental crust during supercontinental coalescence-breakup cycles. The observed positive correlation between global biodiversity and continental fragmentation is not readily attributable to commonly cited vagaries of the fossil record, including changing quantities of marine rock or time-variable sampling effort. Because many different environmental and biotic factors may covary with changes in the geographic arrangement of continental crust, it is difficult to identify a specific causal mechanism. However, cross-correlation indicates that the state of continental fragmentation at a given time is positively correlated with the state of global biodiversity for tens of millions of years afterward. There is also evidence to suggest that continental fragmentation promotes increasing marine richness, but that coalescence alone has only a small negative or stabilizing effect. Together, these results suggest that continental fragmentation, particularly during the Mesozoic breakup of the supercontinent Pangaea, has exerted a first-order control on the long-term trajectory of Phanerozoic marine animal diversity.

The role of ClpP, RpoS and CsrA in growth and filament formation of Salmonella enterica serovar Typhimurium at low temperature

DEFF Research Database (Denmark)

Knudsen, Gitte Maegaard; Nielsen, Maj-Britt; Thomsen, Line Elnif

2014-01-01

that the phenotype of the csrA mutant was independent from RpoS. Conclusions: The cold sensitivity of clpP mutant was associated with increased levels of RpoS and probably caused by toxic levels of RpoS. Although a csrA mutant also accumulated high level of RpoS, growth impairment caused by lack of csr...

Future development of global regulations of Chinese herbal products.

Science.gov (United States)

Fan, Tai-Ping; Deal, Greer; Koo, Hoi-Lun; Rees, Daryl; Sun, He; Chen, Shaw; Dou, Jin-Hui; Makarov, Valery G; Pozharitskaya, Olga N; Shikov, Alexander N; Kim, Yeong Shik; Huang, Yi-Tsau; Chang, Yuan Shiun; Jia, William; Dias, Alberto; Wong, Vivian Chi-Woon; Chan, Kelvin

2012-04-10

GP-TCM is the first EU-funded Coordination Action consortium dedicated to traditional Chinese medicine (TCM) research. One of the key deliverables of the Work Package 7 in GP-TCM was to investigate information of the existing requirements for registration of TCM products listed by global regulatory bodies. The paper aims to collate data and draw comparison of these regulations. Case studies are also presented to illustrate the problems involved in registering TCM products in different regions worldwide. A collaborative network task force was established during the early stage of the GP-TCM project and operated through exchanges, teleconferences and focused discussions at annual meetings. The task force involved coordinators, academics who are actively involved with R&D of Chinese herbal medicines, experts on monographic standards of Chinese materia medica, representatives from regulatory agencies, experts from industries in marketing Chinese medicines/herbal medicines and natural products. The co-ordinators took turns to chair teleconferences, led discussions on specific issues at AGM discussion sessions, at joint workshops with other work-packages such as WP1 (quality issues), WP3 (toxicology issues) and WP6 (clinical trial issues). Collectively the authors were responsible for collating discussion outcomes and updating written information. A global overview of regulations on herbal registration has been compiled during the three years of the consortium. The regulatory requirements for registration of herbal products in the EU and China were compared, and this is extended to other regions/countries: Africa, Australia, Brazil, Canada, Japan, Russia, South Korea, Taiwan, and the United States. A wide variation of the regulations for the categories of herbal products exists: food (functional food, novel foods, dietary food for special medical purpose, foods for particular nutritional use, food supplement); cosmetic, traditional herbal medicine products; herbal

Chokepoints global private regulation on the Internet

CERN Document Server

Tusikov, Natasha

2016-01-01

In January 2012, millions participated in the now-infamous "Internet blackout" against the Stop Online Piracy Act, protesting the power it would have given intellectual property holders over the Internet. However, while SOPA's withdrawal was heralded as a victory for an open Internet, a small group of corporations, tacitly backed by the US and other governments, have implemented much of SOPA via a series of secret, handshake agreements. Drawing on extensive interviews, Natasha Tusikov details the emergence of a global regime in which large Internet firms act as regulators for powerful intellec

Globalization of health insecurity: the World Health Organization and the new International Health Regulations.

Science.gov (United States)

Aginam, Obijiofor

2006-12-01

The transnational spread of communicable and non-communicable diseases has opened new vistas in the discourse of global health security. Emerging and re-emerging pathogens, according to exponents of globalization of public health, disrespect the geo-political boundaries of nation-states. Despite the global ramifications of health insecurity in a globalizing world, contemporary international law still operates as a classic inter-state law within an international system exclusively founded on a coalition of nation-states. This article argues that the dynamic process of globalization has created an opportunity for the World Health Organization to develop effective synergy with a multiplicity of actors in the exercise of its legal powers. WHO's legal and regulatory strategies must transform from traditional international legal approaches to disease governance to a "post-Westphalian public health governance": the use of formal and informal sources from state and non-state actors, hard law (treaties and regulations) and soft law (recommendations and travel advisories) in global health governance. This article assesses the potential promise and problems of WHO's new International Health Regulations (IHR) as a regulatory strategy for global health governance and global health security.

The early activation marker CD69 regulates the expression of chemokines and CD4 T cell accumulation in intestine.

Directory of Open Access Journals (Sweden)

Katarina Radulovic

Full Text Available Migration of naïve and activated lymphocytes is regulated by the expression of various molecules such as chemokine receptors and ligands. CD69, the early activation marker of C-type lectin domain family, is also shown to regulate the lymphocyte migration by affecting their egress from the thymus and secondary lymphoid organs. Here, we aimed to investigate the role of CD69 in accumulation of CD4 T cells in intestine using murine models of inflammatory bowel disease. We found that genetic deletion of CD69 in mice increases the expression of the chemokines CCL-1, CXCL-10 and CCL-19 in CD4(+ T cells and/or CD4(- cells. Efficient in vitro migration of CD69-deficient CD4 T cells toward the chemokine stimuli was the result of increased expression and/or affinity of chemokine receptors. In vivo CD69(-/- CD4 T cells accumulate in the intestine in higher numbers than B6 CD4 T cells as observed in competitive homing assay, dextran sodium sulphate (DSS-induced colitis and antigen-specific transfer colitis. In DSS colitis CD69(-/- CD4 T cell accumulation in colonic lamina propria (cLP was associated with increased expression of CCL-1, CXCL-10 and CCL-19 genes. Furthermore, treatment of DSS-administrated CD69(-/- mice with the mixture of CCL-1, CXCL-10 and CCL-19 neutralizing Abs significantly decreased the histopathological signs of colitis. Transfer of OT-II×CD69(-/- CD45RB(high CD4 T cells into RAG(-/- hosts induced CD4 T cell accumulation in cLP. This study showed CD69 as negative regulator of inflammatory responses in intestine as it decreases the expression of chemotactic receptors and ligands and reduces the accumulation of CD4 T cells in cLP during colitis.

Boolean models of biosurfactants production in Pseudomonas fluorescens.

Directory of Open Access Journals (Sweden)

Adrien Richard

Full Text Available Cyclolipopeptides (CLPs are biosurfactants produced by numerous Pseudomonas fluorescens strains. CLP production is known to be regulated at least by the GacA/GacS two-component pathway, but the full regulatory network is yet largely unknown. In the clinical strain MFN1032, CLP production is abolished by a mutation in the phospholipase C gene (plcC and not restored by plcC complementation. Their production is also subject to phenotypic variation. We used a modelling approach with Boolean networks, which takes into account all these observations concerning CLP production without any assumption on the topology of the considered network. Intensive computation yielded numerous models that satisfy these properties. All models minimizing the number of components point to a bistability in CLP production, which requires the presence of a yet unknown key self-inducible regulator. Furthermore, all suggest that a set of yet unexplained phenotypic variants might also be due to this epigenetic switch. The simplest of these Boolean networks was used to propose a biological regulatory network for CLP production. This modelling approach has allowed a possible regulation to be unravelled and an unusual behaviour of CLP production in P. fluorescens to be explained.

Increased Global Interaction Across Functional Brain Modules During Cognitive Emotion Regulation.

Science.gov (United States)

Brandl, Felix; Mulej Bratec, Satja; Xie, Xiyao; Wohlschläger, Afra M; Riedl, Valentin; Meng, Chun; Sorg, Christian

2017-07-13

Cognitive emotion regulation (CER) enables humans to flexibly modulate their emotions. While local theories of CER neurobiology suggest interactions between specialized local brain circuits underlying CER, e.g., in subparts of amygdala and medial prefrontal cortices (mPFC), global theories hypothesize global interaction increases among larger functional brain modules comprising local circuits. We tested the global CER hypothesis using graph-based whole-brain network analysis of functional MRI data during aversive emotional processing with and without CER. During CER, global between-module interaction across stable functional network modules increased. Global interaction increase was particularly driven by subregions of amygdala and cuneus-nodes of highest nodal participation-that overlapped with CER-specific local activations, and by mPFC and posterior cingulate as relevant connector hubs. Results provide evidence for the global nature of human CER, complementing functional specialization of embedded local brain circuits during successful CER. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Anti-sigma factor YlaD regulates transcriptional activity of sigma factor YlaC and sporulation via manganese-dependent redox-sensing molecular switch in Bacillus subtilis.

Science.gov (United States)

Kwak, Min-Kyu; Ryu, Han-Bong; Song, Sung-Hyun; Lee, Jin-Won; Kang, Sa-Ouk

2018-05-14

YlaD, a membrane-anchored anti-sigma factor of Bacillus subtilis , contains a HX 3 CXXC motif that functions as a redox-sensing domain and belongs to one of the zinc-coordinated anti-sigma factor families. Despite previously showing that the YlaC transcription is controlled by YlaD, experimental evidence of how the YlaC-YlaD interaction is affected by active cysteines and/or metal ions is lacking. Here, we showed that the P yla promoter is autoregulated solely by YlaC. Moreover, reduced YlaD contained zinc and iron, while oxidized YlaD did not. Cysteine substitution in YlaD led to changes in its secondary structure; Cys3 had important structural functions in YlaD, and its mutation caused dissociation from YlaC, indicating the essential requirement of a HX 3 CXXC motif for regulating interactions of YlaC with YlaD. Analyses of the far-UV CD spectrum and metal content revealed that the addition of Mn ions to Zn-YlaD changed its secondary structure and that iron was substituted for manganese. The ylaC gene expression using βGlu activity from P yla : gusA was observed at the late-exponential and early-stationary phase and the ylaC -overexpressing mutant constitutively expressed gene transcripts of clpP and sigH , an important alternative sigma factor regulated by ClpXP. Collectively, our data demonstrated that YlaD senses redox changes and elicits increase in manganese ion concentrations and that, in turn, YlaD-mediated transcriptional activity of YlaC regulates sporulation initiation under oxidative stress and manganese-substituted conditions by regulating clpP gene transcripts. This is the first report of the involvement of oxidative stress-responsive B. subtilis extracytoplasmic function sigma factors during sporulation via a manganese-dependent redox-sensing molecular switch. ©2018 The Author(s).

Impact of Char Livelihood Program (CLP of Char land Dwellers around the Char Areas in Sirajgonj District of Bangladesh

Directory of Open Access Journals (Sweden)

Mohammad Anamul Haque

2017-12-01

Full Text Available In an attempt to address the impact of Char Livelihood Program (CLP of Char land dwellers, this study is carried out to examine the livelihood and income generation activities of the people of Bangala Char in Sirajgonj District, due to intervention of Char Livelihood Program (CLP by the DFID of United Kingdom (UK. The research question of the study was whether and to what extent the Char Livelihood Program (CLP brings any changes in the livelihood and income generation activities of the people of Bangala Char. Two areas have been studied, one area is under the intervention of the project (Bangala Char as program intervention area another is not under the program intervention (Sonatoni Char as control area. Both areas have been chosen of the vicinity of similar characteristics and geographical location for the ease of addressing the problems and analytical comparison. The study uses semi-structured questionnaire for household interview both for the program intervention and the control area as random sampling basis. This study a total of 96 households’ interviews conducted of the study areas among them 48 households from Bangala Char and 48 households from the Sonatoni Char (control area. Primary data collected from house hold respondent and secondary data were used from published and unpublished sources. Four variables are access to land, income and assets , food security and vulnerability identified and the analysis shows that access to land resources among the char dwellers has established legal ownership and entitlement of land and resolve the crisis of permanent settlement which bring change in livelihood in terms of access to land resources to some extent. The islands of char dwellers are in general disadvantaged with respect to their mainland counterparts in terms of physical isolation and vulnerability to flooding and erosion have created seasonal migration and higher dependency on traditional money lenders for accessing credit supply

Autism and increased paternal age related changes in global levels of gene expression regulation.

Directory of Open Access Journals (Sweden)

Mark D Alter

2011-02-01

Full Text Available A causal role of mutations in multiple general transcription factors in neurodevelopmental disorders including autism suggested that alterations in global levels of gene expression regulation might also relate to disease risk in sporadic cases of autism. This premise can be tested by evaluating for changes in the overall distribution of gene expression levels. For instance, in mice, variability in hippocampal-dependent behaviors was associated with variability in the pattern of the overall distribution of gene expression levels, as assessed by variance in the distribution of gene expression levels in the hippocampus. We hypothesized that a similar change in variance might be found in children with autism. Gene expression microarrays covering greater than 47,000 unique RNA transcripts were done on RNA from peripheral blood lymphocytes (PBL of children with autism (n = 82 and controls (n = 64. Variance in the distribution of gene expression levels from each microarray was compared between groups of children. Also tested was whether a risk factor for autism, increased paternal age, was associated with variance. A decrease in the variance in the distribution of gene expression levels in PBL was associated with the diagnosis of autism and a risk factor for autism, increased paternal age. Traditional approaches to microarray analysis of gene expression suggested a possible mechanism for decreased variance in gene expression. Gene expression pathways involved in transcriptional regulation were down-regulated in the blood of children with autism and children of older fathers. Thus, results from global and gene specific approaches to studying microarray data were complimentary and supported the hypothesis that alterations at the global level of gene expression regulation are related to autism and increased paternal age. Global regulation of transcription, thus, represents a possible point of convergence for multiple etiologies of autism and other

Regulation of the csgD promoter by global regulators HN-S, IHF, and RpoS in E. coli O157:H7 isolates

Science.gov (United States)

Introduction: Curli production is essential for the biofilm formation in E. coli and Salmonella. The control of expression of CsgD, the key regulator of the curli operon, is very complex, and has been shown to be regulated by several global regulators and is influenced by various growth and stress...

Patterns of some extracellular matrix gene expression are similar in cells from cleft lip-palate patients and in human palatal fibroblasts exposed to diazepam in culture

International Nuclear Information System (INIS)

Marinucci, Lorella; Balloni, Stefania; Bodo, Maria; Carinci, Francesco; Pezzetti, Furio; Stabellini, Giordano; Carmela, Conte; Lumare, Eleonora

2009-01-01

Prenatal exposure to diazepam, a prototype sedative drug that belongs to Benzodiazepines, can lead to orofacial clefting in human newborns. By using real-time PCR, in the present study we investigated whether diazepam elicits gene expression alterations in extracellular matrix (ECM) components, growth factors and gamma-aminobutyric acid receptor (GABRB3), implicated in the coordinate regulation of palate development. Palate fibroblasts were treated with diazepam (Dz-N fibroblasts) and compared to cleft lip-palate (CLP) fibroblasts obtained from patients with no known exposure to diazepam or other teratogens. Untreated fibroblasts from non-CLP patients were used as control. The results showed significant convergences in gene expression pattern of collagens, fibromodulin, vitronectin, tenascin C, integrins and metalloprotease MMP13 between Dz-N and CLP fibroblasts. Among the growth factors, constitutive Fibroblast Growth Factor 2 (FGF2) was greatly enhanced in Dz-N and CLP fibroblasts and associated with a higher reduction of FGF receptor. Transforming Growth Factor beta 3 (TGFβ 3 ) resulted up-regulated in CLP fibroblasts and decreased in Dz-N fibroblasts. We found phenotypic differences exhibited by Dz-N and CLP fibroblasts in GABRB3 gene regulation, so further studies are necessary to determine whether GABAergic system could be involved in the development of diazepam mediated CLP phenotype. Taken together the results elucidate the molecular mechanisms underlying possible toxicology effects induced by diazepam. Counselling of women on the safety of diazepam exposure is clinically important, also for the forensic consequences

Internet governance and global self regulation: theoretical and empirical building blocks for a general theory of self regulation

NARCIS (Netherlands)

Vey Mestdagh, C.; Rijgersberg, R.

2010-01-01

The following exposition sets out to identify the basic theoretical and empirical building blocks for a general theory of self-regulation. It uses the Internet as an empirical basis since its global reach and technical characteristics create interdependencies between actors that transcend national

C5a regulates IL-12+ DC migration to induce pathogenic Th1 and Th17 cells in sepsis.

Directory of Open Access Journals (Sweden)

Ning Ma

Full Text Available OBJECTIVE: It is well known that complement system C5a is excessively activated during the onset of sepsis. However, it is unclear whether C5a can regulate dentritic cells (DCs to stimulate adaptive immune cells such as Th1 and Th17 in sepsis. METHODS: Sepsis was induced by cecal ligation and puncture (CLP. CLP-induced sepsis was treated with anti-C5a or IL-12. IL-12(+DC, IFNγ(+Th1, and IL-17(+Th17 cells were analyzed by flow cytometry. IL-12 was measured by ELISA. RESULTS: Our studies here showed that C5a induced IL-12(+DC cell migration from the peritoneal cavity to peripheral blood and lymph nodes. Furthermore, IL-12(+DC cells induced the expansion of pathogenic IFNγ(+Th1 and IL-17(+Th17 cells in peripheral blood and lymph nodes. Moreover, IL-12, secreted by DC cells in the peritoneal cavity, is an important factor that prevents the development of sepsis. CONCLUSION: Our data suggests that C5a regulates IL-12(+DC cell migration to induce pathogenic Th1 and Th17 cells in sepsis.

Proteomics Reveals Global Regulation of Protein SUMOylation by ATM and ATR Kinases during Replication Stress

Directory of Open Access Journals (Sweden)

Stephanie Munk

2017-10-01

Full Text Available The mechanisms that protect eukaryotic DNA during the cumbersome task of replication depend on the precise coordination of several post-translational modification (PTM-based signaling networks. Phosphorylation is a well-known regulator of the replication stress response, and recently an essential role for SUMOs (small ubiquitin-like modifiers has also been established. Here, we investigate the global interplay between phosphorylation and SUMOylation in response to replication stress. Using SUMO and phosphoproteomic technologies, we identify thousands of regulated modification sites. We find co-regulation of central DNA damage and replication stress responders, of which the ATR-activating factor TOPBP1 is the most highly regulated. Using pharmacological inhibition of the DNA damage response kinases ATR and ATM, we find that these factors regulate global protein SUMOylation in the protein networks that protect DNA upon replication stress and fork breakage, pointing to integration between phosphorylation and SUMOylation in the cellular systems that protect DNA integrity.

Patterns of globalized reproduction: Egg cells regulation in Israel and Austria.

Science.gov (United States)

Shalev, Carmel; Werner-Felmayer, Gabriele

2012-04-18

Since the successful introduction of in vitro fertilization in 1978, medically assisted reproduction (MAR) has proliferated in multiple clinical innovations. Consequently, egg cells have become an object of demand for both infertility treatment and stem cell research, and this raises complex legal, ethical, social and economic issues.In this paper we compare how the procurement and use of human egg cells is regulated in two countries: Israel and Austria. Israel is known for its scientific leadership, generous public funding, high utilization and liberal regulation of assisted reproductive technology (ART). Austria lies at the other extreme of the regulatory spectrum in terms of restrictions on reproductive interventions.In both countries, however, there is a constant increase in the use of the technology, and recent legal developments make egg cells more accessible. Also, in both countries the scarcity of egg cells in concert with the rising demand for donations has led to the emergence of cross-border markets and global 'reproductive tourism' practices. In Israel, in particular, a scandal known as the 'eggs affair' was followed by regulation that allowed egg cell donations from outside the country under certain conditions.Cross-border markets are developed by medical entrepreneurs, driven by global economic gaps, made possible by trans-national regulatory lacunae and find expression as consumer demand. The transnational practice of egg cell donations indicates the emergence of a global public health issue, but there is a general lack of medical and epidemiological data on its efficacy and safety. We conclude that there is need for harmonisation of domestic laws and formulation of new instruments for international governance.

Patterns of globalized reproduction: Egg cells regulation in Israel and Austria

Directory of Open Access Journals (Sweden)

Shalev Carmel

2012-04-01

Full Text Available Abstract Since the successful introduction of in vitro fertilization in 1978, medically assisted reproduction (MAR has proliferated in multiple clinical innovations. Consequently, egg cells have become an object of demand for both infertility treatment and stem cell research, and this raises complex legal, ethical, social and economic issues. In this paper we compare how the procurement and use of human egg cells is regulated in two countries: Israel and Austria. Israel is known for its scientific leadership, generous public funding, high utilization and liberal regulation of assisted reproductive technology (ART. Austria lies at the other extreme of the regulatory spectrum in terms of restrictions on reproductive interventions. In both countries, however, there is a constant increase in the use of the technology, and recent legal developments make egg cells more accessible. Also, in both countries the scarcity of egg cells in concert with the rising demand for donations has led to the emergence of cross-border markets and global 'reproductive tourism' practices. In Israel, in particular, a scandal known as the 'eggs affair' was followed by regulation that allowed egg cell donations from outside the country under certain conditions. Cross-border markets are developed by medical entrepreneurs, driven by global economic gaps, made possible by trans-national regulatory lacunae and find expression as consumer demand. The transnational practice of egg cell donations indicates the emergence of a global public health issue, but there is a general lack of medical and epidemiological data on its efficacy and safety. We conclude that there is need for harmonisation of domestic laws and formulation of new instruments for international governance.

Salt stress-induced transcription of σB- and CtsR-regulated genes in persistent and non-persistent Listeria monocytogenes strains from food processing plants.

Science.gov (United States)

Ringus, Daina L; Ivy, Reid A; Wiedmann, Martin; Boor, Kathryn J

2012-03-01

Listeria monocytogenes is a foodborne pathogen that can persist in food processing environments. Six persistent and six non-persistent strains from fish processing plants and one persistent strain from a meat plant were selected to determine if expression of genes in the regulons of two stress response regulators, σ(B) and CtsR, under salt stress conditions is associated with the ability of L. monocytogenes to persist in food processing environments. Subtype data were also used to categorize the strains into genetic lineages I or II. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to measure transcript levels for two σ(B)-regulated genes, inlA and gadD3, and two CtsR-regulated genes, lmo1138 and clpB, before and after (t=10 min) salt shock (i.e., exposure of exponential phase cells to BHI+6% NaCl for 10 min at 37°C). Exposure to salt stress induced higher transcript levels relative to levels under non-stress conditions for all four stress and virulence genes across all wildtype strains tested. Analysis of variance (ANOVA) of induction data revealed that transcript levels for one gene (clpB) were induced at significantly higher levels in non-persistent strains compared to persistent strains (p=0.020; two-way ANOVA). Significantly higher transcript levels of gadD3 (p=0.024; two-way ANOVA) and clpB (p=0.053; two-way ANOVA) were observed after salt shock in lineage I strains compared to lineage II strains. No clear association between stress gene transcript levels and persistence was detected. Our data are consistent with an emerging model that proposes that establishment of L. monocytogenes persistence in a specific environment occurs as a random, stochastic event, rather than as a consequence of specific bacterial strain characteristics.

A host-specific biological control of grape crown gall by Agrobacterium vitis strain F2/5: its regulation and population dynamics.

Science.gov (United States)

Kaewnum, Supaporn; Zheng, Desen; Reid, Cheryl L; Johnson, Kameka L; Gee, Jodi C; Burr, Thomas J

2013-05-01

Nontumorigenic Agrobacterium vitis strain F2/5 is able to prevent crown gall caused by tumorigenic A. vitis on grape but not on other plant species such as tobacco. Mutations in a quorum-sensing transcription factor, aviR, and in caseinolytic protease (clp) component genes clpA and clpP1 resulted in reduced or loss of biological control. All mutants were complemented; however, restoration of biological control by complemented clpA and clpP1 mutants was dependent on the copy number of vector that was used as well as timing of application of the complemented mutants to grape wounds in relation to inoculation with pathogen. Mutations in other quorum-sensing and clp genes and in a gene associated with polyketide synthesis did not affect biological control. It was determined that, although F2/5 inhibits transformation by tumorigenic A. vitis strains on grape, it does not affect growth of the pathogen in wounded grape tissue over time.

Post-Transcriptional Regulation by the Csr Global Regulatory System in Escherichia coli

OpenAIRE

Suzuki, Kazushi; 鈴木, 一史

2007-01-01

In many species of bacteria, the Csr (carbon storage regulator) global regulatory system coordinates the expression of various genes. In Escherichia coli, the central component of this system, CsrA, is a RNA-binding protein. The CsrA is a homodimer and binds to leader segments of target mRNAs, affecting their translation and stability. CsrA activity is regulated by two small non-coding RNAs, CsrB and CsrC. These RNAs contain multiple CsrA-binding sequences and act by sequestering CsrA. In thi...

Globalization of environmental regulations for offshore E & P operations

Energy Technology Data Exchange (ETDEWEB)

Shannon, B.E.

1995-12-31

One of the enduring legacies of the Rio Environmental Summit of 1992 (United Nations Conference on Environment and Development, UNCED) is Agenda 21 (Chapter 17 - Protection of the Oceans), which among other things called for the assessment of the need for a global authority to regulate offshore Exploration & Production (E&P) discharges, emissions and safety. Despite advice to the contrary from the International Maritime Organization (IMO), interest is building within the European community for the standardization of regulations for offshore E&P activities. Several international of regulations for offshore E&P activities. Several international frameworks or forums have been mentioned as possible candidates. These include the United Nations Convention on the Law of the Sea, 1982 (UNCLOS); London Convention 1972 (LC 1972) and the International Convention for the Prevention of Pollution from Ships, 1973, as modified by the Protocol of 1978 (MARPOL) 73/78. International offshore oil and gas operators operate within requirements of regional conventions under the United Nations Environmental Program`s (UNEP) - Regional Seas Program. Domestic offshore operations are undertaken under the auspices of the U.S. Environmental Protection Agency and Minerals Management Service.

Global regulation of gene expression by the MafR protein of Enterococcus faecalis

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Sofía eRuiz-Cruz

2016-01-01

Full Text Available Enterococcus faecalis is a natural inhabitant of the human gastrointestinal tract. However, as an opportunistic pathogen, it is able to colonize other host niches and cause life-threatening infections. Its adaptation to new environments involves global changes in gene expression. The EF3013 gene (here named mafR of E. faecalis strain V583 encodes a protein (MafR, 482 residues that has sequence similarity to global response regulators of the Mga/AtxA family. The enterococcal OG1RF genome also encodes the MafR protein (gene OG1RF_12293. In this work, we have identified the promoter of the mafR gene using several in vivo approaches. Moreover, we show that MafR influences positively the transcription of many genes on a genome-wide scale. The most significant target genes encode components of PTS-type membrane transporters, components of ABC-type membrane transporters, and proteins involved in the metabolism of carbon sources. Some of these genes were previously reported to be up-regulated during the growth of E. faecalis in blood and/or in human urine. Furthermore, we show that a mafR deletion mutant strain induces a significant lower degree of inflammation in the peritoneal cavity of mice, suggesting that enterococcal cells deficient in MafR are less virulent. Our work indicates that MafR is a global transcriptional regulator. It might facilitate the adaptation of E. faecalis to particular host niches and, therefore, contribute to its potential virulence.

GLOBAL FINANCIAL CRISIS 2008 CAUSES AND CONSEQUENCES FOR RUSSIAN MACROPRUDENTIAL REGULATION

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Егор Николаевич Поляков

2013-09-01

Full Text Available This article analyzes the impact of volatility in global financial markets on the economy of developing countries and the analysis of factors contributing to a greater or lesser degree of vulnerability of the financial systems of developing countries in the global crisis of 2008-2010. Particular attention is paid to the influence of the global financial crisis on the economies of the two groups of developing countries of Southeast Asia and Central and Eastern Europe. On the basis of the analysis due to the dynamics of the main macroeconomic indicators of the Russian Federation during the acute phase of the crisis. The author presents an analysis of the vulnerability of the Russian economy in the event of possible instability in global financial markets at present. The author came to the conclusion that the main reason for which in 2009 the level of GDP growth Russia won 178 seats out of 184 countries, were 2 groups of errors. The first group of errors - errors are system of macro-prudential regulation made by the Central Bank from 2002 to 2007, such as: lack of control and regulation of borrowings of the private and banking sectors to foreign markets, as well as in the domestic market in foreign currency, the loss of control over domestic financial markets, such as: the interbank lending market, the stock market. The second group of errors - errors it committed securities during the crisis. The first error of the Central Bank - a rejection Vat refinance foreign debt of non-financial sector, resulting in an acute liquidity crisis. The second error is stretched for a few months, not a one-time devaluation of the ruble. Price of the second error was 200 billion USD, which the Central Bank lost and speculators earned.DOI: http://dx.doi.org/10.12731/2218-7405-2013-9-4

New Regional and Global HFC Projections and Effects of National Regulations and Montreal Protocol Amendment Proposals

Science.gov (United States)

Velders, G. J. M.

2015-12-01

Hydrofluorocarbons (HFCs) are used as substitutes for ozone-depleting substances that are being phased out globally under Montreal Protocol regulations. New global scenarios of HFC emissions reach 4.0-5.3 GtCO2-eq yr-1 in 2050, which corresponds to a projected growth from 2015 to 2050 which is 9% to 29% of that for CO2 over the same time period. New baseline scenarios are formulated for 10 HFC compounds, 11 geographic regions, and 13 use categories. These projections are the first to comprehensively assess production and consumption of individual HFCs in multiple use sectors and geographic regions with emission estimates constrained by atmospheric observations. In 2050, in percent of global HFC emissions, China (~30%), India and the rest of Asia (~25%), Middle East and northern Africa (~10%), and USA (~10%) are the principal source regions; and refrigeration and stationary air conditioning are the major use sectors. National regulations to limit HFC use have been adopted recently in the European Union, Japan and USA, and four proposals have been submitted in 2015 to amend the Montreal Protocol to substantially reduce growth in HFC use. Calculated baseline emissions are reduced by 90% in 2050 by implementing the North America Montreal Protocol amendment proposal. Global adoption of technologies required to meet national regulations would be sufficient to reduce 2050 baseline HFC consumption by more than 50% of that achieved with the North America proposal for most developed and developing countries. The new HFC scenarios and effects of national regulations and Montreal Protocol amendment proposals will be presented.

Global parameter estimation for thermodynamic models of transcriptional regulation.

Science.gov (United States)

Suleimenov, Yerzhan; Ay, Ahmet; Samee, Md Abul Hassan; Dresch, Jacqueline M; Sinha, Saurabh; Arnosti, David N

2013-07-15

Deciphering the mechanisms involved in gene regulation holds the key to understanding the control of central biological processes, including human disease, population variation, and the evolution of morphological innovations. New experimental techniques including whole genome sequencing and transcriptome analysis have enabled comprehensive modeling approaches to study gene regulation. In many cases, it is useful to be able to assign biological significance to the inferred model parameters, but such interpretation should take into account features that affect these parameters, including model construction and sensitivity, the type of fitness calculation, and the effectiveness of parameter estimation. This last point is often neglected, as estimation methods are often selected for historical reasons or for computational ease. Here, we compare the performance of two parameter estimation techniques broadly representative of local and global approaches, namely, a quasi-Newton/Nelder-Mead simplex (QN/NMS) method and a covariance matrix adaptation-evolutionary strategy (CMA-ES) method. The estimation methods were applied to a set of thermodynamic models of gene transcription applied to regulatory elements active in the Drosophila embryo. Measuring overall fit, the global CMA-ES method performed significantly better than the local QN/NMS method on high quality data sets, but this difference was negligible on lower quality data sets with increased noise or on data sets simplified by stringent thresholding. Our results suggest that the choice of parameter estimation technique for evaluation of gene expression models depends both on quality of data, the nature of the models [again, remains to be established] and the aims of the modeling effort. Copyright © 2013 Elsevier Inc. All rights reserved.

[Role of immune-related GTPase M1 in cortical neurons autophagy of mice with sepsis-induced brain injury].

Science.gov (United States)

Huang, Qun; Chen, Bin; Li, Yafei; Li, Xihong

2017-12-28

To investigate the role of immune-related GTPase M1 (IRGM1) in cortical neurons autophagy in mice with sepsis induced brain injury (SIBI).
 Methods: Sixty wild-type C57BL/6 mice and sixty IRGM1 gene knockout C57BL/6 mice were randomly divided into 4 groups: a sham-operated wild-type (SWT) group, a cecal ligation and puncture (CLP) model wild-type (MWT) group, a sham-operated knockout (SKO) group, and a CLP model knockout (MKO) group. Models of mice with sepsis were established by CLP. Six hours of after CLP, the neurobehavioral scores for mice were recorded. The mice were diagnosed with SIBI and enrolled for the studies in next step if the neurobehavioral score was less than 6 in the MWT and MKO groups. The sham operation group only opened the abdominal cavity without CLP. Pathological changes in mouse cerebral cortex were observed by HE staining. Electron microscope was used to observe the ultrastructure of autophagy in cortical neurons. The expression of IRGM1 and INF-γ mRNA in the cerebral cortex of mice were detected by Real time quantitative PCR. The protein expression of microtubule-associated protein 1 light chain 3 (LC3)-II, LC3-I, sequestosome-1 (SQSTM1) and IRGM1 were measured by Western blot. Immunofluorescence staining was used to examine the expression of IRGM1 in mouse cortical neurons.
 Results: In the MWT group, the cortical neurons showed dilated endoplasmic reticulum, swelling mitochondria, and increased number of autophagosomes after 6 or 24 h of CLP in contrast to the SWT group. At 6 h after CLP, the expression of LC3-II in the cerebral cortex began to up-regulate, and the up-regulation was maintained till 96 h after CLP; on the contrary, SQSTM1 began to decline after 6 h of CLP. Compared with SWT group, IRGM1 was strongly up-regulated in the cerebral cortex of mice at both mRNA and protein levels in the MWT group after 12 h of CLP, and the mRNA expression of IFN-γ was also increased significantly (PSIBI was 90% (27/30) in the MWT group

Linker Histone Phosphorylation Regulates Global Timing of Replication Origin Firing*S⃞

Science.gov (United States)

Thiriet, Christophe; Hayes, Jeffrey J.

2009-01-01

Despite the presence of linker histone in all eukaryotes, the primary function(s) of this histone have been difficult to clarify. Knock-out experiments indicate that H1s play a role in regulation of only a small subset of genes but are an essential component in mouse development. Here, we show that linker histone (H1) is involved in the global regulation of DNA replication in Physarum polycephalum. We find that genomic DNA of H1 knock-down cells is more rapidly replicated, an effect due at least in part to disruption of the native timing of replication fork firing. Immunoprecipitation experiments demonstrate that H1 is transiently lost from replicating chromatin via a process facilitated by phosphorylation. Our results suggest that linker histones generate a chromatin environment refractory to replication and that their transient removal via protein phosphorylation during S phase is a critical step in the epigenetic regulation of replication timing. PMID:19015270

Reconstruction of the yeast Snf1 kinase regulatory network reveals its role as a global energy regulator

Science.gov (United States)

Usaite, Renata; Jewett, Michael C; Oliveira, Ana Paula; Yates, John R; Olsson, Lisbeth; Nielsen, Jens

2009-01-01

Highly conserved among eukaryotic cells, the AMP-activated kinase (AMPK) is a central regulator of carbon metabolism. To map the complete network of interactions around AMPK in yeast (Snf1) and to evaluate the role of its regulatory subunit Snf4, we measured global mRNA, protein and metabolite levels in wild type, Δsnf1, Δsnf4, and Δsnf1Δsnf4 knockout strains. Using four newly developed computational tools, including novel DOGMA sub-network analysis, we showed the benefits of three-level ome-data integration to uncover the global Snf1 kinase role in yeast. We for the first time identified Snf1's global regulation on gene and protein expression levels, and showed that yeast Snf1 has a far more extensive function in controlling energy metabolism than reported earlier. Additionally, we identified complementary roles of Snf1 and Snf4. Similar to the function of AMPK in humans, our findings showed that Snf1 is a low-energy checkpoint and that yeast can be used more extensively as a model system for studying the molecular mechanisms underlying the global regulation of AMPK in mammals, failure of which leads to metabolic diseases. PMID:19888214

Policy Approaches for Regulating Alcohol Marketing in a Global Context: A Public Health Perspective.

Science.gov (United States)

Esser, Marissa B; Jernigan, David H

2018-04-01

Alcohol consumption is responsible for 3.3 million deaths globally or nearly 6% of all deaths. Alcohol use contributes to both communicable and noncommunicable diseases, as well as violence and injuries. The purpose of this review is to discuss, in the context of the expansion of transnational alcohol corporations and harms associated with alcohol use, policy options for regulating exposure to alcohol marketing. We first provide an overview of the public health problem of harmful alcohol consumption and describe the association between exposure to alcohol marketing and alcohol consumption. We then discuss the growth and concentration of global alcohol corporations and their marketing practices in low- and middle-income countries, as well as in higher-income societies. We review the use and effectiveness of various approaches for regulating alcohol marketing in various countries before discussing challenges and opportunities to protect public health.

Global regulator SATB1 recruits beta-catenin and regulates T(H2 differentiation in Wnt-dependent manner.

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Dimple Notani

2010-01-01

Full Text Available In vertebrates, the conserved Wnt signalling cascade promotes the stabilization and nuclear accumulation of beta-catenin, which then associates with the lymphoid enhancer factor/T cell factor proteins (LEF/TCFs to activate target genes. Wnt/beta -catenin signalling is essential for T cell development and differentiation. Here we show that special AT-rich binding protein 1 (SATB1, the T lineage-enriched chromatin organizer and global regulator, interacts with beta-catenin and recruits it to SATB1's genomic binding sites. Gene expression profiling revealed that the genes repressed by SATB1 are upregulated upon Wnt signalling. Competition between SATB1 and TCF affects the transcription of TCF-regulated genes upon beta-catenin signalling. GATA-3 is a T helper type 2 (T(H2 specific transcription factor that regulates production of T(H2 cytokines and functions as T(H2 lineage determinant. SATB1 positively regulated GATA-3 and siRNA-mediated knockdown of SATB1 downregulated GATA-3 expression in differentiating human CD4(+ T cells, suggesting that SATB1 influences T(H2 lineage commitment by reprogramming gene expression. In the presence of Dickkopf 1 (Dkk1, an inhibitor of Wnt signalling, GATA-3 is downregulated and the expression of signature T(H2 cytokines such as IL-4, IL-10, and IL-13 is reduced, indicating that Wnt signalling is essential for T(H2 differentiation. Knockdown of beta-catenin also produced similar results, confirming the role of Wnt/beta-catenin signalling in T(H2 differentiation. Furthermore, chromatin immunoprecipitation analysis revealed that SATB1 recruits beta-catenin and p300 acetyltransferase on GATA-3 promoter in differentiating T(H2 cells in a Wnt-dependent manner. SATB1 coordinates T(H2 lineage commitment by reprogramming gene expression. The SATB1:beta-catenin complex activates a number of SATB1 regulated genes, and hence this study has potential to find novel Wnt responsive genes. These results demonstrate that SATB1

Quantitative analysis of proteome and lipidome dynamics reveals functional regulation of global lipid metabolism

DEFF Research Database (Denmark)

Casanovas, Albert; Sprenger, Richard R; Tarasov, Kirill

2015-01-01

Elucidating how and to what extent lipid metabolism is remodeled under changing conditions is essential for understanding cellular physiology. Here, we analyzed proteome and lipidome dynamics to investigate how regulation of lipid metabolism at the global scale supports remodeling of cellular...

The national helpdesk activity in Italy: report of the first year (2010

Directory of Open Access Journals (Sweden)

Ludovica Malaguti Aliberti

2011-01-01

Full Text Available National CLP heldpesk is a service established in every Member State providing advice to companies and other stakeholders on the obligations they may have under CLP. In Italy the national helpdesk is located into the Center of Chemical Substances (CSC in the National Institute of Health. Helpdesks will provide with wide ranging information on the provisions of CLP. They will also advice on the responsibilities the suppliers of chemical substances have to fulfill under these Regulations. Too specific questions cannot be answered as the aim of the helpdesk is to give a general interpretation of CLP principles and requirements instead of solving tailor made problems.

The challenges for global harmonisation of food safety norms and regulations: issues for India.

Science.gov (United States)

Prakash, Jamuna

2014-08-01

Safe and adequate food is a human right, safety being a prime quality attribute without which food is unfit for consumption. Food safety regulations are framed to exercise control over all types of food produced, processed and sold so that the customer is assured that the food consumed will not cause any harm. From the Indian perspective, global harmonisation of food regulations is needed to improve food and nutrition security, the food trade and delivery of safe ready-to-eat (RTE) foods at all places and at all times. The Millennium Development Goals (MDGs) put forward to transform developing societies incorporate many food safety issues. The success of the MDGs, including that of poverty reduction, will in part depend on an effective reduction of food-borne diseases, particularly among the vulnerable group, which includes women and children. Food- and water-borne illnesses can be a serious health hazard, being responsible for high incidences of morbidity and mortality across all age groups of people. Global harmonisation of food regulations would assist in facilitating food trade within and outside India through better compliance, ensuring the safety of RTE catered foods, as well as addressing issues related to the environment. At the same time, regulations need to be optimum, as overregulation may have undue negative effects on the food trade. © 2013 Society of Chemical Industry.

The global regulator LaeA controls production of citric acid and endoglucanases in Aspergillus carbonarius

DEFF Research Database (Denmark)

Linde, Tore; Zoglowek, Marta; Lübeck, Mette

2016-01-01

The global regulatory protein LaeA is known for regulating the production of many kinds of secondary metabolites in Aspergillus species, as well as sexual and asexual reproduction, and morphology. In Aspergillus carbonarius, it has been shown that LaeA regulates production of ochratoxin. We have ...

Cell shape regulates global histone acetylation in human mammaryepithelial cells

Energy Technology Data Exchange (ETDEWEB)

Le Beyec, Johanne; Xu, Ren; Lee, Sun-Young; Nelson, Celeste M.; Rizki, Aylin; Alcaraz, Jordi; Bissell, Mina J.

2007-02-28

Extracellular matrix (ECM) regulates cell morphology and gene expression in vivo; these relationships are maintained in three-dimensional (3D) cultures of mammary epithelial cells. In the presence of laminin-rich ECM (lrECM), mammary epithelial cells round up and undergo global histone deacetylation, a process critical for their functional differentiation. However, it remains unclear whether lrECM-dependent cell rounding and global histone deacetylation are indeed part of a common physical-biochemical pathway. Using 3D cultures as well as nonadhesive and micropatterned substrata, here we showed that the cell 'rounding' caused by lrECM was sufficient to induce deacetylation of histones H3 and H4 in the absence of biochemical cues. Microarray and confocal analysis demonstrated that this deacetylation in 3D culture is associated with a global increase in chromatin condensation and a reduction in gene expression. Whereas cells cultured on plastic substrata formed prominent stress fibers, cells grown in 3D lrECM or on micropatterns lacked these structures. Disruption of the actin cytoskeleton with cytochalasin D phenocopied the lrECM-induced cell rounding and histone deacetylation. These results reveal a novel link between ECM-controlled cell shape and chromatin structure, and suggest that this link is mediated by changes in the actin cytoskeleton.

Building Responsive and Responsible Financial Regulators in the Aftermath of the Global Financial Crisis

NARCIS (Netherlands)

Iglesias Rodriguez, P.

2015-01-01

The global financial crisis that started in 2007 sparked several academic debates about the role that financial sector regulators played in the crisis and prompted policy reforms in the financial supervision architectures of several countries. This book focuses on the question of what

Spaceflight Alters Bacterial Gene Expression and Virulence and Reveals Role for Global Regulator Hfq

Science.gov (United States)

Wilson, J. W.; Ott, C. M.; zuBentrup, K. Honer; Ramamurthy R.; Quick, L.; Porwollik, S.; Cheng, P.; McClellan, M.; Tsaprailis, G.; Radabaugh, T.;

Expression of the stress-response regulators CtsR and HrcA in the uropathogen Staphylococcus saprophyticus during heat shock.

Science.gov (United States)

Rossi, Ciro César; de Oliveira, Lorayne Lauria; de Carvalho Rodrigues, Deivid; Ürményi, Turán Peter; Laport, Marinella Silva; Giambiagi-deMarval, Marcia

2017-08-01

The uropathogen Staphylococcus saprophyticus is an ubiquitous bacterium but little is known about mechanisms that allow its persistence in diverse environments. Here we evaluated S. saprophyticus growth and survival during heat shock, the expression of stress response regulators ctsR and hrcA through qRT-PCR and heat shock protein synthesis through 35 S-Met metabolic labeling. S. saprophyticus does not tolerate temperatures much higher than the optimal 37 °C, as its growth is greatly affected at 42 °C, though viability is maintained up to 48 °C. At 42 °C, the expression of ctsR and hrcA repressor genes approximately triple when compared to 37 °C and continue to increase together with temperature till 48 °C. Expression of hrcA peaks after 20 min of heat shock and decreases significantly after 30 min, indicating that heat stress response regulated by this gene may last 20-30 min. An increase in temperature is accompanied by the synthesis of at least eight proteins, three of which are likely the chaperones DnaK, GroEL and ClpB. In silico analysis indicate that the groEL gene may be regulated by HrcA, clpB by CtsR and dnaK by both repressors. This is the first work to discuss heat stress response in S. saprophyticus and a step forward in the understanding of mechanisms that make this a widespread and emergent pathogen.

Proteomics Reveals Global Regulation of Protein SUMOylation by ATM and ATR Kinases during Replication Stress

DEFF Research Database (Denmark)

Munk, Stephanie; Sigurðsson, Jón Otti; Xiao, Zhenyu

2017-01-01

The mechanisms that protect eukaryotic DNA during the cumbersome task of replication depend on the precise coordination of several post-translational modification (PTM)-based signaling networks. Phosphorylation is a well-known regulator of the replication stress response, and recently an essentia....... They analyze changes in the SUMO and phosphoproteome after MMC and hydroxyurea treatments and find that the DNA damage response kinases ATR and ATM globally regulate SUMOylation upon replication stress and fork breakage....

The bacterial response regulator ArcA uses a diverse binding site architecture to regulate carbon oxidation globally.

Directory of Open Access Journals (Sweden)

Dan M Park

Full Text Available Despite the importance of maintaining redox homeostasis for cellular viability, how cells control redox balance globally is poorly understood. Here we provide new mechanistic insight into how the balance between reduced and oxidized electron carriers is regulated at the level of gene expression by mapping the regulon of the response regulator ArcA from Escherichia coli, which responds to the quinone/quinol redox couple via its membrane-bound sensor kinase, ArcB. Our genome-wide analysis reveals that ArcA reprograms metabolism under anaerobic conditions such that carbon oxidation pathways that recycle redox carriers via respiration are transcriptionally repressed by ArcA. We propose that this strategy favors use of catabolic pathways that recycle redox carriers via fermentation akin to lactate production in mammalian cells. Unexpectedly, bioinformatic analysis of the sequences bound by ArcA in ChIP-seq revealed that most ArcA binding sites contain additional direct repeat elements beyond the two required for binding an ArcA dimer. DNase I footprinting assays suggest that non-canonical arrangements of cis-regulatory modules dictate both the length and concentration-sensitive occupancy of DNA sites. We propose that this plasticity in ArcA binding site architecture provides both an efficient means of encoding binding sites for ArcA, σ(70-RNAP and perhaps other transcription factors within the same narrow sequence space and an effective mechanism for global control of carbon metabolism to maintain redox homeostasis.

Classical technical analysis of Latin American market indices. Correlations in Latin American Currencies (ARS, CLP, MXP) exchange rates with respect to DEM, GBP, JPY and USD

Science.gov (United States)

Ausloos, M.; Ivanova, K.

2004-06-01

The classical technical analysis methods of financial time series based on the moving average and momentum is recalled. Illustrations use the IBM share price and Latin American (Argentinian MerVal, Brazilian Bovespa and Mexican IPC) market indices. We have also searched for scaling ranges and exponents in exchange rates between Latin American currencies ($ARS$, $CLP$, $MXP$) and other major currencies $DEM$, $GBP$, $JPY$, $USD$, and $SDR$s. We have sorted out correlations and anticorrelations of such exchange rates with respect to $DEM$, $GBP$, $JPY$ and $USD$. They indicate a very complex or speculative behavior.

Metformin regulates global DNA methylation via mitochondrial one-carbon metabolism.

Science.gov (United States)

Cuyàs, E; Fernández-Arroyo, S; Verdura, S; García, R Á-F; Stursa, J; Werner, L; Blanco-González, E; Montes-Bayón, M; Joven, J; Viollet, B; Neuzil, J; Menendez, J A

2018-02-15

The anti-diabetic biguanide metformin may exert health-promoting effects via metabolic regulation of the epigenome. Here we show that metformin promotes global DNA methylation in non-cancerous, cancer-prone and metastatic cancer cells by decreasing S-adenosylhomocysteine (SAH), a strong feedback inhibitor of S-adenosylmethionine (SAM)-dependent DNA methyltransferases, while promoting the accumulation of SAM, the universal methyl donor for cellular methylation. Using metformin and a mitochondria/complex I (mCI)-targeted analog of metformin (norMitoMet) in experimental pairs of wild-type and AMP-activated protein kinase (AMPK)-, serine hydroxymethyltransferase 2 (SHMT2)- and mCI-null cells, we provide evidence that metformin increases the SAM:SAH ratio-related methylation capacity by targeting the coupling between serine mitochondrial one-carbon flux and CI activity. By increasing the contribution of one-carbon units to the SAM from folate stores while decreasing SAH in response to AMPK-sensed energetic crisis, metformin can operate as a metabolo-epigenetic regulator capable of reprogramming one of the key conduits linking cellular metabolism to the DNA methylation machinery.

Coculture of Bifidobacterium longum and Bifidobacterium breve alters their protein expression profiles and enzymatic activities.

Science.gov (United States)

Ruiz, Lorena; Sánchez, Borja; de Los Reyes-Gavilán, Clara G; Gueimonde, Miguel; Margolles, Abelardo

2009-07-31

Some strains of the genus Bifidobacterium are probiotic bacteria commonly added to functional dairy products. The influence of coculturing Bifidobacterium longum NCIMB8809 and Bifidobacterium breve NCIMB8807 on their physiology was studied. 2DE separation of protein extracts, coupled to MS protein analysis allowed the identification of 16 proteins whose expression drastically changed when cells were grown in compartmentalized coculture, compared to monoculture. These included ribosomal proteins and proteins involved in carbohydrate metabolism, gene regulation, cell envelope biogenesis and transport processes. Significant changes in some glycoside-hydrolysing activities (beta-d-xylopyranosidase, alpha-l-arabinofuranosidase and beta-d-glucopyranosidase) were also detected. Furthermore, qRT-PCR experiments using as targets the B. breve genes clgR (transcriptional regulator) clpP1, clpP2 and clpC (chaperone- and protease-encoding genes positively regulated by clgR) supported the proteomic results, the four genes displaying a higher expression level in coculture. This study provides new insights to understand the communication among Bifidobacterium species.

Linking high-resolution metabolic flux phenotypes and transcriptional regulation in yeast modulated by the global regulator Gcn4p

DEFF Research Database (Denmark)

Moxley, Joel F.; Jewett, Michael Christopher; Antoniewicz, Maciek R.

2009-01-01

. However, the potential of systems biology approaches is limited by difficulties in integrating metabolic measurements across the functional levels of the cell despite their being most closely linked to cellular phenotype. To address this limitation, we developed a model-based approach to correlate m......RNA and metabolic flux data that combines information from both interaction network models and flux determination models. We started by quantifying 5,764 mRNAs, 54 metabolites, and 83 experimental C-13-based reaction fluxes in continuous cultures of yeast under stress in the absence or presence of global regulator...... of metabolic flux (i.e., use of different reaction pathways) by transcriptional regulation and metabolite interaction density (i.e., level of pairwise metabolite-protein interactions) as a key biosynthetic control determinant. Furthermore, this model predicted flux rewiring in studies of follow...

RNAi Reveals Phase-Specific Global Regulators of Human Somatic Cell Reprogramming

Directory of Open Access Journals (Sweden)

Cheng-Xu Delon Toh

2016-06-01

Full Text Available Incomplete knowledge of the mechanisms at work continues to hamper efforts to maximize reprogramming efficiency. Here, we present a systematic genome-wide RNAi screen to determine the global regulators during the early stages of human reprogramming. Our screen identifies functional repressors and effectors that act to impede or promote the reprogramming process. Repressors and effectors form close interacting networks in pathways, including RNA processing, G protein signaling, protein ubiquitination, and chromatin modification. Combinatorial knockdown of five repressors (SMAD3, ZMYM2, SFRS11, SAE1, and ESET synergistically resulted in ∼85% TRA-1-60-positive cells. Removal of the novel splicing factor SFRS11 during reprogramming is accompanied by rapid acquisition of pluripotency-specific spliced forms. Mechanistically, SFRS11 regulates exon skipping and mutually exclusive splicing of transcripts in genes involved in cell differentiation, mRNA splicing, and chromatin modification. Our study provides insights into the reprogramming process, which comprises comprehensive and multi-layered transcriptional, splicing, and epigenetic machineries.

