Neuronal Rap1 regulates energy balance, glucose homeostasis, and leptin actions

OpenAIRE

Kaneko, Kentaro; Xu, Pingwen; Cordonier, Elizabeth L.; Chen, Siyu S.; Ng, Amy; Xu, Yong; Morozov, Alexei; Fukuda, Makoto

2016-01-01

The central nervous system (CNS) contributes to obesity and metabolic disease; however, the underlying neurobiological pathways remain to be fully established. Here we show that the small GTPase Rap1 is expressed in multiple hypothalamic nuclei that control whole-body metabolism and is activated in high-fat diet (HFD)-induced obesity. Genetic ablation of CNS Rap1 protects mice from dietary obesity, glucose imbalance, and insulin resistance in the periphery and from HFD-induced neuropathologic...

NGF-Dependent neurite outgrowth in PC12 cells overexpressing the Src homology 2-domain protein shb requires activation of the Rap1 pathway

NARCIS (Netherlands)

Lu, L.; Annerén, C.; Reedquist, K. A.; Bos, J. L.; Welsh, M.

2000-01-01

The Src homology 2 (SH2) domain adaptor protein Shb has been shown to transmit NGF- and FGF-2-dependent differentiation signals in PC12 cells. To study if this involves signaling through the small GTPase Rap1, Rap1 activity was assessed in Shb-overexpressing PC12 cells. We demonstrate that NGF and

Nucleotide sequence of a human cDNA encoding a ras-related protein (rap1B)

Energy Technology Data Exchange (ETDEWEB)

Pizon, V; Lerosey, I; Chardin, P; Tavitian, A [INSERM, Paris (France)

1988-08-11

The authors have previously characterized two human ras-related genes rap1 and rap2. Using the rap1 clone as probe they isolated and sequenced a new rap cDNA encoding the 184aa rap1B protein. The rap1B protein is 95% identical to rap1 and shares several properties with the ras protein suggesting that it could bind GTP/GDP and have a membrane location. As for rap1, the structural characteristics of rap1B suggest that the rap and ras proteins might interact on the same effector.

A signaling pathway contributing to platelet storage lesion development: targeting PI3-kinase–dependent Rap1 activation slows storage-induced platelet deterioration

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Schubert, Peter; Thon, Jonathan N.; Walsh, Geraldine M.; Chen, Cindy H.I.; Moore, Edwin D.; Devine, Dana V.; Kast, Juergen

2015-01-01

BACKGROUND The term platelet storage lesion (PSL) describes the structural and biochemical changes in platelets (PLTs) during storage. These are typified by alterations of morphologic features and PLT metabolism leading to reduced functionality and hence reduced viability for transfusion. While the manifestations of the storage lesion are well characterized, the biochemical pathways involved in the initiation of this process are unknown. STUDY DESIGN AND METHODS A complementary proteomic approach has recently been applied to analyze changes in the PLT proteome during storage. By employing stringent proteomic criteria, 12 proteins were identified as significantly and consistently changing in relative concentration over a 7-day storage period. Microscopy, Western blot analysis, flow cytometry, and PLT functionality analyses were used to unravel the involvement of a subset of these 12 proteins, which are connected through integrin signaling in one potential signaling pathway underlying storage lesion development. RESULTS Microscopic analysis revealed changes in localization of glycoprotein IIIa, Rap1, and talin during storage. Rap1 activation was observed to correlate with expression of the PLT activation marker CD62P. PLTs incubated for 7 days with the PI3-kinase inhibitor LY294002 showed diminished Rap1 activation as well as a moderate reduction in integrin αIIbβ3 activation and release of α-granules. Furthermore, this inhibitor seemed to improve PLT integrity and quality during storage as several in vitro probes showed a deceleration of PLT activation. CONCLUSION These results provide the first evidence for a signaling pathway mediating PSL in which PI3-kinase–dependent Rap1 activation leads to integrin αIIbβ3 activation and PLT degranulation. PMID:19497060

Rap G protein signal in normal and disordered lymphohematopoiesis.

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Minato, Nagahiro

2013-09-10

Rap proteins (Rap1, Rap2a, b, c) are small molecular weight GTPases of the Ras family. Rap G proteins mediate diverse cellular events such as cell adhesion, proliferation, and gene activation through various signaling pathways. Activation of Rap signal is regulated tightly by several specific regulatory proteins including guanine nucleotide exchange factors and GTPase-activating proteins. Beyond cell biological studies, increasing attempts have been made in the past decade to define the roles of Rap signal in specific functions of normal tissue systems as well as in cancer. In the immune and hematopoietic systems, Rap signal plays crucial roles in the development and function of essentially all lineages of lymphocytes and hematopoietic cells, and importantly, deregulated Rap signal may lead to unique pathological conditions depending on the affected cell types, including various types of leukemia and autoimmunity. The phenotypical studies have unveiled novel, even unexpected functional aspects of Rap signal in cells from a variety of tissues, providing potentially important clues for controlling human diseases, including malignancy. © 2013 Elsevier Inc. All rights reserved.

Binding of Multiple Rap1 Proteins Stimulates Chromosome Breakage Induction during DNA Replication.

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Greicy H Goto

2015-08-01

Full Text Available Telomeres, the ends of linear eukaryotic chromosomes, have a specialized chromatin structure that provides a stable chromosomal terminus. In budding yeast Rap1 protein binds to telomeric TG repeat and negatively regulates telomere length. Here we show that binding of multiple Rap1 proteins stimulates DNA double-stranded break (DSB induction at both telomeric and non-telomeric regions. Consistent with the role of DSB induction, Rap1 stimulates nearby recombination events in a dosage-dependent manner. Rap1 recruits Rif1 and Rif2 to telomeres, but neither Rif1 nor Rif2 is required for DSB induction. Rap1-mediated DSB induction involves replication fork progression but inactivation of checkpoint kinase Mec1 does not affect DSB induction. Rap1 tethering shortens artificially elongated telomeres in parallel with telomerase inhibition, and this telomere shortening does not require homologous recombination. These results suggest that Rap1 contributes to telomere homeostasis by promoting chromosome breakage.

Sequence and organization of the rhoptry-associated-protein-1 (rap-1) locus for the sheep hemoprotozoan Babesia sp. BQ1 Lintan (B. motasi phylogenetic group).

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Niu, Qingli; Bonsergent, Claire; Guan, Guiquan; Yin, Hong; Malandrin, Laurence

2013-11-15

Babesiosis is a frequent infection of animals worldwide by tick borne pathogen Babesia, and several species are responsible for ovine babesiosis. Recently, several Babesia motasi-like isolates were described in sheep in China. In this study, we sequenced the multigenic rap-1 gene locus of one of these isolates, Babesia sp. BQ1 Lintan. The RAP-1 proteins are involved in the process of red blood cells invasion and thus represent a potential target for vaccine development. A complex composition and organization of the rap-1 locus was discovered with: (1) the presence of 3 different types of rap-1 sequences (rap-1a, rap-1b and rap-1c); (2) the presence of multiple copies of rap-1a and rap-1b; (3) polymorphism among the rap-1a copies, with two classes (named rap-1a61 and rap-1a67) having a similarity of 95.7%, each class represented by two close variants; (4) polymorphism between rap-1a61-1 and rap-1a61-2 limited to three nucleotide positions; (5) a difference of eight nucleotides between rap-1a67-1 and rap-1a67-2 from position 1270 to the putative stop site of rap-1a67-1 which might produce two putative proteins of slightly different sizes; (6) the ratio of rap-1a copies corresponding to one rap-1a67, one rap-1a61-1 and one rap-1a61-2; (7) the presence of three different intergenic regions separating rap-1a, rap-1b and rap-1c; (8) interspacing of the rap-1a copies with rap-1b copies; and (9) the terminal position of rap-1c in the locus. A 31kb locus composed of 6 rap-1a sequences interspaced with 5 rap-1b sequences and with a terminal rap-1c copy was hypothesized. A strikingly similar sequence composition (rap-1a, rap-1b and rap-1c), as well as strong gene identities and similar locus organization with B. bigemina were found and highlight the conservation of synteny at this locus in this phylogenetic clade. Copyright © 2013 Elsevier B.V. All rights reserved.

The non-receptor tyrosine kinase Lyn controls neutrophil adhesion by recruiting the CrkL–C3G complex and activating Rap1 at the leading edge

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He, Yuan; Kapoor, Ashish; Cook, Sara; Liu, Shubai; Xiang, Yang; Rao, Christopher V.; Kenis, Paul J. A.; Wang, Fei

2011-01-01

Establishing new adhesions at the extended leading edges of motile cells is essential for stable polarity and persistent motility. Despite recent identification of signaling pathways that mediate polarity and chemotaxis in neutrophils, little is known about molecular mechanisms governing cell–extracellular-matrix (ECM) adhesion in these highly polarized and rapidly migrating cells. Here, we describe a signaling pathway in neutrophils that is essential for localized integrin activation, leading edge attachment and persistent migration during chemotaxis. This pathway depends upon Gi-protein-mediated activation and leading edge recruitment of Lyn, a non-receptor tyrosine kinase belonging to the Src kinase family. We identified the small GTPase Rap1 as a major downstream effector of Lyn to regulate neutrophil adhesion during chemotaxis. Depletion of Lyn in neutrophil-like HL-60 cells prevented chemoattractant-induced Rap1 activation at the leading edge of the cell, whereas ectopic expression of Rap1 largely rescued the defects induced by Lyn depletion. Furthermore, Lyn controls spatial activation of Rap1 by recruiting the CrkL–C3G protein complex to the leading edge. Together, these results provide novel mechanistic insights into the poorly understood signaling network that controls leading edge adhesion during chemotaxis of neutrophils, and possibly other amoeboid cells. PMID:21628423

Requirement of the Caenorhabditis elegans RapGEF pxf-1 and rap-1 for epithelial integrity

Czech Academy of Sciences Publication Activity Database

Pellis-van Berkel, W.; Verheijen, M. H. G.; Cuppen, E.; Asahina, Masako; de Rooij, J.; Jansen, G.; Plasterk, R. H. A.; Bos, J. L.; Zwartkruis, F. J. T.

2005-01-01

Roč. 16, č. 1 (2005), s. 106-116 ISSN 1059-1524 R&D Projects: GA AV ČR KJB5022303 Institutional research plan: CEZ:AV0Z60220518 Keywords : Rap signaling pathway * epidermis * Caenorhabditis elegans Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.520, year: 2005

Neuronal Rap1 regulates energy balance, glucose homeostasis, and leptin actions

Science.gov (United States)

The Central Nervous System (CNS) contributes to obesity and metabolic disease; however, the underlying neurobiological pathways remain to be fully established. Here, we show that the small GTPase Rap1 is expressed in multiple hypothalamic nuclei that control whole-body metabolism and is activated in...

The transcription factor Rap1p is required for tolerance to cell-wall perturbing agents and for cell-wall maintenance in Saccharomyces cerevisiae.

Science.gov (United States)

Azad, Gajendra Kumar; Singh, Vikash; Baranwal, Shivani; Thakare, Mayur Jankiram; Tomar, Raghuvir S

2015-01-02

Yeast repressor activator protein (Rap1p) is involved in genomic stability and transcriptional regulation. We explored the function of Rap1p in yeast physiology using Rap1p truncation mutants. Our results revealed that the N-terminal truncation of Rap1p (Rap1ΔN) leads to hypersensitivity towards elevated temperature and cell-wall perturbing agents. Cell wall analysis showed an increase in the chitin and glucan content in Rap1ΔN cells as compared with wild type cells. Accordingly, mutant cells had a twofold thicker cell wall, as observed by electron microscopy. Furthermore, Rap1ΔN cells had increased levels of phosphorylated Slt2p, a MAP kinase of the cell wall integrity pathway. Mutant cells also had elevated levels of cell wall integrity response transcripts. Taken together, our findings suggest a connection between Rap1p and cell wall homeostasis. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Ageing management studies of RAPS-1

International Nuclear Information System (INIS)

Bohra, A.K.; Jain, L.K.; Joshi, K.M.

2006-01-01

Unit-l of Rajasthan Atomic Power Station (RAPS-1) is the first nuclear power plant of India with pressurized heavy water reactor. The construction of Unit-l of Rajasthan Atomic Power Station (RAPS-1) was started in the year 1966 in collaboration with Canada. The Unit-1 achieved first criticality on August 1972 and was first synchronized to Grid on November 1972. During initial operation of the Unit, several problems were faced in its various systems and these were addressed by incorporating various engineering changes and procedures. In this unit various major innovative repairs were done like end shield leak repair, OPRD leak repair. Considering the operation of various systems of Unit-1, since year 1971 it was imperative to study ageing degradation mechanisms and mitigating measures were to be taken. Although the ageing management is a continuous process the opportunity of Unit-1 shutdown for upgradations from 30-04-2002 to 08-02-2004 was utilized for inspection and assessment of health of various SSC, which otherwise could not have been done with unit in operational state. This paper contains the following in detail. (1) Ageing management programme, its objectives and scope (2) Methodology of ageing management studies - Replacement and upgradation -Additional inspection programme based on ageing management review - Statistical analysis of ageing degradation occurrence - Estimation of residual life span of cables and relays (3) Criteria for selection of components for ageing management programme (4) Findings of ageing management studies-case studies. The ageing study done for RAPS-1 indicated that appropriate ageing monitoring methods and procedures exist in the station for taking timely mitigating measures. The technological obsoleteness has been overcome by installing new components of latest technology. On overall assessment, the Unit-1 was considered fit for further service. (author)

Identification of the functional domains of the telomere protein Rap1 in Schizosaccharomyces pombe.

Directory of Open Access Journals (Sweden)

Ikumi Fujita

Full Text Available The telomere at the end of a linear chromosome plays crucial roles in genome stability. In the fission yeast Schizosaccharomyces pombe, the Rap1 protein, one of the central players at the telomeres, associates with multiple proteins to regulate various telomere functions, such as the maintenance of telomere DNA length, telomere end protection, maintenance of telomere heterochromatin, and telomere clustering in meiosis. The molecular bases of the interactions between Rap1 and its partners, however, remain largely unknown. Here, we describe the identification of the interaction domains of Rap1 with its partners. The Bqt1/Bqt2 complex, which is required for normal meiotic progression, Poz1, which is required for telomere length control, and Taz1, which is required for the recruitment of Rap1 to telomeres, bind to distinct domains in the C-terminal half of Rap1. Intriguingly, analyses of a series of deletion mutants for rap1(+ have revealed that the long N-terminal region (1-456 a.a. [amino acids] of Rap1 (full length: 693 a.a. is not required for telomere DNA length control, telomere end protection, and telomere gene silencing, whereas the C-terminal region (457-693 a.a. containing Poz1- and Taz1-binding domains plays important roles in those functions. Furthermore, the Bqt1/Bqt2- and Taz1-binding domains are essential for normal spore formation after meiosis. Our results suggest that the C-terminal half of Rap1 is critical for the primary telomere functions, whereas the N-terminal region containing the BRCT (BRCA1 C-terminus and Myb domains, which are evolutionally conserved among the Rap1 family proteins, does not play a major role at the telomeres.

Effects of using nursing home residents to serve as group activity leaders: lessons learned from the RAP project.

Science.gov (United States)

Skrajner, Michael J; Haberman, Jessica L; Camp, Cameron J; Tusick, Melanie; Frentiu, Cristina; Gorzelle, Gregg

2014-03-01

Previous research has demonstrated that persons with early to moderate stage dementia are capable of leading small group activities for persons with more advanced dementia. In this study, we built upon this previous work by training residents in long-term care facilities to fill the role of group activity leaders using a Resident-Assisted Programming (RAP) training regimen. There were two stages to the program. In the first stage, RAP training was provided by researchers. In the second stage, RAP training was provided to residents by activities staff members of long-term care facilities who had been trained by researchers. We examine the effects of RAP implemented by researchers and by activities staff member on long-term care resident with dementia who took part in these RAP activities. We also examined effects produced by two types of small group activities: two Montessori-based activities and an activity which focuses on persons with more advanced dementia, based on the work of Jitka Zgola. Results demonstrate that levels of positive engagement seen in players during RAP (resident-led activities) were typically higher than those observed during standard activities programming led by site staff. In general, Montessori-Based Dementia Programming® produced more constructive engagement than Zgola-based programming (ZBP), though ZBP did increase a positive form of engagement involving observing activities with interest. In addition, RAP implemented by activities staff members produced effects that were, on the whole, similar to those produced when RAP was implemented by researchers. Implications of these findings for providing meaningful social roles for persons with dementia residing in long-term care, and suggestions for further research in this area, are discussed.

Re-active Passive (RAP) Devices for Control of Noise Transmission through a Panel

Science.gov (United States)

Carneal, James P.; Giovanardi, Marco; Fuller, Chris R.; Palumbo, Daniel L.

2008-01-01

Re-Active Passive (RAP) devices have been developed to control low frequency (transmission through a panel. These devices use a combination of active, re-active, and passive technologies packaged into a single unit to control a broad frequency range utilizing the strength of each technology over its best suited frequency range. The RAP device uses passive constrained layer damping to cover the relatively high frequency range (>200 Hz), reactive distributed vibration absorber) to cover the medium frequency range (75 to 250 Hz), and active control for controlling low frequencies (transmission through a panel mounted in a transmission loss test facility. Experimental results are presented for the bare panel, and combinations of passive treatment, reactive treatment, and active control. Results indicate that three RAP devices were able to increase the overall broadband (15-1000 Hz) transmission loss by 9.4 dB. These three devices added a total of 285 grams to the panel mass of 6.0 kg, or approximately 5%, not including control electronics.

Efficient transcription of the glycolytic gene ADH1 and three translational component genes requires the GCR1 product, which can act through TUF/GRF/RAP binding sites.

OpenAIRE

Santangelo, G M; Tornow, J

1990-01-01

Glycolytic gene expression in Saccharomyces cerevisiae is thought to be activated by the GCR and TUF proteins. We tested the hypothesis that GCR function is mediated by TUF/GRF/RAP binding sites (UASRPG elements). We found that UASRPG-dependent activation of a heterologous gene and transcription of ADH1, TEF1, TEF2, and RP59 were sensitive to GCR1 disruption. GCR is not required for TUF/GRF/RAP expression or in vitro DNA-binding activity.

Structural Basis of Rap Phosphatase Inhibition by Phr Peptides

Science.gov (United States)

Gallego del Sol, Francisca; Marina, Alberto

2013-01-01

Two-component systems, composed of a sensor histidine kinase and an effector response regulator (RR), are the main signal transduction devices in bacteria. In Bacillus, the Rap protein family modulates complex signaling processes mediated by two-component systems, such as competence, sporulation, or biofilm formation, by inhibiting the RR components involved in these pathways. Despite the high degree of sequence homology, Rap proteins exert their activity by two completely different mechanisms of action: inducing RR dephosphorylation or blocking RR binding to its target promoter. However the regulatory mechanism involving Rap proteins is even more complex since Rap activity is antagonized by specific signaling peptides (Phr) through a mechanism that remains unknown at the molecular level. Using X-ray analyses, we determined the structure of RapF, the anti-activator of competence RR ComA, alone and in complex with its regulatory peptide PhrF. The structural and functional data presented herein reveal that peptide PhrF blocks the RapF-ComA interaction through an allosteric mechanism. PhrF accommodates in the C-terminal tetratricopeptide repeat domain of RapF by inducing its constriction, a conformational change propagated by a pronounced rotation to the N-terminal ComA-binding domain. This movement partially disrupts the ComA binding site by triggering the ComA disassociation, whose interaction with RapF is also sterically impaired in the PhrF-induced conformation of RapF. Sequence analyses of the Rap proteins, guided by the RapF-PhrF structure, unveil the molecular basis of Phr recognition and discrimination, allowing us to relax the Phr specificity of RapF by a single residue change. PMID:23526880

Efficient transcription of the glycolytic gene ADH1 and three translational component genes requires the GCR1 product, which can act through TUF/GRF/RAP binding sites.

Science.gov (United States)

Santangelo, G M; Tornow, J

1990-01-01

Glycolytic gene expression in Saccharomyces cerevisiae is thought to be activated by the GCR and TUF proteins. We tested the hypothesis that GCR function is mediated by TUF/GRF/RAP binding sites (UASRPG elements). We found that UASRPG-dependent activation of a heterologous gene and transcription of ADH1, TEF1, TEF2, and RP59 were sensitive to GCR1 disruption. GCR is not required for TUF/GRF/RAP expression or in vitro DNA-binding activity. Images PMID:2405258

Extracellular adenosine-induced Rac1 activation in pulmonary endothelium: Molecular mechanisms and barrier-protective role.

Science.gov (United States)

Kovacs-Kasa, Anita; Kim, Kyung Mi; Cherian-Shaw, Mary; Black, Stephen M; Fulton, David J; Verin, Alexander D

2018-08-01

We have previously shown that Gs-coupled adenosine receptors (A2a) are primarily involved in adenosine-induced human pulmonary artery endothelial cell (HPAEC) barrier enhancement. However, the downstream events that mediate the strengthening of the endothelial cell (EC) barrier via adenosine signaling are largely unknown. In the current study, we tested the overall hypothesis that adenosine-induced Rac1 activation and EC barrier enhancement is mediated by Gs-dependent stimulation of cAMP-dependent Epac1-mediated signaling cascades. Adenoviral transduction of HPAEC with constitutively-active (C/A) Rac1 (V12Rac1) significantly increases transendothelial electrical resistance (TER) reflecting an enhancement of the EC barrier. Conversely, expression of an inactive Rac1 mutant (N17Rac1) decreases TER reflecting a compromised EC barrier. The adenosine-induced increase in TER was accompanied by activation of Rac1, decrease in contractility (MLC dephosphorylation), but not Rho inhibition. Conversely, inhibition of Rac1 activity attenuates adenosine-induced increase in TER. We next examined the role of cAMP-activated Epac1 and its putative downstream targets Rac1, Vav2, Rap1, and Tiam1. Depletion of Epac1 attenuated the adenosine-induced Rac1 activation and the increase in TER. Furthermore, silencing of Rac1 specific guanine nucleotide exchange factors (GEFs), Vav2 and Rap1a expression significantly attenuated adenosine-induced increases in TER and activation of Rac1. Depletion of Rap1b only modestly impacted adenosine-induced increases in TER and Tiam1 depletion had no effect on adenosine-induced Rac1 activation and TER. Together these data strongly suggest that Rac1 activity is required for adenosine-induced EC barrier enhancement and that the activation of Rac1 and ability to strengthen the EC barrier depends, at least in part, on cAMP-dependent Epac1/Vav2/Rap1-mediated signaling. © 2017 Wiley Periodicals, Inc.

Strong conservation of rhoptry-associated-protein-1 (RAP-1) locus organization and sequence among Babesia isolates infecting sheep from China (Babesia motasi-like phylogenetic group).

Science.gov (United States)

Niu, Qingli; Valentin, Charlotte; Bonsergent, Claire; Malandrin, Laurence

2014-12-01

Rhoptry-associated-protein 1 (RAP-1) is considered as a potential vaccine candidate due to its involvement in red blood cell invasion by parasites in the genus Babesia. We examined its value as a vaccine candidate by studying RAP-1 conservation in isolates of Babesia sp. BQ1 Ningxian, Babesia sp. Tianzhu and Babesia sp. Hebei, responsible for ovine babesiosis in different regions of China. The rap-1 locus in these isolates has very similar features to those described for Babesia sp. BQ1 Lintan, another Chinese isolate also in the B. motasi-like phylogenetic group, namely the presence of three types of rap-1 genes (rap-1a, rap-1b and rap-1c), multiple conserved rap-1b copies (5) interspaced with more or less variable rap-1a copies (6), and the 3' localization of one rap-1c. The isolates Babesia sp. Tianzhu, Babesia sp. BQ1 Lintan and Ningxian were almost identical (average nucleotide identity of 99.9%) over a putative locus of about 31 Kb, including the intergenic regions. Babesia sp. Hebei showed a similar locus organization but differed in the rap-1 locus sequence, for each gene and intergenic region, with an average nucleotide identity of 78%. Our results are in agreement with 18S rDNA phylogenetic studies performed on these isolates. However, in extremely closely related isolates the rap-1 locus seems more conserved (99.9%) than the 18S rDNA (98.7%), whereas in still closely related isolates the identities are much lower (78%) compared with the 18S rDNA (97.7%). The particularities of the rap-1 locus in terms of evolution, phylogeny, diagnosis and vaccine development are discussed. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Apical accumulation of the Sevenless receptor tyrosine kinase during Drosophila eye development is promoted by the small GTPase Rap1.

Science.gov (United States)

Baril, Caroline; Lefrançois, Martin; Sahmi, Malha; Knævelsrud, Helene; Therrien, Marc

2014-08-01

The Ras/MAPK-signaling pathway plays pivotal roles during development of metazoans by controlling cell proliferation and cell differentiation elicited, in several instances, by receptor tyrosine kinases (RTKs). While the internal mechanism of RTK-driven Ras/MAPK signaling is well understood, far less is known regarding its interplay with other co-required signaling events involved in developmental decisions. In a genetic screen designed to identify new regulators of RTK/Ras/MAPK signaling during Drosophila eye development, we identified the small GTPase Rap1, PDZ-GEF, and Canoe as components contributing to Ras/MAPK-mediated R7 cell differentiation. Rap1 signaling has recently been found to participate in assembling cadherin-based adherens junctions in various fly epithelial tissues. Here, we show that Rap1 activity is required for the integrity of the apical domains of developing photoreceptor cells and that reduced Rap1 signaling hampers the apical accumulation of the Sevenless RTK in presumptive R7 cells. It thus appears that, in addition to its role in cell-cell adhesion, Rap1 signaling controls the partitioning of the epithelial cell membrane, which in turn influences signaling events that rely on apico-basal cell polarity. Copyright © 2014 by the Genetics Society of America.

Genetic diversity and natural selection in the rhoptry-associated protein 1 (RAP-1) of recent Plasmodium knowlesi clinical isolates from Malaysia.

Science.gov (United States)

Rawa, Mira Syahfriena Amir; Fong, Mun-Yik; Lau, Yee-Ling

2016-02-05

The Plasmodium rhoptry-associated protein 1 (RAP-1) plays a role in the formation of the parasitophorous vacuole following the parasite's invasion of red blood cells. Although there is some evidence that the protein is recognized by the host's immune system, study of Plasmodium falciparum RAP-1 (PfRAP-1) suggests that it is not under immune pressure. A previous study on five old (1953-1962) P. knowlesi strains suggested that RAP-1 has limited genetic polymorphism and might be under negative selection. In the present study, 30 recent P. knowlesi isolates were studied to obtain a better insight into the polymorphism and natural selection of PkRAP-1. Blood samples from 30 knowlesi malaria patients were used. These samples were collected between 2010 and 2014. The PkRAP-1 gene, which contains two exons, was amplified by PCR, cloned into Escherichia coli and sequenced. Genetic diversity and phylogenetic analyses were performed using MEGA6 and DnaSP ver. 5.10.00 programs. Thirty PkRAP-1 sequences were obtained. The nucleotide diversity (π) of exons 1, 2 and the total coding region (0.00915, 0.01353 and 0.01298, respectively) were higher than those of the old strains. Further analysis revealed a lower rate of non-synonymous (dN) than synonymous (dS) mutations, suggesting negative (purifying) selection of PkRAP-1. Tajima's D test and Fu and Li's D test values were not significant. At the amino acid level, 22 haplotypes were established with haplotype H7 having the highest frequency (7/34, 20.5 %). In the phylogenetic analysis, two distinct haplotype groups were observed. The first group contained the majority of the haplotypes, whereas the second had fewer haplotypes. The present study found higher genetic polymorphism in the PkRAP-1 gene than the polymorphism level reported in a previous study. This observation may stem from the difference in sample size between the present (n = 30) and the previous (n = 5) study. Synonymous and non-synonymous mutation analysis indicated

Synergistic regulation of competence development in Bacillus subtilis by two Rap-Phr systems.

Science.gov (United States)

Bongiorni, Cristina; Ishikawa, Shu; Stephenson, Sophie; Ogasawara, Naotake; Perego, Marta

2005-07-01

The 11 Rap proteins of Bacillus subtilis comprise a conserved family of tetratricopeptide (TPR)-containing regulatory proteins. Their activity is inhibited by specific Phr pentapeptides produced from the product of phr genes through an export-import maturation process. We found that one of the proteins, namely RapF, is involved in the regulation of competence to DNA transformation. The ComA response regulator and transcription factor for initiation of competence development is the target of RapF. Specific binding of RapF to the carboxy-terminal DNA-binding domain of ComA inhibits the response regulator's ability to bind its target DNA promoters. The PhrF C-terminal pentapeptide, QRGMI, inhibits RapF activity. The activity of RapF and PhrF in regulating competence development is analogous to the previously described activity of RapC and PhrC (L. J. Core and M. Perego, Mol. Microbiol. 49:1509-1522, 2003). In fact, the RapF and PhrF pair of proteins acts synergistically with RapC and PhrC in the overall regulation of the ComA transcription factor. Since the transcription of the RapC- and RapF-encoding genes is positively regulated by their own target ComA, an autoregulatory circuit must exist for the competence transcription factor in order to modulate its activity.

RAPS: an innovative active pixel for particle detection integrated in CMOS technology

International Nuclear Information System (INIS)

Passeri, Daniele; Placidi, Pisana; Verducci, Leonardo; Ciampolini, Paolo; Matrella, Guido; Marras, Alessandro; Bilei, G.M.

2004-01-01

In this paper we discuss some design, implementation and test issues, with respect to the development of the RAPS01 chip in the framework of the Radiation Active Pixel Sensors (RAPS) INFN project. The project aimed at verifying feasibility of smart, high-resolution pixel arrays with a fully standard, submicron CMOS technology for particle detection purposes. Layout optimization of the pixel, including sensitive element and local read and amplification circuits has been carried out. Different basic pixel schemes and read-out options have been proposed and devised. Chip fabrication has been completed and test phase is now under way: to this purpose a suitable test environment has been devised and test strategies have been planned

Synergistic Regulation of Competence Development in Bacillus subtilis by Two Rap-Phr Systems† ‡

Science.gov (United States)

Bongiorni, Cristina; Ishikawa, Shu; Stephenson, Sophie; Ogasawara, Naotake; Perego, Marta

2005-01-01

The 11 Rap proteins of Bacillus subtilis comprise a conserved family of tetratricopeptide (TPR)-containing regulatory proteins. Their activity is inhibited by specific Phr pentapeptides produced from the product of phr genes through an export-import maturation process. We found that one of the proteins, namely RapF, is involved in the regulation of competence to DNA transformation. The ComA response regulator and transcription factor for initiation of competence development is the target of RapF. Specific binding of RapF to the carboxy-terminal DNA-binding domain of ComA inhibits the response regulator's ability to bind its target DNA promoters. The PhrF C-terminal pentapeptide, QRGMI, inhibits RapF activity. The activity of RapF and PhrF in regulating competence development is analogous to the previously described activity of RapC and PhrC (L. J. Core and M. Perego, Mol. Microbiol. 49:1509-1522, 2003). In fact, the RapF and PhrF pair of proteins acts synergistically with RapC and PhrC in the overall regulation of the ComA transcription factor. Since the transcription of the RapC- and RapF-encoding genes is positively regulated by their own target ComA, an autoregulatory circuit must exist for the competence transcription factor in order to modulate its activity. PMID:15968044

Molecular characterization of the Babesia caballi rap-1 gene and epidemiological survey in horses in Israel.

Science.gov (United States)

Rapoport, Adi; Aharonson-Raz, Karin; Berlin, Dalia; Tal, Saar; Gottlieb, Yuval; Klement, Eyal; Steinman, Amir

2014-04-01

Equine piroplasmosis imposes great concerns for the equine industry regarding international horse movement, and therefore requires reliable diagnostic tools. Recent studies from South Africa and Jordan, including a preliminary study in Israel, reported extremely low seroprevalence to Babesia caballi (B. caballi) (0-1%) using the acceptable rhoptry-associated protein-1 (RAP-1) cELISA. In accordance with the study from South Africa demonstrating a significant heterogeneity in the rap-1 gene sequence of South African B. caballi isolates, the objectives of this study were to phylogenetically characterize the rap-1 gene of the Israeli isolates and determine the prevalence of B. caballi in horses in Israel. Out of 273 horses tested using the RAP-1 cELISA, only one was sero-positive, while 9.3% were positive on PCR performed on the rap-1 gene. Phylogenetic analysis of the rap-1 gene grouped the Israeli isolates in a cluster together with the South African strains (99% nt identity), but in a separate cluster from the American/Caribbean strains (81-82% nt identity). These findings support the existence of heterogeneity in the RAP-1 amino-acid sequences of the Israeli and South African isolates as compared to that used in the cELISA commercial kit and raise doubts as to the ability of this assay to serve as a sole regulatory test for international horse movement. Risk factor analysis found management and age to significantly associate with prevalence of B. caballi, as higher prevalence was noted in horses held out on pasture and a negative association was recorded with age. In addition, B. caballi was not detected in horses in the steppe-arid and extreme-arid climatic regions as compared to the wetter regions. Findings of this study emphasize the need to combine several detection methods to ameliorate the control and spread of the disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Rap Poetry and Postmodernism

Directory of Open Access Journals (Sweden)

Kirill Molokov

2017-10-01

Full Text Available This article observes several most significant rap albums of this decade within postmodern literature. Today rap culture ceased to be a sort of “outsider” in academic opinion, because of its influences on the culture and art innovations. We study albums as literary objects according to literary aesthetic theories and principles, display the main postmodern features they have, and analyze the role of rap poetry within postmodernism in general. The results suggest that rap poetry is postmodern not only musically, but also lyrically, as an object of literature. The rap music embodies all the postmodern traits and synthesizes them within the syntheses of music and literature and high art and pop culture.

Cobalt production in RAPS-1

International Nuclear Information System (INIS)

Krishnan, P.D.; Purandare, H.D.

1978-01-01

At present in RAPS-1 radioisotope Co 60 is produced by irradiating Co 59 in the adjusters which perform the function of regulation of reactivity, power and xenon override. But the manrem expenditure of the crew handling the charge and discharge of the adjusters is going to be prohibitively high. It is therefore proposed to irradiate Co 59 in the fuel channel positions. The physics optimisation study for such irradiation is presented. The burnup penalty and loss of power are estimated to produce the required quantity of Co 60 after optimising the number of cobalt pencils in a bundle and the positions of the cobalt producing channels in the reactor core. (author)

Molecular characterization and chromosomal assignment of equine cartilage derived retinoic acid sensitive protein (CD-RAP)/melanoma inhibitory activity (MIA)

DEFF Research Database (Denmark)

Berg, Lise Charlotte; Mata, Xavier; Thomsen, Preben Dybdahl

2008-01-01

Cartilage-derived retinoic acid sensitive protein (CD-RAP) also known as melanoma inhibitory activity (MIA) has already been established as a marker for chondrocyte differentiation and a number of cancerous condition sin humans. Studies have also shown that CD-RAP/MIA is a potential marker of joint......RNA in articular cartilage and chondrocytes from horses with no signs of joint disease. The expression decreased as the cells dedifferentiated in monolayer culture. We also identified an equine CD-RAP/MIA splioce variant similar to that reported in humans. The CD_RAP/MIA protein was detected in equine synovial...... fluid, serum and culture medium from chondrocyte cultures. In conclusion, CD-RAP/MIA is expressed in equine cartilage and chondrocytes, and the protein can be detected in equine serum, synovial fluid and in culture medium from chondrocyte cultures. The equine gene and resulting protein share great...

PlexinA2 Forward Signaling through Rap1 GTPases Regulates Dentate Gyrus Development and Schizophrenia-like Behaviors

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Xiao-Feng Zhao

2018-01-01

Full Text Available Summary: Dentate gyrus (DG development requires specification of granule cell (GC progenitors in the hippocampal neuroepithelium, as well as their proliferation and migration into the primordial DG. We identify the Plexin family members Plxna2 and Plxna4 as important regulators of DG development. Distribution of immature GCs is regulated by Sema5A signaling through PlxnA2 and requires a functional PlxnA2 GTPase-activating protein (GAP domain and Rap1 small GTPases. In adult Plxna2−/− but not Plxna2-GAP-deficient mice, the dentate GC layer is severely malformed, neurogenesis is compromised, and mossy fibers form aberrant synaptic boutons within CA3. Behavioral studies with Plxna2−/− mice revealed deficits in associative learning, sociability, and sensorimotor gating—traits commonly observed in neuropsychiatric disorder. Remarkably, while morphological defects are minimal in Plxna2-GAP-deficient brains, defects in fear memory and sensorimotor gating persist. Since allelic variants of human PLXNA2 and RAP1 associate with schizophrenia, our studies identify a biochemical pathway important for brain development and mental health. : Zhao et al. find that Sema5A-PlexinA2 forward signaling through Rap1 GTPases is required for progenitor distribution in the developing mouse dentate gyrus. Adult Plxna2−/−, but not Plxna2-GAP-deficient, mice show defects in dentate morphology, neurogenesis, and mossy fiber connectivity. Plxna2−/− and Plxna2-GAP mice exhibit behavioral defects suggestive of neuropsychiatric illness. Keywords: PlexinA2, semaphoring, Rap1, GAP, dentate gyrus, adult neurogenesis, mossy fiber, fear memory, sensorimotor gating, schizophrenia

Assessment of transferring Sr-90 and Cs-137 in products of processing of seeds raps for getting raps' oil and biodiesel

International Nuclear Information System (INIS)

Yatsino, T.S.; Mironov, V.P.

2009-01-01

The objects of research are soil assays, seeds of raps, straw and the stalks selected on polluted radio nuclides of territory. The work purpose is to measure specific activity of strontium and cesium in assays, to calculate factors of transition Sr 90 and Sr 137 in products of processing of seeds of raps. (authors)

[Cloning of VH and VL Gene of Human anti-IL1RAP McAb and Construction of Recombinant Chimeric Receptor].

Science.gov (United States)

Yin, Ling-Ling; Ruan, Su-Hong; Tian, Yu; Zhao, Kai; Xu, Kai Lin

2015-10-01

To clone the variable region genes of human anti-IL1RAP (IL-1 receptor accessory protein) monoclonal antibodies (McAb) and to construct IL1RAP chimeric antigen receptors (CARs). The VH and VL DNA of IL1RAP single chain antibodies were amplified by RACE and overlap extension PCR from total RNA extracted from 3H6E10 and 10D8A7 hybridoma and ligated into specific IL1RAP single-chain variable fragments (scFv). CD8α transmembrane domain, CD137 intracellular domain, TCR ζ chain, human CD8α signal peptide and scFv-anti-IL1RAP were cloned into plasmid LV-lac. Recombinant lentiviruses were generated by co-transfection of recombinant plasmid LV-lac, pMD2. G, and psPAX2 helper vectors into 293FT packing cells. The VH and VL genes of 2 human anti-IL1RAP McAb were acquired. The 3H6E10 VH and VL genes consisted of 402 bp and 393 bp encoding 134 and 131 aminoacid residues, respectively; 10D8A7 VH and VL genes consisted of 423 bp and 381 bp encoding 141 and 127 amine acid residues, respectively. Recombinant expression vertors LV-3H6E10 scFv-ICD and LV-10D8A7 scFv-ICD (ICD: CD8α transmembrane domain-CD137 intracellular domain-TCR ζ chain) were constructed. The target fragments were demonstrated by sequencing analysis. Recombinant plasmids were transfected into 293FT cells and lentiviral particles were acquired. Human anti-IL1RAP recombinant receptors are constructed successfully and lay a good foundation for the construction of IL1RAP-CAR killer T cell vaccine.

Activation of G protein-coupled estrogen receptor 1 induces coronary artery relaxation via Epac/Rap1-mediated inhibition of RhoA/Rho kinase pathway in parallel with PKA.

Directory of Open Access Journals (Sweden)

Xuan Yu

Full Text Available Previously, we reported that cAMP/PKA signaling is involved in GPER-mediated coronary relaxation by activating MLCP via inhibition of RhoA pathway. In the current study, we tested the hypothesis that activation of GPER induces coronary artery relaxation via inhibition of RhoA/Rho kinase pathway by cAMP downstream targets, exchange proteins directly activated by cAMP (Epac as well as PKA. Our results show that Epac inhibitors, brefeldin A (BFA, 50 μM, or ESI-09 (20 μM, or CE3F4 (100 μM, all partially inhibited porcine coronary artery relaxation response to the selective GPER agonist, G-1 (0.3-3 μM; while concurrent administration of BFA and PKI (5 μM, a PKA inhibitor, almost completely blocked the relaxation effect of G-1. The Epac specific agonist, 8-CPT-2Me-cAMP (007, 1-100 μM, induced a concentration-dependent relaxation response. Furthermore, the activity of Ras-related protein 1 (Rap1 was up regulated by G-1 (1 μM treatment of porcine coronary artery smooth muscle cells (CASMCs. Phosphorylation of vasodilator-stimulated phosphoprotein (p-VASP was elevated by G-1 (1 μM treatment, but not by 007 (50 μM; and the effect of G-1 on p-VASP was blocked by PKI, but not by ESI-09, an Epac antagonist. RhoA activity was similarly down regulated by G-1 and 007, whereas ESI-09 restored most of the reduced RhoA activity by G-1 treatment. Furthermore, G-1 decreased PGF2α-induced p-MYPT1, which was partially reversed with either ESI-09 or PKI; whereas, concurrent administration of ESI-09 and PKI totally prevented the inhibitory effect of G-1. The inhibitory effects of G-1 on p- MLC levels in CASMCs were mostly restored by either ESI-09 or PKI. These results demonstrate that activation of GPER induces coronary artery relaxation via concurrent inhibition of RhoA/Rho kinase by Epac/Rap1 and PKA. GPER could be a potential drug target for preventing and treating cardiovascular diseases.