Self-perceptions of romantic appeal in adolescents with a cleft lip and/or palate.

Science.gov (United States)

Feragen, Kristin Billaud; Stock, Nicola Marie; Sharratt, Nicholas David; Kvalem, Ingela Lundin

2016-09-01

During adolescence, romantic relationships are a key developmental milestone. Coupled with the increasing salience of appearance and social acceptance, adolescents with an appearance-altering condition may feel particularly vulnerable when it comes to romantic relationships. This study aimed to explore the prevalence of romantic experiences among adolescents with a cleft lip and/or palate (CL/P), and to investigate how these experiences could be related to depressive symptoms and global self-worth. The study included 661 Norwegian adolescents with CL/P, who were compared to a large national sample. The prevalence of romantic relationships was lower among adolescents with CL/P compared to the reference group, although the overall impact on depressive symptoms and global self-worth appeared to be low. This study is one of few to explore the impact of a congenital visible condition on experiences of romantic relationships and provides preliminary insight into a significant, yet complex topic. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lvr, a Signaling System That Controls Global Gene Regulation and Virulence in Pathogenic Leptospira

Science.gov (United States)

Adhikarla, Haritha; Wunder, Elsio A.; Mechaly, Ariel E.; Mehta, Sameet; Wang, Zheng; Santos, Luciane; Bisht, Vimla; Diggle, Peter; Murray, Gerald; Adler, Ben; Lopez, Francesc; Townsend, Jeffrey P.; Groisman, Eduardo; Picardeau, Mathieu; Buschiazzo, Alejandro; Ko, Albert I.

2018-01-01

Leptospirosis is an emerging zoonotic disease with more than 1 million cases annually. Currently there is lack of evidence for signaling pathways involved during the infection process of Leptospira. In our comprehensive genomic analysis of 20 Leptospira spp. we identified seven pathogen-specific Two-Component System (TCS) proteins. Disruption of two these TCS genes in pathogenic Leptospira strain resulted in loss-of-virulence in a hamster model of leptospirosis. Corresponding genes lvrA and lvrB (leptospira virulence regulator) are juxtaposed in an operon and are predicted to encode a hybrid histidine kinase and a hybrid response regulator, respectively. Transcriptome analysis of lvr mutant strains with disruption of one (lvrB) or both genes (lvrA/B) revealed global transcriptional regulation of 850 differentially expressed genes. Phosphotransfer assays demonstrated that LvrA phosphorylates LvrB and predicted further signaling downstream to one or more DNA-binding response regulators, suggesting that it is a branched pathway. Phylogenetic analyses indicated that lvrA and lvrB evolved independently within different ecological lineages in Leptospira via gene duplication. This study uncovers a novel-signaling pathway that regulates virulence in pathogenic Leptospira (Lvr), providing a framework to understand the molecular bases of regulation in this life-threatening bacterium. PMID:29600195

SWeRF--A method for estimating the relevant fine particle fraction in bulk materials for classification and labelling purposes.

Science.gov (United States)

Pensis, Ingeborg; Luetzenkirchen, Frank; Friede, Bernd

2014-05-01

In accordance with the European regulation for classification, labelling and packaging of substances and mixtures (CLP) as well as the criteria as set out in the Globally Harmonized System (GHS), fine fraction of crystalline silica (CS) has been classified as a specific target organ toxicity, the specific organ in this case being the lung. Generic cut-off values for products containing a fine fraction of CS trigger the need for a method for the quantification of the fine fraction of CS in bulk materials. This article describes the so-called SWeRF method, the size-weighted relevant fine fraction. The SWeRF method combines the particle size distribution of a powder with probability factors from the EN 481 standard and allows the relevant fine fraction of a material to be calculated. The SWeRF method has been validated with a number of industrial minerals. This will enable manufacturers and blenders to apply the CLP and GHS criteria for the classification of mineral products containing RCS a fine fraction of CS.

Regulation of Neurospora Catalase-3 by global heterochromatin formation and its proximal heterochromatin region.

Science.gov (United States)

Wang, Yajun; Dong, Qing; Ding, Zhaolan; Gai, Kexin; Han, Xiaoyun; Kaleri, Farah Naz; He, Qun; Wang, Ying

2016-10-01

Catalase-3 (CAT-3) constitutes the main catalase activity in growing hyphae of Neurospora crassa, and its activity increases during exponential growth or is induced under different stress conditions. Although extensive progress has been made to identify catalase regulators, the regulation mechanism of CAT-3 at the chromatin level still remains unclear. Here, we aim at investigating the molecular regulation mechanisms of cat-3 at the chromatin level. We found that CAT-3 protein levels increased in mutants defective in proper global heterochromatin formation. Bioinformatics analysis identified a 5-kb AT-rich sequence adjacent to the cat-3 promoter as a heterochromatin region because of its enrichment of H3K9me3 and HP1. Expression of CAT-3 was induced by H 2 O 2 treatment in wild-type and such change occurred along with the accumulation of histone H3 acetylation at 5-kb heterochromatin boundaries and cat-3 locus, but without alteration of its H3K9me3 repressive modification. Moreover, disruption of 5-kb heterochromatin region results in elevated cat-3 expression, and higher levels of cat-3 expression were promoted by the combination with global heterochromatin defective mutants. Interestingly, the molecular weight and activity bands of CAT-3 protein are different in heterochromatin defective mutants compared with those in wild-type, suggesting that its N-terminal processing and modification may be altered. Our study indicates that the local chromatin structure creates a heterochromatin repressive environment to repress nearby gene expression. Copyright © 2016 Elsevier Inc. All rights reserved.

IVF policy and global/local politics: the making of multiple-embryo transfer regulation in Taiwan.

Science.gov (United States)

Wu, Chia-Ling

2012-08-01

This paper analyzes the regulatory trajectory of multiple-embryo transfer in in-vitro fertilization (IVF) in Taiwan. Taking a latecomer to policy-making as the case, it argues the importance of conceptualizing the global/local dynamics in policy-making for assisted reproductive technology (ART). The conceptual framework is built upon recent literature on standardization, science policy, and global assemblage. I propose three interrelated features that reveal the "global in the local": (1) the power relationships among stakeholders, (2) the selected global form that involved actors drew upon, and (3) the re-contextualized assemblage made of local networks. Data included archives, interviews, and participant observation. In different historical periods the specific stakeholders selected different preferred global forms for Taiwan, such as Britain's code of ethics in the 1990s, the American guideline in the early 2000s, and the European trend in the mid-2000s. The global is heterogeneous. The failure to transfer the British regulation, the revision of the American guideline by adding one more embryo than it specified, and the gap between the cited European trend and the "no more than four" in Taiwan's 2007 Human Reproduction Law all show that the local network further transforms the selected global form, confining it to rhetoric only or tailoring it to local needs. Overall, Taiwanese practitioners successfully maintained their medical autonomy to build a 'flexible standardization'. Multiple pregnancy remains the most common health risk of IVF in Taiwan. Copyright © 2012 Elsevier Ltd. All rights reserved.

Global approaches to regulating electronic cigarettes

OpenAIRE

Kennedy, Ryan David; Awopegba, Ayodeji; De Le?n, Elaine; Cohen, Joanna E

2016-01-01

Objectives Classify and describe the policy approaches used by countries to regulate e-cigarettes. Methods National policies regulating e-cigarettes were identified by (1) conducting web searches on Ministry of Health websites, and (2) broad web searches. The mechanisms used to regulate e-cigarettes were classified as new/amended laws, or existing laws. The policy domains identified include restrictions or prohibitions on product: sale, manufacturing, importation, distribution, use, product d...

Structure of Rot, a global regulator of virulence genes in Staphylococcus aureus.

Science.gov (United States)

Zhu, Yuwei; Fan, Xiaojiao; Zhang, Xu; Jiang, Xuguang; Niu, Liwen; Teng, Maikun; Li, Xu

2014-09-01

Staphylococcus aureus is a highly versatile pathogen that can infect human tissue by producing a large arsenal of virulence factors that are tightly regulated by a complex regulatory network. Rot, which shares sequence similarity with SarA homologues, is a global regulator that regulates numerous virulence genes. However, the recognition model of Rot for the promoter region of target genes and the putative regulation mechanism remain elusive. In this study, the 1.77 Å resolution X-ray crystal structure of Rot is reported. The structure reveals that two Rot molecules form a compact homodimer, each of which contains a typical helix-turn-helix module and a β-hairpin motif connected by a flexible loop. Fluorescence polarization results indicate that Rot preferentially recognizes AT-rich dsDNA with ~30-base-pair nucleotides and that the conserved positively charged residues on the winged-helix motif are vital for binding to the AT-rich dsDNA. It is proposed that the DNA-recognition model of Rot may be similar to that of SarA, SarR and SarS, in which the helix-turn-helix motifs of each monomer interact with the major grooves of target dsDNA and the winged motifs contact the minor grooves. Interestingly, the structure shows that Rot adopts a novel dimerization model that differs from that of other SarA homologues. As expected, perturbation of the dimer interface abolishes the dsDNA-binding ability of Rot, suggesting that Rot functions as a dimer. In addition, the results have been further confirmed in vivo by measuring the transcriptional regulation of α-toxin, a major virulence factor produced by most S. aureus strains.

Neoliberalism and the regulation of global labor mobility

NARCIS (Netherlands)

Overbeek, H.W.

2002-01-01

Globalization involves the international expansion of market relations and the global pursuit of economic liberalism. The essential factor in this process is commodification, including the commodification of human labor. Globalization integrates an increasing proportion of the world population

The Global Acetylome of the Human Pathogen Vibrio cholerae V52 Reveals Lysine Acetylation of Major Transcriptional Regulators

DEFF Research Database (Denmark)

Jers, Carsten; Ravikumar, Vaishnavi; Lezyk, Mateusz Jakub

2018-01-01

Protein lysine acetylation is recognized as an important reversible post translational modification in all domains of life. While its primary roles appear to reside in metabolic processes, lysine acetylation has also been implicated in regulating pathogenesis in bacteria. Several global lysine...... acetylome analyses have been carried out in various bacteria, but thus far there have been no reports of lysine acetylation taking place in the important human pathogen Vibrio cholerae. In this study, we analyzed the lysine acetylproteome of the human pathogen V. cholerae V52. By applying a combination...... in direct regulation of virulence in V. cholerae were acetylated. In conclusion, this is the first global protein lysine acetylome analysis of V. cholerae and should constitute a valuable resource for in-depth studies of the impact of lysine acetylation in pathogenesis and other cellular processes....

Enhancing E. coli tolerance towards oxidative stress via engineering its global regulator cAMP receptor protein (CRP.

Directory of Open Access Journals (Sweden)

Souvik Basak

Full Text Available Oxidative damage to microbial hosts often occurs under stressful conditions during bioprocessing. Classical strain engineering approaches are usually both time-consuming and labor intensive. Here, we aim to improve E. coli performance under oxidative stress via engineering its global regulator cAMP receptor protein (CRP, which can directly or indirectly regulate redox-sensing regulators SoxR and OxyR, and other ~400 genes in E. coli. Error-prone PCR technique was employed to introduce modifications to CRP, and three mutants (OM1~OM3 were identified with improved tolerance via H(2O(2 enrichment selection. The best mutant OM3 could grow in 12 mM H(2O(2 with the growth rate of 0.6 h(-1, whereas the growth of wild type was completely inhibited at this H(2O(2 concentration. OM3 also elicited enhanced thermotolerance at 48°C as well as resistance against cumene hydroperoxide. The investigation about intracellular reactive oxygen species (ROS, which determines cell viability, indicated that the accumulation of ROS in OM3 was always lower than in WT with or without H(2O(2 treatment. Genome-wide DNA microarray analysis has shown not only CRP-regulated genes have demonstrated great transcriptional level changes (up to 8.9-fold, but also RpoS- and OxyR-regulated genes (up to 7.7-fold. qRT-PCR data and enzyme activity assay suggested that catalase (katE could be a major antioxidant enzyme in OM3 instead of alkyl hydroperoxide reductase or superoxide dismutase. To our knowledge, this is the first work on improving E. coli oxidative stress resistance by reframing its transcription machinery through its native global regulator. The positive outcome of this approach may suggest that engineering CRP can be successfully implemented as an efficient strain engineering alternative for E. coli.

A Flexible Binding Site Architecture Provides New Insights into CcpA Global Regulation in Gram-Positive Bacteria.

Science.gov (United States)

Yang, Yunpeng; Zhang, Lu; Huang, He; Yang, Chen; Yang, Sheng; Gu, Yang; Jiang, Weihong

2017-01-24

Catabolite control protein A (CcpA) is the master regulator in Gram-positive bacteria that mediates carbon catabolite repression (CCR) and carbon catabolite activation (CCA), two fundamental regulatory mechanisms that enable competitive advantages in carbon catabolism. It is generally regarded that CcpA exerts its regulatory role by binding to a typical 14- to 16-nucleotide (nt) consensus site that is called a catabolite response element (cre) within the target regions. However, here we report a previously unknown noncanonical flexible architecture of the CcpA-binding site in solventogenic clostridia, providing new mechanistic insights into catabolite regulation. This novel CcpA-binding site, named cre var , has a unique architecture that consists of two inverted repeats and an intervening spacer, all of which are variable in nucleotide composition and length, except for a 6-bp core palindromic sequence (TGTAAA/TTTACA). It was found that the length of the intervening spacer of cre var can affect CcpA binding affinity, and moreover, the core palindromic sequence of cre var is the key structure for regulation. Such a variable architecture of cre var shows potential importance for CcpA's diverse and fine regulation. A total of 103 potential cre var sites were discovered in solventogenic Clostridium acetobutylicum, of which 42 sites were picked out for electrophoretic mobility shift assays (EMSAs), and 30 sites were confirmed to be bound by CcpA. These 30 cre var sites are associated with 27 genes involved in many important pathways. Also of significance, the cre var sites are found to be widespread and function in a great number of taxonomically different Gram-positive bacteria, including pathogens, suggesting their global role in Gram-positive bacteria. In Gram-positive bacteria, the global regulator CcpA controls a large number of important physiological and metabolic processes. Although a typical consensus CcpA-binding site, cre, has been identified, it remains

Reconstruction of the yeast Snf1 kinase regulatory network reveals its role as a global energy regulator

DEFF Research Database (Denmark)

Usaite, Renata; Jewett, Michael Christopher; Soberano de Oliveira, Ana Paula

2009-01-01

Highly conserved among eukaryotic cells, the AMP-activated kinase (AMPK) is a central regulator of carbon metabolism. To map the complete network of interactions around AMPK in yeast (Snf1) and to evaluate the role of its regulatory subunit Snf4, we measured global mRNA, protein and metabolite...

Is Green Regulation Effective or a Failure: Comparative Analysis between Bangladesh Bank (BB Green Guidelines and Global Reporting Initiative Guidelines

Directory of Open Access Journals (Sweden)

Md. Abdul Kaium Masud

2018-04-01

Full Text Available Green reporting and green regulation have been commonly used in the sustainability movement. This study evaluates Bangladesh Bank’s (BB’s green regulation by considering the global reporting initiative (GRI of environmental regulation along with self-determined content to justify BB’s institutional effort in the banking sector. The analytical study has considered secondary data of all listed banks on the Dhaka Stock Exchange between 2013 to 2016. A multi-theoretical framework has been adopted in which the research is comprised of institutional, stakeholder, and legitimacy theories. Considering the analytical research, we have drawn-up a green reporting score and undertaken SWOT analysis. The results of the study have identified the narrow coverage of BB’s regulation and strategic limitations. Moreover, the findings of the study show that banking companies disclosed more green information in line with BB’s regulation. Furthermore, our analysis has found the lack of transparency of green reporting in terms of absent global reporting as well as external verification. Additionally, we have documented that BB’s regulation falls into a legitimacy threat owing to political, corporate, and social responsibility. Therefore, we concluded that for BB to overcome all possible weaknesses and threats, it should consider all possible opportunities for a holistic international reporting framework while taking into account a transparent financial sector.

The influence of globalization on medical regulation: a descriptive analysis of international medical graduates registered through alternative licensure routes in Ontario

Science.gov (United States)

Yen, Wendy; Hodwitz, Kathryn; Thakkar, Niels; Martimianakis, Maria Athina (Tina); Faulkner, Dan

2016-01-01

The increasing globalization of the medical profession has influenced health policy, health human resource planning, and medical regulation in Canada. Since the early 2000s, numerous policy initiatives have been created to facilitate the entry of international medical graduates (IMGs) into the Canadian workforce. In Ontario, the College of Physicians and Surgeons of Ontario (CPSO) developed alternative licensure routes to increase the ability of qualified IMGs to obtain licenses to practice. The current study provides demographic and descriptive information about the IMGs registered through the CPSO’s alternative licensure routes between 2000 and 2012. An analysis of the characteristics and career trajectories of all IMGs practicing in the province sheds light on broader globalization trends and raises questions about the future of health human resource planning in Canada. As the medical profession becomes increasingly globalized, health policy and regulation will continue to be influenced by trends in international migration, concerns about global health equity, and the shifting demographics of the Canadian physician workforce. Implications for future policy development in the complex landscape of medical education and practice are discussed. PMID:28344705

The influence of globalization on medical regulation: a descriptive analysis of international medical graduates registered through alternative licensure routes in Ontario.

Science.gov (United States)

Yen, Wendy; Hodwitz, Kathryn; Thakkar, Niels; Martimianakis, Maria Athina Tina; Faulkner, Dan

2016-12-01

The increasing globalization of the medical profession has influenced health policy, health human resource planning, and medical regulation in Canada. Since the early 2000s, numerous policy initiatives have been created to facilitate the entry of international medical graduates (IMGs) into the Canadian workforce. In Ontario, the College of Physicians and Surgeons of Ontario (CPSO) developed alternative licensure routes to increase the ability of qualified IMGs to obtain licenses to practice. The current study provides demographic and descriptive information about the IMGs registered through the CPSO's alternative licensure routes between 2000 and 2012. An analysis of the characteristics and career trajectories of all IMGs practicing in the province sheds light on broader globalization trends and raises questions about the future of health human resource planning in Canada. As the medical profession becomes increasingly globalized, health policy and regulation will continue to be influenced by trends in international migration, concerns about global health equity, and the shifting demographics of the Canadian physician workforce. Implications for future policy development in the complex landscape of medical education and practice are discussed.

The influence of globalization on medical regulation: a descriptive analysis of international medical graduates registered through alternative licensure routes in Ontario

Directory of Open Access Journals (Sweden)

Wendy Yen

2016-12-01

Full Text Available The increasing globalization of the medical profession has influenced health policy, health human resource planning, and medical regulation in Canada. Since the early 2000s, numerous policy initiatives have been created to facilitate the entry of international medical graduates (IMGs into the Canadian workforce. In Ontario, the College of Physicians and Surgeons of Ontario (CPSO developed alternative licensure routes to increase the ability of qualified IMGs to obtain licenses to practice. The current study provides demographic and descriptive information about the IMGs registered through the CPSO’s alternative licensure routes between 2000 and 2012. An analysis of the characteristics and career trajectories of all IMGs practicing in the province sheds light on broader globalization trends and raises questions about the future of health human resource planning in Canada. As the medical profession becomes increasingly globalized, health policy and regulation will continue to be influenced by trends in international migration, concerns about global health equity, and the shifting demographics of the Canadian physician workforce. Implications for future policy development in the complex landscape of medical education and practice are discussed.

Global self-esteem, goal achievement orientations, and self-determined behavioural regulations in a physical education setting.

Science.gov (United States)

Hein, Vello; Hagger, Martin S

2007-01-15

We examined a theoretical model of global self-esteem that incorporated constructs from achievement goal and self-determination theories. The model hypothesized that self-determined or autonomous motives would mediate the influence of achievement goal orientation on global self-esteem. The adapted version of the Behavioural Regulation in Exercise Questionnaire (Mullan et al., 1997), the Perception of Success Questionnaire (Roberts & Balague, 1991), and Rosenberg's (1965) self-esteem scales were administered to 634 high school students aged 11 - 15 years. A structural equation model supported the hypotheses and demonstrated that autonomous motives mediated the effect of goal orientations on global self-esteem. The results suggest that generalized motivational orientations influence self-esteem by affecting autonomous motivation and is consistent with theory that suggests that experiences relating to intrinsic motivation are the mechanism by which global motivational orientations are translated into adaptive outcomes like self-esteem. The findings suggest that physical activity interventions that target autonomous motives in physical activity contexts are likely to enhance young people's general self-esteem.

Promoter Analysis Reveals Globally Differential Regulation of Human Long Non-Coding RNA and Protein-Coding Genes

KAUST Repository

Alam, Tanvir

2014-10-02

Transcriptional regulation of protein-coding genes is increasingly well-understood on a global scale, yet no comparable information exists for long non-coding RNA (lncRNA) genes, which were recently recognized to be as numerous as protein-coding genes in mammalian genomes. We performed a genome-wide comparative analysis of the promoters of human lncRNA and protein-coding genes, finding global differences in specific genetic and epigenetic features relevant to transcriptional regulation. These two groups of genes are hence subject to separate transcriptional regulatory programs, including distinct transcription factor (TF) proteins that significantly favor lncRNA, rather than coding-gene, promoters. We report a specific signature of promoter-proximal transcriptional regulation of lncRNA genes, including several distinct transcription factor binding sites (TFBS). Experimental DNase I hypersensitive site profiles are consistent with active configurations of these lncRNA TFBS sets in diverse human cell types. TFBS ChIP-seq datasets confirm the binding events that we predicted using computational approaches for a subset of factors. For several TFs known to be directly regulated by lncRNAs, we find that their putative TFBSs are enriched at lncRNA promoters, suggesting that the TFs and the lncRNAs may participate in a bidirectional feedback loop regulatory network. Accordingly, cells may be able to modulate lncRNA expression levels independently of mRNA levels via distinct regulatory pathways. Our results also raise the possibility that, given the historical reliance on protein-coding gene catalogs to define the chromatin states of active promoters, a revision of these chromatin signature profiles to incorporate expressed lncRNA genes is warranted in the future.

A microRNA feedback loop regulates global microRNA abundance during aging.

Science.gov (United States)

Inukai, Sachi; Pincus, Zachary; de Lencastre, Alexandre; Slack, Frank J

2018-02-01

Expression levels of many microRNAs (miRNAs) change during aging, notably declining globally in a number of organisms and tissues across taxa. However, little is known about the mechanisms or the biological relevance for this change. We investigated the network of genes that controls miRNA transcription and processing during C. elegans aging. We found that miRNA biogenesis genes are highly networked with transcription factors and aging-associated miRNAs. In particular, miR-71, known to influence life span and itself up-regulated during aging, represses alg-1 /Argonaute expression post-transcriptionally during aging. Increased ALG-1 abundance in mir-71 loss-of-function mutants led to globally increased miRNA expression. Interestingly, these mutants demonstrated widespread mRNA expression dysregulation and diminished levels of variability both in gene expression and in overall life span. Thus, the progressive molecular decline often thought to be the result of accumulated damage over an organism's life may be partially explained by a miRNA-directed mechanism of age-associated decline. © 2018 Inukai et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Strengthening global health security by embedding the International Health Regulations requirements into national health systems.

Science.gov (United States)

Kluge, Hans; Martín-Moreno, Jose Maria; Emiroglu, Nedret; Rodier, Guenael; Kelley, Edward; Vujnovic, Melitta; Permanand, Govin

2018-01-01

The International Health Regulations (IHR) 2005, as the overarching instrument for global health security, are designed to prevent and cope with major international public health threats. But poor implementation in countries hampers their effectiveness. In the wake of a number of major international health crises, such as the 2014 Ebola and 2016 Zika outbreaks, and the findings of a number of high-level assessments of the global response to these crises, it has become clear that there is a need for more joined-up thinking between health system strengthening activities and health security efforts for prevention, alert and response. WHO is working directly with its Member States to promote this approach, more specifically around how to better embed the IHR (2005) core capacities into the main health system functions. This paper looks at how and where the intersections between the IHR and the health system can be best leveraged towards developing greater health system resilience. This merging of approaches is a key component in pursuit of Universal Health Coverage and strengthened global health security as two mutually reinforcing agendas.

The global nitrogen regulator, FNR1, regulates fungal nutrition-genes and fitness during Fusarium oxysporum pathogenesis.

Science.gov (United States)

Divon, Hege Hvattum; Ziv, Carmit; Davydov, Olga; Yarden, Oded; Fluhr, Robert

2006-11-01

SUMMARY Fusarium oxysporum is a soil-borne pathogen that infects plants through the roots and uses the vascular system for host ingress. Specialized for this route of infection, F. oxysporum is able to adapt to the scarce nutrient environment in the xylem vessels. Here we report the cloning of the F. oxysporum global nitrogen regulator, Fnr1, and show that it is one of the determinants for fungal fitness during in planta growth. The Fnr1 gene has a single conserved GATA-type zinc finger domain and is 96% and 48% identical to AREA-GF from Gibberella fujikuroi, and NIT2 from Neurospora crassa, respectively. Fnr1 cDNA, expressed under a constitutive promoter, was able to complement functionally an N. crassa nit-2(RIP) mutant, restoring the ability of the mutant to utilize nitrate. Fnr1 disruption mutants showed high tolerance to chlorate and reduced ability to utilize several secondary nitrogen sources such as amino acids, hypoxanthine and uric acid, whereas growth on favourable nitrogen sources was not affected. Fnr1 disruption also abolished in vitro expression of nutrition genes, normally induced during the early phase of infection. In an infection assay on tomato seedlings, infection rate of disruption mutants was significantly delayed in comparison with the parental strain. Our results indicate that FNR1 mediates adaptation to nitrogen-poor conditions in planta through the regulation of secondary nitrogen acquisition, and as such acts as a determinant for fungal fitness during infection.

Combating global warming. Possible rules, regulations and administrative arrangements for a global market in CO2 emission entitlements

International Nuclear Information System (INIS)

1994-12-01

When in 1991 the UNCTAD secretariat launched its research into the idea of controlling carbon dioxide emissions through a system of 'tradeable permits', there was little support for this approach. Some felt that the idea was premature and should not detract from efforts to introduce more conventional measures, such as environmental taxes and new regulations. However, in a few short years, the idea of using tradeable market-based instruments to combat global warming has gained widespread acceptance. The UNCTAD secretariat's 1992 study on a global system of tradeable carbon emission entitlements (UNCTAD/RDP/DFP/1), was widely regarded as a major breakthrough in this area. This study argued that tradeable permits were both an efficient means of controlling man-made carbon dioxide emissions at minimum cost, and an effective mechanism for transferring resources to developing countries and countries in transition, to help them to contribute to the international effort to abate emissions of greenhouse gases. The study contained a detailed assessment of key technical elements of a tradeable CO 2 entitlements system, including permit allocation techniques, resource transfers, equity/distributional implications, institutional and administrative requirements. The present publication explores the institutional requirements for both policy-making and the organization of a global market in CO 2 emission allowances. It shows that one can start with a simple pilot scheme based on the joint implementation of commitments, which constitutes the cornerstone of the Framework Convention, and evolve gradually to a more complete system on the basis of 'learning by doing'. Since the use of markets can dramatically lower the cost of controlling greenhouse gas emissions, it is clearly in the self-interest of major emitters to act as 'market leaders' willing to pioneer

Model rules and regulations for a global CO2 emissions credit market

International Nuclear Information System (INIS)

Sandor, R.L.; Cole, J.B.; Kelly, M.E.

1994-01-01

On 21 April 1993, on the occasion of Earth Day, the United States affirmed its commitment to reducing emissions of greenhouse gases to their 1990 levels by the year 2000. In doing so, the United States joined the European Union (EU), Japan, and approximately 141 other countries that had either committed themselves to this international objective or subscribed to the general principles contained in the United Nations Framework Convention on Climate Change, signed at UNCED, Rio de Janeiro, June 1992. The commitment of these three trading groups provides the basis for recommending that a market for tradeable carbon dioxide (CO 2 ) emission entitlements among these groups be implemented as soon as an initial set of rules and regulations can be drafted. The goal of a tradeable CO 2 entitlement or credit market is to lower the cost of limiting emissions. The Costs of CO 2 emission abatement are lowered because the market encourages more emission reductions to be produced by the most efficient resources. The ability easily to selI CO 2 credits created through large emission cuts allows cost recovery by, and incentives for, the most efficient sources of emission reductions. The purpose of this paper is to stimulate debate by providing model rules and regulations for a tradeable CO 2 emission credit market. The trading rules and regulations proposed here are meant to initiate a process whereby participants will iterate toward a final set of rules and regulations. Therefore, our proposal should create a point of departure for further adjustments and transformation to the initial set of recommendations. A specific proposal will be advanced at this point in order to provide a basis for the conceptualization of this global market. Moreover, this specific proposal will help focus dialogue and may provide insight into the general recommendations presented in the balance of this paper

Structure analysis of the global metabolic regulator Crc from Pseudomonas aeruginosa.

Science.gov (United States)

Wei, Yong; Zhang, Heng; Gao, Zeng-Qiang; Xu, Jian-Hua; Liu, Quan-Sheng; Dong, Yu-Hui

2013-01-01

The global metabolic regulator catabolite repression control (Crc) has recently been found to modulate the susceptibility to antibiotics and virulence in the opportunistic pathogen Pseudomonas aeruginosa and been suggested as a nonlethal target for novel antimicrobials. In P. aeruginosa, Crc couples with the CA motifs from the small RNA CrcZ to form a post-transcriptional regulator system and is removed from the 5'-end of the target mRNAs. In this study, we first reported the crystal structure of Crc from P. aeruginosa refined to 2.20 Å. The structure showed that it consists of two halves with similar overall topology and there are 11 β strands surrounded by 13 helices, forming a four-layered α/β-sandwich. The circular dichroism spectroscopy revealed that it is thermostable in solution and shares similar characteristics to that in crystal. Comprehensive structural analysis and comparison with the homologies of Crc showed high similarity with several known nucleases and consequently may be classified into a member exodeoxyribonuclease III. However, it shows distinct substrate specificity (RNA as the preferred substrate) compared to these DNA endonucleases. Structural comparisons also revealed potential RNA recognition and binding region mainly consisting of five flexible loops. Our structure study provided the basis for the future application of Crc as a target to develop new antibiotics. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

Platelet-derived microparticles regulates thrombin generation via phophatidylserine in abdominal sepsis.

Science.gov (United States)

Wang, Yongzhi; Zhang, Su; Luo, Lingtao; Norström, Eva; Braun, Oscar Ö; Mörgelin, Matthias; Thorlacius, Henrik

2018-02-01

Sepsis is associated with dysfunctional coagulation. Recent data suggest that platelets play a role in sepsis by promoting neutrophil accumulation. Herein, we show that cecal ligation and puncture (CLP) triggered systemic inflammation, which is characterized by formation of IL-6 and CXC chemokines as well as neutrophil accumulation in the lung. Platelet depletion decreased neutrophil accumulation, IL-6, and CXC chemokines formation in septic lungs. Depletion of platelets increased peak thrombin formation and total thrombin generation (TG) in plasma from septic animals. CLP elevated circulating levels of platelet-derived microparticles (PMPs). In vitro generated PMPs were a potent inducer of TG. Interestingly, in vitro wild-type recombinant annexin V abolished PMP-induced thrombin formation whereas a mutant annexin V protein, which does not bind to phosphatidylserine (PS), had no effect. Administration of wild-type, but not mutant annexin V, significantly inhibited thrombin formation in septic animals. Moreover, CLP-induced formation of thrombin-antithrombin complexes were reduced in platelet-depleted mice and in animals pretreated with annexin V. PMP-induced TG attenuated in FXII- and FVII-deficient plasma. These findings suggest that sepsis-induced TG is dependent on platelets. Moreover, PMPs formed in sepsis are a potent inducer of TG via PS exposure, and activation of both the intrinsic and extrinsic pathway of coagulation. In conclusion, these observations suggest that PMPs and PS play an important role in dysfunctional coagulation in abdominal sepsis. © 2017 Wiley Periodicals, Inc.

Differential modulation of global and local neural oscillations in REM sleep by homeostatic sleep regulation.

Science.gov (United States)

Kim, Bowon; Kocsis, Bernat; Hwang, Eunjin; Kim, Youngsoo; Strecker, Robert E; McCarley, Robert W; Choi, Jee Hyun

2017-02-28

Homeostatic rebound in rapid eye movement (REM) sleep normally occurs after acute sleep deprivation, but REM sleep rebound settles on a persistently elevated level despite continued accumulation of REM sleep debt during chronic sleep restriction (CSR). Using high-density EEG in mice, we studied how this pattern of global regulation is implemented in cortical regions with different functions and network architectures. We found that across all areas, slow oscillations repeated the behavioral pattern of persistent enhancement during CSR, whereas high-frequency oscillations showed progressive increases. This pattern followed a common rule despite marked topographic differences. The findings suggest that REM sleep slow oscillations may translate top-down homeostatic control to widely separated brain regions whereas fast oscillations synchronizing local neuronal ensembles escape this global command. These patterns of EEG oscillation changes are interpreted to reconcile two prevailing theories of the function of sleep, synaptic homeostasis and sleep dependent memory consolidation.

Untreated pain, narcotics regulation, and global health ideologies.

Science.gov (United States)

King, Nicholas B; Fraser, Veronique

2013-01-01

Pain management is marginalized or ignored, with millions of people worldwide unnecessarily living with untreated pain. Reducing global inequalities in untreated pain requires a concerted global effort, say Veronique Fraser and colleagues, which must attend to the complexity of pain and promote multimodal, multidisciplinary pain management.

[Involvement of the global regulators GrrS, RpoS, and SplIR in formation of biofilms in Serratia plymuthica].

Science.gov (United States)

Zaĭtseva, Iu V; Voloshina, P V; Liu, X; Ovadis, M I; Berg, G; Chernin, L S; Khmel', I A

2010-05-01

Most bacteria exist in the natural environment as biofilms, multicellular communities attached to hard surfaces. Biofilms have a characteristic architecture and are enclosed in the exopolymer matrix. Bacterial cells in biofilms are extremely resistant to antibacterial factors. It was shown in this work that the GrrA/GrrS system of global regulators of gene expression and the sigma S subunit of RNA polymerase (RpoS) play a significant role in positive regulation of biofilm formation in the rhizospheric bacterium Serratia plymuthica IC1270. Inactivation of grrS and rpoS genes resulted in an up to six-to-sevenfold and four-to-fivefold reduction in biofilm formation, respectively. Mutations in the grrS gene decreased the capacity of the bacterium for swarming motility. The splIR Quorum Sensing (QS) system was shown to negatively influence the biofilm formation. Transfer of the recombinant plasmid containing cloned genes splI/splR of S. plymuthica HRO-C48 into S. plymuthica IC1270 cells led to a twofold decrease of their ability to form biofilms. Inactivation of the splI gene coding for the synthase of N-acyl-homoserine lactones in S. plymuthica HRO-C48 resulted in a 2-2.5-fold increase in the level of biofilm formation, whereas the inclusion of plasmid carrying the cloned splI/splR genes into these mutant cells restored the biofilm formation to the normal level. The results obtained demonstrate that the formation of biofilms in S. plymuthica is positively regulated by the GrrA/GrrS and RpoS global regulators and is negatively regulated by the SplIR QS system.

Globalization and business ethics

OpenAIRE

Khadartseva, L.; Agnaeva, L.

2014-01-01

It is assumed that local conditions of markets may be different, but some global markets, ethics and social responsibility principles should be applicable to all markets. As markets globalize and an increasing proportion of business activity transcends national borders, institutions need to help manage, regulate, and police the global marketplace, and to promote the establishment of multinational treaties to govern the global business system

Hong Kong's electricity market beyond 2008

International Nuclear Information System (INIS)

Lam, Pun Lee

2004-01-01

In Hong Kong, electricity is supplied by two private utilities: Hongkong Electric and CLP Power (CLP). Both are regulated under the Scheme of Control (SOC). The SOC is a formal, long-term regulatory contract of 15 years, signed between a private firm and the Hong Kong Government. Under the SOC, the two electric utilities are subject to both rate-of-return control and price control. The current scheme will expire by 2008. In this paper, we propose a gradual and cautious approach to the introduction of market reform into the electricity industry in Hong Kong. For regulated markets, the government should consider replacing the SOC with performance-based regulation for wire businesses and the non-contestable market. For competitive markets, the government should consider introducing competitive tendering for new sources in the generation market and liberalising the supply market in phases. (author)

Hong Kong's electricity market beyond 2008

International Nuclear Information System (INIS)

Lam, P.-L.

2004-01-01

In Hong Kong, electricity is supplied by two private utilities: Hongkong Electric and CLP Power (CLP). Both are regulated under the Scheme of Control (SOC). The SOC is a formal, long-term regulatory contract of 15 years, signed between a private firm and the Hong Kong Government. Under the SOC, the two electric utilities are subject to both rate-of-return control and price control. The current scheme will expire by 2008. In this paper, we propose a gradual and cautious approach to the introduction of market reform into the electricity industry in Hong Kong. For regulated markets, the government should consider replacing the SOC with performance-based regulation for wire businesses and the non-contestable market. For competitive markets, the government should consider introducing competitive tendering for new sources in the generation market and liberalising the supply market in phases

State - Level Regulation's Effectiveness in Addressing Global Climate Change and Promoting Solar Energy Deployment

Science.gov (United States)

Peterman, Carla Joy

Paper 1, Local Solutions to Global Problems: Climate Change Policies and Regulatory Jurisdiction, considers the efficacy of various types of environmental regulations when they are applied locally to pollutants whose damages extend beyond the jurisdiction of the local regulators. Local regulations of a global pollutant may be ineffective if producers and consumers can avoid them by transacting outside the reach of the local regulator. In many cases, this may involve the physical relocation of the economic activity, a problem often referred to as "leakage." This paper highlights another way in which local policies can be circumvented: through the shuffling of who buys from whom. The paper maintains that the problems of reshuffling are exacerbated when the options for compliance with the regulations are more flexible. Numerical analyses is presented demonstrating that several proposed policies to limit greenhouse gas emissions from the California electricity sector may have very little effect on carbon emissions if they are applied only within that state. Paper 1 concludes that although local subsidies for energy efficiency, renewable electricity, and transportation biofuels constitute attempts to pick technology winners, they may be the only mechanisms that local jurisdictions, acting alone, have at their disposal to address climate change. Paper 2, Pass-Through of Solar PV Incentives to Consumers: The Early Years of California's Solar PV Incentives, examines the pass through of incentives to California solar PV system owners. The full post-subsidy price consumers pay for solar power is a key metric of the success of solar PV incentive programs and of overall PV market performance. This study examines the early years of California's most recent wave of distributed solar PV incentives (2000-2008) to determine the pass-through of incentives. Examination of this period is both intellectually and pragmatically important due to the high level of incentives provided and

Photometric Evaluation of Soft Tissue Changes in CLP Patients: Le Fort I Advancement Osteotomy (ALO) Versus Anterior Maxillary Distraction (AMD).

Science.gov (United States)

Paulose, Joby; Markose, Eldho

2014-12-01

This paper is a comparative photometric evaluation of soft tissue changes in patients with CLP associated with maxillary deficiency treated with conventional Le Fort I advancement osteotomy (ALO) and anterior maxillary distraction (AMD). Twenty patients with maxillary hypoplasia associated with cleft lip and palate who had undergone either LeFort I osteotomy or distraction osteogenesis with maxillary advancement were included in this study. Frontal and profile photographs were used to ascertain the changes post-surgically. Photographs were obtained before treatment and 1 year after surgical correction in both groups. Vertical as well as horizontal changes in pronasale was well observed in both groups. A substantial increase in nasal parameters was noted in case of AMD group in comparison to ALO group. Though maxillary advancement was quite evident in AMD and ALO groups, a significant and consistent change was observed in AMD group. Significant vertical and horizontal changes were seen with respect to subnasale and labrale superius in AMD group. The hard and soft tissue changes produced by AMD by intra oral distractors were being evaluated so far. The results of the above studies have proved the excellence of AMD over conventional osteotomies. The present study goes hand in hand with the research outcomes till date.

Money Laundering, Corruption and Growth: An Empirical Rationale for a Global Convergence on Anti-Money Laundering Regulation

OpenAIRE

Cavalcante Veiga, Luiz Humberto; Andrade, Joaquim Pinto

2006-01-01

This paper provides empirical evidence on the impact of anti-money laundering regulations on growth and, it examines the rationale for a global adoption of these rules. The empirical results have led us to confirm a positive relation between low corruption levels and high investment and growth. We approached the impact on growth of money laundering prevention (MLP) initiatives in two ways: first, by verifying that the existence of these initiatives affects the perception of corruption. Second...

Global water cycle

Science.gov (United States)

Robertson, Franklin; Goodman, Steven J.; Christy, John R.; Fitzjarrald, Daniel E.; Chou, Shi-Hung; Crosson, William; Wang, Shouping; Ramirez, Jorge

1993-01-01

This research is the MSFC component of a joint MSFC/Pennsylvania State University Eos Interdisciplinary Investigation on the global water cycle extension across the earth sciences. The primary long-term objective of this investigation is to determine the scope and interactions of the global water cycle with all components of the Earth system and to understand how it stimulates and regulates change on both global and regional scales. Significant accomplishments in the past year are presented and include the following: (1) water vapor variability; (2) multi-phase water analysis; (3) global modeling; and (4) optimal precipitation and stream flow analysis and hydrologic processes.

CytR Is a Global Positive Regulator of Competence, Type VI Secretion, and Chitinases in Vibrio cholerae.

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Samit S Watve

Full Text Available The facultative pathogen Vibrio cholerae transitions between its human host and aquatic reservoirs where it colonizes chitinous surfaces. Growth on chitin induces expression of chitin utilization genes, genes involved in DNA uptake by natural transformation, and a type VI secretion system that allows contact-dependent killing of neighboring bacteria. We have previously shown that the transcription factor CytR, thought to primarily regulate the pyrimidine nucleoside scavenging response, is required for natural competence in V. cholerae. Through high-throughput RNA sequencing (RNA-seq, we show that CytR positively regulates the majority of competence genes, the three type VI secretion operons, and the four known or predicted chitinases. We used transcriptional reporters and phenotypic analysis to determine the individual contributions of quorum sensing, which is controlled by the transcription factors HapR and QstR; chitin utilization that is mediated by TfoX; and pyrimidine starvation that is orchestrated by CytR, toward each of these processes. We find that in V. cholerae, CytR is a global regulator of multiple behaviors affecting fitness and adaptability in the environment.

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

Globalization and protection of employment

OpenAIRE

Fischer, Justina A.V.; Somogyi, Frank

2012-01-01

Unionists and politicians frequently claim that globalization lowers employment protection of workers. This paper tests this hypothesis in a panel of 28 OECD countries from 1985 to 2003, differentiating between three dimensions of globalization and two labor market segments. While overall globalization is shown to loosen protection of the regularly employed, it increases regulation in the segment of limited-term contracts. We find economic and political globalization to drive deregulation ...

Examining the global health arena: strengths and weaknesses of a convention approach to global health challenges.

Science.gov (United States)

Haffeld, Just Balstad; Siem, Harald; Røttingen, John-Arne

2010-01-01

The article comprises a conceptual framework to analyze the strengths and weaknesses of a global health convention. The analyses are inspired by Lawrence Gostin's suggested Framework Convention on Global Health. The analytical model takes a starting-point in events tentatively following a logic sequence: Input (global health funding), Processes (coordination, cooperation, accountability, allocation of aid), Output (definition of basic survival needs), Outcome (access to health services), and Impact (health for all). It then examines to what degree binding international regulations can create order in such a sequence of events. We conclude that a global health convention could be an appropriate instrument to deal with some of the problems of global health. We also show that some of the tasks preceding a convention approach might be to muster international support for supra-national health regulations, negotiate compromises between existing stakeholders in the global health arena, and to utilize WHO as a platform for further discussions on a global health convention. © 2010 American Society of Law, Medicine & Ethics, Inc.

Effects of Heat Stress on Construction Labor Productivity in Hong Kong: A Case Study of Rebar Workers.

Science.gov (United States)

Yi, Wen; Chan, Albert P C

2017-09-12

Global warming is bringing more frequent and severe heat waves, and the result will be serious for vulnerable populations such as construction workers. Excessive heat stress has profound effects on physiological responses, which cause occupational injuries, fatalities and low productivity. Construction workers are particularly affected by heat stress, because of the body heat production caused by physically demanding tasks, and hot and humid working conditions. Field studies were conducted between August and September 2016 at two construction training grounds in Hong Kong. Onsite wet-bulb globe temperature (WBGT), workers' heart rate (HR), and labor productivity were measured and monitored. Based on the 378 data sets of synchronized environmental, physiological, construction labor productivity (CLP), and personal variables, a CLP-heat stress model was established. It was found that WBGT, percentage of maximum HR, age, work duration, and alcohol drinking habits were determining factors for predicting the CLP (adjusted R ² = 0.68, p stress reduces CLP, with the percentage of direct work time decreasing by 0.33% when the WBGT increased by 1 °C. The findings in this study extend the existing practice notes by providing scientific data that may be of benefit to the industry in producing solid guidelines for working in hot weather.

Global identification of bursicon-regulated genes in Drosophila melanogaster

Directory of Open Access Journals (Sweden)

Beerntsen Brenda

2008-09-01

Full Text Available Abstract Background Bursicon is a heterodimer neuropeptide responsible for regulating cuticle sclerotization and wing expansion in several insect species. Recent studies indicate that the action of bursicon is mediated by a specific G protein-coupled receptor DLGR2 and the cAMP/PKA signaling pathway. However, little is known regarding the genes that are regulated by bursicon. The identification of bursicon-regulated genes is the focus of this investigation. Results We used DNA microarray analysis to identify bursicon-regulated genes in neck-ligated flies (Drosophila melanogaster that received recombinant bursicon (r-bursicon. Fifty four genes were found to be regulated by bursicon 1 h post r-bursicon injection, 52 being up-regulated and 2 down-regulated while 33 genes were influenced by r-bursicon 3 h post-injection (24 up-regulated and 9 down-regulated genes. Analysis of these genes by inference from the fly database http://flybase.bio.indiana.edu revealed that these genes encode proteins with diverse functions, including cell signaling, gene transcription, DNA/RNA binding, ion trafficking, proteolysis-peptidolysis, metabolism, cytoskeleton formation, immune response and cell-adhesion. Twenty eight genes randomly selected from the microarray-identified list were verified by real time PCR (qPCR which supported the microarray data. Temporal response studies of 13 identified and verified genes by qPCR revealed that the temporal expression patterns of these genes are consistent with the microarray data. Conclusion Using r-bursicon, we identified 87 genes that are regulated by bursicon, 30 of which have no previously known function. Most importantly, all genes randomly selected from the microarray-identified list were verified by real time PCR. Temporal analysis of 13 verified genes revealed that the expression of these genes was indeed induced by bursicon and correlated well with the cuticle sclerotization process. The composite data suggest that

Global DNA methylation synergistically regulates the nuclear and mitochondrial genomes in glioblastoma cells.

Science.gov (United States)

Sun, Xin; Johnson, Jacqueline; St John, Justin C

2018-05-02

Replication of mitochondrial DNA is strictly regulated during differentiation and development allowing each cell type to acquire its required mtDNA copy number to meet its specific needs for energy. Undifferentiated cells establish the mtDNA set point, which provides low numbers of mtDNA copy but sufficient template for replication once cells commit to specific lineages. However, cancer cells, such as those from the human glioblastoma multiforme cell line, HSR-GBM1, cannot complete differentiation as they fail to enforce the mtDNA set point and are trapped in a 'pseudo-differentiated' state. Global DNA methylation is likely to be a major contributing factor, as DNA demethylation treatments promote differentiation of HSR-GBM1 cells. To determine the relationship between DNA methylation and mtDNA copy number in cancer cells, we applied whole genome MeDIP-Seq and RNA-Seq to HSR-GBM1 cells and following their treatment with the DNA demethylation agents 5-azacytidine and vitamin C. We identified key methylated regions modulated by the DNA demethylation agents that also induced synchronous changes to mtDNA copy number and nuclear gene expression. Our findings highlight the control exerted by DNA methylation on the expression of key genes, the regulation of mtDNA copy number and establishment of the mtDNA set point, which collectively contribute to tumorigenesis.

Future-proofing global health: Governance of priorities.

Science.gov (United States)

Bennett, Belinda; Cohen, I Glenn; Davies, Sara E; Gostin, Lawrence O; Hill, Peter S; Mankad, Aditi; Phelan, Alexandra L

2018-05-01

The year 2015 was a significant anniversary for global health: 15 years since the adoption of the Millennium Development Goals and the creation of the Global Alliance for Vaccines and Immunization, followed two years later by the Global Fund to Fight AIDS, TB and Malaria. 2015 was also the 10-year anniversary of the adoption of the International Health Regulations (May 2005) and the formal entering into force of the Framework Convention on the Tobacco Control (February 2005). The anniversary of these frameworks and institutions illustrates the growth and contribution of 'global' health diplomacy. Each initiative has also revealed on-going issues with compliance, sustainable funding and equitable attention in global health governance. In this paper, we present four thematic challenges that will continue to challenge prioritisation within global health governance into the future unless addressed: framing and prioritising within global health governance; identifying stakeholders of the global health community; understanding the relationship between health and behaviour; and the role of governance and regulation in supporting global health.

Global SUMO proteome responses guide gene regulation, mRNA biogenesis, and plant stress responses

Directory of Open Access Journals (Sweden)

Magdalena eMazur

2012-09-01

Full Text Available Small-ubiquitin-like MOdifier (SUMO is a key regulator of abiotic stress, disease resistance and development in plants. The identification of >350 plant SUMO targets has revealed many processes modulated by SUMO and potential consequences of SUMO on its targets. Importantly, highly related proteins are SUMO-modified in plants, yeast, and metazoans. Overlapping SUMO targets include heat-shock proteins, transcription regulators, histones, histone-modifying enzymes, proteins involved in DNA damage repair, but also proteins involved in mRNA biogenesis and nucleo-cytoplasmic transport. Proteomics studies indicate key roles for SUMO in gene repression by controlling histone (deacetylation activity at genomic loci. The responsible heavily sumoylated transcriptional repressor complexes are recruited by EAR (Ethylene-responsive element binding factor [ERF]-associated Amphiphilic Repression-motif containing transcription factors in plants. These transcription factors are not necessarily themselves a SUMO target. Conversely, SUMO acetylation prevents binding of downstream partners by preventing binding of SIMs (SUMO-interaction peptide motifs presents in these partners, while SUMO acetylation has emerged as mechanism to recruit specifically bromodomains; bromodomain are generally linked with gene activation. These findings strengthen the idea of a bidirectional sumo-/acetylation switch in gene regulation. Quantitative proteomics has highlighted that global sumoylation provides a dynamic response to protein damage involving SUMO chain-mediated protein degradation, but also SUMO E3 ligase-dependent transcription of HSP (Heat-shock protein genes. With these insights in SUMO function and novel technical advancements, we can now study SUMO dynamics in responses to (abiotic stress in plants.

The liberal battlefields of global business regulation

Directory of Open Access Journals (Sweden)

Kate Macdonald

2010-11-01

Full Text Available The global justice movement has often been associated with opposition to the broad programme of ‘neoliberalism’ and associated patterns of ‘corporate globalisation’, creating a widespread impression that this movement is opposed to liberalism more broadly conceived. Our goal in this article is to challenge this widespread view. By engaging in critical interpretive analysis of the contemporary ‘corporate accountability’ movement, we argue that the corporate accountability agenda is not opposed to the core values of a liberal project. Rather, it is seeking to reconfigure the design of liberal institutions of individual rights-protection, adjusting these for new material conditions associated with economic globalisation, under which powerful corporations alongside states now pose direct and significant threats to individual rights. This activist agenda is, therefore, much less radical in its challenge to the prevailing liberal global order than it may initially appear, since it functions to buttress rather than corrode many core normative commitments underpinning the liberal political project.

Onboard Hydrogen/Helium Sensors in Support of the Global Technical Regulation: An Assessment of Performance in Fuel Cell Electric Vehicle Crash Tests

Energy Technology Data Exchange (ETDEWEB)

Post, M. B.; Burgess, R.; Rivkin, C.; Buttner, W.; O' Malley, K.; Ruiz, A.

2012-09-01

Automobile manufacturers in North America, Europe, and Asia project a 2015 release of commercial hydrogen fuel cell powered light-duty road vehicles. These vehicles will be for general consumer applications, albeit initially in select markets but with much broader market penetration expected by 2025. To assure international harmony, North American, European, and Asian regulatory representatives are striving to base respective national regulations on an international safety standard, the Global Technical Regulation (GTR), Hydrogen Fueled Vehicle, which is part of an international agreement pertaining to wheeled vehicles and equipment for wheeled vehicles.

Global regulators ExpA (GacA) and KdgR modulate extracellular enzyme gene expression through the RsmA-rsmB system in Erwinia carotovora subsp. carotovora.

Science.gov (United States)

Hyytiäinen, H; Montesano, M; Palva, E T

2001-08-01

The production of the main virulence determinants, the extracellular plant cell wall-degrading enzymes, and hence virulence of Erwinia carotovora subsp. carotovora is controlled by a complex regulatory network. One of the global regulators, the response regulator ExpA, a GacA homolog, is required for transcriptional activation of the extracellular enzyme genes of this soft-rot pathogen. To elucidate the mechanism of ExpA control as well as interactions with other regulatory systems, we isolated second-site transposon mutants that would suppress the enzyme-negative phenotype of an expA (gacA) mutant. Inactivation of kdgR resulted in partial restoration of extracellular enzyme production and virulence to the expA mutant, suggesting an interaction between the two regulatory pathways. This interaction was mediated by the RsmA-rsmB system. Northern analysis was used to show that the regulatory rsmB RNA was under positive control of ExpA. Conversely, the expression of rsmA encoding a global repressor was under negative control of ExpA and positive control of KdgR. This study indicates a central role for the RsmA-rsmB regulatory system during pathogenesis, integrating signals from the ExpA (GacA) and KdgR global regulators of extracellular enzyme production in E. carotovora subsp. carotovora.

Intergenic sequence between Arabidopsis caseinolytic protease B-cytoplasmic/heat shock protein100 and choline kinase genes functions as a heat-inducible bidirectional promoter.

Science.gov (United States)

Mishra, Ratnesh Chandra; Grover, Anil

2014-11-01

In Arabidopsis (Arabidopsis thaliana), the At1g74310 locus encodes for caseinolytic protease B-cytoplasmic (ClpB-C)/heat shock protein100 protein (AtClpB-C), which is critical for the acquisition of thermotolerance, and At1g74320 encodes for choline kinase (AtCK2) that catalyzes the first reaction in the Kennedy pathway for phosphatidylcholine biosynthesis. Previous work has established that the knockout mutants of these genes display heat-sensitive phenotypes. While analyzing the AtClpB-C promoter and upstream genomic regions in this study, we noted that AtClpB-C and AtCK2 genes are head-to-head oriented on chromosome 1 of the Arabidopsis genome. Expression analysis showed that transcripts of these genes are rapidly induced in response to heat stress treatment. In stably transformed Arabidopsis plants harboring this intergenic sequence between head-to-head oriented green fluorescent protein and β-glucuronidase reporter genes, both transcripts and proteins of the two reporters were up-regulated upon heat stress. Four heat shock elements were noted in the intergenic region by in silico analysis. In the homozygous transfer DNA insertion mutant Salk_014505, 4,393-bp transfer DNA is inserted at position -517 upstream of ATG of the AtClpB-C gene. As a result, AtCk2 loses proximity to three of the four heat shock elements in the mutant line. Heat-inducible expression of the AtCK2 transcript was completely lost, whereas the expression of AtClpB-C was not affected in the mutant plants. Our results suggest that the 1,329-bp intergenic fragment functions as a heat-inducible bidirectional promoter and the region governing the heat inducibility is possibly shared between the two genes. We propose a model in which AtClpB-C shares its regulatory region with heat-induced choline kinase, which has a possible role in heat signaling. © 2014 American Society of Plant Biologists. All Rights Reserved.

Strategies for restoration of deep-water coral ecosystems based on a global survey of oil and gas regulations

Science.gov (United States)

Cordes, E. E.; Jones, D.; Levin, L. A.

2016-02-01

The oil and gas industry is one of the most active agents of the global industrialization of the deep sea. The wide array of impacts following the Deepwater Horizon oil spill highlighted the need for a systematic review of existing regulations both in US waters and internationally. Within different exclusive economic zones, there are a wide variety of regulations regarding the survey of deep-water areas prior to leasing and the acceptable set-back distances from vulnerable marine ecosystems once they are discovered. There are also varying mitigation strategies for accidental release of oil and gas, including active monitoring systems, temporary closings of oil and gas production, and marine protected areas. The majority of these regulations are based on previous studies of typical impacts from oil and gas drilling, rather than accidental releases. However, the probability of an accident from standard operations increases significantly with depth. The Oil & Gas working group of the Deep Ocean Stewardship Initiative is an international partnership of scientists, managers, non-governmental organizations, and industry professionals whose goal is to review existing regulations for the oil & gas industry and produce a best practices document to advise both developed and developing nations on their regulatory structure as energy development moves into deeper waters.

HEXIM1 controls satellite cell expansion after injury to regulate skeletal muscle regeneration

Science.gov (United States)

Hong, Peng; Chen, Kang; Huang, Bihui; Liu, Min; Cui, Miao; Rozenberg, Inna; Chaqour, Brahim; Pan, Xiaoyue; Barton, Elisabeth R.; Jiang, Xian-Cheng; Siddiqui, M.A.Q.

2012-01-01

The native capacity of adult skeletal muscles to regenerate is vital to the recovery from physical injuries and dystrophic diseases. Currently, the development of therapeutic interventions has been hindered by the complex regulatory network underlying the process of muscle regeneration. Using a mouse model of skeletal muscle regeneration after injury, we identified hexamethylene bisacetamide inducible 1 (HEXIM1, also referred to as CLP-1), the inhibitory component of the positive transcription elongation factor b (P-TEFb) complex, as a pivotal regulator of skeletal muscle regeneration. Hexim1-haplodeficient muscles exhibited greater mass and preserved function compared with those of WT muscles after injury, as a result of enhanced expansion of satellite cells. Transplanted Hexim1-haplodeficient satellite cells expanded and improved muscle regeneration more effectively than WT satellite cells. Conversely, HEXIM1 overexpression restrained satellite cell proliferation and impeded muscle regeneration. Mechanistically, dissociation of HEXIM1 from P-TEFb and subsequent activation of P-TEFb are required for satellite cell proliferation and the prevention of early myogenic differentiation. These findings suggest a crucial role for the HEXIM1/P-TEFb pathway in the regulation of satellite cell–mediated muscle regeneration and identify HEXIM1 as a potential therapeutic target for degenerative muscular diseases. PMID:23023707

An index-based framework for assessing patterns and trends in river fragmentation and flow regulation by global dams at multiple scales

International Nuclear Information System (INIS)

Grill, Günther; Lehner, Bernhard; Lumsdon, Alexander E; Zarfl, Christiane; MacDonald, Graham K; Reidy Liermann, Catherine

2015-01-01

The global number of dam constructions has increased dramatically over the past six decades and is forecast to continue to rise, particularly in less industrialized regions. Identifying development pathways that can deliver the benefits of new infrastructure while also maintaining healthy and productive river systems is a great challenge that requires understanding the multifaceted impacts of dams at a range of scales. New approaches and advanced methodologies are needed to improve predictions of how future dam construction will affect biodiversity, ecosystem functioning, and fluvial geomorphology worldwide, helping to frame a global strategy to achieve sustainable dam development. Here, we respond to this need by applying a graph-based river routing model to simultaneously assess flow regulation and fragmentation by dams at multiple scales using data at high spatial resolution. We calculated the cumulative impact of a set of 6374 large existing dams and 3377 planned or proposed dams on river connectivity and river flow at basin and subbasin scales by fusing two novel indicators to create a holistic dam impact matrix for the period 1930–2030. Static network descriptors such as basin area or channel length are of limited use in hierarchically nested and dynamic river systems, so we developed the river fragmentation index and the river regulation index, which are based on river volume. These indicators are less sensitive to the effects of network configuration, offering increased comparability among studies with disparate hydrographies as well as across scales. Our results indicate that, on a global basis, 48% of river volume is moderately to severely impacted by either flow regulation, fragmentation, or both. Assuming completion of all dams planned and under construction in our future scenario, this number would nearly double to 93%, largely due to major dam construction in the Amazon Basin. We provide evidence for the importance of considering small to medium

Metrological traceability and harmonization of medical tests: a quantum leap forward is needed to keep pace with globalization and stringent IVD-regulations in the 21st century!

Science.gov (United States)

Cobbaert, Christa; Smit, Nico; Gillery, Philippe

2018-05-07

In our efforts to advance the profession and practice of clinical laboratory medicine, strong coordination and collaboration are needed more than ever before. At the dawn of the 21st century, medical laboratories are facing many unmet clinical needs, a technological revolution promising a plethora of better biomarkers, financial constraints, a growing scarcity of well-trained laboratory technicians and a sharply increasing number of International Organization for Standardization guidelines and new regulations to which medical laboratories should comply in order to guarantee safety and effectiveness of medical test results. Although this is a global trend, medical laboratories across continents and countries are in distinct phases and experience various situations. A universal underlying requirement for safe and global use of medical test results is the standardization and harmonization of test results. Since two decades and after a number of endeavors on standardization/harmonization of medical tests, it is time to reflect on the effectiveness of the approaches used. To keep laboratory medicine sustainable, viable and affordable, clarification of the promises of metrological traceability of test results for improving sick and health care, realization of formal commitment among all stakeholders of the metrological traceability chain and preparation of a joint and global plan for action are essential prerequisites. Policy makers and regulators should not only overwhelm the diagnostic sector with oversight and regulations but should also create the conditions by establishing a global professional forum for anchoring the metrological traceability concept in the medical test domain. Even so, professional societies should have a strong voice in their (inter-) national governments to negotiate long-lasting public policy commitment and funds for global standardization of medical tests.

Salutogenesis, globalization, and communication.

Science.gov (United States)

Petzold, Theodor Dierk; Lehmann, Nadja

2011-12-01

Achieving successful communication in transcultural contexts means integrating emotional communication patterns into a global context. Professional, rational communication is characteristic of the cultural dimension, and emotions are characteristic of the direct, interpersonal dimension of human existence. Humans strive to achieve coherence in all dimensions of their lives; this goal is in the end the most essential aspect of psychophysical self-regulation. A major role in integrating emotional needs and cultural features in global coherence is played by the attractor 'global affinity'. The transitions from emotional coherence to cultural coherence, and likewise from cultural coherence to global coherence, can cause considerable insecurity as well as psychological problems, which previously went by the name 'adjustment disorders'. However, instead of pathologizing these processes, we should understand them in a salutogenic sense as challenges important for both individual and collective development. The development of more coherence is regulated by the neuropsychological approach and avoidance system. This system can be consciously fostered by directing our attention to the commonalities of all human beings. Such a global salutogenic orientation furthers both communication and creativity in teamwork. This article introduces a consequent salutogenic and evolutionary systemic view of transcultural communication and demonstrates its effectiveness in a number of case examples.

Global control of reaction wheel pendulum through energy regulation and extended linearization of the state variables

Directory of Open Access Journals (Sweden)

Oscar D. Montoya-Giraldo

2014-01-01

Full Text Available This paper presents the design and simulation of a global controller for the Reaction Wheel Pendulum system using energy regulation and extended linearization methods for the state feedback. The proposed energy regulation is based on the gradual reduction of the energy of the system to reach the unstable equilibrium point. The signal input for this task is obtained from the Lyapunov stability theory. The extended state feedback controller design is used to get a smooth nonlinear function that extends the region of operation to a bigger range, in contrast with the static linear state feedback obtained through the method of approximate linearization around an operating point. The general designed controller operates with a switching between the two control signals depending upon the region of operation; perturbations are applied in the control signal and the (simulated measured variables to verify the robustness and efficiency of the controller. Finally, simulations and tests using the model of the reaction wheel pendulum system, allow to observe the versatility and functionality of the proposed controller in the entire operation region of the pendulum.

The E. coli Global Regulator DksA Reduces Transcription during T4 Infection

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Jennifer Patterson-West

2018-06-01

Full Text Available Bacteriophage T4 relies on host RNA polymerase to transcribe three promoter classes: early (Pe, requires no viral factors, middle (Pm, requires early proteins MotA and AsiA, and late (Pl, requires middle proteins gp55, gp33, and gp45. Using primer extension, RNA-seq, RT-qPCR, single bursts, and a semi-automated method to document plaque size, we investigated how deletion of DksA or ppGpp, two E. coli global transcription regulators, affects T4 infection. Both ppGpp0 and ΔdksA increase T4 wild type (wt plaque size. However, ppGpp0 does not significantly alter burst size or latent period, and only modestly affects T4 transcript abundance, while ΔdksA increases burst size (2-fold without affecting latent period and increases the levels of several Pe transcripts at 5 min post-infection. In a T4motAam infection, ΔdksA increases plaque size and shortens latent period, and the levels of specific middle RNAs increase due to more transcription from Pe’s that extend into these middle genes. We conclude that DksA lowers T4 early gene expression. Consequently, ΔdksA results in a more productive wt infection and ameliorates the poor expression of middle genes in a T4motAam infection. As DksA does not inhibit Pe transcription in vitro, regulation may be indirect or perhaps requires additional factors.

Public-private interactions in global food safety governance.

Science.gov (United States)

Lin, Ching-Fu

2014-01-01

In response to an apparent decline in global food safety, numerous public and private regulatory initiatives have emerged to restore public confidence. This trend has been particularly marked by the growing influence of private regulators such as multinational food companies, supermarket chains and non-governmental organizations (NGOs), who employ private standards, certification protocols, third-party auditing, and transnational contracting practices. This paper explores how the structure and processes of private food safety governance interact with traditional public governance regimes, focusing on Global Good Agricultural Practices (GlobalGAP) as a primary example of the former. Due to the inefficiency and ineffectiveness of public regulation in the face of global problems, private governance in food safety has gradually replaced states' command-and-control regulation with more flexible, market-oriented mechanisms. The paper concludes by emphasizing the importance of constructive regime interaction instead of institutional boundary building to global food safety governance. Public and private ordering must each play a role as integral parts of a larger, dynamic and evolving governance complex.

Global chemical pollution

International Nuclear Information System (INIS)

Travis, C.C.; Hester, S.T.

1991-01-01

Over the past decade, public and governmental awareness of environmental problems has grown steadily, with an accompanying increase in the regulation of point sources of pollution. As a result, great strides have been made in cleaning polluted rivers and decreasing air pollution near factories. However, traditional regulatory approaches to environmental pollution have focused primarily on protecting the maximally exposed individual located in the immediate vicinity of the pollution source. Little attention has been given to the global implications of human production and use of synthetic chemicals. A consensus is emerging that even trace levels of environmental contamination can have potentially devastating environmental consequences. The authors maintain that ambient levels of pollution have risen to the point where human health is being affected on a global scale. Atmospheric transport is recognized as the primary mode of global distribution and entry into the food chain for organic chemicals. The following are examples of global chemical pollutants that result in human exposure of significant proportions: PCBs, dioxins, benzene, mercury and lead. Current regulatory approaches for environmental pollution do not incorporate ways of dealing with global pollution. Instead the major focus has been on protecting the maximally exposed individual. If we do not want to change our standard of living, the only way to reduce global chemical pollution is to make production and consumption processes more efficient and to lower the levels of production of these toxic chemicals. Thus the only reasonable solution to global pollution is not increased regulation of isolated point sources, but rather an increased emphasis on waste reduction and materials recycling. Until we focus on these issues, we will continue to experience background cancer risk in the 10 -3 range

An Investigation of Adolescent Girls' Global Self-Concept, Physical Self-Concept, Identified Regulation, and Leisure-Time Physical Activity in Physical Education

Science.gov (United States)

Beasley, Emily Kristin; Garn, Alex C.

2013-01-01

This study examined the relationships among identified regulation, physical self-concept, global self-concept, and leisure-time physical activity with a sample of middle and high school girls (N = 319) enrolled in physical education. Based on Marsh's theory of self-concept, it was hypothesized that a) physical self-concept would mediate the…

A global bioheat model with self-tuning optimal regulation of body temperature using Hebbian feedback covariance learning.

Science.gov (United States)

Ong, M L; Ng, E Y K

2005-12-01

In the lower brain, body temperature is continually being regulated almost flawlessly despite huge fluctuations in ambient and physiological conditions that constantly threaten the well-being of the body. The underlying control problem defining thermal homeostasis is one of great enormity: Many systems and sub-systems are involved in temperature regulation and physiological processes are intrinsically complex and intertwined. Thus the defining control system has to take into account the complications of nonlinearities, system uncertainties, delayed feedback loops as well as internal and external disturbances. In this paper, we propose a self-tuning adaptive thermal controller based upon Hebbian feedback covariance learning where the system is to be regulated continually to best suit its environment. This hypothesis is supported in part by postulations of the presence of adaptive optimization behavior in biological systems of certain organisms which face limited resources vital for survival. We demonstrate the use of Hebbian feedback covariance learning as a possible self-adaptive controller in body temperature regulation. The model postulates an important role of Hebbian covariance adaptation as a means of reinforcement learning in the thermal controller. The passive system is based on a simplified 2-node core and shell representation of the body, where global responses are captured. Model predictions are consistent with observed thermoregulatory responses to conditions of exercise and rest, and heat and cold stress. An important implication of the model is that optimal physiological behaviors arising from self-tuning adaptive regulation in the thermal controller may be responsible for the departure from homeostasis in abnormal states, e.g., fever. This was previously unexplained using the conventional "set-point" control theory.

Animal welfare in a global perspective

NARCIS (Netherlands)

Bracke, M.B.M.

2009-01-01

Global survey of animal-welfare regulations, practices and perceptions, with case studies on poultry meat from Brazil and Thailand, eggs from India and the USA, welfare regulations of farmed fish and welfare aspects related to (perceived) overpopulation of wildlife

Development of an operational manual for a consultation-liaison psychiatry service.

Science.gov (United States)

Wand, Anne Pf; Sharma, Swapnil; Carpenter, Lindsay J; Gatsi, Mike

2018-02-01

Consultation-liaison psychiatry (CLP) services sit between mental health and the general hospital, and risk being poorly understood by both systems. The aim of this study was to develop an operational manual for a CLP service, which defined functions and governance. The CLP literature was reviewed with a focus on descriptions of CLP roles, organisational processes, quality measures and service development. The CLP team held service planning meetings and met with members of the mental health and hospital executives. Site visits and collaboration with other CLP services occurred in defining the roles of the CLP service and organisational governance. A CLP operational document was developed, including a description of the service, its functions, staff roles and governance. Procedural information such as the CLP timetable, referral process, triage and assessment, documentation, activity recording, quality assurance and relevant policies were outlined. The development of a dedicated operational manual for CLP clarified the roles, functions and governance of CLP within the general hospital and mental health systems. The development process facilitated the engagement of key clinicians and administrators of these systems, the determination of quality improvement targets and greater transparency and accountability.

Global Structural Flexibility of Metalloproteins Regulates Reactivity of Transition Metal Ion in the Protein Core: An Experimental Study Using Thiol-subtilisin as a Model Protein.

Science.gov (United States)

Matsuo, Takashi; Kono, Takamasa; Shobu, Isamu; Ishida, Masaya; Gonda, Katsuya; Hirota, Shun

2018-02-21

The functions of metal-containing proteins (metalloproteins) are determined by the reactivities of transition metal ions at their active sites. Because protein macromolecular structures have several molecular degrees of freedom, global structural flexibility may also regulate the properties of metalloproteins. However, the influence of this factor has not been fully delineated in mechanistic studies of metalloproteins. Accordingly, we have investigated the relationship between global protein flexibility and the characteristics of a transition metal ion in the protein core using thiol-subtilisin (tSTL) with a Cys-coordinated Cu 2+ ion as a model system. Although tSTL has two Ca 2+ -binding sites, the Ca 2+ -binding status hardly affects its secondary structure. Nevertheless, guanidinium-induced denaturation and amide H/D exchange indicated the increase in the structural flexibility of tSTL by the removal of bound Ca 2+ ions. Electron paramagnetic resonance and absorption spectral changes have revealed that the protein flexibility determines the characteristics of a Cu 2+ ion in tSTL. Therefore, global protein flexibility should be recognized as an important factor that regulates the properties of metalloproteins. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Globalization and deficit and limitations of global governance

Directory of Open Access Journals (Sweden)

Stojanović Stanislav

2016-01-01

Full Text Available Character and dynamics of relationships in international politics, in which the stronger return to real politics content in the functioning of the foreign policy of the great powers, unequivocally affirms that globalization does not work to its declining power that is less credible design concept of modern world society. The global financial collapse that hit the world in 2008 is a convincing indication that most of the globalization is discredited. The belief in one humanity is becoming a less desirable concept. At the same time, with the increase in global issues that require solving, there are numerous human activities that involve unique or international regulation. The world is increasingly one homeostatic system of interdependent parts of a continent where many aspects of the borders between countries are difficult or even impossible to sustain. Hence the importance of global factors, some of which will fully depend on the articulation of individual and community life of people in the future, stressing the importance of the issue of joint management to ensure global peace and security and promote the prosperity around the world in a universally acceptable and effective way. Therefore, the demonstrated substantial shortcomings of global governance of the world, although they discourage belief in humanity, did not reduce the objective need for global access to many amenities of modern human existence. Many aspects of security, ranging from the security of the individual to the energy and environmental security in modern conditions are not conceivable without international access. However, global security management has been associated with numerous limitations and challenges.

Global analysis of epigenetic regulation of gene expression in response to drought stress in Sorghum.

Energy Technology Data Exchange (ETDEWEB)

Reddy, Anireddy [Colorado State Univ., Fort Collins, CO (United States); Ben-Hur, Asa [Colorado State Univ., Fort Collins, CO (United States)

2017-11-22

Abiotic stresses including drought are major limiting factors of crop yields and cause significant crop losses. Acquisition of stress tolerance to abiotic stresses requires coordinated regulation of a multitude of biochemical and physiological changes, and most of these changes depend on alterations in gene expression. The goal of this work is to perform global analysis of differential regulation of gene expression and alternative splicing, and their relationship with chromatin landscape in drought sensitive and tolerant cultivars. our Iso-Seq study revealed transcriptome-wide full-length isoforms at an unprecedented scale with over 11000 novel splice isoforms. Additionally, we uncovered alternative polyadenylation sites of ~11000 expressed genes and many novel genes. Overall, Iso-Seq results greatly enhanced sorghum gene annotations that are not only useful in analyzing all our RNA-seq, ChIP-seq and ATAC-seq data but also serve as a great resource to the plant biology community. Our studies identified differentially expressed genes and splicing events that are correlated with the drought-resistant phenotype. An association between alternative splicing and chromatin accessibility was also revealed. Several computational tools developed here (TAPIS and iDiffIR) have been made freely available to the research community in analyzing alternative splicing and differential alternative splicing.

Mineralogical evidence of reduced East Asian summer monsoon rainfall on the Chinese loess plateau during the early Pleistocene interglacials

Science.gov (United States)

Meng, Xianqiang; Liu, Lianwen; Wang, Xingchen T.; Balsam, William; Chen, Jun; Ji, Junfeng

2018-03-01

The East Asian summer monsoon (EASM) is an important component of the global climate system. A better understanding of EASM rainfall variability in the past can help constrain climate models and better predict the response of EASM to ongoing global warming. The warm early Pleistocene, a potential analog of future climate, is an important period to study EASM dynamics. However, existing monsoon proxies for reconstruction of EASM rainfall during the early Pleistocene fail to disentangle monsoon rainfall changes from temperature variations, complicating the comparison of these monsoon records with climate models. Here, we present three 2.6 million-year-long EASM rainfall records from the Chinese Loess Plateau (CLP) based on carbonate dissolution, a novel proxy for rainfall intensity. These records show that the interglacial rainfall on the CLP was lower during the early Pleistocene and then gradually increased with global cooling during the middle and late Pleistocene. These results are contrary to previous suggestions that a warmer climate leads to higher monsoon rainfall on tectonic timescales. We propose that the lower interglacial EASM rainfall during the early Pleistocene was caused by reduced sea surface temperature gradients across the equatorial Pacific, providing a testable hypothesis for climate models.

THE NONLINEAR IMPACT OF GLOBALIZATION ON CORRUPTION

OpenAIRE

Jayoti Das; Cassandra DiRienzo

2009-01-01

Some researchers have argued that globalization has increased the opportunity for corrupt practices, while others state that globalization has lead to a decrease in corruption as countries wishing to join the global economy must comply with international anti-corruption rules and regulations. This study empirically explores this paradox using the Corruption Perceptions Index (CPI) and the Konjunkturforschungsstelle (KOF) globalization Index. The results suggest that a nonlinear relationship e...

Toward a System of Global Accountability

International Nuclear Information System (INIS)

Cameron, J.

2016-01-01

Post-Fukushima, the public expects and demands that nuclear regulators and operators worldwide have used lessons learned to identify and implement important actions and measures to prevent a similar event from happening again. Considerable work has been done at the national and international levels to achieve this. However, verifying the adequacy and appropriateness of measures taken in each country requires an enhanced level of global accountability that does not presently exist. The current global nuclear regulatory safety framework is based on the principle of national sovereignty and the result is that the world lacks a forum for publicizing safety concerns, beyond the national regulator, to the highest levels of government within member states. This runs the risk of significant deficiencies or non-compliance with internationally approved practices continuing unchecked even though some parties are aware of them. This also applies to flagging cases of insufficiently independent regulators or identifying inadequately prepared regulators in new nuclear countries. There are many vehicles for enhancing this transparency, e.g., WANO/INPO, regional regulatory fora, and international organizations including the OECD/NEA and IAEA. The world has never been more interconnected and it is time that the nuclear sector leverages this reality and adopts a system of global accountability for nuclear safety. (author)

Birth prevalence of non-syndromic orofacial clefts in Saudi Arabia and the effects of parental consanguinity

Science.gov (United States)

Sabbagh, Heba J.; Innes, Nicola P.; Sallout, Bahauddin I.; Alamoudi, Najlaa M.; Hamdan, Mustafa A.; Alhamlan, Nasir; Al-Khozami, Amaal I.; Abdulhameed, Fatma D.; Al-Aama, Jumana Y.; Mossey, Peter A.

2015-01-01

Objectives: To describe the characteristics and prevalence of non-syndromic orofacial clefting (NSOFC) and assess the effects of parental consanguinity on NSOFC phenotypes in the 3 main cities of Saudi Arabia. Methods: All infants (114,035) born at 3 referral centers in Riyadh, and 6 hospitals in Jeddah and Madinah between January 2010 and December 2011 were screened. The NSOFC cases (n=133) were identified and data was collected through clinical examination and records, and information on consanguinity through parent interviews. The diagnosis was confirmed by reviewing medical records and contacting the infants’ pediatricians. Control infants (n=233) matched for gender and born in the same hospitals during the same period, were selected. Results: The prevalence of NSOFC was 1.07/1000 births in Riyadh, and 1.17/1000 births overall; cleft lip (CL) was 0.47/1000 births, cleft lip and palate (CLP) was 0.42/1000 births, and cleft palate (CP) was 0.28/1000 births. Cleft palate was significantly associated with consanguinity (p=0.047, odds ratio: 2.5, 95% confidence interval: 1 to 6.46), particularly for first cousin marriages. Conclusion: The birth prevalence of NSOFC in Riyadh alone, and in the 3 main cities of Saudi Arabia were marginally lower than the mean global prevalence. While birth prevalence for CLP was comparable to global figures, the CL:CLP ratio was high, and only CP was significantly associated with consanguinity. PMID:26318465

Birth prevalence of non-syndromic orofacial clefts in Saudi Arabia and the effects of parental consanguinity

Directory of Open Access Journals (Sweden)

Heba J. Sabbagh

2015-09-01

Full Text Available Objectives: To describe the characteristics and prevalence of non-syndromic orofacial clefting (NSOFC and assess the effects of parental consanguinity on NSOFC phenotypes in the 3 main cities of Saudi Arabia. Methods: All infants (114,035 born at 3 referral centers in Riyadh, and 6 hospitals in Jeddah and Madinah between January 2010 and December 2011 were screened. The NSOFC cases (n=133 were identified and data was collected through clinical examination and records, and information on consanguinity through parent interviews. The diagnosis was confirmed by reviewing medical records and contacting the infants’ pediatricians. Control infants (n=233 matched for gender and born in the same hospitals during the same period, were selected. Results: The prevalence of NSOFC was 1.07/1000 births in Riyadh, and 1.17/1000 births overall; cleft lip (CL was 0.47/1000 births, cleft lip and palate (CLP was 0.42/1000 births, and cleft palate (CP was 0.28/1000 births. Cleft palate was significantly associated with consanguinity (p=0.047, odds ratio: 2.5, 95% confidence interval: 1 to 6.46, particularly for first cousin marriages. Conclusion: The birth prevalence of NSOFC in Riyadh alone, and in the 3 main cities of Saudi Arabia were marginally lower than the mean global prevalence. While birth prevalence for CLP was comparable to global figures, the CL:CLP ratio was high, and only CP was significantly associated with consanguinity.

Does Citrulline Have Protective Effects on Liver Injury in Septic Rats?

Directory of Open Access Journals (Sweden)

Bin Cai

2016-01-01

Full Text Available Citrulline (Cit supplementation was proposed to serve as a therapeutic intervention to restore arginine (Arg concentrations and improve related functions in sepsis. This study explored whether citrulline had positive effects on liver injury and cytokine release in the early stages of sepsis. The cecal ligation and puncture (CLP model was utilized in our study. Rats were divided into four groups: normal, Cit, CLP, and CLP+Cit. The CLP group and CLP+Cit group were separated into 6-, 12-, and 24-hour groups, according to the time points of sacrifice after surgery. Intragastric administration of L-citrulline was applied to rats in Cit and CLP+Cit groups before surgery. Serum AST and ALT levels and levels of MDA, SOD, NO, and iNOS in the liver tissues were evaluated. Plasma concentrations of Cit and Arg were assessed using HPLC-MS/MS. Serum concentrations of cytokines and chemokines were calculated by Luminex. Results showed SOD activities of CLP+Cit groups were significantly higher than that of CLP groups, contrasting with the MDA and NO levels which were significantly lower in CLP+Cit groups than in CLP groups. In addition, plasma concentrations of TNF-α, IL-6, and IL-1β were significantly lower in the CLP+Cit 6-hour group than in the CLP 6-hour group.

A global regulatory science agenda for vaccines.

Science.gov (United States)

Elmgren, Lindsay; Li, Xuguang; Wilson, Carolyn; Ball, Robert; Wang, Junzhi; Cichutek, Klaus; Pfleiderer, Michael; Kato, Atsushi; Cavaleri, Marco; Southern, James; Jivapaisarnpong, Teeranart; Minor, Philip; Griffiths, Elwyn; Sohn, Yeowon; Wood, David

2013-04-18

The Decade of Vaccines Collaboration and development of the Global Vaccine Action Plan provides a catalyst and unique opportunity for regulators worldwide to develop and propose a global regulatory science agenda for vaccines. Regulatory oversight is critical to allow access to vaccines that are safe, effective, and of assured quality. Methods used by regulators need to constantly evolve so that scientific and technological advances are applied to address challenges such as new products and technologies, and also to provide an increased understanding of benefits and risks of existing products. Regulatory science builds on high-quality basic research, and encompasses at least two broad categories. First, there is laboratory-based regulatory science. Illustrative examples include development of correlates of immunity; or correlates of safety; or of improved product characterization and potency assays. Included in such science would be tools to standardize assays used for regulatory purposes. Second, there is science to develop regulatory processes. Illustrative examples include adaptive clinical trial designs; or tools to analyze the benefit-risk decision-making process of regulators; or novel pharmacovigilance methodologies. Included in such science would be initiatives to standardize regulatory processes (e.g., definitions of terms for adverse events [AEs] following immunization). The aim of a global regulatory science agenda is to transform current national efforts, mainly by well-resourced regulatory agencies, into a coordinated action plan to support global immunization goals. This article provides examples of how regulatory science has, in the past, contributed to improved access to vaccines, and identifies gaps that could be addressed through a global regulatory science agenda. The article also identifies challenges to implementing a regulatory science agenda and proposes strategies and actions to fill these gaps. A global regulatory science agenda will enable

Benznidazole, the trypanocidal drug used for Chagas disease, induces hepatic NRF2 activation and attenuates the inflammatory response in a murine model of sepsis

International Nuclear Information System (INIS)

Lambertucci, Flavia; Motiño, Omar; Villar, Silvina; Rigalli, Juan Pablo; Luján Alvarez, María de; Catania, Viviana A; Martín-Sanz, Paloma; Carnovale, Cristina Ester; Quiroga, Ariel Darío; Francés, Daniel Eleazar; Ronco, María Teresa

2017-01-01

Molecular mechanisms on sepsis progression are linked to the imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity. Previous studies demonstrated that benznidazole (BZL), known for its antiparasitic action on Trypanosoma cruzi, has immunomodulatory effects, increasing survival in C57BL/6 mice in a model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). The mechanism by which BZL inhibits inflammatory response in sepsis is poorly understood. Also, our group recently reported that BZL is able to activate the nuclear factor erytroide-derived 2-Like 2 (NRF2) in vitro. The aim of the present work was to delineate the beneficial role of BZL during sepsis, analyzing its effects on the cellular redox status and the possible link to the innate immunity receptor TLR4. Specifically, we analyzed the effect of BZL on Nrf2 regulation and TLR4 expression in liver of mice 24 hours post-CLP. BZL was able to induce NRF2 nuclear protein localization in CLP mice. Also, we found that protein kinase C (PKC) is involved in the NRF2 nuclear accumulation and induction of its target genes. In addition, BZL prompted a reduction in hepatic CLP-induced TLR4 protein membrane localization, evidencing its immunomodulatory effects. Together, our results demonstrate that BZL induces hepatic NRF2 activation with the concomitant increase in the antioxidant defenses, and the attenuation of inflammatory response, in part, by inhibiting TLR4 expression in a murine model of sepsis. - Highlights: • BZL improves survival rate after polymicrobial sepsis • BZL enhances hepatic NRF2 nuclear accumulation in a model of sepsis, in part, by a mechanism dependent on PKC activation • BZL-enhanced NRF2 induction regulates antioxidant enzymes and increases antioxidant cellular defenses in sepsis • BZL blocks liver ROS production and ROS-induced TLR4 plasma membrane expression in septic mice

Benznidazole, the trypanocidal drug used for Chagas disease, induces hepatic NRF2 activation and attenuates the inflammatory response in a murine model of sepsis

Energy Technology Data Exchange (ETDEWEB)

Lambertucci, Flavia [Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina); Motiño, Omar [Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Arturo Duperier 4, 28029 Madrid (Spain); Villar, Silvina [Instituto de Inmunología, Facultad de Ciencias Médicas, UNR, Suipacha 531, 2000 Rosario (Argentina); Rigalli, Juan Pablo; Luján Alvarez, María de; Catania, Viviana A [Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina); Martín-Sanz, Paloma [Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Arturo Duperier 4, 28029 Madrid (Spain); Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Monforte de Lemos 3-5, 28029 Madrid (Spain); Carnovale, Cristina Ester; Quiroga, Ariel Darío; Francés, Daniel Eleazar [Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina); Ronco, María Teresa, E-mail: ronco@ifise-conicet.gov.ar [Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina)

2017-01-15

Molecular mechanisms on sepsis progression are linked to the imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity. Previous studies demonstrated that benznidazole (BZL), known for its antiparasitic action on Trypanosoma cruzi, has immunomodulatory effects, increasing survival in C57BL/6 mice in a model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). The mechanism by which BZL inhibits inflammatory response in sepsis is poorly understood. Also, our group recently reported that BZL is able to activate the nuclear factor erytroide-derived 2-Like 2 (NRF2) in vitro. The aim of the present work was to delineate the beneficial role of BZL during sepsis, analyzing its effects on the cellular redox status and the possible link to the innate immunity receptor TLR4. Specifically, we analyzed the effect of BZL on Nrf2 regulation and TLR4 expression in liver of mice 24 hours post-CLP. BZL was able to induce NRF2 nuclear protein localization in CLP mice. Also, we found that protein kinase C (PKC) is involved in the NRF2 nuclear accumulation and induction of its target genes. In addition, BZL prompted a reduction in hepatic CLP-induced TLR4 protein membrane localization, evidencing its immunomodulatory effects. Together, our results demonstrate that BZL induces hepatic NRF2 activation with the concomitant increase in the antioxidant defenses, and the attenuation of inflammatory response, in part, by inhibiting TLR4 expression in a murine model of sepsis. - Highlights: • BZL improves survival rate after polymicrobial sepsis • BZL enhances hepatic NRF2 nuclear accumulation in a model of sepsis, in part, by a mechanism dependent on PKC activation • BZL-enhanced NRF2 induction regulates antioxidant enzymes and increases antioxidant cellular defenses in sepsis • BZL blocks liver ROS production and ROS-induced TLR4 plasma membrane expression in septic mice.

Impact of global transcriptional regulation by ArcA, ArcB, Cra, Crp, Cya, Fnr, and Mlc on glucose catabolism in Escherichia coli.

Science.gov (United States)

Perrenoud, Annik; Sauer, Uwe

2005-05-01

Even though transcriptional regulation plays a key role in establishing the metabolic network, the extent to which it actually controls the in vivo distribution of metabolic fluxes through different pathways is essentially unknown. Based on metabolism-wide quantification of intracellular fluxes, we systematically elucidated the relevance of global transcriptional regulation by ArcA, ArcB, Cra, Crp, Cya, Fnr, and Mlc for aerobic glucose catabolism in batch cultures of Escherichia coli. Knockouts of ArcB, Cra, Fnr, and Mlc were phenotypically silent, while deletion of the catabolite repression regulators Crp and Cya resulted in a pronounced slow-growth phenotype but had only a nonspecific effect on the actual flux distribution. Knockout of ArcA-dependent redox regulation, however, increased the aerobic tricarboxylic acid (TCA) cycle activity by over 60%. Like aerobic conditions, anaerobic derepression of TCA cycle enzymes in an ArcA mutant significantly increased the in vivo TCA flux when nitrate was present as an electron acceptor. The in vivo and in vitro data demonstrate that ArcA-dependent transcriptional regulation directly or indirectly controls TCA cycle flux in both aerobic and anaerobic glucose batch cultures of E. coli. This control goes well beyond the previously known ArcA-dependent regulation of the TCA cycle during microaerobiosis.

Endothelin receptor antagonist attenuates oxidative stress in a neonatal sepsis piglet model.

Science.gov (United States)

Goto, Tatenobu; Hussein, Mohamed Hamed; Kato, Shin; Daoud, Ghada Abdel-Hamid; Kato, Takenori; Sugiura, Takahiro; Kakita, Hiroki; Nobata, Masanori; Kamei, Michi; Mizuno, Haruo; Imai, Masaki; Ito, Tetsuya; Kato, Ineko; Suzuki, Satoshi; Okada, Noriko; Togari, Hajime; Okada, Hidechika

2012-12-01

Oxidative stress (oxidant-antioxidant imbalance) plays an important role in the pathophysiology of neonatal sepsis. This study evaluated whether an antisense peptide endothelin receptor antagonist, ETR-P1/fl, could attenuate oxidative stress in a neonatal sepsis model. A total of 18 3-d-old piglets were anesthetized and mechanically ventilated. Six piglets received cecal ligation and perforation (CLP group) for induction of sepsis. Six piglets also received continuous infusion (0.05 mg/kg/h) of ETR-P1/fl 30 min after CLP (ETR-P1/fl group). Six piglets received a sham operation. Serum total hydroperoxide (TH), biological antioxidant potentials (BAPs), oxidative stress index (OSI, calculated as TH/BAP), interleukin (IL)-6, serum glutamic oxaloacetic transaminase (GOT), and creatinine were measured before CLP and at 1, 3, and 6 h after CLP. CLP evoked a state of shock resulting in elevated TH, OSI, and IL-6 levels. ETR-P1/fl administration after CLP resulted in lower serum TH at 1 and 3 h after CLP, OSI at 1 and 3 h after CLP, IL-6 at 1 and 3 h after CLP, and GOT at 3 and 6 h after CLP as compared with the CLP group. ETR-P1/fl treatment significantly attenuated the elevation of serum oxidative stress markers (TH and OSI), IL-6, and GOT in a progressive neonatal sepsis CLP model.

A comparison of cervical vertebral maturation assessment of skeletal growth stages with chronological age in Thai between cleft lip and palate and non-cleft patients.

Science.gov (United States)

Pisek, Poonsak; Godfrey, Keith; Manosudprasit, Montian; Wangsrimongkol, Tasanee; Leelasinjaroen, Pornnapha

2013-09-01

(1) To search for any difference in chronological age related to stages of the cervical vertebral maturation index stages (CVMIs) comparing groups of cleft lip and palate (CLP) and non-cleft (non-CLP) subjects; (2) To investigate the relationship between chronological age and CVMIs in both groups of subjects. Cervical vertebrae C2, C3, C4 were assessed on 1,549 cephalometric films (503 CLP films, 1,046 non-CLP films of subjects aged 5 to 18 years) using Hassel and Farman's method. T-tests showed mean chronological ages of CVMIs 2, 3 and 6 were different at p = 0.001, 0.024 and 0.016, respectively. CVMIs 1, 4 and 5 showed no significant differences. The CLP group achieved each CVMI score one year ahead of the non-CLP group, except for CVMI 4. Spearman's rank order correlations were r = 0.80 (95% CI: 0.76-0.83) for CLP, and 0.77 (95% CI: 0.74-0.79) for non-CLP. CLP subjects tended to have a slightly advanced growth compared with non-CLP subjects. A high correlation coefficient was found between chronological age and cervical vertebral skeletal maturation.

31 CFR 594.310 - Specially designated global terrorist; SDGT.

Science.gov (United States)

2010-07-01

... (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY GLOBAL TERRORISM SANCTIONS REGULATIONS General Definitions § 594.310 Specially designated global terrorist; SDGT. The term specially...

Coordinated Regulation of the EIIMan and fruRKI Operons of Streptococcus mutans by Global and Fructose-Specific Pathways.

Science.gov (United States)

Zeng, Lin; Chakraborty, Brinta; Farivar, Tanaz; Burne, Robert A

2017-11-01

The glucose/mannose-phosphotransferase system (PTS) permease EII Man encoded by manLMN in the dental caries pathogen Streptococcus mutans has a dominant influence on sugar-specific, CcpA-independent catabolite repression (CR). Mutations in manL affect energy metabolism and virulence-associated traits, including biofilm formation, acid tolerance, and competence. Using promoter::reporter fusions, expression of the manLMN and the fruRKI operons, encoding a transcriptional regulator, a fructose-1-phosphate kinase and a fructose-PTS permease EII Fru , respectively, was monitored in response to carbohydrate source and in mutants lacking CcpA, FruR, and components of EII Man Expression of genes for EII Man and EII Fru was directly regulated by CcpA and CR, as evinced by in vivo and in vitro methods. Unexpectedly, not only was the fruRKI operon negatively regulated by FruR, but also so was manLMN Carbohydrate transport by EII Man had a negative influence on expression of manLMN but not fruRKI In agreement with the proposed role of FruR in regulating these PTS operons, loss of fruR or fruK substantially altered growth on a number of carbohydrates, including fructose. RNA deep sequencing revealed profound changes in gene regulation caused by deletion of fruK or fruR Collectively, these findings demonstrate intimate interconnection of the regulation of two major PTS permeases in S. mutans and reveal novel and important contributions of fructose metabolism to global regulation of gene expression. IMPORTANCE The ability of Streptococcus mutans and other streptococcal pathogens to survive and cause human diseases is directly dependent upon their capacity to metabolize a variety of carbohydrates, including glucose and fructose. Our research reveals that metabolism of fructose has broad influences on the regulation of utilization of glucose and other sugars, and mutants with changes in certain genes involved in fructose metabolism display profoundly different abilities to grow and

A Flexible Binding Site Architecture Provides New Insights into CcpA Global Regulation in Gram-Positive Bacteria

Directory of Open Access Journals (Sweden)

Yunpeng Yang

2017-01-01

Full Text Available Catabolite control protein A (CcpA is the master regulator in Gram-positive bacteria that mediates carbon catabolite repression (CCR and carbon catabolite activation (CCA, two fundamental regulatory mechanisms that enable competitive advantages in carbon catabolism. It is generally regarded that CcpA exerts its regulatory role by binding to a typical 14- to 16-nucleotide (nt consensus site that is called a catabolite response element (cre within the target regions. However, here we report a previously unknown noncanonical flexible architecture of the CcpA-binding site in solventogenic clostridia, providing new mechanistic insights into catabolite regulation. This novel CcpA-binding site, named crevar, has a unique architecture that consists of two inverted repeats and an intervening spacer, all of which are variable in nucleotide composition and length, except for a 6-bp core palindromic sequence (TGTAAA/TTTACA. It was found that the length of the intervening spacer of crevar can affect CcpA binding affinity, and moreover, the core palindromic sequence of crevar is the key structure for regulation. Such a variable architecture of crevar shows potential importance for CcpA’s diverse and fine regulation. A total of 103 potential crevar sites were discovered in solventogenic Clostridium acetobutylicum, of which 42 sites were picked out for electrophoretic mobility shift assays (EMSAs, and 30 sites were confirmed to be bound by CcpA. These 30 crevar sites are associated with 27 genes involved in many important pathways. Also of significance, the crevar sites are found to be widespread and function in a great number of taxonomically different Gram-positive bacteria, including pathogens, suggesting their global role in Gram-positive bacteria.

Oligarchy versus Democracy and Regulation versus Deregulation under the Globalization Effect

Directory of Open Access Journals (Sweden)

Dumitru-Alexandru BODISLAV

2012-05-01

Full Text Available On capitalism that is created under the pressure of globalization there are created many economic systems that derived into a new model: the asymmetric model created from propriety rights’ perspective and the influence of interest groups, an asymmetric model that is called “oligarchy”(1. For a better understanding of oligarchy we consider an oligarchic society, where the political power is in the hands of the producers of goods, that tend to protect their propriety rights, but this way they create entry barriers, destroying the propriety rights of future potential producers. Capitalism was and is stressed by the (deregulation phenomena created by the competition which is shaped through globalization. With ease we can go from (deregulating to oligarchic pressure, which from the globalization’s perspective can give birth to the lagging or decoupling in the global economic system. This paper researches these two cases and inserts them into the global framework to result the evolution of society’s members’ welfare.

Ketamine and international regulations.

Science.gov (United States)

Liao, Yanhui; Tang, Yi-Lang; Hao, Wei

2017-09-01

Ketamine is an anesthetic commonly used in low-income countries and has recently been shown to be effective for treatment-resistant depression. However, the illicit manufacturing, trafficking, and nonmedical use of ketamine are increasing globally, and its illicit use poses major public health challenges in many countries. To review the nonmedical use of ketamine in selected countries and its regulatory control. We conducted a review of literature identified from searches of the China National Knowledge Infrastructure (CNKI) (1979-2016) and PubMed databases, supplemented by additional references identified by the authors. Special attention was given to the regulation of ketamine. Illicit manufacturing, trafficking, and use of ketamine appear to have begun on a large scale in several Asian nations, and it has subsequently spread to other regions. Regulations governing availability of ketamine vary across countries, but there is a clear trend toward tighter regulations. As nonmedical use of ketamine and its harmful consequences have worsened globally, stricter controls are necessary. Appropriate regulation of ketamine is important for international efforts to control ketamine's cross-border trafficking and its nonmedical use.

Overview of codes and tools for nuclear engineering education

Science.gov (United States)

Yakovlev, D.; Pryakhin, A.; Medvedeva, L.

2017-01-01

The recent world trends in nuclear education have been developed in the direction of social education, networking, virtual tools and codes. MEPhI as a global leader on the world education market implements new advanced technologies for the distance and online learning and for student research work. MEPhI produced special codes, tools and web resources based on the internet platform to support education in the field of nuclear technology. At the same time, MEPhI actively uses codes and tools from the third parties. Several types of the tools are considered: calculation codes, nuclear data visualization tools, virtual labs, PC-based educational simulators for nuclear power plants (NPP), CLP4NET, education web-platforms, distance courses (MOOCs and controlled and managed content systems). The university pays special attention to integrated products such as CLP4NET, which is not a learning course, but serves to automate the process of learning through distance technologies. CLP4NET organizes all tools in the same information space. Up to now, MEPhI has achieved significant results in the field of distance education and online system implementation.

Globalization of the energy sector - a U.S. regulator`s perspective

Energy Technology Data Exchange (ETDEWEB)

Kallaur, Carolita [Offshore Minerals Management, U.S. Department of the Interior (United States)

1998-12-01

This publication relates to globalization of the energy sector addressing issues of significant importance to the United States. The author touches upon a number of activities MMS (Mineral Management Service) is involved in with a focus on a joint project being engaged in with NPD (Norwegian Petroleum Directorate) to help the Russian Federation develop a safety and environment regime for its offshore. The aim of the project are national standards that set requirements for local and regional governments, safety and environment requirements that conform to international standards, apply to both Russian and foreign firms, and sharing of best practices between NPD, MMS and Russian authorities

IRAK-M regulates chromatin remodeling in lung macrophages during experimental sepsis.

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Kenneth Lyn-Kew

2010-06-01

Full Text Available Sepsis results in a profound state of immunosuppression, which is temporally associated with impaired leukocyte function. The mechanism of leukocyte reprogramming in sepsis is incompletely understood. In this study, we explored mechanisms contributing to dysregulated inflammatory cytokine expression by pulmonary macrophages during experimental sepsis. Pulmonary macrophages (PM recovered from the lungs of mice undergoing cecal ligation and puncture (CLP display transiently reduced expression of some, but not all innate genes in response to LPS. Impaired expression of TNF-alpha and iNOS was associated with reduced acetylation and methylation of specific histones (AcH4 and H3K4me3 and reduced binding of RNA polymerase II to the promoters of these genes. Transient impairment in LPS-induced cytokine responses in septic PM temporally correlated with induction of IRAK-M mRNA and protein, which occurred in a MyD88-dependent fashion. PM isolated from IRAK-M(-/- mice were largely refractory to CLP-induced impairment in cytokine expression, chromatin remodeling, recruitment of RNA polymerase II, and induction of histone deacetylase-2 observed during sepsis. Our findings indicate that systemic sepsis induces epigenetic silencing of cytokine gene expression in lung macrophages, and IRAK-M appears to be a critical mediator of this response.

Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control.

Science.gov (United States)

Carroni, Marta; Franke, Kamila B; Maurer, Michael; Jäger, Jasmin; Hantke, Ingo; Gloge, Felix; Linder, Daniela; Gremer, Sebastian; Turgay, Kürşad; Bukau, Bernd; Mogk, Axel

2017-11-22

Ring-forming AAA+ chaperones exert ATP-fueled substrate unfolding by threading through a central pore. This activity is potentially harmful requiring mechanisms for tight repression and substrate-specific activation. The AAA+ chaperone ClpC with the peptidase ClpP forms a bacterial protease essential to virulence and stress resistance. The adaptor MecA activates ClpC by targeting substrates and stimulating ClpC ATPase activity. We show how ClpC is repressed in its ground state by determining ClpC cryo-EM structures with and without MecA. ClpC forms large two-helical assemblies that associate via head-to-head contacts between coiled-coil middle domains (MDs). MecA converts this resting state to an active planar ring structure by binding to MD interaction sites. Loss of ClpC repression in MD mutants causes constitutive activation and severe cellular toxicity. These findings unravel an unexpected regulatory concept executed by coiled-coil MDs to tightly control AAA+ chaperone activity.

The Kontiki of Global Accounting.

OpenAIRE

George Mickhail

2000-01-01

Global financial reporting is experiencing a “credibility crisis” due to concerns about the quality of reporting of financial results by corporations, which has been eroding in the rush to meet market expectations. This controversy highlights the need to examine the increasing expectation of ‘harmonisation’ by stock exchanges around the world, companies seeking global capital flows and the financial statement users. Meanwhile, securities regulators attempt to redefine their accounting standar...

The Growth of Private Regulation of Labor Standards in Global Supply Chains

DEFF Research Database (Denmark)

Knudsen, Jette Steen

2013-01-01

Multinational corporations (MNCs) have come under pressure to adopt private regulatory initiatives such as supplier codes of conduct in order to address poor working conditions in global supply chain factories. While a well-known literature explores drivers and outcomes of such monitoring schemes...... requirements in global supply chains even though compliance is a “mission impossible” for many smaller firms. As a result of this development, the private regulatory system is facing growing strain.......Multinational corporations (MNCs) have come under pressure to adopt private regulatory initiatives such as supplier codes of conduct in order to address poor working conditions in global supply chain factories. While a well-known literature explores drivers and outcomes of such monitoring schemes......, this literature focuses mainly on large firms and has ignored the growing integration of small- and medium-sized enterprises (SMEs) into global supply chains. Furthermore, the literature on corporate social responsibility (CSR) in SMEs primarily emphasizes domestic initiatives and not global challenges. Focusing...

Contract & agency labour: beyond self-regulation?