"Everybody Gotta Have a Dream": Rap-centered Aspirations among Young Black Males Involved in Rap Music Production - A Qualitative Study.

Science.gov (United States)

Foster, B Brian

Youth express diverse desires for their educational and occupational futures. Sometimes these aspirations are directed towards somewhat unconventional careers such as rapping and other types of involvement in rap music production. Although many studies have examined traditional educational and occupational aspirations, less is known about the factors that give rise to rap-centered aspirations and how individuals pursue them, particularly as they transition to early adulthood. Drawing on 54 semi- and unstructured interviews with 29 black young men involved in rap music production, I find that rap-centered aspirations are shaped by a range of factors, most notably feedback regarding one's rap skills, access to recording and production equipment, and the financial means to maintain involvement in rap music production while also ensuring personal and family economic stability. The young men in the study attached different meanings to their aspirations and sometimes recast their motivations for participating in rap music production in response to various social and economic factors.

Rhoptry-associated protein (rap-1) genes in the sheep pathogen Babesia sp. Xinjiang: Multiple transcribed copies differing by 3' end repeated sequences.

Science.gov (United States)

Niu, Qingli; Marchand, Jordan; Yang, Congshan; Bonsergent, Claire; Guan, Guiquan; Yin, Hong; Malandrin, Laurence

2015-07-30

Sheep babesiosis occurs mainly in tropical and subtropical areas. The sheep parasite Babesia sp. Xinjiang is widespread in China, and our goal is to characterize rap-1 (rhoptry-associated protein 1) gene diversity and expression as a first step of a long term goal aiming at developing a recombinant subunit vaccine. Seven different rap-1a genes were amplified in Babesia sp. Xinjiang, using degenerate primers designed from conserved motifs. Rap-1b and rap-1c gene types could not be identified. In all seven rap-1a genes, the 5' regions exhibited identical sequences over 936 nt, and the 3' regions differed at 28 positions over 147 nt, defining two types of genes designated α and β. The remaining 3' part varied from 72 to 360 nt in length, depending on the gene. This region consists of a succession of two to ten 36 nt repeats, which explains the size differences. Even if the nucleotide sequences varied, 6 repeats encoded the same stretch of amino acids. Transcription of at least four α and two β genes was demonstrated by standard RT-PCR. Copyright © 2015 Elsevier B.V. All rights reserved.

Species-Specific Expression of Full-Length and Alternatively Spliced Variant Forms of CDK5RAP2.

Directory of Open Access Journals (Sweden)

John S Y Park

Full Text Available CDK5RAP2 is one of the primary microcephaly genes that are associated with reduced brain size and mental retardation. We have previously shown that human CDK5RAP2 exists as a full-length form (hCDK5RAP2 or an alternatively spliced variant form (hCDK5RAP2-V1 that is lacking exon 32. The equivalent of hCDK5RAP2-V1 has been reported in rat and mouse but the presence of full-length equivalent hCDK5RAP2 in rat and mouse has not been examined. Here, we demonstrate that rat expresses both a full length and an alternatively spliced variant form of CDK5RAP2 that are equivalent to our previously reported hCDK5RAP2 and hCDK5RAP2-V1, repectively. However, mouse expresses only one form of CDK5RAP2 that is equivalent to the human and rat alternatively spliced variant forms. Knowledge of this expression of different forms of CDK5RAP2 in human, rat and mouse is essential in selecting the appropriate model for studies of CDK5RAP2 and primary microcephaly but our findings further indicate the evolutionary divergence of mouse from the human and rat species.

MiR-203 involves in neuropathic pain development and represses Rap1a expression in nerve growth factor differentiated neuronal PC12 cells.

Science.gov (United States)

Li, Haixia; Huang, Yuguang; Ma, Chao; Yu, Xuerong; Zhang, Zhiyong; Shen, Le

2015-01-01

Although microRNAs (miRNAs) have been shown to play a role in numerous biological processes, their function in neuropathic pain is not clear. The rat bilateral sciatic nerve chronic constriction injury (bCCI) is an established model of neuropathic pain, so we examined miRNA expression and function in the spinal dorsal horn in bCCI rats. Microarray and real-time polymerase chain reaction were used to examine the expression of miRNA in nerve system of bCCI rats, and the targets of miRNA were predicted by bioinformatic approaches. The function of specific miRNA was estimated through the methods of gene engineering. This study revealed substantially (∼10-fold) decreased miR-203 expression in the spinal dorsal horns but not the dorsal root ganglions, hippocampus, or anterior cingulate cortexes of bCCI rats. Rap1a protein expression was upregulated in bCCI rat spinal dorsal horns. We further verified that miR-203 directly targeted the 3'-untranslated region of the rap1a gene, thereby decreasing rap1a protein expression in neuron-like cells. Rap1a has diverse neuronal functions and their perturbation is responsible for several mental disorders. For example, Rap1a/MEK/ERK is involved in peripheral sensitization. These data suggest a potential role for miR-203 in regulating neuropathic pain development, and Rap1a is a validated target gene in vitro. Results from our study and others indicate the possibility that Rap1a may be involved in pain. We hope that these results can provide support for future research into miR-203 in gene therapy for neuropathic pain.

Mutations in CDK5RAP2 cause Seckel syndrome.

Science.gov (United States)

Yigit, Gökhan; Brown, Karen E; Kayserili, Hülya; Pohl, Esther; Caliebe, Almuth; Zahnleiter, Diana; Rosser, Elisabeth; Bögershausen, Nina; Uyguner, Zehra Oya; Altunoglu, Umut; Nürnberg, Gudrun; Nürnberg, Peter; Rauch, Anita; Li, Yun; Thiel, Christian Thomas; Wollnik, Bernd

2015-09-01

Seckel syndrome is a heterogeneous, autosomal recessive disorder marked by prenatal proportionate short stature, severe microcephaly, intellectual disability, and characteristic facial features. Here, we describe the novel homozygous splice-site mutations c.383+1G>C and c.4005-9A>G in CDK5RAP2 in two consanguineous families with Seckel syndrome. CDK5RAP2 (CEP215) encodes a centrosomal protein which is known to be essential for centrosomal cohesion and proper spindle formation and has been shown to be causally involved in autosomal recessive primary microcephaly. We establish CDK5RAP2 as a disease-causing gene for Seckel syndrome and show that loss of functional CDK5RAP2 leads to severe defects in mitosis and spindle organization, resulting in cells with abnormal nuclei and centrosomal pattern, which underlines the important role of centrosomal and mitotic proteins in the pathogenesis of the disease. Additionally, we present an intriguing case of possible digenic inheritance in Seckel syndrome: A severely affected child of nonconsanguineous German parents was found to carry heterozygous mutations in CDK5RAP2 and CEP152. This finding points toward a potential additive genetic effect of mutations in CDK5RAP2 and CEP152.

Mutations in CDK5RAP2 cause Seckel syndrome

Science.gov (United States)

Yigit, Gökhan; Brown, Karen E; Kayserili, Hülya; Pohl, Esther; Caliebe, Almuth; Zahnleiter, Diana; Rosser, Elisabeth; Bögershausen, Nina; Uyguner, Zehra Oya; Altunoglu, Umut; Nürnberg, Gudrun; Nürnberg, Peter; Rauch, Anita; Li, Yun; Thiel, Christian Thomas; Wollnik, Bernd

2015-01-01

Seckel syndrome is a heterogeneous, autosomal recessive disorder marked by prenatal proportionate short stature, severe microcephaly, intellectual disability, and characteristic facial features. Here, we describe the novel homozygous splice-site mutations c.383+1G>C and c.4005-9A>G in CDK5RAP2 in two consanguineous families with Seckel syndrome. CDK5RAP2 (CEP215) encodes a centrosomal protein which is known to be essential for centrosomal cohesion and proper spindle formation and has been shown to be causally involved in autosomal recessive primary microcephaly. We establish CDK5RAP2 as a disease-causing gene for Seckel syndrome and show that loss of functional CDK5RAP2 leads to severe defects in mitosis and spindle organization, resulting in cells with abnormal nuclei and centrosomal pattern, which underlines the important role of centrosomal and mitotic proteins in the pathogenesis of the disease. Additionally, we present an intriguing case of possible digenic inheritance in Seckel syndrome: A severely affected child of nonconsanguineous German parents was found to carry heterozygous mutations in CDK5RAP2 and CEP152. This finding points toward a potential additive genetic effect of mutations in CDK5RAP2 and CEP152. PMID:26436113

Rapid Refresh (RAP) [13 km

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The Rapid Refresh (RAP) numerical weather model took the place of the Rapid Update Cycle (RUC) on May 1, 2012. Run by the National Centers for Environmental...

Rapid Refresh (RAP) [20 km

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The Rapid Refresh (RAP) numerical weather model took the place of the Rapid Update Cycle (RUC) on May 1, 2012. Run by the National Centers for Environmental...

Overview of the remedial action priority system (RAPS)

International Nuclear Information System (INIS)

Whelan, G.; Steelman, B.L.; Strenge, D.L.; Droppo, J.G.

1986-01-01

To provide DOE with a better management tool for prioritizing funding allocations for further site investigations and possible remediations, Pacific Northwest Laboratory developed a more objective, physics-based risk assessment methodology called the Remedial Action Priority System (RAPS). This methodology uses empirically, analytically, and semianalytically based mathematical algorithms and a pathways analysis to predict the potential for contaminant transport from a hazardous waste disposal site to local populations. Four major pathways for contaminant migration are considered in the RAPS methodology: groundwater, overland, surface water, and atmospheric. Using the predications of contaminant transport, simplified exposure assessments are performed for important receptors. The risks associated with the sites can then be calculated relative to other sites for each pathway and for all pathways together. The RAPS methodology addresses many of the typical limitations associated with other ranking systems; it considers: (1) more site information and constituent characteristics associated with the transport pathways; (2) chemical and radioactive wastes; (3) the potential direction of contaminant movement; (4) contaminant retention (e.g., dispersion and decay/degradation), where applicable; (5) population distributions; (6) various routes of exposure (e.g., inhalations, ingestion, and external exposure); (7) contaminant toxicities; (8) duration of exposure of the surrounding population; and (9) contaminant arrival time to sensitive receptors. Because RAPS is based on more site information and constituent characteristics, the scoring system of the RAPS methodology also reduces the subjectivity associated with prioritizing hazardous waste sites. The RAPS methodology requires minimum user knowledge of risk assessment and a minimum amount of input data

Specificity versus redundancy in the RAP2.4 transcription factor family of Arabidopsis thaliana: transcriptional regulation of genes for chloroplast peroxidases.

Science.gov (United States)

Rudnik, Radoslaw; Bulcha, Jote Tafese; Reifschneider, Elena; Ellersiek, Ulrike; Baier, Margarete

2017-08-23

The Arabidopsis ERFIb / RAP2.4 transcription factor family consists of eight members with highly conserved DNA binding domains. Selected members have been characterized individually, but a systematic comparison is pending. The redox-sensitive transcription factor RAP2.4a mediates chloroplast-to-nucleus redox signaling and controls induction of the three most prominent chloroplast peroxidases, namely 2-Cys peroxiredoxin A (2CPA) and thylakoid- and stromal ascorbate peroxidase (tAPx and sAPx). To test the specificity and redundancy of RAP2.4 transcription factors in the regulation of genes for chloroplast peroxidases, we compared the DNA-binding sites of the transcription factors in tertiary structure models, analyzed transcription factor and target gene regulation by qRT-PCR in RAP2.4, 2-Cys peroxiredoxin and ascorbate peroxidase T-DNA insertion lines and RAP2.4 overexpressing lines of Arabidopsis thaliana and performed promoter binding studies. All RAP2.4 proteins bound the tAPx promoter, but only the four RAP2.4 proteins with identical DNA contact sites, namely RAP2.4a, RAP2.4b, RAP2.4d and RAP2.4h, interacted stably with the redox-sensitive part of the 2CPA promoter. Gene expression analysis in RAP2.4 knockout lines revealed that RAP2.4a is the only one supporting 2CPA and chloroplast APx expression. Rap2.4h binds to the same promoter region as Rap2.4a and antagonizes 2CPA expression. Like the other six RAP2.4 proteins, Rap2.4 h promotes APx mRNA accumulation. Chloroplast ROS signals induced RAP2.4b and RAP2.4d expression, but these two transcription factor genes are (in contrast to RAP2.4a) insensitive to low 2CP availability, and their expression decreased in APx knockout lines. RAP2.4e and RAP2.4f gradually responded to chloroplast APx availability and activated specifically APx expression. These transcription factors bound, like RAP2.4c and RAP2.4g, the tAPx promoter, but hardly the 2CPA promoter. The RAP2.4 transcription factors form an environmentally and

The Remedial Action Priority System (RAPS): Mathematical formulations

International Nuclear Information System (INIS)

Whelan, G.; Strenge, D.L.; Droppo, J.G. Jr.; Steelman, B.L.; Buck, J.W.

1987-08-01

The Remedial Action Priority System (RAPS) represents a methodology that prioritizes inactive hazardous and radioactive mixed-waste disposal sites in a scientific and objective manner based on limited site information. This methodology is intended to bridge the technology gap between the initial site evaluation using the Hazard Ranking System (HRS) and the time-consuming process of actual field site characterization, assessment, and remediation efforts. The RAPS methodology provides the US Department of Energy with a management tool for assistance in prioritizing funding and human resource allocations for further investigations and possible remediations at its inactive waste sites. Use of RAPS will help DOE ensure that those sites posing the highest potential risk are addressed first. Chapters 1 through 10 were processed separately for the Energy Data Base

Life extension and replacement management for RAPS type steam generators

International Nuclear Information System (INIS)

Arya, R.C.; Rastogi, A.K.

1996-01-01

The steam generating equipment in first four units of Indian PHWRs Rajasthan Atomic Power Station (RAPS) 1-2 and Madras Atomic Power Station (MAPS) 1-2 are hairpin type and comprise of eight boiler assemblies. Each assembly consists of identical, single pass, inverted and vertical hairpin heat exchangers (10 for RAPS and 11 for MAPS) containing 195 monel-400 U tubes of 12.7 mm dia x 1.242 mm thick. The hot heavy water flows through these tubes and imparts heat to feed, light demineralized water entering the shell at the bottom of preheat leg. The heat is generated on the outer surface of the tubes. Details of studies carried out for life extension and replacement management for RAPS type steam generators are given. 1 fig., 5 tabs

Translating Chicana Rap: Snow Tha Product

Directory of Open Access Journals (Sweden)

Adriana Onita

2017-06-01

Full Text Available This project examines rap lyrics, interviews, and music videos by Chicana artist Snow Tha Product to show how rap has been culturally translated, performed, and appropriated by females in order to “flip the script,” or subvert the dichotomous model of female sexuality that has been imposed upon them. Weaving insights from three academic fields (cultural translation, Chican@ studies, and hip-hop feminism, this paper also aims to creatively expand the definition of translation by positioning rap music as a performative language in its own right, capable of encoding and translating complex cultural issues related to race, gender, and sexuality.

Polymorphisms of ST2-IL18R1-IL18RAP gene cluster: a new risk for autoimmune thyroid diseases.

Science.gov (United States)

Wang, X; Zhu, Y F; Li, D M; Qin, Q; Wang, Q; Muhali, F S; Jiang, W J; Zhang, J A

2016-02-01

Interleukin 33 (IL33) / ST2 pathway and ST2-interlukin18 receptor1-interlukin18 receptor accessory protein (ST2-IL18R1-IL18RAP) gene cluster have been involved in many autoimmune diseases but few report in autoimmune thyroid diseases (AITD). In this study, we investigated whether polymorphisms of IL33, ST2, IL18R1, and IL18RAP are associated with Graves' disease (GD) and Hashimoto's thyroiditis (HT), two major forms of AITD, among a Chinese population. A total of 11 SNPs were explored in a case-control study including 417 patients with GD, 250 HT patients and 301 controls, including rs1929992, rs10975519, rs10208293, rs6543116, rs1041973, rs3732127, rs11465597, rs1035130, rs2293225, rs1035127, rs917997 of IL 33, ST2-IL18R1-IL18RAP gene cluster. Genotyping of these SNPs was performed using matrix-assisted laser desorption / ionization-time-of-flight mass spectrometer (MALDI-TOF-MS) platform from Sequenom. The frequencies of allele A and AA+AG genotype of rs6543116 (ST2) in HT patients were significantly increased compared with those of the controls (P = 0.029/0.021, OR = 1.31/1.62). And in another SNP rs917997, AA+AG genotype presented an increased frequency in HT subjects compared with controls (P = 0.046, OR = 1.53). Furthermore, the haplotype GAGCCCG from ST2-IL18R1-IL18RAP gene cluster (rs6543116, rs1041973, rs1035130, rs3732127, rs1035127, rs2293225, rs917997) was associated with increased susceptibility to GD with an OR of 2.03 (P = 0.022, 95% CI = 1.07-3.86). Some SNPs of ST2-IL18R1-IL18RAP gene cluster might increase the risk of susceptibility of HT and GD in Chinese Han population. © 2015 John Wiley & Sons Ltd.

Rap Music Genres and Deviant Behaviors in French-Canadian Adolescents

Science.gov (United States)

Miranda, Dave; Claes, Michel

2004-01-01

This study investigated the links between the preference for 4 rap music genres (American rap, French rap, hip hop/soul, and gangsta/hardcore rap) and 5 types of deviant behaviors in adolescence (violence, theft, street gangs, mild drug use, and hard drug use). The effects of peers' deviancy, violent media, and importance given to lyrics were…

Epac activation sensitizes rat sensory neurons via activation of Ras

Science.gov (United States)

Shariati, Behzad; Thompson, Eric L.; Nicol, Grant D.; Vasko, Michael R.

2015-01-01

Guanine nucleotide exchange factors directly activated by cAMP (Epacs) have emerged as important signaling molecules mediating persistent hypersensitivity in animal models of inflammation, by augmenting the excitability of sensory neurons. Although Epacs activate numerous downstream signaling cascades, the intracellular signaling which mediates Epac-induced sensitization of capsaicin-sensitive sensory neurons remains unknown. Here, we demonstrate that selective activation of Epacs with 8-CPT-2′-O-Me-cAMP-AM (8CPT-AM) increases the number of action potentials (APs) generated by a ramp of depolarizing current and augments the evoked release of calcitonin gene-related peptide (CGRP) from isolated rat sensory neurons. Internal perfusion of capsaicin-sensitive sensory neurons with GDP-βS, substituted for GTP, blocks the ability of 8CPT-AM to increase AP firing, demonstrating that Epac-induced sensitization is G-protein dependent. Treatment with 8CPT-AM activates the small G-proteins Rap1 and Ras in cultures of sensory neurons. Inhibition of Rap1, by internal perfusion of a Rap1-neutralizing antibody or through a reduction in the expression of the protein using shRNA does not alter the Epac-induced enhancement of AP generation or CGRP release, despite the fact that in most other cell types, Epacs act as Rap-GEFs. In contrast, inhibition of Ras through expression of a dominant negative Ras (DN-Ras) or through internal perfusion of a Ras-neutralizing antibody blocks the increase in AP firing and attenuates the increase in the evoked release of CGRP induced by Epac activation. Thus, in this subpopulation of nociceptive sensory neurons, it is the novel interplay between Epacs and Ras, rather than the canonical Epacs and Rap1 pathway, that is critical for mediating Epac-induced sensitization. PMID:26596174

Epac activation sensitizes rat sensory neurons through activation of Ras.

Science.gov (United States)

Shariati, Behzad; Thompson, Eric L; Nicol, Grant D; Vasko, Michael R

2016-01-01

Guanine nucleotide exchange factors directly activated by cAMP (Epacs) have emerged as important signaling molecules mediating persistent hypersensitivity in animal models of inflammation, by augmenting the excitability of sensory neurons. Although Epacs activate numerous downstream signaling cascades, the intracellular signaling which mediates Epac-induced sensitization of capsaicin-sensitive sensory neurons remains unknown. Here, we demonstrate that selective activation of Epacs with 8-CPT-2'-O-Me-cAMP-AM (8CPT-AM) increases the number of action potentials (APs) generated by a ramp of depolarizing current and augments the evoked release of calcitonin gene-related peptide (CGRP) from isolated rat sensory neurons. Internal perfusion of capsaicin-sensitive sensory neurons with GDP-βS, substituted for GTP, blocks the ability of 8CPT-AM to increase AP firing, demonstrating that Epac-induced sensitization is G-protein dependent. Treatment with 8CPT-AM activates the small G-proteins Rap1 and Ras in cultures of sensory neurons. Inhibition of Rap1, by internal perfusion of a Rap1-neutralizing antibody or through a reduction in the expression of the protein using shRNA does not alter the Epac-induced enhancement of AP generation or CGRP release, despite the fact that in most other cell types, Epacs act as Rap-GEFs. In contrast, inhibition of Ras through expression of a dominant negative Ras (DN-Ras) or through internal perfusion of a Ras-neutralizing antibody blocks the increase in AP firing and attenuates the increase in the evoked release of CGRP induced by Epac activation. Thus, in this subpopulation of nociceptive sensory neurons, it is the novel interplay between Epacs and Ras, rather than the canonical Epacs and Rap1 pathway, that is critical for mediating Epac-induced sensitization. Copyright © 2015 Elsevier Inc. All rights reserved.

Microstructure of shear-induced thixoformed Al- 4.5Cu-1.5Mg alloy via RAP and SSTT processes

Directory of Open Access Journals (Sweden)

Siamak Nikzad

2017-07-01

Full Text Available In this research, the effect of the thixoforming temperature on the microstructure and mechanical properties was investigated in the thixoforming of the feedstock produced by the RAP (recrystallization and partial melting and SSTT (semi-solid thermal transformation processes for Al-4.5Cu-1.5Mg alloy. In the RAP process, the percentage reduction in area was approximately 35%. Thixoforming was done at 610, 620, and 630 °C. Globular microstructure was observed at all temperatures and conditions. The minimum average globule size was 39 μm, and it was obtained in the thixoforming of the feedstock produced by the RAP process in the section of 4 mm in diameter at 620 ° C after applying shear. Its corresponding compressive strength was -877.44 MPa. The maximum average globule size was 136 μm, and it was obtained in the thixoforming of the feedstock produced by the SSTT process in the section of 10 mm in diameter at 630 °C before applying shear. Its corresponding compressive strength was -769.18 MPa. The finest and most spherical globules, as well as the highest compressive strength were obtained at 620 °C in both RAP and SSTT states.

Molas Baju Wara: Hybridity in Manggarai Rap Music

Directory of Open Access Journals (Sweden)

Ans. Prawati Yuliantari

2017-06-01

Full Text Available Rap music which has been popular since 2007 in Manggarai region, East Nusa Tenggara, Indonesia, gave rise to rap hybrid phenomenon. The mixture between American rap music formats and local elements of Manggarai attracted the attention of young people in the region. One of the local songs that feature hybridity in rap Manggarai is "Molas Baju Wara" created by Lipooz, one of the pioneers of rap in Ruteng, the capital city of Manggarai district. To discuss this phenomenon, the concept of hybridity in cultural territory proposed by James Lull is adopted. This concept is used particularly to analyze the forms of hybridity reflected in " Molas Baju Wara" and the ways they are used in showing the social and cultural conditions of Manggarai. "Molas Baju Wara" was selected as the object of study because the song is clearly showing the characteristics of hybridity in music. The study shows that hybridity could be perceived in Manggarai rap music specifically in the use of local musical instruments like drums, cajon, and tambourine as a substitute for percussive sounds of drums, boombox, or turn-table which are commonly used by rap musicians in their home country, the U.S.A. In addition, there are elements of local sound such as the sound of rain that represents Ruteng as the rain city. Hybridity characteristics can also be found in the use of Manggarai vernacular in the whole lyrics as well as the narration of local themes and certain sites that represent Ruteng.

miR-203a is involved in HBx-induced inflammation by targeting Rap1a

Energy Technology Data Exchange (ETDEWEB)

Wu, AiRong [Department of gastroenterology, The First affiliated Hospital of Soochow University, Suzhou 215006 (China); Chen, Huo [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123 (China); Xu, ChunFang [Department of gastroenterology, The First affiliated Hospital of Soochow University, Suzhou 215006 (China); Zhou, Ji; Chen, Si [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123 (China); Shi, YuQi [Department of gastroenterology, The First affiliated Hospital of Soochow University, Suzhou 215006 (China); Xu, Jie [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123 (China); Gan, JianHe, E-mail: j_pzhang@suda.edu.cn [Department of gastroenterology, The First affiliated Hospital of Soochow University, Suzhou 215006 (China); Zhang, JinPing, E-mail: ganjianhe@aliyun.com [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123 (China)

2016-11-15

Hepatitis B virus (HBV) causes acute and chronic hepatitis, and is one of the major causes of cirrhosis and hepatocellular carcinoma. Accumulating evidence suggests that inflammation is the key factor for liver cirrhosis and hepatocellular carcinoma. MicroRNAs play important roles in many biological processes. Here, we aim to explore the function of microRNAs in the HBX-induced inflammation. First, microarray experiment showed that HBV{sup +} liver samples expressed higher level of miR-203a compared to HBV{sup -} liver samples. To verify these alterations, HBx-coding plasmid was transfected into HepG2 cells to overexpress HBx protein. The real-time PCR results suggested that over-expression of HBx could induce up-regulation of miR-203a. To define how up-regulation of miR-203a can induce liver cells inflammation, we over-expressed miR-203a in HepG2 cells. Annexin V staining and BrdU staining suggested that overexpression of miR-203a significantly increased the cell apoptosis and proliferation, meanwhile, over-expression of miR-203a could lead to a decrease in G0/G1 phase cells and an increase in G2/M phase cells. Some cytokines production including IL-6 and IL-8 were significantly increased, but TGFβ and IFNγ were decreased in miR-203a over-expressed HepG2 cells. Luciferase reporter assay experiments, protein mass-spectrum assay and real-time PCR all together demonstrated that Rap1a was the target gene of miR-203a. Further experiments showed that these alterations were modulated through PI3K/ERK/p38/NFκB pathways. These data suggested that HBV-infection could up-regulate the expression of miR-203a, thus down regulated the expression of Rap1a and affected the PI3K/ERK/p38/NFκB pathways, finally induced the hepatitis inflammation. - Highlights: • HBX induces the over-expression of miR-203a in HepG2 cells. • miR-203a targets Rap1a to induce the inflammation in HepG2 cells. • miR-203a regulates the apoptosis and cell cycles of HepG2 cells. • miR-203a alters

Transcriptional activation of peroxisome proliferator-activated receptor-γ requires activation of both protein kinase A and Akt during adipocyte differentiation

International Nuclear Information System (INIS)

Kim, Sang-pil; Ha, Jung Min; Yun, Sung Ji; Kim, Eun Kyoung; Chung, Sung Woon; Hong, Ki Whan; Kim, Chi Dae; Bae, Sun Sik

2010-01-01

Research highlights: → Elevated cAMP activates both PKA and Epac. → PKA activates CREB transcriptional factor and Epac activates PI3K/Akt pathway via Rap1. → Akt modulates PPAR-γ transcriptional activity in concert with CREB. -- Abstract: Peroxisome proliferator-activated receptor-γ (PPAR-γ) is required for the conversion of pre-adipocytes. However, the mechanism underlying activation of PPAR-γ is unclear. Here we showed that cAMP-induced activation of protein kinase A (PKA) and Akt is essential for the transcriptional activation of PPAR-γ. Hormonal induction of adipogenesis was blocked by a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002), by a protein kinase A (PKA) inhibitor (H89), and by a Rap1 inhibitor (GGTI-298). Transcriptional activity of PPAR-γ was markedly enhanced by 3-isobutyl-1-methylxanthine (IBMX), but not insulin and dexamethasone. In addition, IBMX-induced PPAR-γ transcriptional activity was blocked by PI3K/Akt, PKA, or Rap1 inhibitors. 8-(4-Chlorophenylthio)-2'-O-methyl-cAMP (8-pCPT-2'-O-Me-cAMP) which is a specific agonist for exchanger protein directly activated by cAMP (Epac) significantly induced the activation of Akt. Furthermore, knock-down of Akt1 markedly attenuated PPAR-γ transcriptional activity. These results indicate that both PKA and Akt signaling pathways are required for transcriptional activation of PPAR-γ, suggesting post-translational activation of PPAR-γ might be critical step for adipogenic gene expression.

Anti-inflammatory and analgesic activity of r.a.p . ( Radix Angelicae ...

African Journals Online (AJOL)

The objective of this paper was to study the anti-inflammatory and analgesic effects of Radix Angelicae Pubescentis (R.A.P) ethanol extracts. Three classic anti-inflammatory models and two analgesic models were used in this research. In anti-inflammatory tests, all the extracts have a certain inhibition on the acute ...

Rapping dyslexia : learning rhythm, rhyme and flow in dyslectic children

NARCIS (Netherlands)

Tittarelli, M.; Marti, P.; Peppoloni, D.

2014-01-01

The paper presents a design case that draws inspiration from rap music as a way to tell stories rhythmically, with simple instruments for accompaniment. Rhythm, rhymes and flow are key features of rap music. In this study, we attempted to apply rap principles and dynamics to a very specific field of

LHC rap: a global phenomenon

CERN Multimedia

2008-01-01

Do you think the LHC is super duper fly? Does it make you want to compose some slick rhymes and bust out some killer beats? It did for one CERN rapper, and the results have become a YouTube smash hit! Katie McAlpine will sing for the CMS party on 24 September, and for the ATLAS Fest on 4 October.The Large Hadron Rap, to give it its full name, is the brainchild of AlpineKat, AKA Katie McAlpine, who is currently working for ATLAS e-News and outreach. To date, the YouTube video rap has been viewed more than 2.5 million times, to say nothing of the media coverage. Featured in newspapers around the world, including the New York Times in the US, The Telegraph in the UK and Geneva’s very own Matin Bleu, the rap is officially a sensation! Katie wrote the inspired (and pretty accurate) physics lyrics during her commute on the number 56 bus between Geneva and CERN. After obtaining permission to film in the experiment caverns and tunnel,...

Volumetric Analysis and Performance of Hot Mix Asphalt with Variable Rap Content

Directory of Open Access Journals (Sweden)

Arshad Ahmad Kamil

2017-01-01

Full Text Available Incorporating Reclaimed Asphalt Pavement (RAP to the asphalt concrete mixture for highway construction offer many benefits including energy consumption, conservation of natural resources and preservation of the environment to associated emissions. This paper presents a study on performance of Hot Mix Asphalt with variable RAP content. The study is carried out to evaluate the Marshall Properties and Performance of RAP-Asphalt mixes using conventional asphaltic concrete mix AC14. Marshall Mix Design Method was used to produce control mix (0% RAP and RAP-Asphalt mixes samples which consist of 15% RAP, 25% RAP and 35% RAP in accordance with Specifications for Road Works of Public Works Department, Malaysia. The Marshall Properties analysis was performed to ensure compliance with Marshall Requirements, The resilient modulus test was performed to measure the stiffness of the mixes while Modified Lottman test was conducted to evaluate the moisture susceptibility of these mixes. The results obtained showed that there were no substantial difference in Marshall Properties, moisture susceptibility and indirect tensile strength between RAP-Asphalt mixes with the control mix. The test results indicated that recycled mixes performed as good as the performance of conventional HMA in terms of moisture susceptibility and resilient modulus. It is recommended that further research be carried out for asphalt mixes containing more than 35% of RAP material.

Product (P1) from project 0-6738 : performance studies and future directions for mixes containing RAP and RAS.

Science.gov (United States)

2013-01-01

In recent years both reclaimed asphalt pavement (RAP) and recycled asphalt shingles (RAS) have been widely used in asphalt mixes by the asphalt paving industry in Texas. The use of RAP and RAS can save tax payers money, and it is also good for the...

Performance Evaluation of Hot Mix Asphalt with Different Proportions of RAP Content

Science.gov (United States)

Kamil Arshad, Ahmad; Awang, Haryati; Shaffie, Ekarizan; Hashim, Wardati; Rahman, Zanariah Abd

2018-03-01

Reclaimed Asphalt Pavement (RAP) is old asphalt pavement that has been removed from a road by milling or full depth removal. The use of RAP in hot mix asphalt (HMA) eliminates the need to dispose old asphalt pavements and conserves asphalt binders and aggregates, resulting in significant cost savings and benefits to society. This paper presents a study on HMA with different RAP proportions carried out to evaluate the volumetric properties and performance of asphalt mixes containing different proportions of RAP. Marshall Mix Design Method was used to produce control mix (0% RAP) and asphalt mixes containing 15% RAP, 25% RAP and 35% RAP in accordance with Specifications for Road Works of Public Works Department, Malaysia for AC14 dense graded asphalt gradation. Volumetric analysis was performed to ensure that the result is compliance with specification requirements. The resilient modulus test was performed to measure the stiffness of the mixes while the Modified Lottman test was conducted to evaluate the moisture susceptibility of these mixes. The Hamburg wheel tracking test was used to evaluate the rutting performance of these mixes. The results obtained showed that there were no substantial difference in Marshall Properties, moisture susceptibility, resilient modulus and rutting resistance between asphalt mixes with RAP and the control mix. The test results indicated that recycled mixes performed as good as the performance of conventional HMA in terms of moisture susceptibility and resilient modulus. It is recommended that further research be carried out for asphalt mixes containing more than 35% RAP material.

Performance Evaluation of Hot Mix Asphalt with Different Proportions of RAP Content

Directory of Open Access Journals (Sweden)

Kamil Arshad Ahmad

2018-01-01

Full Text Available Reclaimed Asphalt Pavement (RAP is old asphalt pavement that has been removed from a road by milling or full depth removal. The use of RAP in hot mix asphalt (HMA eliminates the need to dispose old asphalt pavements and conserves asphalt binders and aggregates, resulting in significant cost savings and benefits to society. This paper presents a study on HMA with different RAP proportions carried out to evaluate the volumetric properties and performance of asphalt mixes containing different proportions of RAP. Marshall Mix Design Method was used to produce control mix (0% RAP and asphalt mixes containing 15% RAP, 25% RAP and 35% RAP in accordance with Specifications for Road Works of Public Works Department, Malaysia for AC14 dense graded asphalt gradation. Volumetric analysis was performed to ensure that the result is compliance with specification requirements. The resilient modulus test was performed to measure the stiffness of the mixes while the Modified Lottman test was conducted to evaluate the moisture susceptibility of these mixes. The Hamburg wheel tracking test was used to evaluate the rutting performance of these mixes. The results obtained showed that there were no substantial difference in Marshall Properties, moisture susceptibility, resilient modulus and rutting resistance between asphalt mixes with RAP and the control mix. The test results indicated that recycled mixes performed as good as the performance of conventional HMA in terms of moisture susceptibility and resilient modulus. It is recommended that further research be carried out for asphalt mixes containing more than 35% RAP material.

Analysis of the finescale timing of repeated signals: does shell rapping in hermit crabs signal stamina?

Science.gov (United States)

Briffa; Elwood

2000-01-01

Hermit crabs, Pagurus bernhardus, sometimes exchange shells after a period of shell rapping, when the initiating or attacking crab brings its shell rapidly and repeatedly into contact with the shell of the noninitiator or defender in a series of bouts. Bouts are separated by pauses, and raps within bouts are separated by very short periods called 'gaps'. Since within-contest variation is missed when signals are studied by averaging performance rates over entire contests, we analysed the fine within-bout structure of this repeated, aggressive signal. We found that the pattern is consistent with high levels of fatigue in initiators. The duration of the gaps between individual raps increased both within bouts and from bout to bout, and we conclude that this activity is costly to perform. Furthermore, long pauses between bouts is correlated with increased vigour of rapping in the subsequent bout, which suggests that the pause allows for recovery from fatigue induced by rapping. These between-bout pauses may be assessed by noninitiators and provide a signal of stamina. Copyright 2000 The Association for the Study of Animal Behaviour.

Cep169, a Novel Microtubule Plus-End-Tracking Centrosomal Protein, Binds to CDK5RAP2 and Regulates Microtubule Stability.

Directory of Open Access Journals (Sweden)

Yusuke Mori

Full Text Available The centrosomal protein, CDK5RAP2, is a microcephaly protein that regulates centrosomal maturation by recruitment of a γ-tubulin ring complex (γ-TuRC onto centrosomes. In this report, we identified a novel human centrosomal protein, Cep169, as a binding partner of CDK5RAP2, a member of microtubule plus-end-tracking proteins (+TIPs. Cep169 interacts directly with CDK5RAP2 through CM1, an evolutionarily conserved domain, and colocalizes at the pericentriolar matrix (PCM around centrioles with CDK5RAP2. In addition, Cep169 interacts with EB1 through SxIP-motif responsible for EB1 binding, and colocalizes with CDK5RAP2 at the microtubule plus-end. EB1-binding-deficient Cep169 abolishes EB1 interaction and microtubule plus-end attachment, indicating Cep169 as a novel member of +TIPs. We further show that ectopic expression of either Cep169 or CDK5RAP2 induces microtubule bundling and acetylation in U2OS cells, and depletion of Cep169 induces microtubule depolymerization in HeLa cells, although Cep169 is not required for assembly of γ-tubulin onto centrosome by CDK5RAP2. These results show that Cep169 targets microtubule tips and regulates stability of microtubules with CDK5RAP2.

Remote Area Power Supply (RAPS) load and resource profiles.

Energy Technology Data Exchange (ETDEWEB)

Giles, Lauren (Energetics, Inc., Washington, DC); Skolnik, Edward G. (Energetics, Inc., Washington, DC); Marchionini, Brian (Energetics, Inc., Washington, DC); Fall, Ndeye K. (Energetics, Inc., Washington, DC)

2007-07-01

In 1997, an international team interested in the development of Remote Area Power Supply (RAPS) systems for rural electrification projects around the world was organized by the International Lead Zinc Research Organization (ILZRO) with the support of Sandia National Laboratories (SNL). The team focused on defining load and resource profiles for RAPS systems. They identified single family homes, small communities, and villages as candidates for RAPS applications, and defined several different size/power requirements for each. Based on renewable energy and resource data, the team devised a ''strawman'' series of load profiles. A RAPS system typically consists of a renewable and/or conventional generator, power conversion equipment, and a battery. The purpose of this report is to present data and information on insolation levels and load requirements for ''typical'' homes, small communities, and larger villages around the world in order to facilitate the development of robust design practices for RAPS systems, and especially for the storage battery component. These systems could have significant impact on areas of the world that would otherwise not be served by conventional electrical grids.

Two biomarker-directed randomized trials in European and Chinese patients with nonsmall-cell lung cancer: the BRCA1-RAP80 Expression Customization (BREC) studies.

Science.gov (United States)

Moran, T; Wei, J; Cobo, M; Qian, X; Domine, M; Zou, Z; Bover, I; Wang, L; Provencio, M; Yu, L; Chaib, I; You, C; Massuti, B; Song, Y; Vergnenegre, A; Lu, H; Lopez-Vivanco, G; Hu, W; Robinet, G; Yan, J; Insa, A; Xu, X; Majem, M; Chen, X; de Las Peñas, R; Karachaliou, N; Sala, M A; Wu, Q; Isla, D; Zhou, Y; Baize, N; Zhang, F; Garde, J; Germonpre, P; Rauh, S; ALHusaini, H; Sanchez-Ronco, M; Drozdowskyj, A; Sanchez, J J; Camps, C; Liu, B; Rosell, R

2014-11-01

In a Spanish Lung Cancer Group (SLCG) phase II trial, the combination of BRCA1 and receptor-associated protein 80 (RAP80) expression was significantly associated with outcome in Caucasian patients with nonsmall-cell lung cancer (NSCLC). The SLCG therefore undertook an industry-independent collaborative randomized phase III trial comparing nonselected cisplatin-based chemotherapy with therapy customized according to BRCA1/RAP80 expression. An analogous randomized phase II trial was carried out in China under the auspices of the SLCG to evaluate the effect of BRCA1/RAP80 expression in Asian patients. Eligibility criteria included stage IIIB-IV NSCLC and sufficient tumor specimen for molecular analysis. Randomization to the control or experimental arm was 1 : 1 in the SLCG trial and 1 : 3 in the Chinese trial. In both trials, patients in the control arm received docetaxel/cisplatin; in the experimental arm, patients with low RAP80 expression received gemcitabine/cisplatin, those with intermediate/high RAP80 expression and low/intermediate BRCA1 expression received docetaxel/cisplatin, and those with intermediate/high RAP80 expression and high BRCA1 expression received docetaxel alone. The primary end point was progression-free survival (PFS). Two hundred and seventy-nine patients in the SLCG trial and 124 in the Chinese trial were assessable for PFS. PFS in the control and experimental arms in the SLCG trial was 5.49 and 4.38 months, respectively [log rank P = 0.07; hazard ratio (HR) 1.28; P = 0.03]. In the Chinese trial, PFS was 4.74 and 3.78 months, respectively (log rank P = 0.82; HR 0.95; P = 0.82). Accrual was prematurely closed on the SLCG trial due to the absence of clinical benefit in the experimental over the control arm. However, the BREC studies provide proof of concept that an international, nonindustry, biomarker-directed trial is feasible. Thanks to the groundwork laid by these studies, we expect that ongoing further research on alternative biomarkers to

A demonstration of the applicability of implementing the enhanced Remedial Action Priority System (RAPS) for environmental releases

Energy Technology Data Exchange (ETDEWEB)

Whelan, G.; Droppo, J.G. Jr.; Strenge, D.L.; Walter, M.B.; Buck, J.W.