OpenAIRE

Cotton, Elizabeth

2010-01-01

A paper about the regulation of contract labour. Academic and legal aspects as well as case studies of global union federation work to organise and regulate contract labour in Thailand, Pakistan, Colombia, South Korea and at international level.

The global environment: An overview

International Nuclear Information System (INIS)

Tolba, M.K.

1992-01-01

Global environmental chemistry today involves a rapidly expanding need both for new research and for the development of an interdiciplinary approach to the multiplicity of interconnected environmental problems. Every ecosystem shows signs of damage: growing quantities of wastes; decreasing water supplies; soil degradation; coastal zone deterioration; deforestation and climatic change; global warming due to ozone depletion. Solutions must involve a cooperative and holistic global effort in three areas: scientific understanding of how the interactive physical, chemical and biological processes regulate the total Earth system; public policy implications including closer liaison between scientists and policymakers;and understanding of the state of the global environment, what is going wrong, why, and whether it is getting worse

Sapfluxnet: a global database of sap flow measurements to unravel the ecological factors of transpiration regulation in woody plants

Science.gov (United States)

Poyatos, Rafael; Martínez-Vilalta, Jordi; Molowny-Horas, Roberto; Steppe, Kathy; Oren, Ram; Katul, Gabriel; Mahecha, Miguel

2016-04-01

Plant transpiration is one of the main components of the global water cycle, it controls land energy balance, determines catchment hydrological responses and exerts strong feedbacks on regional and global climate. At the same time, plant productivity, growth and survival are severely constrained by water availability, which is expected to decline in many areas of the world because of global-change driven increases in drought conditions. While global surveys of drought tolerance traits at the organ level are rapidly increasing our knowledge of the diversity in plant functional strategies to cope with drought stress, a whole-plant perspective of drought vulnerability is still lacking. Sap flow measurements using thermal methods have now been applied to measure seasonal patterns in water use and the response of transpiration to environmental drivers across hundreds of species of woody plants worldwide, covering a wide range of climates, soils and stand structural characteristics. Here, we present the first effort to build a global database of sub-daily, tree-level sap flow (SAPFLUXNET) that will be used to improve our understanding of physiological and structural determinants of plant transpiration and to further investigate the role of vegetation in controlling global water balance. We already have the expression of interest of data contributors representing >115 globally distributed sites, > 185 species and > 700 trees, measured over at least one growing season. However, the potential number of available sites and species is probably much higher given that > 2500 sap flow-related papers have been identified in a Scopus literature search conducted in November 2015. We will give an overview of how data collection, harmonisation and quality control procedures are implemented within the project. We will also discuss potential analytical strategies to synthesize hydroclimatic controls on sap flow into biologically meaningful traits related to whole-plant transpiration

Market, Regulation, Market, Regulation

DEFF Research Database (Denmark)

Frankel, Christian; Galland, Jean-Pierre

2015-01-01

barriers to trade in Europe, realized the free movement of products by organizing progressively several orders of markets and regulation. Based on historical and institutional documents, on technical publications, and on interviews, this article relates how the European Commission and the Member States had......This paper focuses on the European Regulatory system which was settled both for opening the Single Market for products and ensuring the consumers' safety. It claims that the New Approach and Standardization, and the Global Approach to conformity assessment, which suppressed the last technical...... alternatively recourse to markets and to regulations, at the three main levels of the New Approach Directives implementation. The article focuses also more specifically on the Medical Devices sector, not only because this New Approach sector has long been controversial in Europe, and has recently been concerned...

NCBI nr-aa BLAST: CBRC-TBEL-01-2084 [SEVENS

Lifescience Database Archive (English)

Full Text Available CBRC-TBEL-01-2084 ref|YP_865674.1| ATP-dependent Clp protease, ATP-binding subunit clpA [Magnet...ococcus sp. MC-1] gb|ABK44268.1| ATP-dependent Clp protease ATP-binding subunit ClpA [Magnetococcus sp. MC-1] YP_865674.1 1.0 34% ...

A non-lethal traumatic/hemorrhagic insult strongly modulates the compartment-specific PAI-1 response in the subsequent polymicrobial sepsis.

Directory of Open Access Journals (Sweden)

Pierre Raeven

Full Text Available INTRODUCTION: Plasminogen activator inhibitor 1 (PAI-1 is a key factor in trauma- and sepsis-induced coagulopathy. We examined how trauma-hemorrhage (TH modulates PAI-1 responses in subsequent cecal ligation and puncture (CLP-induced sepsis, and the association of PAI-1 with septic outcomes. METHODS: Mice underwent TH and CLP 48 h later in three separate experiments. In experiment 1, mice were sacrificed pre- and post-CLP to characterize the trajectory of PAI-1 in plasma (protein and tissues (mRNA. Post-CLP dynamics in TH-CLP (this study and CLP-Only mice (prior study were then compared for modulatory effects of TH. In experiment 2, to relate PAI-1 changes to outcome, mice underwent TH-CLP and were sampled daily and followed for 14 days to compare non-survivors (DEAD and survivors (SUR. In experiment 3, plasma and tissue PAI-1 expression were compared between mice predicted to die (P-DIE and to live (P-LIVE. RESULTS: In experiment 1, an early post-TH rise of circulating PAI-1 was contrasted by a delayed (post-TH decrease of PAI-1 mRNA in organs. In the post-CLP phase, profiles of circulating PAI-1 were similar between TH-CLP and CLP-Only mice. Conversely, PAI-1 mRNA declined in the liver and heart of TH-CLP mice versus CLP-Only. In experiment 2, there were no DEAD/SUR differences in circulating PAI-1 prior to CLP. Post-CLP, circulating PAI-1 in DEAD was 2-4-fold higher than in SUR. PAI-1 increase heralded septic deaths up to 48 h prior but DEAD/SUR thrombomodulin (endothelial injury marker levels were identical. In experiment 3, levels of circulating PAI-1 and its hepatic gene expression were higher in P-DIE versus P-LIVE mice and those increases closely correlated with liver dysfunction. CONCLUSIONS: Trauma modulated septic PAI-1 responses in a compartment-specific fashion. Only post-CLP increases in circulating PAI-1 predicted septic outcomes. In posttraumatic sepsis, pre-lethal release of PAI-1 was mostly of hepatic origin and was independent

Globalization and protection of environment

International Nuclear Information System (INIS)

Panahandeh, M.

2003-01-01

In recent years two trends have come into conflict in the international arena. The first is the globalization of economy and the second is the increased public concern over the environmental impact of economic activities and awareness of the global dimensions of many environmental problems. Nowadays confrontation of the issue of globalization and economic liberalization and protect of the environment is a matter of heated debate and environmentalists see globalization posing a threat to environment standards. The effects of liberalization on environment in the developing world have been analyzed from the perspective of the pollution- have hypothesis. The hypothesis suggests that the liberalization encourages a spatial displacement of the so-called d irty o r pollution- intensive industries from the developed countries with stricter environmental regulations to their preferential location in developing countries which enjoy minimal environmental regulations or capacity for environmental monitoring and enforcement. It also suggests that economic policies which promote foreign investment in the natural resources of developing countries will increase rates of natural-resource extraction in the developing world. according to the theory, the translational firms will employ cheep technologies in developing countries which are not environmental sound and no longer permitted to use in the industrialized world

NEW INTERNATIONAL FINANCIAL REGULATION: NECESSITY OR REQUIRED BY CRISIS

Directory of Open Access Journals (Sweden)

Cojocari Anatol

2010-07-01

Full Text Available The global economic and financial crisis showed the limits faced by the international financial system. International financial regulations in general, and especially the banking sector regulations, should be refined and adapted to build a stronger and stable international financial system. We analyze the main trends in international regulations: the proposed amendments on capital requirements, the introduction of a global standard for liquidity and indebtedness, the winding-up directive, as well as their impact on the Romanian financial system.

The early psychological adjustment of cleft patients after maxillary distraction osteogenesis and conventional orthognathic surgery: a preliminary study.

Science.gov (United States)

Cheung, Lim Kwong; Loh, John Ser Pheng; Ho, Samuel M Y

2006-12-01

To compare the early psychological changes of cleft lip and palate (CLP) and noncleft patients after maxillofacial corrective surgery, including maxillary distraction osteogenesis and conventional orthognathic surgery. Nine CLP patients were compared with a group of 9 non-CLP patients having similar dentofacial deformities in a prospective longitudinal cohort study. Five of the CLP patients underwent maxillary distraction osteogenesis and 4 underwent conventional orthognathic surgery. A control group of 9 noncleft patients received conventional orthognathic surgery. All patients completed a set of questionnaires to enable their psychological profile to be assessed. The data were collected immediately before surgery (T1), and at 3 weeks (T2) and 12 weeks (T3) after surgery. The CLP patients treated with distraction osteogenesis were happier, but had a higher level of social anxiety and distress than the CLP patients receiving conventional orthognathic surgery. On the other hand, the CLP patients overall were happier, with lower social anxiety and distress, than the noncleft control group. The CLP patients showed a higher level of parental self-esteem than the noncleft patients. This preliminary study shows that CLP patients were generally happier, and had a higher level of parental support, than normal patients suffering from dentofacial deformities. Maxillary distraction osteogenesis seemed to induce a higher level of anxiety and distress in CLP patients than conventional orthognathic surgery in both cleft and noncleft patients.

PspF-binding domain PspA1-144 and the PspA·F complex: New insights into the coiled-coil-dependent regulation of AAA+ proteins.

Science.gov (United States)

Osadnik, Hendrik; Schöpfel, Michael; Heidrich, Eyleen; Mehner, Denise; Lilie, Hauke; Parthier, Christoph; Risselada, H Jelger; Grubmüller, Helmut; Stubbs, Milton T; Brüser, Thomas

2015-11-01

Phage shock protein A (PspA) belongs to the highy conserved PspA/IM30 family and is a key component of the stress inducible Psp system in Escherichia coli. One of its central roles is the regulatory interaction with the transcriptional activator of this system, the σ(54) enhancer-binding protein PspF, a member of the AAA+ protein family. The PspA/F regulatory system has been intensively studied and serves as a paradigm for AAA+ enzyme regulation by trans-acting factors. However, the molecular mechanism of how exactly PspA controls the activity of PspF and hence σ(54) -dependent expression of the psp genes is still unclear. To approach this question, we identified the minimal PspF-interacting domain of PspA, solved its structure, determined its affinity to PspF and the dissociation kinetics, identified residues that are potentially important for PspF regulation and analyzed effects of their mutation on PspF in vivo and in vitro. Our data indicate that several characteristics of AAA+ regulation in the PspA·F complex resemble those of the AAA+ unfoldase ClpB, with both proteins being regulated by a structurally highly conserved coiled-coil domain. The convergent evolution of both regulatory domains points to a general mechanism to control AAA+ activity for divergent physiologic tasks via coiled-coil domains. © 2015 John Wiley & Sons Ltd.

Risk of Breast Cancer in Families with Cleft Lip and Palate

DEFF Research Database (Denmark)

Dietz, Alexander; Pedersen, Dorthe Almind; Jacobsen, Rune

2012-01-01

PURPOSE: To test whether female subjects in families with cleft lip and/or palate (CL/P) have an increased risk of breast cancer. METHODS: By using the Danish Facial Cleft Registry, we identified female subjects with CL/P, mothers of children with CL/P, and sisters to CL/P cases for the Danish...

Cosmetic Surgery: Regulatory Challenges in a Global Beauty Market.

Science.gov (United States)

Griffiths, Danielle; Mullock, Alex

2017-02-28

The market for cosmetic surgery tourism is growing with an increase in people travelling abroad for cosmetic surgery. While the reasons for seeking cosmetic surgery abroad may vary the most common reason is financial, but does cheaper surgery abroad carry greater risks? We explore the risks of poorly regulated cosmetic surgery to society generally before discussing how harm might be magnified in the context of cosmetic tourism, where the demand for cheaper surgery drives the market and makes surgery accessible for increasing numbers of people. This contributes to the normalisation of surgical enhancement, creating unhealthy cultural pressure to undergo invasive and risky procedures in the name of beauty. In addressing the harms of poorly regulated surgery, a number of organisations purport to provide a register of safe and ethical plastic surgeons, yet this arguably achieves little and in the absence of improved regulation the risks are likely to grow as the global market expands to meet demand. While the evidence suggests that global regulation is needed, the paper concludes that since a global regulatory response is unlikely, more robust domestic regulation may be the best approach. While domestic regulation may increase the drive towards foreign providers it may also have a symbolic effect which will reduce this drive by making people more aware of the dangers of surgery, both to society and individual physical wellbeing.

Markets, religion, regulation

DEFF Research Database (Denmark)

Fischer, Johan

2016-01-01

Most recent scholarship on moral economies or religious markets argues for the compatibility of economies/markets and religious practices in particular national or regional contexts. However, over the last couple of decades or so religious markets have entered a new phase characterized by new forms...... of regulation, certification and standardization on a global scale. Building on research on global kosher (a Hebrew term meaning “fit” or “proper”), halal (an Arabic word that literally means “permissible” or “lawful”) and Hindu vegetarianism this paper argues that these economies or markets to a large extent...... are conditioned by and themselves condition forms of transnational governmentality, that is, new and often overlapping practices of government and grassroots politics. I explore religious economies and markets at three interrelated levels of the social scale: state and non-state regulation, the marketplace...

Manager of financial globalization? The European Union in global anti-money laundering and international accounting standard setting

OpenAIRE

Hilgers, Sven

2014-01-01

How does the European Union (EU) perform in international financial regulation? According to various scholars the global financial architecture has been shaped by the USA and the EU. But whereas the USA is without doubt the dominant actor or even described as hegemon in writing the rules for the global political economy and global financial markets, the EU seems to be a special kind of actor. The European Union is not only one of the biggest single financial markets in the world but also has ...

Edaravone Improves Septic Cardiac Function by Inducing an HIF-1α/HO-1 Pathway

Directory of Open Access Journals (Sweden)

Chao He

2018-01-01

Full Text Available Septic myocardial dysfunction remains prevalent and raises mortality rate in patients with sepsis. During sepsis, tissues undergo tremendous oxidative stress which contributes critically to organ dysfunction. Edaravone, a potent radical scavenger, has been proved beneficial in ischemic injuries involving hypoxia-inducible factor- (HIF- 1, a key regulator of a prominent antioxidative protein heme oxygenase- (HO- 1. However, its effect in septic myocardial dysfunction remains unclarified. We hypothesized that edaravone may prevent septic myocardial dysfunction by inducing the HIF-1/HO-1 pathway. Rats were subjected to cecal ligation and puncture (CLP with or without edaravone infusion at three doses (50, 100, or 200 mg/kg, resp. before CLP and intraperitoneal injection of the HIF-1α antagonist, ME (15 mg/kg, after CLP. After CLP, rats had cardiac dysfunction, which was associated with deformed myocardium, augmented lipid peroxidation, and increased myocardial apoptosis and inflammation, along with decreased activities of catalase, HIF-1α, and HO-1 in the myocardium. Edaravone pretreatment dose-dependently reversed the changes, of which high dose most effectively improved cardiac function and survival rate of septic rats. However, inhibition of HIF-1α by ME demolished the beneficial effects of edaravone at high dose, reducing the survival rate of the septic rats without treatments. Taken together, edaravone, by inducing the HIF-1α/HO-1 pathway, suppressed oxidative stress and protected the heart against septic myocardial injury and dysfunction.

Global ethics: the nature and purpose

Directory of Open Access Journals (Sweden)

Ye. M. Sulima

2017-07-01

Full Text Available The article discusses the factors of forming, the essence and importance of a global ethic as a moral regulator of intercultural interaction in the modern global society. The current global ethics built around basic common goals - peace and dignity of people, social justice, individual freedom, cultural pluralism, sustainable development - and allow plans to achieve different objectives, functioning set of identities and nationalities. It lies in increasing awareness of common fate, common human and social rights, interests, shared vulnerability to global environmental, social and political crises of necessity, consequent, to find common solutions and act on the basis of cultural dialogue and cooperation.

Modulating the Global Response Regulator, LuxO of V. cholerae Quorum Sensing System Using a Pyrazine Dicarboxylic Acid Derivative (PDCApy: An Antivirulence Approach

Directory of Open Access Journals (Sweden)

M. Hema

2017-10-01

Full Text Available Vibrio cholerae is a Gram-negative pathogen which causes acute diarrhoeal disease, cholera by the expression of virulence genes through quorum sensing (QS mechanism. The QS circuit of V. cholerae is controlled by the global quorum regulator, LuxO, which at low cell density (LCD state produces major virulence factors such as, toxin co-regulated pilus (TCP and cholera toxin (CT to mediate infection. On the contrary, at the high cell density (HCD state the virulent genes are downregulated and the vibrios are detached from the host intestinal epithelial cells, promoted by HapA protease. Hence, targeting the global regulator LuxO would be a promising approach to modulate the QS to curtail V. cholerae pathogenesis. In our earlier studies, LuxO targeted ligand, 2,3 pyrazine dicarboxylic acid (PDCA and its derivatives having desired pharmacophore properties were chemically synthesized and were shown to have biofilm inhibition as well as synergistic activity with the conventionally used antibiotics. In the present study, the QS modulatory effect of the PDCA derivative with pyrrolidine moiety designated as PDCApy against the V. cholerae virulence gene expression was analyzed at various growth phases. The data significantly showed a several fold reduction in the expression of the genes, tcp and ct whereas the expression of hapR was upregulated at the LCD state. In addition, PDCApy reduced the adhesion and invasion of the vibrios onto the INT407 intestinal cell lines. Collectively, our data suggest that PDCApy could be a potential QS modulator (QSM for the antivirulence therapeutic approach.

Ideological Hegemony and Global Governance

OpenAIRE

Thomas Ford Brown

2015-01-01

In this paper, I analyze libertarian discourse from the perspective of regulation theory, a~ a hegemonic ideology that underlies the emergence of a new mode of regulation. Within this general theoretical approach, I will also employ frames from regime theory as developed by international relations scholars, as well as the "epistemic community" approach from the same discipline. I want to suggest that free-market ideology could engender the emergence of rationalized global governance in order ...

[Effect of compound hypertonic saline solution on septic rats].

Science.gov (United States)

Dong, Fang; Xu, Liang; Xu, Gang; Wang, Huabing; Lu, Huizhi; Cai, Liping

2015-01-01

To study the effect of compound hypertonic saline solution ( HSD ) on sepsis. 133 male Wistar rats were divided into four groups, sham operation group ( n = 15 ), cecal ligation and puncture ( CLP ) group ( n = 45 ), CLP plus normal saline ( NS ) group ( n = 45 ), and CLP plus HSD group ( n = 28 ). A rat model of sepsis was reproduced by CLP, and the rats in sham operation group received celiotomy without ligation and puncture. All rats in four groups received subcutaneous injection of 30 mL/kg 0.9% sodium chloride after laparotomy. The rats in CLP plus NS group and CLP plus HSD group received infusion of 5 mL/kg 0.9% sodium chloride or 7.5% sodium chloride/6% dextran post CLP via jugular vein for 3 hours, with the infusion rate of 0.4 mL×kg(-1)×min(-1). The survival rate of each group was observed 9 hours and 18 hours after laparotomy. Mean arterial pressure ( MAP ) at 0, 9, 18 hours were monitored. Blood specimens were collected from all rats 0, 9 and 18 hours after laparotomy, respectively, for measurement of the plasma levels of tumor necrosis factor-α ( TNF-α), interleukin-1β ( IL-1β ), and procalcitonin ( PCT ). The rats were all sacrificed, and their lung tissues were harvested for the neutrophil count in bronchoalveolar lavage fluid ( BALF ), myeloperoxidase ( MPO ) activity in lung tissue, wet/dry weight ratio ( W/D ) of lung, and pathological changes in lung tissue. There was no death in the sham operation group. The survival rates at 9 hours and 18 hours were 62.2% and 31.1% in the CLP group, 57.8% and 35.6% in the CLP plus NS group, 85.7% and 64.3% in the CLP plus HSD group, and they were all significantly higher compared with those of the CLP group and the CLP plus NS group ( Pmicroscope, no pathobiological changes were found in sham operation group. The lung tissues in the CLP group and the CLP plus NS group showed congestion, edema, infiltrating inflammatory changes, while the inflammatory changes in the lung tissue in the CLP plus HSD group

Global regulation of robots using only position measurements

NARCIS (Netherlands)

Berghuis, Harry; Berghuis, Harry; Nijmeijer, Henk

1993-01-01

In this note we propose a simple solution to the regulation problem of rigid robots based on the availability of only joint position measurements. The controller consists of two parts: (1) a gravitation compensation, (2) a linear dynamic first-order compensator. The gravitation compensation part can

Cecal ligation and puncture followed by MRSA pneumonia increases mortality in mice and blunts production of local and systemic cytokines

Science.gov (United States)

Jung, Enjae; Perrone, Erin E.; Liang, Zhe; Breed, Elise R.; Dominguez, Jessica A.; Clark, Andrew T.; Fox, Amy C.; Dunne, W. Michael; Burd, Eileen M.; Farris, Alton B.; Hotchkiss, Richard S.; Coopersmith, Craig M.

2011-01-01

Mortality in the ICU frequently results from the synergistic effect of two temporally-distinct infections. This study examined the pathophysiology of a new model of intraabdominal sepsis followed by methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Mice underwent cecal ligation and puncture (CLP) or sham laparotomy followed three days later by an intratracheal injection of MRSA or saline. Both CLP/saline and sham/MRSA mice had 100% survival while animals with CLP followed by MRSA pneumonia had 67% seven-day survival. Animals subjected to CLP/MRSA had increased bronchoalveolar lavage (BAL) concentrations of MRSA compared to sham/MRSA animals. Animals subjected to sham/MRSA pneumonia had increased BAL levels of IL-6, TNF-α, and G-CSF compared to those given intratracheal saline while CLP/MRSA mice had a blunted local inflammatory response with markedly decreased cytokine levels. Similarly, animals subjected to CLP/saline had increased peritoneal lavage levels of IL-6 and IL-1β compared to those subjected to sham laparotomy while this response was blunted in CLP/MRSA mice. Systemic cytokines were upregulated in both CLP/saline and sham/MRSA mice, and this was blunted by the combination of CLP/MRSA. In contrast, no synergistic effect on pneumonia severity, white blood cell count or lymphocyte apoptosis was identified in CLP/MRSA mice compared to animals with either insult in isolation. These results indicate that a clinically relevant model of CLP followed by MRSA pneumonia causes higher mortality than could have been predicted from studying either infection in isolation, and this was associated with a blunted local (pulmonary and peritoneal) and systemic inflammatory response and decreased ability to clear infection. PMID:21937950

Antiseptic Effects of New 3'-N-Substituted Carbazole Derivatives In Vitro and In Vivo.

Science.gov (United States)

Lee, Wonhwa; Kwak, Soyoung; Yun, Eunju; Lee, Jee Hyun; Na, MinKyun; Song, Gyu-Yong; Bae, Jong-Sup

2015-08-01

Inhibition of high-mobility group box 1 (HMGB1) protein and restoration of endothelial integrity are emerging as attractive therapeutic strategies in the management of sepsis. Here, new five structurally related 3'-N-substituted carbazole derivatives were examined for their effects on lipopolysaccharide (LPS)-mediated or cecal ligation and puncture (CLP)-mediated release of HMGB1 and on modulation of HMGB1-mediated inflammatory responses. We accessed this question by monitoring the effects of posttreatment carbazole derivatives on LPS- and CLP-mediated release of HMGB1 and HMGB1-mediated regulation of proinflammatory responses in human umbilical vein endothelial cells (HUVECs) and septic mice. The new 3'-N-substituted carbazole derivatives 1-5 inhibited the release of HMGB1 and downregulated HMGB1-dependent inflammatory responses in human endothelial cells. New compounds also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with each compound reduced CLP-induced release of HMGB1 and sepsis-related mortality and pulmonary injury in mice. These results indicate that the new 3'-N-substituted carbazole derivatives could be candidate therapeutic agents for various severe vascular inflammatory diseases owing to their inhibition of the HMGB1 signaling pathway.

EU effect: Exporting emission standards for vehicles through the global market economy.

Science.gov (United States)

Crippa, M; Janssens-Maenhout, G; Guizzardi, D; Galmarini, S

2016-12-01

Emission data from EDGAR (Emissions Database for Global Atmospheric Research), rather than economic data, are used to estimate the effect of policies and of the global exports of policy-regulated goods, such as vehicles, on global emissions. The results clearly show that the adoption of emission standards for the road transport sector in the two main global markets (Europe and North America) has led to the global proliferation of emission-regulated vehicles through exports, regardless the domestic regulation in the country of destination. It is in fact more economically convenient for vehicle manufacturers to produce and sell a standard product to the widest possible market and in the greatest possible amounts. The EU effect (European Union effect) is introduced as a global counterpart to the California effect. The former is a direct consequence of the penetration of the EURO standards in the global markets by European and Japanese manufacturers, which effectively export the standard worldwide. We analyze the effect on PM 2.5 emissions by comparing a scenario of non-EURO standards against the current estimates provided by EDGAR. We find that PM 2.5 emissions were reduced by more than 60% since the 1990s worldwide. Similar investigations on other pollutants confirm the hypothesis that the combined effect of technological regulations and their diffusion through global markets can also produce a positive effect on the global environment. While we acknowledge the positive feedback, we also demonstrate that current efforts and standards will be totally insufficient should the passenger car fleets in emerging markets reach Western per capita figures. If emerging countries reach the per capita vehicle number of the USA and Europe under current technological conditions, then the world will suffer pre-1990 emission levels. Copyright © 2016 Elsevier Ltd. All rights reserved.

The regulation of appetite

OpenAIRE

Druce, M; Bloom, S R

2006-01-01

The worsening global obesity epidemic, particularly the increase in childhood obesity, has prompted research into the mechanisms of appetite regulation. Complex pathways modulate energy balance, involving appetite centres in the hypothalamus and brain stem, and hormonal signals of energy status released by the gut and by the periphery. Better understanding of appetite regulation improves understanding of the aetiology of obesity. Manipulation of this homoeostatic system offers potentially use...

Environmental Upgrading in Global Value Chains

DEFF Research Database (Denmark)

Poulsen, René Taudal; Ponte, Stefano; Sornn-Friese, Henrik

2018-01-01

Ports are crucial hubs in the functioning of the global economy, and maritime transport is a major emitter of air pollutants. Ports have considerable potential for promoting environmental upgrading in maritime transport and along global value chains more generally, but so far have been only...... partially successful in doing so. We examine results, limitations and future potential of voluntary initiatives that have been carried out by selected European and North American port authorities, which are considered frontrunners in environmental management. Drawing from the insights of global value chain...... their organizational and physical boundaries: by lowering tool implementation complexity through stronger collaboration within global value chains; and by enhancing emission visibility through alliances with cargo-owners and regulators....

Changes of Global Infectious Disease Governance in 2000s: Rise of Global Health Security and Transformation of Infectious Disease Control System in South Korea

Directory of Open Access Journals (Sweden)

Eun Kyung CHOI

2016-12-01

Full Text Available This paper focus upon the changes of global infectious disease governance in 2000s and the transformation of infectious disease control system in South Korea. Traditionally, infectious disease was globally governed by the quarantine regulated by the international conventions. When an infectious disease outbreak occurred in one country, each country prevented transmission of the disease through the standardized quarantine since the installation of international sanitary convention in 1892. Republic of Korea also organized the infectious disease control system with quarantine and disease report procedure after the establishment of government. Additionally, Korea National Health Institute(KNIH was founded as research and training institute for infectious disease. However, traditional international health regulation system faced a serious challenge by the appearance of emerging and re-emerging infectious disease in 1990s. As a result, global infectious disease governance was rapidly changed under the demand to global disease surveillance and response. Moreover, global health security frame became important after 2001 bioterror and 2003 SARS outbreak. Consequently, international health regulation was fully revised in 2005, which included not only infectious disease but also public health emergency. The new international health regime was differently characterized in several aspects; reinforcement of global cooperation and surveillance, enlargement of the role of supranational and international agencies, and reorganization of national capacity. KNIH was reorganized with epidemic control and research since late 1990s. However, in 2004 Korea Center for Disease Control and Prevention(KCDC was established as a disease control institution with combining quarantine and other functions after 2003 SARS outbreak. KCDC unified national function against infectious disease including prevention, protection, response and research, as a national representative in

Changes of Global Infectious Disease Governance in 2000s: Rise of Global Health Security and Transformation of Infectious Disease Control System in South Korea.

Science.gov (United States)

Choi, Eun Kyung; Lee, Jong-Koo

2016-12-01

This paper focus upon the changes of global infectious disease governance in 2000s and the transformation of infectious disease control system in South Korea. Traditionally, infectious disease was globally governed by the quarantine regulated by the international conventions. When an infectious disease outbreak occurred in one country, each country prevented transmission of the disease through the standardized quarantine since the installation of international sanitary convention in 1892. Republic of Korea also organized the infectious disease control system with quarantine and disease report procedure after the establishment of government. Additionally, Korea National Health Institute(KNIH) was founded as research and training institute for infectious disease. However, traditional international health regulation system faced a serious challenge by the appearance of emerging and re-emerging infectious disease in 1990s. As a result, global infectious disease governance was rapidly changed under the demand to global disease surveillance and response. Moreover, global health security frame became important after 2001 bioterror and 2003 SARS outbreak. Consequently, international health regulation was fully revised in 2005, which included not only infectious disease but also public health emergency. The new international health regime was differently characterized in several aspects; reinforcement of global cooperation and surveillance, enlargement of the role of supranational and international agencies, and reorganization of national capacity. KNIH was reorganized with epidemic control and research since late 1990s. However, in 2004 Korea Center for Disease Control and Prevention(KCDC) was established as a disease control institution with combining quarantine and other functions after 2003 SARS outbreak. KCDC unified national function against infectious disease including prevention, protection, response and research, as a national representative in disease control. The

Antibodies against homologous microbial caseinolytic proteases P characterise primary biliary cirrhosis.

Science.gov (United States)

Bogdanos, Dimitrios-Petrou; Baum, Harold; Sharma, Umesh C; Grasso, Alessandro; Ma, Yun; Burroughs, Andrew K; Vergani, Diego

2002-01-01

Antibodies to caseinolytic protease P(177-194) (ClpP(177-194)) of the proteolytic subunit of the Clp complex of Escherichia coli (E. coli) are uniquely present in primary biliary cirrhosis (PBC). Molecular mimicry between the regulatory subunit ClpX and the principal T-cell epitope of pyruvate dehydrogenase complex (PDC-E2) in PBC, has been proposed to account for this. Since ClpP is highly conserved among bacteria we investigated whether the micro-organisms triggering these antibodies may be other than E. coli. E. coli ClpP(177-194) is homologous with ClpP peptides of Yersinia enterocolitica (YEREN) and Haemophilus influenzae (HAEIN). Enzyme linked immunosorbent assay (ELISA) reactivity to these peptides was tested in 45 patients with PBC, 44 pathological and 32 healthy controls. Reactivity to at least one of the ClpP peptides was observed in 21 (47%) PBC patients, 5.8% pathological and 3.1% healthy controls (PECOLI ClpP(177-194), alone or in association with YEREN and/or HAEIN peptides, compared to three (14.2%) reactive with YEREN, two (9.5%) with YEREN/HAEIN and one (4.7%) with HAEIN peptide. Simultaneous reactivity to homologous sequences was due to cross-reactivity as confirmed by competition ELISAs. The PBC-specificity of anti-microbial ClpP reactivity is confirmed: the questions as to primary trigger(s) and relevance to PBC pathogenesis remain open.

Regulation of alcohol marketing: a global view.

Science.gov (United States)

Casswell, Sally; Maxwell, Anna

2005-09-01

The marketing of alcohol produces a new challenge for policy development internationally, in part because of the increase in the use of new, unmeasured technologies. Many of these new developments are, as yet, relatively invisible in the policy arena. New approaches in branding, the utilization of marketing opportunities via branded events and new products provide additional complexity to attempts to monitor and to restrict the impact of marketing on young people and other vulnerable groups. Current attempts to restrict marketing globally, which rely primarily on voluntary codes and focus on traditional media, are inadequate to these challenges. A new statutory framework is required to enable the monitoring and control of the full marketing mix in ways which match the sophistication of the marketing efforts themselves.

The global energy industry: is competition among suppliers ensured?

International Nuclear Information System (INIS)

Regibeau, P.

2000-01-01

Over the last 15 years, many factors have affected the effective degree of competition in coal, electricity, gas and oil. This paper concentrates on the effects of globalization, regulatory reform, privatization and inter-fuel mergers. While demand side globalization has led to increased competition, greater supply side globalization might lead to more collusive behaviour in sectors such as coal and electricity. Regulatory reform has helped foster competition in the US gas market and in several electricity markets. Still, regulators have imposed insufficient vertical separation and the regulation of international electricity transmission remains problematic. Privatization is very useful in enforcing initial changes in industry structure. Inter-fuel mergers might entail efficiency gains but they also raise significant issues for competition policy authorities. (orig.)

Remarks - Global energy outlook and externalities

International Nuclear Information System (INIS)

Gray, J.E.

1994-01-01

The author presents a global energy outlook, for the period 1990-2010. Then, he presents some views on the subject of externalities, some regulations and proscriptions about internalization of costs are detailed. (TEC)

Expression of the alaE gene is positively regulated by the global regulator Lrp in response to intracellular accumulation of l-alanine in Escherichia coli.

Science.gov (United States)

Ihara, Kohei; Sato, Kazuki; Hori, Hatsuhiro; Makino, Yumiko; Shigenobu, Shuji; Ando, Tasuke; Isogai, Emiko; Yoneyama, Hiroshi

2017-04-01

The alaE gene in Escherichia coli encodes an l-alanine exporter that catalyzes the active export of l-alanine using proton electrochemical potential. In our previous study, alaE expression was shown to increase in the presence of l-alanyl-l-alanine (Ala-Ala). In this study, the global regulator leucine-responsive regulatory protein (Lrp) was identified as an activator of the alaE gene. A promoter less β-galactosidase gene was fused to an alaE upstream region (240 nucleotides). Cells that were lacZ-deficient and harbored this reporter plasmid showed significant induction of β-galactosidase activity (approximately 17-fold) in the presence of 6 mM l-alanine, l-leucine, and Ala-Ala. However, a reporter plasmid possessing a smaller alaE upstream region (180 nucleotides) yielded transformants with strikingly low enzyme activity under the same conditions. In contrast, lrp-deficient cells showed almost no β-galactosidase induction, indicating that Lrp positively regulates alaE expression. We next performed an electrophoretic mobility shift assay (EMSA) and a DNase I footprinting assay using purified hexahistidine-tagged Lrp (Lrp-His). Consequently, we found that Lrp-His binds to the alaE upstream region spanning nucleotide -161 to -83 with a physiologically relevant affinity (apparent K D , 288.7 ± 83.8 nM). Furthermore, the binding affinity of Lrp-His toward its cis-element was increased by l-alanine and l-leucine, but not by Ala-Ala and d-alanine. Based on these results, we concluded that the gene expression of the alaE is regulated by Lrp in response to intracellular levels of l-alanine, which eventually leads to intracellular homeostasis of l-alanine concentrations. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

The contradictory impact of globalization and migration on gender equality

DEFF Research Database (Denmark)

Siim, Birte

2009-01-01

Globalization and migration have increased diversities and inequalities within and between nation-states and have created new problems regarding public policies intented to regulate political and socio-economic problems on national and global levels. Globalization and increased migration thus rep...... represent a thoeretical, normative and political challenge to understanding how gender and diversity at the national level are linked to processes of globalization. This article identifies some of the many issues involved in the Asia-Nordic 'local-global dialectic'....

Cecal ligation and puncture followed by methicillin-resistant Staphylococcus aureus pneumonia increases mortality in mice and blunts production of local and systemic cytokines.

Science.gov (United States)

Jung, Enjae; Perrone, Erin E; Liang, Zhe; Breed, Elise R; Dominguez, Jessica A; Clark, Andrew T; Fox, Amy C; Dunne, W Michael; Burd, Eileen M; Farris, Alton B; Hotchkiss, Richard S; Coopersmith, Craig M

2012-01-01

Mortality in the intensive care unit frequently results from the synergistic effect of two temporally distinct infections. This study examined the pathophysiology of a new model of intra-abdominal sepsis followed by methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Mice underwent cecal ligation and puncture (CLP) or sham laparotomy followed 3 days later by an intratracheal injection of MRSA or saline. Both CLP/saline and sham/MRSA mice had 100% survival, whereas animals with CLP followed by MRSA pneumonia had 67% 7-day survival. Animals subjected to CLP/MRSA had increased bronchoalveolar lavage concentrations of MRSA compared with sham/MRSA animals. Animals subjected to sham/MRSA pneumonia had increased bronchoalveolar lavage levels of interleukin 6 (IL-6), tumor necrosis factor α, and granulocyte colony-stimulating factor compared with those given intratracheal saline, whereas CLP/MRSA mice had a blunted local inflammatory response with markedly decreased cytokine levels. Similarly, animals subjected to CLP/saline had increased peritoneal lavage levels of IL-6 and IL-1β compared with those subjected to sham laparotomy, whereas this response was blunted in CLP/MRSA mice. Systemic cytokines were upregulated in both CLP/saline and sham/MRSA mice, and this was blunted by the combination of CLP/MRSA. In contrast, no synergistic effect on pneumonia severity, white blood cell count, or lymphocyte apoptosis was identified in CLP/MRSA mice compared with animals with either insult in isolation. These results indicate that a clinically relevant model of CLP followed by MRSA pneumonia causes higher mortality than could have been predicted from studying either infection in isolation, and this was associated with a blunted local (pulmonary and peritoneal) and systemic inflammatory response and decreased ability to clear infection.

Complications of ventilation tube insertion in children with and without cleft palate: a nested case-control comparison.

Science.gov (United States)

Smillie, Ian; Robertson, Sophie; Yule, Anna; Wynne, David M; Russell, Craig J H

2014-10-01

Optimizing hearing in patients with cleft lip and/or palate (CLP) by early recognition and management of otitis media with effusion is essential for speech development. Some evidence has suggested higher complication rates from ventilation tube (VT) insertion in patients with CLP and has led to a trend not to treat these patients surgically. However, studies have failed to match comparison groups for age and sex. To compare complication rates from VT insertion in pediatric patients with and without CLP. The study used a nested case-control design to evaluate 60 pediatric patients with CLP who underwent VT insertion at a children's hospital. The control group of age- and sex-matched patients was selected from a database of 2943 VT insertions. All patients were administered general anesthesia and underwent VT insertion by a pediatric otorhinolaryngology (ENT) team. The primary outcomes were numbers of otorrhea complications. Secondarily, rates of attendance at an ENT clinic specifically for complications were evaluated. Finally, numbers of complications other than otorrhea were assessed but not statistically analyzed owing to the varied types and low numbers in each group. The control cohort had 151 documented cases of otorrhea compared with 121 in the CLP group (ratio 1.25:1); the difference between groups was not statistically significant (P = .52). There was no significant difference in mean ENT clinic visits per patient for complications between groups (0.80 in the CLP group, 0.78 for controls) (P = .66). Regarding complications other than otorrhea, the control group reported more than the CLP group (43 vs 25; ratio, 1.7:1). Complication rates of VT placement among patients with CLP were not higher than those among patients without CLP. Therefore, treatment with VT insertion should be administered to patients with CLP under the same guidelines as for those without CLP. Indeed, there could be an argument for a shift in practice toward more aggressive

Evidence for an association between non-syndromic cleft lip with or without cleft palate and a gene located on the long arm of chromosome 4

Energy Technology Data Exchange (ETDEWEB)

Healey, S.C.; Chenevix-Trench, G. [Queensland Institute of Medical Research, Brisbane (Australia); Mitchell, L.E. [Saint Louis Univ., MO (United States)

1994-09-01

Evidence of linkage has been reported for non-syndromic cleft lip with or without cleft palate (CL{+-}P) and two markers (D4S175 and D4S192) in the region 4q25-4q31.3. The linkage evidence comes from a single Caucasian pedigree with multiple cases of CL{+-}P in five generations. High-density pedigrees are, however, atypical of CL{+-}P and linkage evidence obtained from such a family may not be relevant to the majority of CL{+-}P families. We have, therefore, examined the association of CL{+-}P with both D4S175 and D4S192 in 95 unrelated CL{+-}P patients and 161 unselected controls. There was no evidence for an association between D4S175 and CL{+-}P in these data. There was, however, a significant association between D4S192 and CL{+-}P ({chi}{sup 2}{sub 4}=15.5,P=0.006), and the genotypic distribution was significantly heterogeneous between CL{+-}P patients and controls (P=0.025). Comparison of each of the four most common alleles (i.e A87, A89, A91 and A95), to all other alleles combined, indicated that A87 was significantly less common (OR=0.56,95% C.I. 0.34-0.90), and A95 was significantly more common (OR=1.88,95% C.I. 1.03-3.43) among the CL{+-}P patients than the controls. Although of only borderline significance, A89 also appeared to be more common among patients than controls (OR=1.43,95% C.I. 0.99-2.60). Hence, it appears that genetic variation at a CL{+-}P susceptibility locus (CSL) linked to D4S192 may be associated with both increased and decreased risk of CL{+-}P. In combination, A89 and A95 are significantly more common in CL{+-}P patients than in controls (OR=1.80;95% C.I. 1.24-2.60) and account for a risk ratio of 1.08 in the first degree relatives of CL{+-}P patients. These results provide further evidence for the presence of a CSL in the region 4q25-4q31.1, and indicate that the putative CSL is located closer to D4S192 than to D4S175.

The Global Regulator Spx Functions in the Control of Organosulfur Metabolism in Bacillus subtilis†

Science.gov (United States)

Choi, Soon-Yong; Reyes, Dindo; Leelakriangsak, Montira; Zuber, Peter

2006-01-01

Spx is a global transcriptional regulator of the oxidative stress response in Bacillus subtilis. Its target is RNA polymerase, where it contacts the α subunit C-terminal domain. Recently, evidence was presented that Spx participates in sulfate-dependent control of organosulfur utilization operons, including the ytmI, yxeI, ssu, and yrrT operons. The yrrT operon includes the genes that function in cysteine synthesis from S-adenosylmethionine through intermediates S-adenosylhomocysteine, ribosylhomocysteine, homocysteine, and cystathionine. These operons are also negatively controlled by CymR, the repressor of cysteine biosynthesis operons. All of the operons are repressed in media containing cysteine or sulfate but are derepressed in medium containing the alternative sulfur source, methionine. Spx was found to negatively control the expression of these operons in sulfate medium, in part, by stimulating the expression of the cymR gene. In addition, microarray analysis, monitoring of yrrT-lacZ fusion expression, and in vitro transcription studies indicate that Spx directly activates yrrT operon expression during growth in medium containing methionine as sole sulfur source. These experiments have uncovered additional roles for Spx in the control of gene expression during unperturbed, steady-state growth. PMID:16885442

A global comparative overview of the legal regulation of stem cell research and therapy: Lessons for South Africa

Directory of Open Access Journals (Sweden)

Melodie Slabbert

2015-09-01

Full Text Available Stem cell research and its potential translation to regenerative medicine, tissue engineering and cell and gene therapy, have led to controversy and debates similar to the calls nearly 25 years ago for a ban involving recombinant DNA. Global legislative efforts in this field have been characterised by many legal, ethical and practical challenges, stemming from conflicting views regarding human embryonic research and cloning. National policy and regulatory developments have primarily been shaped by different understandings of relevant scientific objectives, as well as those relating to the moral and legal status of the human embryo, which have been used to justify or limit a range of permissible activities. Legal obscurity in this field, a consequence of inconsistent or vague legislative responses at a national and international level, leads to negative results, which include, among others, ethical violations; lack of collaboration and co-operation among researchers across national borders; stunted scientific progress; lack of public trust in stem cell research; proliferation of untested ‘stem cell therapies’; and safety issues. The purpose of this article is to explore the legal regulation of stem cell research and therapy globally, by comparing the permissibility of specific stem cell research activities in 35 selected jurisdictions, followed by a comparison of the regulatory approaches with regard to stem cell-based products in the European Union and the USA. A clearer understanding of the global regulatory framework will assist in formulating more effective legal responses at a national level and in navigating the uncertainties and risks associated with this complex and evolving scientific field.

Phosphatase Rtr1 Regulates Global Levels of Serine 5 RNA Polymerase II C-Terminal Domain Phosphorylation and Cotranscriptional Histone Methylation.

Science.gov (United States)

Hunter, Gerald O; Fox, Melanie J; Smith-Kinnaman, Whitney R; Gogol, Madelaine; Fleharty, Brian; Mosley, Amber L

2016-09-01

In eukaryotes, the C-terminal domain (CTD) of Rpb1 contains a heptapeptide repeat sequence of (Y1S2P3T4S5P6S7)n that undergoes reversible phosphorylation through the opposing action of kinases and phosphatases. Rtr1 is a conserved protein that colocalizes with RNA polymerase II (RNAPII) and has been shown to be important for the transition from elongation to termination during transcription by removing RNAPII CTD serine 5 phosphorylation (Ser5-P) at a selection of target genes. In this study, we show that Rtr1 is a global regulator of the CTD code with deletion of RTR1 causing genome-wide changes in Ser5-P CTD phosphorylation and cotranscriptional histone H3 lysine 36 trimethylation (H3K36me3). Using chromatin immunoprecipitation and high-resolution microarrays, we show that RTR1 deletion results in global changes in RNAPII Ser5-P levels on genes with different lengths and transcription rates consistent with its role as a CTD phosphatase. Although Ser5-P levels increase, the overall occupancy of RNAPII either decreases or stays the same in the absence of RTR1 Additionally, the loss of Rtr1 in vivo leads to increases in H3K36me3 levels genome-wide, while total histone H3 levels remain relatively constant within coding regions. Overall, these findings suggest that Rtr1 regulates H3K36me3 levels through changes in the number of binding sites for the histone methyltransferase Set2, thereby influencing both the CTD and histone codes. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Emerging Global Political Economy and Implications for the Nigerian ...

African Journals Online (AJOL)

The world has been transformed into a global political economy as a result of the unprecedented level of interconnectedness of political, economic, social and technological forces that permeate the contemporary global system. This paper identifies trade regulations, technology and capitalism as core factors responsible for ...

The Governance of Global Wealth Chains

DEFF Research Database (Denmark)

Seabrooke, Leonard; Wigan, Duncan

) innovation capacities among suppliers of products used in wealth chains. We then differentiate five types of global value chain governance - market, modular, relational, captive, and hierarchy - which range from simple ‘off shelf’ products shielded from regulators by advantageous international tax laws...... to highly complex and flexible innovative financial products produced by large financial institutions and corporations. This paper highlights how Global Wealth Chains intersect with value chains and real economies, and provides three brief case studies on offshore shell companies, family property trusts......This working paper creates a theoretical framework to explain how Global Wealth Chains are created, maintained, and governed. We draw upon different strands of literature, including scholarship in international political economy and economic geography on Global Value Chains, literature on finance...

Global Picture of Protein Regulation in Response to Dibutyl Phthalate (DBP) Stress of Two Brassica parachinensis Cultivars Differing in DBP Accumulation.

Science.gov (United States)

Zhao, Hai-Ming; Huang, He-Biao; Du, Huan; Xiang, Lei; Mo, Ce-Hui; Li, Yan-Wen; Cai, Quan-Ying; Li, Hui; Liu, Jie-Sheng; Zhou, Dong-Mei; Wong, Ming-Hung

2018-05-09

iTRAQ analysis was used to map the proteomes of two Brassica parachinensis cultivars that differed in dibutyl phthalate (DBP) accumulation. A total of 5699 proteins were identified to obtain 152 differentially regulated proteins, of which 64 and 48 were specific to a high- and a low-DBP-accumulation cultivar, respectively. Genotype-specific biological processes were involved in coping with DBP stress, accounting for the variation in DBP tolerance and accumulation. Formation of high DBP accumulation in B. parachinensis might attribute to the more effective regulation of protein expression in physiology and metabolism, including (a) enhanced cell wall biosynthesis and modification, (b) better maintenance of photosynthesis and energy balance, (c) greatly improved total capacity for antioxidation and detoxification, and (d) enhanced cellular transport and signal transduction. Our novel findings contribute to a global picture of DBP-induced alterations of protein profiles in crops and provide valuable information for the development of molecular-assisted breeds of low-accumulation cultivars.

77 FR 35944 - Renewal of the Global Markets Advisory Committee

Science.gov (United States)

2012-06-15

... international standards for regulating futures, swaps, options, and derivatives markets, as well as..., competitive, and financially sound futures and options markets. Meetings of the Global Markets Advisory... COMMODITY FUTURES TRADING COMMISSION Renewal of the Global Markets Advisory Committee AGENCY...

Regulation of fatty acid biosynthesis by the global regulator CcpA and the local regulator FabT in Streptococcus mutans

OpenAIRE

Faustoferri, R.C.; Hubbard, C.J.; Santiago, B.; Buckley, A.A.; Seifert, T.B.; Quivey, R.G.

2014-01-01

SMU.1745c, encoding a putative transcriptional regulator of the MarR family, maps to a location proximal to the fab gene cluster in Streptococcus mutans. Deletion of the SMU.1745c (fabTSm) coding region resulted in a membrane fatty acid composition comprised of longer-chained, unsaturated fatty acids (UFA), compared with the parent strain. Previous reports have indicated a role for FabT in regulation of genes in the fab gene cluster in other organisms, through binding to a palindromic DNA seq...

Global Health Security Demands a Strong International Health Regulations Treaty and Leadership From a Highly Resourced World Health Organization.

Science.gov (United States)

Burkle, Frederick M

2015-10-01

If the Ebola tragedy of West Africa has taught us anything, it should be that the 2005 International Health Regulations (IHR) Treaty, which gave unprecedented authority to the World Health Organization (WHO) to provide global public health security during public health emergencies of international concern, has fallen severely short of its original goal. After encouraging successes with the 2003 severe acute respiratory syndrome (SARS) pandemic, the intent of the legally binding Treaty to improve the capacity of all countries to detect, assess, notify, and respond to public health threats has shamefully lapsed. Despite the granting of 2-year extensions in 2012 to countries to meet core surveillance and response requirements, less than 20% of countries have complied. Today it is not realistic to expect that these gaps will be solved or narrowed in the foreseeable future by the IHR or the WHO alone under current provisions. The unfortunate failures that culminated in an inadequate response to the Ebola epidemic in West Africa are multifactorial, including funding, staffing, and poor leadership decisions, but all are reversible. A rush by the Global Health Security Agenda partners to fill critical gaps in administrative and operational areas has been crucial in the short term, but questions remain as to the real priorities of the G20 as time elapses and critical gaps in public health protections and infrastructure take precedence over the economic and security needs of the developed world. The response from the Global Outbreak Alert and Response Network and foreign medical teams to Ebola proved indispensable to global health security, but both deserve stronger strategic capacity support and institutional status under the WHO leadership granted by the IHR Treaty. Treaties are the most successful means the world has in preventing, preparing for, and controlling epidemics in an increasingly globalized world. Other options are not sustainable. Given the gravity of ongoing

Cervical vertebral maturation of children with orofacial clefts.

Science.gov (United States)

Sun, Ling; Li, Wei Ran

2012-11-01

To evaluate the skeletal maturation of male children with orofacial clefts using the cervical vertebral maturation (CVM) method. Case-control study. The School of Stomatology, Peking University. Subjects were 443 boys with cleft lip and/or cleft palate (CL/P) aged 8 to 16 years who were compared with 1772 boys without clefts in an age-matched control group. The 8- to 10-year-old boys of both groups were in CS1. Most of the 11- to 14-year-old boys without CL/P were in CS3 and CS4, though it was not so obvious in boys with CL/P. Most 15- to 16-year-old boys without CL/P were in CS5 and CS6, while there were a lot of boys with CL/P who were still in cervical stages before CS5. Clefts had a significant effect on growth, and boys without CL/P were 1.737 times more likely to have achieved higher cervical stages. From Mann-Whitney test of every age phase, the difference existed in each year of the age range of 11 to 16 years, except from 12 to 13 years (p  =  .100). In these age phases, the cervical stages of boys with CL/P were lower than those for boys without CL/P. By the age of 14, children with CL/P had a 4.679 times higher risk of delayed CS3, and the 95% confidence interval for the odds ratio was 2.129 to 10.286. Boys with CL/P are at a higher risk of delayed growth period and retarded pubertal growth peak.

75 FR 33788 - Renewal of the Global Markets Advisory Committee

Science.gov (United States)

2010-06-15

... appropriate international standards for regulating futures and derivatives markets, as well as intermediaries... financially sound futures and options markets. Meetings of the Global Markets Advisory Committee are open to... COMMODITY FUTURES TRADING COMMISSION Renewal of the Global Markets Advisory Committee AGENCY...

Genetics and Management of the Patient with Orofacial Cleft

Directory of Open Access Journals (Sweden)

Luciano Abreu Brito

2012-01-01

Full Text Available Cleft lip or palate (CL/P is a common facial defect present in 1 : 700 live births and results in substantial burden to patients. There are more than 500 CL/P syndromes described, the causes of which may be single-gene mutations, chromosomopathies, and exposure to teratogens. Part of the most prevalent syndromic CL/P has known etiology. Nonsyndromic CL/P, on the other hand, is a complex disorder, whose etiology is still poorly understood. Recent genome-wide association studies have contributed to the elucidation of the genetic causes, by raising reproducible susceptibility genetic variants; their etiopathogenic roles, however, are difficult to predict, as in the case of the chromosomal region 8q24, the most corroborated locus predisposing to nonsyndromic CL/P. Knowing the genetic causes of CL/P will directly impact the genetic counseling, by estimating precise recurrence risks, and the patient management, since the patient, followup may be partially influenced by their genetic background. This paper focuses on the genetic causes of important syndromic CL/P forms (van der Woude syndrome, 22q11 deletion syndrome, and Robin sequence-associated syndromes and depicts the recent findings in nonsyndromic CL/P research, addressing issues in the conduct of the geneticist.

Morphometric analysis of craniofacial features in mono- and dizygotic twins discordant for unilateral cleft lip and palate.

Science.gov (United States)

Tessler, Alexis Y; Franchi, Lorenzo; McNamara, James A; Baccetti, Tiziano

2011-09-01

To compare craniofacial differences between twins discordant for surgically repaired unilateral cleft lip and palate (CLP) during the developmental ages and to test the effect of zygosity on the shape and size of the craniofacial skeleton of the same twins by means of thin plate spline (TPS) analysis. Lateral and posteroanterior (PA) cephalometric films from 19 sets of monozygotic (MZ) twins (15 male and 4 female) and 10 dizygotic (DZ) twins (7 male and 3 female) were analyzed. TPS analysis evaluated statistically significant differences in the craniofacial shape and size between affected and unaffected twins within MZ and DZ twin couples. No statistically significant differences in craniofacial shape or size between CLP and non-CLP MZ or DZ twins were observed. The level of morphological similarity in CLP vs non-CLP MZ twins was statistically greater than in DZ twins. Morphometric analysis showed that surgically repaired CLP does not produce significant shape or size differences in the craniofacial features of MZ or DZ twins discordant for unilateral CLP.

Global regulator SoxR is a negative regulator of efflux pump gene expression and affects antibiotic resistance and fitness in Acinetobacter baumannii.

Science.gov (United States)

Li, Henan; Wang, Qi; Wang, Ruobing; Zhang, Yawei; Wang, Xiaojuan; Wang, Hui

2017-06-01

SoxR is a global regulator contributing to multidrug resistance in Enterobacteriaceae. However, the contribution of SoxR to antibiotic resistance and fitness in Acinetobacter baumannii has not yet been studied. Comparisons of molecular characteristics were performed between 32 multidrug-resistant A. baumannii isolates and 11 susceptible isolates. A soxR overexpression mutant was constructed, and its resistance phenotype was analyzed. The impact of SoxR on efflux pump gene expression was measured at the transcription level. The effect of SoxR on the growth and fitness of A. baumannii was analyzed using a growth rate assay and an in vitro competition assay. The frequency of the Gly39Ser mutation in soxR was higher in multidrug-resistant A. baumannii, whereas the soxS gene was absent in all strains analyzed. SoxR overexpression led to increased susceptibility to chloramphenicol (4-fold), tetracycline (2-fold), tigecycline (2-fold), ciprofloxacin (2-fold), amikacin (2-fold), and trimethoprim (2-fold), but it did not influence imipenem susceptibility. Decreased expression of abeS (3.8-fold), abeM (1.3-fold), adeJ (2.4-fold), and adeG (2.5-fold) were correlated with soxR overexpression (P baumannii.

Prevalence and characteristics of non-syndromic orofacial clefts and the influence of consanguinity.

Science.gov (United States)

Alamoudi, N M; Sabbagh, H J; Innes, N P T; El Derwi, D; Hanno, A Z; Al-Aama, J Y; Habiballah, A H; Mossey, P A

2014-01-01

The Objective of this study was to identify the prevalence and describe the characteristics of non-syndromic orofacial cleft (NSOFC) in Jeddah, Saudi Arabia and examine the influence of consanguinity. Six hospitals were selected to represent Jeddah's five municipal districts. New born infants with NSOFC born between 1st of January 2010 to 31st of December 2011 were clinically examined and their number compared to the total number of infants born in these hospitals to calculate the prevalence of NSOFC types and sub-phenotypes. Referred Infants were included for the purpose of studying NSOFC characteristics and their relationship to consanguinity. Information on NSOFC infants was gathered through parents' interviews, infants 'files and patient examinations. Prospective surveillance of births resulted in identifying 37 NSOFC infants born between 1st of January 2010 to 31st of December 2011 giving a birth prevalence of 0.80/1000 living births. The total infants seen, including referred cases, were 79 children. Consanguinity among parents of cleft palate (CP) cases was statistically higher than that among cleft lip with or without cleft palate (CL/P) patients (P = 0.039). Although there appears to be a trend in the relationship between consanguinity and severity of CL/P sub-phenotype, it was not statistically significant (P = 0.248). Birth prevalence of NSOFC in Jeddah City was 0.8/1000 live births with CL/P: 0.68/1000 and CP: 0.13/1000. Both figures were low compared to the global birth prevalence (NSOFC: 1.25/1000, CL/P: 0.94/1000 and CP: 0.31/1000 live births). Consanguineous parents were statistically higher among CP cases than among other NSOFC phenotypes.

Regulation of water resources for sustaining global future socioeconomic development

Science.gov (United States)

Chen, J.; SHI, H.; Sivakumar, B.

2016-12-01

With population projections indicating continued growth during this century, socio-economic problems (e.g., water, food, and energy shortages) will be most likely to occur, especially if proper planning, development, and management strategies are not adopted. In the present study, firstly, we explore the vital role of dams in promoting economic growth through analyzing the relationship between dams and Gross Domestic Product (GDP) at both global and national scales. Secondly, we analyze the current situation of global water scarcity based on the data representing water resources availability, dam development, and the level of economic development. Third, with comprehensive consideration of population growth as the major driving force, water resources availability as the basic supporting factor, and topography as the important constraint, this study addresses the question of dam development in the future and predicts the locations of future dams around the world.

The Challenge of Global Poliomyelitis Eradication.

Science.gov (United States)

Garon, Julie R; Cochi, Stephen L; Orenstein, Walter A

2015-12-01

In the United States during the 1950's, polio was on the forefront of every provider and caregiver's mind. Today, most providers in the United States have never seen a case. The Global Polio Eradication Initiative (GPEI), which began in 1988 has reduced the number of cases by over 99%. The world is closer to achieving global eradication of polio than ever before but as long as poliovirus circulates anywhere in the world, every country is vulnerable. The global community can support the polio eradication effort through continued vaccination, surveillance, enforcing travel regulations and contributing financial support, partnerships and advocacy. Copyright © 2015 Elsevier Inc. All rights reserved.

Global Metabolic Regulation of the Snow Alga Chlamydomonas nivalis in Response to Nitrate or Phosphate Deprivation by a Metabolome Profile Analysis.

Science.gov (United States)

Lu, Na; Chen, Jun-Hui; Wei, Dong; Chen, Feng; Chen, Gu

2016-05-10

In the present work, Chlamydomonas nivalis, a model species of snow algae, was used to illustrate the metabolic regulation mechanism of microalgae under nutrient deprivation stress. The seed culture was inoculated into the medium without nitrate or phosphate to reveal the cell responses by a metabolome profile analysis using gas chromatography time-of-flight mass spectrometry (GC/TOF-MS). One hundred and seventy-one of the identified metabolites clustered into five groups by the orthogonal partial least squares discriminant analysis (OPLS-DA) model. Among them, thirty of the metabolites in the nitrate-deprived group and thirty-nine of the metabolites in the phosphate-deprived group were selected and identified as "responding biomarkers" by this metabolomic approach. A significant change in the abundance of biomarkers indicated that the enhanced biosynthesis of carbohydrates and fatty acids coupled with the decreased biosynthesis of amino acids, N-compounds and organic acids in all the stress groups. The up- or down-regulation of these biomarkers in the metabolic network provides new insights into the global metabolic regulation and internal relationships within amino acid and fatty acid synthesis, glycolysis, the tricarboxylic acid cycle (TCA) and the Calvin cycle in the snow alga under nitrate or phosphate deprivation stress.

The prevalence of specific dental anomalies in a group of Saudi cleft lip and palate patients

Directory of Open Access Journals (Sweden)

Ghada H. Al-Kharboush

2015-04-01

Conclusions: Dental anomalies were common in Saudi subjects with CLP type. This will complicate the health care required for the CL/P subjects. This study was conducted to epidemiologically explore the prevalence of dental anomalies among Saudi Arabian subjects with CLP.

The Governance of Global Wealth Chains

DEFF Research Database (Denmark)

Seabrooke, Leonard; Wigan, Duncan

liability and (3) innovation capacities among suppliers of products used in wealth chains. We then differentiate five types of global value chain governance - market, modular, relational, captive, an d hierarchy – which range from simple ‘off shelf’ products shielded from regulators by advantageous...... international tax laws to highly complex and flexible innovative financial products produced by large financial institutions and corporations. This article highlights how Global Wealth Cha ins intersect with value chains and real economies, and provides three brief case studies on offshore shell companies......This introduction to the Special Issue creates a theoretical framework to explain how Global Wealth Chains are created, maintained, and governed. We draw upon different strands of literature, including scholarship in international political economy and economic geography on Global Value Chains...

Conserved regulators of nucleolar size revealed by global phenotypic analyses.

Science.gov (United States)

Neumüller, Ralph A; Gross, Thomas; Samsonova, Anastasia A; Vinayagam, Arunachalam; Buckner, Michael; Founk, Karen; Hu, Yanhui; Sharifpoor, Sara; Rosebrock, Adam P; Andrews, Brenda; Winston, Fred; Perrimon, Norbert

2013-08-20

Regulation of cell growth is a fundamental process in development and disease that integrates a vast array of extra- and intracellular information. A central player in this process is RNA polymerase I (Pol I), which transcribes ribosomal RNA (rRNA) genes in the nucleolus. Rapidly growing cancer cells are characterized by increased Pol I-mediated transcription and, consequently, nucleolar hypertrophy. To map the genetic network underlying the regulation of nucleolar size and of Pol I-mediated transcription, we performed comparative, genome-wide loss-of-function analyses of nucleolar size in Saccharomyces cerevisiae and Drosophila melanogaster coupled with mass spectrometry-based analyses of the ribosomal DNA (rDNA) promoter. With this approach, we identified a set of conserved and nonconserved molecular complexes that control nucleolar size. Furthermore, we characterized a direct role of the histone information regulator (HIR) complex in repressing rRNA transcription in yeast. Our study provides a full-genome, cross-species analysis of a nuclear subcompartment and shows that this approach can identify conserved molecular modules.

Conserved Regulators of Nucleolar Size Revealed by Global Phenotypic Analyses

Science.gov (United States)

Neumüller, Ralph A.; Gross, Thomas; Samsonova, Anastasia A.; Vinayagam, Arunachalam; Buckner, Michael; Founk, Karen; Hu, Yanhui; Sharifpoor, Sara; Rosebrock, Adam P.; Andrews, Brenda; Winston, Fred; Perrimon, Norbert

2014-01-01

Regulation of cell growth is a fundamental process in development and disease that integrates a vast array of extra- and intracellular information. A central player in this process is RNA polymerase I (Pol I), which transcribes ribosomal RNA (rRNA) genes in the nucleolus. Rapidly growing cancer cells are characterized by increased Pol I–mediated transcription and, consequently, nucleolar hypertrophy. To map the genetic network underlying the regulation of nucleolar size and of Pol I–mediated transcription, we performed comparative, genome-wide loss-of-function analyses of nucleolar size in Saccharomyces cerevisiae and Drosophila melanogaster coupled with mass spectrometry–based analyses of the ribosomal DNA (rDNA) promoter. With this approach, we identified a set of conserved and nonconserved molecular complexes that control nucleolar size. Furthermore, we characterized a direct role of the histone information regulator (HIR) complex in repressing rRNA transcription in yeast. Our study provides a full-genome, cross-species analysis of a nuclear subcompartment and shows that this approach can identify conserved molecular modules. PMID:23962978

High-resolution detection of DNA binding sites of the global transcriptional regulator GlxR in Corynebacterium glutamicum

DEFF Research Database (Denmark)

Jungwirth, Britta; Sala, Claudia; Kohl, Thomas A

2013-01-01

of the 6C non-coding RNA gene and to non-canonical DNA binding sites within protein-coding regions. The present study underlines the dynamics within the GlxR regulon by identifying in vivo targets during growth on glucose and contributes to the expansion of knowledge of this important transcriptional......The transcriptional regulator GlxR has been characterized as a global hub within the gene-regulatory network of Corynebacterium glutamicum. Chromatin immunoprecipitation with a specific anti-GlxR antibody and subsequent high-throughput sequencing (ChIP-seq) was applied to C. glutamicum to get new...... mapping of these data on the genome sequence of C. glutamicum, 107 enriched DNA fragments were detected from cells grown with glucose as carbon source. GlxR binding sites were identified in the sequence of 79 enriched DNA fragments, of which 21 sites were not previously reported. Electrophoretic mobility...

The Staphylococcus aureus Global Regulator MgrA Modulates Clumping and Virulence by Controlling Surface Protein Expression.

Directory of Open Access Journals (Sweden)

Heidi A Crosby

2016-05-01

Full Text Available Staphylococcus aureus is a human commensal and opportunistic pathogen that causes devastating infections in a wide range of locations within the body. One of the defining characteristics of S. aureus is its ability to form clumps in the presence of soluble fibrinogen, which likely has a protective benefit and facilitates adhesion to host tissue. We have previously shown that the ArlRS two-component regulatory system controls clumping, in part by repressing production of the large surface protein Ebh. In this work we show that ArlRS does not directly regulate Ebh, but instead ArlRS activates expression of the global regulator MgrA. Strains lacking mgrA fail to clump in the presence of fibrinogen, and clumping can be restored to an arlRS mutant by overexpressing either arlRS or mgrA, indicating that ArlRS and MgrA constitute a regulatory pathway. We used RNA-seq to show that MgrA represses ebh, as well as seven cell wall-associated proteins (SraP, Spa, FnbB, SasG, SasC, FmtB, and SdrD. EMSA analysis showed that MgrA directly represses expression of ebh and sraP. Clumping can be restored to an mgrA mutant by deleting the genes for Ebh, SraP and SasG, suggesting that increased expression of these proteins blocks clumping by steric hindrance. We show that mgrA mutants are less virulent in a rabbit model of endocarditis, and virulence can be partially restored by deleting the genes for the surface proteins ebh, sraP, and sasG. While mgrA mutants are unable to clump, they are known to have enhanced biofilm capacity. We demonstrate that this increase in biofilm formation is partially due to up-regulation of SasG, a surface protein known to promote intercellular interactions. These results confirm that ArlRS and MgrA constitute a regulatory cascade, and that they control expression of a number of genes important for virulence, including those for eight large surface proteins.

Genetically modified foods as global public goods

Directory of Open Access Journals (Sweden)

Susana Herrero Olarte

2014-07-01

Full Text Available "Genetically modified (GM food has become very important in the field of research, as a result of its expansion in recent decades. As the right to food is a human right, it cannot be left in the hands of private sector developments exclusively, due to the capacity of the public sector to limit or drive it, and in any case, contributing to food safety. To achieve this, and for its cross-border development, GM needs to be treated as Global Public Goods (GPG, defined as pure or impure public goods that cannot be provided or regulated from a national or regional level, but from a global perspective. Its definition as GPG, and the fact of being public goods, assumes greater involvement by the public sector for its supply or regulation. It is therefore necessary to analyze the positive and negative externalities generated by transgenic foods becoming public goods, but from a global perspective. The difficulty is, that according to the author, GMs are positive or negative, so that there is no consensus to restrict and even prevent them or encourage them. But, there is a consensus on some key issues of GM food, such as improving productivity, contributing to the reduction of the species, the dependence of farmers, or monopoly companies with the patent. Identifying these issues can serve to initiate the appropriate regulation."

Sensing the environment: regulation of local and global homeostasis by the skin's neuroendocrine system.

Science.gov (United States)

Slominski, Andrzej T; Zmijewski, Michal A; Skobowiat, Cezary; Zbytek, Blazej; Slominski, Radomir M; Steketee, Jeffery D

2012-01-01

endings to alert the brain on changes in the epidermal or dermal environments, or alternatively to activate other coordinating centers by direct (spinal cord) neurotransmission without brain involvement. Furthermore, rapid and reciprocal communications between epidermal and dermal and adnexal compartments are also mediated by neurotransmission including antidromic modes of conduction. In conclusion, skin cells and skin as an organ coordinate and/or regulate not only peripheral but also global homeostasis.

Post-Modernity and Consumerism in the Globalized World

Directory of Open Access Journals (Sweden)

Cláudia Maria Moreira Kloper Mendonça

2016-06-01

Full Text Available This work is the result of bibliographic research , aiming to address the issues relevant for the understanding of the subject " globalization and consumption front postmodernity ." The postmodern society is a globalized and consumerist society and the individual must be protected since it vulnerable to consumer market dictates in this globalized era . And in this respect , the law comes to the important role of regulating these consumer relations for the protection of vulnerable and hypervulnerable people such as the elderly and children .

Medical devices regulations, standards and practices

CERN Document Server

Ramakrishna, Seeram; Wang, Charlene

2015-01-01

Medical Devices and Regulations: Standards and Practices will shed light on the importance of regulations and standards among all stakeholders, bioengineering designers, biomaterial scientists and researchers to enable development of future medical devices. Based on the authors' practical experience, this book provides a concise, practical guide on key issues and processes in developing new medical devices to meet international regulatory requirements and standards. Provides readers with a global perspective on medical device regulationsConcise and comprehensive information on how to desig

The Primary Care Pediatrician and the Care of Children With Cleft Lip and/or Cleft Palate.

Science.gov (United States)

Lewis, Charlotte W; Jacob, Lisa S; Lehmann, Christoph U

2017-05-01

Orofacial clefts, specifically cleft lip and/or cleft palate (CL/P), are among the most common congenital anomalies. CL/P vary in their location and severity and comprise 3 overarching groups: cleft lip (CL), cleft lip with cleft palate (CLP), and cleft palate alone (CP). CL/P may be associated with one of many syndromes that could further complicate a child's needs. Care of patients with CL/P spans prenatal diagnosis into adulthood. The appropriate timing and order of specific cleft-related care are important factors for optimizing outcomes; however, care should be individualized to meet the specific needs of each patient and family. Children with CL/P should receive their specialty cleft-related care from a multidisciplinary cleft or craniofacial team with sufficient patient and surgical volume to promote successful outcomes. The primary care pediatrician at the child's medical home has an essential role in making a timely diagnosis and referral; providing ongoing health care maintenance, anticipatory guidance, and acute care; and functioning as an advocate for the patient and a liaison between the family and the craniofacial/cleft team. This document provides background on CL/P and multidisciplinary team care, information about typical timing and order of cleft-related care, and recommendations for cleft/craniofacial teams and primary care pediatricians in the care of children with CL/P. Copyright © 2017 by the American Academy of Pediatrics.

The Analysis of the Impact of Globalization on Employment in Ukraine

Directory of Open Access Journals (Sweden)

Gryshkin Vadym O.

2016-08-01

Full Text Available The aim of the article is analyzing the impact of globalization on employment in Ukraine and studying foreign experience in regulation of the labor market under conditions of globalization. The theoretical aspects of employment of population at the stage of market transformation of economy have been analyzed. The comprehensive analysis of the current state of employment in Ukraine has been conducted. The dynamics of the main indicators of employment of population and labor migration has been considered and analyzed. The shortcomings in the mechanism of employment regulation are revealed and measures to overcome them on the basis of the positive experience of developed countries are proposed. The necessity of adapting the foreign experience to the Ukrainian realities and the possibility of its use in the national territory is justified. The main tasks of the state policy on regulating the employment of Ukraine’s population under conditions of globalization are presented.

A "footprint" of plant carbon fixation cycle functions during the development of a heterotrophic fungus.

Science.gov (United States)

Lyu, Xueliang; Shen, Cuicui; Xie, Jiatao; Fu, Yanping; Jiang, Daohong; Hu, Zijin; Tang, Lihua; Tang, Liguang; Ding, Feng; Li, Kunfei; Wu, Song; Hu, Yanping; Luo, Lilian; Li, Yuanhao; Wang, Qihua; Li, Guoqing; Cheng, Jiasen

2015-08-11

Carbon fixation pathway of plants (CFPP) in photosynthesis converts solar energy to biomass, bio-products and biofuel. Intriguingly, a large number of heterotrophic fungi also possess enzymes functionally associated with CFPP, raising the questions about their roles in fungal development and in evolution. Here, we report on the presence of 17 CFPP associated enzymes (ten in Calvin-Benson-Basham reductive pentose phosphate pathway and seven in C4-dicarboxylic acid cycle) in the genome of Sclerotinia sclerotiorum, a heterotrophic phytopathogenic fungus, and only two unique enzymes: ribulose-1, 5-bisphosphate carboxylase-oxygenase (Rubisco) and phosphoribulokinase (PRK) were absent. This data suggested an incomplete CFPP-like pathway (CLP) in fungi. Functional profile analysis demonstrated that the activity of the incomplete CLP was dramatically regulated during different developmental stages of S. sclerotiorum. Subsequent experiments confirmed that many of them were essential to the virulence and/or sclerotial formation. Most of the CLP associated genes are conserved in fungi. Phylogenetic analysis showed that many of them have undergone gene duplication, gene acquisition or loss and functional diversification in evolutionary history. These findings showed an evolutionary links in the carbon fixation processes of autotrophs and heterotrophs and implicated the functions of related genes were in course of continuous change in different organisms in evolution.

An approach to scoring cursorial limb proportions in carnivorous dinosaurs and an attempt to account for allometry

Science.gov (United States)

Persons, W. Scott, IV; Currie, Philip J.

2016-01-01

From an initial dataset of 53 theropod species, the general relationship between theropod lower-leg length and body mass is identified. After factoring out this allometric relationship, theropod hindlimb proportions are assessed irrespective of body mass. Cursorial-limb-proportion (CLP) scores derived for each of the considered theropod taxa offer a measure of the extent to which a particular species deviates in favour of higher or lower running speeds. Within the same theropod species, these CLP scores are found to be consistent across multiple adult specimens and across disparate ontogenetic stages. Early theropods are found to have low CLP scores, while the coelurosaurian tyrannosauroids and compsognathids are found to have high CLP scores. Among deinonychosaurs, troodontids have consistently high CLP scores, while many dromaeosaur taxa, including Velociraptor and Deinonychus, have low CLP scores. This indicates that dromaeosaurs were not, overall, a particularly cursorily adapted group. Comparisons between the CLP scores of Tyrannosaurus and specimens referred to the controversial genus Nanotyrannus indicate a strong discrepancy in cursorial adaptations, which supports the legitimacy of Nanotyrannus and the previous suggestions of ecological partitioning between Nanotyrannus and the contemporaneous Tyrannosaurus.

An approach to scoring cursorial limb proportions in carnivorous dinosaurs and an attempt to account for allometry.

Science.gov (United States)

Persons, W Scott; Currie, Philip J

2016-01-27

From an initial dataset of 53 theropod species, the general relationship between theropod lower-leg length and body mass is identified. After factoring out this allometric relationship, theropod hindlimb proportions are assessed irrespective of body mass. Cursorial-limb-proportion (CLP) scores derived for each of the considered theropod taxa offer a measure of the extent to which a particular species deviates in favour of higher or lower running speeds. Within the same theropod species, these CLP scores are found to be consistent across multiple adult specimens and across disparate ontogenetic stages. Early theropods are found to have low CLP scores, while the coelurosaurian tyrannosauroids and compsognathids are found to have high CLP scores. Among deinonychosaurs, troodontids have consistently high CLP scores, while many dromaeosaur taxa, including Velociraptor and Deinonychus, have low CLP scores. This indicates that dromaeosaurs were not, overall, a particularly cursorily adapted group. Comparisons between the CLP scores of Tyrannosaurus and specimens referred to the controversial genus Nanotyrannus indicate a strong discrepancy in cursorial adaptations, which supports the legitimacy of Nanotyrannus and the previous suggestions of ecological partitioning between Nanotyrannus and the contemporaneous Tyrannosaurus.

Global regulation of mRNA translation and stability in the early Drosophila embryo by the Smaug RNA-binding protein.

Science.gov (United States)

Chen, Linan; Dumelie, Jason G; Li, Xiao; Cheng, Matthew Hk; Yang, Zhiyong; Laver, John D; Siddiqui, Najeeb U; Westwood, J Timothy; Morris, Quaid; Lipshitz, Howard D; Smibert, Craig A

2014-01-07

Smaug is an RNA-binding protein that induces the degradation and represses the translation of mRNAs in the early Drosophila embryo. Smaug has two identified direct target mRNAs that it differentially regulates: nanos and Hsp83. Smaug represses the translation of nanos mRNA but has only a modest effect on its stability, whereas it destabilizes Hsp83 mRNA but has no detectable effect on Hsp83 translation. Smaug is required to destabilize more than one thousand mRNAs in the early embryo, but whether these transcripts represent direct targets of Smaug is unclear and the extent of Smaug-mediated translational repression is unknown. To gain a panoramic view of Smaug function in the early embryo, we identified mRNAs that are bound to Smaug using RNA co-immunoprecipitation followed by hybridization to DNA microarrays. We also identified mRNAs that are translationally repressed by Smaug using polysome gradients and microarrays. Comparison of the bound mRNAs to those that are translationally repressed by Smaug and those that require Smaug for their degradation suggests that a large fraction of Smaug's target mRNAs are both translationally repressed and degraded by Smaug. Smaug directly regulates components of the TRiC/CCT chaperonin, the proteasome regulatory particle and lipid droplets, as well as many metabolic enzymes, including several glycolytic enzymes. Smaug plays a direct and global role in regulating the translation and stability of a large fraction of the mRNAs in the early Drosophila embryo, and has unanticipated functions in control of protein folding and degradation, lipid droplet function and metabolism.

The Legal Regulation of Cybersecurity

OpenAIRE

Darius Štitilis

2013-01-01

Cybercrime has become a global phenomenon, which is causing more harm to individual citizens, organizations, society and the state. Most countries in the world compare cybercrime with offences such as terrorism and drug trafficking due to its risks and profitability. Cybersecurity is the central category to fight cybercrime in cyberspace. Therefore, the strategic legal regulation of cybersecurity is one of the most relevant problems in EU, including Lithuania. So far cybersecurity legal regul...

Liquidity regulation and bank behavior

OpenAIRE

Bonner, C.

2014-01-01

In response to the 2007-08 financial crisis, the Basel Committee on Banking Supervision proposed two liquidity standards to reinforce banks’ resilience to liquidity risks. The purpose of this thesis is to analyze the impact of liquidity regulation on bank behavior. The first of four main chapters analyzes the development of global liquidity standards, their objectives as well as their interaction with capital standards. The analysis suggests that regulating capital is associated with declinin...

Facial tissue depths in children with cleft lip and palate.

Science.gov (United States)

Starbuck, John M; Ghoneima, Ahmed; Kula, Katherine

2015-03-01

Cleft lip and palate (CLP) is a craniofacial malformation affecting more than seven million people worldwide that results in defects of the hard palate, teeth, maxilla, nasal spine and floor, and maxillodental asymmetry. CLP facial soft-tissue depth (FSTD) values have never been published. The purpose of this research is to report CLP FSTD values and compare them to previously published FSTD values for normal children. Thirty-eight FSTDs were measured on cone beam computed tomography images of CLP children (n = 86; 7-17 years). MANOVA and ANOVA tests determined whether cleft type, age, sex, and bone graft surgical status affect tissue depths. Both cleft type (unilateral/bilateral) and age influence FSTDs. CLP FSTDs exhibit patterns of variation that differ from normal children, particularly around the oronasal regions of the face. These differences should be taken into account when facial reconstructions of children with CLP are created. © 2014 American Academy of Forensic Sciences.

A globally integrated climate policy for Canada

International Nuclear Information System (INIS)

Bernstein, S.; Brunnee, J.; Duff, D.G.; Green, A.J.

2008-01-01

This book explored policy ideas and options from various perspectives, including science, law, political science, economics and sociology. The costs, opportunities and imperatives to participate in international diplomatic initiatives were considered along with the opportunities of regional global carbon markets. Canada's current policy on climate change negotiations have been focused on domestic regulation and incentives for technological responses and the setting of a domestic carbon price. The sense of urgency about global warming was discussed and the need for action to respond to the threat of global climate change was emphasized. The book also reviewed Canada's role in international climate policies and presented parameters and imperatives for global regime building in Canada. Domestic policy tools were also reviewed along with policy obstacles and opportunities. refs., tabs., figs.

Recent Activities on Global Nuclear Safety Regime

International Nuclear Information System (INIS)

Cho, Kun-Woo; Park, Jeong-Seop; Kim, Do-Hyoung

2006-01-01

Recently, rapid progress on the globalization of the nuclear safety issues is being made in IAEA (International Atomic Energy Agency) and its member states. With the globalization, the need for international cooperation among international bodies and member states continues to grow for resolving these universal nuclear safety issues. Furthermore, the importance of strengthening the global nuclear safety regime is emphasized through various means, such as efforts in application of IAEA safety standards to all nuclear installations in the world and in strengthening the code of conduct and the convention on nuclear safety. In this regards, it is important for us to keep up with the activities related with the global nuclear safety regime as an IAEA member state and a leading country in nuclear safety regulation

Research, climate, energy : Questions of destiny for the chemical industry

Energy Technology Data Exchange (ETDEWEB)

Kastinen, A., email: aimo.kastinen@chemind.fi

2010-07-01

Registration for the first phase of Reach finishes at the end of November. Then we will see whether the standard of legislation has been set correctly in respect of the EU's operational ability. If it isn't, significant problems will result for the community's treatment of materials and the EU's competitiveness, and Reach's value as a global model will become questionable. Also, the CLP regulation concerning classification, labelling and packaging of chemicals will start to come into effect as from the beginning of December. In the first phase, the question is one of classification of substances, and gradually the requirements will be applied to mixtures too. At the same time, Safety Data Sheets shall be renewed in accordance with their own transition period. The current product legislation concerning chemicals shall be fully revised by the mid-point of the decade, but before then company safety officers will have to do lots of work to change the previous routines

Sinomenine Hydrochloride Protects against Polymicrobial Sepsis via Autophagy

Directory of Open Access Journals (Sweden)

Yu Jiang

2015-01-01

Full Text Available Sepsis, a systemic inflammatory response to infection, is the major cause of death in intensive care units (ICUs. The mortality rate of sepsis remains high even though the treatment and understanding of sepsis both continue to improve. Sinomenine (SIN is a natural alkaloid extracted from Chinese medicinal plant Sinomenium acutum, and its hydrochloride salt (Sinomenine hydrochloride, SIN-HCl is widely used to treat rheumatoid arthritis (RA. However, its role in sepsis remains unclear. In the present study, we investigated the role of SIN-HCl in sepsis induced by cecal ligation and puncture (CLP in BALB/c mice and the corresponding mechanism. SIN-HCl treatment improved the survival of BALB/c mice that were subjected to CLP and reduced multiple organ dysfunction and the release of systemic inflammatory mediators. Autophagy activities were examined using Western blotting. The results showed that CLP-induced autophagy was elevated, and SIN-HCl treatment further strengthened the autophagy activity. Autophagy blocker 3-methyladenine (3-MA was used to investigate the mechanism of SIN-HCl in vitro. Autophagy activities were determined by examining the autophagosome formation, which was shown as microtubule-associated protein light chain 3 (LC3 puncta with green immunofluorescence. SIN-HCl reduced lipopolysaccharide (LPS-induced inflammatory cytokine release and increased autophagy in peritoneal macrophages (PM. 3-MA significantly decreased autophagosome formation induced by LPS and SIN-HCl. The decrease of inflammatory cytokines caused by SIN-HCl was partially aggravated by 3-MA treatment. Taken together, our results indicated that SIN-HCl could improve survival, reduce organ damage, and attenuate the release of inflammatory cytokines induced by CLP, at least in part through regulating autophagy activities.

Inhibition of histone deacetylases protects septic mice from lung and splenic apoptosis.

Science.gov (United States)

Takebe, Mariko; Oishi, Hirofumi; Taguchi, Kumiko; Aoki, Yuta; Takashina, Michinori; Tomita, Kengo; Yokoo, Hiroki; Takano, Yasuo; Yamazaki, Mitsuaki; Hattori, Yuichi

2014-04-01

Epigenetic programming, dynamically regulated by histone acetylation, may play a key role in the pathophysiology of sepsis. We examined whether histone deacetylase (HDAC) can contribute to sepsis-associated inflammation and apoptosis. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in BALB/c mice. An intraperitoneal injection of CG200745 (10 mg/kg), a novel broad-spectrum HDAC inhibitor, or valproic acid (500 mg/kg), a predominant inhibitor of class I HDACs, was given 3 h before surgery. HDAC1, HDAC2, and HDAC3 protein levels were decreased in lungs after CLP. Furthermore, CLP-induced sepsis increased both histone H3 and H4 acetylation levels in lungs. When CG200745 was given, apoptosis induction was strongly suppressed in lungs and spleens of septic mice. This antiapoptotic effect of CG200745 was not accompanied by upregulation of antiapoptotic and downregulation of proapoptotic Bcl-2 family member proteins. Treatment with CG200745 failed to inhibit elevated levels of serum cytokines and prevent lung inflammation in septic mice. Valproic acid also showed antiapoptotic but not anti-inflammatory effects in septic mice. These findings imply that HDAC inhibitors are a unique agent to prevent cell apoptosis in sepsis at their doses that do not improve inflammatory features, indicating that septic inflammation and apoptosis may not necessarily be essential for one another's existence. This study also represents the first report that CLP-induced sepsis downregulates HDACs. Nevertheless, the data with HDAC inhibitors suggest that imbalance in histone acetylation may play a contributory role in expression or repression of genes involved in septic cell apoptosis. Copyright © 2014 Elsevier Inc. All rights reserved.

The Current Approaches to the Harmonization of Interests of Participants of Competitive Relationships at the Global Level

Directory of Open Access Journals (Sweden)

Shvydanenko Oleg A.

2017-11-01

Full Text Available The key problems of development of participants of global competitive relationships, approaches to harmonization of their interests have been considered. The article defines essence of the global system of regulation of competitive relationships, the technology of its formation, improvement and development, taking into account the reasonable assemblage of relevant principles. The main tasks and processes of formation of the competitive culture in the context of globalization changes have been highlighted. The strategic directions of improvement of the system of regulation of competitive relationships in accordance with transformation of external conditions of development of globalizing space and strengthening of international character of competition have been specified. The organizational-economic mechanism of the system of regulation of competitive relationships has been provided.

Regulatory Competition in Global Financial Markets

DEFF Research Database (Denmark)

Ringe, Georg

2015-01-01

competition are a reality in today’s global financial market, and the financial sector is different from their traditional fields of application: the ease of arbitrage, the fragility of banking and the risks involved are exceptional. Most importantly, regulatory arbitrage does not or only rarely occurs......The decades-long discussion on the merits of regulatory competition appears in a new light on the global financial market. There are a number of strategies that market participants use to avoid the reach of regulation, in particular by virtue of shifting trading abroad or else relocating activities...

Regulation of metabolic networks by small molecule metabolites

Directory of Open Access Journals (Sweden)

Kanehisa Minoru

2007-03-01

Full Text Available Abstract Background The ability to regulate metabolism is a fundamental process in living systems. We present an analysis of one of the mechanisms by which metabolic regulation occurs: enzyme inhibition and activation by small molecules. We look at the network properties of this regulatory system and the relationship between the chemical properties of regulatory molecules. Results We find that many features of the regulatory network, such as the degree and clustering coefficient, closely match those of the underlying metabolic network. While these global features are conserved across several organisms, we do find local differences between regulation in E. coli and H. sapiens which reflect their different lifestyles. Chemical structure appears to play an important role in determining a compounds suitability for use in regulation. Chemical structure also often determines how groups of similar compounds can regulate sets of enzymes. These groups of compounds and the enzymes they regulate form modules that mirror the modules and pathways of the underlying metabolic network. We also show how knowledge of chemical structure and regulation could be used to predict regulatory interactions for drugs. Conclusion The metabolic regulatory network shares many of the global properties of the metabolic network, but often varies at the level of individual compounds. Chemical structure is a key determinant in deciding how a compound is used in regulation and for defining modules within the regulatory system.

The impact and cost-effectiveness of the Amref Health Africa-Smile ...

African Journals Online (AJOL)

Introduction: Cleft lip with or without cleft palate (CLP) is a congenital malformation that causes significant morbidity in low and middle income countries. Amref Health Africa has partnered with Smile Train to provide CLP surgeries since 2006. Methods: We analyzed anonymized data of 37,274 CLP patients from the Smile ...

Nursing care system development for patients with cleft lip-palate and craniofacial deformities in operating room Srinagarind Hospital.

Science.gov (United States)

Riratanapong, Saowaluck; Sroihin, Waranya; Kotepat, Kingkan; Volrathongchai, Kanittha

2013-09-01

For a successful surgical outcome for patients with cleft lip/palate (CLP), the attending nurses must continuously develop their potential, knowledge, capacity and skills. The goal is to meet international standards of patient safety and efficiency. To assess and improve the nursing care system for patients with CLP and craniofacial deformities at the operating room (OR), Srinagarind Hospital, Khon Kaen University. Data were collected for two months (between March 1, 2011 and April 30, 2011). Part I was an enquiry regarding the attitude of OR staff on serving patients with CLP; and, Part 2.1) patient and caregiver satisfaction with service from the OR staff and 2.2) patient and caregiver satisfaction with the OR transfer service. The authors interviewed 28 staff in OR unit 2 of the OR nursing division and 30 patients with CLP and his/her caregiver. The respective validity according to the Cronbach's alpha coefficient was 0.87 and 0.93. The OR staff attitude visa-vis service provision for patients with CLP service was middling. Patient and caregiver satisfaction with both OR staff and the transfer service was very satisfactory. Active development of the nursing care system for patients with CLP and craniofacial deformities in the operating room, Srinagarind Hospital improved staff motivation with respect to serving patients with CLP. The operating theater staff was able to co-ordinate the multidisciplinary team through the provision of surgical service for patients with CLP.

Implications of differences in bioanalytical regulations between Canada, USA and South America.

Science.gov (United States)

Arnold, Mark E

2011-02-01

To complete globally, pharmaceutical companies desire to use bioanalytical data and reports as a single version for all filings; not revising for specific countries or regions. Historically, this meant following the US FDA and International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guidance/guidelines; finding them sufficient to achieve global acceptance. However, a growing challenge of the past decade has been additional country-specific and regional regulations that have been released. The differences between the bioanalytical regulations among countries have been recognized as a challenge to the pharmaceutical industry and its CRO partners. Harmonization of the regulations at a global level has been the subject of a number of recent articles and editorials, and the topic has been vigorously discussed at several conferences over the past year. Since all have been in agreement about the need to harmonize regulations, this article will not focus on harmonization but rather it will provide a comparison of the USA/Canadian regulations versus those of South America, in particular Brazil, noting the additional work needed to achieve compliance with country-specific regulations. All countries discussed have specific guidance or regulations on clinical bioequivalence studies, and due to the higher standards for these studies, the regulations for bioequivalence studies will be used as the basis for comparison in the article.

Enamel Hypomineralization in Children With Clefts and the Relationship to Treatment: A Cross-sectional Retrospective Study.

Science.gov (United States)

Allam, Eman; Ghoneima, Ahmed; Tholpady, Sunil S; Kula, Katherine

2018-06-19

The aim of this study was to determine whether molar incisor hypomineralization (MIH) is greater in patients with cleft lip and palate (CLP) who underwent primary alveolar grafting (PAG) as compared with CLP waiting for secondary alveolar grafting (SAG) and with controls. A retrospective analysis of intraoral photographs of 13 CLP patients who underwent a PAG, 28 CLP prior to SAG, and 60 controls without CLP was performed. Mantel-Haenszel χ tests were used to compare the 3 groups for differences in MIH scores, and Wilcoxon rank sum tests were used to compare the groups for differences in average MIH scores. A 5% significance level was used for all tests. Molar incisor hypomineralization scores were significantly higher for the PAG and SAG groups compared with the control group (P MIH (P = 0.016) compared with the SAG group. Molar incisor hypomineralization average scores were significantly higher for the 2 graft groups compared with the controls (P MIH score and average MIH score for incisors compared with the SAG group (P = 0.03). Cleft lip and palate patients have significantly greater MIH compared with controls, and CLP patients with PAGs have significantly greater MIH in the incisor region compared with CLP patients with SAGs, indicating that subjects with PAGs have more severely affected dentition.

Bilingual Children with Nonsyndromic Cleft Lip and/or Palate: Language and Memory Skills

Science.gov (United States)

Young, Selena Ee-Li; Purcell, Alison Anne; Ballard, Kirrie Jane; Liow, Susan Jane Rickard; Ramos, Sara Da Silva; Heard, Robert

2012-01-01

Purpose: Research shows that monolingual children with cleft lip and/or palate (CLP) have a higher incidence of cognitive-linguistic deficits, but it is not clear whether bilingual preschool children with CLP are especially vulnerable because they need to acquire 2 languages. We tested the hypothesis that bilingual children with CLP score lower…

REGULATION OF NATIONAL QUALIFICATIONS SYSTEMS

Directory of Open Access Journals (Sweden)

Anna A. Muravyeva

2014-01-01

Full Text Available The paper looks into the diverse aspects of qualifications system regulation, designed for balancing the supply and demand in the labor and educational service markets. Both the objects and mechanisms of such regulation are described. Special attention is given to institutions, involved in regulation of qualifications, and their jurisdiction. Another emphasis is on the industry-related regulation of qualifications which proved to be effective both on the national and European level. Such structures were first established on the national levels to regulate the qualifications and ensure their comparability and compatibility, given the economic globalization and growing labor and academic mobility. The author points out the role of the ministries of education and labor in maintaining a steady qualifications system, and outlines the positive experience of Great Britain using the industry councils for continuing development of qualifications system.

Pleistocene climate change inferred from multi-proxy analyses of a loess-paleosol sequence in China

Science.gov (United States)

Wu, Yi; Qiu, Shifan; Fu, Shuqing; Rao, Zhiguo; Zhu, Zhaoyu

2018-04-01

The aeolian loess blanketing the Chinese Loess Plateau (CLP) is sensitive to climate change in monsoonal East Asia. Here, we present a multi-proxy climatic record from a Pleistocene loess-paleosol sequence from the Lantian Basin on the southern margin of the CLP. The measurements include magnetic susceptibility and related magnetic properties, bulk median grain-size, color reflectance, and the color-inferred hematite versus goethite ratio (Hm/Gt). A long-term aridification and cooling trend during the interval from ca 2.22-0.43 Ma is indicated by two magnetic grain-size proxies, corresponding to the global climatic cooling of the late Cenozoic. In addition, at least four intervals of climatic extremes are evident in the record of Hm/Gt ratio: at 1.71-1.65 Ma, 1.26-1.24 Ma, 0.94-0.86 Ma, and 0.62-0.48 Ma. These intervals are characterized by distinct regional climates, which contrast with the global climatic conditions represented in marine sediments. For example, a relatively arid climate is documented from 1.71 to 1.65 Ma, which was rapidly succeeded by a relatively humid climate which is associated with the earliest hominin (with an age of ca 1.63 Ma) in the Lantian Basin.

Prevalence of Cleft Lip/Palate in the Fangshan District of Beijing, 2006-2012.

Science.gov (United States)

Yang, Yanfen; Liu, Hui; Ma, Ruixin; Jin, Lei

2018-01-01

To estimate the cleft lip with or without cleft palate (CL/P) prevalence among births between 2006 and 2012 in Fangshan district of Beijing, China. Surveillance data analysis. All hospitals that provide obstetric services in the district. The CL/P cases presented for this report were from 13 weeks' gestation to 7 days postpartum. The CL/P prevalence was defined as the number of cases per 10 000 births, including live births and stillbirths at 28 weeks' gestation or beyond. The overall CL/P prevalence was 18.9 (95% confidence interval [CI]: 15.1-22.7) per 10 000 births. From 2006 to 2012, the CL/P prevalence was 19.3, 20.2, 10.9, 16.1, 17.5, 25.4, and 22.3 per 10 000 births; annually, no significant change was noted ( P for trend = .311). The prevalence of cleft palate, cleft lip, and cleft lip and palate were 3.4 (95% CI: 2.0-5.4), 6.2 (95% CI: 4.2-8.8), and 9.4 (95% CI: 6.9-12.4) per 10 000 births, respectively. The CL/P prevalence among the nonpermanent residents (31.4 per 10 000 births) was 2.31 times that of permanent residents (13.6 per 10 000 births). Among nonpermanent residents, the CL/P prevalence showed an upward trend over the study period ( P for trend = .036), that increased from 38.8 (95% CI: 16.5-76.6) per 10 000 births in 2006 to 54.6 (95% CI: 25.7-100.4) per 10 000 births in 2012. The overall CL/P prevalence was stable in the Fangshan district. However, the CL/P prevalence of the nonpermanent residents increased significantly.

OxyR of Haemophilus parasuis is a global transcriptional regulator important in oxidative stress resistance and growth.

Science.gov (United States)

Wen, Yongping; Wen, Yiping; Wen, Xintian; Cao, Sanjie; Huang, Xiaobo; Wu, Rui; Zhao, Qin; Liu, Mafeng; Huang, Yong; Yan, Qigui; Han, Xinfeng; Ma, Xiaoping; Dai, Ke; Ding, Lingqiang; Liu, Sitong; Yang, Jian

2018-02-15

Haemophilus parasuis is an opportunistic pathogen and the causative agent of Glässer's disease in swine. This disease has high morbidity and mortality rates in swine populations, and is responsible for major economic losses worldwide. Survival of H. parasuis within the host requires mechanisms for coping with oxidative stress conditions. In many bacteria, OxyR is known to mediate protection against oxidative stress; however, little is known about the role of OxyR in H. parasuis. In the current study, an oxyR mutant strain was constructed in H. parasuis strain SC1401 and designated H. parasuis SC1401∆oxyR. The oxyR mutant strain had a slower growth rate and impaired biofilm formation compared to the wild type strain. Complementation restored the growth-associated phenotypes to wild type levels. Oxidative stress susceptibility testing, using a range of concentrations of H 2 O 2 , indicated that H. parasuis SC1401∆oxyR was more sensitive to oxidative stress than the wild type strain. RNA sequencing transcriptome analysis comparing H. parasuis SC1401 with H. parasuis SC1401∆oxyR identified 466 differentially expressed genes. These genes were involved in a wide range of biological processes, including: oxidative stress, transcriptional regulation, and DNA replication, recombination, and repair. These findings provide a foundation for future research to examine the role of OxyR as a global transcriptional regulator and to better define its role in oxidative stress resistance in H. parasuis. Copyright © 2017 Elsevier B.V. All rights reserved.

Foreign experience of regulating international trade transactions

Directory of Open Access Journals (Sweden)

Klymenko L. V.

2015-05-01

Full Text Available The article deals with the international experience of state regulating international trade transactions; nature, directions and contradictions of contemporary processes of globalization are defined; components of regulatory and incentive means in system of state supporting foreign trade activity of commodity producers are considered; general provisions for the improvement of state regulation mechanisms of export-import activities in Ukraine are determined.

Hard work in soft regulation

DEFF Research Database (Denmark)

Hohnen, Pernille; Hasle, Peter; Helbo Jespersen, Anne

Certified occupational health and safety management (OHSM) systems have become a global instrument in the regulation of work environment. However, their actual impact on occupational health and safety – in particular on ‘softer’ psychosocial areas of the working environment – has been questioned...

A Population-Based Study of Effects of Genetic Loci on Orofacial Clefts

DEFF Research Database (Denmark)

Moreno Uribe, L M; Fomina, T; Munger, R G

2017-01-01

, and MAFB and isolated cleft lip only (CLO) and cleft lip and palate (CLP). Significant associations were observed between isolated CLO and fetal SNPs near TPM1 and NOG1 and between CLP and fetal SNPs at ABCA4-ARHGAP29, THADA, FOXE1, and SPRY2. Overall, effects were similar for isolated CLO and CLP, except...

Increased activation of the hippocampus during a Chinese character subvocalization task in adults with cleft lip and palate palatoplasty and speech therapy.

Science.gov (United States)

Zhang, Wenjing; Li, Chunlin; Chen, Long; Xing, Xiyue; Li, Xiangyang; Yang, Zhi; Zhang, Haiyan; Chen, Renji

2017-08-16

This study aimed to explore brain activation in patients with cleft lip and palate (CLP) using a Chinese character subvocalization task, in which the stimuli were selected from a clinical articulation evaluation test. CLP is a congenital disability. Individuals with CLP usually have articulation disorder caused by abnormal lip and palate structure. Previous studies showed that primary somatosensory and motor areas had a significant difference in activation in patients with CLP. However, whether brain activation was restored to a normal level after palatoplasty and speech rehabilitation is not clear. Two groups, adults after palatoplasty with speech training and age-matched and sex-matched controls, participated in this study. Brain activation during Chinese character subvocalization task and behavioral data were recorded using functional MRI. Patients with CLP responded to the target significantly more slowly compared with the controls, whereas no significant difference in accuracy was found between the groups. Brain activation had similar patterns between groups. Broca's area, Wernicke's area, motor areas, somatosensory areas, and insula in both hemispheres, and the dorsolateral prefrontal cortex and the ventrolateral prefrontal cortex in the right hemisphere were activated in both groups, with no statistically significant difference. Furthermore, the two-sample t-test showed that the hippocampus in the left hemisphere was activated significantly in patients with CLP compared with the controls. The results suggested that the hippocampus might be involved in the language-related neural circuit in patients with CLP and play a role of pronunciation retrieval to help patients with CLP to complete the pronunciation effectively.

The Governance of Global Wealth Chains

DEFF Research Database (Denmark)

Seabrooke, Leonard; Wigan, Duncan

2017-01-01

This article offers a theoretical framework to explain how Global Wealth Chains (GWCs) are created, maintained, and governed. We draw upon different strands of literature, including scholarship in International Political Economy and Economic Geography on Global Value Chains, literature on finance...... innovative financial products produced by large financial institutions and corporations. This article highlights how GWCs intersect with value chains, and provides brief case examples of wealth chains and how they interact.......This article offers a theoretical framework to explain how Global Wealth Chains (GWCs) are created, maintained, and governed. We draw upon different strands of literature, including scholarship in International Political Economy and Economic Geography on Global Value Chains, literature on finance...... capacities among suppliers of products used in wealth chains. We then differentiate five types of GWC governance – Market, Modular, Relational, Captive, and Hierarchy – which range from simple ‘off shelf’ products shielded from regulators by advantageous international tax laws to highly complex and flexible...

Ideological Hegemony and Global Governance

Directory of Open Access Journals (Sweden)

Thomas Ford Brown

2015-08-01

Full Text Available In this paper, I analyze libertarian discourse from the perspective of regulation theory, a~ a hegemonic ideology that underlies the emergence of a new mode of regulation. Within this general theoretical approach, I will also employ frames from regime theory as developed by international relations scholars, as well as the "epistemic community" approach from the same discipline. I want to suggest that free-market ideology could engender the emergence of rationalized global governance in order to maintain free trade, property rights, and other regulatory concerns of the emerging mode of accumulation, and that such a world state could conceivably extend liberalism's life by carrying liberalism to its extreme.

"With human health it's a global thing": Canadian perspectives on ethics in the global governance of an influenza pandemic.

Science.gov (United States)

Thompson, Alison K; Smith, Maxwell J; McDougall, Christopher W; Bensimon, Cécile; Perez, Daniel Felipe

2015-03-01

We live in an era where our health is linked to that of others across the globe, and nothing brings this home better than the specter of a pandemic. This paper explores the findings of town hall meetings associated with the Canadian Program of Research on Ethics in a Pandemic (CanPREP), in which focus groups met to discuss issues related to the global governance of an influenza pandemic. Two competing discourses were found to be at work: the first was based upon an economic rationality and the second upon a humanitarian rationality. The implications for public support and the long-term sustainability of new global norms, networks, and regulations in global public health are discussed.

Facial soft-tissue asymmetry in three-dimensional cone-beam computed tomography images of children with surgically corrected unilateral clefts.