1989-12-01

The Remedial Action Priority System (RAPS) and the Multimedia Environmental Pollutant Assessment System (MEPAS) were developed to prioritize problems associated with potential releases of hazardous chemical and radioactive materials in a scientific and objective manner based on limited site information. This report documents the model testing efforts of the RAPS/MEPAS methodology for the atmospheric, surface water, groundwater, and exposure components. Comparisons are given of model outputs with measured data at three sites: the US Department of Energy's Mound facility in Ohio and Hanford facility in Washington, and a chromium-cadmium plating site in New York. The results show that the simulated magnitudes, spacial and temporal trends, and distributions of contaminants corresponded well with the measured data. 25 refs., 86 figs., 26 tabs.

Changing images of violence in Rap music lyrics: 1979-1997.

Science.gov (United States)

Herd, Denise

2009-12-01

Rap music has been at the center of concern about the potential harmful effects of violent media on youth social behavior. This article explores the role of changing images of violence in rap music lyrics from the 1970s to the 1990s. The results indicate that there has been a dramatic and sustained increase in the level of violence in rap music. The percentage of songs mentioning violence increased from 27 per cent during 1979-1984 to 60 per cent during 1994-1997. In addition, portrayals of violence in later songs are viewed in a more positive light as shown by their increased association with glamor, wealth, masculinity, and personal prowess. Additional analyses revealed that genre, specifically gangster rap, is the most powerful predictor of the increased number of violent references in songs. The discussion suggests that violence in rap music has increased in response to the complex interplay of changing social conditions such as the elevated levels of youth violence in the 1980s and changing commercial practices within the music industry.

Crystal structure of the C-terminal domain of the RAP74 subunit of human transcription factor IIF

Energy Technology Data Exchange (ETDEWEB)

Kamada, Katsuhiko; De Angelis, Jacqueline; Roeder, Robert G.; Burley, Stephen K. (Rockefeller)

2012-12-13

The x-ray structure of a C-terminal fragment of the RAP74 subunit of human transcription factor (TF) IIF has been determined at 1.02-{angstrom} resolution. The {alpha}/{beta} structure is strikingly similar to the globular domain of linker histone H5 and the DNA-binding domain of hepatocyte nuclear factor 3{gamma} (HNF-3{gamma}), making it a winged-helix protein. The surface electrostatic properties of this compact domain differ significantly from those of bona fide winged-helix transcription factors (HNF-3{gamma} and RFX1) and from the winged-helix domains found within the RAP30 subunit of TFIIF and the {beta} subunit of TFIIE. RAP74 has been shown to interact with the TFIIF-associated C-terminal domain phosphatase FCP1, and a putative phosphatase binding site has been identified within the RAP74 winged-helix domain.

Radiological Assistance Program (RAP) Regions

Data.gov (United States)

Department of Homeland Security — The U.S. Department of Energy (DOE) created the Radiological Assistance Program (RAP) in the 1950s to make DOE resources and expertise available to organizations...

Chance Encounters: Rap Music as a Relational and Pedagogical Resource in Clinical Pastoral Education.

Science.gov (United States)

Gilmore, Jeremy

2018-03-01

Music has long been regarded as a valuable tool for educators. Over the last three decades, rap music has grown to become a global phenomenon. However, due to historical and cultural factors, rap music is often underutilized in Clinical Pastoral Education. This article discusses the social significance of rap music, highlights how rap music informed my supervision of a clinical pastoral education student, and examines Chance the Rapper's mixtape Coloring Book as a case study on the utilization of rap music as a relational and pedagogical resource in spiritual education.

Ultrastructural and biochemical localization of N-RAP at the interface between myofibrils and intercalated disks in the mouse heart.

Science.gov (United States)

Zhang, J Q; Elzey, B; Williams, G; Lu, S; Law, D J; Horowits, R

2001-12-11

N-RAP is a recently discovered muscle-specific protein found at cardiac intercalated disks. Double immunogold labeling of mouse cardiac muscle reveals that vinculin is located immediately adjacent to the fascia adherens region of the intercalated disk membrane, while N-RAP extends approximately 100 nm further toward the interior of the cell. We partially purified cardiac intercalated disks using low- and high-salt extractions followed by density gradient centrifugation. Immunoblots show that this preparation is highly enriched in desmin and junctional proteins, including N-RAP, talin, vinculin, beta1-integrin, N-cadherin, and connexin 43. Electron microscopy and immunolabeling demonstrate that N-RAP and vinculin are associated with the large fragments of intercalated disks that are present in this preparation, which also contains numerous membrane vesicles. Detergent treatment of the partially purified intercalated disks removed the membrane vesicles and extracted vinculin and beta1-integrin. Further separation on a sucrose gradient removed residual actin and myosin and yielded a fraction morphologically similar to fasciae adherentes that was highly enriched in N-RAP, N-cadherin, connexin 43, talin, desmin, and alpha-actinin. The finding that N-RAP copurifies with detergent-extracted intercalated disk fragments even though beta-integrin and vinculin have been completely removed suggests that N-RAP association with the adherens junction region is mediated by the cadherin system. Consistent with this hypothesis, we found that recombinant N-RAP fragments bind alpha-actinin in a gel overlay assay. In addition, immunofluorescence shows that N-RAP remains bound at the ends of isolated, detergent-treated cardiac myofibrils. These results demonstrate that N-RAP remains tightly bound to myofibrils and fasciae adherentes during biochemical purification and may be a key constituent in the mechanical link between these two structures.

Literature review : performance of RAP/RAS mixes and new direction.

Science.gov (United States)

2014-04-01

In the last several years reclaimed asphalt pavement (RAP) and recycled asphalt shingles (RAS) have been : widely used in asphalt mixes in Texas. The use of RAP/RAS can significantly reduce the initial cost of : asphalt mixtures, conserve energy, and...

Fatigue Durability Analysis of Collecting Rapping System in Electrostatic Precipitators under Impact Loading

Directory of Open Access Journals (Sweden)

Ali Akbar Lotfi Neyestanak

2014-01-01

Full Text Available Due to the importance of collecting rapping system in electrostatic precipitators (ESP and controlling the relevant damage under impact loading, fatigue durability of this system is analyzed in the present study based on the numerical and experimental results considering fatigue damage growth and vibration acceleration in the collecting system because of the successive impact of rapping hammers. By microscopic examination of the fracture surface of rapping hammer, beach marks obviously show typical fatigue failure in the rapping hammer arm. In addition, the microscopic examination of the cross section of the collecting plates indicates the corrosion voids which cause crack and eventually fatigue failure. The finite element method is applied to determine both the stress and concentration positions of dynamic stress on the rapping system under impact loading. The paper results can be utilized in system optimization and new material selection for the system by evaluating rapping system durability.

Rap Music Use, Perceived Peer Behavior, and Sexual Initiation Among Ethnic Minority Youth.

Science.gov (United States)

Johnson-Baker, Kimberly A; Markham, Christine; Baumler, Elizabeth; Swain, Honora; Emery, Susan

2016-03-01

Research shows that rap music use is associated with risky sexual behavior in ethnic minority youth; however, it is unknown whether rap music use impacts sexual initiation specifically and, if so, which factors mediate this impact. Thus, we investigated the longitudinal relationship between hours spent listening to rap music in seventh grade and sexual initiation in ninth grade. We also examined the role of perceived peer sexual behavior as a potential mediator of this relationship. We analyzed data from students (n = 443) enrolled in a school-based randomized controlled trial of a sexual health education curriculum collected at baseline and at 18-month follow-up. Rap music use and perceived peer sexual behavior were assessed in seventh grade, whereas sexual initiation was assessed in ninth grade. Univariate, multivariate, and mediation analyses were conducted. At baseline, rap music use was significantly associated with race/ethnicity, parental music rules, and sexual behavior, but not with gender or parental education. Rap music use was a significant predictor of sexual initiation on univariate analysis but not multivariate analysis. Mediation analysis showed that the association between hours spent listening to rap music and sexual initiation was significantly mediated by perceived peer sexual behavior. Rap music use in early adolescence significantly impacts sexual initiation in late adolescence, partially mediated by perceived peer sexual behavior. More research is needed to understand how rap music influences perceptions of peer sexual behavior, which, in turn, influence early sexual initiation. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Loss of γ-tubulin, GCP-WD/NEDD1 and CDK5RAP2 from the Centrosome of Neurons in Developing Mouse Cerebral and Cerebellar Cortex

International Nuclear Information System (INIS)

Yonezawa, Satoshi; Shigematsu, Momoko; Hirata, Kazuto; Hayashi, Kensuke

2015-01-01

It has been recently reported that the centrosome of neurons does not have microtubule nucleating activity. Microtubule nucleation requires γ-tubulin as well as its recruiting proteins, GCP-WD/NEDD1 and CDK5RAP2 that anchor γ-tubulin to the centrosome. Change in the localization of these proteins during in vivo development of brain, however, has not been well examined. In this study we investigate the localization of γ-tubulin, GCP-WD and CDK5RAP2 in developing cerebral and cerebellar cortex with immunofluorescence. We found that γ-tubulin and its recruiting proteins were localized at centrosomes of immature neurons, while they were lost at centrosomes in mature neurons. This indicated that the loss of microtubule nucleating activity at the centrosome of neurons is due to the loss of γ-tubulin-recruiting proteins from the centrosome. RT-PCR analysis revealed that these proteins are still expressed after birth, suggesting that they have a role in microtubule generation in cell body and dendrites of mature neurons. Microtubule regrowth experiments on cultured mature neurons showed that microtubules are nucleated not at the centrosome but within dendrites. These data indicated the translocation of microtubule-organizing activity from the centrosome to dendrites during maturation of neurons, which would explain the mixed polarity of microtubules in dendrites

The Effect of Rap/Hip-Hop Music on Young Adult Smoking: An Experimental Study.

Science.gov (United States)

Harakeh, Zeena; Bogt, Tom F M Ter

2018-02-16

Music may influence young people's behavior through its lyrics. Substance use references occur more frequently in rap/hip-hop than in other music genres. The aim was to examine whether the exposure to rap/hip-hop lyrics referring to substance use affected cigarette smoking. An experiment with a 3-group between subject design was conducted among 74 daily-smoking young adults ranging in age from 17 to 25 years old. Three conditions were tested in a mobile lab (camper vehicle) from May to December 2011, i.e., regular chart pop music (N = 28), rap/hip-hop with non-frequent references to substance use (N = 24), and rap/hip-hop with frequent references to substance use (N = 22). One-way ANOVA showed that participants listening to substance use infused rap/hip-hop songs felt significantly less pleasant, liked the songs less, and comprehended the songs less compared to participants listening to pop songs. Poisson loglinear analyses revealed that compared to the pop music condition, none of the two rap/hip-hop music conditions had a significant effect on acute smoking. Thus, contrary to expectations, the two different rap/hip-hop conditions did not have a significantly different effect on acute smoking. Listening to rap/hip-hop, even rap hip/hop with frequent referrals to substance use (primarily alcohol and drug use, and general smoking referrals), does not seem to encourage cigarette smoking among Dutch daily-smoking young adults, at least short term.

Investigation on the Combined Effect of Fibers and Cement on the Mechanical Performance of Foamed Bitumen Mixtures Containing 100% RAP

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Ehsan Ashouri Taziani

2016-01-01

Full Text Available Concerns about virgin aggregate sources and increasing demands for construction materials of transport infrastructures as the key parameters in development are the most important reasons, which convinced pavement engineers to develop new methods in order to use higher amount of recycled asphalt pavement (RAP. One of the common methodologies to produce mixtures containing RAP is foamed bitumen mix (FBM. In addition, according to previous research studies, incorporating various types of fibers and hydraulic binders such as cement could significantly improve the mechanical performance of mixtures. The present research study evaluated FBM containing 100% RAP and two types of fiber and Portland cement. Dynamic modulus, unconfined dynamic creep compression, and indirect tensile strength were evaluated in the laboratory at optimum moisture content, which was investigated in this research. Both types of fiber and cement proved to enhance specific properties of mixtures.

Influence of slope and gradation on rip rap stability and degradation mechanisms

International Nuclear Information System (INIS)

Lefebvre, G.; Rohan, K.; Belfahdel, M. B.

1997-01-01

A major investigation was undertaken at the La Grande hydroelectric complex with some 220 dikes and dams to study rip rap stability and repair. Degradation mechanisms were also studied under laboratory conditions to verify the main field study conclusions and to test different repair techniques. The result of both laboratory and field observation was that rip rap gradation has only marginal effect on slope stability and degradation mechanisms. On the other hand, the inclusion of even a small fraction of fine blocks (as little as 10 per cent) into the rip rap was shown to be very detrimental to the stability of steep rip rap but only marginally effective on flat slopes. 15 refs., 8 figs

3D printing with RepRap cookbook

CERN Document Server

Salinas, Richard

2014-01-01

A systematic guide consisting of over 100 recipes which focus on helping you understand the process of 3D printing using RepRap machines. The book aims at providing professionals with a series of working recipes to help make their fuzzy notions into real, saleable projects/objects using 3D printing technology. This book is for novice designers and artists who own a RepRap-based 3D printer, have fundamental knowledge of its working, and who desire to gain better mastery of the printing process. For the more experienced user, it will provide a handy visual resource, with side-by-side comparisons

Affiliation and Alienation: Hip-Hop, Rap, and Urban Science Education

Science.gov (United States)

Emdin, Christopher

2010-01-01

The critiques of rap artists and other participants in hip-hop culture provide data for teachers and researchers to investigate the attitudes of US urban youth towards schooling. This study explores the complex relationships between hip-hop and science education by examining how rap lyrics project beliefs about schooling, the relevance of existing…

Mortality in American Hip-Hop and Rap Recording Artists, 1987-2014.

Science.gov (United States)

Lawson, Carl J

2015-12-01

The deaths of American hip-hop and rap recording artists often receive considerable media attention. However, these artists' deaths have not been examined as a distinct group like the deaths of rock, classical, jazz, and pop music artists. This is a seminal epidemiological analysis on the deaths of an understudied group, American hip-hop and rap music recording artists. Media reports were analyzed of the deaths of American hip-hop and rap music recording artists that occurred from January 1, 1987 to December 31, 2014. The decedents' age, sex, race, cause of death, stage names, and city and state of death were recorded for analysis. The most commonly reported cause of death was homicide. The 280 deaths were categorized as homicide (55%), unintentional injury (13%), cardiovascular (7%), undetermined/undisclosed (7%), cancer (6%), other (5%), suicide (4%), and infectious disease (3%). The mean reported age at death was 30 yrs (range 15-75) and the median was 29 yrs; 97% were male and 92% were black. All but one of the homicides were committed with firearms. Homicide was the most commonly reported cause of death. Public health focus and guidance for hip-hop and rap recording artists should mirror that for African-American men and adolescent males ages 15-54 yrs, for whom the leading causes of death are homicide, unintentional injury, and heart disease. Given the preponderance of homicide deaths in this analysis, premature mortality reduction efforts should focus on violence prevention and conflict mitigation.

Truncated RAP-MUSIC (TRAP-MUSIC) for MEG and EEG source localization.

Science.gov (United States)

Mäkelä, Niko; Stenroos, Matti; Sarvas, Jukka; Ilmoniemi, Risto J

2018-02-15

Electrically active brain regions can be located applying MUltiple SIgnal Classification (MUSIC) on magneto- or electroencephalographic (MEG; EEG) data. We introduce a new MUSIC method, called truncated recursively-applied-and-projected MUSIC (TRAP-MUSIC). It corrects a hidden deficiency of the conventional RAP-MUSIC algorithm, which prevents estimation of the true number of brain-signal sources accurately. The correction is done by applying a sequential dimension reduction to the signal-subspace projection. We show that TRAP-MUSIC significantly improves the performance of MUSIC-type localization; in particular, it successfully and robustly locates active brain regions and estimates their number. We compare TRAP-MUSIC and RAP-MUSIC in simulations with varying key parameters, e.g., signal-to-noise ratio, correlation between source time-courses, and initial estimate for the dimension of the signal space. In addition, we validate TRAP-MUSIC with measured MEG data. We suggest that with the proposed TRAP-MUSIC method, MUSIC-type localization could become more reliable and suitable for various online and offline MEG and EEG applications. Copyright © 2017 Elsevier Inc. All rights reserved.

Entre ritmo e poesia: rap e literatura oral urbana

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Marcus Rogerio Salgado

2015-11-01

Full Text Available O objetivo do presente artigo é um estudo do rap enquanto manifestação de literatura oral urbana e forma de oralidade tecnológica. Para tanto, o artigo passará em revista as relações entre literatura e palavra falada/cantada, assim como as possibilidades de interface estética entre a literatura e a música que estão em questão quando tratamos do rap.

Source localization using recursively applied and projected (RAP) MUSIC

Energy Technology Data Exchange (ETDEWEB)

Mosher, J.C. [Los Alamos National Lab., NM (United States); Leahy, R.M. [Univ. of Southern California, Los Angeles, CA (United States). Signal and Image Processing Inst.

1998-03-01

A new method for source localization is described that is based on a modification of the well known multiple signal classification (MUSIC) algorithm. In classical MUSIC, the array manifold vector is projected onto an estimate of the signal subspace, but errors in the estimate can make location of multiple sources difficult. Recursively applied and projected (RAP) MUSIC uses each successively located source to form an intermediate array gain matrix, and projects both the array manifold and the signal subspace estimate into its orthogonal complement. The MUSIC projection is then performed in this reduced subspace. Using the metric of principal angles, the authors describe a general form of the RAP-MUSIC algorithm for the case of diversely polarized sources. Through a uniform linear array simulation, the authors demonstrate the improved Monte Carlo performance of RAP-MUSIC relative to MUSIC and two other sequential subspace methods, S and IES-MUSIC.

Drosophila-Cdh1 (Rap/Fzr) a regulatory subunit of APC/C is required for synaptic morphology, synaptic transmission and locomotion.

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Wise, Alexandria; Schatoff, Emma; Flores, Julian; Hua, Shao-Ying; Ueda, Atsushi; Wu, Chun-Fang; Venkatesh, Tadmiri

2013-11-01

The assembly of functional synapses requires the orchestration of the synthesis and degradation of a multitude of proteins. Protein degradation and modification by the conserved ubiquitination pathway has emerged as a key cellular regulatory mechanism during nervous system development and function (Kwabe and Brose, 2011). The anaphase promoting complex/cyclosome (APC/C) is a multi-subunit ubiquitin ligase complex primarily characterized for its role in the regulation of mitosis (Peters, 2002). In recent years, a role for APC/C in nervous system development and function has been rapidly emerging (Stegmuller and Bonni, 2005; Li et al., 2008). In the mammalian central nervous system the activator subunit, APC/C-Cdh1, has been shown to be a regulator of axon growth and dendrite morphogenesis (Konishi et al., 2004). In the Drosophila peripheral nervous system (PNS), APC2, a ligase subunit of the APC/C complex has been shown to regulate synaptic bouton size and activity (van Roessel et al., 2004). To investigate the role of APC/C-Cdh1 at the synapse we examined loss-of-function mutants of Rap/Fzr (Retina aberrant in pattern/Fizzy related), a Drosophila homolog of the mammalian Cdh1 during the development of the larval neuromuscular junction in Drosophila. Our cell biological, ultrastructural, electrophysiological, and behavioral data showed that rap/fzr loss-of-function mutations lead to changes in synaptic structure and function as well as locomotion defects. Data presented here show changes in size and morphology of synaptic boutons, and, muscle tissue organization. Electrophysiological experiments show that loss-of-function mutants exhibit increased frequency of spontaneous miniature synaptic potentials, indicating a higher rate of spontaneous synaptic vesicle fusion events. In addition, larval locomotion and peristaltic movement were also impaired. These findings suggest a role for Drosophila APC/C-Cdh1 mediated ubiquitination in regulating synaptic morphology

Bacillus subtilis RapA phosphatase domain interaction with its substrate, phosphorylated Spo0F, and its inhibitor, the PhrA peptide.

Science.gov (United States)

Diaz, Alejandra R; Core, Leighton J; Jiang, Min; Morelli, Michela; Chiang, Christina H; Szurmant, Hendrik; Perego, Marta

2012-03-01

Rap proteins in Bacillus subtilis regulate the phosphorylation level or the DNA-binding activity of response regulators such as Spo0F, involved in sporulation initiation, or ComA, regulating competence development. Rap proteins can be inhibited by specific peptides generated by the export-import processing pathway of the Phr proteins. Rap proteins have a modular organization comprising an amino-terminal alpha-helical domain connected to a domain formed by six tetratricopeptide repeats (TPR). In this study, the molecular basis for the specificity of the RapA phosphatase for its substrate, phosphorylated Spo0F (Spo0F∼P), and its inhibitor pentapeptide, PhrA, was analyzed in part by generating chimeric proteins with RapC, which targets the DNA-binding domain of ComA, rather than Spo0F∼P, and is inhibited by the PhrC pentapeptide. In vivo analysis of sporulation efficiency or competence-induced gene expression, as well as in vitro biochemical assays, allowed the identification of the amino-terminal 60 amino acids as sufficient to determine Rap specificity for its substrate and the central TPR3 to TPR5 (TPR3-5) repeats as providing binding specificity toward the Phr peptide inhibitor. The results allowed the prediction and testing of key residues in RapA that are essential for PhrA binding and specificity, thus demonstrating how the widespread structural fold of the TPR is highly versatile, using a common interaction mechanism for a variety of functions in eukaryotic and prokaryotic organisms.

Investigation on performances of asphalt mixtures made with Reclaimed Asphalt Pavement: Effects of interaction between virgin and RAP bitumen

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Luca Noferini

2017-07-01

Full Text Available According to most recent surveys, the European area produced 265 mil tonnes of asphalt for road applications in 2014. In the same year, the amount of available RAP was more than 50 mil tonnes. The use of RAP in new blended mixes reduces the need of neat bitumen, making RAP recycling economically attractive. Despite the economic and environmental benefits, road authorities tend to limit the use of RAP in asphalt mixes due to uncertainty about field performances. The present study focuses on the interaction between neat and RAP bitumen in asphalt mixes made with different RAP content. The effects of RAP on physical and rheological properties of the final bituminous blend were investigated. This study is part of a wider research, where a specific type of asphalt mixture was produced with different RAP contents being 10%, 20% and 30% by mass of the mix. Bitumen was extracted and recovered from asphalt mixes, then it was subjected to the following laboratory tests: standard characterization, dynamic viscosity and rheological analysis with DSR. Findings showed that the effects of RAP bitumen on the final blend varied in proportion to RAP content. A threshold value of RAP content was found, below which bitumen was not subjected to significant changes in physical and rheological properties. Practical implications on production methods and paving of RAP mixes are also proposed. Keywords: Reclaimed Asphalt Pavement (RAP, Recycling, Bitumen blending, Bitumen rheology

Development of low-cost open source 3D gel printer "RepRap SWIM-ER"

Science.gov (United States)

Sato, Kei; Basher, Samiul; Ota, Takafumi; Tase, Taishi; Takamatsu, Kyuichiro; Saito, Azusa; Khosla, Ajit; Kawakami, Masaru; Furuawa, Hidemitsu

2017-04-01

Gels are soft and wet materials having low friction, good biocompatibility, and material permeability. It is expected that gel materials will be used as new kinds of industrial materials in the engineering and medical applications. But it cannot build a complicated shape. Soft & Wet Matter Engineering Laboratory developed a 3D gel Printer "SWIM-ER", has enabled modeling of complex shapes of the gel. However, this is expensive. Therefore not all of the gel researchers and the companies have such a device. To solve this problem, we manufacture a low-cost open-source 3D gel printer "RepRap SWIM-ER" from the RepRap. We made the components required to manufacture the "RepRap SWIM-ER" from the 3D printer and chose a light source. In addition, we produced the P-DN gel for RepRap SWIM-ER and conducted the molding test to confirm whether RepRap SWIM-ER can used it.

As mensagens sobre drogas no rap: como sobreviver na periferia Messages about drugs from rap: how to survive in the periferia

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Vinícius Gonçalves Bento da Silva

2004-12-01

Full Text Available O objetivo é analisar as mensagens sobre drogas nas letras de rap de grupos com representatividade e influência entre jovens da periferia de São Paulo. O rap é um gênero musical que faz parte de um movimento cultural - o hip hop -, que difunde uma visão social de mundo, principalmente nas periferias das grandes cidades. Por meio da Análise de Discurso estudaram-se 11 letras de 9 grupos. O tema marcante é a vida na periferia retratada pelo tráfico e consumo de drogas, pela violência e pela discriminação. O uso de drogas é compreendido por alguns grupos como conseqüência do modo de produção, e por outros, pelas características individuais, pela influência da família e dos amigos. As propostas para o enfrentamento e para a superação dos problemas estão voltadas à responsabilização do sujeito que, através de um esforço pessoal, não se envolveria com o tráfico e consumo de drogas consideradas perigosas e destrutivas como o crack e a cocaína. O fortalecimento de laços familiares e de amizade e a educação são também vistos como saídas para os problemas advindos do envolvimento com as drogas. As propostas invocam um discurso que, além de denunciar a situação dos jovens da periferia, propõe mecanismos de proteção para criar uma alternativa de "vida possível" - de convivência com a violência, com o tráfico e consumo de drogas.The objective was to analyze the messages about drugs of the rap lyrics from representative and influential groups among the youth living in the periferias of São Paulo. It understands that rap is a kind of music that is part of cultural movement - the hip hop - that disseminates a particular set of ideas, mainly in the periferias of the big cities. Through Discourse Analysis 11 lyrics of 9 rap groups were taken as a sample. The outstanding theme of the lyrics is the situation of the segregated areas of the city, including the presence of drug trafficking and consumption, as well as

Redox active polymers and colloidal particles for flow batteries

Science.gov (United States)

Gavvalapalli, Nagarjuna; Moore, Jeffrey S.; Rodriguez-Lopez, Joaquin; Cheng, Kevin; Shen, Mei; Lichtenstein, Timothy

2018-05-29

The invention provides a redox flow battery comprising a microporous or nanoporous size-exclusion membrane, wherein one cell of the battery contains a redox-active polymer dissolved in the non-aqueous solvent or a redox-active colloidal particle dispersed in the non-aqueous solvent. The redox flow battery provides enhanced ionic conductivity across the electrolyte separator and reduced redox-active species crossover, thereby improving the performance and enabling widespread utilization. Redox active poly(vinylbenzyl ethylviologen) (RAPs) and redox active colloidal particles (RACs) were prepared and were found to be highly effective redox species. Controlled potential bulk electrolysis indicates that 94-99% of the nominal charge on different RAPs is accessible and the electrolysis products are stable upon cycling. The high concentration attainable (>2.0 M) for RAPs in common non-aqueous battery solvents, their electrochemical and chemical reversibility, and their hindered transport across porous separators make them attractive materials for non-aqueous redox flow batteries based on size-selectivity.

Rap Music Literacy: A Case Study of Millennial Audience Reception to Rap Lyrics Depicting Independent Women

Science.gov (United States)

Moody-Ramirez, Mia; Scott, Lakia M.

2015-01-01

Using a feminist lens and a constructivist approach as the theoretical framework, we used rap lyrics and videos to help college students explore mass media's representation of the "independent" Black woman and the concept of "independence" in general. Students must be able to formulate their own concept of independence to…

O rap radical e a "nova classe média"

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Ricardo Indig Teperman

2015-04-01

Full Text Available Este artigo discute a recente alteração na posição relativa do rap e dos rappers no campo da produção cultural no Brasil. O grupo Racionais MCs, tão central no campo do rap nacional que acaba por determinar a tendência hegemônica do gênero, vem se afastando do posicionamento revolucionário que marcou seus primeiros anos. Proponho que o aumento do poder de consumo e a democratização do acesso à tecnologia e à educação são aspectos que marcam a experiência da nova geração do rap (a chamada "nova escola", personificada em Emicida, e que provocaram o reposicionamento do Racionais. Recupero uma formulação de Antonio Candido para propor que essa nova posição pode ser considerada "radical".

Novel Alternative Splice Variants of Mouse Cdk5rap2.

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Nadine Kraemer

Full Text Available Autosomal recessive primary microcephaly (MCPH is a rare neurodevelopmental disorder characterized by a pronounced reduction of brain volume and intellectual disability. A current model for the microcephaly phenotype invokes a stem cell proliferation and differentiation defect, which has moved the disease into the spotlight of stem cell biology and neurodevelopmental science. Homozygous mutations of the Cyclin-dependent kinase-5 regulatory subunit-associated protein 2 gene CDK5RAP2 are one genetic cause of MCPH. To further characterize the pathomechanism underlying MCPH, we generated a conditional Cdk5rap2 LoxP/hCMV Cre mutant mouse. Further analysis, initiated on account of a lack of a microcephaly phenotype in these mutant mice, revealed the presence of previously unknown splice variants of the Cdk5rap2 gene that are at least in part accountable for the lack of microcephaly in the mice.

External radiation monitoring in TAPS and RAPS environs (1980-81) using TLD

International Nuclear Information System (INIS)

Basu, A.S.; Nambi, K.S.V.; Sunta, C.M.

1983-01-01

Results of environmental external radiation monitoring using quarterly integrated TLD measurements are presented for environments of the Tarapur Atomic Power Station (TAPS) and the Rajasthan Atomic Power Station (RAPS) for the two year monitoring period (1980-81). The data fit into the unimodal log-normal distribution except for locations where gaseous radioactivity escaping from the plant makes a significant contribution. The average natural radiation background in TAPS and RAPS environment is estimated to be 59.6 +- 4.7 mR yr -1 and 65.1 +- 9.8 mR yr -1 respectively. Contribution from the plant superimposed over the natural level leads frequently to bi-normal distribution. The effect of stack-released gaseous radioactivity is seen in locations within 1.6 km of TAPS: for example Ghivoli village registered an excess of 9.3 mR yr -1 over the natural background. The quarterly background values indicate minor temporal and spatial variations which can be attributed to changes in natural as well as stack released radioactivity. (author)

Constitutively active signaling by the G protein βγ-subunit mediates intrinsically increased phosphodiesterase-4 activity in human asthmatic airway smooth muscle cells.

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Aihua Hu

Full Text Available Signaling by the Gβγ subunit of Gi protein, leading to downstream c-Src-induced activation of the Ras/c-Raf1/MEK-ERK1/2 signaling pathway and its upregulation of phosphodiesterase-4 (PDE4 activity, was recently shown to mediate the heightened contractility in proasthmatic sensitized isolated airway smooth muscle (ASM, as well as allergen-induced airway hyperresponsiveness and inflammation in an in vivo animal model of allergic asthma. This study investigated whether cultured human ASM (HASM cells derived from asthmatic donor lungs exhibit constitutively increased PDE activity that is attributed to intrinsically upregulated Gβγ signaling coupled to c-Src activation of the Ras/MEK/ERK1/2 cascade. We show that, relative to normal cells, asthmatic HASM cells constitutively exhibit markedly increased intrinsic PDE4 activity coupled to heightened Gβγ-regulated phosphorylation of c-Src and ERK1/2, and direct co-localization of the latter with the PDE4D isoform. These signaling events and their induction of heightened PDE activity are acutely suppressed by treating asthmatic HASM cells with a Gβγ inhibitor. Importantly, along with increased Gβγ activation, asthmatic HASM cells also exhibit constitutively increased direct binding of the small Rap1 GTPase-activating protein, Rap1GAP, to the α-subunit of Gi protein, which serves to cooperatively facilitate Ras activation and, thereby, enable enhanced Gβγ-regulated ERK1/2-stimulated PDE activity. Collectively, these data are the first to identify that intrinsically increased signaling via the Gβγ subunit, facilitated by Rap1GAP recruitment to the α-subunit, mediates the constitutively increased PDE4 activity detected in asthmatic HASM cells. These new findings support the notion that interventions targeted at suppressing Gβγ signaling may lead to novel approaches to treat asthma.

Changes in the prevalence of alcohol in rap music lyrics 1979-2009.

Science.gov (United States)

Herd, Denise

2014-02-01

This study examines the prevalence and context of alcohol references in rap music lyrics from 1979 through 2009. Four hundred nine top-ranked rap music songs released were sampled from Billboard magazine rating charts. Songs were analyzed using systematic content analysis and were coded for alcohol beverage types and brand names, drinking behaviors, drinking contexts, attitudes towards alcohol, and consequences of drinking. Trends were analyzed using regression analyses. The results of the study reveal significant increases in the presence of alcohol in rap songs; a decline in negative attitudes towards alcohol; decreases in consequences attributed to alcohol; increases in the association of alcohol with glamour and wealth, drugs, and nightclubs; and increases in references to liquor and champagne.

Analysis of the usage of rubberized asphalt in hot mix asphalt using Reclaimed Asphalt Pavement (RAP)

Science.gov (United States)

Dwidarma Nataadmadja, Adelia; Prahara, Eduardi; Sumbung, Pierre Christian

2017-12-01

There has been an increasing demand in using more environmentally friendly materials in pavement construction. One of the alternative materials that have been widely used is the Reclaimed Asphalt Pavement (RAP) aggregates. The RAP aggregates are derived from the crushed and screened pavement materials that contain asphalt and aggregates. This material is usually combined with natural aggregates and virgin asphalt binder to construct a new pavement. There have been numerous positive feedbacks in using this material although RAP aggregates also have certain weaknesses, such as questionable interaction between virgin and recycled materials and increased stiffness of RAP binder. Moreover, there has been a push on using rubber as an additive to asphalt binder to improve the welfare of rubber farmers. This research combines the usage of both latex and RAP as the ingredients to design hot mix asphalt (HMA) as latex could help in improving the flexibility of HMA and the interaction between the virgin and recycled materials. The main objective of this research is to find a suitable percentage of RAP aggregates to be used in HMA with certain percentage of latex as the binder additive.

Thermodynamics between RAP/RAS and virgin aggregates during asphalt concrete production : a literature review.

Science.gov (United States)

2015-09-01

In hot-mix asphalt (HMA) plants, virgin aggregates are heated and dried separately before being mixed with : RAP/RAS and virgin asphalt binder. RAP/RAS materials are not heated or dried directly by a burner to avoid : burning of aged binder coating o...

An Interview with Cathy Fowler about Sharing a Love of Reading through Book Raps.

Science.gov (United States)

Strangman, Nicole

2002-01-01

Includes an interview with Cathy Fowler, a Year 7 teacher at Kawungan State School in Queensland, Australia. Explains that Cathy is a participant and coordinator of the extremely popular Harry Potter Book Rap, a guided Internet book discussion among students all over the world. Discusses how this activity fueled her students' love for reading. (PM)

From Rage to Rap and Prison to Print:

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Josephine Metcalf

2009-11-01

Full Text Available 1. IntroductionBy the late 1980s, while thousands of former gang members were either dead or incarcerated, their legacy and the gang subculture was being celebrated and commodified through gangsta rap music and videos, film and fashion. In the early 1990s this lucrative cultural trend sparked interest from potential authors and publishers. Such literary attention was partially fuelled by a public fascination with life in the ghettos following the 1992 Los Angeles (LA riots, resulting in a ne...

Changes in the prevalence of alcohol use in rap song lyrics, 1979-97.

Science.gov (United States)

Herd, Denise

2005-09-01

This paper explores the role of changing images of drinking and alcoholic beverage use in rap music from its beginnings in the United States in the late 1970s to the late 1990s. A sample of 341 rap music song lyrics released from 1979 to 1997 were selected using Billboard and Gavin rating charts. Song lyrics were coded for music genres, alcohol beverage types and brand names, drinking behaviors, drinking contexts, intoxication, attitudes towards alcohol and consequences of drinking. From 1979 to 1997, songs with references to alcohol increased fivefold (from 8 to 44%); those exhibiting positive attitudes rose from 43% to 73%; and brand name mentions increased from 46% to 71%. There were also significant increases in songs mentioning champagne and liquor (mainly expensive brand names) when comparing songs released after 1994 with those from previous years. In addition, there were significant increases in references to alcohol to signify glamour and wealth, and using alcohol with drugs and for recreational purposes. The findings also showed that alcohol use in rap music was much more likely to result in positive than negative consequences. Many of these findings are consistent with the idea that rap music has been profoundly affected by commercial forces and the marketing of alcoholic beverages. In addition, it is possible that the increase in references to alcoholic beverages in rap music, particularly spirits, is a reflection of a broader advertising culture which increasingly associates African Americans with alcohol use.

Metric Ambiguity and Flow in Rap Music: A Corpus-Assisted Study of Outkast's "Mainstream" (1996

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Mitchell Ohriner

2017-01-01

Full Text Available Recent years have seen the rise of musical corpus studies, primarily detailing harmonic tendencies of tonal music. This article extends this scholarship by addressing a new genre (rap music and a new parameter of focus (rhythm. More specifically, I use corpus methods to investigate the relation between metric ambivalence in the instrumental parts of a rap track (i.e., the beat and an emcee's rap delivery (i.e., the flow. Unlike virtually every other rap track, the instrumental tracks of Outkast's "Mainstream" (1996 simultaneously afford hearing both a four-beat and a three-beat metric cycle. Because three-beat durations between rhymes, phrase endings, and reiterated rhythmic patterns are rare in rap music, an abundance of them within a verse of "Mainstream" suggests that an emcee highlights the three-beat cycle, especially if that emcee is not prone to such durations more generally. Through the construction of three corpora, one representative of the genre as a whole, and two that are artist specific, I show how the emcee T-Mo Goodie's expressive practice highlights the rare three-beat affordances of the track.

Determination of usable residual asphalt binder in RAP.

Science.gov (United States)

2009-01-01

For current recycled mix designs, the Illinois Department of Transportation (IDOT) assumes 100% contribution of : working binder from Recycled Asphalt Pavement (RAP) materials when added to Hot Mix Asphalt (HMA). However, it is : unclear if this assu...

RAP2.4a Is Transported through the Phloem to Regulate Cold and Heat Tolerance in Papaya Tree (Carica papaya cv. Maradol: Implications for Protection Against Abiotic Stress.

Directory of Open Access Journals (Sweden)

Luis Figueroa-Yañez

Full Text Available Plants respond to stress through metabolic and morphological changes that increase their ability to survive and grow. To this end, several transcription factor families are responsible for transmitting the signals that are required for these changes. Here, we studied the transcription factor superfamily AP2/ERF, particularly, RAP2.4 from Carica papaya cv. Maradol. We isolated four genes (CpRap2.4a, CpRAap2.4b, CpRap2.1 and CpRap2.10, and an in silico analysis showed that the four genes encode proteins that contain a conserved APETALA2 (AP2 domain located within group I and II transcription factors of the AP2/ERF superfamily. Semiquantitative PCR experiments indicated that each CpRap2 gene is differentially expressed under stress conditions, such as extreme temperatures. Moreover, genetic transformants of tobacco plants overexpressing CpRap2.4a and CpRap2.4b genes show a high level of tolerance to cold and heat stress compared to non-transformed plants. Confocal microscopy analysis of tobacco transgenic plants showed that CpRAP2.4a and CpRAP2.4b proteins were mainly localized to the nuclei of cells from the leaves and roots and also in the sieve elements. Moreover, the movement of CpRap2.4a RNA in tobacco grafting was analyzed. Our results indicate that CpRap2.4a and CpRap2.4b RNA in the papaya tree have a functional role in the response to stress conditions such as exposure to extreme temperatures via direct translation outside the parental RNA cell.

O rap dos Racionais MC\\'s em sala de aula como via de emancipação de jovens na periferia de São Paulo: análises de oficinas musicais com ênfase no rap

OpenAIRE

Raquel Mendonça Martins

2015-01-01

A presente dissertação de mestrado teve o propósito de pesquisar em que medida a estética multifacetada do rap pode ser utilizada nos processos de formação de adolescentes pobres e moradores das periferias, em sua maioria, afrodescendentes. Ao identificar no rap um potencial de ruptura e de resistência frente às formas atuais de discriminação racial - tanto em seus aspectos musicais, quanto narrativos - foram realizadas oficinas de música com ênfase no rap, envolvendo jovens entre treze e qui...

Mutation of praR in Rhizobium leguminosarum enhances root biofilms, improving nodulation competitiveness by increased expression of attachment proteins.

Science.gov (United States)

Frederix, Marijke; Edwards, Anne; Swiderska, Anna; Stanger, Andrew; Karunakaran, Ramakrishnan; Williams, Alan; Abbruscato, Pamela; Sanchez-Contreras, Maria; Poole, Philip S; Downie, J Allan

2014-08-01

In Rhizobium leguminosarum bv. viciae, quorum-sensing is regulated by CinR, which induces the cinIS operon. CinI synthesizes an AHL, whereas CinS inactivates PraR, a repressor. Mutation of praR enhanced biofilms in vitro. We developed a light (lux)-dependent assay of rhizobial attachment to roots and demonstrated that mutation of praR increased biofilms on pea roots. The praR mutant out-competed wild-type for infection of pea nodules in mixed inoculations. Analysis of gene expression by microarrays and promoter fusions revealed that PraR represses its own transcription and mutation of praR increased expression of several genes including those encoding secreted proteins (the adhesins RapA2, RapB and RapC, two cadherins and the glycanase PlyB), the polysaccharide regulator RosR, and another protein similar to PraR. PraR bound to the promoters of several of these genes indicating direct repression. Mutations in rapA2, rapB, rapC, plyB, the cadherins or rosR did not affect the enhanced root attachment or nodule competitiveness of the praR mutant. However combinations of mutations in rapA, rapB and rapC abolished the enhanced attachment and nodule competitiveness. We conclude that relief of PraR-mediated repression determines a lifestyle switch allowing the expression of genes that are important for biofilm formation on roots and the subsequent initiation of infection of legume roots. © 2014 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.

Addiction and Lifestyles in Contemporary Europe: Reframing Addictions Project (ALICE RAP). Final Evaluation Report Deliverable 21.1, Work Package 21

OpenAIRE

Mittelmark, Maurice B.

2016-01-01

At the onset of the ALICE RAP project, the following objectives, description of work, and main tasks were agreed for Work Package 21: 1. To evaluate the overall functioning of the collaborative research project, using a state-of-art systems model of partnership functioning. 2. To document the interactions and linkages between project inputs, throughputs and outputs as the project unfolds over five years. 3. To facilitate structured discussions involving all pa...