Science.gov (United States)

Starbuck, John Marlow; Ghoneima, Ahmed; Kula, Katherine

2014-03-01

Cleft lip with or without cleft palate (CL/P) is a relatively common craniofacial malformation involving bony and soft-tissue disruptions of the nasolabial and dentoalveolar regions. The combination of CL/P and subsequent craniofacial surgeries to close the cleft and improve appearance of the cutaneous upper lip and nose can cause scarring and muscle pull, possibly resulting in soft-tissue depth asymmetries across the face. We tested the hypothesis that tissue depths in children with unilateral CL/P exhibit differences in symmetry across the sides of the face. Twenty-eight tissue depths were measured on cone-beam computed tomography images of children with unilateral CL/P (n = 55), aged 7 to 17 years, using Dolphin software (version 11.5). Significant differences in tissue depth symmetry were found around the cutaneous upper lip and nose in patients with unilateral CL/P.

Global gene expression in muscle from fasted/refed trout reveals up-regulation of genes promoting myofibre hypertrophy but not myofibre production.

Science.gov (United States)

Rescan, Pierre-Yves; Le Cam, Aurelie; Rallière, Cécile; Montfort, Jérôme

2017-06-07

Compensatory growth is a phase of rapid growth, greater than the growth rate of control animals, that occurs after a period of growth-stunting conditions. Fish show a capacity for compensatory growth after alleviation of dietary restriction, but the underlying cellular mechanisms are unknown. To learn more about the contribution of genes regulating hypertrophy (an increase in muscle fibre size) and hyperplasia (the generation of new muscle fibres) in the compensatory muscle growth response in fish, we used high-density microarray analysis to investigate the global gene expression in muscle of trout during a fasting-refeeding schedule and in muscle of control-fed trout displaying normal growth. The compensatory muscle growth signature, as defined by genes up-regulated in muscles of refed trout compared with control-fed trout, showed enrichment in functional categories related to protein biosynthesis and maturation, such as RNA processing, ribonucleoprotein complex biogenesis, ribosome biogenesis, translation and protein folding. This signature was also enriched in chromatin-remodelling factors of the protein arginine N-methyl transferase family. Unexpectedly, functional categories related to cell division and DNA replication were not inferred from the molecular signature of compensatory muscle growth, and this signature contained virtually none of the genes previously reported to be up-regulated in hyperplastic growth zones of the late trout embryo myotome and to potentially be involved in production of new myofibres, notably genes encoding myogenic regulatory factors, transmembrane receptors essential for myoblast fusion or myofibrillar proteins predominant in nascent myofibres. Genes promoting myofibre growth, but not myofibre formation, were up-regulated in muscles of refed trout compared with continually fed trout. This suggests that a compensatory muscle growth response, resulting from the stimulation of hypertrophy but not the stimulation of hyperplasia

Whither tobacco product regulation?

Science.gov (United States)

McNeill, Ann; Hammond, David; Gartner, Coral

2012-03-01

Despite decades of industry innovation and regulatory efforts, the harmfulness of conventional cigarettes has not changed. There are several pitfalls in this area, including the long time lag before health impacts of product regulatory changes become apparent, the danger of consumers deriving false reassurance of lesser harm in the interim period, the lack of relevant expertise and the lack of an internationally agreed and evidence-based strategic approach. Articles 9 and 10 of the Framework Convention on Tobacco Control provide the potential for such a global strategy, and knowledge and research has increased significantly over recent years. However, there are huge opportunity costs in implementing product disclosure and regulatory strategies: most national regulators have very limited human and financial resources, which should be focused on other evidence-based tobacco control interventions. We believe therefore that it is now time to abandon the notion of safe or safer cigarettes while moving consumers towards cleaner nicotine products as soon as possible. In parallel to this, we recommend a number of other strategies be implemented including: reducing the appeal of all tobacco products, forbidding new tobacco products or brand variants being marketed without evidence of reduced harm, appeal or addictiveness, and developing a tobacco industry resourced, but industry independent, Framework Convention on Tobacco Control global repository to assist national regulators in understanding and regulating the products on their markets.

Global climate change

International Nuclear Information System (INIS)

Gugele, B.; Radunsky, K.; Spangl, W.

2001-01-01

In Austria the CO 2 emissions increased by 5.9 % from 1990 to 1999, the other greenhouse gases by 2.6 %. The Federal Ministry for Agriculture, Environment and Water Management, in cooperation with other ministries and the countries, has worked out an action plan for reduction of greenhouse gas emissions, to meet the targets of the Kyoto protocol. This study analyzes the greenhouse gas emissions in Austria, in the European Union and globally. The measured emission values throughout Austria and in the other European countries are given in tables, the environmental impact for Austria and globally is discussed, statistical data and time series of the emission sources are given and legal regulations and measures for an effective environmental emission control in Austria, the European Union and worldwide are discussed. In particular the impact of fossil-fuel power plants on the greenhouse gas emissions is analysed. (a.n.)

Ethical leadership and regulation in the business scene

Directory of Open Access Journals (Sweden)

José Luis Álvarez Arce

2011-06-01

Full Text Available In an increasingly integrated global business arena, local singularities still play a crucial role in many aspects. Business ethics is affected by this duality in profound ways. Legislators have tried to provide uniform ethical guidelines for transnational companies. In this effort to streamline the ethical management of the multinational corporation, regulation could be thought of as an attempt to reduce the role of the leader. We argue that this solution mistakenly presumes a high degree of uniformity across countries. In this paper, we consider how different legal traditions can be used to explain the divergences in implementation and configuration of ethics hotlines. We find that although national regulators established a legal standard (Sarbanes Oxley Act for global companies, significant differences exist across legal traditions, which sometimes go even deeper, to region and country specific nuances. Legal regulation may never substitute a leader in ethical matters.

Longitudinal Comparison of Early Speech and Language Milestones in Children with Cleft Palate: A Comparison of US and Slovak Children

Science.gov (United States)

Scherer, Nancy J.; Oravkinova, Zuzana; McBee, Matthew T.

2013-01-01

The purpose of this study was to compare early speech and language development of children with and without cleft lip and/or palate (CLP) in the US and Slovakia from 6 to 24 months of age. Thirty-two children from the US (eight with CLP and eight noncleft) and Slovakia (eight with CLP and eight noncleft) participated in this study. The children…

Global warming description using Daisyworld model with greenhouse gases.

Science.gov (United States)

Paiva, Susana L D; Savi, Marcelo A; Viola, Flavio M; Leiroz, Albino J K

2014-11-01

Daisyworld is an archetypal model of the earth that is able to describe the global regulation that can emerge from the interaction between life and environment. This article proposes a model based on the original Daisyworld considering greenhouse gases emission and absorption, allowing the description of the global warming phenomenon. Global and local analyses are discussed evaluating the influence of greenhouse gases in the planet dynamics. Numerical simulations are carried out showing the general qualitative behavior of the Daisyworld for different scenarios that includes solar luminosity variations and greenhouse gases effect. Nonlinear dynamics perspective is of concern discussing a way that helps the comprehension of the global warming phenomenon. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Regulation and Supervision of The Global Financial System. A Proposal for Institutional Reform

NARCIS (Netherlands)

Denters, H.M.G.

2009-01-01

nternational financial markets are supervised primarily by national authorities. However, national authorities are inherently incapable to regulate and supervise seamless globalised financial markets. To the extent international regulators exist, they constitute a disorderly patchwork of

Regulation of online pharmacy: an Australian perspective.

Science.gov (United States)

Bernath, Paul

2003-02-01

This article argues that existing Australian regulations do not adequately cover online pharmacies or Internet advertising of medicines and that existing penalties and sanctions are often ineffective, potentially placing public health and safety at risk. Suggestions are made for future regulatory approaches. It is concluded that as well as an effective program of public education, cautious domestic legislative reform is necessary to ensure specific regulation of Australian online pharmacy practice and Internet advertising of medicines. In addition, the global nature of the Internet demands international co-operation and increased regulator and consumer vigilance.

The Impact of Globalization on Career and Technical Education in Taiwan, Republic of China

Science.gov (United States)

Wu, Robert T. Y.

2004-01-01

The purpose of this paper is to explore the impact of globalization on career and technical education in Taiwan, Republic of China. Globalization has been characterized as a fundamental process of change. Especially after our country joined the WTO in 2001, the effects of globalization and the WTO regulations compelled career and technical…

Globalization in the post - colonial world

Directory of Open Access Journals (Sweden)

Korobeynikova Larisa A.

2016-01-01

Full Text Available The paper presents a new interpretation of globalization within the boundaries of the author’s concept of soft globalization, which exploits a normatively attractive alternative to the concept of the Empire. It is argued here that the conditions of development of contemporary post - colonial world communities do not require any unification in the form of the Empire, but instead the creation of a non repressive mechanism of social regulation - the implementation of a form of soft globalization, a globalization with a mental form are expedient here. Historically, globalization occurred in a strict material(i.e. economical and military form that prompted the conditions for the evolution of civilization as the Empire: a case in which the development of the world occurs under the power of a single dominating state. Imperialistic politics leads to colonial politics formation. The history of the phenomena of civilization shows many instances of Empire globalization. Globalization in the Empire form was already observed at the time of the Roman Empire. At this time processes of development inside the Empire were manifestations of globalization in its highest cultural shape. But ancient Rome was also a social and political experiment that acquired the attributes of a purely material globalization in the end, and historically brought about the irreversible crash of the Roman Empire itself. Contemporary fluctuations referring to the process of globalization can be registered in the US’s attempts of material domination inside this or that existing case of civilization, which causes colonialism appearance. The main idea stressed in the paper is that only a mental globalization could succeed in the end.

From Protectionism to Neo-Protectionism: New Dimensions of Liberal Regulation

Directory of Open Access Journals (Sweden)

Panchenko Volodymyr

2017-12-01

Full Text Available The article summarizes the main concepts of the policy of protectionism. It was proved that the shaded or semi-open nature of protectionism of the 21st century model does not fall under classical manifestations of protectionism recorded in the WTO documents, and therefore further hybridization of its forms actualizes the need for their classification in order to attract the attention of the scientific community to new challenges to the global regulation of the system of international economic relations. It was discovered, that protectionism in the process of economical globalization has evolved from trade policy based on introduction of tariff limitations, and later from non-tariff protection instruments, into a complex comprehensive state mechanism for increasing competitiveness of the national economy in the process of globalization, which we call neo-protectionism. Was provided a classification of neo-protectionism and were singled out forms of manifestation of each of its types. Were established country features of neo-protectionism policy. Was established that flexibility of tools for implementing neo-protectionism policy, absence of a unified approach to interpreting the methods of achieving goals announced by the state, differences in priorities and unity of the goals of all instruments, which are to stimulate restoration of economic growth, can be considered as determinative signs of new regulation. It was found that state intervention becomes an inherent characteristic of liberal politics. Was observed that neo-protectionism with its flexible instruments becomes a policy of reducing asymmetric distribution of benefits from globalization and reaction to global imbalances, which again emphasizes the thesis that state participation in regulation of economic processes is an objective reality, and we are witnessing transformation of the previously announced trend towards deregulation into re-regulation.

Nasal airway and septal variation in unilateral and bilateral cleft lip and palate.

Science.gov (United States)

Starbuck, John M; Friel, Michael T; Ghoneima, Ahmed; Flores, Roberto L; Tholpady, Sunil; Kula, Katherine

2014-10-01

Cleft lip and palate (CLP) affects the dentoalveolar and nasolabial facial regions. Internal and external nasal dysmorphology may persist in individuals born with CLP despite surgical interventions. 7-18 year old individuals born with unilateral and bilateral CLP (n = 50) were retrospectively assessed using cone beam computed tomography. Anterior, middle, and posterior nasal airway volumes were measured on each facial side. Septal deviation was measured at the anterior and posterior nasal spine, and the midpoint between these two locations. Data were evaluated using principal components analysis (PCA), multivariate analysis of variance (MANOVA), and post-hoc ANOVA tests. PCA results show partial separation in high dimensional space along PC1 (48.5% variance) based on age groups and partial separation along PC2 (29.8% variance) based on CLP type and septal deviation patterns. MANOVA results indicate that age (P = 0.007) and CLP type (P ≤ 0.001) significantly affect nasal airway volume and septal deviation. ANOVA results indicate that anterior nasal volume is significantly affected by age (P ≤ 0.001), whereas septal deviation patterns are significantly affected by CLP type (P ≤ 0.001). Age and CLP type affect nasal airway volume and septal deviation patterns. Nasal airway volumes tend to be reduced on the clefted sides of the face relative to non-clefted sides of the face. Nasal airway volumes tend to strongly increase with age, whereas septal deviation values tend to increase only slightly with age. These results suggest that functional nasal breathing may be impaired in individuals born with the unilateral and bilateral CLP deformity. © 2014 Wiley Periodicals, Inc.

Incremental passivity and output regulation for switched nonlinear systems

Science.gov (United States)

Pang, Hongbo; Zhao, Jun

2017-10-01

This paper studies incremental passivity and global output regulation for switched nonlinear systems, whose subsystems are not required to be incrementally passive. A concept of incremental passivity for switched systems is put forward. First, a switched system is rendered incrementally passive by the design of a state-dependent switching law. Second, the feedback incremental passification is achieved by the design of a state-dependent switching law and a set of state feedback controllers. Finally, we show that once the incremental passivity for switched nonlinear systems is assured, the output regulation problem is solved by the design of global nonlinear regulator controllers comprising two components: the steady-state control and the linear output feedback stabilising controllers, even though the problem for none of subsystems is solvable. Two examples are presented to illustrate the effectiveness of the proposed approach.

Risk, regulation and biotechnology: the case of GM crops.

Science.gov (United States)

Smyth, Stuart J; Phillips, Peter W B

2014-07-03

The global regulation of products of biotechnology is increasingly divided. Regulatory decisions for genetically modified (GM) crops in North America are predictable and efficient, with numerous countries in Latin and South America, Australia and Asia following this lead. While it might have been possible to argue that Europe's regulations were at one time based on real concerns about minimizing risks and ensuring health and safety, it is increasingly apparent that the entire European Union (EU) regulatory system for GM crops and foods is now driven by political agendas. Countries within the EU are at odds with each other as some have commercial production of GM crops, while others refuse to even develop regulations that could provide for the commercial release of GM crops. This divide in regulatory decision-making is affecting international grain trade, creating challenges for feeding an increasing global population.

Global Trends in Mercury Management

Science.gov (United States)

Choi, Kyunghee

2012-01-01

The United Nations Environmental Program Governing Council has regulated mercury as a global pollutant since 2001 and has been preparing the mercury convention, which will have a strongly binding force through Global Mercury Assessment, Global Mercury Partnership Activities, and establishment of the Open-Ended Working Group on Mercury. The European Union maintains an inclusive strategy on risks and contamination of mercury, and has executed the Mercury Export Ban Act since December in 2010. The US Environmental Protection Agency established the Mercury Action Plan (1998) and the Mercury Roadmap (2006) and has proposed systematic mercury management methods to reduce the health risks posed by mercury exposure. Japan, which experienced Minamata disease, aims vigorously at perfection in mercury management in several ways. In Korea, the Ministry of Environment established the Comprehensive Plan and Countermeasures for Mercury Management to prepare for the mercury convention and to reduce risks of mercury to protect public health. PMID:23230466

The politics of global warming

International Nuclear Information System (INIS)

Moss, N.

1991-01-01

The probable warming of the world over the next few decades due to human activity presents a unique threat. The threat of global warming has been brought about by the activities of the entire human race, and only action by a large part of the human race can slow down the process or halt it. Other unwanted effects of industrial activity are trans-national, and require international agreements to regulate them, most obviously radioactivity from nuclear power accidents, acid rain and river pollution; but climatic change, unlike these, is global. International negotiations are going on now to deal with the problem of global warming, mostly by reducing the emission of gases that contribute to it. These are preliminary, yet already different perceptions and conflicting interests are emerging. The aim of the present negotiations is a convention for the UN Conference on Environment and Development (UNCED) to be held in June 1992, the so-called ''Earth Summit''. (author)

Potential application of cyclic lipopeptide biosurfactants produced by Bacillus subtilis strains in laundry detergent formulations.

Science.gov (United States)

Mukherjee, A K

2007-09-01

Crude cyclic lipopeptide (CLP) biosurfactants from two Bacillus subtilis strains (DM-03 and DM-04) were studied for their compatibility and stability with some locally available commercial laundry detergents. CLP biosurfactants from both B. subtilis strains were stable over the pH range of 7.0-12.0, and heating them at 80 degrees C for 60 min did not result in any loss of their surface-active property. Crude CLP biosurfactants showed good emulsion formation capability with vegetable oils, and demonstrated excellent compatibility and stability with all the tested laundry detergents. CLP biosurfactants from B. subtilis strains act additively with other components of the detergents to further improve the wash quality of detergents. The thermal resistance and extreme alkaline pH stability of B. subtilis CLP biosurfactants favour their inclusion in laundry detergent formulations. This study has great significance because it is already known that microbial biosurfactants are considered safer alternative to chemical or synthetic surfactants owing to lower toxicity, ease of biodegradability and low ecological impact. The present study provides further evidence that CLP biosurfactants from B. subtilis strains can be employed in laundry detergents.

Global Supply and Demand of Opioids for Pain Management.

Science.gov (United States)

Kunnumpurath, Sreekumar; Julien, Natasha; Kodumudi, Gopal; Kunnumpurath, Anamika; Kodumudi, Vijay; Vadivelu, Nalini

2018-04-04

The goal of this review is to evaluate the global supply and demand of opioids used for pain management and discuss how it relates to the utilization of opioids around the world. The purpose of the review is also to determine the factors that contribute to inappropriate pain management. The total global production of opium for opioid manufacturing is enough to supply the growing global demands. However, licit opioids are only consumed by 20% of the world population. Most people throughout the world had no access to opioid analgesics for pain relief in case of need. Opioid misuse and abuse is not only a phenomena plague by the USA but globally across many countries. Many countries have a lack of availability of opioids, contributing factors being strict government regulations limiting access, lack of knowledge of the efficacy of opioid analgesics in treating acute and chronic pain and palliative care, and the stigma that opioids are highly addictive. For the countries in which opioids are readily available and prescribed heavily, diversion, misuse, abuse, and the resurgence of heroin have become problems leading to morbidity and mortality. It is pertinent to find a balance between having opioids accessible to patients in need, with ensuring that opioids are regulated along with other illicit drugs to decrease abuse potential.

Nonsyndromic cleft lip and palate: No evidence of linkage to HLA or factor 13A

Energy Technology Data Exchange (ETDEWEB)

Hecht, J.T.; Yaping Wang; Connor, B.; Daiger, S.P. (Univ. of Texas, Houston (United States)); Blanton, S.H. (Univ. of Texas, Houston (United States) Univ. of Virginia, Charlottesville (United States))

1993-06-01

Nonsyndromic cleft lip with or without cleft palate (CLP) is a common craniofacial anomaly, the etiology of which is not known. Population studies have shown that a large proportion of cases occur sporadically. Recently, segregation analyses applied to CLP families have demonstrated that an autosomal dominant/codominant gene(s) may cause clefting in cases. Associations of autosomal dominant CLP and nonsyndromic cleft palate (CP) with HLA and F13A genes on chromosome 6p have been suggested previously. Linkage to these two areas on chromosome 6p were tested in 12 autosomal dominant families with CLP. With a LOD score of [minus]2 or less for exclusion, no evidence of linkage was found to four chromosome 6p markers. Multipoint analysis showed no evidence of a clefting locus in this region spanning 54 cM on chromosome 6p in these CLP families. 30 refs., 2 figs., 1 tab.

RegA, an AraC-Like Protein, Is a Global Transcriptional Regulator That Controls Virulence Gene Expression in Citrobacter rodentium▿

Science.gov (United States)

Hart, Emily; Yang, Ji; Tauschek, Marija; Kelly, Michelle; Wakefield, Matthew J.; Frankel, Gad; Hartland, Elizabeth L.; Robins-Browne, Roy M.

2008-01-01

Citrobacter rodentium is an attaching and effacing pathogen which causes transmissible colonic hyperplasia in mice. Infection with C. rodentium serves as a model for infection of humans with enteropathogenic and enterohemorrhagic Escherichia coli. To identify novel colonization factors of C. rodentium, we screened a signature-tagged mutant library of C. rodentium in mice. One noncolonizing mutant had a single transposon insertion in an open reading frame (ORF) which we designated regA because of its homology to genes encoding members of the AraC family of transcriptional regulators. Deletion of regA in C. rodentium resulted in markedly reduced colonization of the mouse intestine. Examination of lacZ transcriptional fusions using promoter regions of known and putative virulence-associated genes of C. rodentium revealed that RegA strongly stimulated transcription of two newly identified genes located close to regA, which we designated adcA and kfcC. The cloned adcA gene conferred autoaggregation and adherence to mammalian cells to E. coli strain DH5α, and a kfc mutation led to a reduction in the duration of intestinal colonization, but the kfc mutant was far less attenuated than the regA mutant. These results indicated that other genes of C. rodentium whose expression required activation by RegA were required for colonization. Microarray analysis revealed a number of RegA-regulated ORFs encoding proteins homologous to known colonization factors. Transcription of these putative virulence determinants was activated by RegA only in the presence of sodium bicarbonate. Taken together, these results show that RegA is a global regulator of virulence in C. rodentium which activates factors that are required for intestinal colonization. PMID:18765720

RegA, an AraC-like protein, is a global transcriptional regulator that controls virulence gene expression in Citrobacter rodentium.

Science.gov (United States)

Hart, Emily; Yang, Ji; Tauschek, Marija; Kelly, Michelle; Wakefield, Matthew J; Frankel, Gad; Hartland, Elizabeth L; Robins-Browne, Roy M

2008-11-01

Citrobacter rodentium is an attaching and effacing pathogen which causes transmissible colonic hyperplasia in mice. Infection with C. rodentium serves as a model for infection of humans with enteropathogenic and enterohemorrhagic Escherichia coli. To identify novel colonization factors of C. rodentium, we screened a signature-tagged mutant library of C. rodentium in mice. One noncolonizing mutant had a single transposon insertion in an open reading frame (ORF) which we designated regA because of its homology to genes encoding members of the AraC family of transcriptional regulators. Deletion of regA in C. rodentium resulted in markedly reduced colonization of the mouse intestine. Examination of lacZ transcriptional fusions using promoter regions of known and putative virulence-associated genes of C. rodentium revealed that RegA strongly stimulated transcription of two newly identified genes located close to regA, which we designated adcA and kfcC. The cloned adcA gene conferred autoaggregation and adherence to mammalian cells to E. coli strain DH5alpha, and a kfc mutation led to a reduction in the duration of intestinal colonization, but the kfc mutant was far less attenuated than the regA mutant. These results indicated that other genes of C. rodentium whose expression required activation by RegA were required for colonization. Microarray analysis revealed a number of RegA-regulated ORFs encoding proteins homologous to known colonization factors. Transcription of these putative virulence determinants was activated by RegA only in the presence of sodium bicarbonate. Taken together, these results show that RegA is a global regulator of virulence in C. rodentium which activates factors that are required for intestinal colonization.

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

Global warming -- Science and anti-science

Energy Technology Data Exchange (ETDEWEB)

Preining, O. [Univ. of Vienna, Wien (Austria). Inst. for Experimental Physics]|[Austrian Academy of Sciences, Wien (Austria). Clean Air Commission

1995-06-01

The global warming debate has sparked many facts activities in almost all sectors of human endeavors. There are the hard facts, the measurements of the greenhouse gases, the statistics of human activities responsible for emissions, the demographic figures. There are the soft facts, the interpretations of the hard facts requiring additional assumptions. There are the media, the press, television, for whom environmental problems make good stories, these can be used to rise emotions, to make heroes and antiheroes. There are politicians, the global warming debate can be used even in electron campaigns. Global warming is a topic within and beyond science. The judgment (and hence use) of scientific facts is overwhelmingly influenced by the ``Weltbild`` (underlying beliefs how the world operates), and consequently opposing positions of well-known scientists arise. There are the attempts to invent futures of man on Earth: policies, regulations, laws on nation, international, and global levels shall facilitate a change in the basic behavior of all men. The global warming issue has many facets and cannot be successfully discussed without including, e.g., the North-South dialogue, world population, etc.

Creating a Global Law Graduate: The Need, Benefits and Practical Approaches to Internationalise the Curriculum

Science.gov (United States)

O'Sullivan, Carmel; McNamara, Judith

2015-01-01

The increasingly integrated world has facilitated important international and trans-border trends, such as a progressively connected global economy, a significant growth in transnational business transactions and an increase in global regulation of global issues. Such globalisation has had a transformational impact on the legal profession in a…

Methodology for qualification of wood-based ash according to REACH - prestudy

Energy Technology Data Exchange (ETDEWEB)

Sjoeblom, Rolf [Tekedo AB, Nykoeping (Sweden); Tivegaard, Anna-Maria [SSAB Merox AB, Oxeloesund (Sweden)

2010-02-15

The new European Union framework directive on waste is to be implemented during the year 2010. According to this directive, much of what today is regarded as waste will instead be assessed as by-products and in many cases fall under the new European union regulation REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals). REACH applies in conjunction with the new European Union regulation CLP (Classification, Labelling and Packaging of substances and mixtures). There are introductory periods for both of these regulations, and in the case of CLP this regards transition from the present and previous rules under the dangerous substances and dangerous preparations directives (DSD and DPD, respectively). Similarly, the new framework directive on waste supersedes the previous directive and some other statements. There is a connection between the directives of waste and the rules for classification and labelling in that the classification of waste (in the categories hazardous and non-hazardous) build on (but are not identical to) the rules for labelling. Similarly, the national Swedish rules for acceptance of recycled material (waste) for use in geotechnical constructions relate to the provisions in REACH on assessment of chemical safety in the both request that the risk be assessed to be small, and that the same or similar methodologies can be applied to verify this. There is a 'reference alternative' in REACH that implies substantial testing prior to registration. Registration is the key to use of a substance even though a substance may be used as such, in a mixture, or to be released from an article. However, REACH as well as CLP contain a number of provisions for using literature data, data on similar chemicals e t c in order to avoid unnecessary testing. This especially applies to testing on humans and vertebrate animals. Vaermeforsk, through its Programme on Environmentally Friendly Use of Non-Coal Ashes has developed methodologies and

Methodology for qualification of wood-based ash according to REACH - prestudy

Energy Technology Data Exchange (ETDEWEB)

Sjoeblom, Rolf (Tekedo AB, Nykoeping (Sweden)); Tivegaard, Anna-Maria (SSAB Merox AB, Oxeloesund (Sweden))

2010-02-15

The new European Union framework directive on waste is to be implemented during the year 2010. According to this directive, much of what today is regarded as waste will instead be assessed as by-products and in many cases fall under the new European union regulation REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals). REACH applies in conjunction with the new European Union regulation CLP (Classification, Labelling and Packaging of substances and mixtures). There are introductory periods for both of these regulations, and in the case of CLP this regards transition from the present and previous rules under the dangerous substances and dangerous preparations directives (DSD and DPD, respectively). Similarly, the new framework directive on waste supersedes the previous directive and some other statements. There is a connection between the directives of waste and the rules for classification and labelling in that the classification of waste (in the categories hazardous and non-hazardous) build on (but are not identical to) the rules for labelling. Similarly, the national Swedish rules for acceptance of recycled material (waste) for use in geotechnical constructions relate to the provisions in REACH on assessment of chemical safety in the both request that the risk be assessed to be small, and that the same or similar methodologies can be applied to verify this. There is a 'reference alternative' in REACH that implies substantial testing prior to registration. Registration is the key to use of a substance even though a substance may be used as such, in a mixture, or to be released from an article. However, REACH as well as CLP contain a number of provisions for using literature data, data on similar chemicals e t c in order to avoid unnecessary testing. This especially applies to testing on humans and vertebrate animals. Vaermeforsk, through its Programme on Environmentally Friendly Use of Non-Coal Ashes has developed methodologies and

Possibilities for global governance of converging technologies

Science.gov (United States)

Roco, Mihail C.

2008-01-01

The convergence of nanotechnology, modern biology, the digital revolution and cognitive sciences will bring about tremendous improvements in transformative tools, generate new products and services, enable opportunities to meet and enhance human potential and social achievements, and in time reshape societal relationships. This paper focuses on the progress made in governance of such converging, emerging technologies and suggests possibilities for a global approach. Specifically, this paper suggests creating a multidisciplinary forum or a consultative coordinating group with members from various countries to address globally governance of converging, emerging technologies. The proposed framework for governance of converging technologies calls for four key functions: supporting the transformative impact of the new technologies; advancing responsible development that includes health, safety and ethical concerns; encouraging national and global partnerships; and establishing commitments to long-term planning and investments centered on human development. Principles of good governance guiding these functions include participation of all those who are forging or affected by the new technologies, transparency of governance strategies, responsibility of each participating stakeholder, and effective strategic planning. Introduction and management of converging technologies must be done with respect for immediate concerns, such as privacy, access to medical advancements, and potential human health effects. At the same time, introduction and management should also be done with respect for longer-term concerns, such as preserving human integrity, dignity and welfare. The suggested governance functions apply to four levels of governance: (a) adapting existing regulations and organizations; (b) establishing new programs, regulations and organizations specifically to handle converging technologies; (c) building capacity for addressing these issues into national policies and

Possibilities for global governance of converging technologies

International Nuclear Information System (INIS)

Roco, Mihail C.

2008-01-01

The convergence of nanotechnology, modern biology, the digital revolution and cognitive sciences will bring about tremendous improvements in transformative tools, generate new products and services, enable opportunities to meet and enhance human potential and social achievements, and in time reshape societal relationships. This paper focuses on the progress made in governance of such converging, emerging technologies and suggests possibilities for a global approach. Specifically, this paper suggests creating a multidisciplinary forum or a consultative coordinating group with members from various countries to address globally governance of converging, emerging technologies. The proposed framework for governance of converging technologies calls for four key functions: supporting the transformative impact of the new technologies; advancing responsible development that includes health, safety and ethical concerns; encouraging national and global partnerships; and establishing commitments to long-term planning and investments centered on human development. Principles of good governance guiding these functions include participation of all those who are forging or affected by the new technologies, transparency of governance strategies, responsibility of each participating stakeholder, and effective strategic planning. Introduction and management of converging technologies must be done with respect for immediate concerns, such as privacy, access to medical advancements, and potential human health effects. At the same time, introduction and management should also be done with respect for longer-term concerns, such as preserving human integrity, dignity and welfare. The suggested governance functions apply to four levels of governance: (a) adapting existing regulations and organizations; (b) establishing new programs, regulations and organizations specifically to handle converging technologies; (c) building capacity for addressing these issues into national policies and

Possibilities for global governance of converging technologies

Energy Technology Data Exchange (ETDEWEB)

Roco, Mihail C. [National Science Foundation (NSF) (United States)], E-mail: mroco@nsf.gov

2008-01-15

The convergence of nanotechnology, modern biology, the digital revolution and cognitive sciences will bring about tremendous improvements in transformative tools, generate new products and services, enable opportunities to meet and enhance human potential and social achievements, and in time reshape societal relationships. This paper focuses on the progress made in governance of such converging, emerging technologies and suggests possibilities for a global approach. Specifically, this paper suggests creating a multidisciplinary forum or a consultative coordinating group with members from various countries to address globally governance of converging, emerging technologies. The proposed framework for governance of converging technologies calls for four key functions: supporting the transformative impact of the new technologies; advancing responsible development that includes health, safety and ethical concerns; encouraging national and global partnerships; and establishing commitments to long-term planning and investments centered on human development. Principles of good governance guiding these functions include participation of all those who are forging or affected by the new technologies, transparency of governance strategies, responsibility of each participating stakeholder, and effective strategic planning. Introduction and management of converging technologies must be done with respect for immediate concerns, such as privacy, access to medical advancements, and potential human health effects. At the same time, introduction and management should also be done with respect for longer-term concerns, such as preserving human integrity, dignity and welfare. The suggested governance functions apply to four levels of governance: (a) adapting existing regulations and organizations; (b) establishing new programs, regulations and organizations specifically to handle converging technologies; (c) building capacity for addressing these issues into national policies and

Competition, Regulation and Development Research Forum ...

International Development Research Centre (IDRC) Digital Library (Canada)

Many developing countries have adopted market-oriented reforms as a part of the globalization and liberalization process. However, due to market distortions, the need to ensure proper access to essential services requires effective regulation. Accordingly, developing countries are legislating or revising their ...

Global Nuclear Safety and Security Network

International Nuclear Information System (INIS)

Guo Lingquan

2013-01-01

The objectives of the Regulatory Network are: - to contribute to the effectiveness of nuclear regulatory systems; - to contribute to continuous enhancements, and - to achieve and promote radiation and nuclear safety and security by: • Enhancing the effectiveness and efficiency of international cooperation in the regulation of nuclear and radiation safety of facilities and activities; • Enabling adequate access by regulators to relevant safety and security information; • Promoting dissemination of information on safety and security issues as well as information of good practices for addressing and resolving these issues; • Enabling synergies among different web based networks with a view to strengthening and enhancing the global nuclear safety framework and serving the specific needs of regulators and international organizations; • Providing additional information to the public on international regulatory cooperation in safety and security matters

July: "Soils are living: Overview of soil biodiversity, global issues, and new resources"

Science.gov (United States)

The July poster will provide an overview of soil biology and the many ecosystem functions that soil organisms drive including their impact on global biodiversity, climate regulation, soil health/stability, and plant growth. Five main global issues related to soil biodiversity will be presented such ...

The prevalence of specific dental anomalies in a group of Saudi cleft lip and palate patients.

Science.gov (United States)

Al-Kharboush, Ghada H; Al-Balkhi, Khalid M; Al-Moammar, Khalid

2015-04-01

The aims of this study were to investigate the prevalence and distribution of dental anomalies in a group of Saudi subjects with cleft lip and palate (CLP), to examine potential sex-based associations of these anomalies, and to compare dental anomalies in Saudi subjects with CLP with published data from other population groups. This retrospective study involved the examination of pre-treatment records obtained from three CLP centers in Riyadh, Saudi Arabia, in February and March 2010. The pre-treatment records of 184 subjects with cleft lip and palate were identified and included in this study. Pre-treatment maxillary occlusal radiographs of the cleft region, panoramic radiographs, and orthodontic study models of subjects with CLP were analyzed for dental anomalies. Orthopantomographs and occlusal radiographs may not be reliable for the accurate evaluation of root malformation anomalies. A total of 265 dental anomalies were observed in the 184 study subjects. Hypodontia was observed most commonly (66.8%), followed by microdontia (45.6%), intra-oral ectopic eruption (12.5%), supernumerary teeth (12.5%), intra-nasal ectopic eruption (3.2), and macrodontia (3.2%). No gender difference in the prevalence of these anomalies was observed. Dental anomalies were common in Saudi subjects with CLP type. This will complicate the health care required for the CL/P subjects. This study was conducted to epidemiologically explore the prevalence of dental anomalies among Saudi Arabian subjects with CLP.

The effect of systematic pediatric care on neonatal mortality and hospitalizations of infants born with oral clefts

Directory of Open Access Journals (Sweden)

Wehby George L

2011-12-01

Full Text Available Abstract Background Cleft lip and/or palate (CL/P increase mortality and morbidity risks for affected infants especially in less developed countries. This study aimed at assessing the effects of systematic pediatric care on neonatal mortality and hospitalizations of infants with cleft lip and/or palate (CL/P in South America. Methods The intervention group included live-born infants with isolated or associated CL/P in 47 hospitals between 2003 and 2005. The control group included live-born infants with CL/P between 2001 and 2002 in the same hospitals. The intervention group received systematic pediatric care between the 7th and 28th day of life. The primary outcomes were mortality between the 7th and 28th day of life and hospitalization days in this period among survivors adjusted for relevant baseline covariates. Results There were no significant mortality differences between the intervention and control groups. However, surviving infants with associated CL/P in the intervention group had fewer hospitalization days by about six days compared to the associated control group. Conclusions Early systematic pediatric care may significantly reduce neonatal hospitalizations of infants with CL/P and additional birth defects in South America. Given the large healthcare and financial burden of CL/P on affected families and the relatively low cost of systematic pediatric care, improving access to such care may be a cost-effective public policy intervention. Trial Registration ClinicalTrials.gov: NCT00097149

Protective effects of oridonin on the sepsis in mice

Directory of Open Access Journals (Sweden)

Yan-Jun Zhao

2016-09-01

Full Text Available This study aimed to investigate the protective effects of oridonin (ORI on cecal ligation and puncture (CLP-induced sepsis in mice. Male C57BL/6 mice weighing 22–30 g and aged 8–10 weeks were randomly assigned to three groups: Sham group, CLP group, or CLP plus ORI group. In the CLP group and ORI group, CLP was induced, and intraperitoneal injection of normal saline and oridonin (100 μg/kg was conducted, respectively. The survival rate was determined within the following 7 days. The blood, liver, and lung were collected at 24 hours after injury. Hematoxylin–eosin staining of the lung, detection of lung wet-to-dry ratio, and serum cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-6, and examination of intraperitoneal and blood bacterial clearance were conducted to evaluate the therapeutic efficacy. Results showed that ORI treatment significantly reduced the lung wet-to-dry ratio, decreased serum TNF-α and IL-6, and improved liver pathology compared with the CLP group (p < 0.05. Moreover, the intraperitoneal and blood bacterial clearance increased markedly after ORI treatment (p < 0.05. The 7-day survival rate in the ORI group was also dramatically higher than in the CLP group (p < 0.05. Our findings indicate that ORI can attenuate liver and lung injuries and elevate bacterial clearance to increase the survival rate of sepsis mice.

Enhancing Global Competitiveness: Benchmarking Airline Operational Performance in Highly Regulated Environments

Science.gov (United States)

Bowen, Brent D.; Headley, Dean E.; Kane, Karisa D.

1998-01-01

Enhancing competitiveness in the global airline industry is at the forefront of attention with airlines, government, and the flying public. The seemingly unchecked growth of major airline alliances is heralded as an enhancement to global competition. However, like many mega-conglomerates, mega-airlines will face complications driven by size regardless of the many recitations of enhanced efficiency. Outlined herein is a conceptual model to serve as a decision tool for policy-makers, managers, and consumers of airline services. This model is developed using public data for the United States (U.S.) major airline industry available from the U/S. Department of Transportation, Federal Aviation Administration, the National Aeronautics and Space Administration, the National Transportation Safety Board, and other public and private sector sources. Data points include number of accidents, pilot deviations, operational performance indicators, flight problems, and other factors. Data from these sources provide opportunity to develop a model based on a complex dot product equation of two vectors. A row vector is weighted for importance by a key informant panel of government, industry, and consumer experts, while a column vector is established with the factor value. The resulting equation, known as the national Airline Quality Rating (AQR), where Q is quality, C is weight, and V is the value of the variables, is stated Q=C[i1-19] x V[i1-19]. Looking at historical patterns of AQR results provides the basis for establishment of an industry benchmark for the purpose of enhancing airline operational performance. A 7 year average of overall operational performance provides the resulting benchmark indicator. Applications from this example can be applied to the many competitive environments of the global industry and assist policy-makers faced with rapidly changing regulatory challenges.

Effects of RoHs and REACH regulations on firm-level production and export, and the role of global value chains : the cases of Malaysia and Vietnam

OpenAIRE

Otsuki, Tsunehiro; Honda, Keiichiro; Michida, Etsuyo; Nabeshima, Kaoru; Ueki, Yasushi

2015-01-01

This paper uses firm-level data to examine the impact of foreign chemical safety regulations such as RoHS and REACH on the production costs and export performance of firms in Malaysia and Vietnam. This paper also investigates the role of global value chains in enhancing the likelihood that a firm complies with RoHS and REACH. We find that in addition to the initial setup costs for compliance, EU RoHS (REACH) implementation imposes on firms additional variable production costs by requiring add...

Outcome and value uncertainties in global-change policy

International Nuclear Information System (INIS)

Hammitt, J.K.

1995-01-01

Choices among environmental policies can be informed by analysis of the potential physical, biological, and social outcomes of alternative choices, and analysis of social preferences among these outcomes. Frequently, however, the consequences of alternative policies cannot be accurately predicted because of substantial outcome uncertainties concerning physical, chemical, biological, and social processes linking policy choices to consequences. Similarly, assessments of social preferences among alternative outcomes are limited by value uncertainties arising from limitations of moral principles, the absence of economic markets for many environmental attributes, and other factors. Outcome and value uncertainties relevant to global-change policy are described and their magnitudes are examined for two cases: stratospheric-ozone depletion and global climate change. Analysis of information available in the mid 1980s, when international ozone regulations were adopted, suggests that contemporary uncertainties surrounding CFC emissions and the atmospheric response were so large that plausible ozone depletion, absent regulation, ranged from negligible to catastrophic, a range that exceeded the plausible effect of the regulations considered. Analysis of climate change suggests that, important as outcome uncertainties are, uncertainties about values may be even more important for policy choice. 53 refs., 3 figs., 3 tabs

Tackling the global NCD crisis: innovations in law and governance.

Science.gov (United States)

Thomas, Bryan; Gostin, Lawrence O

2013-01-01

35 million people die annually of non-communicable diseases (NCDs), 80% of them in low- and middle-income countries - representing a marked epidemiological transition from infectious to chronic diseases and from richer to poorer countries. The total number of NCDs is projected to rise by 17% over the coming decade, absent significant interventions. The NCD epidemic poses unique governance challenges: the causes are multifactorial, the affected populations diffuse, and effective responses require sustained multi-sectorial cooperation. The authors propose a range of regulatory options available at the domestic level, including stricter food labeling laws, regulation of food advertisements, tax incentives for healthy lifestyle choices, changes to the built environment, and direct regulation of food and drink producers. Given the realities of globalization, such interventions require global cooperation. In 2011, the UN General Assembly held a High-level meeting on NCDs, setting a global target of a 25% reduction in premature mortality from NCDs by 2025. Yet concrete plans and resource commitments for reaching this goal are not yet in the offing, and the window is rapidly closing for achieving these targets through prevention - as opposed to treatment, which is more costly. Innovative global governance for health is urgently needed to engage private industry and civil society in the global response to the NCD crisis. © 2013 American Society of Law, Medicine & Ethics, Inc.

The CLP(OIH) Language

DEFF Research Database (Denmark)

Hougaard, Ole Ildsgaard

1998-01-01

Type inference is generally thought of as being an exclusive property of the functional programming paradigm. We argue that such a feature may be of significant benefit for also standard imperative languages. We present a working tool (available by WWW) providing these benefits for a full version...... of Turbo Pascal. It has the form of a preprocessor that analyzes programs in which the type annotations are only partial or even absent. The resulting program has full type annotations, will be accepted by the standard Turbo Pascal compiler, and has polymorphic use of procedures resolved by means of code...

International Maritime Transport Sector Regulation Systems and their Impact on World Shipping and Global Trade

Directory of Open Access Journals (Sweden)

Andrzej Grzelakowski

2013-09-01

Full Text Available The main purpose of the paper is to analyze the impact of two nowadays existing global regulatory systems of the world maritime transport sector on international shipping industry and global trade development. The author has focused on the characterization of the autonomous regulatory system represented in this sector by freight market with typical for it mechanism as well as on public regulatory system expressed in form of the existing international regulatory scheme introduced by IMO and other international organizations. Both regulatory mechanisms has been analyzed and viewed in terms of efficiency and effectiveness of their influence upon shipping industry and global commodity markets. At the end, the results of functioning of both regulatory subsystems have been assessed with the aim to indicate how they are able to create growth potential for the world maritime transport and trade sector as well as the global economy.

Cryptocurrencies & the Challenge of Global Governance

Directory of Open Access Journals (Sweden)

Garry Jacbs

2018-05-01

Full Text Available The recent explosive development of new forms of digital currency opens up unprecedented opportunities and poses significant regulatory challenges. This new form of digital currency lowers the costs and other barriers to the global movement of money, international trade, foreign investment and speculation, while simultaneously enhancing the anonymity on which tax evasion, money-laundering and other illegal activities thrive. It also liberates the creation of money and regulation of economic activities from the political control of national governments and central banks. Since the value of a currency is related to the size of the population, strength of the economy and value of transactions that utilize it, a basket of cryptocurrencies could emerge as the first prototype of a world currency whose value is backed by the total productive capacity of the entire human community. Moreover, the triad of Internet, distributed ledger technologies and cryptocurrencies could serve as the basis for the development of new global economic potentials in a manner similar and a degree far exceeding the economic impact of the World Wide Web over the past two decades. At the same time, the rapid deployment of cryptocurrencies could have profound impact on the capacity of governments to tax transactions, income and wealth, one of the main pillars of the modern nation state. The development of autonomous global cryptocurrencies could dramatically reduce the control and effectiveness of existing regulatory mechanisms at the national level and generate considerable pressure for the evolution of more effective institutions for global governance. They could provide compelling incentives for national governments to enhance international cooperation and strengthen the functioning of international institutions to fill the regulatory void. International organizations will play an important role in harnessing the potentials and minimizing the risks arising from the growing

ATTACHMENT IN INFANTS WITH CLEFT LIP AND/OR PALATE: MARGINAL SECURITY AND ITS CHANGES OVER TIME.

Science.gov (United States)

Borghini, Ayala; Despars, Josée; Habersaat, Stéphanie; Turpin, Hélène; Monnier, Maryline; Ansermet, François; Hohlfeld, Judith; Muller-Nix, Carole

2018-03-01

This study examines the attachment quality and how this changed over time among infants who had cleft lip and palate (CLP), by conducting a prospective longitudinal study addressing the effects of this type of perinatal event on the parent-infant relationship and the emotional development of the infants. At 12 months of age, the Strange Situation Paradigm (SSP; M. Ainsworth, M.C. Blehar, E. Waters, & T. Wall, 1978) was administered to a sample of 38 CLP infants (born between 2003 and 2010) and 17 healthy controls. At 4 years of age, the Attachment Story Completion Task (ASCT; I. Bretherton, D. Ridgeway, & J. Cassidy, 1990) was administered to 32 individuals from the CLP sample and 14 from the control group. As reported in the literature, CLP infants display secure attachment behaviors as frequently as do control infants (55%). However, a more detailed analysis of the attachment scales revealed that CLP infants show more avoidance and less proximity seeking. In addition, a closer examination of the subcategories of attachment styles revealed that most CLP infants (71%) displayed distal attachment strategies such as the B1/B2 or A1/A2 subcategories. At 4 years old, CLP infants clearly displayed more deactivation and less security than did the control sample. Moreover, when detailing the evolution of attachment individually, almost 60% of the CLP children showing distal strategies at 12 months became deactivated or disorganized when they reached 4 years. Indeed, subtle differences in attachment behaviors at 12 months old-which can be considered marginally secure at that age-may reveal attachment vulnerabilities, which seem to be more apparent over the course of development. © 2018 Michigan Association for Infant Mental Health.

Structural color changes in permanent enamel of patients with cleft lip and palate: a case-control study.

Science.gov (United States)

Kulas, Antje; Illge, Christina; Bekes, Katrin; Eckert, Alexander W; Fuhrmann, Robert A W; Hirsch, Christian

2016-01-01

White spots are more common in patients with cleft lip and palate (CLP) than in the normal population. Whether these are due to the cleft itself or concomitant circumstances (e.g., surgical procedures, orthodontic treatments, systemic fluoridation, increased caries risk) remains unclear. This case-control study evaluated both their prevalence in CLP patients versus control subjects and associated risk factors. A total of 73 CLP patients (average age 8.7 years, range 6-18 years, 42 % male) and a control group of 73 age- and gender-matched non-CLP patients were included. Enamel color changes, subsuming mineralization defects (DDE index), mild dental fluorosis (Dean's index), and initial caries (ICDAS score 2), were recorded. Caries index (dmf-t/DMF-T) scores were also recorded to distinguish between high or low caries risk as defined by the Deutsche Arbeitsgemeinschaft für Jugendzahnpflege criteria. Histories of systemic fluoridation, trauma to primary teeth, surgery, and orthodontic treatment were obtained using a questionnaire. Statistical analysis included t test, χ (2) test, and multivariable logistic regression. Enamel color changes were observed three times more often in the CLP group than in the control group (39.7 vs. 12.3 %; p enamel color changes was associated with CLP itself [OR (odds ratio) 3.6; 95 % confidence interval (CI) 1.3-9.9] and table salt plus tablets combined for systemic fluoridation (OR 2.7, 95 % CI 1.1-6.9). No increased risks were identified for increased caries risk, history of primary-tooth trauma, or history of orthodontic treatment. The higher prevalence of enamel color changes in the CLP group (more than threefold compared to the control group) was not related to previous orthodontic treatments; however, systemic fluoridation (table salt and tablets) constituted a risk factor for the enamel color changes seen in the CLP patients.

Population-based study of birth prevalence and factors associated with cleft lip and/or palate in Taiwan 2002-2009.

Directory of Open Access Journals (Sweden)

Ruoh-Lih Lei

Full Text Available BACKGROUND: Facial cleft deformities, including cleft lip with or without cleft palate (CL/P and cleft palate (CP, are common congenital birth anomalies, especially in Asia. This study aimed to analyze the prevalence of CL/P and CP and to identify associated factors in Taiwan. METHODS: This population-based epidemiological study retrospectively analyzed birth data obtained from the Department of Health in Taiwan for years 2002-2009. Frequency distribution, percentages and related predictors were investigated, and findings were presented by types of cleft deformities. Logistic regression analysis was performed to identify factors associated with cleft deformities. RESULTS: Overall prevalence of cleft deformities among 1,705,192 births was 0.1% for CL/P and 0.04% for CP over the 8-year study period. Higher prevalence of CL/P or CP was observed with multiple pregnancies, being male for CL/P, being female for CP, gestational age ≤37 weeks and lower birth weight (<1.5 kg. Both CL/P and CP were significantly associated with gestational age <37 weeks and birth weight<1.5 kg (all P <0.0001. CL/P was significantly associated with multiple parities (P = 0.0004-0.002. Male newborns and female newborns were significantly associated with CL/P and CP, respectively (both P<0.0001. CONCLUSIONS: Overall prevalence for congenital cleft deformities in study subjects was 0.1%, in keeping with high rates in Asia. Results suggest the need for awareness and early identification of those at high risk for cleft deformities, including newborns with gestational age <37 weeks, weighing <1.5 kg at birth and women with multiple parities, as a potential strategy to counter long-term adverse effects on speech and language in this population.

Stabilization and regulation of nonlinear systems a robust and adaptive approach

CERN Document Server

Chen, Zhiyong

2015-01-01

The core of this textbook is a systematic and self-contained treatment of the nonlinear stabilization and output regulation problems. Its coverage embraces both fundamental concepts and advanced research outcomes and includes many numerical and practical examples. Several classes of important uncertain nonlinear systems are discussed. The state-of-the art solution presented uses robust and adaptive control design ideas in an integrated approach which demonstrates connections between global stabilization and global output regulation allowing both to be treated as stabilization problems. Stabilization and Regulation of Nonlinear Systems takes advantage of rich new results to give students up-to-date instruction in the central design problems of nonlinear control, problems which are a driving force behind the furtherance of modern control theory and its application. The diversity of systems in which stabilization and output regulation become significant concerns in the mathematical formulation of practical contr...

THE ROLE AND PLACE TRANSNATIONAL CORPORATIONS IN GLOBALIZATION

Directory of Open Access Journals (Sweden)

Lytvynenko Kristina

2018-01-01

Full Text Available Introduction. At present, transnational corporations (TNCs are leading the world economy. Each year, the number of TNCs increases, which increases their share in the global economy as a whole. The largest investment projects in the world are concentrated in such corporations, which are a major impetus for the development of countries in which all the capacities of transnational corporations are located. Through the structure of TNCs there are financial and commodity flows that are crucial for the development and improvement of the world economy. The above shows that the study and further research of transnational corporations in the globalization processes is an actual topic of the present. Purpose. The purpose of the paper is to study the peculiarities and trends of the activities of transnational corporations in the conditions of globalization of the world economy. Results. The basis of the new global economic system are TNCs that have large financial resources, implement advanced technologies, have significant spatial markets and conduct an active, globally, investment policy. Conclusions. A transnational corporation is part of the world economy, which is subject to the laws of the development of TNCs and reflects the reciprocal impact on the world economy, a product of globalization processes. The direct relationship between TNCs and the process of globalization comes from the study of the stages of the evolution of transnational corporations. The role of TNCs in the modern world is intensifying, in this connection, the role of national economies is falling, which leads to a conflict of interest between multinational corporations and states. Such conflicts can have a bad effect on the state of the economy and the stability of the state. Therefore, it is necessary to regulate the activities of TNCs. Modern activity of transnationalization has acquired many new features, it can affect not only the world economy, but also the country�

Explaining (Missing) Regulator Paradigm Shifts

DEFF Research Database (Denmark)

Wigger, Angela; Buch-Hansen, Hubert

2014-01-01

The global financial and economic crisis has prompted some scholars to suggest that a fundamental regulatory shift away from neoliberalism will take place – both in general and in the field of EU competition regulation. This paper shows that so far no radical break with the neoliberal type...... regulation after the crisis in the 1970s, the paper argues that the preconditions for a fundamental shift in this issue area are not present this time around. Several reasons account for this: the current crisis has been construed by economic and political elites as a crisis within and not of neoliberal...