Rap-rimas afetivas da periferia: reflexões na perspectiva sócio-histórica Rap-affective rhymes of the periphery: reflections in the social-historical perspective

Directory of Open Access Journals (Sweden)

Jaison Hinkel

2007-01-01

Full Text Available Considerando a dimensão afetiva como constitutiva do agir e do pensar humano, e reconhecendo que sua presença é uma constante no Rap, este artigo busca investigar como a afetividade é expressa nas músicas de quatro grupos de Rap nacional. A partir da análise das músicas, pode-se considerar que estas expressam as vivências advindas de uma ordem social baseada na inclusão social perversa. Há instantes em que a tônica está no sentimento da vergonha, culpa, humilhação, tristeza, revolta e medo que assola os moradores da periferia. Em contrapartida, há propostas de enfrentamento desta condição, expressando a importância da união, irmandade, humildade, esperança, amor, alegria e solidariedade. Assim, nestas canções, a afetividade expressa tanto a denúncia do sofrimento ético-político, como a possibilidade de aumentar a potência de ação do sujeito para a superação da condição de padecimento humano, indicando a música, especialmente o Rap, como temática importante na compreensão psicossocial do sujeito em contextos de exclusão social.Considering the affectionate dimension as the constituent of act and of human thought, and recognizing that his presence is a constant one in the Rap, this article seeks to investigate like the affection is espress in the music of four groups of Rap national. Starting from the analysis of the music, we can consider that these express the resulting experiences of a social order based on the perverse social inclusion. There are instants in that to tonic is in the feeling of the shame, blame, humiliation, sorrow, revolt and fear that devastates the inhabitants of the periphery. In compensation, there is proposals to face of this condition, expressing the importance of the union, fraternity, humility, hope, love, joy and solidarity. Like this, in these songs, the so much express affection the denunciation of the ethical-political suffering, as the possibility of potency the action of the

A Histidine pH sensor regulates activation of the Ras-specific guanine nucleotide exchange factor RasGRP1.

Science.gov (United States)

Vercoulen, Yvonne; Kondo, Yasushi; Iwig, Jeffrey S; Janssen, Axel B; White, Katharine A; Amini, Mojtaba; Barber, Diane L; Kuriyan, John; Roose, Jeroen P

2017-09-27

RasGRPs are guanine nucleotide exchange factors that are specific for Ras or Rap, and are important regulators of cellular signaling. Aberrant expression or mutation of RasGRPs results in disease. An analysis of RasGRP1 SNP variants led to the conclusion that the charge of His 212 in RasGRP1 alters signaling activity and plasma membrane recruitment, indicating that His 212 is a pH sensor that alters the balance between the inactive and active forms of RasGRP1. To understand the structural basis for this effect we compared the structure of autoinhibited RasGRP1, determined previously, to those of active RasGRP4:H-Ras and RasGRP2:Rap1b complexes. The transition from the autoinhibited to the active form of RasGRP1 involves the rearrangement of an inter-domain linker that displaces inhibitory inter-domain interactions. His 212 is located at the fulcrum of these conformational changes, and structural features in its vicinity are consistent with its function as a pH-dependent switch.

Whats the Rap about Ecstasy? Popular Music Lyrics and Drug Trends among American Youth

Science.gov (United States)

Diamond, Sarah; Bermudez, Rey; Schensul, Jean

2006-01-01

Trends in ecstasy use in America during the past decade were reflected in mainstream, American rap-music lyrics between 1996 and 2003. Drawing on communication and cultural studies theory, this article provides a content analysis of 69 rap songs mentioning the club drug ecstasy. The songs are coded according to whether they contain positive, mixed…

Activation of the polyomavirus enhancer by a murine activator protein 1 (AP1) homolog and two contiguous proteins.

OpenAIRE

Martin, M E; Piette, J; Yaniv, M; Tang, W J; Folk, W R

1988-01-01

The polyomavirus enhancer is composed of multiple DNA sequence elements serving as binding sites for proteins present in mouse nuclear extracts that activate transcription and DNA replication. We have identified three such proteins and their binding sites and correlate them with enhancer function. Mutation of nucleotide (nt) 5140 in the enhancer alters the binding site (TGACTAA, nt 5139-5145) for polyomavirus enhancer A binding protein 1 (PEA1), a murine homolog of the human transcription fac...

Enhancement of hypoxia-activated prodrug TH-302 anti-tumor activity by Chk1 inhibition.

Science.gov (United States)

Meng, Fanying; Bhupathi, Deepthi; Sun, Jessica D; Liu, Qian; Ahluwalia, Dharmendra; Wang, Yan; Matteucci, Mark D; Hart, Charles P

2015-05-21

The hypoxia-activated prodrug TH-302 is reduced at its nitroimidazole group and selectively under hypoxic conditions releases the DNA cross-linker bromo-isophosphoramide mustard (Br-IPM). Here, we have explored the effect of Chk1 inhibition on TH-302-mediated pharmacological activities. We employed in vitro cell viability, DNA damage, cellular signaling assays and the in vivo HT29 human tumor xenograft model to study the effect of Chk1inhibition on TH-302 antitumor activities. TH-302 cytotoxicity is greatly enhanced by Chk1 inhibition in p53-deficient but not in p53-proficient human cancer cell lines. Chk1 inhibitors reduced TH-302-induced cell cycle arrest via blocking TH-302-induced decrease of phosphorylation of histone H3 and increasing Cdc2-Y15 phosphorylation. Employing the single-cell gel electrophoresis (comet) assay, we observed a potentiation of the TH-302 dependent tail moment. TH-302 induced γH2AX and apoptosis were also increased upon the addition of Chk1 inhibitor. Potentiation of TH-302 cytotoxicity by Chk1 inhibitor was only observed in cell lines proficient in, but not deficient in homology-directed DNA repair. We also show that combination treatment led to lowering of Rad51 expression levels as compared to either agent alone. In vivo data demonstrate that Chk1 inhibitor enhances TH-302 anti-tumor activity in p53 mutant HT-29 human tumor xenografts, supporting the hypothesis that these in vitro results can translate to enhanced in vivo efficacy of the combination. TH-302-mediated in vitro and in vivo anti-tumor activities were greatly enhanced by the addition of Chk1 inhibitors. The preclinical data presented in this study support a new approach for the treatment of p53-deficient hypoxic cancers by combining Chk1 inhibitors with the hypoxia-activated prodrug TH-302.

Feeling the beat: the meaning of rap music for ethnically diverse Midwestern college students--a phenomenological study.

Science.gov (United States)

Iwamoto, Derek K; Creswell, John; Caldwell, Leon

2007-01-01

Despite its national and international appeal, rap is considered one of the most controversial of music genres. Given the political charge it generates, rap music has spawned research across the social and health sciences. The majority of the research has investigated its impact on African Americans. Further, the research has tended to focus on negative aspects of the music; there has been a dearth of in-depth qualitative studies that explore how rap impacts the listener. Our phenomenological study explores that impact on ethnically diverse college students. Results indicate a profound psychological and educational effect and the discussion goes on to highlight the potential and innovative ways rap music can be utilized with adolescents in fields such as education, risk reduction programs, and counseling psychology.

PTP1B Inhibition Causes Rac1 Activation by Enhancing Receptor Tyrosine Kinase Signaling

Directory of Open Access Journals (Sweden)

Ayako Tsuchiya

2014-04-01

Full Text Available Background/Aims: The present study investigated the signaling pathway underlying Rac1 activation induced by the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl-cyclopropyl]-octanoic acid (DCP-LA. Methods: Activity of protein tyrosine phosphatase 1B (PTP1B was assayed under cell-free conditions. Western blot was carried out to quantify phosphorylation of insulin receptor substrate-1 (IRS-1 and Akt in PC-12 cells. Rac1 activity was monitored in the föerster resonance energy transfer (FRET analysis using living and fixed PC-12 cells. Results: DCP-LA markedly suppressed PTP1B activity in a concentration (100 pM-100 µM-dependent manner. In the DCP-LA binding assay, fluorescein-conjugated DCP-LA produced a single fluorescent signal band at 60 kDa, corresponding to the molecule of PTP1B, and the signal was attenuated or abolished by co-treatment or pretreatment with non-conjugated DCP-LA. DCP-LA significantly enhanced nerve growth factor (NGF-stimulated phosphorylation of IRS-1 at Tyr1222 and Akt1/2 at Thr308/309 and Ser473/474 in PC-12 cells. In the FRET analysis, DCP-LA significantly enhanced NGF-stimulated Rac1 activation, which is abrogated by the phosphatidylinositol 3 kinase (PI3K inhibitor wortmannin, the 3-phosphoinositide-dependent protein kinase-1 (PDK1 inhibitor BX912, or the Akt inhibitor MK2206. Conclusion: The results of the present study show that DCP-LA-induced PTP1B inhibition, possibly through its direct binding, causes Rac1 activation by enhancing a pathway along a receptor tyrosine kinase (RTK/IRS-1/PI3K/Akt/Rac1 axis.

Evaluation of the RapID-ANA system for identification of anaerobic bacteria of veterinary origin.

Science.gov (United States)

Adney, W S; Jones, R L

1985-12-01

This study evaluated the ability of the RapID-ANA system (Innovative Diagnostic Systems, Inc., Atlanta, Ga.) to accurately identify a spectrum of freshly isolated veterinary anaerobes. A total of 183 isolates were tested and included 7 Actinomyces spp., 53 Bacteroides spp., 32 Clostridium spp., 2 Eubacterium spp., 65 Fusobacterium spp., 1 Peptococcus spp., 22 Peptostreptococcus spp., and 1 Propionibacterium spp. All isolates were initially identified by conventional biochemical testing and gas-liquid chromatography of short-chain fatty acid metabolites. Additional tests were performed as required by the RapID-ANA system. Of these isolates, 81.4% were correctly identified to the genus level, including 59.6% to the species level, 14.2% were incorrectly identified at the genus level, and 4.4% were not identified. Initially, 20.2% of the strains were not identified because the microcodes were not in the code book. The majority of the incorrect identifications were caused by the misidentification of Fusobacterium spp. as Bacteroides spp. Errors also occurred when veterinary anaerobes not included in the data base were assigned an identification from the existing data base. The RapID-ANA system appears to be a promising new method for rapid identification of veterinary anaerobes; however, further evaluation with an extended data base is needed before the system can accurately identify all clinically significant anaerobes.

Hybrid Texts: Fifth Graders, Rap Music, and Writing

Science.gov (United States)

Christianakis, Mary

2011-01-01

Consistent with a sociocritical frame and the analytic tools of hybridity theory, this article explicates how urban fifth-grade children made language hybrids using rap and poetry to participate in classroom literacy. Ethnographic data from a yearlong study illustrate two key findings. First, standards-based and canon-driven writing models…

Sphingosine 1-phosphate receptor activation enhances BMP-2-induced osteoblast differentiation

International Nuclear Information System (INIS)

Sato, Chieri; Iwasaki, Tsuyoshi; Kitano, Sachie; Tsunemi, Sachi; Sano, Hajime

2012-01-01

Highlights: ► We investigated the role of S1P signaling for osteoblast differentiation. ► Both S1P and FTY enhanced BMP-2-stimulated osteoblast differentiation by C2C12 cells. ► S1P signaling enhanced BMP-2-stimulated Smad and ERK phosphorylation by C2C12 cells. ► MEK/ERK signaling is a pathway underlying S1P signaling for osteoblast differentiation. -- Abstract: We previously demonstrated that sphingosine 1-phosphate (S1P) receptor-mediated signaling induced proliferation and prostaglandin productions by synovial cells from rheumatoid arthritis (RA) patients. In the present study we investigated the role of S1P receptor-mediated signaling for osteoblast differentiation. We investigated osteoblast differentiation using C2C12 myoblasts, a cell line derived from murine satellite cells. Osteoblast differentiation was induced by the treatment of bone morphogenic protein (BMP)-2 in the presence or absence of either S1P or FTY720 (FTY), a high-affinity agonist of S1P receptors. Osteoblast differentiation was determined by osteoblast-specific transcription factor, Runx2 mRNA expression, alkaline phosphatase (ALP) activity and osteocalcin production by the cells. Smad1/5/8 and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation was examined by Western blotting. Osteocalcin production by C2C12 cells were determined by ELISA. Runx2 expression and ALP activity by BMP-2-stimulated C2C12 cells were enhanced by addition of either S1P or FTY. Both S1P and FTY enhanced BMP-2-induced ERK1/2 and Smad1/5/8 phosphorylation. The effect of FTY was stronger than that of S1P. S1P receptor-mediated signaling on osteoblast differentiation was inhibited by addition of mitogen-activated protein kinase/ERK kinase (MEK) 1/2 inhibitor, indicating that the S1P receptor-mediated MEK1/2-ERK1/2 signaling pathway enhanced BMP-2-Smad signaling. These results indicate that S1P receptor-mediated signaling plays a crucial role for osteoblast differentiation.

Performance evaluation of reactor operated zircaloy-2 pressure tubes of RAPS-1

International Nuclear Information System (INIS)

Chatterjee, S.; Ramadasan, E.; Balakrishnan, K.S.; Bahl, J.K.

1992-01-01

Detailed post irradiation examination was carried out on pressure tube sections from E-10, F-9 and F-10 locations of RAPS-1 after an in-reactor residence equivalent to 3.6 effective full power years. The F-10 pressure tube was studied in detail on sections obtained from one end to the other, whereas in the case of E-9 and F-9 pressure tubes only the end sections were examined. The studies carried out were visual examination, metallography, hydrogen i.e. H(D) analysis and mechanical testing at 300 C. Microstructural observations revealed uniform and random hydride/deuteride platelet distribution and absence of blisters or hydride segregation. The H(D) content in the F-10 pressure tube was found to vary in the range 6-12 ppm. The typical H(D) content in the three tubes was around 1 ppm. The H(D) pick-up evaluated from the observed oxide layer thickness was 8 ppm. Longitudinal tensile specimens fabricated from the F-10 pressure tube section and tested at 300 C exhibited increase in yield strength and tensile strength of 39% and 30% respectively. The residual uniform elongation was typically 1.8%. The observed changes in the tensile properties were found to be lower than those reported on unstressed specimens irradiated to similar neutron fluences. The observed hydrogen content and tensile properties obtained in F-10 pressure tube would not be detrimental under normal reactor operating conditions. (author). 10 refs., 4 figs., 2 tabs., 1 annexure

Open-Source Wax RepRap 3-D Printer for Rapid Prototyping Paper-Based Microfluidics.

Science.gov (United States)

Pearce, J M; Anzalone, N C; Heldt, C L

2016-08-01

The open-source release of self-replicating rapid prototypers (RepRaps) has created a rich opportunity for low-cost distributed digital fabrication of complex 3-D objects such as scientific equipment. For example, 3-D printable reactionware devices offer the opportunity to combine open hardware microfluidic handling with lab-on-a-chip reactionware to radically reduce costs and increase the number and complexity of microfluidic applications. To further drive down the cost while improving the performance of lab-on-a-chip paper-based microfluidic prototyping, this study reports on the development of a RepRap upgrade capable of converting a Prusa Mendel RepRap into a wax 3-D printer for paper-based microfluidic applications. An open-source hardware approach is used to demonstrate a 3-D printable upgrade for the 3-D printer, which combines a heated syringe pump with the RepRap/Arduino 3-D control. The bill of materials, designs, basic assembly, and use instructions are provided, along with a completely free and open-source software tool chain. The open-source hardware device described here accelerates the potential of the nascent field of electrochemical detection combined with paper-based microfluidics by dropping the marginal cost of prototyping to nearly zero while accelerating the turnover between paper-based microfluidic designs. © 2016 Society for Laboratory Automation and Screening.

Acoustic detection of particles, the RAP experiment: present status and results

International Nuclear Information System (INIS)

Bassan, M; Buonomo, B; Coccia, E; Blair, D; D'Antonio, S; Monache, G Delle; Gioacchino, D Di; Fafone, V; Ligi, C; Marini, A; Mazzitelli, G; Modestino, G; Pizzella, G; Quintieri, L; Roccella, S; Rocchi, A; Ronga, F; Tripodi, P; Valente, P

2006-01-01

Cosmic ray events with rate and energy much higher than expected were detected by the ultracryogenic gravitational antenna Nautilus located at the Laboratori Nazionali di Frascati, when it was operating in superconducting state. Mechanisms related to the superconductivity state of the material could be involved in such a way to enhance the conversion efficiency of the particle energy into vibrational energy of the detector. The RAP experiment has the aim to study the mechanical response of a small metallic resonant bar to short pulses of high energy electron beam, investigating the response of the bar both in normal and in superconducting state. The results obtained for an Al5056 bar down to a temperature of 4 K are reported and the preliminary results for a niobium bar at temperature below and above the superconducting-normal transition are also discussed

Rap as the language of conflict in hip-hop subculture

Directory of Open Access Journals (Sweden)

Т М Кожелупенко

2008-12-01

Full Text Available This article is devoted to such notions of sociolinguistics as subculture and the language of conflict. These aspects are studied by the example of the rapidly developing hip-hop subculture and rap-texts as its main component.

Assessing the impact of electrolyte conductivity and viscosity on the reactor cost and pressure drop of redox-active polymer flow batteries

Science.gov (United States)

Iyer, Vinay A.; Schuh, Jonathon K.; Montoto, Elena C.; Pavan Nemani, V.; Qian, Shaoyi; Nagarjuna, Gavvalapalli; Rodríguez-López, Joaquín; Ewoldt, Randy H.; Smith, Kyle C.

2017-09-01

Redox-active small molecules, used traditionally in redox flow batteries (RFBs), are susceptible to crossover and require expensive ion exchange membranes (IEMs) to achieve long lifetimes. Redox-active polymer (RAP) solutions show promise as candidate electrolytes to mitigate crossover through size-exclusion, enabling the use of porous separators instead of IEMs. Here, poly(vinylbenzyl ethyl viologen) is studied as a surrogate RAP for RFBs. For oxidized RAPs, ionic conductivity varies weakly between 1.6 and 2.1 S m-1 for RAP concentrations of 0.13-1.27 mol kg-1 (monomeric repeat unit per kg solvent) and 0.32 mol kg-1 LiBF4 with a minor increase upon reduction. In contrast, viscosity varies between 1.8 and 184.0 mPa s over the same concentration range with weakly shear-thinning rheology independent of oxidation state. Techno-economic analysis is used to quantify reactor cost as a function of electrolyte transport properties for RAP concentrations of 0.13-1.27 mol kg-1, assuming a hypothetical 3V cell and facile kinetics. Among these concentrations, reactor cost is minimized over a current density range of 600-1000 A m-2 with minimum reactor cost between 11-17 per kWh, and pumping pressures below 10 kPa. The predicted low reactor cost of RAP RFBs is enabled by sustained ionic mobility in spite of the high viscosity of concentrated RAP solutions.

Feeling the Beat: The Meaning of Rap Music for Ethnically Diverse Midwestern College Students--A Phenomenological Study

Science.gov (United States)

Iwamoto, Derek K.; Creswell, John; Caldwell, Leon

2007-01-01

Despite its national and international appeal, rap is considered one of the most controversial of music genres. Given the political charge it generates, rap music has spawned research across the social and health sciences. The majority of the research has investigated its impact on African Americans. Further, the research has tended to focus on…

O negro drama do rap: entre a lei do cão e a lei da selva

Directory of Open Access Journals (Sweden)

Bruno Zeni

2004-04-01

Full Text Available NESTE texto são feitas algumas considerações que partem de interesses e preocupações pessoais do autor a respeito do rap, tais como a elaboração das letras, a relação entre essa manifestação e o universo da pobreza e da prisão, o diálogo do ritmo com a tradição da música e da literatura brasileiras. São discutidas ainda algumas das questões estéticas e éticas relacionadas ao rap feito em São Paulo.IN THIS text I set out some considerations that stem from keen personal interests and concerns regarding rap - e.g., the production of lyrics, the relationship between such manifestations and the universe of poverty and imprisonment, and the dialogue between this rhythm and the broader tradition of Brazilian music and literature. I discuss some aesthetic and ethical issues related to the variety of rap that I am most intimately involved with, namely, the one made in São Paulo.

Sphingosine 1-phosphate receptor activation enhances BMP-2-induced osteoblast differentiation

Energy Technology Data Exchange (ETDEWEB)

Sato, Chieri [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Iwasaki, Tsuyoshi, E-mail: tsuyo-i@huhs.ac.jp [Division of Pharmacotherapy, Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe 650-8530 (Japan); Kitano, Sachie; Tsunemi, Sachi; Sano, Hajime [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan)

2012-06-22

Highlights: Black-Right-Pointing-Pointer We investigated the role of S1P signaling for osteoblast differentiation. Black-Right-Pointing-Pointer Both S1P and FTY enhanced BMP-2-stimulated osteoblast differentiation by C2C12 cells. Black-Right-Pointing-Pointer S1P signaling enhanced BMP-2-stimulated Smad and ERK phosphorylation by C2C12 cells. Black-Right-Pointing-Pointer MEK/ERK signaling is a pathway underlying S1P signaling for osteoblast differentiation. -- Abstract: We previously demonstrated that sphingosine 1-phosphate (S1P) receptor-mediated signaling induced proliferation and prostaglandin productions by synovial cells from rheumatoid arthritis (RA) patients. In the present study we investigated the role of S1P receptor-mediated signaling for osteoblast differentiation. We investigated osteoblast differentiation using C2C12 myoblasts, a cell line derived from murine satellite cells. Osteoblast differentiation was induced by the treatment of bone morphogenic protein (BMP)-2 in the presence or absence of either S1P or FTY720 (FTY), a high-affinity agonist of S1P receptors. Osteoblast differentiation was determined by osteoblast-specific transcription factor, Runx2 mRNA expression, alkaline phosphatase (ALP) activity and osteocalcin production by the cells. Smad1/5/8 and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation was examined by Western blotting. Osteocalcin production by C2C12 cells were determined by ELISA. Runx2 expression and ALP activity by BMP-2-stimulated C2C12 cells were enhanced by addition of either S1P or FTY. Both S1P and FTY enhanced BMP-2-induced ERK1/2 and Smad1/5/8 phosphorylation. The effect of FTY was stronger than that of S1P. S1P receptor-mediated signaling on osteoblast differentiation was inhibited by addition of mitogen-activated protein kinase/ERK kinase (MEK) 1/2 inhibitor, indicating that the S1P receptor-mediated MEK1/2-ERK1/2 signaling pathway enhanced BMP-2-Smad signaling. These results indicate that S1P

RAP: RNA-Seq Analysis Pipeline, a new cloud-based NGS web application.

Science.gov (United States)

D'Antonio, Mattia; D'Onorio De Meo, Paolo; Pallocca, Matteo; Picardi, Ernesto; D'Erchia, Anna Maria; Calogero, Raffaele A; Castrignanò, Tiziana; Pesole, Graziano

2015-01-01

The study of RNA has been dramatically improved by the introduction of Next Generation Sequencing platforms allowing massive and cheap sequencing of selected RNA fractions, also providing information on strand orientation (RNA-Seq). The complexity of transcriptomes and of their regulative pathways make RNA-Seq one of most complex field of NGS applications, addressing several aspects of the expression process (e.g. identification and quantification of expressed genes and transcripts, alternative splicing and polyadenylation, fusion genes and trans-splicing, post-transcriptional events, etc.). In order to provide researchers with an effective and friendly resource for analyzing RNA-Seq data, we present here RAP (RNA-Seq Analysis Pipeline), a cloud computing web application implementing a complete but modular analysis workflow. This pipeline integrates both state-of-the-art bioinformatics tools for RNA-Seq analysis and in-house developed scripts to offer to the user a comprehensive strategy for data analysis. RAP is able to perform quality checks (adopting FastQC and NGS QC Toolkit), identify and quantify expressed genes and transcripts (with Tophat, Cufflinks and HTSeq), detect alternative splicing events (using SpliceTrap) and chimeric transcripts (with ChimeraScan). This pipeline is also able to identify splicing junctions and constitutive or alternative polyadenylation sites (implementing custom analysis modules) and call for statistically significant differences in genes and transcripts expression, splicing pattern and polyadenylation site usage (using Cuffdiff2 and DESeq). Through a user friendly web interface, the RAP workflow can be suitably customized by the user and it is automatically executed on our cloud computing environment. This strategy allows to access to bioinformatics tools and computational resources without specific bioinformatics and IT skills. RAP provides a set of tabular and graphical results that can be helpful to browse, filter and export

Use of technology in implementing radiation protection good practices at RAPS-5 and 6

International Nuclear Information System (INIS)

Nawal, S.R.; Kakkar, Amandeep; Yadav, Umed; Venkataramana, K.; Ramasomayajulu, M.; Khot, Pankaj

2014-01-01

Nuclear Power Corporation of India Ltd (NPCIL), is committed to perform all its activities while providing high level of radiological protection and continue to meet international standards on radiological safety. In continuation to reducing in expenditure of station collective dose/individual dose both in terms of external and internal dose is attained by adopting many new and innovative good radiological practices as per ALARA principle. Some of these improved radiological practices of RAPS-5 and 6 are discussed in this paper

‘When i rap, i feel more like myself’

DEFF Research Database (Denmark)

Vitus, Kathrine

2016-01-01

This article analyzes the relationship between subjectivity and ideology in a short film, Rapper Girl, produced by young women living in multiethnic Copenhagen, and develops the concept of the ‘RapX fantasy’. Through Jacques Rancière’s and Slavoj Žižek’s theoretical lenses, the article explores how...

Epigenetic switch involved in activation of pioneer factor FOXA1-dependent enhancers

Science.gov (United States)

Sérandour, Aurélien A.; Avner, Stéphane; Percevault, Frédéric; Demay, Florence; Bizot, Maud; Lucchetti-Miganeh, Céline; Barloy-Hubler, Frédérique; Brown, Myles; Lupien, Mathieu; Métivier, Raphaël; Salbert, Gilles; Eeckhoute, Jérôme

2011-01-01

Transcription factors (TFs) bind specifically to discrete regions of mammalian genomes called cis-regulatory elements. Among those are enhancers, which play key roles in regulation of gene expression during development and differentiation. Despite the recognized central regulatory role exerted by chromatin in control of TF functions, much remains to be learned regarding the chromatin structure of enhancers and how it is established. Here, we have analyzed on a genomic-scale enhancers that recruit FOXA1, a pioneer transcription factor that triggers transcriptional competency of these cis-regulatory sites. Importantly, we found that FOXA1 binds to genomic regions showing local DNA hypomethylation and that its cell-type-specific recruitment to chromatin is linked to differential DNA methylation levels of its binding sites. Using neural differentiation as a model, we showed that induction of FOXA1 expression and its subsequent recruitment to enhancers is associated with DNA demethylation. Concomitantly, histone H3 lysine 4 methylation is induced at these enhancers. These epigenetic changes may both stabilize FOXA1 binding and allow for subsequent recruitment of transcriptional regulatory effectors. Interestingly, when cloned into reporter constructs, FOXA1-dependent enhancers were able to recapitulate their cell type specificity. However, their activities were inhibited by DNA methylation. Hence, these enhancers are intrinsic cell-type-specific regulatory regions of which activities have to be potentiated by FOXA1 through induction of an epigenetic switch that includes notably DNA demethylation. PMID:21233399

Diaspora portoricaine et musique rap à New-York : entre latinité et culture africaine américaine Puerto Rican diaspora and rap music in New-York city: between “latininad” and African American culture

Directory of Open Access Journals (Sweden)

Stéphane Partel

2012-05-01

Full Text Available Le rap a atteint un succès sans précédent auprès des jeunes urbains aux Etats-Unis et dans les grandes mégalopoles du monde entier. Ce genre musical, figure de proue du hip-hop, s’est affirmé dès les années 1970 comme un moyen d’expression diasporique reflétant les expériences, les rapports complexes et les interactions culturelles entre Africains Américains, Jamaïcains et Portoricains de la diaspora vivant à New York. Cependant, le positionnement des artistes issus de la diaspora portoricaine a été peu étudié. Nourri de séjours d’observation participante et de recherches réalisés entre 2005 et 2008, ainsi que de la fréquentation assidue des concerts du collectif artistique portoricain The Terror Squad auxquels l’auteur a pu assister, cet article se propose doncd’analyser le rôle central des artistes issus de la diaspora portoricaine de New York à travers l’étude du rap, élément le plus médiatisé du hip-hop. Il devient ainsi possible de mieux entrevoir les tensions, convergences et interactions culturelles qui régissent les rapports complexes qui s’établissent entre la latinité des Portoricains et la culture africaine-américaine urbaine depuis plus d’une trentaine d’années dans le milieu du rap.Rap music has achieved unprecedented success among urban youth in the United States and in big cities around the world. As a key element of hip-hop this musical style has been asserting its strength since the 1970s as a reflection of the diasporic experience and the complex cultural interactions between African Americans, Jamaicans and Puerto Ricans of the diaspora living in New York. However, scant research has been conducted on the role of Puerto Rican artists of the diaspora living in New York. Therefore, based on field trips and participant observation undertaken between 2005 and 2008 and the concerts of the Puerto Rican rap group The Terror Squad that the author was able to attend frequently, the

Laboratory testing and economic analysis of high RAP warm mixed asphalt.

Science.gov (United States)

2009-03-24

This report contains laboratory testing, economic analysis, literature review, and information obtained from multiple producers throughout the state of Mississippi regarding the use of high RAP (50 % to 100%) mixtures containing warm mix additives. T...

Nitrogen-responsive Regulation of GATA Protein Family Activators Gln3 and Gat1 Occurs by Two Distinct Pathways, One Inhibited by Rapamycin and the Other by Methionine Sulfoximine*

Science.gov (United States)

Georis, Isabelle; Tate, Jennifer J.; Cooper, Terrance G.; Dubois, Evelyne

2011-01-01

Nitrogen availability regulates the transcription of genes required to degrade non-preferentially utilized nitrogen sources by governing the localization and function of transcription activators, Gln3 and Gat1. TorC1 inhibitor, rapamycin (Rap), and glutamine synthetase inhibitor, methionine sulfoximine (Msx), elicit responses grossly similar to those of limiting nitrogen, implicating both glutamine synthesis and TorC1 in the regulation of Gln3 and Gat1. To better understand this regulation, we compared Msx- versus Rap-elicited Gln3 and Gat1 localization, their DNA binding, nitrogen catabolite repression-sensitive gene expression, and the TorC1 pathway phosphatase requirements for these responses. Using this information we queried whether Rap and Msx inhibit sequential steps in a single, linear cascade connecting glutamine availability to Gln3 and Gat1 control as currently accepted or alternatively inhibit steps in two distinct parallel pathways. We find that Rap most strongly elicits nuclear Gat1 localization and expression of genes whose transcription is most Gat1-dependent. Msx, on the other hand, elicits nuclear Gln3 but not Gat1 localization and expression of genes that are most Gln3-dependent. Importantly, Rap-elicited nuclear Gln3 localization is absolutely Sit4-dependent, but that elicited by Msx is not. PP2A, although not always required for nuclear GATA factor localization, is highly required for GATA factor binding to nitrogen-responsive promoters and subsequent transcription irrespective of the gene GATA factor specificities. Collectively, our data support the existence of two different nitrogen-responsive regulatory pathways, one inhibited by Msx and the other by rapamycin. PMID:22039046

Nitrogen-responsive regulation of GATA protein family activators Gln3 and Gat1 occurs by two distinct pathways, one inhibited by rapamycin and the other by methionine sulfoximine.

Science.gov (United States)

Georis, Isabelle; Tate, Jennifer J; Cooper, Terrance G; Dubois, Evelyne

2011-12-30

Nitrogen availability regulates the transcription of genes required to degrade non-preferentially utilized nitrogen sources by governing the localization and function of transcription activators, Gln3 and Gat1. TorC1 inhibitor, rapamycin (Rap), and glutamine synthetase inhibitor, methionine sulfoximine (Msx), elicit responses grossly similar to those of limiting nitrogen, implicating both glutamine synthesis and TorC1 in the regulation of Gln3 and Gat1. To better understand this regulation, we compared Msx- versus Rap-elicited Gln3 and Gat1 localization, their DNA binding, nitrogen catabolite repression-sensitive gene expression, and the TorC1 pathway phosphatase requirements for these responses. Using this information we queried whether Rap and Msx inhibit sequential steps in a single, linear cascade connecting glutamine availability to Gln3 and Gat1 control as currently accepted or alternatively inhibit steps in two distinct parallel pathways. We find that Rap most strongly elicits nuclear Gat1 localization and expression of genes whose transcription is most Gat1-dependent. Msx, on the other hand, elicits nuclear Gln3 but not Gat1 localization and expression of genes that are most Gln3-dependent. Importantly, Rap-elicited nuclear Gln3 localization is absolutely Sit4-dependent, but that elicited by Msx is not. PP2A, although not always required for nuclear GATA factor localization, is highly required for GATA factor binding to nitrogen-responsive promoters and subsequent transcription irrespective of the gene GATA factor specificities. Collectively, our data support the existence of two different nitrogen-responsive regulatory pathways, one inhibited by Msx and the other by rapamycin.

Migrant Rap in the Periphery: Performing Politics of Belonging

Science.gov (United States)

Leppänen, Sirpa; Westinen, Elina

2017-01-01

Focusing on a YouTube performance by an emergent Finnish Somali rapper and the audience responses it has generated, this paper looks at ways in which rap music engages with the issue of belonging. Drawing on recent theorizations of belonging as a multi-dimensional, contingent and fluid process, along with sociolinguistic work on globalization and…

Rap Therapy? An Innovative Approach to Groupwork with Urban Adolescents.

Science.gov (United States)

DeCarlo, Alonzo

2001-01-01

Describes a study in which young, urban African American adolescents with behavior problems participated in weekly group sessions that used rap music to promote the development of appropriate social skills related to morality, identity, judgement, decision making, anger management, impulse control, and crime and punishment. Overall, student…

Physics evaluation for testino. of RAPS and TAPS fuel pins in CIRUS pressurised water loop

International Nuclear Information System (INIS)

John, Benjamin; Paul, O.P.K.

1976-01-01

Relevant calculations carried out to assess the reactivity effect, heat generation and other parameters for testing of RAPS and TAPS fuel pins in the Cirus pressurised water loop are summarised. The Cirus neutron flux level being low, in order to simulate the RAPS design heat rating of ∫ Kdtheta = 40 w/cm, the required plutonium enrichment in mixed plutonium uranium oxide fuel pin was worked out. The results showed that a PuO 2 enrichment of 1.5 wt percent would be necessary to meet the above requirement. The analysis for the TAPS pin indicated that the desired heat flux of 115w/cm 2 cannot be obtained in the Cirus loop with either a 7 pin cluster geometry, or with a single pin with the enrichment level as used in TAPS pin. Lattice code DUMLAC and the core simulation code AECLHEX were used for these studies. (author)

RAP-2A Computer code for transients analysis in fast reactors

International Nuclear Information System (INIS)

Iftode, I.; Popescu, C.; Turcu, I.; Biro, L.

1975-10-01

The RAP-2A computer code is designed for analyzing thermohydraulic transients and/or steady state problems for large LMFBR cores. Physical and mathematical models, main input-output data, the flow chart of the code and a sample problem are given. RAP-2A calculates the power and the thermoydraulic transients initiated by a flow or reactivity changes, from a normal operating state of the reactor up to core disassembly. In this analysis a representative fuel pin is considered: a one-group space-independent (point) kinetics model to describe the neutron kinetics and a one-dimensional model describing the heat transfer (radial in the fuel and axial in the coolant) are used. Mechanical deformations due to temperature gradient, pressure losses, fuel melting, etc., are also calculated. The code is written in FORTRAN-4 language and is running on a IBM-370/135 computer

Rap como identidade cultural negra e periférica: a aversão de rappers brasileiros a Rede Globo

OpenAIRE

Júnior, Francisco Carlos Guerra de Mendonça

2014-01-01

Dissertação de Mestrado em Comunicação e Jornalismo, apresentada à Faculdade de Letras da Universidade de Coimbra. O rap (rhythm and poetry – ritmo e poesia) é a vertente musical do movimento hip hop, que surgiu nos Estados Unidos na década de 1960. Além do rap, o hip hop conta com MC´s (Mestres de Cerimônia), os DJ´s (disc-joqueys), a dança (break dance) e a pintura (grafith). O rap passou a ser um método utilizado para conscientizar a população sobre os problemas vivenciados pelos negros...

Remote ultrasonic characterisation of an irradiated pressure tube from RAPS-II

Energy Technology Data Exchange (ETDEWEB)

Gangotra, S; Muralidhar, S; Raut, S D; Ouseph, P M; Ghosh, J K; Sahoo, K C [Bhabha Atomic Research Centre, Bombay (India). Radiometallurgy Div.

1994-12-31

The Rajasthan Atomic Power Station Unit-2 (RAPS-2) has reached a stage of operation where the contacting pressure tubes are suspect to failure as a result of irradiation creep and displacement of the garter springs, the hot pressure tube coming in contact with the cold calandria tube. To study and assess the safety of these pressure tubes, two channels believed to be in contact with the calandria tubes, have been removed from the reactor for detailed full length post irradiation examination. Some of the test results are presented. 2 refs., 3 figs., 1 tab.

The second extracellular loop of the adenosine A1 receptor mediates activity of allosteric enhancers.

Science.gov (United States)

Kennedy, Dylan P; McRobb, Fiona M; Leonhardt, Susan A; Purdy, Michael; Figler, Heidi; Marshall, Melissa A; Chordia, Mahendra; Figler, Robert; Linden, Joel; Abagyan, Ruben; Yeager, Mark

2014-02-01

Allosteric enhancers of the adenosine A1 receptor amplify signaling by orthosteric agonists. Allosteric enhancers are appealing drug candidates because their activity requires that the orthosteric site be occupied by an agonist, thereby conferring specificity to stressed or injured tissues that produce adenosine. To explore the mechanism of allosteric enhancer activity, we examined their action on several A1 receptor constructs, including (1) species variants, (2) species chimeras, (3) alanine scanning mutants, and (4) site-specific mutants. These findings were combined with homology modeling of the A1 receptor and in silico screening of an allosteric enhancer library. The binding modes of known docked allosteric enhancers correlated with the known structure-activity relationship, suggesting that these allosteric enhancers bind to a pocket formed by the second extracellular loop, flanked by residues S150 and M162. We propose a model in which this vestibule controls the entry and efflux of agonists from the orthosteric site and agonist binding elicits a conformational change that enables allosteric enhancer binding. This model provides a mechanism for the observations that allosteric enhancers slow the dissociation of orthosteric agonists but not antagonists.

Opposing roles for RhoH GTPase during T-cell migration and activation

Science.gov (United States)

Baker, Christina M.; Comrie, William A.; Hyun, Young-Min; Chung, Hung-Li; Fedorchuk, Christine A.; Lim, Kihong; Brakebusch, Cord; McGrath, James L.; Waugh, Richard E.; Meier-Schellersheim, Martin; Kim, Minsoo

2012-01-01

T cells spend the majority of their time perusing lymphoid organs in search of cognate antigen presented by antigen presenting cells (APCs) and then quickly recirculate through the bloodstream to another lymph node. Therefore, regulation of a T-cell response is dependent upon the ability of cells to arrive in the correct location following chemokine gradients (“go” signal) as well as to receive appropriate T-cell receptor (TCR) activation signals upon cognate antigen recognition (“stop” signal). However, the mechanisms by which T cells regulate these go and stop signals remain unclear. We found that overexpression of the hematopoietic-specific RhoH protein in the presence of chemokine signals resulted in decreased Rap1–GTP and LFA-1 adhesiveness to ICAM-1, thus impairing T-cell chemotaxis; while in the presence of TCR signals, there were enhanced and sustained Rap1–GTP and LFA-1 activation as well as prolonged T:APC conjugates. RT-PCR analyses of activated CD4+ T cells and live images of T-cell migration and immunological synapse (IS) formation revealed that functions of RhoH took place primarily at the levels of transcription and intracellular distribution. Thus, we conclude that RhoH expression provides a key molecular determinant that allows T cells to switch between sensing chemokine-mediated go signals and TCR-dependent stop signals. PMID:22689994

Rap and singing are used by music therapists to enhance emotional self-regulation of youth: Results of a survey of music therapists in the Netherlands.

NARCIS (Netherlands)

Uhlig, S.; Dimitriadis, Theo; Hackvoort, Laurien; Scherder, E.J.A.

2016-01-01

Music therapists use rap and singing for at-risk youth and young adults in different treatment settings. However, it is unclear how often and what kind of interventions they apply, and what kind of treatment goals are pursued. The purpose of this study was to examine approaches of music therapists

Vitek 2 ANC card versus BBL Crystal Anaerobe and RapID ANA II for identification of clinical anaerobic bacteria.

Science.gov (United States)

Blairon, Laurent; Maza, Mengi L; Wybo, Ingrid; Piérard, Denis; Dediste, Anne; Vandenberg, Olivier

2010-08-01

The Vitek 2 Anaerobe and Corynebacterium Identification Card (ANC) was recently evaluated in a multicentre study. In the present work, this system was compared with the BBL Crystal Anaerobe and RapID ANA II panels. These kits were tested using 196 strains of anaerobes that had been previously identified by gas-liquid chromatography. Identification to the species or to the genus level was 75.0%, 81.1% and 70.9% for Crystal, RapID and Vitek, respectively. Vitek ANC failed to provide any identification in 20.4% of the strains, but it had fewer misidentifications than RapID. The confidence factors provided on the results report of each kit were not always correlated with a lower risk of major errors, with the exception of Vitek 2 in which a confidence factor higher than 0.86 excluded the risk of misidentification in more than 87% of isolates. The lower rate of identification by the Vitek and Crystal panels is mostly due the lower ability of these systems to identify the Clostridia. Overall, the three panels are comparable but need improvement to a better accuracy. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

CDK5RAP2 gene and tau pathophysiology in late-onset sporadic Alzheimer's disease.