Atmospheric pollution: history, science, and regulation

National Research Council Canada - National Science Library

Jacobson, Mark Z

2002-01-01

..., stratospheric ozone reduction, and global climate change - is provided. Each chapter discusses the history and science behind these problems, their consequences, and the effort made through government intervention and regulation to mitigate them. The book contains numerous student examples and problems, more than 200 color illustrations,...

Global civil society: between nation states and transnational corporations

Directory of Open Access Journals (Sweden)

S. A. Kvitka

2017-06-01

Full Text Available Global civil society is the subject of the formation of a new world order and the modern humanitarian outlook, which is based on the primacy of justice and human rights. One of the actors head of global civil society is an international non-governmental organizations. But wrong to equate global civil society with the activities of these organizations only. Mostly they influence governments and their humanitarian and international politics. Meanwhile, the role of global civil and its society various institutions is much greater and significant. The article discusses the various aspects of the civil society from the position that it took place between transnational companies (TNCs and nation-states. The role of the latter is gradually reduced - economic regulation take on multinationals and public administration is a field of activity of various institutions and structures that scientists considered it as a manifestation of global civil society. In Ukraine, which is also involved in the process of globalization, global civil society is one of the main factors of its national civil society.

Groundwater development stress: Global-scale indices compared to regional modeling

Science.gov (United States)

Alley, William; Clark, Brian R.; Ely, Matt; Faunt, Claudia

2018-01-01

The increased availability of global datasets and technologies such as global hydrologic models and the Gravity Recovery and Climate Experiment (GRACE) satellites have resulted in a growing number of global-scale assessments of water availability using simple indices of water stress. Developed initially for surface water, such indices are increasingly used to evaluate global groundwater resources. We compare indices of groundwater development stress for three major agricultural areas of the United States to information available from regional water budgets developed from detailed groundwater modeling. These comparisons illustrate the potential value of regional-scale analyses to supplement global hydrological models and GRACE analyses of groundwater depletion. Regional-scale analyses allow assessments of water stress that better account for scale effects, the dynamics of groundwater flow systems, the complexities of irrigated agricultural systems, and the laws, regulations, engineering, and socioeconomic factors that govern groundwater use. Strategic use of regional-scale models with global-scale analyses would greatly enhance knowledge of the global groundwater depletion problem.

Effects of gamma oryzanol on factors of oxidative stress and sepsis-induced lung injury in experimental animal model

Directory of Open Access Journals (Sweden)

Elmira Zolali

2015-12-01

Full Text Available Objective (s: There is corroborating evidence to substantiate redox imbalance and oxidative stress in sepsis that finally leads to organ damage or even death. Gamma oryzanol (GO is one of the major bioactive components in rice bran has been considered to function as an antioxidant. The present study was carried out to evaluate the antioxidant activity of gamma oryzanol in vitro and its efficacy in sepsis. Materials and Methods: To induce sepsis, cecal ligation and puncture (CLP method was performed on the rats. A study group of forty male Wistar rats were divided into the following groups: sham group; CLP group; 50 mg/kg GO- treated CLP group and 100 mg/kg GO- treated CLP group. GO was administered with an oral gavage 2 hr prior to inducing sepsis. Tissue and blood samples were collected 12 hr after CLP to prepare tissue sections for histopathological study and assay the oxidative stress biomarkers including: SOD (Superoxide Dismutase, TAC (total antioxidant capacity, MDA (Malondialdehyde, MPO (Myeloperoxidase and PAI-1 (Plasminogen Activator Inhibitor-1. Data are given as mean ± SD. The ANOVA with Tukey post hoc test was used to determine the differences between groups and P Results: TAC level increased in GO- treated CLP groups (P

Empowering Volunteers at Tawanchai Centre for Patients with Cleft Lip and Palate.

Science.gov (United States)

Pradubwong, Suteera; Augsornwan, Darawan; Pathumwiwathana, Pornpen; Prathanee, Benjamas; Chowchuen, Bowornsilp

2015-08-01

Cleft lip and palate (CLP) congenital anomalies have a high prevalence in the Northeast of Thailand. A care team's understand of treatment plan would help to guide the family of patients with CLP to achieve the treatment. To examine the impact of the empowering volunteer project, established in the northeast Thailand. The Empowering Volunteer project was conducted in 2008 under the Tawanchai Royal Granted project. The patients and family's general information, treatment, the group brainstorming, and satisfaction with the project were analysed. Participants were 12 children with CLP their families and five volunteers with CLP; the participating patients were predominantly females and the mean age was 12.2 years. The treatment comprised of speech training, dental hygiene care, bone graft and orthodontic treatment. Four issues were addressed including: problems in taking care of breast feeding, instructions' needs for care at birth, difficulty in access information and society impact, and needs in having a network of volunteers. Empowering volunteer is important for holistic care of patients with CLP which provides easy access and multiple channels for patients and their families. It should be developed as part of the self-help and family support group, the development of community based team and comprehensive CLP care program.

On the social nature of global self-esteem: a replication study.

Science.gov (United States)

Stephan, Yannick; Maiano, Christophe

2007-10-01

Few researchers have considered the relationship between global self-esteem and the reflected appraisal of others in one's life, or how reflected appraisals and global self-esteem may change as a result of interpersonal feedback. In this study, the authors collected data from 110 undergraduate students on (a) their global self-esteem and the reflected appraisals of multiple others in their lives and (b) how these dimensions changed in hypothetical interpersonal-feedback situations. Results showed that participants' global self-esteem was related to the reflected appraisals of their fathers, teachers, and friends. The results also indicated that others' reflected appraisals and the individual's global self-esteem fluctuated according to the nature (i.e., positive vs. negative) of the hypothetical interpersonal feedback. Overall, the findings emphasize the social nature and regulation of global self-esteem.

The Destructuring and Restructuring of Global Labor Markets

DEFF Research Database (Denmark)

Schmidt, Johannes Dragsbæk

in global labor markets and industrial relations. The third part situates more squarely the impact of globalization on the catching-up strategies of Russia and China, while the next section digs into the transformation of the industrial relations regimes in Russia and China in comparative perspective....... Finally, the paper rounds up by pointing to the main similarities and differences between industrial relations, work and labor market regulation in Russia and China, but also with implications for a broader context. In order to come to terms with the crisis of former socialist type societ...

The Crc global regulator inhibits the Pseudomonas putida pWW0 toluene/xylene assimilation pathway by repressing the translation of regulatory and structural genes.

Science.gov (United States)

Moreno, Renata; Fonseca, Pilar; Rojo, Fernando

2010-08-06

In Pseudomonas putida, the expression of the pWW0 plasmid genes for the toluene/xylene assimilation pathway (the TOL pathway) is subject to complex regulation in response to environmental and physiological signals. This includes strong inhibition via catabolite repression, elicited by the carbon sources that the cells prefer to hydrocarbons. The Crc protein, a global regulator that controls carbon flow in pseudomonads, has an important role in this inhibition. Crc is a translational repressor that regulates the TOL genes, but how it does this has remained unknown. This study reports that Crc binds to sites located at the translation initiation regions of the mRNAs coding for XylR and XylS, two specific transcription activators of the TOL genes. Unexpectedly, eight additional Crc binding sites were found overlapping the translation initiation sites of genes coding for several enzymes of the pathway, all encoded within two polycistronic mRNAs. Evidence is provided supporting the idea that these sites are functional. This implies that Crc can differentially modulate the expression of particular genes within polycistronic mRNAs. It is proposed that Crc controls TOL genes in two ways. First, Crc inhibits the translation of the XylR and XylS regulators, thereby reducing the transcription of all TOL pathway genes. Second, Crc inhibits the translation of specific structural genes of the pathway, acting mainly on proteins involved in the first steps of toluene assimilation. This ensures a rapid inhibitory response that reduces the expression of the toluene/xylene degradation proteins when preferred carbon sources become available.

A Surfactant-Induced Functional Modulation of a Global Virulence Regulator from Staphylococcus aureus.

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Sukhendu Mandal

Full Text Available Triton X-100 (TX-100, a useful non-ionic surfactant, reduced the methicillin resistance in Staphylococcus aureus significantly. Many S. aureus proteins were expressed in the presence of TX-100. SarA, one of the TX-100-induced proteins, acts as a global virulence regulator in S. aureus. To understand the effects of TX-100 on the structure, and function of SarA, a recombinant S. aureus SarA (rSarA and its derivative (C9W have been investigated in the presence of varying concentrations of this surfactant using various probes. Our data have revealed that both rSarA and C9W bind to the cognate DNA with nearly similar affinity in the absence of TX-100. Interestingly, their DNA binding activities have been significantly increased in the presence of pre-micellar concentration of TX-100. The increase of TX-100 concentrations to micellar or post-micellar concentration did not greatly enhance their activities further. TX-100 molecules have altered the secondary and tertiary structures of both proteins to some extents. Size of the rSarA-TX-100 complex appears to be intermediate to those of rSarA and TX-100. Additional analyses show a relatively moderate interaction between C9W and TX-100. Binding of TX-100 to C9W has, however, occurred by a cooperative pathway particularly at micellar and higher concentrations of this surfactant. Taken together, TX-100-induced structural alteration of rSarA and C9W might be responsible for their increased DNA binding activity. As TX-100 has stabilized the somewhat weaker SarA-DNA complex effectively, it could be used to study its structure in the future.

The effectiveness of consultation-liaison psychiatry in the general hospital setting: a systematic review.

Science.gov (United States)

Wood, Rebecca; Wand, Anne P F

2014-03-01

The aim of this study was to review how the effectiveness of consultation liaison psychiatry (CLP) services has been measured and to evaluate the strength of the evidence for effectiveness. Systematic review of medical databases using broad search terms as well as expert opinion was sought. The literature search was restricted to studies of general, whole-of-hospital inpatient CLP services. Forty articles were found and grouped into five measurements of effectiveness: cost effectiveness including length of stay, concordance, staff and patient feedback, and follow-up outcome studies. All measurements contributed to the evaluation of CLP services, but no one measure in isolation could adequately cover the multifaceted roles of CLP. Concordance was the only measurement with an established, consistent approach for evaluation. Cost effectiveness and follow-up outcome studies were the only measures with levels of evidence above four, however the three follow-up outcome studies reported conflicting results. Subjective evidence derived from patient and staff feedback is important but presently lacking due to methodological problems. The effectiveness of CLP services was demonstrated by cost-effectiveness, earlier referrals to CLP predicting shorter length of stay, and concordance with some management recommendations. There is evidence that some CLP services are cost-effective and reduce length of stay when involved early and that referrers follow certain recommendations. However, many studies had disparate results and were methodologically flawed. Future research should focus on standardising patient and staff feedback, and short-term patient outcomes. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Dental Anomalies in Different Types of Cleft Lip and Palate: Is There Any Relation?

Science.gov (United States)

Germec Cakan, Derya; Nur Yilmaz, Rahime Burcu; Bulut, Feyza Nur; Aksoy, Ayca

2018-02-26

The aims of this study were to evaluate the prevalence of dental anomalies in Turkish patients with different types of cleft lip and palate (CLP) and investigate the relationship between the type of cleft and the dental anomaly. Eighty-eight patients with cleft lip and/or palate (mean age: 14.1 ± 6.4 years) were enrolled in this retrospective study. Dental models, panoramic radiographs, and intraoral photographs of these patients were evaluated to detect any maxillary dental anomaly (number and size anomalies). Two hundred fifty unaffected subjects (mean age: 15.2 ± 7.2 years) composed the control group. Data were evaluated using the independent t test, χ, Fischer exact test, and the odds ratio. Dental anomaly frequency was significantly higher in the cleft group compared with the control group. Tooth agenesis was the most common dental anomaly, followed by microdontia and supernumerary tooth. Lateral incisor agenesis was seen in 69% of the unilateral CLP, in 78% of the bilateral CLP, and in 18% of the cleft palate patients. A significant association was revealed between the right unilateral CLP and the right lateral incisor agenesis (P = 0.0001), the left unilateral CLP and the left lateral incisor agenesis (P = 0.002), and the bilateral CLP and the bilateral lateral incisor agenesis (P = 0.0001). Dental anomalies are more frequently seen in patients with CLP compared with the general population. There is a relationship between the cleft type and the ipsilateral lateral incisor agenesis.

Mitochondria-Targeted Antioxidants SkQ1 and MitoTEMPO Failed to Exert a Long-Term Beneficial Effect in Murine Polymicrobial Sepsis

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Pia Rademann

2017-01-01

Full Text Available Mitochondrial-derived reactive oxygen species have been deemed an important contributor in sepsis pathogenesis. We investigated whether two mitochondria-targeted antioxidants (mtAOX; SkQ1 and MitoTEMPO improved long-term outcome, lessened inflammation, and improved organ homeostasis in polymicrobial murine sepsis. 3-month-old female CD-1 mice (n=90 underwent cecal ligation and puncture (CLP and received SkQ1 (5 nmol/kg, MitoTEMPO (50 nmol/kg, or vehicle 5 times post-CLP. Separately, 52 SkQ1-treated CLP mice were sacrificed at 24 h and 48 h for additional endpoints. Neither MitoTEMPO nor SkQ1 exerted any protracted survival benefit. Conversely, SkQ1 exacerbated 28-day mortality by 29%. CLP induced release of 10 circulating cytokines, increased urea, ALT, and LDH, and decreased glucose but irrespectively of treatment. Similar occurred for CLP-induced lymphopenia/neutrophilia and the NO blood release. At 48 h post-CLP, dying mice had approximately 100-fold more CFUs in the spleen than survivors, but this was not SkQ1 related. At 48 h, macrophage and granulocyte counts increased in the peritoneal lavage but irrespectively of SkQ1. Similarly, hepatic mitophagy was not altered by SkQ1 at 24 h. The absence of survival benefit of mtAOX may be due to the extended treatment and/or a relatively moderate-risk-of-death CLP cohort. Long-term effect of mtAOX in abdominal sepsis appears different to sepsis/inflammation models arising from other body compartments.

Lessons and policy implications from the global financial crisis

NARCIS (Netherlands)

Claessens, S.; Dell'Ariccia, G.; Igan, D.; Laeven, L.A.H.; Caprio, G.; Beck, T.; Claessens, S.; Schmukler, S.L.

2013-01-01

The crisis has brought to light a number of deficiencies in financial regulation and architecture, particularly in the treatment of systemically important financial institutions, the assessments of systemic risks and vulnerabilities, and the resolution of financial institutions. The global nature of

Competition, the Global Crisis, and Alternatives to Neoliberal Capitalism

DEFF Research Database (Denmark)

Wigger, Angela; Buch-Hansen, Hubert

2013-01-01

regulation and other regulatory provisions, excessive competition (over-competition) in the process of capital accumulation has become a major global force with highly detrimental social and environmental downsides. From the vantage point of a historical materialist perspective, the article provides...

Vascular barrier protective effects of baicalin, baicalein and wogonin in vitro and in vivo

Energy Technology Data Exchange (ETDEWEB)

Kwak, Soyoung [College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Ku, Sae-Kwang [Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan 712-715 (Korea, Republic of); Han, Min-Su [Laboratory for Arthritis and Bone Biology, Fatima Research Institute, Fatima Hospital, Daegu 701-600 (Korea, Republic of); Bae, Jong-Sup, E-mail: baejs@knu.ac.kr [College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701 (Korea, Republic of)

2014-11-15

Inhibition of high mobility group box 1 (HMGB1) protein and restoration of endothelial integrity is emerging as an attractive therapeutic strategy in the management of sepsis. Here, three structurally related polyphenols found in the Chinese herb Huang Qui, baicalin (BCL), baicalein (BCN), and wogonin (WGN), were examined for their effects on lipopolysaccharide (LPS)- or cecal ligation and puncture (CLP)-mediated release of HMGB1 and on modulation of HMGB1-mediated inflammatory responses. According to our data, BCL, BCN, and WGN inhibited the release of HMGB1 and down-regulated HMGB1-dependent inflammatory responses in human endothelial cells. BCL, BCN, and WGN also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with BCL, BCN, and WGN reduced CLP-induced release of HMGB1 and sepsis-related mortality and pulmonary injury in mice. These results indicate that BCL, BCN, and WGN could be candidate therapeutic agents for various severe vascular inflammatory diseases owing to their inhibition of the HMGB1 signaling pathway. - Highlights: • HMGB1 is an inflammatory mediator for vascular inflammation. • Baicalin, baicalein and wogonin inhibited HMGB1-induced hyperpermeability in vitro and in vivo. • Baicalin, baicalein and wogonin inhibited HMGB1-mediated inflammatory responses. • Baicalin, baicalein and wogonin suppressed the activation of NF-κB and ERK1/2 and production of TNF-α and IL-6. • Baicalin, baicalein and wogonin prevent CLP-induced septic mortality.

Osteopontin, osteocalcin, and osteoprotegerin expression in human tissue affected by cleft lip and palate

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Smane L.

2016-01-01

Full Text Available Cleft lip and palate (CLP is a common congenital anomaly with a complex etiology which has not been elucidated yet. This study investigated whether expression of osteopontin (OPN, osteoprotegerin (OPG, and osteocalcin (OC, which are essential for the normal craniofacial bone remodelling, is not regulated in children with CLP. Alveolar bone tissue samples were obtained from patients with complete bilateral (CB CLP (n = 14 during corrective plastic surgery and unaffected control subjects (n = 9. OPN, OPG, and OC expression was assessed by immunohistochemistry, and data were analyzed with the Mann-Whitney test. OPN expression was observed only sporadically in the alveolar bone of 3 patients, in contrast to the control group (z = −2.962; P < 0.003. The number of OPG-positive bone cells varied from occasional to moderate, in contrast to the control group (z = −2.247; P = 0.025. OC-positive osteocytes were present in moderate to numerous numbers in both patients and controls, with no significant difference between them (z = −1.356; P < 0.175. The prominent expression of OC characteristic for CBCLP affected hard tissue indicates a high potential of bone mineralization. Few OPG-positive osteocytes in the bone tissue implicate the disregulation of osteoclast differentiation, maturation, and activity, but few OPN-containing cells may prove the common disregulation of bone remodelling during cleft morphopathogenesis.

Environmental transcriptome analysis reveals physiological differences between biofilm and planktonic modes of life of the iron oxidizing bacteria Leptospirillum spp. in their natural microbial community

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Parro Víctor

2010-06-01

Full Text Available Abstract Background Extreme acidic environments are characterized by their high metal content and lack of nutrients (oligotrophy. Macroscopic biofilms and filaments usually grow on the water-air interface or under the stream attached to solid substrates (streamers. In the Río Tinto (Spain, brown filaments develop under the water stream where the Gram-negative iron-oxidizing bacteria Leptospirillum spp. (L. ferrooxidans and L. ferriphilum and Acidithiobacillus ferrooxidans are abundant. These microorganisms play a critical role in bioleaching processes for industrial (biominery and environmental applications (acid mine drainage, bioremediation. The aim of this study was to investigate the physiological differences between the free living (planktonic and the sessile (biofilm associated lifestyles of Leptospirillum spp. as part of its natural extremely acidophilic community. Results Total RNA extracted from environmental samples was used to determine the composition of the metabolically active members of the microbial community and then to compare the biofilm and planktonic environmental transcriptomes by hybridizing to a genomic microarray of L. ferrooxidans. Genes up-regulated in the filamentous biofilm are involved in cellular functions related to biofilm formation and maintenance, such as: motility and quorum sensing (mqsR, cheAY, fliA, motAB, synthesis of cell wall structures (lnt, murA, murB, specific proteases (clpX/clpP, stress response chaperons (clpB, clpC, grpE-dnaKJ, groESL, etc. Additionally, genes involved in mixed acid fermentation (poxB, ackA were up-regulated in the biofilm. This result, together with the presence of small organic acids like acetate and formate (1.36 mM and 0.06 mM respectively in the acidic (pH 1.8 water stream, suggests that either L. ferrooxidans or other member of the microbial community are producing acetate in the acidophilic biofilm under microaerophilic conditions. Conclusions Our results indicate that the

Environmental transcriptome analysis reveals physiological differences between biofilm and planktonic modes of life of the iron oxidizing bacteria Leptospirillum spp. in their natural microbial community.

Science.gov (United States)

Moreno-Paz, Mercedes; Gómez, Manuel J; Arcas, Aida; Parro, Víctor

2010-06-24

Extreme acidic environments are characterized by their high metal content and lack of nutrients (oligotrophy). Macroscopic biofilms and filaments usually grow on the water-air interface or under the stream attached to solid substrates (streamers). In the Río Tinto (Spain), brown filaments develop under the water stream where the Gram-negative iron-oxidizing bacteria Leptospirillum spp. (L. ferrooxidans and L. ferriphilum) and Acidithiobacillus ferrooxidans are abundant. These microorganisms play a critical role in bioleaching processes for industrial (biominery) and environmental applications (acid mine drainage, bioremediation). The aim of this study was to investigate the physiological differences between the free living (planktonic) and the sessile (biofilm associated) lifestyles of Leptospirillum spp. as part of its natural extremely acidophilic community. Total RNA extracted from environmental samples was used to determine the composition of the metabolically active members of the microbial community and then to compare the biofilm and planktonic environmental transcriptomes by hybridizing to a genomic microarray of L. ferrooxidans. Genes up-regulated in the filamentous biofilm are involved in cellular functions related to biofilm formation and maintenance, such as: motility and quorum sensing (mqsR, cheAY, fliA, motAB), synthesis of cell wall structures (lnt, murA, murB), specific proteases (clpX/clpP), stress response chaperons (clpB, clpC, grpE-dnaKJ, groESL), etc. Additionally, genes involved in mixed acid fermentation (poxB, ackA) were up-regulated in the biofilm. This result, together with the presence of small organic acids like acetate and formate (1.36 mM and 0.06 mM respectively) in the acidic (pH 1.8) water stream, suggests that either L. ferrooxidans or other member of the microbial community are producing acetate in the acidophilic biofilm under microaerophilic conditions. Our results indicate that the acidophilic filaments are dynamic structures

Tezosentan reduces the microvascular filtration coefficient in isolated lungs from rats subjected to cecum ligation and puncture.

Science.gov (United States)

Kuklin, Vladimir; Sovershaev, Mikhail; Andreasen, Thomas; Skogen, Vegard; Ytrehus, Kirsti; Bjertnaes, Lars

2005-01-01

We recently demonstrated that the non-selective endothelin-1 (ET-1) receptor blocker tezosentan antagonizes ovine acute lung injury (ALI) following infusion of endotoxin or ET-1 by reducing the enhanced lung microvascular pressure, although we could not exclude the possibility of a simultaneous decline in microvascular permeability. In the present study, our aim was to find out if tezosentan reverses the rise in microvascular filtration coefficient (Kfc) in rat lungs that have been isolated and perfused 12 h after cecum ligation and puncture (CLP) or infusion of ET-1. Wistar rats (n = 42) were subjected to CLP. Postoperatively, rats were randomized to a CLP group (n = 7) and a CLP + tezosentan group (n = 7); the latter received tezosentan 30 mg/kg. A sham-operated group (n = 5) underwent laparotomy without CLP. Twelve hours postoperatively, the lungs were isolated and perfused with blood from similarly treated rats that also were used to assess plasma concentration of ET-1 and protein kinase Calpha (PKCalpha) in lung tissue. Additionally, isolated blood perfused lungs from healthy rats were randomized to a control group (n = 8), an ET-1 group (n = 7) subjected to pulmonary arterial injection of ET-1 10 nM, and an ET-1 + tezosentan group (n = 7) that received tezosentan 30 mg/kg. All lung preparations received papaverine 0.1 microg/kg added to the perfusate for vasoplegia. Pulmonary hemodynamic variables, Kfc and lung compliance (CL) were assessed. After CLP, the plasma concentration of ET-1 increased. Papaverine abolished the vasoconstrictor response to ET-1 and the pulmonary vascular pressures remained close to baseline throughout the experiments. Both CLP and injection of ET-1 caused significant changes in Kfc and CL that were prevented in tezosentan-treated rats. Compared to sham-operated animals, CLP increased the content of PKCalpha by 50% and 70% in the cytosolic and the membrane fractions of lung tissue homogenates, respectively. Tezosentan prevented the

Global financial reform since 2008: Achievements and shortcomings

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Šoškić Dejan

2015-01-01

Full Text Available The global financial crisis that started in the U.S. had an immediate spillover to the rest of the world financial markets. Next, a decrease in real economic output throughout the developed world occurred simultaneously with high bailout costs for the salvaging of banks and other financial institutions. This vicious combination was at the core of the bank-sovereign interdependence and the sovereign debt crisis of the eurozone. As early as 2008, the G20 announced a thorough global reform agenda with an aim to tackle the root causes of the crises and to transform the system of global financial regulation. Some important reform steps have been made; still, more than six years on, the job is not finished. Where are we in terms of global financial reform, and are we close to creating a more secure global financial system significantly less prone to crisis and bailouts with taxpayers’ money? [Projekat Ministarstva nauke Republike Srbije, br. 179005: Risks of Financial Institutions and Markets in Serbia - A Microeconomic and Macroeconomic Approach

Disclosure of congenital cleft lip and palate to Japanese patients: reported patient experiences and relationship to self-esteem

OpenAIRE

Omiya, Tomoko; Ito, Mikiko; Yamazaki, Yoshihiko

2014-01-01

Background The present study investigated when and how Japanese people with cleft lip and palate (CL/P) learn that their condition is congenital; the perceived effects of withholding the CL/P diagnosis on patients; and whether the resulting social experience and self-esteem are related. A questionnaire survey was conducted in 71 adults with CL/P recruited through a hospital, a patients? association, and by snowball sampling. Results The participants became aware of their physical difference i...

Ranking of persister genes in the same Escherichia coli genetic background demonstrates varying importance of individual persister genes in tolerance to different antibiotics

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Nan eWu

2015-09-01

Full Text Available Despite the identification of many genes and pathways involved in the persistence phenomenon of bacteria, the relative importance of these genes in a single organism remains unclear. Here, using Escherichia coli as a model, we generated mutants of 21 known candidate persister genes and compared the relative importance of these mutants in persistence to various antibiotics (ampicillin, gentamicin, norfloxacin, and trimethoprim at different times. We found that oxyR, dnaK, sucB, relA, rpoS, clpB, mqsR, and recA were prominent persister genes involved in persistence to multiple antibiotics. These genes map to the following pathways: antioxidative defense pathway (oxyR, global regulators (dnaK, clpB, and rpoS, energy production (sucB, stringent response (relA, toxin–antitoxin (TA module (mqsR, and SOS response (recA. Among the TA modules, the ranking order was mqsR, lon, relE, tisAB, hipA, and dinJ. Intriguingly, rpoS deletion caused a defect in persistence to gentamicin but increased persistence to ampicillin and norfloxacin. Mutants demonstrated dramatic differences in persistence to different antibiotics at different time points: some mutants (oxyR, dnaK, phoU, lon, recA, mqsR, and tisAB displayed defect in persistence from early time points, while other mutants (relE, smpB, glpD, umuD, and tnaA showed defect only at later time points. These results indicate that varying hierarchy and importance of persister genes exist and that persister genes can be divided into those involved in shallow persistence and those involved in deep persistence. Our findings suggest that the persistence phenomenon is a dynamic process with different persister genes playing roles of variable significance at different times. These findings have implications for improved understanding of persistence phenomenon and developing new drugs targeting persisters for more effective cure of persistent infections.

Mechanisms of private meta-governance: an analysis of global private governance for sustainable development

NARCIS (Netherlands)

Glasbergen, P.

2011-01-01

One of the main characteristics of global governance for sustainable development is its fragmentation. Next to public regulations, there are often many private regulations in force on the same issue, which are induced by collaborations between businesses and NGOs. Traditionally, it is assumed that

Electric power globalization and reforming

International Nuclear Information System (INIS)

Soares Neto, Jose Lino

1999-01-01

The central issue of debate was the need to align the energy sector's options and organization with changing global patterns of economic and social development, characterized by the increasing role played by the private sector, greater integration in the world economy, and new economic and social priorities such as efficiency, decentralization, deregulation, and a closer attention to environmental issues. The aim of the work was to define the economic and political forces of the electric power sector regulation restructuring

Adenoviral transfer of HSP-70 into pulmonary epithelium ameliorates experimental acute respiratory distress syndrome.

Science.gov (United States)

Weiss, Yoram G; Maloyan, Alina; Tazelaar, John; Raj, Nichelle; Deutschman, Clifford S

2002-09-01

The acute respiratory distress syndrome (ARDS) provokes three pathologic processes: unchecked inflammation, interstitial/alveolar protein accumulation, and destruction of pulmonary epithelial cells. The highly conserved heat shock protein HSP-70 can limit all three responses but is not appropriately expressed in the lungs after cecal ligation and double puncture (2CLP), a clinically relevant model of ARDS. We hypothesize that restoring expression of HSP-70 using adenovirus-mediated gene therapy will limit pulmonary pathology following 2CLP. We administered a vector containing the porcine HSP-70 cDNA driven by a CMV promoter (AdHSP) into the lungs of rats subjected to 2CLP or sham operation. Administration of AdHSP after either sham operation or 2CLP increased HSP-70 protein expression in lung tissue, as determined by immunohistochemistry and Western blot hybridization. Administration of AdHSP significantly attenuated interstitial and alveolar edema and protein exudation and dramatically decreased neutrophil accumulation, relative to a control adenovirus. CLP-associated mortality at 48 hours was reduced by half. Modulation of HSP-70 production reduces pathologic changes and may improve outcome in experimental ARDS.

Effects of methyl palmitate on cytokine release, liver injury and survival in mice with sepsis.

Science.gov (United States)

Villa, P; Demitri, M T; Meazza, C; Sironi, M; Gnocchi, P; Ghezzi, P

1996-12-01

The effects of methyl palmitate (MP), a known inhibitor of Kupffer cells, were studied in a model of polymicrobial sepsis induced in CD-1 mice by cecal ligation and puncture (CLP). The inhibition of Kupffer cells by pretreatment with MP was shown by the reduced phagocytosis, the production of tumor necrosis factor (TNF) and interleukin-6 (IL-6) after lipopolysaccharide (LPS) challenge. The reduced activation of Kupffer cells resulted in lower levels of inflammatory products after CLP. TNF and IL-6 were significantly reduced in serum 2 h and 24 h respectively after CLP, interleukin-1 beta (IL-1 beta) was reduced in liver 4 h after CLP, nitric oxide (NO) and serum amyloid A (SAA) were significantly reduced 8 and 24 h respectively after CLP. Liver toxicity was significantly reduced in MP-treated mice and survival was significantly prolonged at all intervals, reaching 45% after six to ten days compared with 3% in control mice. These findings suggest that Kupffer cells play an important role in liver damage and survival in sepsis.

Review of Antimicrobial Resistance in the Environment and its Relevance to Environmental Regulators

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Andrew C Singer

2016-11-01

Full Text Available The environment is increasingly being recognised for the role it might play in the global spread of clinically-relevant antibiotic resistance. Environmental regulators monitor and control many of the pathways responsible for the release of resistance-driving chemicals into the environment (e.g., antimicrobials, metals, biocides. Hence, environmental regulators should be contributing significantly to the development of global and national antimicrobial resistance (AMR action plans. It is argued that the lack of environment-facing mitigation actions included in existing AMR action plans is likely a function of our poor fundamental understanding of many of the key issues. Here, we aim to present the problem with AMR in the environment through the lens of an environmental regulator, using the Environment Agency (England’s regulator as an example from which parallels can be drawn globally. The issues that are pertinent to environmental regulators are drawn out to answer: What are the drivers and pathways of AMR? How do these relate to the normal work, powers and duties of environmental regulators? What are the knowledge gaps that hinder the delivery of environmental protection from AMR? We offer several thought experiments for how different mitigation strategies might proceed. We conclude that: 1 AMR Action Plans do not tackle all the potentially relevant pathways and drivers of AMR in the environment; and 2 AMR Action Plans are deficient, in part, because the science to inform policy is lacking and this needs to be addressed.

Integrating international students into a project organized problem based learning environment

DEFF Research Database (Denmark)

Hansen, Søren; Du, Xiangyun

2004-01-01

The paper describes a recent developed didactic model for CLP teaching at Aalborg University in Denmark.......The paper describes a recent developed didactic model for CLP teaching at Aalborg University in Denmark....

Economy of education: National and global aspects

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Oksana Ishchenko-Padukova

2017-12-01

Full Text Available Our paper focuses on the national economy of education. We assume that under the current conditions of the globalized world, the economy of education reveals its two-fold nature: on the one hand, it represents an element of the national economic system, and on the other, it is also a structural component of the global education system. Therefore, national economy of education is shaped up by both internal and external factors represented by national and international influences. We analyze here the functional composition and the methods of legal regulation of the economy of education under the conditions and provisions of the global geopolitical transformations. In addition, we use the empirical model of returns to education for showing the factors that impact the employability of young graduates at the labor market. Our results confirm the importance of education for achieving higher levels of income, both nationally and internationally. Finally, we come to the conclusion that its target function consists of the global promotion of national education and consolidation of national competitive position within the world education space.

The Importance of Multidisciplinary Management during Prenatal Care for Cleft Lip and Palate

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Hyun Ho Han

2016-03-01

Full Text Available BackgroundThe prenatal ultrasound detection of cleft lip with or without cleft palate (CL/P and its continuous management in the prenatal, perinatal, and postnatal periods using a multidisciplinary team approach can be beneficial for parents and their infants. In this report, we share our experiences with the prenatal detection of CL/P and the multidisciplinary management of this malformation in our institution's Congenital Disease Center.MethodsThe multidisciplinary team of the Congenital Disease Center for mothers of children with CL/P is composed of obstetricians, plastic and reconstructive surgeons, pediatricians, and psychiatrists. A total of 11 fetuses were diagnosed with CL/P from March 2009 to December 2013, and their mothers were referred to the Congenital Disease Center of our hospital. When CL/P is suspected in the prenatal ultrasound screening examination, the pregnant woman is referred to our center for further evaluation.ResultsThe abortion rate was 28% (3/11. The concordance rate of the sonographic and final diagnoses was 100%. Ten women (91% reported that they were satisfied with the multidisciplinary management in our center.ConclusionsAlthough a child with a birth defect is unlikely to be received well, the women whose fetuses were diagnosed with CL/P on prenatal ultrasound screening and who underwent multidisciplinary team management were more likely to decide to continue their pregnancy.

Hydroclimatic variability in loess δDwax records from the central Chinese Loess Plateau over the past 250 ka

Science.gov (United States)

Wang, Zheng; An, Zhisheng; Liu, Zhonghui; Qiang, Xiaoke; Zhang, Fan; Liu, Weiguo

2018-04-01

This study reports hydrogen isotopic records from the central Chinese Loess Plateau (CLP) over the past 250 ka. After eliminating the influence of ice and local temperatures, the δDwax records extracted from two loess sites at Xifeng and Luochuan can be taken to represent arid/humid alternations in the hydrological environment in this marginal Asian Summer Monsoon (ASM) region; they also contain integrated information on summer precipitation patterns and the corresponding responses to these changes by predominant vegetation cover types. These arid/humid alternations show 100 ka, 40 ka and 20 ka cycles. An increase in precipitation in association with an enhanced summer monsoon has historically been taken to be the major factor driving a humid environment in the central CLP. However, hydroclimatic changes in δDwax records differ for the central CLP, central China and southern China. Over a 20 ka cycle, the influence of solar insolation on hydroclimatic changes can be shown to be consistent throughout the central CLP. However, changes in the relative location of the land and sea may have caused different hydroclimatic responses between southern China and the central CLP on a glacial-interglacial scale. The hydroclimatic variability in the central CLP would suggest that an enhanced summer monsoon due to climatic warming is the key to understanding decreased drought degree in this marginal monsoonal region.

Association between maternal smoking, gender, and cleft lip and palate

Directory of Open Access Journals (Sweden)

Daniella Reis Barbosa Martelli

2015-10-01

Full Text Available ABSTRACT INTRODUCTION: Cleft lip and/or palate (CL/P represent the most common congenital anomalies of the face. OBJECTIVE: To assess the relationship between maternal smoking, gender and CL/P. METHODS: This is an epidemiological cross-sectional study. We interviewed 1519 mothers divided into two groups: Cases: mothers of children with CL/P (n = 843 and Controls: mothers of children without CL/P (n = 676. All mothers were classified as smoker or non-smoker subjects during the first trimester of pregnancy. To determine an association among maternal smoking, gender, and CL/P, odds ratios were calculated and the adjustment was made by a logistic regression model. RESULTS: An association between maternal smoking and the presence of cleft was observed. There was also a strong association between male gender and the presence of cleft (OR = 3.51; 95% CI 2.83-4.37. By binary logistic regression analysis, it was demonstrated that both variables were independently associated with clefts. In a multivariate analysis, male gender and maternal smoking had a 2.5- and a 1.5-time greater chance of having a cleft, respectively. CONCLUSION: Our findings are consistent with a positive association between maternal smoking during pregnancy and CL/P in male gender. The results support the importance of smoking prevention and introduction of cessation programs among women with childbearing potential.

Electrical Stimulation at the ST36 Acupoint Protects against Sepsis Lethality and Reduces Serum TNF Levels through Vagus Nerve- and Catecholamine-Dependent Mechanisms

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Albino Villegas-Bastida

2014-01-01

Full Text Available Electrical vagus nerve (VN stimulation during sepsis attenuates tumor necrosis factor (TNF production through the cholinergic anti-inflammatory pathway, which depends on the integrity of the VN and catecholamine production. To characterize the effect of electroacupuncture at ST36 (EA-ST36 on serum TNF, IL-6, nitrite, and HMGB1 levels and survival rates, based on VN integrity and catecholamine production, a sepsis model was induced in rats using cecal ligation and puncture (CLP. The septic rats were subsequently treated with EA-ST36 (CLP+ST36, and serum samples were collected and analyzed for cytokines levels. The serum TNF, IL-6, nitrite, and HMGB1 levels in the CLP+ST36 group were significantly lower compared with the group without treatment, the survival rates were significantly higher (P<0.05, and the acute organ injury induced by CLP was mitigated by EA-ST36; however, when subdiaphragmatic vagotomy was performed, the serum levels of TNF in the CLP+ST36 group did not show a significant difference compared with the group without electrostimulation, and, similarly, no significant difference in serum TNF levels was found under the pharmacological blockade of catecholamines. These results suggest that in rats with CLP sepsis models EA-ST36 reduces serum TNF levels through VN- and atecholamine-dependent mechanisms.

Construction of a global pain systems network highlights phospholipid signaling as a regulator of heat nociception.

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G Gregory Neely

Full Text Available The ability to perceive noxious stimuli is critical for an animal's survival in the face of environmental danger, and thus pain perception is likely to be under stringent evolutionary pressure. Using a neuronal-specific RNAi knock-down strategy in adult Drosophila, we recently completed a genome-wide functional annotation of heat nociception that allowed us to identify α2δ3 as a novel pain gene. Here we report construction of an evolutionary-conserved, system-level, global molecular pain network map. Our systems map is markedly enriched for multiple genes associated with human pain and predicts a plethora of novel candidate pain pathways. One central node of this pain network is phospholipid signaling, which has been implicated before in pain processing. To further investigate the role of phospholipid signaling in mammalian heat pain perception, we analysed the phenotype of PIP5Kα and PI3Kγ mutant mice. Intriguingly, both of these mice exhibit pronounced hypersensitivity to noxious heat and capsaicin-induced pain, which directly mapped through PI3Kγ kinase-dead knock-in mice to PI3Kγ lipid kinase activity. Using single primary sensory neuron recording, PI3Kγ function was mechanistically linked to a negative regulation of TRPV1 channel transduction. Our data provide a systems map for heat nociception and reinforces the extraordinary conservation of molecular mechanisms of nociception across different species.

Construction of a Global Pain Systems Network Highlights Phospholipid Signaling as a Regulator of Heat Nociception

Science.gov (United States)

Mair, Norbert; Racz, Ildiko; Milinkeviciute, Giedre; Meixner, Arabella; Nayanala, Swetha; Griffin, Robert S.; Belfer, Inna; Dai, Feng; Smith, Shad; Diatchenko, Luda; Marengo, Stefano; Haubner, Bernhard J.; Novatchkova, Maria; Gibson, Dustin; Maixner, William; Pospisilik, J. Andrew; Hirsch, Emilio; Whishaw, Ian Q.; Zimmer, Andreas; Gupta, Vaijayanti; Sasaki, Junko; Kanaho, Yasunori; Sasaki, Takehiko; Kress, Michaela; Woolf, Clifford J.; Penninger, Josef M.

2012-01-01

The ability to perceive noxious stimuli is critical for an animal's survival in the face of environmental danger, and thus pain perception is likely to be under stringent evolutionary pressure. Using a neuronal-specific RNAi knock-down strategy in adult Drosophila, we recently completed a genome-wide functional annotation of heat nociception that allowed us to identify α2δ3 as a novel pain gene. Here we report construction of an evolutionary-conserved, system-level, global molecular pain network map. Our systems map is markedly enriched for multiple genes associated with human pain and predicts a plethora of novel candidate pain pathways. One central node of this pain network is phospholipid signaling, which has been implicated before in pain processing. To further investigate the role of phospholipid signaling in mammalian heat pain perception, we analysed the phenotype of PIP5Kα and PI3Kγ mutant mice. Intriguingly, both of these mice exhibit pronounced hypersensitivity to noxious heat and capsaicin-induced pain, which directly mapped through PI3Kγ kinase-dead knock-in mice to PI3Kγ lipid kinase activity. Using single primary sensory neuron recording, PI3Kγ function was mechanistically linked to a negative regulation of TRPV1 channel transduction. Our data provide a systems map for heat nociception and reinforces the extraordinary conservation of molecular mechanisms of nociception across different species. PMID:23236288

The impact of chronic mild stress on long-term depressive behavior in rats which have survived sepsis.

Science.gov (United States)

Steckert, Amanda V; Dominguini, Diogo; Michels, Monique; Abelaira, Helena M; Tomaz, Débora B; Sonai, Beatriz; de Moura, Airam B; Matos, Danyela; da Silva, Júlia B I; Réus, Gislaine Z; Barichello, Tatiana; Quevedo, João; Dal-Pizzol, Felipe

2017-11-01

The present study was created to investigate the effects of chronic mild stress (CMS) on the depressive behavior and neurochemical parameters of rats that were subjected to sepsis. Wistar rats were subjected to a CMS protocol, and sepsis was induced by cecal ligation and perforation (CLP). The animals were then divided into 4 separate groups; Control + Sham (n = 20), Control + CLP (n = 30), CMS + Sham (n = 20) and CMS + CLP (n = 30). Body weight, food and water intake and mortality were measured on a daily basis for a period of 10 days after the induction of sepsis. Locomotor activity, splash and forced swimming tests were performed ten days after CLP. At the end of the test period, the animals were euthanized, and the prefrontal cortex and hippocampus were removed to determine the levels of cytokines and oxidative damage. Our results show that there was no significant interaction between CMS and CLP in relation to locomotor activity and the forced swimming test. However, we did observe a significant decrease in total grooming time in the Control + CLP and CMS + Sham groups, with the CMS + CLP group showing behavior similar to that of the control animals. This was found to be related to a decrease in the levels of brain cytokines, and not to oxidative damage parameters. Collectively, our results suggest that a previous stress caused by CMS can protect the brain against the systemic acute and severe stress elicited by sepsis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Regulation of Adult CNS Axonal Regeneration by the Post-transcriptional Regulator Cpeb1

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Wilson Pak-Kin Lou

2018-01-01

Full Text Available Adult mammalian central nervous system (CNS neurons are unable to regenerate following axonal injury, leading to permanent functional impairments. Yet, the reasons underlying this regeneration failure are not fully understood. Here, we studied the transcriptome and translatome shortly after spinal cord injury. Profiling of the total and ribosome-bound RNA in injured and naïve spinal cords identified a substantial post-transcriptional regulation of gene expression. In particular, transcripts associated with nervous system development were down-regulated in the total RNA fraction while remaining stably loaded onto ribosomes. Interestingly, motif association analysis of post-transcriptionally regulated transcripts identified the cytoplasmic polyadenylation element (CPE as enriched in a subset of these transcripts that was more resistant to injury-induced reduction at the transcriptome level. Modulation of these transcripts by overexpression of the CPE binding protein, Cpeb1, in mouse and Drosophila CNS neurons promoted axonal regeneration following injury. Our study uncovered a global evolutionarily conserved post-transcriptional mechanism enhancing regeneration of injured CNS axons.

Evolving Role of the Power Sector Regulator: A Clean Energy Regulators Initiative Report

Energy Technology Data Exchange (ETDEWEB)

Zinaman, O.; Miller, M.; Bazilian, M.

2014-04-01

This paper seeks to briefly characterize the evolving role of power sector regulation. Given current global dynamics, regulation of the power sector is undergoing dramatic changes. This transformation is being driven by various factors including technological advances and cost reductions in renewable energy, energy efficiency, and demand management; increasing air pollution and climate change concerns; and persistent pressure for ensuring sustainable economic development and increased access to energy services by the poor. These issues add to the already complex task of power sector regulation, of which the fundamental remit remains to objectively and transparently ensure least-cost service delivery at high quality. While no single regulatory task is trivial to undertake, it is the prioritization and harmonization of a multitude of objectives that exemplifies the essential challenge of power sector regulation. Evolving regulatory roles can be understood through the concept of existing objectives and an additional layer of emerging objectives. Following this categorization, we describe seven existing objectives of power sector regulators and nine emerging objectives, highlighting key challenges and outlining interdependencies. This essay serves as a preliminary installment in the Clean Energy Regulatory Initiative (CERI) series, and aims to lay the groundwork for subsequent reports and case studies that will explore these topics in more depth.

Diminished responsiveness to dobutamine as an inotrope in mice with cecal ligation and puncture-induced sepsis: attribution to phosphodiesterase 4 upregulation.

Science.gov (United States)

Sakai, Mari; Suzuki, Tokiko; Tomita, Kengo; Yamashita, Shigeyuki; Palikhe, Sailesh; Hattori, Kohshi; Yoshimura, Naoki; Matsuda, Naoyuki; Hattori, Yuichi

2017-06-01

Dobutamine has been used in septic shock for many years as an only inotrope, but its benefit has been questioned. We weighed the effects of dobutamine and milrinone as inotropes in mice with cecal ligation and puncture (CLP)-induced polymicrobial sepsis. CLP-induced septic mice exhibited significant cardiac inflammation, as indicated by greatly increased mRNAs of proinflammatory cytokines and robust infiltration of inflammatory cells in the ventricular myocardium. Elevations of plasma cardiac troponin-I showed cardiac injury in CLP mice. Noninvasive echocardiographic assessment of cardiac function revealed that despite preserved left ventricular function in the presence of fluid replacement, the dobutamine inotropic response was significantly impaired in CLP mice compared with sham-operated controls. By contrast, milrinone exerted inotropic effects in sham-operated and CLP mice in an equally effective manner. Surface expression levels of β 1 -adrenoceptors and α-subunits of three main G protein families in the myocardium were unaffected by CLP-induced sepsis. Plasma cAMP levels were significantly elevated in both sham-operated and CLP mice in response to milrinone but only in sham-operated controls in response to dobutamine. Of phosphodiesterase (PDE) isoforms, PDE4D, but not PDE3A, both of which are responsible for cardiac cAMP hydrolysis, was significantly upregulated in CLP mouse myocardium. We define a novel mechanism for the impaired responsiveness to dobutamine as an inotrope in sepsis, and understanding the role of PDE4D in modulating cardiac functional responsiveness in sepsis may open the potential of a PDE4D-targeted therapeutic option in septic patients with low cardiac output who have a need for inotropic support. NEW & NOTEWORTHY Advisability of the usefulness of dobutamine in septic shock management is limited. Here, we reveal that the effect of dobutamine as a positive inotrope is impaired in mice with cecal ligation and puncture-induced sepsis

Globalisation of tobacco industry influence and new global responses

Science.gov (United States)

Yach, D.; Bettcher, D.

2000-01-01

The globalisation of tobacco marketing, trade, research, and industry influence represents a major threat to public health worldwide. Drawing upon tobacco industry strategy documents prepared over several decades, this paper will demonstrate how the tobacco industry operates as a global force, regarding the world as its operating market by planning, developing, and marketing its products on a global scale. The industry has used a wide range of methods to buy influence and power, and penetrate markets across the world. It has an annual turnover of almost US$400 billion. In contrast, until recently tobacco control lacked global leadership and strategic direction and had been severely underfunded. As part of moving towards a more sustainable form of globalisation, a global enabling environment linked to local actions should focus on the following strategies: global information management; development of nationally and locally grounded action; global regulation, legal instruments, and foreign policy; and establishment of strong partnerships with purpose. As the vector of the tobacco epidemic, the tobacco industry's actions fall far outside of the boundaries of global corporate responsibility. Therefore, global and local actions should not provide the tobacco industry with the two things that it needs to ensure its long term profitability: respectability and predictability.


Keywords: globalisation of tobacco marketing PMID:10841858

Counteraction of Oxidative Stress by Vitamin E Affects Epigenetic Regulation by Increasing Global Methylation and Gene Expression of MLH1 and DNMT1 Dose Dependently in Caco-2 Cells

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Katja Zappe

2018-01-01

Full Text Available Obesity- or diabetes-induced oxidative stress is discussed as a major risk factor for DNA damage. Vitamin E and many polyphenols exhibit antioxidative activities with consequences on epigenetic regulation of inflammation and DNA repair. The present study investigated the counteraction of oxidative stress by vitamin E in the colorectal cancer cell line Caco-2 under normal (1 g/l and high (4.5 g/l glucose cell culture condition. Malondialdehyde (MDA as a surrogate marker of lipid peroxidation and reactive oxygen species (ROS was analyzed. Gene expression and promoter methylation of the DNA repair gene MutL homolog 1 (MLH1 and the DNA methyltransferase 1 (DNMT1 as well as global methylation by LINE-1 were investigated. Results revealed a dose-dependent counteracting effect of vitamin E on H2O2-induced oxidative stress. Thereby, 10 μM vitamin E proved to be more efficient than did 50 μM in reducing MDA. Further, an induction of MLH1 and DNMT1 gene expression was noticed, accompanied by an increase in global methylation. Whether LINE-1 hypomethylation is a cause or effect of oxidative stress is still unclear. In conclusion, supplementation of exogenous antioxidants like vitamin E in vitro exhibits beneficial effects concerning oxidative stress as well as epigenetic regulation involved in DNA repair.

AFSC/ABL: Global Ocean Ecosystems Dynamics (GLOBEC) fish and oceanography data

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Understanding the processes that regulate early marine survival of salmon is a major goal of the Global Ocean Ecosystems Dynamics (GLOBEC) Northeast Pacific (NEP)...

Diverse Regulators of Human Ribosome Biogenesis Discovered by Changes in Nucleolar Number

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Katherine I. Farley-Barnes

2018-02-01

Full Text Available Ribosome biogenesis is a highly regulated, essential cellular process. Although studies in yeast have established some of the biological principles of ribosome biogenesis, many of the intricacies of its regulation in higher eukaryotes remain unknown. To understand how ribosome biogenesis is globally integrated in human cells, we conducted a genome-wide siRNA screen for regulators of nucleolar number. We found 139 proteins whose depletion changed the number of nucleoli per nucleus from 2–3 to only 1 in human MCF10A cells. Follow-up analyses on 20 hits found many (90% to be essential for the nucleolar functions of rDNA transcription (7, pre-ribosomal RNA (pre-rRNA processing (16, and/or global protein synthesis (14. This genome-wide analysis exploits the relationship between nucleolar number and function to discover diverse cellular pathways that regulate the making of ribosomes and paves the way for further exploration of the links between ribosome biogenesis and human disease.

Development of methods and means to improve the financial monitoring system

International Nuclear Information System (INIS)

Spiridonov, A.M.

2011-01-01

The paper discusses the ways of enhancing the effectiveness of National system of financial monitoring, or Russian national system of counteraction to legalization (laundering) of proceeds from crime and financing of terrorism (NS CLP/FT). The author suggests that to achieve this goal it is necessary to solve the following main objectives: to study the current state of the NS CLP/FT, and to build its structural and functional models, to determine the criteria of efficiency of the system, to develop a methodology to assess the effectiveness of the NS CLP/FT, to apply it and to identify promising trends of this system development. On the basis of the obtained data, it is proposed to develop a means of increasing the effectiveness of the NS CLP/FT [ru

A global picture of pharmacy technician and other pharmacy support workforce cadres.