Science.gov (United States)

Miron, Justin; Picard, Cynthia; Nilsson, Nathalie; Frappier, Josée; Dea, Doris; Théroux, Louise; Poirier, Judes

2018-06-01

Because currently known Alzheimer's disease (AD) single-nucleotide polymorphisms only account for a small fraction of the genetic variance in this disease, there is a need to identify new variants associated with AD. Our team performed a genome-wide association study in the Quebec Founder Population isolate to identify novel protective or risk genetic factors for late-onset sporadic AD and examined the impact of these variants on gene expression and AD pathology. The rs10984186 variant is associated with an increased risk of developing AD and with a higher CDK5RAP2 mRNA prevalence in the hippocampus. On the other hand, the rs4837766 variant, which is among the best cis-expression quantitative trait loci in the CDK5RAP2 gene, is associated with lower mild cognitive impairment/AD risk and conversion rate. The rs10984186 risk and rs4837766 protective polymorphic variants of the CDK5RAP2 gene might act as potent genetic modifiers for AD risk and/or conversion by modulating the expression of this gene. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Fundamental evaluation of the interaction between RAS/RAP and virgin asphalt binders.

Science.gov (United States)

2017-08-01

A comprehensive laboratory testing program was conducted in this research project to examine the blending between reclaimed asphalt pavement (RAP)/recycled asphalt shingles (RAS) and virgin asphalt binders and to evaluate the factors that may affect ...

Composite mechanisms for improving Bubble Rap in delay tolerant networks

Directory of Open Access Journals (Sweden)

Sweta Jain

2014-01-01

Full Text Available Delay tolerant networks (DTNs are a subset of mobile ad hoc networks where connections are sparse and intermittent. This often results in a network graph which is rarely connected which introduces a challenge in message forwarding because of a lack of end-to-end connectivity towards the destination. Recently, social-based forwarding algorithms are gaining popularity because of the social nature displayed by the node movements in a DTN, especially in application areas like the pocket switched networks. The social-based metrics like community, similarity, centrality etc. are used to determine the carrier to which a node has to forward its message. Composite methods are used to improve the performance of Bubble Rap social-based forwarding algorithm. In the proposed mechanism, a new social metric termed ‘friendship’ has been introduced along with a time-to-live (TTL-based ‘threshold’ and acknowledgement (ACK IDs. Real trace data and working day movement models are used for simulations in the opportunistic network environment simulator to demonstrate that the proposed algorithm gives better delivery ratio than the original Bubble Rap algorithm.

Rap and Resistance: A Social Movement of the Wu-Tang Clan.

Science.gov (United States)

Chasteen, Amy L.; Shriver, Thomas

1998-01-01

Examines specific collective identity and political expression of the rap group the Wu-Tang Clan. Reveals a multi-layered political strategy that has been conscientiously designed and implemented to instigate a social movement. Prioritizes the voices of marginalized Black peoples and provides raw narratives about oppression. (MMU)

The nucleosome assembly activity of NAP1 is enhanced by Alien.

Science.gov (United States)

Eckey, Maren; Hong, Wei; Papaioannou, Maria; Baniahmad, Aria

2007-05-01

The assembly of nucleosomes into chromatin is essential for the compaction of DNA and inactivation of the DNA template to modulate and repress gene expression. The nucleosome assembly protein 1, NAP1, assembles nucleosomes independent of DNA synthesis and was shown to enhance coactivator-mediated gene expression, suggesting a role for NAP1 in transcriptional regulation. Here, we show that Alien, known to harbor characteristics of a corepressor of nuclear hormone receptors such as of the vitamin D receptor (VDR), binds in vivo and in vitro to NAP1 and modulates its activity by enhancing NAP1-mediated nucleosome assembly on DNA. Furthermore, Alien reduces the accessibility of the histones H3 and H4 for NAP1-promoted assembly reaction. This indicates that Alien sustains and reinforces the formation of nucleosomes. Employing deletion mutants of Alien suggests that different regions of Alien are involved in enhancement of NAP1-mediated nucleosome assembly and in inhibiting the accessibility of the histones H3 and H4. In addition, we provide evidence that Alien is associated with chromatin and with micrococcus nuclease-prepared nucleosome fractions and interacts with the histones H3 and H4. Furthermore, chromatin immunoprecipitation and reimmunoprecipitation experiments suggest that NAP1 and Alien localize to the endogenous CYP24 promoter in vivo, a VDR target gene. Based on these findings, we present here a novel pathway linking corepressor function with nucleosome assembly activity.

RAP-IA code for calculus thermodinamic of the fast reactors

International Nuclear Information System (INIS)

Popescu, C.; Turcu, I.; Boeriu, S.; Biro, L.

1975-01-01

The RAP-IA code is developed in order to perform a complete calculation for a thermal channel of a Na-cooled fast reactor. Calculation may be effected for both stationary state and dynamic regime following modification of some in-put data: total thermal power, multiplication coefficient, flow-rate and in-put temperature of the thermal agent, pressure level

Effect of Bio based rejuvenator on mix design, Energy consumption and GHG Emission of High RAP Mixture

Science.gov (United States)

Abdullahi Ahmad, Kabiru; Ezree Abdullah, Mohd; Hassan, Norhidayah Abdul; Usman, Nura; Hassan, Mohd Rosli Mohd; Bilema, Munder A. M.; Modibbo Saeed, Saeed; Batari, Ahmad

2018-04-01

Concerns about the cost, availability, and environmental impact of using petroleum-based materials have led to increased usage of reclaimed asphalt pavement (RAP). Mean-while, the demand of the road industry to decrease the energy consumptions and reduce the release of greenhouse gases as well as other harmful gases, which cause serious air pollution has increased due to the amount of energy consumed is a major component of pavement construction that significantly contributes to the total cost. This paper evaluates the effects of Biobased rejuvenator known as JCO on the required heat energy and the amount of CO2 produced to increase the temperature of RAP and virgin aggregates and one binder from 25C to the point of mixing. The results showed that incorporating Biobased rejuvenator (JCO) can potentially reduce the required heat energy and amount of greenhouse gas produced by RAP and virgin, respectively.

Rapping in Catalan in Class and the Empowerment of the Learner

Science.gov (United States)

Aliagas, Cristina; Fernández, Júlia-Alba; Llonch, Pau

2016-01-01

Despite the well-known educational possibilities afforded by "Rhythm And Poetry" (RAP) for the development of musical, lyrical and critical skills [Morrell, E., & Duncan-Andrade, J. M. R. (2002). Promoting Academic Literacy with Urban Youth through Engaging Hip-hop Culture. "The English Journal," 91(6), 88-92. Retrieved…

Illuminating Chaucer through Poetry, Manuscript Illuminations, and a Critical Rap Album

Science.gov (United States)

Lynch, Tom Liam

2007-01-01

Drawing connections between Chaucer, Eminem, and social issues, New York City high school teacher Tom Liam Lynch helped students become familiar with "The Canterbury Tales." Students wrote poems of rhymed couplets about today's social and political issues, created illuminated manuscripts, and recorded a rap CD. A book and album were…

A educação informal e o rap como agente educativo

Directory of Open Access Journals (Sweden)

Alexandre Felipe Fiuza

2013-01-01

Full Text Available In this text are broached the relationship between rap music and the educational processes. To achieve this goal, the study deals with the conceptualization of the modalities of education, namely formal, non-formal and informal education, based on national and foreign bibliography. Considering the object of study, this paper is based on interdisciplinary reflections, consisting of theoretical and methodological approaches from the fields of Education, Music, Communication and Sociology of Culture. These theoretical frameworks contribute to the accuracy of concepts and the observation of the multiple dimensions that hip hop, and specifically rap, holds as a social and cultural phenomenon. By focusing on the particularity of informal education, which is even more prevalent in the so-called knowledge or media society, this study aims to contribute to the discussion of educational processes intrinsic to the culture industry and the media, and their significant influence on the audience.

Activation of RhoA, but Not Rac1, Mediates Early Stages of S1P-Induced Endothelial Barrier Enhancement.

Science.gov (United States)

Zhang, Xun E; Adderley, Shaquria P; Breslin, Jerome W

2016-01-01

Compromised endothelial barrier function is a hallmark of inflammation. Rho family GTPases are critical in regulating endothelial barrier function, yet their precise roles, particularly in sphingosine-1-phosphate (S1P)-induced endothelial barrier enhancement, remain elusive. Confluent cultures of human umbilical vein endothelial cells (HUVEC) or human dermal microvascular endothelial cells (HDMEC) were used to model the endothelial barrier. Barrier function was assessed by determining the transendothelial electrical resistance (TER) using an electrical cell-substrate impedance sensor (ECIS). The roles of Rac1 and RhoA were tested in S1P-induced barrier enhancement. The results show that pharmacologic inhibition of Rac1 with Z62954982 failed to block S1P-induced barrier enhancement. Likewise, expression of a dominant negative form of Rac1, or knockdown of native Rac1 with siRNA, failed to block S1P-induced elevations in TER. In contrast, blockade of RhoA with the combination of the inhibitors Rhosin and Y16 significantly reduced S1P-induced increases in TER. Assessment of RhoA activation in real time using a fluorescence resonance energy transfer (FRET) biosensor showed that S1P increased RhoA activation primarily at the edges of cells, near junctions. This was complemented by myosin light chain-2 phosphorylation at cell edges, and increased F-actin and vinculin near intercellular junctions, which could all be blocked with pharmacologic inhibition of RhoA. The results suggest that S1P causes activation of RhoA at the cell periphery, stimulating local activation of the actin cytoskeleton and focal adhesions, and resulting in endothelial barrier enhancement. S1P-induced Rac1 activation, however, does not appear to have a significant role in this process.

Activation of RhoA, but Not Rac1, Mediates Early Stages of S1P-Induced Endothelial Barrier Enhancement.

Directory of Open Access Journals (Sweden)

Xun E Zhang

Full Text Available Compromised endothelial barrier function is a hallmark of inflammation. Rho family GTPases are critical in regulating endothelial barrier function, yet their precise roles, particularly in sphingosine-1-phosphate (S1P-induced endothelial barrier enhancement, remain elusive. Confluent cultures of human umbilical vein endothelial cells (HUVEC or human dermal microvascular endothelial cells (HDMEC were used to model the endothelial barrier. Barrier function was assessed by determining the transendothelial electrical resistance (TER using an electrical cell-substrate impedance sensor (ECIS. The roles of Rac1 and RhoA were tested in S1P-induced barrier enhancement. The results show that pharmacologic inhibition of Rac1 with Z62954982 failed to block S1P-induced barrier enhancement. Likewise, expression of a dominant negative form of Rac1, or knockdown of native Rac1 with siRNA, failed to block S1P-induced elevations in TER. In contrast, blockade of RhoA with the combination of the inhibitors Rhosin and Y16 significantly reduced S1P-induced increases in TER. Assessment of RhoA activation in real time using a fluorescence resonance energy transfer (FRET biosensor showed that S1P increased RhoA activation primarily at the edges of cells, near junctions. This was complemented by myosin light chain-2 phosphorylation at cell edges, and increased F-actin and vinculin near intercellular junctions, which could all be blocked with pharmacologic inhibition of RhoA. The results suggest that S1P causes activation of RhoA at the cell periphery, stimulating local activation of the actin cytoskeleton and focal adhesions, and resulting in endothelial barrier enhancement. S1P-induced Rac1 activation, however, does not appear to have a significant role in this process.

An ALARA approach to collective dose control at RAPS-3 and 4

International Nuclear Information System (INIS)

Khandelwal, Narendra; Dhakar, P.C.; Gupta, Ashok

2016-01-01

At Rajasthan Atomic Power Station-3 and 4 (RAPS 3 and 4) immense efforts were put to achieve continual reduction in man rem consumption in every subsequent year and this could be done successfully through implementing design changes based on experience, reducing radiation levels by removing radioactive material from undesired locations, flushing of active system/equipment's, shielding of hot spots, minimizing D20 leaks, manpower optimization, improvement in work culture and strong management commitment etc. Radiation protection is a never ending process and scope is always available to reduce the doses at all levels. Routine radiation survey sometimes does not provide exact idea about potential of significant collective exposure that can take place when ambient radiation levels are comparable to background radiation levels

Frequency of helicobacter pylori (hp) infection in children with recurrent abdominal pain (rap)

International Nuclear Information System (INIS)

Mahmud, S.; Ali, S.

2015-01-01

To study the frequency of Helicobacter Pylori (HP) infection among children with recurrent abdominal pain (RAP) Study Design: Cross-sectional comparative study. Place and Duration of Study: Military Hospital (MH), Rawalpindi from December 2011 to February 2012. Patients and Methods: One hundred children of either gender aged 2 to 12 years presenting with RAP were tested for HP at Paediatric OPD MH, Rawalpindi who consented to participate in the study. Those children who tested positive for Helicobacter Pylori Stool Antigen Test (HPSAT) were labeled as those having Hp infection. The stool assay was performed using the HpSAT kit and the socio-demographic and clinical profiles of children were associated. Results: Out of 100 children included in the study HpSAT was positive in 38% children. Frequency of Hp infection was significantly associated with source of drinking water (p = 0.014), socioeconomic status (p = 0.001) and positive family history of yspepsia (p= 0.023). While age and gender have no significant association with HP infection. Conclusion: Hp infection is very common in children presenting with RAP in our Paediatric OPD. Children with family history of dyspepsia, from low socioeconomic class and those drinking filtered water are at greater risk for HP infection. It is recommended that children from other populations in our country should also be tested in their medical health facilities in order to have a wider analysis of this problem in our setup. (author)

Expression analysis and biological characterization of Babesia sp. BQ1 (Lintan) (Babesia motasi-like) rhoptry-associated protein 1 and its potential use in serodiagnosis via ELISA.

Science.gov (United States)

Niu, Qingli; Liu, Zhijie; Yang, Jifei; Yu, Peifa; Pan, Yuping; Zhai, Bintao; Luo, Jianxun; Moreau, Emmanuelle; Guan, Guiquan; Yin, Hong

2016-05-31

In China, ovine babesiosis is one of the most important tick-borne haemoparasitic diseases of small ruminants. It has a significant economic impact, and several Babesia motasi-like isolates have been recently shown to be responsible for ovine babesiosis in this country. Full-length and C-terminal-truncated forms of the rap-1a61-1 gene of Babesia sp. BQ1 (Lintan) were cloned into the pET-30a plasmid and subsequently expressed as His-fusion proteins. The resulting recombinant RAP-1a proteins (rRAP-1a61-1 and rRAP-1a61-1/CT) were purified and evaluated as diagnostic antigens using Western blot analysis and ELISA. The native Babesia sp. BQ1 (Lintan) RAP-1 protein was recognized using Western blots and IFAT by antibodies that were raised in rabbits against rRAP-1a61-1/CT. The specificity, sensitivity and positive threshold values for rRAP-1a61-1/CT in ELISA were evaluated. Cross-reactivity was observed between rRAP-1a61-1/CT and positive sera for Babesia sp. BQ1 (Lintan), Babesia sp. BQ1 (Ningxian) and Babesia sp. Tianzhu isolates obtained from infected sheep. At one week post-inoculation, a significant increase was observed in the amount of antibodies produced against RAP-1a, and high levels of antibodies against RAP-1a were observed for 3 months (at 84 days p.i.). A total of 3198 serum samples were collected from small ruminants in 54 different regions in 23 provinces of China. These samples were tested using ELISA based on the rRAP-1a61-1/CT protein. The results indicated that the average positive rate was 36.02 %. The present study suggests that rRAP-1a61-1/CT might be a potential diagnostic antigen for detecting several isolates of B. motasi-like parasites infection.

Enhancement of synchronized activity between hippocampal CA1 neurons during initial storage of associative fear memory.

Science.gov (United States)

Liu, Yu-Zhang; Wang, Yao; Shen, Weida; Wang, Zhiru

2017-08-01

Learning and memory storage requires neuronal plasticity induced in the hippocampus and other related brain areas, and this process is thought to rely on synchronized activity in neural networks. We used paired whole-cell recording in vivo to examine the synchronized activity that was induced in hippocampal CA1 neurons by associative fear learning. We found that both membrane potential synchronization and spike synchronization of CA1 neurons could be transiently enhanced after task learning, as observed on day 1 but not day 5. On day 1 after learning, CA1 neurons showed a decrease in firing threshold and rise times of suprathreshold membrane potential changes as well as an increase in spontaneous firing rates, possibly contributing to the enhancement of spike synchronization. The transient enhancement of CA1 neuronal synchronization may play important roles in the induction of neuronal plasticity for initial storage and consolidation of associative memory. The hippocampus is critical for memory acquisition and consolidation. This function requires activity- and experience-induced neuronal plasticity. It is known that neuronal plasticity is largely dependent on synchronized activity. As has been well characterized, repetitive correlated activity of presynaptic and postsynaptic neurons can lead to long-term modifications at their synapses. Studies on network activity have also suggested that memory processing in the hippocampus may involve learning-induced changes of neuronal synchronization, as observed in vivo between hippocampal CA3 and CA1 networks as well as between the rhinal cortex and the hippocampus. However, further investigation of learning-induced synchronized activity in the hippocampus is needed for a full understanding of hippocampal memory processing. In this study, by performing paired whole-cell recording in vivo on CA1 pyramidal cells (PCs) in anaesthetized adult rats, we examined CA1 neuronal synchronization before and after associative fear

End-joining inhibition at telomeres requires the translocase and polySUMO-dependent ubiquitin ligase Uls1.

Science.gov (United States)

Lescasse, Rachel; Pobiega, Sabrina; Callebaut, Isabelle; Marcand, Stéphane

2013-03-20

In eukaryotes, permanent inhibition of the non-homologous end joining (NHEJ) repair pathway at telomeres ensures that chromosome ends do not fuse. In budding yeast, binding of Rap1 to telomere repeats establishes NHEJ inhibition. Here, we show that the Uls1 protein is required for the maintenance of NHEJ inhibition at telomeres. Uls1 protein is a non-essential Swi2/Snf2-related translocase and a Small Ubiquitin-related Modifier (SUMO)-Targeted Ubiquitin Ligase (STUbL) with unknown targets. Loss of Uls1 results in telomere-telomere fusions. Uls1 requirement is alleviated by the absence of poly-SUMO chains and by rap1 alleles lacking SUMOylation sites. Furthermore, Uls1 limits the accumulation of Rap1 poly-SUMO conjugates. We propose that one of Uls1 functions is to clear non-functional poly-SUMOylated Rap1 molecules from telomeres to ensure the continuous efficiency of NHEJ inhibition. Since Uls1 is the only known STUbL with a translocase activity, it can be the general molecular sweeper for the clearance of poly-SUMOylated proteins on DNA in eukaryotes.

Improving Quality Control of Asphalt Pavement with RAP Using a Portable Infrared Spectroscopy Device

Science.gov (United States)

2016-04-01

This project has investigated the effectiveness of a Portable Infrared Spectrometer (PIRS) device in estimating percent of Reclaimed Asphalt Pavement (RAP) and its contribution into oxidative aging of a new asphalt mixture immediately after productio...

Investigation on the Combined Effect of Fibers and Cement on the Mechanical Performance of Foamed Bitumen Mixtures Containing 100% RAP

OpenAIRE

Ehsan Ashouri Taziani; Emanuele Toraldo; Filippo Giustozzi; Maurizio Crispino

2016-01-01

Concerns about virgin aggregate sources and increasing demands for construction materials of transport infrastructures as the key parameters in development are the most important reasons, which convinced pavement engineers to develop new methods in order to use higher amount of recycled asphalt pavement (RAP). One of the common methodologies to produce mixtures containing RAP is foamed bitumen mix (FBM). In addition, according to previous research studies, incorporating various types of fiber...

Apropriação musical: a arte de ouvir Rap

Directory of Open Access Journals (Sweden)

Jaison Hinkel

2011-09-01

Full Text Available Esta pesquisa teve por objetivo investigar se há e como se processa a relação estética entre sujeitos ouvintes e a música Rap, no processo de apropriação musical. Partimos da perspectiva sócio-histórica, segundo a qual nas reflexões metodológicas propostas por Vigotski estiveram tecidas as ideias de Bakhtin, como também as contribuições de Sartre, em um movimento dialógico com alguns leitores que se fazem interlocutores destes autores. Realizamos entrevistas individuais e abertas com cinco jovens moradores de periferia da região de Blumenau - SC. As análises indicaram a apropriação musical dos sujeitos investigados como um complexo processo que envolve aspectos referentes às propriedades físico-perceptuais do objeto estético Rap e a biografia de cada sujeito/ouvinte. A apropriação musical se mostrou como um complexo processo de conversão do coletivo em singular, fenômeno que exige um lugar cocriador do sujeito-ouvinte que se apropria dos significados expressos nas músicas e produz, a partir destes, novas zonas de sentido.

An Action Research Study on the Influence of Gangsta Rap on Academic and Behavioral Issues of 5th Grade African-American Males

Science.gov (United States)

Lewis, Shaun; Boes, Susan R.; Chibbaro, Julie S.

2015-01-01

This small action research study (ARS) began with a review of the literature examining the relationship of gangsta rap in regards to academic achievement, self-esteem, decision-making, identity issues and development of young African American males. The purpose of the ARS was to examine the correlation between gangsta rap and its influence on 5th…

KAI1 suppresses HIF-1α and VEGF expression by blocking CDCP1-enhanced Src activation in prostate cancer

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Park Jung-Jin

2012-03-01

Full Text Available Abstract Background KAI1 was initially identified as a metastasis-suppressor gene in prostate cancer. It is a member of the tetraspan transmembrane superfamily (TM4SF of membrane glycoproteins. As part of a tetraspanin-enriched microdomain (TEM, KAI1 inhibits tumor metastasis by negative regulation of Src. However, the underlying regulatory mechanism has not yet been fully elucidated. CUB-domain-containing protein 1 (CDCP1, which was previously known as tetraspanin-interacting protein in TEM, promoted metastasis via enhancement of Src activity. To better understand how KAI1 is involved in the negative regulation of Src, we here examined the function of KAI1 in CDCP1-mediated Src kinase activation and the consequences of this process, focusing on HIF-1 α and VEGF expression. Methods We used the human prostate cancer cell line PC3 which was devoid of KAI1 expression. Vector-transfected cells (PC3-GFP clone #8 and KAI1-expressing PC3 clones (PC3-KAI1 clone #5 and #6 were picked after stable transfection with KAI1 cDNA and selection in 800 μg/ml G418. Protein levels were assessed by immunoblotting and VEGF reporter gene activity was measured by assaying luciferase activitiy. We followed tumor growth in vivo and immunohistochemistry was performed for detection of HIF-1, CDCP1, and VHL protein level. Results We demonstrated that Hypoxia-inducible factor 1α (HIF-1α and VEGF expression were significantly inhibited by restoration of KAI1 in PC3 cells. In response to KAI1 expression, CDCP1-enhanced Src activation was down-regulated and the level of von Hippel-Lindau (VHL protein was significantly increased. In an in vivo xenograft model, KAI1 inhibited the expression of CDCP1 and HIF-1α. Conclusions These novel observations may indicate that KAI1 exerts profound metastasis-suppressor activity in the tumor malignancy process via inhibition of CDCP1-mediated Src activation, followed by VHL-induced HIF-1α degradation and, ultimately, decreased VEGF

THERAPIE - THErmix-RAps-Plot-InterfacE. A graphic software for representation of THERMIX-2D results with the interactive plot program RAPS

International Nuclear Information System (INIS)

Duensing, P.; Jahn, W.; Rehm, W.

1986-09-01

The performance of safety analyses for gas-cooled high temperature reactor power plants requires efficient plot codes for the evaluation and representation of computer results. The report describes the coupling between the thermodynamic simulation code THERMIX and the graphic plot code RAPS via the interface program THERAPIE. Especially the structure and the handling of the interface program are explained as well as the dialogue with the plot code. Further options of the colour graphic system are demonstrated for the representation of temperature distributions in components of HTR concepts (HTR-500). (orig.) [de

MAML1 enhances the transcriptional activity of Runx2 and plays a role in bone development.

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Takashi Watanabe

Full Text Available Mastermind-like 1 (MAML1 is a transcriptional co-activator in the Notch signaling pathway. Recently, however, several reports revealed novel and unique roles for MAML1 that are independent of the Notch signaling pathway. We found that MAML1 enhances the transcriptional activity of runt-related transcription factor 2 (Runx2, a transcription factor essential for osteoblastic differentiation and chondrocyte proliferation and maturation. MAML1 significantly enhanced the Runx2-mediated transcription of the p6OSE2-Luc reporter, in which luciferase expression was controlled by six copies of the osteoblast specific element 2 (OSE2 from the Runx2-regulated osteocalcin gene promoter. Interestingly, a deletion mutant of MAML1 lacking the N-terminal Notch-binding domain also enhanced Runx2-mediated transcription. Moreover, inhibition of Notch signaling did not affect the action of MAML1 on Runx2, suggesting that the activation of Runx2 by MAML1 may be caused in a Notch-independent manner. Overexpression of MAML1 transiently enhanced the Runx2-mediated expression of alkaline phosphatase, an early marker of osteoblast differentiation, in the murine pluripotent mesenchymal cell line C3H10T1/2. MAML1(-/- embryos at embryonic day 16.5 (E16.5 had shorter bone lengths than wild-type embryos. The area of primary spongiosa of the femoral diaphysis was narrowed. At E14.5, extended zone of collagen type II alpha 1 (Col2a1 and Sox9 expression, markers of chondrocyte differentiation, and decreased zone of collagen type X alpha 1 (Col10a1 expression, a marker of hypertrophic chondrocyte, were observed. These observations suggest that chondrocyte maturation was impaired in MAML1(-/- mice. MAML1 enhances the transcriptional activity of Runx2 and plays a role in bone development.

Transport activity of the sodium bicarbonate cotransporter NBCe1 is enhanced by different isoforms of carbonic anhydrase.

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Christina Schueler

Full Text Available Transport metabolons have been discussed between carbonic anhydrase II (CAII and several membrane transporters. We have now studied different CA isoforms, expressed in Xenopus oocytes alone and together with the electrogenic sodium bicarbonate cotransporter 1 (NBCe1, to determine their catalytic activity and their ability to enhance NBCe1 transport activity. pH measurements in intact oocytes indicated similar activity of CAI, CAII and CAIII, while in vitro CAIII had no measurable activity and CAI only 30% of the activity of CAII. All three CA isoforms increased transport activity of NBCe1, as measured by the transport current and the rate of intracellular sodium rise in oocytes. Two CAII mutants, altered in their intramolecular proton pathway, CAII-H64A and CAII-Y7F, showed significant catalytic activity and also enhanced NBCe1 transport activity. The effect of CAI, CAII, and CAII mutants on NBCe1 activity could be reversed by blocking CA activity with ethoxyzolamide (EZA, 10 µM, while the effect of the less EZA-sensitive CAIII was not reversed. Our results indicate that different CA isoforms and mutants, even if they show little enzymatic activity in vitro, may display significant catalytic activity in intact cells, and that the ability of CA to enhance NBCe1 transport appears to depend primarily on its catalytic activity.

Selectively enhanced expression of prophenoloxidase activating enzyme 1 (PPAE1 at a bacteria clearance site in the white shrimp, Litopenaeus vannamei

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Jang In-Kwon

2011-12-01

Full Text Available Abstract Background The prophenoloxidase-activating (PO activating system plays an important role in the crustacean innate immunity, particularly in wound healing and pathogen defense. A key member of this system is prophenoloxidase-activating enzyme (PPAE, which is the direct activator of prophenoloxidase (proPO. Despite their importance in crustacean PO activating system, the studies on them remain limited. Results Here we report on a PPAE of white shrimp, Litopenaeus vannamei (lvPPAE1, which showed 94% similarity to PPAE1 of Penaeus monodon. We found that lvPPAE1 in fluid hemocytes was down regulated after challenge by Vibrio harveyi but was enhanced when shrimps were exposed to a bacteria-rich environment for long-term. In vivo gene silence of lvPPAE1 by RNAi can significantly reduce the phenoloxidase activity (PO and increase the susceptibility of shrimps to V. harveyi. Although lvPPAE1 was down-regulated in fluid hemocytes by Vibrio challenge, its expression increased significantly in gill after bacteria injection, which is the primary bacteria-clearance tissue. Conclusion Suppressed expression in fluid hemocytes and enhanced expression in gill indicates selectively enhanced expression at the bacterial clearance site. This is a novel feature for PPAE expression. The results will contribute to our understanding of the PO activating system in crustaceans.

Økologisk risikovurdering af en genmodificeret glyfosat-tolerant raps GT73 i anmeldelse til godkendelse vedr. import til markedsføring under forordning 1829/2003/EF

DEFF Research Database (Denmark)

Kjellsson, Gøsta; Sørensen, Jesper Givskov; Damgaard, Christian

2012-01-01

"BIOSCIENCE konklusioner vedr. den økolo-giske risikovurdering af den genmodifice-rede GT73-raps i Danmark Den genmodificerede raps, GT73, adskiller sig fra konventionel raps ved at have indsat gener der gør planten tolerant over for herbicidet glyfosat. Rapsen søges kun godkendt til import til f...... to monitor such dispersal of the GMO-plant into cultivated fields and surroundings. Although, not directly an environmental issue, dispersal of the GT73 could result in problems for co-existence with non-GMO-cultivation. "...

Økologisk risikovurdering af en genmodificeret glyfosat-tolerant raps GT73 i anmeldelse til godkendelse vedr. import til markedsføring under Forordning 1829/2003/EF

DEFF Research Database (Denmark)

Damgaard, Christian; Sørensen, Jesper Givskov; Kjellsson, Gøsta

2012-01-01

BIOSCIENCE konklusioner vedr. den økolo-giske risikovurdering af den genmodifice-rede GT73-raps i Danmark Den genmodificerede raps, GT73, adskiller sig fra konventionel raps ved at have indsat gener der gør planten tolerant over for herbicidet glyfosat. Rapsen søges kun godkendt til import til fo...... to monitor such dispersal of the GMO-plant into cultivated fields and surroundings. Although, not directly an environmental issue, dispersal of the GT73 could result in problems for co-existence with non-GMO-cultivation....

Neural correlates of lyrical improvisation: an FMRI study of freestyle rap.

Science.gov (United States)

Liu, Siyuan; Chow, Ho Ming; Xu, Yisheng; Erkkinen, Michael G; Swett, Katherine E; Eagle, Michael W; Rizik-Baer, Daniel A; Braun, Allen R

2012-01-01

The neural correlates of creativity are poorly understood. Freestyle rap provides a unique opportunity to study spontaneous lyrical improvisation, a multidimensional form of creativity at the interface of music and language. Here we use functional magnetic resonance imaging to characterize this process. Task contrast analyses indicate that improvised performance is characterized by dissociated activity in medial and dorsolateral prefrontal cortices, providing a context in which stimulus-independent behaviors may unfold in the absence of conscious monitoring and volitional control. Connectivity analyses reveal widespread improvisation-related correlations between medial prefrontal, cingulate motor, perisylvian cortices and amygdala, suggesting the emergence of a network linking motivation, language, affect and movement. Lyrical improvisation appears to be characterized by altered relationships between regions coupling intention and action, in which conventional executive control may be bypassed and motor control directed by cingulate motor mechanisms. These functional reorganizations may facilitate the initial improvisatory phase of creative behavior.

Neariminio žemės dirbimo poveikis vasarinių rapsų agroekosistemos komponentams

OpenAIRE

Petrauskas, Tomas

2014-01-01

Tikslas – įvertinti tiesioginės sėjos, supaprastinto žemės dirbimo ir augalinių liekanų įtaką kai kuriems vasarinių rapsų agroekosistemos komponentams. Stacionarus dviejų veiksnių lauko eksperimentas įrengtas 1999 m. Aleksandro Stulginskio universiteto Bandymų stotyje. A veiksnys − šiaudų panaudojimas: šiaudai pašalinti (-Š); šiaudai susmulkinti ir paskleisti (+Š). B veiksnys − žemės dirbimos sistemos: įprastas gilus arimas 23–25 cm gyliu rudenį (GA), kontrolinis variantas; seklus arimas 10–1...

1,25D3 enhances antitumor activity of gemcitabine and cisplatin in human bladder cancer models

Science.gov (United States)

Ma, Yingyu; Yu, Wei-Dong; Trump, Donald L.; Johnson, Candace S.

2010-01-01

Background 1,25 dihydroxyvitamin D3 (1,25D3) potentiates the cytotoxic effects of several common chemotherapeutic agents. The combination of gemcitabine and cisplatin (GC) is a current standard chemotherapy regimen for bladder cancer. We investigated whether 1,25D3 could enhance the antitumor activity of GC in bladder cancer model systems. Methods Human bladder cancer T24 and UMUC3 cells were pretreated with 1,25D3 followed by GC. Apoptosis were assessed by annexin V staining. Caspase activation was examined by immunoblot analysis and substrate-based caspase activity assay. The cytotoxic effects were examined using MTT and in vitro clonogenic assay. p73 protein levels were assessed by immunoblot analysis. Knockdown of p73 was achieved by siRNA. The in vivo antitumor activity was assessed by in vivo excision clonogenic assay and tumor regrowth delay in the T24 xenograft model. Results 1,25D3 pretreatment enhanced GC-induced apoptosis and the activities of caspases- 8, 9 and 3 in T24 and UMUC3 cells. 1,25D3 synergistically reduced GC-suppressed surviving fraction in T24 cells. 1,25D3, gemcitabine, or cisplatin induced p73 accumulation, which was enhanced by GC or 1,25D3 and GC. p73 expression was lower in human primary bladder tumor tissue compared with adjacent normal tissue. Knockdown of p73 increased clonogenic capacity of T24 cells treated with 1,25D3, GC or 1,25D3 and GC. 1,25D3 and GC combination enhanced tumor regression compared with 1,25D3 or GC alone. Conclusions 1,25D3 potentiates GC-mediated growth inhibition in human bladder cancer models in vitro and in vivo, which involves p73 induction and apoptosis. PMID:20564622

Butyrate transcriptionally enhances peptide transporter PepT1 expression and activity.

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Guillaume Dalmasso

Full Text Available BACKGROUND: PepT1, an intestinal epithelial apical di/tripeptide transporter, is normally expressed in the small intestine and induced in colon during chronic inflammation. This study aimed at investigating PepT1 regulation by butyrate, a short-chain fatty acid produced by commensal bacteria and accumulated inside inflamed colonocyte. RESULTS: We found that butyrate treatment of human intestinal epithelial Caco2-BBE cells increased human PepT1 (hPepT1 promoter activity in a dose- and time-dependent manner, with maximal activity observed in cells treated with 5 mM butyrate for 24 h. Under this condition, hPepT1 promoter activity, mRNA and protein expression levels were increased as assessed by luciferase assay, real-time RT-PCR and Western blot, respectively. hPepT1 transport activity was accordingly increased by approximately 2.5-fold. Butyrate did not alter hPepT1 mRNA half-life indicating that butyrate acts at the transcriptional level. Molecular analyses revealed that Cdx2 is the most important transcription factor for butyrate-induced increase of hPepT1 expression and activity in Caco2-BBE cells. Butyrate-activated Cdx2 binding to hPepT1 promoter was confirmed by gel shift and chromatin immunoprecipitation. Moreover, Caco2-BBE cells overexpressing Cdx2 exhibited greater hPepT1 expression level than wild-type cells. Finally, treatment of mice with 5 mM butyrate added to drinking water for 24 h increased colonic PepT1 mRNA and protein expression levels, as well as enhanced PepT1 transport activity in colonic apical membranes vesicles. CONCLUSIONS: Collectively, our results demonstrate that butyrate increases PepT1 expression and activity in colonic epithelial cells, which provides a new understanding of PepT1 regulation during chronic inflammation.

El vídeo, el cómic y el rap: una forma diferente de desbloquear al candidato del DELE

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Florencia Battagliero Bocco

2017-11-01

Full Text Available Resumen: El objetivo del presente artículo es trabajar y reforzar las destrezas y competencias necesarias para aprobar el Diploma de Español como Lengua Extranjera. Para ello, se planteará una serie de recursos que buscan desbloquear al estudiante en un ambiente distendido, sobre todo los días previos al examen. La propuesta se centrará en la Prueba de Expresión e Interacción Orales, concretamente en la tarea 3 del nivel B1 y en la tarea 2 del nivel B2, que corresponden a la descripción de una fotografía. Se empleará, por una parte, un vídeo de carácter estático (donde el interlocutor no expresa movimientos corporales pronunciados y por otra, cómics de Argentina que a su vez servirán para ampliar el léxico en la variante rioplatense. Por último, se tratará el uso del rap como herramienta para mejorar la pronunciación, entonación y el empleo del lenguaje no verbal. Palabras claves: DELE, vídeo, cómic, rap.   Abstract: The purpose of the following essay is to train and to strengthen the skills and the competences required to pass the “Spanish as a Foreign Language Certificate”. In order to do so, we will first consider various resources which aim to release students from any kind of stress by setting up a relaxed atmosphere – especially a few days before the exam. The focus of the present essay has to be linked to the Expression and Oral Interaction tests and above all to the assignments 3 (B1 level and 2 (B2 level, and their picture descriptions. On the one hand, we will use a static video and, on the other hand, we will tackle Argentinian comics in order to expand students’ knowledge of the Río de la Plata lexicon. Finally, we will deal with the use of rap as a tool to improve pronunciation, intonation, and non-verbal communication. Key words: DELE, video, comic, rap.

JMJD1C demethylates MDC1 to regulate the RNF8 and BRCA1-mediated chromatin response to DNA breaks

DEFF Research Database (Denmark)

Watanabe, Sugiko; Watanabe, Kenji; Akimov, Vyacheslav

2013-01-01

Chromatin ubiquitylation flanking DNA double-strand breaks (DSBs), mediated by RNF8 and RNF168 ubiquitin ligases, orchestrates a two-branch pathway, recruiting repair factors 53BP1 or the RAP80-BRCA1 complex. We report that human demethylase JMJD1C regulates the RAP80-BRCA1 branch of this DNA...

O circuito rap “indé” em Paris: dinâmicas socioterritoriais e mensagem ultramar

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Cristiano Nunes Alves

2016-05-01

Full Text Available Aborda-se o circuito rap independente em Paris, o chamado “rap indé”, produção musical da cultura hip hop, constituída por materialidades e fluxos dinamizados por agentes cujas raízes estão em territórios ultramarinos. Lançando mão de um levantamento documental e bibliográfico, e, de uma série de entrevistas e visitas técnicas, problematiza-se a relação do hip hop com o lugar, e propõe-se uma análise do rap indé a partir da teoria dos circuitos da economia urbana nos países subdesenvolvidos. Observa-se que o circuito indé, fortalecido na Île-de-France, sobretudo desde meados dos anos 1990, mobiliza toda a região, tendo em Clignancourt, importante lugar de encontro e articulação.  Sua produção dá-se em estúdios e selos de menor porte, caracterizando-se ainda por pequenas espessuras ligadas aos eventos musicais, e, divulgação e comercialização alternativas aos grandes circuitos da economia. Trata-se de um estudo buscando alternativas para pensar os modos de se analisar, a partir da música, as dinâmicas socioterritoriais na cidade contemporânea.

Overexpression of OLE1 enhances stress tolerance and constitutively activates the MAPK HOG pathway in Saccharomyces cerevisiae.

Science.gov (United States)

Nasution, Olviyani; Lee, Young Mi; Kim, Eunjung; Lee, Yeji; Kim, Wankee; Choi, Wonja

2017-03-01

OLE1 of Saccharomyces cerevisiae encodes the sole and essential Δ-9 desaturase catalyzing the conversion of saturated to unsaturated fatty acids. Upon ectopic overexpression of OLE1 in S. cerevisiae, significant increases in the membrane oleic acid content were observed. OLE1-overexpressing strains displayed enhanced tolerance to various stresses, better proton efflux, lower membrane permeability, and lessened internal hydrogen peroxide content. The OLE1-mediated enhanced stress tolerance was considerably diminished upon deletion of HOG1, which encodes the mitogen-activated protein kinase (MAPK) Hog1 of the high osmolarity glycerol (HOG) pathway. Furthermore, OLE1 overexpression constitutively activated Hog1, which remained in the cytoplasm. Hog1 activation was accomplished through the MAPK kinase kinase (MAPKKK) Ssk2, but not Ste11 and Ssk22, the other MAPKKKs of the HOG pathway. Despite its cytoplasmic location, activated Hog1 was able to activate the expression of its canonical targets, including CTT1, HSP12, and STL1, and further, the cAMP and stress response elements present in the promoter. OLE1 overexpression neither caused nor relieved endoplasmic reticulum stress. Individually or in combination, the physiological and molecular changes caused by OLE1 overexpression may contribute to enhanced tolerance to various types of stress. Biotechnol. Bioeng. 2017;114: 620-631. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Critical role for Epac1 in inflammatory pain controlled by GRK2-mediated phosphorylation of Epac1

NARCIS (Netherlands)

Singhmar, Pooja; Huo, XiaoJiao; Eijkelkamp, Niels; Berciano, Susana Rojo; Baameur, Faiza; Mei, Fang C; Zhu, Yingmin; Cheng, Xiaodong; Hawke, David; Mayor, Federico; Murga, Cristina; Heijnen, Cobi J.; Kavelaars, Annemieke

2016-01-01

cAMP signaling plays a key role in regulating pain sensitivity. Here, we uncover a previously unidentified molecular mechanism in which direct phosphorylation of the exchange protein directly activated by cAMP 1 (EPAC1) by G protein kinase 2 (GRK2) suppresses Epac1-to-Rap1 signaling, thereby

Impaired TIP60-mediated H4K16 acetylation accounts for the aberrant chromatin accumulation of 53BP1 and RAP80 in Fanconi anemia pathway-deficient cells.

Science.gov (United States)

Renaud, Emilie; Barascu, Aurelia; Rosselli, Filippo

2016-01-29

To rescue collapsed replication forks cells utilize homologous recombination (HR)-mediated mechanisms to avoid the induction of gross chromosomal abnormalities that would be generated by non-homologous end joining (NHEJ). Using DNA interstrand crosslinks as a replication barrier, we investigated how the Fanconi anemia (FA) pathway promotes HR at stalled replication forks. FA pathway inactivation results in Fanconi anemia, which is associated with a predisposition to cancer. FANCD2 monoubiquitination and assembly in subnuclear foci appear to be involved in TIP60 relocalization to the chromatin to acetylates histone H4K16 and prevents the binding of 53BP1 to its docking site, H4K20Me2. Thus, FA pathway loss-of-function results in accumulation of 53BP1, RIF1 and RAP80 at damaged chromatin, which impair DNA resection at stalled replication fork-associated DNA breaks and impede HR. Consequently, DNA repair in FA cells proceeds through the NHEJ pathway, which is likely responsible for the accumulation of chromosome abnormalities. We demonstrate that the inhibition of NHEJ or deacetylase activity rescue HR in FA cells. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Rap van tong, scherp van pen. Literaire discussiecultuur in Nederlandse praatjespamfletten (circa 1600-1750)

NARCIS (Netherlands)

Dingemanse, C.W.

2008-01-01

In the early modern period pamphlets constituted the most important medium to influence public opinion in the Netherlands. The thesis Rap van tong, scherp van pen (Glib tongues, sharp pens) focuses on the literary and rhetorical aspects of a remarkable type of pamphlet called praatje (small-talk),

6-Mercaptopurine, an activator of Nur77, enhances transcriptional activity of HIF-1alpha resulting in new vessel formation.

Science.gov (United States)

Yoo, Y-G; Na, T-Y; Yang, W-K; Kim, H-J; Lee, I-K; Kong, G; Chung, J-H; Lee, M-O

2007-05-31

Hypoxia-inducible factor-1alpha (HIF-1alpha) plays a central role in oxygen homeostasis. Previously, we reported that the orphan nuclear receptor Nur77 functions in stabilizing HIF-1alpha. Here, we demonstrate that 6-mercaptopurine (6-MP), an activator of the NR4A family members, enhances transcriptional activity of HIF-1. 6-MP enhanced the protein-level of HIF-1alpha as well as vascular endothelial growth factor (VEGF) in a dose- and time-dependent manner. The induction of HIF-1alpha was abolished by the transfection of either a dominant-negative Nur77 mutant or si-Nur77, indicating a critical role of Nur77 in the 6-MP action. The HIF-1alpha protein level remained up to 60 min in the presence of 6-MP when de novo protein synthesis was blocked by cycloheximide, suggesting that 6-MP induces stabilization of the HIF-1alpha protein. The fact that 6-MP decreased the association of HIF-1alpha with von Hippel-Lindau protein and the acetylation of HIF-1alpha, may explain how 6-MP induced stability of HIF-1alpha. Further, 6-MP induced the transactivation function of HIF-1alpha by recruiting co-activator cyclic-AMP-response-element-binding protein. Finally, 6-MP enhanced the expression of HIF-1alpha and VEGF, and the formation of capillary tubes in human umbilical vascular endothelial cells. Together, our results provide a new insight for 6-MP action in the stabilization of HIF-1alpha and imply a potential application of 6-MP in hypoxia-associated human vascular diseases.

Sequential sentinel SNP Regional Association Plots (SSS-RAP): an approach for testing independence of SNP association signals using meta-analysis data.

Science.gov (United States)

Zheng, Jie; Gaunt, Tom R; Day, Ian N M

2013-01-01

Genome-Wide Association Studies (GWAS) frequently incorporate meta-analysis within their framework. However, conditional analysis of individual-level data, which is an established approach for fine mapping of causal sites, is often precluded where only group-level summary data are available for analysis. Here, we present a numerical and graphical approach, "sequential sentinel SNP regional association plot" (SSS-RAP), which estimates regression coefficients (beta) with their standard errors using the meta-analysis summary results directly. Under an additive model, typical for genes with small effect, the effect for a sentinel SNP can be transformed to the predicted effect for a possibly dependent SNP through a 2×2 2-SNP haplotypes table. The approach assumes Hardy-Weinberg equilibrium for test SNPs. SSS-RAP is available as a Web-tool (http://apps.biocompute.org.uk/sssrap/sssrap.cgi). To develop and illustrate SSS-RAP we analyzed lipid and ECG traits data from the British Women's Heart and Health Study (BWHHS), evaluated a meta-analysis for ECG trait and presented several simulations. We compared results with existing approaches such as model selection methods and conditional analysis. Generally findings were consistent. SSS-RAP represents a tool for testing independence of SNP association signals using meta-analysis data, and is also a convenient approach based on biological principles for fine mapping in group level summary data. © 2012 Blackwell Publishing Ltd/University College London.

Structural integrity test of Indian PHWR containment of Kaiga- 1 and 2 and RAPS- 3 and 4 atomic power stations

International Nuclear Information System (INIS)

Samota, Arun; Verma, U.S.P.; Warudkar, A.S.; Mohan, Nalini; Bhawal, R.N.; Bajaj, S.S.

2002-01-01

Full text: The structural integrity tests of Kaiga 1, 2 and RAPS 3, 4 primary containment were carried out as per requirements specified in RCC-G code by pressurizing the containment with oil free air at design pressure of 1.73 Kg/cm 2 (g). Dilations were monitored in vertical and radial directions by installing dial gauges at various locations on the outer surface of primary containment. The dilations were generally observed to be linear with the pressure and the residual displacements were within the acceptable limit. Strains were measured in meridional and circumferential directions at different pressure levels by using a large number of different types of strain gauge. While the behaviour of embedded type vibrating wire strain gauges was excellent, the behaviour of surface mounted electrical resistance (SMER) was satisfactory. Other parameters monitored were crack, differential and absolute settlements. No crack was noticed in any of the containment. No absolute and differential settlements were noticed. The results of the tests have demonstrated elastic behaviour of the containment. The acceptance criteria of the tests were met with good margin

Ubiquitin fold modifier 1 (UFM1 and its target UFBP1 protect pancreatic beta cells from ER stress-induced apoptosis.

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Katleen Lemaire

Full Text Available UFM1 is a member of the ubiquitin like protein family. While the enzymatic cascade of UFM1 conjugation has been elucidated in recent years, the biological function remains largely unknown. In this report we demonstrate that the recently identified C20orf116, which we name UFM1-binding protein 1 containing a PCI domain (UFBP1, and CDK5RAP3 interact with UFM1. Components of the UFM1 conjugation pathway (UFM1, UFBP1, UFL1 and CDK5RAP3 are highly expressed in pancreatic islets of Langerhans and some other secretory tissues. Co-localization of UFM1 with UFBP1 in the endoplasmic reticulum (ER depends on UFBP1. We demonstrate that ER stress, which is common in secretory cells, induces expression of Ufm1, Ufbp1 and Ufl1 in the beta-cell line INS-1E. siRNA-mediated Ufm1 or Ufbp1 knockdown enhances apoptosis upon ER stress. Silencing the E3 enzyme UFL1, results in similar outcomes, suggesting that UFM1-UFBP1 conjugation is required to prevent ER stress-induced apoptosis. Together, our data suggest that UFM1-UFBP1 participate in preventing ER stress-induced apoptosis in protein secretory cells.

Granzyme B-dependent proteolysis acts as a switch to enhance the proinflammatory activity of IL-1α.

LENUS (Irish Health Repository)

Afonina, Inna S

2011-10-21

Granzyme B is a cytotoxic lymphocyte-derived protease that plays a central role in promoting apoptosis of virus-infected target cells, through direct proteolysis and activation of constituents of the cell death machinery. However, previous studies have also implicated granzymes A and B in the production of proinflammatory cytokines, via a mechanism that remains undefined. Here we show that IL-1α is a substrate for granzyme B and that proteolysis potently enhanced the biological activity of this cytokine in vitro as well as in vivo. Consistent with this, compared with full-length IL-1α, granzyme B-processed IL-1α exhibited more potent activity as an immunoadjuvant in vivo. Furthermore, proteolysis of IL-1α within the same region, by proteases such as calpain and elastase, was also found to enhance its biological potency. Thus, IL-1α processing by multiple immune-related proteases, including granzyme B, acts as a switch to enhance the proinflammatory properties of this cytokine.

Specific T-cell recognition of the merozoite proteins rhoptry-associated protein 1 and erythrocyte-binding antigen 1 of Plasmodium falciparum

DEFF Research Database (Denmark)

Jakobsen, P H; Hviid, L; Theander, T G

1993-01-01

The merozoite proteins merozoite surface protein 1 (MSP-1) and rhoptry-associated protein 1 (RAP-1) and synthetic peptides containing sequences of MSP-1, RAP-1, and erythrocyte-binding antigen 1, induced in vitro proliferative responses of lymphocytes collected from Ghanaian blood donors living i...... by individuals living in an area with a high transmission rate of malaria. Most of the donor plasma samples tested contained immunoglobulin G (IgG) and IgM antibodies recognizing the merozoite proteins, while only a minority showed high IgG reactivity to the synthetic peptides.......The merozoite proteins merozoite surface protein 1 (MSP-1) and rhoptry-associated protein 1 (RAP-1) and synthetic peptides containing sequences of MSP-1, RAP-1, and erythrocyte-binding antigen 1, induced in vitro proliferative responses of lymphocytes collected from Ghanaian blood donors living...

Customized treatment in non-small-cell lung cancer based on EGFR mutations and BRCA1 mRNA expression.

Directory of Open Access Journals (Sweden)

Rafael Rosell

Full Text Available BACKGROUND: Median survival is 10 months and 2-year survival is 20% in metastatic non-small-cell lung cancer (NSCLC treated with platinum-based chemotherapy. A small fraction of non-squamous cell lung cancers harbor EGFR mutations, with improved outcome to gefitinib and erlotinib. Experimental evidence suggests that BRCA1 overexpression enhances sensitivity to docetaxel and resistance to cisplatin. RAP80 and Abraxas are interacting proteins that form complexes with BRCA1 and could modulate the effect of BRCA1. In order to further examine the effect of EGFR mutations and BRCA1 mRNA levels on outcome in advanced NSCLC, we performed a prospective non-randomized phase II clinical trial, testing the hypothesis that customized therapy would confer improved outcome over non-customized therapy. In an exploratory analysis, we also examined the effect of RAP80 and Abraxas mRNA levels. METHODOLOGY/PRINCIPAL FINDINGS: We treated 123 metastatic non-squamous cell lung carcinoma patients using a customized approach. RNA and DNA were isolated from microdissected specimens from paraffin-embedded tumor tissue. Patients with EGFR mutations received erlotinib, and those without EGFR mutations received chemotherapy with or without cisplatin based on their BRCA1 mRNA levels: low, cisplatin plus gemcitabine; intermediate, cisplatin plus docetaxel; high, docetaxel alone. An exploratory analysis examined RAP80 and Abraxas expression. Median survival exceeded 28 months for 12 patients with EGFR mutations, and was 11 months for 38 patients with low BRCA1, 9 months for 40 patients with intermediate BRCA1, and 11 months for 33 patients with high BRCA1. Two-year survival was 73.3%, 41.2%, 15.6% and 0%, respectively. Median survival was influenced by RAP80 expression in the three BRCA1 groups. For example, for patients with both low BRCA1 and low RAP80, median survival exceeded 26 months. RAP80 was a significant factor for survival in patients treated according to BRCA1

Sphingosine-1-phosphate (S1P) enhances glomerular endothelial cells activation mediated by anti-myeloperoxidase antibody-positive IgG.

Science.gov (United States)

Sun, Xiao-Jing; Chen, Min; Zhao, Ming-Hui

2018-03-01

Cumulating evidences suggested an important role of sphingosine-1-phosphate (S1P) and its receptors in regulating endothelial barrier integrity. Our previous study revealed that the circulating S1P levels and renal expression of S1PRs correlated with disease activity and renal damage in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This study investigated the role of S1P and its receptors in myeloperoxidase (MPO)-ANCA-positive IgG-mediated glomerular endothelial cell (GEnC) activation. The effect of S1P on morphological alteration of GEnCs in the presence of MPO-ANCA-positive IgG was observed. Permeability assay was performed to determine endothelial monolayer activation in quantity. Both membrane-bound and soluble ICAM-1 and VCAM-1 levels were measured. Furthermore, antagonists and/or agonists of various S1PRs were employed to determine the role of different S1PRs. S1P enhanced MPO-ANCA-positive IgG-induced disruption of tight junction and disorganization of cytoskeleton in GEnCs. S1P induced further increase in monolayer permeability of GEnC monolayers in the presence of MPO-ANCA-positive IgG. S1P enhanced MPO-ANCA-positive IgG-induced membrane-bound and soluble ICAM-1/VCAM-1 up-regulation of GEnCs. Soluble ICAM-1 levels in the supernatants of GEnCs stimulated by S1P and MPO-ANCA-positive IgG increased upon pre-incubation of S1PR1 antagonist, while pre-incubation of GEnCs with the S1PR1 agonist down-regulated sICAM-1 level. Blocking S1PR2-4 reduced sICAM-1 levels in the supernatants of GEnCs stimulated by S1P and MPO-ANCA-positive IgG. Pre-incubation with S1PR5 agonist could increase sICAM-1 level in the supernatants of GEnC stimulated by S1P and MPO-ANCA-positive IgG. S1P can enhance MPO-ANCA-positive IgG-mediated GEnC activation through S1PR2-5. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

The cognition-enhancing activity of E1R, a novel positive allosteric modulator of sigma-1 receptors

Science.gov (United States)

Zvejniece, L; Vavers, E; Svalbe, B; Vilskersts, R; Domracheva, I; Vorona, M; Veinberg, G; Misane, I; Stonans, I; Kalvinsh, I; Dambrova, M

2014-01-01

Background and Purpose Here, we describe the in vitro and in vivo effects of (4R,5S)-2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide (E1R), a novel positive allosteric modulator of sigma-1 receptors. Experimental Approach E1R was tested for sigma receptor binding activity in a [3H](+)-pentazocine assay, in bradykinin (BK)-induced intracellular Ca2+ concentration ([Ca2+]i) assays and in an electrically stimulated rat vas deferens model. E1R's effects on cognitive function were tested using passive avoidance (PA) and Y-maze tests in mice. A selective sigma-1 receptor antagonist (NE-100), was used to study the involvement of the sigma-1 receptor in the effects of E1R. The open-field test was used to detect the effects of E1R on locomotion. Key Results Pretreatment with E1R enhanced the selective sigma-1 receptor agonist PRE-084's stimulating effect during a model study employing electrically stimulated rat vasa deferentia and an assay measuring the BK-induced [Ca2+]i increase. Pretreatment with E1R facilitated PA retention in a dose-related manner. Furthermore, E1R alleviated the scopolamine-induced cognitive impairment during the PA and Y-maze tests in mice. The in vivo and in vitro effects of E1R were blocked by treatment with the selective sigma-1 receptor antagonist NE-100. E1R did not affect locomotor activity. Conclusion and Implications E1R is a novel 4,5-disubstituted derivative of piracetam that enhances cognition and demonstrates efficacy against scopolamine-induced cholinergic dysfunction in mice. These effects are attributed to its positive modulatory action on the sigma-1 receptor and this activity may be relevant when developing new drugs for treating cognitive symptoms related to neurodegenerative diseases. PMID:24490863

From Violent Rap to Lovely Blues: The Transformation of Aggressive Behavior through Vocal Music Therapy.

NARCIS (Netherlands)

Meadows, Tony; Uhlig, S.

2011-01-01

The voice as a primary therapeutic instrument will be addressed in this chapter. Through vocal expression, chaos can be transformed into order – crying into singing, aggressive shouting into the structure of a rap song. This transformation of emotions demonstrates the ability to change behavior and

Soluble ICAM-1 activates lung macrophages and enhances lung injury

DEFF Research Database (Denmark)

Schmal, H; Czermak, B J; Lentsch, A B

1998-01-01

production of TNF-alpha and the CXC chemokine, macrophage inflammatory protein-2 (MIP-2). Alveolar macrophages exhibited cytokine responses to both sICAM-1 and immobilized sICAM-1, while rat PBMCs failed to demonstrate similar responses. Exposure of alveolar macrophages to sICAM-1 resulted in NFkappa......B activation (which was blocked by the presence of the aldehyde peptide inhibitor of 28S proteosome and by genistein, a tyrosine kinase inhibitor). As expected, cross-linking of CD18 on macrophages with Ab resulted in generation of TNF-alpha and MIP-2. This response was also inhibited in the presence...... of TNF-alpha and MIP-2 and increased neutrophil recruitment. Therefore, through engagement of beta2 integrins, sICAM-1 enhances alveolar macrophage production of MIP-2 and TNF-alpha, the result of which is intensified lung injury after intrapulmonary disposition of immune complexes....

Using rap music to promote adolescent health: pilot study of VoxBox.

Science.gov (United States)

Paukste, Ernesta; Harris, Neil

2015-04-01

Alcohol, tobacco and other drugs (ATODs) usage among adolescents, particularly those living in lower socioeconomic communities, is a population health problem in Australia that requires innovative health promotion strategies. There is a growing recognition of the potential of arts-based approaches to engage youth in health promoting activities. This paper presents the process evaluation of the pilot VoxBox intervention that used rap to build adolescents' awareness of risks associated with ATODs. The VoxBox intervention was piloted in Logan, Queensland, at five high schools with 18 adolescents completing the intervention. Data collection methods included observation, focus groups, semi-structured interviews and a survey of adolescent participants. The intervention was well received by participants and stakeholders. Three factors characterising the project's successful engagement of adolescents were: participate - go with the flow, learning from the real deal and resourced to make some noise. In VoxBox, the emphasis on engaging adolescents in an activity of real interest that was appropriately resourced and delivered was central to credibility and success. SO WHAT?: The findings highlight the importance of interventions matching the interests of the targeted population group.

Operating experience and radiation protection in RAPS-3 and 4 operations

International Nuclear Information System (INIS)

Khandelwal, Narendra; Dhakar, P.C.; Singh, G.K.; Gupta, Ashok

2008-01-01

Rajasthan Atomic Power Station (RAPS)-3 and 4 was designed and constructed using latest technological advancements in the field of nuclear energy. Operating experience of the station have taught many lessons and provided opportunities to take proactive corrective actions. Design modifications, effective implementation of radiological surveillance program and improvements in work culture have helped in achieving continual reduction in radiation exposures and effluent releases at the station. This paper discusses some of the modifications carried out at the station along with their radiological impacts. (author)

Rac1-stimulated macropinocytosis enhances Gβγ activation of PI3Kβ.

Science.gov (United States)

Erami, Zahra; Khalil, Bassem D; Salloum, Gilbert; Yao, Yanhua; LoPiccolo, Jaclyn; Shymanets, Aliaksei; Nürnberg, Bernd; Bresnick, Anne R; Backer, Jonathan M

2017-11-16

Phosphoinositide 3-kinases (PI 3-kinases) are regulated by a diverse range of upstream activators, including receptor tyrosine kinases (RTKs), G-protein-coupled receptors (GPCRs), and small GTPases from the Ras, Rho and Rab families. For the Class IA PI 3-kinase PI3Kβ, two mechanisms for GPCR-mediated regulation have been described: direct binding of Gβγ subunits to the C2-helical domain linker of p110β, and Dock180/Elmo1-mediated activation of Rac1, which binds to the Ras-Binding Domain of p110β. We now show that the integration of these dual pathways is unexpectedly complex. In breast cancer cells, expression of constitutively activated Rac1 (CA-Rac1) along with either GPCR stimulation or expression of Gβγ led to an additive PI3Kβ-dependent activation of Akt. Whereas CA-Rac1-mediated activation of Akt was blocked in cells expressing a mutated PI3Kβ that cannot bind Gβγ, Gβγ and GPCR-mediated activation of Akt was preserved when Rac1 binding to PI3Kβ was blocked. Surprisingly, PI3Kβ-dependent CA-Rac1 signaling to Akt was still seen in cells expressing a mutant p110β that cannot bind Rac1. Instead of directly binding to PI3Kβ, CA-Rac1 acts by enhancing Gβγ coupling to PI3Kβ, as CA-Rac1-mediated Akt activation was blocked by inhibitors of Gβγ. Cells expressing CA-Rac1 exhibited a robust induction of macropinocytosis, and inhibitors of macropinocytosis blocked the activation of Akt by CA-Rac1 or lysophosphatidic acid. Our data suggest that Rac1 can potentiate the activation of PI3Kβ by GPCRs through an indirect mechanism, by driving the formation of macropinosomes that serve as signaling platforms for Gβγ coupling to PI3Kβ. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Eviction of linker histone H1 by NAP-family histone chaperones enhances activated transcription.

Science.gov (United States)

Zhang, Qian; Giebler, Holli A; Isaacson, Marisa K; Nyborg, Jennifer K

2015-01-01

In the Metazoan nucleus, core histones assemble the genomic DNA to form nucleosome arrays, which are further compacted into dense chromatin structures by the linker histone H1. The extraordinary density of chromatin creates an obstacle for accessing the genetic information. Regulation of chromatin dynamics is therefore critical to cellular homeostasis, and histone chaperones serve as prominent players in these processes. In the current study, we examined the role of specific histone chaperones in negotiating the inherently repressive chromatin structure during transcriptional activation. Using a model promoter, we demonstrate that the human nucleosome assembly protein family members hNap1 and SET/Taf1β stimulate transcription in vitro during pre-initiation complex formation, prior to elongation. This stimulatory effect is dependent upon the presence of activators, p300, and Acetyl-CoA. We show that transcription from our chromatin template is strongly repressed by H1, and that both histone chaperones enhance RNA synthesis by overcoming H1-induced repression. Importantly, both hNap1 and SET/Taf1β directly bind H1, and function to enhance transcription by evicting the linker histone from chromatin reconstituted with H1. In vivo studies demonstrate that SET/Taf1β, but not hNap1, strongly stimulates activated transcription from the chromosomally-integrated model promoter, consistent with the observation that SET/Taf1β is nuclear, whereas hNap1 is primarily cytoplasmic. Together, these observations indicate that SET/Taf1β may serve as a critical regulator of H1 dynamics and gene activation in vivo. These studies uncover a novel function for SET that mechanistically couples transcriptional derepression with H1 dynamics. Furthermore, they underscore the significance of chaperone-dependent H1 displacement as an essential early step in the transition of a promoter from a dense chromatin state into one that is permissive to transcription factor binding and robust

RAPS. A threedimensional plotprogram for testing of the model and for plotting of the results of finite-element calculations

International Nuclear Information System (INIS)

Koschmieder, D.; Altes, J.

1979-06-01

Usually in Finite-Element calculations a large amount of data is produced and because individual results have no meaning, graphic representation is bestsuited. It is convenient to link the F E Software-System with pre- and postprocessors. The plotting system RAPS, presented on the following pages, offers many possibilities for testing and description of two- or threedimensional structures, as well as for interpretation of results of static and dynamic calculations. The programm was developed for the F E System ASKA but it is possible to fit it to other F E Systems. At present the program is laid out for batchoperation. However it is planned to develop an interactive version of RAPS and to enlarge the postprocessor. (orig.) [de

AML1/ETO trans-activates c-KIT expression through the long range interaction between promoter and intronic enhancer.

Science.gov (United States)

Tian, Ying; Wang, Genjie; Hu, Qingzhu; Xiao, Xichun; Chen, Shuxia

2018-04-01

The AML1/ETO onco-fusion protein is crucial for the genesis of t(8;21) acute myeloid leukemia (AML) and is well documented as a transcriptional repressor through dominant-negative effect. However, little is known about the transactivation mechanism of AML1/ETO. Through large cohort of patient's expression level data analysis and a series of experimental validation, we report here that AML1/ETO transactivates c-KIT expression through directly binding to and mediating the long-range interaction between the promoter and intronic enhancer regions of c-KIT. Gene expression analyses verify that c-KIT expression is significantly high in t(8;21) AML. Further ChIP-seq analysis and motif scanning identify two regulatory regions located in the promoter and intronic enhancer region of c-KIT, respectively. Both regions are enriched by co-factors of AML1/ETO, such as AML1, CEBPe, c-Jun, and c-Fos. Further luciferase reporter assays show that AML1/ETO trans-activates c-KIT promoter activity through directly recognizing the AML1 motif and the co-existence of co-factors. The induction of c-KIT promoter activity is reinforced with the existence of intronic enhancer region. Furthermore, ChIP-3C-qPCR assays verify that AML1/ETO mediates the formation of DNA-looping between the c-KIT promoter and intronic enhancer region through the long-range interaction. Collectively, our data uncover a novel transcriptional activity mechanism of AML1/ETO and enrich our knowledge of the onco-fusion protein mediated transcription regulation. © 2017 Wiley Periodicals, Inc.

Impairment of GABA transporter GAT-1 terminates cortical recurrent network activity via enhanced phasic inhibition

Directory of Open Access Journals (Sweden)

Daniel Simon Razik

2013-09-01

Full Text Available In the central nervous system, GABA transporters (GATs very efficiently clear synaptically released GABA from the extracellular space, and thus exert a tight control on GABAergic inhibition. In neocortex, GABAergic inhibition is heavily recruited during recurrent phases of spontaneous action potential activity which alternate with neuronally quiet periods. Therefore, such activity should be quite sensitive to minute alterations of GAT function. Here, we explored the effects of a gradual impairment of GAT-1 and GAT-2/3 on spontaneous recurrent network activity – termed network bursts and silent periods – in organotypic slice cultures of rat neocortex. The GAT-1 specific antagonist NO-711 depressed activity already at nanomolar concentrations (IC50 for depression of spontaneous multiunit firing rate of 42 nM, reaching a level of 80% at 500-1000 nM. By contrast, the GAT-2/3 preferring antagonist SNAP-5114 had weaker and less consistent effects. Several lines of evidence pointed towards an enhancement of phasic GABAergic inhibition as the dominant activity-depressing mechanism: network bursts were drastically shortened, phasic GABAergic currents decayed slower, and neuronal excitability during ongoing activity was diminished. In silent periods, NO-711 had little effect on neuronal excitability or membrane resistance, quite in contrast to the effects of muscimol, a GABA mimetic which activates GABAA receptors tonically. Our results suggest that an enhancement of phasic GABAergic inhibition efficiently curtails cortical recurrent activity and may mediate antiepileptic effects of therapeutically relevant concentrations of GAT-1 antagonists.

Sphingosine-1-phosphate enhances satellite cell activation in dystrophic muscles through a S1PR2/STAT3 signaling pathway.

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Kenneth C Loh

Full Text Available Sphingosine-1-phosphate (S1P activates a widely expressed family of G protein-coupled receptors, serves as a muscle trophic factor and activates muscle stem cells called satellite cells (SCs through unknown mechanisms. Here we show that muscle injury induces dynamic changes in S1P signaling and metabolism in vivo. These changes include early and profound induction of the gene encoding the S1P biosynthetic enzyme SphK1, followed by induction of the catabolic enzyme sphingosine phosphate lyase (SPL 3 days later. These changes correlate with a transient increase in circulating S1P levels after muscle injury. We show a specific requirement for SphK1 to support efficient muscle regeneration and SC proliferation and differentiation. Mdx mice, which serve as a model for muscular dystrophy (MD, were found to be S1P-deficient and exhibited muscle SPL upregulation, suggesting that S1P catabolism is enhanced in dystrophic muscle. Pharmacological SPL inhibition increased muscle S1P levels, improved mdx muscle regeneration and enhanced SC proliferation via S1P receptor 2 (S1PR2-dependent inhibition of Rac1, thereby activating Signal Transducer and Activator of Transcription 3 (STAT3, a central player in inflammatory signaling. STAT3 activation resulted in p21 and p27 downregulation in a S1PR2-dependent fashion in myoblasts. Our findings suggest that S1P promotes SC progression through the cell cycle by repression of cell cycle inhibitors via S1PR2/STAT3-dependent signaling and that SPL inhibition may provide a therapeutic strategy for MD.

Residual β activity of particulate 234Th as a novel proxy for tracking sediment resuspension in the ocean

Science.gov (United States)

Lin, Wuhui; Chen, Liqi; Zeng, Shi; Li, Tao; Wang, Yinghui; Yu, Kefu

2016-01-01

Sediment resuspension occurs in the global ocean, which greatly affects material exchange between the sediment and the overlying seawater. The behaviours of carbon, nutrients, heavy metals, and other pollutants at the sediment-seawater boundary will further link to climate change, eutrophication, and marine pollution. Residual β activity of particulate 234Th (RAP234) is used as a novel proxy to track sediment resuspension in different marine environments, including the western Arctic Ocean, the South China Sea, and the Southern Ocean. Sediment resuspension identified by high activity of RAP234 is supported by different lines of evidence including seawater turbidity, residence time of total 234Th, Goldschmidt’s classification, and ratio of RAP234 to particulate organic carbon. A conceptual model is proposed to elucidate the mechanism for RAP234 with dominant contributions from 234Th-238U and 212Bi-228Th. The ‘slope assumption’ for RAP234 indicated increasing intensity of sediment resuspension from spring to autumn under the influence of the East Asian monsoon system. RAP234 can shed new light on 234Th-based particle dynamics and should benefit the interpretation of historical 234Th-238U database. RAP234 resembles lithophile elements and has broad implications for investigating particle dynamics in the estuary-shelf-slope-ocean continuum and linkage of the atmosphere-ocean-sediment system. PMID:27252085

Residual β activity of particulate (234)Th as a novel proxy for tracking sediment resuspension in the ocean.

Science.gov (United States)

Lin, Wuhui; Chen, Liqi; Zeng, Shi; Li, Tao; Wang, Yinghui; Yu, Kefu

2016-06-02

Sediment resuspension occurs in the global ocean, which greatly affects material exchange between the sediment and the overlying seawater. The behaviours of carbon, nutrients, heavy metals, and other pollutants at the sediment-seawater boundary will further link to climate change, eutrophication, and marine pollution. Residual β activity of particulate (234)Th (RAP234) is used as a novel proxy to track sediment resuspension in different marine environments, including the western Arctic Ocean, the South China Sea, and the Southern Ocean. Sediment resuspension identified by high activity of RAP234 is supported by different lines of evidence including seawater turbidity, residence time of total (234)Th, Goldschmidt's classification, and ratio of RAP234 to particulate organic carbon. A conceptual model is proposed to elucidate the mechanism for RAP234 with dominant contributions from (234)Th-(238)U and (212)Bi-(228)Th. The 'slope assumption' for RAP234 indicated increasing intensity of sediment resuspension from spring to autumn under the influence of the East Asian monsoon system. RAP234 can shed new light on (234)Th-based particle dynamics and should benefit the interpretation of historical (234)Th-(238)U database. RAP234 resembles lithophile elements and has broad implications for investigating particle dynamics in the estuary-shelf-slope-ocean continuum and linkage of the atmosphere-ocean-sediment system.

Radiosensitivity of the swiss-rap mouse as a function of its growth rate

International Nuclear Information System (INIS)

Legeay, G.; Glas, J.F.

1969-01-01

The results of an exhaustive study of the age dependence of the radiosensitivity of female Swiss-Rap mice are given. A close relationship of radiosensitivity versus age could not be brought out, whereas the weekly growth rate could be accurately related to radiosensitivity. Thus, the latter should be studied when a strain is to be used for biological experiments, as the rates of growth are different with the strains. (author) [fr

Mechanical Stimulation and IGF-1 Enhance mRNA Translation Rate in Osteoblasts Via Activation of the AKT-mTOR Pathway.

Science.gov (United States)

Bakker, Astrid D; Gakes, Tom; Hogervorst, Jolanda M A; de Wit, Gerard M J; Klein-Nulend, Jenneke; Jaspers, Richard T

2016-06-01

Insulin-like growth factor-1 (IGF-1) is anabolic for muscle by enhancing the rate of mRNA translation via activation of AKT and subsequent activation of the mammalian target of rapamycin complex 1 (mTOR), thereby increasing cellular protein production. IGF-1 is also anabolic for bone, but whether the mTOR pathway plays a role in the rate of bone matrix protein production by osteoblasts is unknown. We hypothesized that anabolic stimuli such as mechanical loading and IGF-1 stimulate protein synthesis in osteoblasts via activation of the AKT-mTOR pathway. MC3T3-E1 osteoblasts were either or not subjected for 1 h to mechanical loading by pulsating fluid flow (PFF) or treated with or without human recombinant IGF-1 (1-100 ng/ml) for 0.5-6 h, to determine phosphorylation of AKT and p70S6K (downstream of mTOR) by Western blot. After 4 days of culture with or without the mTOR inhibitor rapamycin, total protein, DNA, and gene expression were quantified. IGF-1 (100 ng/ml) reduced IGF-1 gene expression, although PFF enhanced IGF-1 expression. IGF-1 did not affect collagen-I gene expression. IGF-1 dose-dependently enhanced AKT and p70S6K phosphorylation at 2 and 6 h. PFF enhanced phosphorylation of AKT and p70S6K already within 1 h. Both IGF-1 and PFF enhanced total protein per cell by ∼30%, but not in the presence of rapamycin. Our results show that IGF-1 and PFF activate mTOR, thereby stimulating the rate of mRNA translation in osteoblasts. The known anabolic effect of mechanical loading and IGF-1 on bone may thus be partly explained by mTOR-mediated enhanced protein synthesis in osteoblasts. © 2015 Wiley Periodicals, Inc.

Degrees of Intersectionality: Male Rap Artists in Sweden Negotiating Class, Race and Gender

Directory of Open Access Journals (Sweden)

Kalle Berggren

2013-06-01

Full Text Available “Intersectionality” has become a highly influential concept in gender research over the last 25 years. Debates have focused on differences and power asymmetries between women, in terms of race but also addressing class, age, sexuality, ability and nation. However, intersectional paradigms have been used to a much lesser extent in gender studies on men. This article seeks to contribute to an emerging discussion about intersectionality and masculinity by analyzing rap lyrics in Swe-dish songs. The data consists of a broad sample of rap lyrics by male artists 1991-2011, which is analyzed through poststructuralist discourse analysis and queer phenomenology. The analysis shows how classed discourses can be described in terms of orientation and flow, how racialization is articulated in terms of place, and the role of normative notions of gender and sexuality in anti-racist discourses. It is argued that this interconnectedness – class being related to race, which in turn is profoundly gendered – is neither well captured by the prevailing notion of “masculinities” in gender studies on men, nor by the “constitution” vs. “addition” dichotomy in intersectionality debates. Instead, it is suggested that degrees of in-tersectionality might be a more fruitful way of theorizing intersectionality in rela-tion to men.

University-Community Collaboration to Promote Healthy Mothers and Infants: The Relationships and Parenting Support (RAPS) Program

Science.gov (United States)

Williams, Patricia Hrusa; Oravecz, Linda M.

2016-01-01

Research highlights the vulnerability of Black mothers and their infants, who experience higher rates of stress, preterm birth, low birth weight, and infant mortality than other racial groups. This article describes the development and implementation of the Relationships and Parenting Support (RAPS) Program, a community-based, family-focused…

Enhanced activation of the left hemisphere promotes normative decision making.

Science.gov (United States)

Corser, Ryan; Jasper, John D

2014-01-01

Previous studies have reported that enhanced activation of the left cerebral hemisphere reduces risky-choice, attribute, and goal-framing effects relative to enhanced activation of the right cerebral hemisphere. The present study sought to extend these findings and show that enhanced activation of the left hemisphere also reduces violations of other normative principles, besides the invariance principle. Participants completed ratio bias (Experiment 1, N = 296) and base rate neglect problems (Experiment 2, N = 145) under normal (control) viewing or with the right or left hemisphere primarily activated by imposing a unidirectional gaze. In Experiment 1 we found that enhanced left hemispheric activation reduced the ratio bias relative to normal viewing and a group experiencing enhanced right hemispheric activation. In Experiment 2 enhanced left hemispheric activation resulted in using base rates more than normal viewing, but not significantly more than enhanced right hemispheric activation. Results suggest that hemispheric asymmetries can affect higher-order cognitive processes, such as decision-making biases. Possible theoretical accounts are discussed as well as implications for dual-process theories.

El rap español en el ámbito de los discursos de especialidad

Directory of Open Access Journals (Sweden)

Francisco Jiménez Calderón

2012-11-01

Full Text Available Normal 0 21 false false false ES X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tabla normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} El presente artículo tiene como objetivo definir el rap español como un discurso de especialidad. Para ello, se revisa el concepto de ‘discurso de especialidad’, al que se alude con expresiones a menudo imprecisas como ‘lenguaje especial’, ‘lengua de especialidad’ o ‘jerga’. Ninguna, por distintas razones, parece adecuada; debe hablarse, en efecto, de ‘discurso de especialidad’, aunque una denominación como ‘discurso de actividad’ sería aún más precisa, pues nombraría el producto de comunicación que resulta de utilizar la lengua en un ámbito determinado, no necesariamente profesional, sino relativo a cualquier actividad concreta. Para situar al rap español en tal ámbito, se ha analizado un corpus de más de cien textos, que revela que, efectivamente, el rap presenta unos rasgos definitorios que le otorgan singularidad como discurso especial: terminología, desarrollo entre la escritura y la oralidad, reflexión metalingüística y acercamiento al género poético mediante el recurso a figuras retóricas consolidadas.

Molecular evolution of Theta-class glutathione transferase for enhanced activity with the anticancer drug 1,3-bis-(2-chloroethyl)-1-nitrosourea and other alkylating agents.

Science.gov (United States)

Larsson, Anna-Karin; Shokeer, Abeer; Mannervik, Bengt

2010-05-01

Glutathione transferase (GST) displaying enhanced activity with the cytostatic drug 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) and structurally related alkylating agents was obtained by molecular evolution. Mutant libraries created by recursive recombination of cDNA coding for human and rodent Theta-class GSTs were heterologously expressed in Escherichia coli and screened with the surrogate substrate 4-nitrophenethyl bromide (NPB) for enhanced alkyltransferase activity. A mutant with a 70-fold increased catalytic efficiency with NPB, compared to human GST T1-1, was isolated. The efficiency in degrading BCNU had improved 170-fold, significantly more than with the model substrate NPB. The enhanced catalytic activity of the mutant GST was also 2-fold higher with BCNU than wild-type mouse GST T1-1, which is 80-fold more efficient than wild-type human GST T1-1. We propose that GSTs catalyzing inactivation of anticancer drugs may find clinical use in protecting sensitive normal tissues to toxic side-effects in treated patients, and as selectable markers in gene therapy. Copyright 2010 Elsevier Inc. All rights reserved.

Degrees of Intersectionality: Male Rap Artists in Sweden Negotiating Class, Race and Gender

OpenAIRE

Kalle Berggren

2013-01-01

“Intersectionality” has become a highly influential concept in gender research over the last 25 years. Debates have focused on differences and power asymmetries between women, in terms of race but also addressing class, age, sexuality, ability and nation. However, intersectional paradigms have been used to a much lesser extent in gender studies on men. This article seeks to contribute to an emerging discussion about intersectionality and masculinity by analyzing rap lyrics in Swe-dish songs. ...

Analysis of a two-domain binding site for the urokinase-type plasminogen activator-plasminogen activator inhibitor-1 complex in low-density-lipoprotein-receptor-related protein.

Science.gov (United States)

Andersen, O M; Petersen, H H; Jacobsen, C; Moestrup, S K; Etzerodt, M; Andreasen, P A; Thøgersen, H C

2001-07-01

The low-density-lipoprotein-receptor (LDLR)-related protein (LRP) is composed of several classes of domains, including complement-type repeats (CR), which occur in clusters that contain binding sites for a multitude of different ligands. Each approximately 40-residue CR domain contains three conserved disulphide linkages and an octahedral Ca(2+) cage. LRP is a scavenging receptor for ligands from extracellular fluids, e.g. alpha(2)-macroglobulin (alpha(2)M)-proteinase complexes, lipoprotein-containing particles and serine proteinase-inhibitor complexes, like the complex between urokinase-type plasminogen activator (uPA) and the plasminogen activator inhibitor-1 (PAI-1). In the present study we analysed the interaction of the uPA-PAI-1 complex with an ensemble of fragments representing a complete overlapping set of two-domain fragments accounting for the ligand-binding cluster II (CR3-CR10) of LRP. By ligand blotting, solid-state competition analysis and surface-plasmon-resonance analysis, we demonstrate binding to multiple CR domains, but show a preferential interaction between the uPA-PAI-1 complex and a two-domain fragment comprising CR domains 5 and 6 of LRP. We demonstrate that surface-exposed aspartic acid and tryptophan residues at identical positions in the two homologous domains, CR5 and CR6 (Asp(958,CR5), Asp(999,CR6), Trp(953,CR5) and Trp(994,CR6)), are critical for the binding of the complex as well as for the binding of the receptor-associated protein (RAP) - the folding chaperone/escort protein required for transport of LRP to the cell surface. Accordingly, the present work provides (1) an identification of a preferred binding site within LRP CR cluster II; (2) evidence that the uPA-PAI-1 binding site involves residues from two adjacent protein domains; and (3) direct evidence identifying specific residues as important for the binding of uPA-PAI-1 as well as for the binding of RAP.