Science.gov (United States)

Koehler, Tamara; Brown, Andrew

Understanding how pharmacy technicians and other pharmacy support workforce cadres assist pharmacists in the healthcare system will facilitate developing health systems with the ability to achieve universal health coverage as it is defined in different country contexts. The aim of this paper is to provide an overview of the present global variety in the technician and other pharmacy support workforce cadres considering; their scope, roles, supervision, education and legal framework. A structured online survey instrument was administered globally using the Survey Monkey platform, designed to address the following topic areas: roles, responsibilities, supervision, education and legislation. The survey was circulated to International Pharmaceutical Federation (FIP) member organisations and a variety of global list serves where pharmaceutical services are discussed. 193 entries from 67 countries and territories were included in the final analysis revealing a vast global variety with respect to the pharmacy support workforce. From no pharmacy technicians or other pharmacy support workforce cadres in Japan, through a variety of cadre interactions with pharmacists, to the autonomous practice of pharmacy support workforce cadres in Malawi. From strictly supervised practice with a focus on supply, through autonomous practice for a variety of responsibilities, to independent practice. From complete supervision for all tasks, through geographical varied supervision, to independent practice. From on the job training, through certificate level vocational courses, to 3-4 year diploma programs. From well-regulated and registered, through part regulation with weak implementation, to completely non-regulated contexts. This paper documents wide differences in supervision requirements, education systems and supportive legislation for pharmacy support workforce cadres globally. A more detailed understanding of specific country practice settings is required if the use of pharmacy

Filling some black holes: modeling the connection between urbanization, infrastructure, and global service intensity

OpenAIRE

Van De Vijver, Elien; Derudder, Ben; Bassens, David; Witlox, Frank

2014-01-01

This empirical article combines insights from previous research on the level of knowledge-intensive service in metropolitan areas with the aim to develop an understanding of the spatial structure of the global service economy. We use a stepwise regression model with the Globalization and World Cities research network's measure of globalized service provisioning as the dependent variable and a range of variables focusing on population, infrastructure, urban primacy, and national regulation as ...

Globalizing animal care and use: making the dream a reality

Science.gov (United States)

Bielitzki, J. T.

1999-01-01

What will drive the globalization of animal care in the 21st century? Will targeted concerns from privately funded groups be the motivating factors? Will the threat of disease, and the concomitant hue and cry from a threatened public, be responsible for bringing nations together to collaborate on rules and regulations? The author, who is responsible for the animal use protocols on NASA's space station, explains why globalization on Planet Earth may be guided by what happens in outer space.

Global Analysis of RNA Secondary Structure in Two Metazoans

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Fan Li

2012-01-01

Full Text Available The secondary structure of RNA is necessary for its maturation, regulation, processing, and function. However, the global influence of RNA folding in eukaryotes is still unclear. Here, we use a high-throughput, sequencing-based, structure-mapping approach to identify the paired (double-stranded RNA [dsRNA] and unpaired (single-stranded RNA [ssRNA] components of the Drosophila melanogaster and Caenorhabditis elegans transcriptomes, which allows us to identify conserved features of RNA secondary structure in metazoans. From this analysis, we find that ssRNAs and dsRNAs are significantly correlated with specific epigenetic modifications. Additionally, we find key structural patterns across protein-coding transcripts that indicate that RNA folding demarcates regions of protein translation and likely affects microRNA-mediated regulation of mRNAs in animals. Finally, we identify and characterize 546 mRNAs whose folding pattern is significantly correlated between these metazoans, suggesting that their structure has some function. Overall, our findings provide a global assessment of RNA folding in animals.

Simulation analysis of globally integrated logistics and recycling strategies

Energy Technology Data Exchange (ETDEWEB)

Song, S.J.; Hiroshi, K. [Hiroshima Inst. of Tech., Graduate School of Mechanical Systems Engineering, Dept. of In formation and Intelligent Systems Engineering, Hiroshima (Japan)

2004-07-01

This paper focuses on the optimal analysis of world-wide recycling activities associated with managing the logistics and production activities in global manufacturing whose activities stretch across national boundaries. Globally integrated logistics and recycling strategies consist of the home country and two free trading economic blocs, NAFTA and ASEAN, where significant differences are found in production and disassembly cost, tax rates, local content rules and regulations. Moreover an optimal analysis of globally integrated value-chain was developed by applying simulation optimization technique as a decision-making tool. The simulation model was developed and analyzed by using ProModel packages, and the results help to identify some of the appropriate conditions required to make well-performed logistics and recycling plans in world-wide collaborated manufacturing environment. (orig.)

Ethical food standard schemes and global trade

DEFF Research Database (Denmark)

Daugbjerg, Carsten; Botterill, Linda Courtenay

2012-01-01

Global food trade embodies a range of different interpretations of the nature of food and its role in society. On the one hand, the WTO food regulation regime, in particular the SPS agreement, is based upon a somewhat instrumental value of food consumption in which food is seen as a commodity...... base of each institution while giving expression to both materialist and postmaterialist understandings of the nature of food....... to be traded in accordance with international trade rules. At the same time, a number of private standards, such as GlobalG.A.P and various organic standards, are emerging which embody broadly postmaterialist values that suggest that food purchasing and consumption are also social, ethical and perhaps even...

Impaired chromatin remodelling at STAT1-regulated promoters leads to global unresponsiveness of Toxoplasma gondii-infected macrophages to IFN-γ.

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Christine Lang

2012-01-01

Full Text Available Intracellular pathogens including the apicomplexan and opportunistic parasite Toxoplasma gondii profoundly modify their host cells in order to establish infection. We have shown previously that intracellular T. gondii inhibit up-regulation of regulatory and effector functions in murine macrophages (MΦ stimulated with interferon (IFN-γ, which is the cytokine crucial for controlling the parasites' replication. Using genome-wide transcriptome analysis we show herein that infection with T. gondii leads to global unresponsiveness of murine macrophages to IFN-γ. More than 61% and 89% of the transcripts, which were induced or repressed by IFN-γ in non-infected MΦ, respectively, were not altered after stimulation of T. gondii-infected cells with IFN-γ. These genes are involved in a variety of biological processes, which are mostly but not exclusively related to immune responses. Analyses of the underlying mechanisms revealed that IFN-γ-triggered nuclear translocation of STAT1 still occurred in Toxoplasma-infected MΦ. However, STAT1 bound aberrantly to oligonucleotides containing the IFN-γ-responsive gamma-activated site (GAS consensus sequence. Conversely, IFN-γ did not induce formation of active GAS-STAT1 complexes in nuclear extracts from infected MΦ. Mass spectrometry of protein complexes bound to GAS oligonucleotides showed that T. gondii-infected MΦ are unable to recruit non-muscle actin to IFN-γ-responsive DNA sequences, which appeared to be independent of stimulation with IFN-γ and of STAT1 binding. IFN-γ-induced recruitment of BRG-1 and acetylation of core histones at the IFN-γ-regulated CIITA promoter IV, but not β-actin was diminished by >90% in Toxoplasma-infected MΦ as compared to non-infected control cells. Remarkably, treatment with histone deacetylase inhibitors restored the ability of infected macrophages to express the IFN-γ regulated genes H2-A/E and CIITA. Taken together, these results indicate that Toxoplasma

The present effect of global warming on U.S. industry

International Nuclear Information System (INIS)

Bendel, W.B.

1993-01-01

This paper will discuss how global warming issues are currently affecting U.S. industry. Global climate models are projecting global temperature increases in the 1.5-4.5 degrees C range within the next 50-60 years. This increase is based on the assumption that CO 2 emissions into the atmosphere will continue to increase 1-2% per year, resulting in a doubling of preindustrial CO 2 levels by mid twenty-first century. These projections may cause U.S. industry to readjust its thinking with respect to the benefits of pollution prevention as they relate to global warming, corporate image enhancement, global competitiveness and risk assessment or balance. Real or perceived impacts of global warming are already influencing U.S. competitiveness within the global economy because Japan and the European countries are taking the global warming threat more seriously than is the U.S. Mitigation of CO 2 emissions through carbon taxes or permitting will be discussed. Options available to U.S. industry to deal with the current uncertainties of global warming will be presented. Examples of how specific companies are coping with this issue will be given. Finally, recommendations are presented for proactive planning to determine which segments, divisions or facilities in a multinational company would be most sensitive to CO 2 stabilization regulations

Regulation of mRNA translation during mitosis.

Science.gov (United States)

Tanenbaum, Marvin E; Stern-Ginossar, Noam; Weissman, Jonathan S; Vale, Ronald D

2015-08-25

Passage through mitosis is driven by precisely-timed changes in transcriptional regulation and protein degradation. However, the importance of translational regulation during mitosis remains poorly understood. Here, using ribosome profiling, we find both a global translational repression and identified ~200 mRNAs that undergo specific translational regulation at mitotic entry. In contrast, few changes in mRNA abundance are observed, indicating that regulation of translation is the primary mechanism of modulating protein expression during mitosis. Interestingly, 91% of the mRNAs that undergo gene-specific regulation in mitosis are translationally repressed, rather than activated. One of the most pronounced translationally-repressed genes is Emi1, an inhibitor of the anaphase promoting complex (APC) which is degraded during mitosis. We show that full APC activation requires translational repression of Emi1 in addition to its degradation. These results identify gene-specific translational repression as a means of controlling the mitotic proteome, which may complement post-translational mechanisms for inactivating protein function.

Hazardous substances in electronics: the effects of European Union risk regulation on China

NARCIS (Netherlands)

Biedenkopf, K.

2012-01-01

This article argues that European Union (EU) risk regulation of hazardous substances in electrical and electronic equipment (EEE) was both a trigger and formative factor in the development of similar Chinese regulation. The attractiveness and global interdependence of the EU market in EEE impelled a

Regulatory Competition in Global Financial Markets

DEFF Research Database (Denmark)

Ringe, Georg

2016-01-01

Regulatory arbitrage in financial markets refers to a number of strategies that market participants use to avoid the reach of regulation, in particular by virtue of moving trading abroad or relocating activities or operations of financial institutions to other jurisdictions. Where this happens...... institutions' excessive risk-taking. If such risk-taking would be judged by market discipline instead of posing a risk to global financial stability, the main downside of regulatory competition could be restrained. Within the boundaries of such a system, competition could then operate and contribute...... their standards solely to attract business and thereby impose externalities on the worldwide financial market by undermining financial stability as a global public good. Policymakers worldwide are experimenting with remedies to respond to the phenomenon. I introduce the importance of an effective special...

A direct link between the global regulator PhoP and the Csr regulon in Y. pseudotuberculosis through the small regulatory RNA CsrC.

Science.gov (United States)

Nuss, Aaron M; Schuster, Franziska; Kathrin Heroven, Ann; Heine, Wiebke; Pisano, Fabio; Dersch, Petra

2014-01-01

In this study we investigated the influence of the global response regulator PhoP on the complex regulatory cascade controlling expression of early stage virulence genes of Yersinia pseudotuberculosis via the virulence regulator RovA. Our analysis revealed the following novel features: (1) PhoP activates expression of the CsrC RNA in Y. pseudotuberculosis, leading to activation of RovA synthesis through the CsrABC-RovM cascade, (2) activation of csrC transcription is direct and PhoP is shown to bind to two separate PhoP box-like sites, (3) PhoP-mediated activation results in transcription from two different promoters closely downstream of the PhoP binding sites, leading to two distinct CsrC RNAs, and (4) the stability of the CsrC RNAs differs significantly between the Y. pseudotuberculosis strains YPIII and IP32953 due to a 20 nucleotides insertion in CsrC(IP32953), which renders the transcript more susceptible to degradation. In summary, our study showed that PhoP-mediated influence on the regulatory cascade controlling the Csr system and RovA in Y. pseudotuberculosis varies within the species, suggesting that the Csr system is a focal point to readjust and adapt the genus to different hosts and reservoirs.

Agricultural insecticides threaten surface waters at the global scale.

Science.gov (United States)

Stehle, Sebastian; Schulz, Ralf

2015-05-05

Compared with nutrient levels and habitat degradation, the importance of agricultural pesticides in surface water may have been underestimated due to a lack of comprehensive quantitative analysis. Increasing pesticide contamination results in decreasing regional aquatic biodiversity, i.e., macroinvertebrate family richness is reduced by ∼30% at pesticide concentrations equaling the legally accepted regulatory threshold levels (RTLs). This study provides a comprehensive metaanalysis of 838 peer-reviewed studies (>2,500 sites in 73 countries) that evaluates, for the first time to our knowledge on a global scale, the exposure of surface waters to particularly toxic agricultural insecticides. We tested whether measured insecticide concentrations (MICs; i.e., quantified insecticide concentrations) exceed their RTLs and how risks depend on insecticide development over time and stringency of environmental regulation. Our analysis reveals that MICs occur rarely (i.e., an estimated 97.4% of analyses conducted found no MICs) and there is a complete lack of scientific monitoring data for ∼90% of global cropland. Most importantly, of the 11,300 MICs, 52.4% (5,915 cases; 68.5% of the sites) exceeded the RTL for either surface water (RTLSW) or sediments. Thus, the biological integrity of global water resources is at a substantial risk. RTLSW exceedances depend on the catchment size, sampling regime, and sampling date; are significantly higher for newer-generation insecticides (i.e., pyrethroids); and are high even in countries with stringent environmental regulations. These results suggest the need for worldwide improvements to current pesticide regulations and agricultural pesticide application practices and for intensified research efforts on the presence and effects of pesticides under real-world conditions.

Liquidity regulation and the implementation of monetary policy

OpenAIRE

Morten L. Bech; Todd Keister

2013-01-01

In addition to revamping existing rules for bank capital, Basel III introduces a new global framework for liquidity regulation. One part of this framework is the liquidity coverage ratio (LCR), which requires banks to hold sufficient high-quality liquid assets to survive a 30-day period of market stress. As monetary policy typically involves targeting the interest rate on loans of one of these assets — central bank reserves — it is important to understand how this regulation may impact the ef...

An increase in CD3+CD4+CD25+ regulatory T cells after administration of umbilical cord-derived mesenchymal stem cells during sepsis.

Directory of Open Access Journals (Sweden)

Yu-Hua Chao

Full Text Available Sepsis remains an important cause of death worldwide, and vigorous immune responses during sepsis could be beneficial for bacterial clearance but at the price of collateral damage to self tissues. Mesenchymal stem cells (MSCs have been found to modulate the immune system and attenuate sepsis. In the present study, MSCs derived from bone marrow and umbilical cord were used and compared. With a cecal ligation and puncture (CLP model, the mechanisms of MSC-mediated immunoregulation during sepsis were studied by determining the changes of circulating inflammation-associated cytokine profiles and peripheral blood mononuclear cells 18 hours after CLP-induced sepsis. In vitro, bone marrow-derived MSCs (BMMSCs and umbilical cord-derived MSCs (UCMSCs showed a similar morphology and surface marker expression. UCMSCs had stronger potential for osteogenesis but lower for adipogenesis than BMMSCs. Compared with rats receiving PBS only after CLP, the percentage of circulating CD3+CD4+CD25+ regulatory T (Treg cells and the ratio of Treg cells/T cells were elevated significantly in rats receiving MSCs. Further experiment regarding Treg cell function demonstrated that the immunosuppressive capacity of Treg cells from rats with CLP-induced sepsis was decreased, but could be restored by administration of MSCs. Compared with rats receiving PBS only after CLP, serum levels of interleukin-6 and tumor necrosis factor-α were significantly lower in rats receiving MSCs after CLP. There were no differences between BMMSCs and UCMSCs. In summary, this work provides the first in vivo evidence that administering BMMSCs or UCMSCs to rats with CLP-induced sepsis could increase circulating CD3+CD4+CD25+ Treg cells and Treg cells/T cells ratio, enhance Treg cell suppressive function, and decrease serum levels of interleukin-6 and tumor necrosis factor-α, suggesting the immunomodulatory association of Treg cells and MSCs during sepsis.

Opportunities and Challenges in Establishing a Cohort Study: An Example From Cleft Lip/Palate Research in the United Kingdom.

Science.gov (United States)

Stock, Nicola Marie; Humphries, Kerry; Pourcain, Beate St; Bailey, Maggie; Persson, Martin; Ho, Karen M; Ring, Susan; Marsh, Cathy; Albery, Liz; Rumsey, Nichola; Sandy, Jonathan

2016-05-01

Cleft lip and/or palate (CL/P) is one of the most common birth conditions in the world, but little is known about its causes. Professional opinion remains divided as to which treatments may be the most beneficial for patients with CL/P, and the factors that contribute to psychological adjustment are poorly understood. The use of different methodological approaches and tools plays a key role in hampering efforts to address discrepancies within the evidence base. A new UK-wide program of research, The Cleft Collective, was established to combat many of these methodological challenges and to address some of the key research questions important to all CL/P stakeholders. To describe the establishment of CL/P cohort studies in the United Kingdom and to consider the many opportunities this resource will generate. To date, protocols have been developed and implemented within most UK cleft teams. Biological samples, environmental information, and data pertaining to parental psychological well-being and child development are being collected successfully. Recruitment is currently on track to meet the ambitious target of approximately 9800 individuals from just more than 3000 families. The Cleft Collective cohort studies represent a significant step forward for research in the field of CL/P. The data collected will form a comprehensive resource of information about individuals with CL/P and their families. This resource will provide the basis for many future projects and collaborations, both in the United Kingdom and around the world.

A Population-Based Exploration of the Social Implications Associated with Cleft Lip and/or Palate.

Science.gov (United States)

Glener, Adam D; Allori, Alexander C; Shammas, Ronnie L; Carlson, Anna R; Pien, Irene J; Aylsworth, Arthur S; Meyer, Robert; Pimenta, Luiz; Strauss, Ronald; Watkins, Stephanie; Marcus, Jeffrey R

2017-06-01

Clefts of the lip and/or palate (CL/P) carry a social stigma that often causes psychosocial stress. The purpose of this study was to consider the association of cleft phenotype and age with self-reported aspects of psychosocial stress. Children with nonsyndromic CL/P and unaffected children born between 1997 and 2003 were identified through the North Carolina Birth Defects Monitoring Program and North Carolina birth records, respectively. The psychosocial concerns of children with CL/P were assessed via a 29-question subset of a larger survey. Responses were analyzed according to school age and cleft phenotype (cleft lip with/without cleft alveolus, CL ± A; cleft palate only, CP; or cleft lip with cleft palate, CL + P). Surveys were returned for 176 children with CL/P and 333 unaffected children. When compared with unaffected children, responses differed for CL ± A in 4/29 questions, for CP in 7/29 questions, and for CL + P in 8/29 questions ( P aesthetic concerns, bullying, and difficulties with friendship, and social interaction. Children with CL + P reported more severe aesthetic-related concerns than children with CL ± A or CP but experienced similar speech-related distress as children with CP only. Social implications associated with CL/P are most pronounced during middle school, and less so during elementary and high school. This information identifies areas of social improvement aimed at reducing the stigma of CL/P.

Nonsyndromic cleft lip with or without cleft palate: Evidence of linkage to BCL3 in 17 multigenerational families

Energy Technology Data Exchange (ETDEWEB)

Stein, J.; Hecht, T. [Univ. of Texas, Houston, TX (United States); Stal, S. [Texas Children`s Hospital, Houston, TX (United States)] [and others

1995-08-01

Nonsyndromic cleft lip with or without cleft palate (CL/P) is a common craniofacial developmental defect. Recent segregation analyses have suggested that major genes play a role in the etiology of CL/P. Linkage to 22 candidate genes was tested in 11 multigenerational families with CL/P, and 21 of these candidates were excluded. APOC2, 19q13.1, which is linked to the proto-oncogene BCL3, gave suggestive evidence for linkage to CL/P. The study was expanded to include a total of 39 multigenerational CL/P families. Linkage was tested in all families, using anonymous marker, D19S178, and intragenic markers in BCL3 and APOC2. Linkage was tested under two models, autosomal dominant with reduced penetrance and affecteds-only model. Both models showed evidence of heterogeneity, with 43% of families linked at zero recombination to BCL3 when marker data from BCL3 and APOC2 were included. A maximum multipoint LOD score of 7.00 at BCL3 was found among the 17 families that had posterior probabilities {ge}50% in favor of linkage. The transmission disequilibrium test provided additional evidence for linkage with the 3 allele of BCL3 more often transmitted to affected children. These results suggest that BCL3, or a nearby gene, plays a role in the etiology of CL/P in some families. 39 refs., 8 figs., 4 tabs.

Association between maternal smoking, gender, and cleft lip and palate.

Science.gov (United States)

Martelli, Daniella Reis Barbosa; Coletta, Ricardo D; Oliveira, Eduardo A; Swerts, Mário Sérgio Oliveira; Rodrigues, Laíse A Mendes; Oliveira, Maria Christina; Martelli Júnior, Hercílio

2015-01-01

Cleft lip and/or palate (CL/P) represent the most common congenital anomalies of the face. To assess the relationship between maternal smoking, gender and CL/P. This is an epidemiological cross-sectional study. We interviewed 1519 mothers divided into two groups: mothers of children with CL/P (n=843) and mothers of children without CL/P (n=676). All mothers were classified as smoker or non-smoker subjects during the first trimester of pregnancy. To determine an association among maternal smoking, gender, and CL/P, odds ratios were calculated and the adjustment was made by a logistic regression model. An association between maternal smoking and the presence of cleft was observed. There was also a strong association between male gender and the presence of cleft (OR=3.51; 95% CI 2.83-4.37). By binary logistic regression analysis, it was demonstrated that both variables were independently associated with clefts. In a multivariate analysis, male gender and maternal smoking had a 2.5- and a 1.5-time greater chance of having a cleft, respectively. Our findings are consistent with a positive association between maternal smoking during pregnancy and CL/P in male gender. The results support the importance of smoking prevention and introduction of cessation programs among women with childbearing potential. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

THREE-DIMENSIONAL ASSESSMENT OF THE PHARYNGEAL AIRWAY AND MAXILLARY SINUS VOLUMES IN INDIVIDUALS WITH NON-SYNDROMIC CLEFT LIP AND PALATE

Directory of Open Access Journals (Sweden)

Ana NEMȚOI

2015-09-01

Full Text Available Introduction: Children with cleft lip and palate (CLP are known to have airway problems. Introduction of ConeBeam CT (CBCT and imaging software has facilitated generation of 3D images for assessing the volume of maxillary sinuses and pharyngeal airway. Consequently, the present study aimed at evaluating and comparing the maxillary sinus and pharyngeal airway volume of patients with cleft lip and palate in healthy patients, using cone beam computed tomography (CBCT images. Materials and method: The sample group included 27 individuals (15 with cleft lip and palate subjects and 12 healthy subjects. The pharyngeal airway and each maxillary sinus were three-dimensionally assessed, segmented and their volume was calculated. A comparison between the right and left sinus was performed by Student t-test, and the differences between the control and cleft groups were calculated using ANOVA. Results: No statistically significant differences were found when the maxillary sinuses volumes from each side were compared (p >0.05. The unilateral CLP patients presented the lowest sinus volume. Individuals with CLP did not exhibit a total airway volume smaller than the nonCLP controls. Conclusions: 3D imaging using CBCT and Romexis software is reliable for assessing maxillary sinus and pharyngeal airway volume. The present study showed that the pharyngeal airway is not compromised in CLP individuals. The unilateral CLP individuals present maxillary sinuses with smaller volumes, no differences being recorded between the cleft and non-cleft side.

Development in the Regulation of Wages and Working Conditions

DEFF Research Database (Denmark)

Høgedahl, Laust Kristian; Jørgensen, Henning

2017-01-01

The Nordic countries are renowned for their high level of unionization and collective bargaining. However, globalization, Europeanization, and an increasing individualization are often pictured as factors suppressing collective regulation. In this article, we look at the developments in the regul...... and in employee awareness, but Danish wage and salary earners also have an interest in extra support in the form of generalization and/or a politically regulated minimum wage....... in the regulation of wages and working conditions from a macro perspective by combing two large crosssectional surveys into a longitudinal study with point of departure in the Danish case. We find that collective bargaining coverage continues to stand surprisingly strong, both in terms of being very widespread...

Current status of presurgical infant orthopaedic treatment for cleft lip and palate patients: A critical review

Directory of Open Access Journals (Sweden)

P Priyanka Niranjane

2014-01-01

Full Text Available Rehabilitation of cleft lip and palate (CLP patients is a challenge for all the concerned members of the cleft team, and various treatment modalities have been attempted to obtain aesthetic results. Presurgical infant orthopaedics (PSIO was introduced to reshape alveolar and nasal segments prior to surgical repair of cleft lip. However, literature reports lot of controversy regarding the use of PSIO in patients with CLP. Evaluation of long-term results of PSIO can provide scientific evidence on the efficacy and usefulness of PSIO in CLP patients. The aim was to assess the scientific evidence on the efficiency of PSIO appliances in patients with CLP and to critically analyse the current status of PSIO. A PubMed search was performed using the terms PSIO, presurgical nasoalveolar moulding and its long-term results and related articles were selected for the review. The documented studies report no beneficial effect of PSIO on maxillary arch dimensions, facial aesthetics and in the subsequent development of dentition and occlusion in CLP patients. Nasal moulding seems to be more beneficial and effective in unilateral cleft lip and palate patients with better long-term results.

Maternal plasma pyridoxal-5'-phosphate concentrations and risk of isolated oral clefts in the Philippines.

Science.gov (United States)

Tamura, Tsunenobu; Munger, Ronald G; Nepomuceno, Buena; Corcoran, Christopher; Cembrano, Joselito; Solon, Florentino

2007-04-01

We report that inadequate vitamin B-6 status of Filipino mothers, assessed by erythrocyte aspartate aminotransferase activity coefficient (EAST-AC), is associated with an increased risk for isolated cleft lip with or without cleft palate (CL/P) in their children. Its association with the status assessed by plasma pyridoxal-5'-phosphate (PLP) concentrations is unknown. In a case-control study in the Philippines including 46 cases (mothers of a child with CL/P) and 392 controls (mothers of an unaffected child), we evaluated the association between the risk for CL/P and maternal vitamin B-6 status assessed by PLP and EAST-AC. The ORs of CL/P were estimated by classifying mothers by PLP (>30, 20-30, and values, compared to those with adequate status by both values. Inadequate vitamin B-6 status assessed by maternal PLP and EAST-AC values independently and both combined was associated with an increased risk for CL/P. The association was highest when both values were considered, suggesting that the measurement of both PLP and EAST-AC provides better assessment of vitamin B-6 status than either measurement alone.

Expression analyses of human cleft palate tissue suggest a role for osteopontin and immune related factors in palatal development

DEFF Research Database (Denmark)

Jakobsen, L.P.; Borup, R.; Vestergaard, J.

2009-01-01

. Moreover, selected differentially expressed genes were analyzed by quantitative RT-PCR, and by immunohistochemical staining of craniofacial tissue from human embryos. Osteopontin (SPP1) and other immune related genes were significantly higher expressed in palate tissue from patients with CLP compared to CP...... and palate (CLP). In order to understand the biological basis in these cleft lip and palate subgroups better we studied the expression profiles in human tissue from patients with CL/P. In each of the CL/P subgroups, samples were obtained from three patients and gene expression analysis was performed...... and immunostaining in palatal shelves against SPP1, chemokine receptor 4 (CXCR4) and serglycin (PRG1) in human embryonic craniofacial tissue were positive, supporting a role for these genes in palatal development. However, gene expression profiles are subject to variations during growth and therefore we recommend...

SAPFLUXNET: towards a global database of sap flow measurements.

Science.gov (United States)

Poyatos, Rafael; Granda, Víctor; Molowny-Horas, Roberto; Mencuccini, Maurizio; Steppe, Kathy; Martínez-Vilalta, Jordi

2016-12-01

Plant transpiration is the main evaporative flux from terrestrial ecosystems; it controls land surface energy balance, determines catchment hydrological responses and influences regional and global climate. Transpiration regulation by plants is a key (and still not completely understood) process that underlies vegetation drought responses and land evaporative fluxes under global change scenarios. Thermometric methods of sap flow measurement have now been widely used to quantify whole-plant and stand transpiration in forests, shrublands and orchards around the world. A large body of research has applied sap flow methods to analyse seasonal and diurnal patterns of transpiration and to quantify their responses to hydroclimatic variability, but syntheses of sap flow data at regional to global scales are extremely rare. Here we present the SAPFLUXNET initiative, aimed at building the first global database of plant-level sap flow measurements. A preliminary metadata survey launched in December 2015 showed an encouraging response by the sap flow community, with sap flow data sets from field studies representing >160 species and >120 globally distributed sites. The main goal of SAPFLUXNET is to analyse the ecological factors driving plant- and stand-level transpiration. SAPFLUXNET will open promising research avenues at an unprecedented global scope, namely: (i) exploring the spatio-temporal variability of plant transpiration and its relationship with plant and stand attributes, (ii) summarizing physiological regulation of transpiration by means of few water-use traits, usable for land surface models, (iii) improving our understanding of the coordination between gas exchange and plant-level traits (e.g., hydraulics) and (iv) analysing the ecological factors controlling stand transpiration and evapotranspiration partitioning. Finally, SAPFLUXNET can provide a benchmark to test models of physiological controls of transpiration, contributing to improve the accuracy of

Coordinated approaches to quantify long-term ecosystem dynamics in response to global change

DEFF Research Database (Denmark)

Liu, Y.; Melillo, J.; Niu, S.

2011-01-01

a coordinated approach that combines long-term, large-scale global change experiments with process studies and modeling. Long-term global change manipulative experiments, especially in high-priority ecosystems such as tropical forests and high-latitude regions, are essential to maximize information gain......Many serious ecosystem consequences of climate change will take decades or even centuries to emerge. Long-term ecological responses to global change are strongly regulated by slow processes, such as changes in species composition, carbon dynamics in soil and by long-lived plants, and accumulation...... to be the most effective strategy to gain the best information on long-term ecosystem dynamics in response to global change....

Understanding the Role of the Master Regulator XYR1 in Trichoderma reesei by Global Transcriptional Analysis

Science.gov (United States)

dos Santos Castro, Lilian; de Paula, Renato G.; Antoniêto, Amanda C. C.; Persinoti, Gabriela F.; Silva-Rocha, Rafael; Silva, Roberto N.

2016-01-01

We defined the role of the transcriptional factor—XYR1—in the filamentous fungus Trichoderma reesei during cellulosic material degradation. In this regard, we performed a global transcriptome analysis using RNA-Seq of the Δxyr1 mutant strain of T. reesei compared with the parental strain QM9414 grown in the presence of cellulose, sophorose, and glucose as sole carbon sources. We found that 5885 genes were expressed differentially under the three tested carbon sources. Of these, 322 genes were upregulated in the presence of cellulose, while 367 and 188 were upregulated in sophorose and glucose, respectively. With respect to genes under the direct regulation of XYR1, 30 and 33 are exclusive to cellulose and sophorose, respectively. The most modulated genes in the Δxyr1 belong to Carbohydrate-Active Enzymes (CAZymes), transcription factors, and transporters families. Moreover, we highlight the downregulation of transporters belonging to the MFS and ABC transporter families. Of these, MFS members were mostly downregulated in the presence of cellulose. In sophorose and glucose, the expression of these transporters was mainly upregulated. Our results revealed that MFS and ABC transporters could be new players in cellulose degradation and their role was shown to be carbon source-dependent. Our findings contribute to a better understanding of the regulatory mechanisms of XYR1 to control cellulase gene expression in T. reesei in the presence of cellulosic material, thereby potentially enhancing its application in several biotechnology fields. PMID:26909077

Dermatoglyphics and Cheiloscopy in the Inheritance of Cleft Lip and Palate: Unraveling the Mystery

Directory of Open Access Journals (Sweden)

Naveen Reddy Admala

2014-01-01

Conclusion: A highly significant correlation was observed in finger prints and lip patterns in parents with CL(P affected children and hence can prove to be an extremely useful screening tool for CL(P and other associated genetic anomalies.

Epigenetic regulation of open chromatin in pluripotent stem cells

Science.gov (United States)

Kobayashi, Hiroshi; Kikyo, Nobuaki

2014-01-01

The recent progress in pluripotent stem cell research has opened new avenues of disease modeling, drug screening, and transplantation of patient-specific tissues that had been unimaginable until a decade ago. The central mechanism underlying pluripotency is epigenetic gene regulation; the majority of cell signaling pathways, both extracellular and cytoplasmic, eventually alter the epigenetic status of their target genes during the process of activating or suppressing the genes to acquire or maintain pluripotency. It has long been thought that the chromatin of pluripotent stem cells is globally open to enable the timely activation of essentially all genes in the genome during differentiation into multiple lineages. The current article reviews descriptive observations and the epigenetic machinery relevant to what is supposed to be globally open chromatin in pluripotent stem cells. This includes microscopic appearance, permissive gene transcription, chromatin remodeling complexes, histone modifications, DNA methylation, noncoding RNAs, dynamic movement of chromatin proteins, nucleosome accessibility and positioning, and long-range chromosomal interactions. Detailed analyses of each element, however, have revealed that the globally open chromatin hypothesis is not necessarily supported by some of the critical experimental evidence, such as genome-wide nucleosome accessibility and nucleosome positioning. Further understanding of the epigenetic gene regulation is expected to determine the true nature of the so-called globally open chromatin in pluripotent stem. PMID:24695097

Identification of transcription factors linked to cell cycle regulation in Arabidopsis

OpenAIRE

Dehghan Nayeri, Fatemeh

2014-01-01

Cell cycle is an essential process in growth and development of living organisms consists of the replication and mitotic phases separated by 2 gap phases; G1 and G2. It is tightly controlled at the molecular level and especially at the level of transcription. Precise regulation of the cell cycle is of central significance for plant growth and development and transcription factors are global regulators of gene expression playing essential roles in cell cycle regulation. This study has uncovere...

An International Model for Antibiotics Regulation.

Science.gov (United States)

Aguirre, Emilie

We face a global antibiotics resistance crisis. Antibiotic drugs are rapidly losing their effectiveness, potentially propelling us toward a post-antibiotic world. The largest use of antibiotics in the world is in food-producing animals. Food producers administer these drugs in routine, low doses—the types of doses that are incidentally the most conducive to breeding antibiotic resistance. In general, individual countries have been too slow to act in regulating misuse and overuse of antibiotics in foodproducing animals. This problem will only worsen with the significant projected growth in meat consumption and production expected in emerging economies in the near future. Although individual countries regulating antibiotics can have important effects, one country alone cannot insulate itself entirely from the effects of antibiotic resistance, nor can one country solve the crisis for itself or for the world. The global nature of the food system and the urgency of the problem require immediate global solutions. Adapting a democratic experimentalist approach at the international level can help achieve this goal. Using an international democratic experimentalist framework in conjunction with the World Organization for Animal Health (OIE) would provide for increased systematized data collection and lead to heightened, scientifically informed OIE standards, enforceable by the World Trade Organization (WTO), which could have a significant impact on the reduction of subtherapeutic use of antibiotics internationally. International democratic experimentalism addresses the global intricacy, time sensitivity, context- and culture-specificity, and knowledgeintensiveness of this problem. By encouraging more countries to experiment to solve this problem, the democratic experimentalist model would help develop a larger database of solutions to enable more meaningful cross-country comparisons across a wider range of contexts. This approach maintains democratic governance and

Genome-wide Analysis of Gene Regulation

DEFF Research Database (Denmark)

Chen, Yun

to protein: through epigenetic modifications, transcription regulators or post-transcriptional controls. The following papers concern several layers of gene regulation with questions answered by different HTS approaches. Genome-wide screening of epigenetic changes by ChIP-seq allowed us to study both spatial...... and temporal alterations of histone modifications (Papers I and II). Coupling the data with machine learning approaches, we established a prediction framework to assess the most informative histone marks as well as their most influential nucleosome positions in predicting the promoter usages. (Papers I...... they regulated or if the sites had global elevated usage rates by multiple TFs. Using RNA-seq, 5’end-seq in combination with depletion of 5’exonuclease as well as nonsensemediated decay (NMD) factors, we systematically analyzed NMD substrates as well as their degradation intermediates in human cells (Paper V...

Caracterização anestésica da nanoemulsão não lipídica de propofol Caracterización anestésica de la nanoemulsión no lipídica de propofol Anesthetic profile of a non-lipid propofol nanoemulsion

Directory of Open Access Journals (Sweden)

Roberto Takashi Sudo

2010-10-01

Full Text Available JUSTIFICATIVA E OBJETIVOS: Uso clínico de formulação lipídica de propofol causa dor durante injeção, reação alérgica e crescimento microbiano. Propofol tem sido reformulado em diferentes apresentações não lipídicas para reduzir os efeitos adversos, mas essas mudanças podem modificar sua farmacocinética e farmacodinâmica. Neste trabalho, investigamos a farmacologia e a toxicologia do propofol lipídico (CLP e da nanoemulsão não lipídica (NLP. MÉTODO: CLP and NLP foram infundidos na veia jugular de ratos sob medida da pressão arterial (PA, frequência cardíaca (FC e frequência respiratória (FR. Ambas as formulações (1% foram infundidas (40 µL.min-1 durante 1 hora. Doses hipnóticas e anestésicas, assim como recuperações, foram determinadas. A dor induzida pelo veículo do CLP e NLP foi comparada por meio da contagem do número de contorções abdominais ("writhing test" após injeção intraperitonial (i.p. em camundongos. Ácido acético (0,6% foi usado como controle positivo. RESULTADOS: As doses hipnóticas e anestésicas com 1% CLP (6,0 ± 1,3 e 17,8 ± 2,6 mg.kg-1, respectivamente e 1% NLP (5,4 ± 1,0 e 16,0 ± 1,4 mg.kg-1, respectivamente não foram significativamente diferentes. A recuperação da hipnose e da anestesia foi mais rápida com NLP do que com CLP. As alterações de FC, PA e FR causadas pelo NLP não foram significativamente diferentes das do CLP. Ácido acético e veículo do CLP provocaram 46,0 ± 2,0 e 12,5 ± 0,6 contorções em 20 min após injeção i.p., respectivamente. Observou-se ausência de contorções abdominais com veículo de NLP. Nenhuma resposta inflamatória abdominal foi notada com a injeção i.p. de ambos os veículos de propofol. CONCLUSÕES: O NLP pode representar melhor alternativa do que o CLP para anestesia venosa com menores efeitos adversosJUSTIFICATIVA Y OBJETIVOS: El uso clínico de la formulación lipídica del propofol, causa dolor durante la inyección, reacci

The global prospects of taxation

Directory of Open Access Journals (Sweden)

Anđelković Mileva

2015-01-01

Full Text Available As the process of establishing international economic and financial relations between national economies is on the rise, many states encounter substantial difficulties in the process of collecting their tax claims. The most powerful countries in the world try to overcome this controversy by changing the international tax rules. The turning point was the financial-economic crisis of2008-2009, when the international community more vigorously embarked on resolving international tax issues. The OECD, the G20, the UN, the EU and a number of other powerful international organizations continued their activities on establishing a stronger framework of the international tax system. Global tax initiatives embodied in the soft law regulations have changed (to a varied extent the structure of national tax systems as well as the direction of national policies, and ultimately undermined the financial foundations of the social welfare state. The world's 'taxation landscape' is indisputably dominated by two major processes embodied in the concepts of tax harmonization and tax competition. The global crisis in financing contemporary states has weakened their resistance towards more extensive international tax cooperation. As a result, they increasingly accept global tax standards and are more vigorously involved in the international exchange of tax information for the purpose of counteracting international tax fraud. Changes in national tax systems are necessarily accompanied by changing relations between tax administrations and multinational companies as large taxpayers. The traditional public law relations are gradually changed by introducing some elements of 'negotiations and mutual agreement', which are aimed at strengthening mutual trust and avoiding unnecessary disputes and costs. Although they are currently no more than theoretical assumptions and political considerations, there are proposals for introducing global taxes and establishing the world tax

Frequency and socio-psychological impact of taunting in school-age patients with cleft lip-palate surgical repair.

Science.gov (United States)

Lorot-Marchand, A; Guerreschi, P; Pellerin, P; Martinot, V; Gbaguidi, C C; Neiva, C; Devauchelle, B; Frochisse, C; Poli-Merol, M L; Francois-Fiquet, C

2015-07-01

Cleft lip-palate (CLP) is a "social" pathology because of its impact on the child's facial appearance and speech. School is the first place where children are confronted to others and when they start socializing. Taunting and bullying are common and their psychological impact remains hard to assess. The aim of this study was to evaluate the importance of taunting in school and its impact in CLP patients who had surgical repair. We conducted a multicenter prospective study where we consecutively included patients ≥ 12 years who had CLP repair. During a multidisciplinary consultation they were asked to complete a questionnaire (3 parts: surgical outcomes, taunting and its impact, socio-economic status) previously approved by our psychologists. 55 patients were included (37 B, 18 G) (mean age 15.5 years): 11 CL, 13 CP and 31 CLP. 69% of patients reported having suffered from taunting and peer victimization in school. In 84% of the cases, taunting was linked to the CLP defect itself. The teasing started in primary school to reach a peak of aggressiveness in middle school. 42% of patients reported that bullying occurred at least once a day (16/38). Regarding the psychological impact of taunting, 50% of patients reported sadness, 31% depression and 26.3% were marked for life. At one time or another 29% of patients did not want to attend school because of the teasing. The grade retention rate amounted to 37.7% (20/53), and 2 patients were in special education classes. As a matter of fact, 50% of these children repeated their 1st or 2nd year of primary school. Furthermore, 47% of patients wanted to change something to their face, but 63% of them never spoke to their surgeon about additional surgeries even though they were teased in school. Taunting is common in children with CLP. This study highlights the high frequency and impact of taunting on the daily lives and self-perception of patients with CLP or CLP repair. It is important for healthcare professionals to be

Bioseguridad in Mexico: Pursuing Security between Local and Global Biologies.

Science.gov (United States)

Wanderer, Emily Mannix

2017-09-01

In the aftermath of the 2009 outbreak of H1N1 influenza, scientists in Mexico sought to develop bioseguridad, that is, to protect biological life in Mexico by safely conducting research on infectious disease. Drawing on ethnographic research in laboratories and with scientists in Mexico, I look at how scientists make claims about local differences in regulations, infrastructure, bodies, and culture. The scientists working with infectious microbes sought to establish how different microbial ecologies, human immune systems, and political and regulatory systems made the risks of research different in Mexico from other countries. In developing bioseguridad, the idea of globalized biology that animates many public health projects was undermined as scientists attended to the elements of place that affected human health and safety. Scientists argued for the importance of local biologies, generating tension with global public health projects and regulations premised on the universality of biology. © 2016 by the American Anthropological Association.

Challenges in global ballast water management

International Nuclear Information System (INIS)

Endresen, Oyvind; Lee Behrens, Hanna; Brynestad, Sigrid; Bjoern Andersen, Aage; Skjong, Rolf

2004-01-01

Ballast water management is a complex issue raising the challenge of merging international regulations, ship's specific configurations along with ecological conservation. This complexity is illustrated in this paper by considering ballast water volume, discharge frequency, ship safety and operational issues aligned with regional characteristics to address ecological risk for selected routes. A re-estimation of ballast water volumes gives a global annual level of 3500 Mton. Global ballast water volume discharged into open sea originating from ballast water exchange operations is estimated to approximately 2800 Mton. Risk based decision support systems coupled to databases for different ports and invasive species characteristics and distributions can allow for differentiated treatment levels while maintaining low risk levels. On certain routes, the risk is estimated to be unacceptable and some kind of ballast water treatment or management should be applied

Globalization, Inequality & International Economic Law

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Frank J. Garcia

2017-04-01

Full Text Available International law in general, and international economic law in particular, to the extent that either has focused on the issue of inequality, has done so in terms of inequality between states. Largely overlooked has been the topic of inequality within states and how international law has influenced that reality. From the perspective of international economic law, the inequality issue is closely entwined with the topics of colonialism and post-colonialism, the proper meaning of development, and globalization. While international economic law has undoubtedly contributed to the rise of inequality, it is now vital that the subject of international economic law be examined for how it may contribute to the lessening of inequality. To do so will require a shift in the way that we think, in order to address inequality as a problem of an emerging global market society, and how best to regulate that society and its institutions.

From European Union to World Union: Building Effective and Democratic Global Governance

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John McClintock

2012-04-01

Full Text Available Sovereignty-sharing has placed European countries in a position to resolve their common problems through law, not war. As a result, the EU member states now live in peace together and take peace, justice and order for granted. The system of global governance is dysfunctional – some states are failing and the Security Council lacks legitimacy. Humanity does not have a mechanism to resolve its global problems through law, making it difficult – if not impossible – to resolve global problems such as famine, hunger, climate change, war and terrorism, nuclear proliferation, regulation of corporations – including banks, destruction of fish stocks, and population. Sharing of sovereignty at the global level can address these problems, starting in the area of food security, then proceeding to climate management and other fields. Shared sovereignty can eliminate famine and hunger globally.

UniProt search blastx result: AK318569 [KOME

Lifescience Database Archive (English)

Full Text Available AK318569 J080307D05 B0TZA5|CLPP_FRAP2 ATP-dependent Clp protease proteolytic subunit OS=Francisella philo...miragia subsp. philomiragia (strain ATCC 25017) GN=clpP PE=3 SV=1 6.00E-34 ...

Design principles for global commons: Natural resources and emerging technologies

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Paul C. Stern

2011-09-01

Full Text Available Ostrom’s design principles for managing common pool resources were developed largely by examining local commons involving natural resources. This paper enumerates several key characteristics that distinguish such commons from more complex commons involving global resources and the risks of emerging technologies. It considers the degree to which the design principles transfer to those commons and concludes that although they have considerable external validity, the list needs some modification and elaboration to apply to global resources and risk commons. A list of design principles is offered for global resource commons and the risks of emerging technologies. Applying Ostrom’s approach to global resources and emerging technologies can improve understanding and expand the solution set for these problems from international treaties, top-down national regulation, and interventions in market pricing systems to include non-governmental institutions that embody principles of self-governance.

Behavioral deficits in sepsis-surviving rats induced by cecal ligation and perforation

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T. Barichello

2007-06-01

Full Text Available Sepsis and its complications are the leading causes of mortality in intensive care units, accounting for 10-50% of deaths. Intensive care unit survivors present long-term cognitive impairment, including alterations in memory, attention, concentration, and/or global loss of cognitive function. In the present study, we investigated behavioral alterations in sepsis-surviving rats. One hundred and ten male Wistar rats (3-4 months, 250-300 g were submitted to cecal ligation and puncture (CLP, and 44 were submitted to sham operation. Forty-four rats (40% survived after CLP, and all sham-operated animals survived and were used as control. Twenty animals of each group were used in the object recognition task (10 in short-term memory and 10 in long-term memory, 12 in the plus-maze test and 12 in the forced swimming test. Ten days after surgery, the animals were submitted individually to an object recognition task, plus-maze and forced swimming tests. A significant impairment of short- and long-term recognition memory was observed in the sepsis group (recognition index 0.75 vs 0.55 and 0.74 vs 0.51 for short- and long-term memory, respectively (P < 0.05. In the elevated plus-maze test no difference was observed between groups in any of the parameters assessed. In addition, sepsis survivors presented an increase in immobility time in the forced swimming test (180 vs 233 s, P < 0.05, suggesting the presence of depressive-like symptoms in these animals after recovery from sepsis. The present results demonstrated that rats surviving exposure to CLP, a classical sepsis model, presented recognition memory impairment and depressive-like symptoms but not anxiety-like behavior.

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Yousry M. Issa

2017-03-01

Full Text Available The solubility and solubility product of the two ion-associates clomipraminium tetraphenylborate (CLP-TPB and silicotungstate ((CLP4-ST were determined using conductimetric and potentiometric measurements applying the standard addition method. The obtained values from both conductimetric measurements and standard addition method are close to each other. Thermodynamic parameters ΔG, ΔH and ΔS have been determined. Sodium tetraphenylborate has been used for the determination of CLP.Cl in model solution and pharmaceutical preparation by conductimetric titrations. The proposed method allowed the determination of CLP.Cl within the range of 0.17–35.15 mg. The accuracy of the method is indicated by the excellent recovery 99.95–101.23%, and the precision is supported by the low relative standard deviation 0.50–1.21%. The ruggedness and robustness of the proposed method were also studied.

The evolution, etiology and eventualities of the global health security regime.

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Hoffman, Steven J

2010-11-01

Attention to global health security governance is more important now than ever before. Scientists predict that a possible influenza pandemic could affect 1.5 billion people, cause up to 150 million deaths and leave US$3 trillion in economic damages. A public health emergency in one country is now only hours away from affecting many others. Using regime analysis from political science, the principles, norms, rules and decision-making procedures by which states govern health security are examined in the historical context of their punctuated evolution. This methodology illuminates the catalytic agents of change, distributional consequences and possible future orders that can help to better inform progress in this area. Four periods of global health security governance are identified. The first is characterized by unilateral quarantine regulations (1377-1851), the second by multiple sanitary conferences (1851-92), the third by several international sanitary conventions and international health organizations (1892-1946) and the fourth by the hegemonic leadership of the World Health Organization (1946-????). This final regime, like others before it, is challenged by globalization (e.g. limitations of the new International Health Regulations), changing diplomacy (e.g. proliferation of global health security organizations), new tools (e.g. global health law, human rights and health diplomacy) and shock-activated vulnerabilities (e.g. bioterrorism and avian/swine influenza). This understanding, in turn, allows us to appreciate the impact of this evolving regime on class, race and gender, as well as to consider four possible future configurations of power, including greater authority for the World Health Organization, a concert of powers, developing countries and civil society organizations. This regime analysis allows us to understand the evolution, etiology and eventualities of the global health security regime, which is essential for national and international health

Institutional preconditions of socio-ecological-economic regulation of environmental management activities

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T. A. Plaksunova

2017-01-01

Full Text Available The need to regulate environmental management activities of institutional entities arises when it affects the interests of third-party entities or threatened by the ongoing entity manufacturing practices its own resilience, to achieve the main goal. The complexity and diversity of the forms of socio-ecological and ecological-economic issues at different levels of the economic system leads to the development of many directions and views on the expansion of the management process of these levels (global, national, regional, local and techniques from rigid-deklorative state before combination with the market. In this respect, the neoclassical economic theory actively generated new analytical ideas and concept that enables to respond adequately to emerging economic realities. So we can distinguish the following approaches to regulate environmental management activities: T. Malthus and D. Ricardo, revealing issues of social, ecological and economic implications of limited natural resources in the context of the law of diminishing effectiveness and the need to regulate environmental management activities. John. St. Mill and George proved to be ineffective in addressing environmental problems in the industrial economy of the type of the imperfection of the institutions of society, justifying the occurrence of crises protohistoric speculation nature's benefits. A. Pigou developed the theory of externalities, which revealed the need for state regulation of the environmental management activities of economic entities, harmonization of individual and social interests. Research I. Kula, F. Khan and P. Samuelson identified a pattern about the formation of the system of regulation nature-safety activities, not only within individual States but also on a global level. R. Crows have shown that the methods of direct state regulation of nature economic activity is not as good as it seems at first glance and so you should not underestimate the role and potential

The Global Enery and Water Cycle Experiment Science Strategy

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Chahine, M. T.

1997-01-01

The distribution of water in the atmosphere and at the surface of the Earth is the most influential factor regulating our environment, not only because water is essential for life but also because through phase transitions it is the main energy source that control clouds and radiation and drives the global circulation of the atmosphere.

Basel III – Between Global Thinking and Local Acting

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Vasile DEDU

2012-06-01

Full Text Available The financial crisis has demonstrated that self-regulation is not sufficient to markets and financial institutions with systemic importance.Permissive regulatory policies, allowing the development speed of global banking financial system, have played an important role in emphasizing the upward slope of the financial crisis.The new regulations known as Basel III framework aimed the strengthening of prudential capital and liquidity of financial institutions and create a stronger banking and financial system more resilient to shocks.Basel III is trying to eliminate the shortcomings of Basel II, by more extensive rules on integrated risk management in banking and financial environment.

Pattern of clefts and dental anomalies in six-year-old children: a retrospective observational study in western Norway.

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Sæle, Paul; Østhus, Eirik; Ådalen, Sondre; Nasir, Elwalid F; Mustafa, Manal

2017-03-01

Clefts of the lip and/or palate (CL/P) are the most common congenital disorders of the head and neck. In Norway, the incidence is 1.9/1000 live births. The aim of this study was to investigate the frequency and distribution of various types of clefts and dental anomalies in patients treated by the cleft lip and palate (CLP) team in Bergen, Norway. The material comprised the records of patients 6 years of age, examined by the CLP team in Bergen from spring 1993 to autumn 2012, incomplete records were excluded. The records of 989 patients were analysed, using frequencies and Chi-square test to compare differences in percentages between groups. The gender distribution was 58.8% male and 41.2% female. Isolated cleft palate (CP) was the most common condition (39.5%). Clefts of the lip, jaw and palate (CLP) constituted (30%) of cases and (30.5%) had isolated cleft lip (CL). The frequencies of agenesis, supernumerary and peg-shaped teeth were (36.5%), (17.8%) and (7.5%), respectively. Over 50% of the study population were diagnosed with one or more malocclusion. Of the CLP patients, 61.4% had Angle Class III occlusion. Statistical analysis disclosed a positive association of agenesis with Class III occlusion (OR =1.8, p≤ 0.001). The findings supported the hypothesis that the distribution of dental anomalies and occlusal disorders varied among patients with CL, CP and CLP. In patients with cleft, there is a twofold chance to get Class III malocclusion in the presence of agenesis.