Rap jako muzyka tożsamościowa: od czarnego getta do polskiego pop-nacjonalizmu

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Piotr Majewski

2016-01-01

Full Text Available Rap as identity music: from the black ghetto to Polish pop-nationalism In today’s world, cultural products, technologies, information and ideologies more and more permeate from one society to another, crossing all kinds of borders in the least expected way. Rap career is an illustration of this process. It was created in the late seventies and eighties of the twentieth century in New York ghettos and today it represents one of the most popular genres on the global scale. Rap is not only a symbol of revolution and the domination of Western capitalist business practices but also a cultural tool by which different groups, often marginalized or considering themselves as such, express their own identity. I am analyzing the indicated above phenomenon using two, extreme at first glance, examples. First, I present the story of the emergence and development of hip-hop culture in the United States. I try to show how rap music, which is an important element of this culture, allowed a marginalized part of American society for manifesting and communicating their views, beliefs and values, becoming a “transmission channel” for various ideologies, including the ideology of black nationalism. In the second part of the text, I am additionally analyzing the artwork and public appearances by Tadeusz “Tadek“ Polkowski, a Polish rapper, whom I consider a representative of an expanding hip-hop society relating to or sympathizing with the national movement. The music he creates is designed not only to restore the Poles’ “memory”, and therefore also the pride in their heroic and admirable past, but also to open their eyes to what is happening in their country that he believes is being colonized by the occupants.   Rap jako muzyka tożsamościowa: od czarnego getta do polskiego pop-nacjonalizmu We współczesnym świecie wytwory kultury, technologie, informacje i ideologie coraz częściej przenikają z jednego społeczeństwa do drugiego, przekraczaj

B-Raf and CRHR1 internalization mediate biphasic ERK1/2 activation by CRH in hippocampal HT22 Cells.

Science.gov (United States)

Bonfiglio, Juan J; Inda, Carolina; Senin, Sergio; Maccarrone, Giuseppina; Refojo, Damián; Giacomini, Damiana; Turck, Christoph W; Holsboer, Florian; Arzt, Eduardo; Silberstein, Susana

2013-03-01

CRH is a key regulator of neuroendocrine, autonomic, and behavioral response to stress. CRH-stimulated CRH receptor 1 (CRHR1) activates ERK1/2 depending on intracellular context. In a previous work, we demonstrated that CRH activates ERK1/2 in limbic areas of the mouse brain (hippocampus and basolateral amygdala). ERK1/2 is an essential mediator of hippocampal physiological processes including emotional behavior, synaptic plasticity, learning, and memory. To elucidate the molecular mechanisms by which CRH activates ERK1/2 in hippocampal neurons, we used the mouse hippocampal cell line HT22. We document for the first time that ERK1/2 activation in response to CRH is biphasic, involving a first cAMP- and B-Raf-dependent early phase and a second phase that critically depends on CRHR1 internalization and β-arrestin2. By means of mass-spectrometry-based screening, we identified B-Raf-associated proteins that coimmunoprecipitate with endogenous B-Raf after CRHR1 activation. Using molecular and pharmacological tools, the functional impact of selected B-Raf partners in CRH-dependent ERK1/2 activation was dissected. These results indicate that 14-3-3 proteins, protein kinase A, and Rap1, are essential for early CRH-induced ERK1/2 activation, whereas dynamin and vimentin are required for the CRHR1 internalization-dependent phase. Both phases of ERK1/2 activation depend on calcium influx and are affected by calcium/calmodulin-dependent protein kinase II inactivation. Thus, this report describes the dynamics and biphasic nature of ERK1/2 activation downstream neuronal CRHR1 and identifies several new critical components of the CRHR1 signaling machinery that selectively controls the early and late phases of ERK1/2 activation, thus providing new potential therapeutic targets for stress-related disorders.

Leucine stimulates protein synthesis in skeletal muscle of neonatal pigs by enhancing mTORC1 activation.

Science.gov (United States)

Suryawan, Agus; Jeyapalan, Asumthia S; Orellana, Renan A; Wilson, Fiona A; Nguyen, Hanh V; Davis, Teresa A

2008-10-01

Skeletal muscle in the neonate grows at a rapid rate due in part to an enhanced sensitivity to the postprandial rise in amino acids, particularly leucine. To elucidate the molecular mechanism by which leucine stimulates protein synthesis in neonatal muscle, overnight-fasted 7-day-old piglets were treated with rapamycin [an inhibitor of mammalian target of rapamycin (mTOR) complex (mTORC)1] for 1 h and then infused with leucine for 1 h. Fractional rates of protein synthesis and activation of signaling components that lead to mRNA translation were determined in skeletal muscle. Rapamycin completely blocked leucine-induced muscle protein synthesis. Rapamycin markedly reduced raptor-mTOR association, an indicator of mTORC1 activation. Rapamycin blocked the leucine-induced phosphorylation of mTOR, S6 kinase 1 (S6K1), and eukaryotic initiation factor (eIF)4E-binding protein-1 (4E-BP1) and formation of the eIF4E.eIF4G complex and increased eIF4E.4E-BP1 complex abundance. Rapamycin had no effect on the association of mTOR with rictor, a crucial component for mTORC2 activation, or G protein beta-subunit-like protein (GbetaL), a component of mTORC1 and mTORC2. Neither leucine nor rapamycin affected the phosphorylation of AMP-activated protein kinase (AMPK), PKB, or tuberous sclerosis complex (TSC)2, signaling components that reside upstream of mTOR. Eukaryotic elongation factor (eEF)2 phosphorylation was not affected by leucine or rapamycin, although current dogma indicates that eEF2 phosphorylation is mTOR dependent. Together, these in vivo data suggest that leucine stimulates muscle protein synthesis in neonates by enhancing mTORC1 activation and its downstream effectors.

La influencia de la Web 2.0 y sus condicionantes técnicos en la producción del videoclip de rap español

Directory of Open Access Journals (Sweden)

Olga HEREDERO-DÍAZ

2017-07-01

Full Text Available El videoclip es un producto audiovisual definido a partir de sus fines, generalmente comerciales, pero también un ejercicio de expresión y experimentación artística. Tomando como punto de partida la transformación del modo de distribución y consumo del videoclip por la democratización del acceso a Internet del público juvenil, el objetivo principal de esta investigación será describir los cambios que han tenido lugar en la producción del videoclip de rap español de los últimos cinco años debido a la influencia de la Web 2.0 y sus condicionantes técnicos. A partir del análisis de los videoclips difundidos a través de la sección de rap del programa Ritmo Urbano de La 2 de RTVE durante sus cinco temporadas en antena (desde 2011 hasta 2016, se concluye que a día de hoy el vídeo musical de rap es un género que se produce mayoritariamente para Internet, lo que en el caso del videoclip de rap español ha supuesto una mayor autonomía y libertad creativa para los artistas, al tiempo que una merma en el estándar de calidad de la imagen y del sonido de las piezas finales que su público objetivo consume.

O rap e o funk na socialização da juventude

Directory of Open Access Journals (Sweden)

Dayrell Juarez

2002-01-01

Full Text Available O texto se propõe a discutir a importância dos grupos musicais juvenis nos processos de socialização vivenciados por jovens pobres na periferia de Belo Horizonte, problematizando o peso e o significado de ser membro de um grupo musical no conjunto da vida de cada um. Tem como foco os integrantes de três grupos de rap e três duplas de funk, procurando analisar as suas experiências culturais e o sentido que tais práticas adquirem no conjunto dos processos sociais que os constituem como sujeitos. Significa compreender como eles elaboram as suas vivências em torno do estilo, e os significados que atribuem a elas, no contexto social onde se inserem como jovens pobres. A discussão aponta que os jovens rappers e funkeiros encontram poucos espaços nas instituições do mundo adulto para construir referências e valores por meio dos quais possam se construir como sujeitos. Os estilos rap e funk assumem uma centralidade na vida desses jovens por intermédio das formas de sociabilidade que constroem, da música que criam, e dos eventos culturais que promovem. Esses estilos possibilitaram e vem possibilitando a esses jovens práticas, relações e símbolos por meio dos quais criam espaços próprios, significando uma referência na elaboração e vivência da sua condição juvenil, além de proporcionar a construção de uma auto-estima e identidades positivas.

Wnt signaling in ovarian development inhibits Sf1 activation of Sox9 via the Tesco enhancer.

Science.gov (United States)

Bernard, Pascal; Ryan, Janelle; Sim, Helena; Czech, Daniel P; Sinclair, Andrew H; Koopman, Peter; Harley, Vincent R

2012-02-01

Genome analysis of patients with disorders of sex development, and gain- and loss-of-function studies in mice indicate that gonadal development is regulated by opposing signals. In females, the Wnt/β-catenin canonical pathway blocks testicular differentiation by repressing the expression of the Sertoli cell-specific gene Sox9 by an unknown mechanism. Using cell and embryonic gonad culture models, we show that activation of the Wnt/β-catenin pathway inhibits the expression of Sox9 and Amh, whereas mRNA and protein levels of Sry and steroidogenic factor 1 (Sf1), two key transcriptional regulators of Sox9, are not altered. Ectopic activation of Wnt/β-catenin signaling in male gonads led to a loss of Sf1 binding to the Tesco enhancer and absent Sox9 expression that we also observed in wild-type ovaries. Moreover, ectopic Wnt/β-catenin signaling induced the expression of the female somatic cell markers, Bmp2 and Rspo1, as a likely consequence of Sox9 loss. Wnt/β-catenin signaling in XY gonads did not, however, affect gene expression of the steroidogenic Leydig cell Sf1 target gene, Cyp11a1, or Sf1 binding to the Cyp11a1 promoter. Our data support a model in ovary development whereby activation of β-catenin prevents Sf1 binding to the Sox9 enhancer, thereby inhibiting Sox9 expression and Sertoli cell differentiation.

Consideration on application of RAP to G-II NPP

International Nuclear Information System (INIS)

Shen Shen

2010-01-01

The design (D-RAP) for nuclear power plant has been adopted internationally in new-build advanced nuclear power plant design, which increases the ability of the risk-significant SSCs to carry out its functions during the accident circumstances especially in the severe accident situation, and reduces the risk of a nuclear power plant. The concept of reliability assurance program for advanced nuclear power plant can also be applied to nuclear power plants which second-generation NPP technology is used. Through analysis and research, the risk-significant SSCs in actual NPP can also be screened, and these SSCs can be managed appropriately, so that can improve the overall plant ability to against the severe accident, reduce the risk, and improve their safety and economy. Also such technology used does not exist any insurmountable technical difficulties and a lot of money input. (authors)

SG2NA enhances cancer cell survival by stabilizing DJ-1 and thus activating Akt

Energy Technology Data Exchange (ETDEWEB)

Tanti, Goutam Kumar, E-mail: goutamjnu@hotmail.com; Pandey, Shweta; Goswami, Shyamal K.

2015-08-07

SG2NA in association with striatin and zinedin forms a striatin family of WD-40 repeat proteins. This family of proteins functions as scaffold in different signal transduction pathways. They also act as a regulatory subunit of protein phosphatase 2A. We have shown that SG2NA which evolved first in the metazoan evolution among the striatin family members expresses different isoforms generated out of alternative splicing. We have also shown that SG2NA protects cells from oxidative stress by recruiting DJ-1 and Akt to mitochondria and membrane in the post-mitotic neuronal cells. DJ-1 is both cancer and Parkinson's disease related protein. In the present study we have shown that SG2NA protects DJ-1 from proteasomal degradation in cancer cells. Hence, downregulation of SG2NA reduces DJ-1/Akt colocalization in cancer cells resulting in the reduction of anchorage dependent and independent growth. Thus SG2NA enhances cancer cell survival. Reactive oxygen species enhances SG2NA, DJ-1 and Akt trimerization. Removal of the reactive oxygen species by N-acetyl-cysteine thus reduces cancer cell growth. - Highlights: • Reactive oxygen species (ROS) play potential role in cancer cell proliferation. • It enhances the association between DJ-1 and Akt mediated by SG2NA. • In cancer cells SG2NA stabilizes DJ-1 by inhibiting it from proteosomal degradation. • DJ-1 then activates Akt and cancer cells get their property of enhanced proliferation by sustained activation of Akt. • Further study on this field could lead to new target for cancer therapy.

SG2NA enhances cancer cell survival by stabilizing DJ-1 and thus activating Akt

International Nuclear Information System (INIS)

Tanti, Goutam Kumar; Pandey, Shweta; Goswami, Shyamal K.

2015-01-01

SG2NA in association with striatin and zinedin forms a striatin family of WD-40 repeat proteins. This family of proteins functions as scaffold in different signal transduction pathways. They also act as a regulatory subunit of protein phosphatase 2A. We have shown that SG2NA which evolved first in the metazoan evolution among the striatin family members expresses different isoforms generated out of alternative splicing. We have also shown that SG2NA protects cells from oxidative stress by recruiting DJ-1 and Akt to mitochondria and membrane in the post-mitotic neuronal cells. DJ-1 is both cancer and Parkinson's disease related protein. In the present study we have shown that SG2NA protects DJ-1 from proteasomal degradation in cancer cells. Hence, downregulation of SG2NA reduces DJ-1/Akt colocalization in cancer cells resulting in the reduction of anchorage dependent and independent growth. Thus SG2NA enhances cancer cell survival. Reactive oxygen species enhances SG2NA, DJ-1 and Akt trimerization. Removal of the reactive oxygen species by N-acetyl-cysteine thus reduces cancer cell growth. - Highlights: • Reactive oxygen species (ROS) play potential role in cancer cell proliferation. • It enhances the association between DJ-1 and Akt mediated by SG2NA. • In cancer cells SG2NA stabilizes DJ-1 by inhibiting it from proteosomal degradation. • DJ-1 then activates Akt and cancer cells get their property of enhanced proliferation by sustained activation of Akt. • Further study on this field could lead to new target for cancer therapy

Isolation and killing of candidate chronic myeloid leukemia stem cells by antibody targeting of IL-1 receptor accessory protein

DEFF Research Database (Denmark)

Järås, Marcus; Johnels, Petra; Hansen, Nils Gunder

2010-01-01

stem cells could be prospectively separated. In addition, by generating an anti-IL1RAP antibody, we provide proof of concept that IL1RAP can be used as a target on CML CD34(+)CD38(-) cells to induce antibody-dependent cell-mediated cytotoxicity. This study thus identifies IL1RAP as a unique cell...... will require full eradication of Ph chromosome-positive (Ph(+)) CML stem cells. Here we used gene-expression profiling to identify IL-1 receptor accessory protein (IL1RAP) as up-regulated in CML CD34(+) cells and also in cord blood CD34(+) cells as a consequence of retroviral BCR/ABL1 expression. To test...... whether IL1RAP expression distinguishes normal (Ph(-)) and leukemic (Ph(+)) cells within the CML CD34(+)CD38(-) cell compartment, we established a unique protocol for conducting FISH on small numbers of sorted cells. By using this method, we sorted cells directly into drops on slides to investigate...

Insulin-like growth factor 1 (IGF1) and its active peptide (1-3)IGF1 enhance the expression of synaptic markers in neuronal circuits through different cellular mechanisms.

LENUS (Irish Health Repository)

Corvin, Aiden P

2012-06-27

Insulin-like growth factor-1 (IGF1) and its active peptide (1-3)IGF1 modulate brain growth and plasticity and are candidate molecules for treatment of brain disorders. IGF1 N-terminal portion is naturally cleaved to generate the tri-peptide (1-3)IGF1 (glycine-praline-glutamate). IGF1 and (1-3)IGF have been proposed as treatment for neuropathologies, yet their effect on nerve cells has not been directly compared. In this study we examine the effects of IGF1 and (1-3)IGF1 in primary cortical cultures and measure the expression levels of markers for intracellular pathways and synaptic function. We find that both treatments activate the IGF1 receptor and enhance the expression of synaptic markers, however, they activate different intracellular pathways. Furthermore, (1-3)IGF1 administration increases the expression of endogenous IGF1, suggesting a direct interaction between the two molecules. The results show that the two molecules increase the expression of synaptic proteins through activating different cellular mechanisms.

A Yersinia effector with enhanced inhibitory activity on the NF-κB pathway activates the NLRP3/ASC/caspase-1 inflammasome in macrophages.

Directory of Open Access Journals (Sweden)

Ying Zheng

2011-04-01

Full Text Available A type III secretion system (T3SS in pathogenic Yersinia species functions to translocate Yop effectors, which modulate cytokine production and regulate cell death in macrophages. Distinct pathways of T3SS-dependent cell death and caspase-1 activation occur in Yersinia-infected macrophages. One pathway of cell death and caspase-1 activation in macrophages requires the effector YopJ. YopJ is an acetyltransferase that inactivates MAPK kinases and IKKβ to cause TLR4-dependent apoptosis in naïve macrophages. A YopJ isoform in Y. pestis KIM (YopJ(KIM has two amino acid substitutions, F177L and K206E, not present in YopJ proteins of Y. pseudotuberculosis and Y. pestis CO92. As compared to other YopJ isoforms, YopJ(KIM causes increased apoptosis, caspase-1 activation, and secretion of IL-1β in Yersinia-infected macrophages. The molecular basis for increased apoptosis and activation of caspase-1 by YopJ(KIM in Yersinia-infected macrophages was studied. Site directed mutagenesis showed that the F177L and K206E substitutions in YopJ(KIM were important for enhanced apoptosis, caspase-1 activation, and IL-1β secretion. As compared to YopJ(CO92, YopJ(KIM displayed an enhanced capacity to inhibit phosphorylation of IκB-α in macrophages and to bind IKKβ in vitro. YopJ(KIM also showed a moderately increased ability to inhibit phosphorylation of MAPKs. Increased caspase-1 cleavage and IL-1β secretion occurred in IKKβ-deficient macrophages infected with Y. pestis expressing YopJ(CO92, confirming that the NF-κB pathway can negatively regulate inflammasome activation. K+ efflux, NLRP3 and ASC were important for secretion of IL-1β in response to Y. pestis KIM infection as shown using macrophages lacking inflammasome components or by the addition of exogenous KCl. These data show that caspase-1 is activated in naïve macrophages in response to infection with a pathogen that inhibits IKKβ and MAPK kinases and induces TLR4-dependent apoptosis. This pro

Mechanical Stimulation and IGF-1 Enhance mRNA Translation Rate in Osteoblasts via Activation of the AKT-mTOR Pathway.

NARCIS (Netherlands)

Bakker, A.D.; Gakes, T.; Hogervorst, J.M.; de Wit, G.M.J.; Klein-Nulend, J.; Jaspers, R.T.

Insulin-like growth factor-1 (IGF-1) is anabolic for muscle by enhancing the rate of mRNA translation via activation of AKT and subsequent activation of the mammalian target of rapamycin complex 1 (mTOR), thereby increasing cellular protein production. IGF-1 is also anabolic for bone, but whether

Mechanical stimulation and IGF-1 enhance mRNA translation rate in osteoblasts via activation of the AKT-mTOR pathway

NARCIS (Netherlands)

Bakker, A.D.; Gakes, T.; Hogervorst, J.M.A.; de Wit, G.M.J.; Klein-Nulend, J.; Jaspers, R.T.

2016-01-01

Insulin-like growth factor-1 (IGF-1) is anabolic for muscle by enhancing the rate of mRNA translation via activation of AKT and subsequent activation of the mammalian target of rapamycin complex 1 (mTOR), thereby increasing cellular protein production. IGF-1 is also anabolic for bone, but whether

Mast cell activation is enhanced by Tim1:Tim4 interaction but not by Tim-1 antibodies [version 2; referees: 2 approved

Directory of Open Access Journals (Sweden)

Binh Phong

2016-07-01

Full Text Available Polymorphisms in the T cell (or transmembrane immunoglobulin and mucin domain 1 (TIM-1 gene, particularly in the mucin domain, have been associated with atopy and allergic diseases in mice and human. Genetic- and antibody-mediated studies revealed that Tim-1 functions as a positive regulator of Th2 responses, while certain antibodies to Tim-1 can exacerbate or reduce allergic lung inflammation. Tim-1 can also positively regulate the function of B cells, NKT cells, dendritic cells and mast cells. However, the precise molecular mechanisms by which Tim-1 modulates immune cell function are currently unknown. In this study, we have focused on defining Tim-1-mediated signaling pathways that enhance mast cell activation through the high affinity IgE receptor (FceRI. Using a Tim-1 mouse model lacking the mucin domain (Tim-1Dmucin, we show for the first time that the polymorphic Tim-1 mucin region is dispensable for normal mast cell activation. We further show that Tim-4 cross-linking of Tim-1 enhances select signaling pathways downstream of FceRI in mast cells, including mTOR-dependent signaling, leading to increased cytokine production but without affecting degranulation.

HDAC inhibitors enhance neratinib activity and when combined enhance the actions of an anti-PD-1 immunomodulatory antibody in vivo.

Science.gov (United States)

Booth, Laurence; Roberts, Jane L; Poklepovic, Andrew; Avogadri-Connors, Francesca; Cutler, Richard E; Lalani, Alshad S; Dent, Paul

2017-10-27

Patients whose NSCLC tumors become afatinib resistant presently have few effective therapeutic options to extend their survival. Afatinib resistant NSCLC cells were sensitive to clinically relevant concentrations of the irreversible pan-HER inhibitor neratinib, but not by the first generation ERBB1/2/4 inhibitor lapatinib. In multiple afatinib resistant NSCLC clones, HDAC inhibitors reduced the expression of ERBB1/3/4, but activated c-SRC, which resulted in higher total levels of ERBB1/3 phosphorylation. Neratinib also rapidly reduced the expression of ERBB1/2/3/4, c-MET and of mutant K-/N-RAS; K-RAS co-localized with phosphorylated ATG13 and with cathepsin B in vesicles. Combined exposure of cells to [neratinib + HDAC inhibitors] caused inactivation of mTORC1 and mTORC2, enhanced autophagosome and subsequently autolysosome formation, and caused an additive to greater than additive induction of cell death. Knock down of Beclin1 or ATG5 prevented HDAC inhibitors or neratinib from reducing ERBB1/3/4 and K-/N-RAS expression and reduced [neratinib + HDAC inhibitor] lethality. Neratinib and HDAC inhibitors reduced the expression of multiple HDAC proteins via autophagy that was causal in the reduced expression of PD-L1, PD-L2 and ornithine decarboxylase, and increased expression of Class I MHCA. In vivo , neratinib and HDAC inhibitors interacted to suppress the growth of 4T1 mammary tumors, an effect that was enhanced by an anti-PD-1 antibody. Our data support the premises that neratinib lethality can be enhanced by HDAC inhibitors, that neratinib may be a useful therapeutic tool in afatinib resistant NSCLC, and that [neratinib + HDAC inhibitor] exposure facilitates anti-tumor immune responses.

Data base management activities for the Remedial Action Program at ORNL: Calendar year 1988

International Nuclear Information System (INIS)

Voorhees, L.D.; Hook, L.A.; Gentry, M.J.; McCord, R.A.; Faulkner, M.A.; Bledsoe, J.L.; Newman, K.A.; Owen, P.T.; Rosen, A.E.

1989-04-01

The ORNL Remedial Action Program (RAP) was established in 1985 in response to state and federal regulations mandating corrective actions at contaminated sites. To achieve this goal, numerous and varied studies are being conducted to characterize the type and extent of contamination. Environmental data collected in support of other programs at ORNL are also of use to RAP. Collectively, these studies are generating a voluminous amount of data. A computerized Data and Information Management System (DIMS) was developed for RAP to (1) provide a centralized repository for data pertinent to RAP and (2) provide support for the investigations and assessments leading to the long-term remediation of contaminated facilities and sites. The current DIMS and its role in supporting RAP during 1988 are described. The DIMS consists of three components: (1) the Numeric Data Base, (2) the Bibliographic Data Base, and (3) the Records Control Data Base. This report addresses all three data bases, but focuses on a description of the contents of the Numeric Data Base. The types of numeric data currently available are summarized in the tables and figures. More detailed information on the contents of the RAP Numeric Data Base has been assembled in a menu-driven format on IBM PC diskettes, which are available upon request. 6 refs

Transient receptor potential ankyrin 1 activation enhances hapten sensitization in a T-helper type 2-driven fluorescein isothiocyanate-induced contact hypersensitivity mouse model

International Nuclear Information System (INIS)

Shiba, Takahiro; Tamai, Takuma; Sahara, Yurina; Kurohane, Kohta; Watanabe, Tatsuo; Imai, Yasuyuki

2012-01-01

Some chemicals contribute to the development of allergies by increasing the immunogenicity of other allergens. We have demonstrated that several phthalate esters, including dibutyl phthalate (DBP), enhance skin sensitization to fluorescein isothiocyanate (FITC) in a mouse contact hypersensitivity model, in which the T-helper type 2 (Th2) response is essential. On the other hand, some phthalate esters were found to activate transient receptor potential ankyrin 1 (TRPA1) cation channels on sensory neurons. We then found a positive correlation between the enhancing effects of several types of phthalate esters on skin sensitization to FITC and their ability to activate TRPA1. Here we examined the involvement of TRPA1 in sensitization to FITC by using TRPA1 agonists other than phthalate esters. During skin sensitization to FITC, the TRPA1 agonists (menthol, carvacrol, cinnamaldehyde and DBP) augmented the ear-swelling response as well as trafficking of FITC-presenting dendritic cells to draining lymph nodes. We confirmed that these TRPA1 agonists induced calcium influx into TRPA1-expressing Chinese hamster ovary (CHO) cells. We also found that TRPA1 antagonist HC-030031 inhibited DBP-induced calcium influx into TRPA1-expressing CHO cells. After pretreatment with this antagonist upon skin sensitization to FITC, the enhancing effect of DBP on sensitization was suppressed. These results suggest that TRPA1 activation will become a useful marker to find chemicals that facilitate sensitization in combination with other immunogenic haptens. -- Highlights: ► Role of TRPA1 activation was revealed in a mouse model of skin sensitization to FITC. ► TRPA1 agonists enhanced skin sensitization as well as dendritic cell trafficking. ► Dibutyl phthalate (DBP) has been shown to enhance skin sensitization to FITC. ► TRPA1 activation by DBP was inhibited by a selective antagonist, HC-030031. ► HC-030031 inhibited the enhancing effect of DBP on skin sensitization to FITC.

Transient receptor potential ankyrin 1 activation enhances hapten sensitization in a T-helper type 2-driven fluorescein isothiocyanate-induced contact hypersensitivity mouse model

Energy Technology Data Exchange (ETDEWEB)

Shiba, Takahiro; Tamai, Takuma; Sahara, Yurina; Kurohane, Kohta [Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan); Watanabe, Tatsuo [Laboratory of Food Chemistry, School of Food and Nutritional Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan); Imai, Yasuyuki, E-mail: imai@u-shizuoka-ken.ac.jp [Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan)

2012-11-01

Some chemicals contribute to the development of allergies by increasing the immunogenicity of other allergens. We have demonstrated that several phthalate esters, including dibutyl phthalate (DBP), enhance skin sensitization to fluorescein isothiocyanate (FITC) in a mouse contact hypersensitivity model, in which the T-helper type 2 (Th2) response is essential. On the other hand, some phthalate esters were found to activate transient receptor potential ankyrin 1 (TRPA1) cation channels on sensory neurons. We then found a positive correlation between the enhancing effects of several types of phthalate esters on skin sensitization to FITC and their ability to activate TRPA1. Here we examined the involvement of TRPA1 in sensitization to FITC by using TRPA1 agonists other than phthalate esters. During skin sensitization to FITC, the TRPA1 agonists (menthol, carvacrol, cinnamaldehyde and DBP) augmented the ear-swelling response as well as trafficking of FITC-presenting dendritic cells to draining lymph nodes. We confirmed that these TRPA1 agonists induced calcium influx into TRPA1-expressing Chinese hamster ovary (CHO) cells. We also found that TRPA1 antagonist HC-030031 inhibited DBP-induced calcium influx into TRPA1-expressing CHO cells. After pretreatment with this antagonist upon skin sensitization to FITC, the enhancing effect of DBP on sensitization was suppressed. These results suggest that TRPA1 activation will become a useful marker to find chemicals that facilitate sensitization in combination with other immunogenic haptens. -- Highlights: ► Role of TRPA1 activation was revealed in a mouse model of skin sensitization to FITC. ► TRPA1 agonists enhanced skin sensitization as well as dendritic cell trafficking. ► Dibutyl phthalate (DBP) has been shown to enhance skin sensitization to FITC. ► TRPA1 activation by DBP was inhibited by a selective antagonist, HC-030031. ► HC-030031 inhibited the enhancing effect of DBP on skin sensitization to FITC.

Le jeu incertain des générations An uncertain play of generations. How rap artists settle as a professional group within the French music industry

Directory of Open Access Journals (Sweden)

Karim Hammou

2011-11-01

Full Text Available Le rap en français peut être aujourd’hui considéré comme un univers professionnel établi, tout en étant une innovation relativement récente. Cet article montre que sa pérennisation est le fruit des rapports complexes entre trois générations d’artistes, et entre ces générations et les acteurs des industries musicales. Il s’appuie en particulier sur l’examen des conventions discographiques (refrains, collaborations, producteurs… privilégiées par les rappeurs qui se succèdent en France de 1990 à 2004. Une première génération émerge en 1990-1993 d’un pari ponctuel des grandes maisons de disques sur le rap. Une nouvelle génération de rappeurs, celle de 1994-1997, ne bénéfice pas d’un même contexte. Les clivages internes qui la traversent, liés à la médiation des radios, éclipsent ses tentatives de distinction à l’égard de la première génération. Dans le jeu de rivalités et de collaborations entre ces fractions de la scène rap naît un système d’accréditation informelle entre rappeurs qui marginalise une frange de la deuxième génération. La pratique professionnelle du rap connaît alors une autonomie relative, descriptible comme une concession au sein de l’industrie du disque. Enfin, les artistes qui accèdent à la notoriété à partir de 1998 se distinguent par leur rapport d’aspirant à l’égard d’un monde social désormais perçu comme prévisible. L’étude d’un tel processus d’intégration d’une nouvelle technique d’interprétation vocale dans les industries musicales françaises révèle la pertinence de l’outil conceptuel des générations sociologiques pour saisir le renouvellement des univers artistiques et des dynamiques professionnelles.French rap music is now an established industry, although it is still a recent innovation. This paper shows that its establishment is the result of the complex relationship between three generations of artists, oligopolistic

Cortactin deficiency is associated with reduced neutrophil recruitment but increased vascular permeability in vivo.

Science.gov (United States)

Schnoor, Michael; Lai, Frank P L; Zarbock, Alexander; Kläver, Ruth; Polaschegg, Christian; Schulte, Dörte; Weich, Herbert A; Oelkers, J Margit; Rottner, Klemens; Vestweber, Dietmar

2011-08-01

Neutrophil extravasation and the regulation of vascular permeability require dynamic actin rearrangements in the endothelium. In this study, we analyzed in vivo whether these processes require the function of the actin nucleation-promoting factor cortactin. Basal vascular permeability for high molecular weight substances was enhanced in cortactin-deficient mice. Despite this leakiness, neutrophil extravasation in the tumor necrosis factor-stimulated cremaster was inhibited by the loss of cortactin. The permeability defect was caused by reduced levels of activated Rap1 (Ras-related protein 1) in endothelial cells and could be rescued by activating Rap1 via the guanosine triphosphatase (GTPase) exchange factor EPAC (exchange protein directly activated by cAMP). The defect in neutrophil extravasation was caused by enhanced rolling velocity and reduced adhesion in postcapillary venules. Impaired rolling interactions were linked to contributions of β(2)-integrin ligands, and firm adhesion was compromised by reduced ICAM-1 (intercellular adhesion molecule 1) clustering around neutrophils. A signaling process known to be critical for the formation of ICAM-1-enriched contact areas and for transendothelial migration, the ICAM-1-mediated activation of the GTPase RhoG was blocked in cortactin-deficient endothelial cells. Our results represent the first physiological evidence that cortactin is crucial for orchestrating the molecular events leading to proper endothelial barrier function and leukocyte recruitment in vivo.

Activation of D1/5 Dopamine Receptors: A Common Mechanism for Enhancing Extinction of Fear and Reward-Seeking Behaviors.

Science.gov (United States)

Abraham, Antony D; Neve, Kim A; Lattal, K Matthew

2016-07-01

Dopamine is critical for many processes that drive learning and memory, including motivation, prediction error, incentive salience, memory consolidation, and response output. Theories of dopamine's function in these processes have, for the most part, been developed from behavioral approaches that examine learning mechanisms in appetitive tasks. A parallel and growing literature indicates that dopamine signaling is involved in consolidation of memories into stable representations in aversive tasks such as fear conditioning. Relatively little is known about how dopamine may modulate memories that form during extinction, when organisms learn that the relation between previously associated events is severed. We investigated whether fear and reward extinction share common mechanisms that could be enhanced with dopamine D1/5 receptor activation. Pharmacological activation of dopamine D1/5 receptors (with SKF 81297) enhanced extinction of both cued and contextual fear. These effects also occurred in the extinction of cocaine-induced conditioned place preference, suggesting that the observed effects on extinction were not specific to a particular type of procedure (aversive or appetitive). A cAMP/PKA biased D1 agonist (SKF 83959) did not affect fear extinction, whereas a broadly efficacious D1 agonist (SKF 83822) promoted fear extinction. Together, these findings show that dopamine D1/5 receptor activation is a target for the enhancement of fear or reward extinction.

Kopūstinės kandies (Plutella xylostella L.) (Lepidoptera: Plutelidae) skraidymo ir kenkimo intensyvumo dinamika vasarinių rapsų ir gūžinių kopūstų pasėliuose

OpenAIRE

Vyšniauskaitė, Sigrida

2013-01-01

Magistrantūros studijų baigiamajame darbe pateikiami kopūstinės kandies skraidymo bei kenkimo dinamikos vasarinių rapsų ir gūžinių kopūstų pasėliuose tyrimų rezultatai. Darbo objektas – kopūstinė kandis (Plutella xylostella L.) Darbo metodai – kopūstinės kandies skraidymo dinamika tirta naudojant feromonines “delta” tipo gaudykles, 2012 m. gegužės – rugpjūčio mėnesiais, vasarinių rapsų ir ankstyvųjų bei vėlyvųjų baltagūžių kopūstų pasėliuose. Vasarinių rapsų pasėlyje buvo įrengta 12 ga...

EEG and MEG source localization using recursively applied (RAP) MUSIC

Energy Technology Data Exchange (ETDEWEB)

Mosher, J.C. [Los Alamos National Lab., NM (United States); Leahy, R.M. [University of Southern California, Los Angeles, CA (United States). Signal and Image Processing Inst.

1996-12-31

The multiple signal characterization (MUSIC) algorithm locates multiple asynchronous dipolar sources from electroencephalography (EEG) and magnetoencephalography (MEG) data. A signal subspace is estimated from the data, then the algorithm scans a single dipole model through a three-dimensional head volume and computes projections onto this subspace. To locate the sources, the user must search the head volume for local peaks in the projection metric. Here we describe a novel extension of this approach which we refer to as RAP (Recursively APplied) MUSIC. This new procedure automatically extracts the locations of the sources through a recursive use of subspace projections, which uses the metric of principal correlations as a multidimensional form of correlation analysis between the model subspace and the data subspace. The dipolar orientations, a form of `diverse polarization,` are easily extracted using the associated principal vectors.

Epstein Barr virus Latent Membrane Protein-1 enhances dendritic cell therapy lymph node migration, activation, and IL-12 secretion.

Directory of Open Access Journals (Sweden)

James M Termini

Full Text Available Dendritic cells (DC are a promising cell type for cancer vaccines due to their high immunostimulatory capacity. However, improper maturation of DC prior to treatment may account for the limited efficacy of DC vaccine clinical trials. Latent Membrane Protein-1 (LMP1 of Epstein-Barr virus was examined for its ability to mature and activate DC as a gene-based molecular adjuvant for DC vaccines. DC were transduced with an adenovirus 5 vector (Ad5 expressing LMP1 under the control of a Tet-inducible promoter. Ad5-LMP1 was found to mature and activate both human and mouse DC. LMP1 enhanced in vitro migration of DC toward CCL19, as well as in vivo migration of DC to the inguinal lymph nodes of mice following intradermal injection. LMP1-transduced DC increased T cell proliferation in a Pmel-1 adoptive transfer model and enhanced survival in B16-F10 melanoma models. LMP1-DC also enhanced protection in a vaccinia-Gag viral challenge assay. LMP1 induced high levels of IL-12p70 secretion in mouse DC when compared to standard maturation protocols. Importantly, LMP1-transduced human DC retained the capacity to secrete IL-12p70 and TNF in response to DC restimulation. In contrast, DC matured with Monocyte Conditioned Media-Mimic cocktail (Mimic were impaired in IL-12p70 secretion following restimulation. Overall, LMP1 matured and activated DC, induced migration to the lymph node, and generated high levels of IL-12p70 in a murine model. We propose LMP1 as a promising molecular adjuvant for DC vaccines.

Inhibition of protein kinase CK2 reduces CYP24A1 expression and enhances 1,25-dihydroxyvitamin D3 anti-tumor activity in human prostate cancer cells

Science.gov (United States)

Luo, Wei; Yu, Wei-Dong; Ma, Yingyu; Chernov, Mikhail; Trump, Donald L.; Johnson, Candace S.

2013-01-01

Vitamin D has broad range of physiological functions and anti-tumor effects. 24-hydroxylase, encoded by the CYP24A1 gene, is the key enzyme for degrading many forms of vitamin D including the most active form, 1,25D3. Inhibition of CYP24A1 enhances 1,25D3 anti-tumor activity. In order to isolate regulators of CYP24A1 expression in prostate cancer cells, we established a stable prostate cancer cell line PC3 with CYP24A1 promoter driving luciferase expression to screen a small molecular library for compounds that inhibit CYP24A1 promoter activity. From this screening, we identified, 4,5,6,7-tetrabromobenzimidazole (TBBz), a protein kinase CK2 selective inhibitor as a disruptor of CYP24A1 promoter activity. We show that TBBz inhibits CYP24A1 promoter activity induced by 1,25D3 in prostate cancer cells. In addition, TBBz downregulates endogenous CYP24A1 mRNA level in TBBz treated PC3 cells. Furthermore, siRNA-mediated CK2 knockdown reduces 1,25D3 induced CYP24A1 mRNA expression in PC3 cells. These results suggest that CK2 contributes to 1,25D3 mediated target gene expression. Lastly, inhibition of CK2 by TBBz or CK2 siRNA significantly enhanced 1,25D3 mediated anti-proliferative effect in vitro and in vivo in a xenograft model. In summary, our findings reveal that protein kinase CK2 is involved in the regulation of CYP24A1 expression by 1,25D3 and CK2 inhibitor enhances 1,25D3 mediated anti-tumor effect. PMID:23358686

Biotransformation of Pueraria lobata Extract with Lactobacillus rhamnosus vitaP1 Enhances Anti-Melanogenic Activity.

Science.gov (United States)

Kwon, Jeong Eun; Lee, Jin Woo; Park, Yuna; Sohn, Eun-Hwa; Choung, Eui Su; Jang, Seon-A; Kim, Inhye; Lee, Da Eun; Koo, Hyun Jung; Bak, Jong Phil; Lee, Sung Ryul; Kang, Se Chan

2018-01-28

Isoflavone itself is less available in the body without the aid of intestinal bacteria. In this study, we searched for isoflavone-transforming bacteria from human fecal specimens ( n = 14) using differential selection media. Isoflavone-transforming activity as the production of dihydrogenistein and dihydrodaidzein was assessed by high-performance liquid chromatography and we found Lactobacillus rhamnosus , named L. rhamnosus vitaP1, through 16S rDNA sequence analysis. Extract from Pueraria lobata (EPL) and soy hypocotyl extract were fermented with L. rhamnosus vitaP1 for 24 and 48 h at 37°C. Fermented EPL (FEPL) showed enhanced anti-tyrosinase activity and antioxidant capacities, important suppressors of the pigmentation process, compared with that of EPL ( p Lactobacillus rhamnosus vitaP1 was found to be able to biotransform isoflavones in EPL. FEPL showed augmented anti-melanogenic potential.

Comprehensive behavioral analysis of mice deficient in Rapgef2 and Rapgef6, a subfamily of guanine nucleotide exchange factors for Rap small GTPases possessing the Ras/Rap-associating domain.

Science.gov (United States)

Maeta, Kazuhiro; Hattori, Satoko; Ikutomo, Junji; Edamatsu, Hironori; Bilasy, Shymaa E; Miyakawa, Tsuyoshi; Kataoka, Tohru

2018-05-10

Rapgef2 and Rapgef6 define a subfamily of guanine nucleotide exchange factors for Rap small GTPases, characterized by the possession of the Ras/Rap-associating domain. Previous genomic analyses suggested their possible involvement in the etiology of schizophrenia. We recently demonstrated the development of an ectopic cortical mass (ECM), which resembles the human subcortical band heterotopia, in the dorsal telencephalon-specific Rapgef2 conditional knockout (Rapgef2-cKO) brains. Additional knockout of Rapgef6 in Rapgef2-cKO mice resulted in gross enlargement of the ECM whereas knockout of Rapgef6 alone (Rapgef6-KO) had no discernible effect on the brain morphology. Here, we performed a battery of behavioral tests to examine the effects of Rapgef2 or Rapgef6 deficiency on higher brain functions. Rapgef2-cKO mice exhibited hyperlocomotion phenotypes. They showed decreased anxiety-like behavior in the elevated plus maze and the open-field tests as well as increased depression-like behavior in the Porsolt forced swim and tail suspension tests. They also exhibited increased sociability especially in novel environments. They showed defects in cognitive function as evidenced by reduced learning ability in the Barnes circular maze test and by impaired working memory in the T maze tests. In contrast, although Rapgef6 and Rapgef2 share similarities in biochemical roles, Rapgef6-KO mice exhibited mild behavioral abnormalities detected with a number of behavioral tests, such as hyperlocomotion phenotype in the open-field test and the social interaction test with a novel environment and working-memory defects in the T-maze test. In conclusion, although there were differences in their brain morphology and the magnitude of the behavioral abnormalities, Rapgef2-cKO mice and Rapgef6-KO mice exhibited hyperlocomotion phenotype and working-memory defect, both of which could be recognized as schizophrenia-like behavior.

Rock gabion, rip-rap, and culvert treatments: Successes and failures in post-fire erosion mitigation, Schultz Fire 2010

Science.gov (United States)

Daniel G. Neary; Karen A. Koestner

2011-01-01

Following the Schultz Fire in June of 2010, several erosion mitigation efforts were undertaken to reduce the impacts of post-fire flooding expected during the 2010 monsoon. One treatment consisted of the placement of large rock rip-rap on targeted fill slopes of a high elevation forest road that contains a buried pipeline supplying water to the city of Flagstaff....

Discovery of stimulation-responsive immune enhancers with CRISPR activation

Science.gov (United States)

Simeonov, Dimitre R.; Gowen, Benjamin G.; Boontanrart, Mandy; Roth, Theodore L.; Gagnon, John D.; Mumbach, Maxwell R.; Satpathy, Ansuman T.; Lee, Youjin; Bray, Nicolas L.; Chan, Alice Y.; Lituiev, Dmytro S.; Nguyen, Michelle L.; Gate, Rachel E.; Subramaniam, Meena; Li, Zhongmei; Woo, Jonathan M.; Mitros, Therese; Ray, Graham J.; Curie, Gemma L.; Naddaf, Nicki; Chu, Julia S.; Ma, Hong; Boyer, Eric; Van Gool, Frederic; Huang, Hailiang; Liu, Ruize; Tobin, Victoria R.; Schumann, Kathrin; Daly, Mark J.; Farh, Kyle K; Ansel, K. Mark; Ye, Chun J.; Greenleaf, William J.; Anderson, Mark S.; Bluestone, Jeffrey A.; Chang, Howard Y.; Corn, Jacob E.; Marson, Alexander

2017-01-01

The majority of genetic variants associated with common human diseases map to enhancers, non-coding elements that shape cell-type-specific transcriptional programs and responses to extracellular cues1–3. Systematic mapping of functional enhancers and their biological contexts is required to understand the mechanisms by which variation in non-coding genetic sequences contributes to disease. Functional enhancers can be mapped by genomic sequence disruption4–6, but this approach is limited to the subset of enhancers that are necessary in the particular cellular context being studied. We hypothesized that recruitment of a strong transcriptional activator to an enhancer would be sufficient to drive target gene expression, even if that enhancer was not currently active in the assayed cells. Here we describe a discovery platform that can identify stimulus-responsive enhancers for a target gene independent of stimulus exposure. We used tiled CRISPR activation (CRISPRa)7 to synthetically recruit a transcriptional activator to sites across large genomic regions (more than 100 kilobases) surrounding two key autoimmunity risk loci, CD69 and IL2RA. We identified several CRISPRa-responsive elements with chromatin features of stimulus-responsive enhancers, including an IL2RA enhancer that harbours an autoimmunity risk variant. Using engineered mouse models, we found that sequence perturbation of the disease-associated Il2ra enhancer did not entirely block Il2ra expression, but rather delayed the timing of gene activation in response to specific extracellular signals. Enhancer deletion skewed polarization of naive T cells towards a pro-inflammatory T helper (TH17) cell state and away from a regulatory T cell state. This integrated approach identifies functional enhancers and reveals how non-coding variation associated with human immune dysfunction alters context-specific gene programs. PMID:28854172

Xenobiotics enhance laccase activity in alkali-tolerant γ-proteobacterium JB.

Science.gov (United States)

Singh, Gursharan; Batish, Mona; Sharma, Prince; Capalash, Neena

2009-01-01

Various genotoxic textile dyes, xenobiotics, substrates (10 µM) and agrochemicals (100 µg/ml) were tested for enhancement of alkalophilic laccase activity in γ-proteobacterium JB. Neutral Red, Indigo Carmine, Naphthol Base Bordears and Sulphast Ruby dyes increased the activity by 3.7, 2.7, 2.6 and 2.3 fold respectively. Xenobiotics/substrates like p-toluidine, 8-hydroxyquinoline and anthracine increased it by 3.4, 2.8 and 2.3 fold respectively. Atrazine and trycyclozole pesticides enhanced the activity by 1.95 and 1.5 fold respectively.

Data base management activities for the Remedial Action Program at ORNL, calendar year 1987

International Nuclear Information System (INIS)

Voorhees, L.D.; Hook, L.A.; Gentry, M.J.; McCord, R.A.; Faulkner, M.A.; Newman, K.A.; Owen, P.T.

1988-05-01

The Oak Ridge National Laboratory (ORNL) Remedial Action Program (RAP) was established in FY 1985 to apply corrective measures at areas contaminated with radioactive and/or hazardous chemical wastes. To achieve this goal, numerous and varied studies are being conducted to characterize the waste disposal sites. Environmental data collected in support of other programs at ORNL are also of use to RAP. These studies are generating a voluminous amount of data on a scale unprecedented for ORNL. A computerized Data and Information Management System (DIMS) was developed for RAP to (1) provide a centralized repository for data pertinent to RAP and (2) provide support for the investigations and assessments leading to the long-term remediation of contaminated facilities and sites. 10 refs., 25 figs., 16 tabs

Comparison of wrist and head TLD doses with whole body TLD doses during high active jobs at RAPS-5 and 6

International Nuclear Information System (INIS)

Sharma, Ravi Kant; Abhishek, Neel; Kakkar, Amandeep; Kumar, Rajesh

2016-01-01

In nuclear power plant radiation dose monitoring and assessment is done to control the individual dose and station collective doses. While performing a radioactive job on systems or equipment with significant radiation levels of non uniform and beaming radiation; there is potential of localized exposure to extremities hands in particular and lens of the eye in comparison to other body parts. Keeping in view of this, separate equivalent dose limit to the extremities (hands and feet) and lens of the eye are defined by ICRP. A study has been carried out during Biennial Shutdown (BSD) of RAPS-6 in the month of October-2015 to establish the correlation between the doses received by chest TLDs which is being used to estimate the effective whole body dose of the radiation worker and the doses received in wrist TLD and head TLDs which are being used to monitor the equivalent dose received by hands and lens of the eye with applying a suitable correction factor

Stat1-Vitamin D Receptor Interactions Antagonize 1,25-Dihydroxyvitamin D Transcriptional Activity and Enhance Stat1-Mediated Transcription

Science.gov (United States)

Vidal, Marcos; Ramana, Chilakamarti V.; Dusso, Adriana S.

2002-01-01

The cytokine gamma interferon (IFN-γ) and the calcitropic steroid hormone 1,25-dihydroxyvitamin D (1,25D) are activators of macrophage immune function. In sarcoidosis, tuberculosis, and several granulomatoses, IFN-γ induces 1,25D synthesis by macrophages and inhibits 1,25D induction of 24-hydroxylase, a key enzyme in 1,25D inactivation, causing high levels of 1,25D in serum and hypercalcemia. This study delineates IFN-γ-1,25D cross talk in human monocytes-macrophages. Nuclear accumulation of Stat1 and vitamin D receptor (VDR) by IFN-γ and 1,25D promotes protein-protein interactions between Stat1 and the DNA binding domain of the VDR. This prevents VDR-retinoid X receptor (RXR) binding to the vitamin D-responsive element, thus diverting the VDR from its normal genomic target on the 24-hydroxylase promoter and antagonizing 1,25D-VDR transactivation of this gene. In contrast, 1,25D enhances IFN-γ action. Stat1-VDR interactions, by preventing Stat1 deactivation by tyrosine dephosphorylation, cooperate with IFN-γ/Stat1-induced transcription. This novel 1,25D-IFN-γ cross talk explains the pathogenesis of abnormal 1,25D homeostasis in granulomatous processes and provides new insights into 1,25D immunomodulatory properties. PMID:11909970

Expression of sheep pathogen Babesia sp. Xinjiang rhoptry-associated protein 1 and evaluation of its diagnostic potential by enzyme-linked immunosorbent assay.

Science.gov (United States)

Niu, Qingli; Liu, Zhijie; Yang, Jifei; Yu, Peifa; Pan, Yuping; Zhai, Bintao; Luo, Jianxun; Guan, Guiquan; Yin, Hong

2016-12-01

Ovine babesiosis is one of the most important tick-borne haemoparasitic diseases of small ruminants. The ovine parasite Babesia sp. Xinjiang is widespread in China. In this study, recombinant full-length XJrRAP-1aα2 (rhoptry-associated protein 1aα2) and C-terminal XJrRAP-1aα2 CT of Babesia sp. Xinjiang were expressed and used to evaluate their diagnostic potential for Babesia sp. Xinjiang infections by indirect enzyme-linked immunosorbent assay (ELISA). Purified XJrRAP-1aα2 was tested for reactivity with sera from animals experimentally infected with Babesia sp. Xinjiang and other haemoparasites using Western blotting and ELISA. The results showed no cross-reactivities between XJrRAP-1aα2 CT and sera from animals infected by other pathogens. High level of antibodies against RAP-1a usually lasted 10 weeks post-infection (wpi). A total of 3690 serum samples from small ruminants in 23 provinces located in 59 different regions of China were tested by ELISA. The results indicated that the average positive rate was 30·43%, and the infections were found in all of the investigated provinces. This is the first report on the expression and potential use of a recombinant XJrRAP-1aα2 CT antigen for the development of serological assays for the diagnosis of ovine babesiosis, caused by Babesia sp. Xinjiang.

TRAF1 Coordinates Polyubiquitin Signaling to Enhance Epstein-Barr Virus LMP1-Mediated Growth and Survival Pathway Activation.

Directory of Open Access Journals (Sweden)

Hannah Greenfeld

2015-05-01

Full Text Available The Epstein-Barr virus (EBV encoded oncoprotein Latent Membrane Protein 1 (LMP1 signals through two C-terminal tail domains to drive cell growth, survival and transformation. The LMP1 membrane-proximal TES1/CTAR1 domain recruits TRAFs to activate MAP kinase, non-canonical and canonical NF-kB pathways, and is critical for EBV-mediated B-cell transformation. TRAF1 is amongst the most highly TES1-induced target genes and is abundantly expressed in EBV-associated lymphoproliferative disorders. We found that TRAF1 expression enhanced LMP1 TES1 domain-mediated activation of the p38, JNK, ERK and canonical NF-kB pathways, but not non-canonical NF-kB pathway activity. To gain insights into how TRAF1 amplifies LMP1 TES1 MAP kinase and canonical NF-kB pathways, we performed proteomic analysis of TRAF1 complexes immuno-purified from cells uninduced or induced for LMP1 TES1 signaling. Unexpectedly, we found that LMP1 TES1 domain signaling induced an association between TRAF1 and the linear ubiquitin chain assembly complex (LUBAC, and stimulated linear (M1-linked polyubiquitin chain attachment to TRAF1 complexes. LMP1 or TRAF1 complexes isolated from EBV-transformed lymphoblastoid B cell lines (LCLs were highly modified by M1-linked polyubiqutin chains. The M1-ubiquitin binding proteins IKK-gamma/NEMO, A20 and ABIN1 each associate with TRAF1 in cells that express LMP1. TRAF2, but not the cIAP1 or cIAP2 ubiquitin ligases, plays a key role in LUBAC recruitment and M1-chain attachment to TRAF1 complexes, implicating the TRAF1:TRAF2 heterotrimer in LMP1 TES1-dependent LUBAC activation. Depletion of either TRAF1, or the LUBAC ubiquitin E3 ligase subunit HOIP, markedly impaired LCL growth. Likewise, LMP1 or TRAF1 complexes purified from LCLs were decorated by lysine 63 (K63-linked polyubiqutin chains. LMP1 TES1 signaling induced K63-polyubiquitin chain attachment to TRAF1 complexes, and TRAF2 was identified as K63-Ub chain target. Co-localization of M1- and K63

Rediseño y fabricación de una impresora 3D RepRap.

OpenAIRE

Huertas González, Joan

2014-01-01

El objetivo principal de este proyecto es conseguir las habilidades necesarias para fabricar una impresora 3D del tipo Rep Rap, una tipología de impresoras Open source. Una vez conseguido este objetivo se rediseñan piezas de la propia impresora con el objetivo de mejorar el diseño actual. Se plantea el proyecto como iniciación al mundo de la impresión 3D y de los materiales plásticos con los que se puede trabajar, PLA, HDPE, ABS o NYLON. Se instruye al lector para que tambié...

Effects of growing location on the production of main active components and antioxidant activity of Dasiphora fruticosa (L.) Rydb. by chemometric methods.

Science.gov (United States)

Liu, Wei; Wang, Dongmei; Hou, Xiaogai; Yang, Yueqin; Xue, Xian; Jia, Qishi; Zhang, Lixia; Zhao, Wei; Yin, Dongxue

2018-05-17

Traditional Chinese medicine (TCM) plays a very important role in the health system of China. The content and activity of active component are main indexes that evaluate the quality of TCM, however they may vary with environmental factors in their growing locations. In this study, effects of environmental factors on the contents of active components and antioxidant activity of Dasiphora fruticosa from the five main production areas of China were investigated. The contents of tannin, total flavonoid and rutin were determined and varied within the range of 7.65-10.69%, 2.30-5.39% and 0.18-0.81%, respectively. Antioxidant activity was determined by DPPH assay, with the DPPH IC 50 values ranged from 8.791 to 32.534μg mL -1 . In order to further explore the cause of these significant geographical variations, the chemometric methods including correlation analysis, principal component analysis, gray correlation analysis, and path analysis were conducted. The results showed environmental factors had significant effect on the active component contents and antioxidant activity. Rapidly available phosphorus (RAP) and rapidly available nitrogen (RAN) were common dominant factors, and a significant positive correlation was observed between RAP and active components and antioxidant activity (Pcomponents and strong antioxidant activity, Bange in Tibet and Geermu in Qinghai Province was selected as a favorable growing location, respectively. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Ficus Deltoidea Enhance Glucose Uptake Activity in Cultured Muscle Cells

International Nuclear Information System (INIS)

Zainah Adam; Shafii Khamis; Amin Ismail; Muhajir Hamid

2015-01-01

Ficus deltoidea or locally known as Mas cotek is one of the common medicinal plants used in Malaysia. Our previous studies showed that this plant have blood glucose lowering effect. Glucose uptake into muscle and adipocytes cells is one of the known mechanisms of blood glucose lowering effect. This study was performed to evaluate the effect of Ficus deltoidea on glucose uptake activity into muscle cells. The cells were incubated with Ficus deltoidea extracts either alone or combination with insulin. Amount of glucose uptake by L6 myotubes was determined using glucose tracer, 2-deoxy-(1- 3 H 1 )-glucose. The results showed that Ficus deltoidea extracts at particular doses enhanced basal or insulin-mediated glucose uptake into muscle cells significantly. Hot aqueous extract enhanced glucose uptake at the low concentration (10 μg/ ml) whereas methanolic extract enhanced glucose uptake at low and high concentrations. Methanolic extract also mimicked insulin activity during enhancing glucose uptake into L^ muscle cells. Glucose uptake activity of Ficus deltoidea could be attributed by the phenolic compound presence in the plant. This study had shown that Ficus deltoidea has the ability to enhance glucose uptake into muscle cells which is partly contributed the antidiabetic activity of this plant. (author)

The French Accelerometer Network (RAP): Current state in 2007

International Nuclear Information System (INIS)

Gueguen, P.; Bard, P.-Y.; Pequegnat, C.; Souriau, A.; Dominique, P.; Regnier, M.

2007-01-01

France is a country of moderate seismicity but, due to dense urbanized and industrial areas, the seismic risk is significant. Furthermore, recent developments in numerical and semi-empirical methods requires a good knowledge of several parameters. The mission of the French accelerometer network programme (RAP-Reseau Accelerometrique Permanent) is to expand and modernize significantly the acquisition and application of French accelerometer data (both strong and weak motion) in order to improve earthquake related research and public safety from earthquakes. This network is the result of co-operative efforts including academic institutions (INSU-CNRS, Universities of Grenoble, Nice, Strasbourg, Toulouse, IPG Paris) and several state agencies (BRGM, CEA, IRSN, LCPC). Since 1995, around 120 stations have been installed in some seismic areas of France. This network also includes specific research actions (site effects, building monitoring, deep borehole). Other French accelerometer stations devoted to strong motion recording are also associated to the network. All data are archived and freely distributed in a database center, data being available in SAC, ASCII and SEED format. (authors)

Adiponectin enhances osteogenic differentiation in human adipose-derived stem cells by activating the APPL1-AMPK signaling pathway

Energy Technology Data Exchange (ETDEWEB)

Chen, Tong; Wu, Yu-wei; Lu, Hui; Guo, Yuan [Second Dental Center, Peking University School and Hospital of Stomatology, Beijing (China); National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing (China); Tang, Zhi-hui, E-mail: tang_zhihui@live.cn [Second Dental Center, Peking University School and Hospital of Stomatology, Beijing (China); National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing (China)

2015-05-29

Human adipose-derived stem cells (hASCs) are multipotent progenitor cells with multi-lineage differentiation potential including osteogenesis and adipogenesis. While significant progress has been made in understanding the transcriptional control of hASC fate, little is known about how hASC differentiation is regulated by the autocrine loop. The most abundant adipocytokine secreted by adipocytes, adiponectin (APN) plays a pivotal role in glucose metabolism and energy homeostasis. Growing evidence suggests a positive association between APN and bone formation yet little is known regarding the direct effects of APN on hASC osteogenesis. Therefore, this study was designed to investigate the varied osteogenic effects and regulatory mechanisms of APN in the osteogenic commitment of hASCs. We found that APN enhanced the expression of osteoblast-related genes in hASCs, such as osteocalcin, alkaline phosphatase, and runt-related transcription factor-2 (Runx2, also known as CBFa1), in a dose- and time-dependent manner. This was further confirmed by the higher expression levels of alkaline phosphatase and increased formation of mineralization nodules, along with the absence of inhibition of cell proliferation. Importantly, APN at 1 μg/ml was the optimal concentration, resulting in maximum deposition of calcium nodules, and was significant superior to bone morphogenetic protein 2. Mechanistically, we found for the first time that APN increased nuclear translocation of the leucine zipper motif (APPL)-1 as well as AMP-activated protein kinase (AMPK) phosphorylation, which were reversed by pretreatment with APPL1 siRNA. Our results indicate that APN promotes the osteogenic differentiation of hASCs by activating APPL1-AMPK signaling, suggesting that manipulation of APN is a novel therapeutic target for controlling hASC fate. - Highlights: • Adiponectin enhances osteogenic differentiation in human adipose-derived stem cells. • The knock-down of APPL1 block the enhancement of

Medical surveillance of occupational Noise Induced Hearing Loss (NIHL) at RAPS hospital

International Nuclear Information System (INIS)

Manuwal, A.K.; Ganesan, S.

2009-01-01

Full text: One of the most challenging roles of a Certifying Surgeon is to act as catalyst for change. This paper is a presentation of the impact of such an effort. Noise is the insidious of all industrial pollutants, involving every industry and causing severe hearing loss. Exposure to excessive noise is the major avoidable cause of permanent hearing impairment. Noise - induced hearing loss (NIHL) is bilateral and symmetrical, usually affecting the higher frequencies 3 k, 4 k or 6 kHz ) and then spreading to the lower frequencies (0.5 k,1 k or 2 kHz). The major health effects are lack of concentration, irritation, fatigue, headache, sleep disturbances etc. Hearing protectors should be used when engineering controls and work practices are not feasible for reducing noise exposure to safe levels. Ear muffs, ear plugs and ear canal caps are the main types of hearing protectors. Awareness should be created among workers about the harmful effects of noise on hearing and other body systems by implementing compulsory education noise conservation programmes. The practice followed at RAPS Hospital for medical surveillance of Occupational Noise Induced Hearing Loss is being briefed

Tet1 overexpression leads to anxiety-like behavior and enhanced fear memories via the activation of calcium-dependent cascade through Egr1 expression in mice.

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Kwon, Wookbong; Kim, Hyeng-Soo; Jeong, Jain; Sung, Yonghun; Choi, Minjee; Park, Song; Lee, Jinhee; Jang, Soyoung; Kim, Sung Hyun; Lee, Sanggyu; Kim, Myoung Ok; Ryoo, Zae Young

2018-01-01

Ten-eleven translocation methylcytosine dioxygenase 1 ( Tet1 ) initiates DNA demethylation by converting 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) at CpG-rich regions of genes, which have key roles in adult neurogenesis and memory. In addition, the overexpression of Tet1 with 5-hmC alteration in patients with psychosis has also been reported, for instance in schizophrenia and bipolar disorders. The mechanism underlying Tet1 overexpression in the brain; however, is still elusive. In the present study, we found that Tet1-transgenic (Tet1-TG) mice displayed abnormal behaviors involving elevated anxiety and enhanced fear memories. We confirmed that Tet1 overexpression affected adult neurogenesis with oligodendrocyte differentiation in the hippocampal dentate gyrus of Tet1-TG mice. In addition, Tet1 overexpression induced the elevated expression of immediate early genes, such as Egr1 , c-fos , Arc , and Bdnf , followed by the activation of intracellular calcium signals ( i.e. , CamKII, ERK, and CREB) in prefrontal and hippocampal neurons. The expression of GABA receptor subunits ( Gabra2 and Gabra4 ) fluctuated in the prefrontal cortex and hippocampus. We evaluated the effects of Tet1 overexpression on intracellular calcium-dependent cascades by activating the Egr1 promoter in vitro Tet1 enhanced Egr1 expression, which may have led to alterations in Gabra2 and Gabra4 expression in neurons. Taken together, we suggest that the Tet1 overexpression in our Tet1-TG mice can be applied as an effective model for studying various stress-related diseases that show hyperactivation of intracellular calcium-dependent cascades in the brain.-Kwon, W., Kim, H.-S., Jeong, J., Sung, Y., Choi, M., Park, S., Lee, J., Jang, S., Kim, S. H., Lee, S., Kim, M. O., Ryoo, Z. Y. Tet1 overexpression leads to anxiety-like behavior and enhanced fear memories via the activation of calcium-dependent cascade through Egr1 expression in mice. © FASEB.

Triolimus: A Multi-Drug Loaded Polymeric Micelle Containing Paclitaxel, 17-AAG, and Rapamycin as a Novel Radiosensitizer.

Science.gov (United States)

Tomoda, Keishiro; Tam, Yu Tong; Cho, Hyunah; Buehler, Darya; Kozak, Kevin R; Kwon, Glen S

2017-01-01

Triolimus is a multi-drug loaded polymeric micelle containing paclitaxel (PTX), 17-allylamino-17-demethoxygeldanamycin (17-AAG), and rapamycin (RAP). This study examines the radiosensitizing effect of Triolimus in vitro and in vivo. Radiosensitizing effects of Triolimus on A549 cells are dose dependent and at 2 × 10 -9 m, Triolimus shows significant radiosensitization even at low radiation doses (2 Gy). By sensitivity enhancement ratio, PTX alone, dual drug combinations, and Triolimus treatment at 2 × 10 -9 m have radiosensitizing effects with potency as follows: PTX alone (PTX) > PTX and RAP (P/R) > Triolimus (TRIO) > PTX and 17-AAG (P/17) >17-AAG and RAP (17/R). In vivo, fractionated radiation of 15 Gy preceded by infusion of PTX alone, dual drug combinations, or an intermediate dose of Triolimus (Int. TRIO: PTX/17-AAG/RAP at 15/15/7.5 mg kg -1 ) strongly inhibits A549 tumor growth. Notably, pretreatment with high dose of Triolimus (High TRIO: PTX/17-AAG/RAP at 60/60/30 mg kg -1 ) before the fractionated radiation leads to tumor control for up to 24 weeks. An enhanced radiosensitizing effect is observed without an increase in acute toxicity compared to PTX alone or radiation alone. These results suggest that further investigations of Triolimus in combination with radiation therapy are merited. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polymethoxylated flavones potentiate the cytolytic activity of NK leukemia cell line KHYG-1 via enhanced expression of granzyme B.

Science.gov (United States)

Saito, Takeshi; Abe, Daigo; Nogata, Yoichi

2015-01-16

Polymethoxylated flavones (PMFs) are found in the peel tissues of some citrus species. Here, we report that PMFs, such as nobiletin, potentiate the cytolytic activity of KHYG-1 natural killer (NK) leukemia cells. Nobiletin markedly enhanced the expression of granzyme B, a serine protease that plays critical roles in the cytolytic activity of NK cells. The potentiated cytolytic activity induced by nobiletin was canceled by the granzyme B inhibitor Z-AAD-CMK. Nobiletin also increased the levels of phosphorylated CREB, ERK1/2, and p38 MAPK in KHYG-1 cells, which are known to participate in NK cell function. Inhibition of an upstream kinase of ERK1/2 failed to reduce the granzyme B expression and KHYG-1 cytolytic activity. Meanwhile, inhibition of p38 MAPK attenuated both granzyme B expression and KHYG-1 cytolytic activity. These results suggest that the primary role of nobiletin in KHYG-1 cytolytic activity lies in upregulation of granzyme B expression, at least in part, mediated through p38 MAPK function. Copyright © 2014 Elsevier Inc. All rights reserved.

Enhanced basal contractility but reduced excitation-contraction coupling efficiency and beta-adrenergic reserve of hearts with increased Cav1.2 activity.

Science.gov (United States)

Tang, Mingxin; Zhang, Xiaoying; Li, Yingxin; Guan, Yinzheng; Ai, Xiaojie; Szeto, Christopher; Nakayama, Hiroyuki; Zhang, Hongyu; Ge, Shuping; Molkentin, Jeffery D; Houser, Steven R; Chen, Xiongwen

2010-08-01

Cardiac remodeling during heart failure development induces a significant increase in the activity of the L-type Ca(2+) channel (Cav1.2). However, the effects of enhanced Cav1.2 activity on myocyte excitation-contraction (E-C) coupling, cardiac contractility, and its regulation by the beta-adrenergic system are not clear. To recapitulate the increased Cav1.2 activity, a double transgenic (DTG) mouse model overexpressing the Cavbeta2a subunit in a cardiac-specific and inducible manner was established. We studied cardiac (in vivo) and myocyte (in vitro) contractility at baseline and upon beta-adrenergic stimulation. E-C coupling efficiency was evaluated in isolated myocytes as well. The following results were found: 1) in DTG myocytes, L-type Ca(2+) current (I(Ca,L)) density, myocyte fractional shortening (FS), peak Ca(2+) transients, and sarcoplasmic reticulum (SR) Ca(2+) content (caffeine-induced Ca(2+) transient peak) were significantly increased (by 100.8%, 48.8%, 49.8%, and 46.8%, respectively); and 2) cardiac contractility evaluated with echocardiography [ejection fraction (EF) and (FS)] and invasive intra-left ventricular pressure (maximum dP/dt and -dP/dt) measurements were significantly greater in DTG mice than in control mice. However, 1) the cardiac contractility (EF, FS, dP/dt, and -dP/dt)-enhancing effect of the beta-adrenergic agonist isoproterenol (2 microg/g body wt ip) was significantly reduced in DTG mice, which could be attributed to the loss of beta-adrenergic stimulation on contraction, Ca(2+) transients, I(Ca,L), and SR Ca(2+) content in DTG myocytes; and 2) E-C couplng efficiency was significantly lower in DTG myocytes. In conclusion, increasing Cav1.2 activity by promoting its high-activity mode enhances cardiac contractility but decreases E-C coupling efficiency and the adrenergic reserve of the heart.

Complex formation of p65/RelA with nuclear Akt1 for enhanced transcriptional activation of NF-κB

International Nuclear Information System (INIS)

Kwon, Osong; Kim, Kyung A; He, Long; Jung, Mira; Jeong, Sook Jung; Ahn, Jong Seog; Kim, Bo Yeon

2008-01-01

Akt1 was revealed to interact with Ki-Ras in the cytoplasm of Ki-Ras-transformed human prostate epithelial cells, 267B1/K-ras. Moreover, p65/RelA in the nucleus was found to interact with both Ki-Ras and Akt1, suggesting the nuclear translocation of Akt1:Ki-Ras complex for NF- κB activation. In support of this, compared with wild type Akt1, the dominant negative Akt1 mutant was decreased in its nuclear expression, reducing the Ki-Ras-induced NF-κB transcriptional activation. Moreover, inhibitors of Ras (sulindac sulfide and farnesyltransferase inhibitor I) or PI3K/Akt (wortmannin), reduced the amounts of Akt1 and Ki-Ras in the nucleus as well as partial NF-κB activity. The complete inhibition of Ki-Ras-induced NF-κB activation, however, could only be obtained by combined treatment with wortmannin and proteasome inhibitor-1. Accordingly, clonogenic assay showed Akt1 contribution to IκBα-mediated NF-κB activation for oncogenic cell growth by Ki-Ras. Our data suggest a crucial role of Ki-Ras:Akt1 complex in NF-κB transcriptional activation and enhancement of cell survival

Age-dependent regulation of ERF-VII transcription factor activity in Arabidopsis thaliana.

Science.gov (United States)

Giuntoli, Beatrice; Shukla, Vinay; Maggiorelli, Federica; Giorgi, Federico M; Lombardi, Lara; Perata, Pierdomenico; Licausi, Francesco

2017-10-01

The Group VII Ethylene Responsive Factors (ERFs-VII) RAP2.2 and RAP2.12 have been mainly characterized with regard to their contribution as activators of fermentation in plants. However, transcriptional changes measured in conditions that stabilize these transcription factors exceed the mere activation of this biochemical pathway, implying additional roles performed by the ERF-VIIs in other processes. We evaluated gene expression in transgenic Arabidopsis lines expressing a stabilized form of RAP2.12, or hampered in ERF-VII activity, and identified genes affected by this transcriptional regulator and its homologs, including some involved in oxidative stress response, which are not universally induced under anaerobic conditions. The contribution of the ERF-VIIs in regulating this set of genes in response to chemically induced or submergence-stimulated mitochondria malfunctioning was found to depend on the plant developmental stage. A similar age-dependent mechanism also restrained ERF-VII activity upon the core-hypoxic genes, independently of the N-end rule pathway, which is accounted for the control of the anaerobic response. To conclude, this study shed new light on a dual role of ERF-VII proteins under submergence: as positive regulators of the hypoxic response and as repressors of oxidative-stress related genes, depending on the developmental stage at which plants are challenged by stress conditions. © 2017 John Wiley & Sons Ltd.

Enhancement of the Electrocatalytic Activity of Gold Nanoparticles via Anodic Treatment and the Decrease of the Enhanced Activity with Aging

International Nuclear Information System (INIS)

Jo, Kyung Min; Kang, Hyun Ju; Yang, Hae Sik

2011-01-01

We have recently shown that the electrocatalytic activity of Au nanoparticles (AuNPs) can be enhanced via NaBH 4 treatment and cathodic treatment and that the enhanced activity slowly decreases with aging. We have also demonstrated that the electrocatalytic activity of the AuNPs freshly prepared by electrochemical or chemical reduction slowly decreases with aging in both air and solution. Likewise, the electrocatalytic activity of anodically treated Au electrodes or AuNPs might change with aging. Herein, we report that the electrocatalytic activity of long-aged AuNPs can be enhanced via anodic treatment and that the enhanced electrocatalytic activity decreases with aging in air. The change in the electrocatalytic activity of AuNPs was evaluated by comparing cyclic voltammograms for the electrooxi-dation of hydrogen peroxide (H 2 O 2 ) and formic acid

A meta-analysis of genome-wide association scans identifies IL18RAP, PTPN2, TAGAP, and PUS10 as shared risk loci for Crohn's disease and celiac disease.

Directory of Open Access Journals (Sweden)

Eleonora A M Festen

2011-01-01

Full Text Available Crohn's disease (CD and celiac disease (CelD are chronic intestinal inflammatory diseases, involving genetic and environmental factors in their pathogenesis. The two diseases can co-occur within families, and studies suggest that CelD patients have a higher risk to develop CD than the general population. These observations suggest that CD and CelD may share common genetic risk loci. Two such shared loci, IL18RAP and PTPN2, have already been identified independently in these two diseases. The aim of our study was to explicitly identify shared risk loci for these diseases by combining results from genome-wide association study (GWAS datasets of CD and CelD. Specifically, GWAS results from CelD (768 cases, 1,422 controls and CD (3,230 cases, 4,829 controls were combined in a meta-analysis. Nine independent regions had nominal association p-value <1.0 x 10⁻⁵ in this meta-analysis and showed evidence of association to the individual diseases in the original scans (p-value < 1 x 10⁻² in CelD and < 1 x 10⁻³ in CD. These include the two previously reported shared loci, IL18RAP and PTPN2, with p-values of 3.37 x 10⁻⁸ and 6.39 x 10⁻⁹, respectively, in the meta-analysis. The other seven had not been reported as shared loci and thus were tested in additional CelD (3,149 cases and 4,714 controls and CD (1,835 cases and 1,669 controls cohorts. Two of these loci, TAGAP and PUS10, showed significant evidence of replication (Bonferroni corrected p-values <0.0071 in the combined CelD and CD replication cohorts and were firmly established as shared risk loci of genome-wide significance, with overall combined p-values of 1.55 x 10⁻¹⁰ and 1.38 x 10⁻¹¹ respectively. Through a meta-analysis of GWAS data from CD and CelD, we have identified four shared risk loci: PTPN2, IL18RAP, TAGAP, and PUS10. The combined analysis of the two datasets provided the power, lacking in the individual GWAS for single diseases, to detect shared loci with a

Non-redundant roles of phosphoinositide 3-kinase isoforms alpha and beta in glycoprotein VI-induced platelet signaling and thrombus formation.

Science.gov (United States)

Gilio, Karen; Munnix, Imke C A; Mangin, Pierre; Cosemans, Judith M E M; Feijge, Marion A H; van der Meijden, Paola E J; Olieslagers, Servé; Chrzanowska-Wodnicka, Magdalena B; Lillian, Rivka; Schoenwaelder, Simone; Koyasu, Shigeo; Sage, Stewart O; Jackson, Shaun P; Heemskerk, Johan W M

2009-12-04

Platelets are activated by adhesion to vascular collagen via the immunoglobulin receptor, glycoprotein VI (GPVI). This causes potent signaling toward activation of phospholipase Cgamma2, which bears similarity to the signaling pathway evoked by T- and B-cell receptors. Phosphoinositide 3-kinase (PI3K) plays an important role in collagen-induced platelet activation, because this activity modulates the autocrine effects of secreted ADP. Here, we identified the PI3K isoforms directly downstream of GPVI in human and mouse platelets and determined their role in GPVI-dependent thrombus formation. The targeting of platelet PI3Kalpha or -beta strongly and selectively suppressed GPVI-induced Ca(2+) mobilization and inositol 1,4,5-triphosphate production, thus demonstrating enhancement of phospholipase Cgamma2 by PI3Kalpha/beta. That PI3Kalpha and -beta have a non-redundant function in GPVI-induced platelet activation and thrombus formation was concluded from measurements of: (i) serine phosphorylation of Akt, (ii) dense granule secretion, (iii) intracellular Ca(2+) increases and surface expression of phosphatidylserine under flow, and (iv) thrombus formation, under conditions where PI3Kalpha/beta was blocked or p85alpha was deficient. In contrast, GPVI-induced platelet activation was insensitive to inhibition or deficiency of PI3Kdelta or -gamma. Furthermore, PI3Kalpha/beta, but not PI3Kgamma, contributed to GPVI-induced Rap1b activation and, surprisingly, also to Rap1b-independent platelet activation via GPVI. Together, these findings demonstrate that both PI3Kalpha and -beta isoforms are required for full GPVI-dependent platelet Ca(2+) signaling and thrombus formation, partly independently of Rap1b. This provides a new mechanistic explanation for the anti-thrombotic effect of PI3K inhibition and makes PI3Kalpha an interesting new target for anti-platelet therapy.

Hydrogen sulfide potentiates interleukin-1β-induced nitric oxide production via enhancement of extracellular signal-regulated kinase activation in rat vascular smooth muscle cells

International Nuclear Information System (INIS)

Jeong, Sun-Oh; Pae, Hyun-Ock; Oh, Gi-Su; Jeong, Gil-Saeng; Lee, Bok-Soo; Lee, Seoul; Kim, Du Yong; Rhew, Hyun Yul; Lee, Kang-Min; Chung, Hun-Taeg

2006-01-01

Hydrogen sulfide (H 2 S) and nitric oxide (NO) are endogenously synthesized from L-cysteine and L-arginine, respectively. They might constitute a cooperative network to regulate their effects. In this study, we investigated whether H 2 S could affect NO production in rat vascular smooth muscle cells (VSMCs) stimulated with interleukin-1β (IL-1β). Although H 2 S by itself showed no effect on NO production, it augmented IL-β-induced NO production and this effect was associated with increased expression of inducible NO synthase (iNOS) and activation of nuclear factor (NF)-κB. IL-1β activated the extracellular signal-regulated kinase 1/2 (ERK1/2), and this activation was also enhanced by H 2 S. Inhibition of ERK1/2 activation by the selective inhibitor U0126 inhibited IL-1β-induced NF-κB activation, iNOS expression, and NO production either in the absence or presence of H 2 S. Our findings suggest that H 2 S enhances NO production and iNOS expression by potentiating IL-1β-induced NF-κB activation through a mechanism involving ERK1/2 signaling cascade in rat VSMCs

Enhancing eNOS activity with simultaneous inhibition of IKKβ restores vascular function in Ins2(Akita+/-) type-1 diabetic mice.

Science.gov (United States)

Krishnan, Manickam; Janardhanan, Preethi; Roman, Linda; Reddick, Robert L; Natarajan, Mohan; van Haperen, Rien; Habib, Samy L; de Crom, Rini; Mohan, Sumathy

2015-10-01

The balance of nitric oxide (NO) versus superoxide generation has a major role in the initiation and progression of endothelial dysfunction. Under conditions of high glucose, endothelial nitric oxide synthase (eNOS) functions as a chief source of superoxide rather than NO. In order to improve NO bioavailability within the vessel wall in type-1 diabetes, we investigated treatment strategies that improve eNOS phosphorylation and NO-dependent vasorelaxation. We evaluated methods to increase the eNOS activity by (1) feeding Ins2(Akita) spontaneously diabetic (type-1) mice with l-arginine in the presence of sepiapterin, a precursor of tetrahydrobiopterin; (2) preventing eNOS/NO deregulation by the inclusion of inhibitor kappa B kinase beta (IKKβ) inhibitor, salsalate, in the diet regimen in combination with l-arginine and sepiapterin; and (3) independently increasing eNOS expression to improve eNOS activity and associated NO production through generating Ins2(Akita) diabetic mice that overexpress human eNOS predominantly in vascular endothelial cells. Our results clearly demonstrated that diet supplementation with l-arginine, sepiapterin along with salsalate improved phosphorylation of eNOS and enhanced vasorelaxation of thoracic/abdominal aorta in type-1 diabetic mice. More interestingly, despite the overexpression of eNOS, the in-house generated transgenic eNOS-GFP (TgeNOS-GFP)-Ins2(Akita) cross mice showed an unanticipated effect of reduced eNOS phosphorylation and enhanced superoxide production. Our results demonstrate that enhancement of endogenous eNOS activity by nutritional modulation is more beneficial than increasing the endogenous expression of eNOS by gene therapy modalities.

Data base management activities for the Remedial Action Program at Oak Ridge National Laboratories (ORNL)

Energy Technology Data Exchange (ETDEWEB)

Hook, L.A.; Voorhees, L.D.; Gentry, M.J.; Faulkner, M.A.; Shaakir-Ali, J.A.; Newman, K.A.; McCord, R.A.; Goins, L.F.; Owen, P.T.

1990-07-01

The Oak Ridge National Laboratory (ORNL) Remedial Action Program (RAP) was established in 1985 in response to state and federal regulations requiring comprehensive control over facility discharges and cleanup of contaminated sites. A computerized Data and Information Management System (DIMS) was developed for RAP to (1) provide a centralized repository for data pertinent to RAP and (2) provide support for the investigations and assessments leading to the long-term remediation of contaminated facilities and sites. The current status of DIMS and its role in supporting RAP during 1989 are described. The DIMS consists of three components: (1) the Numeric Data Base, (2) the Bibliographic Data Base, and (3) the Records Control Data Base. This report addresses all three data bases, but focuses on the contents of the Numeric Data Base. Significant progress was made last year with the geographic information system (GIS) and ARC/INFO, which can be interfaced with SAS/GRAPH to provide combined mapping and statistical graphic products. Several thematic layers of GIS data for the Oak Ridge Reservation are now available. 18 refs., 8 figs., 19 tabs.

PAR-2 activation enhances weak acid-induced ATP release through TRPV1 and ASIC sensitization in human esophageal epithelial cells.

Science.gov (United States)

Wu, Liping; Oshima, Tadayuki; Shan, Jing; Sei, Hiroo; Tomita, Toshihiko; Ohda, Yoshio; Fukui, Hirokazu; Watari, Jiro; Miwa, Hiroto

2015-10-15

Esophageal visceral hypersensitivity has been proposed to be the pathogenesis of heartburn sensation in nonerosive reflux disease. Protease-activated receptor-2 (PAR-2) is expressed in human esophageal epithelial cells and is believed to play a role in inflammation and sensation. PAR-2 activation may modulate these responses through adenosine triphosphate (ATP) release, which is involved in transduction of sensation and pain. The transient receptor potential vanilloid receptor 1 (TRPV1) and acid-sensing ion channels (ASICs) are both acid-sensitive nociceptors. However, the interaction among these molecules and the mechanisms of heartburn sensation are still not clear. We therefore examined whether ATP release in human esophageal epithelial cells in response to acid is modulated by TRPV1 and ASICs and whether PAR-2 activation influences the sensitivity of TRPV1 and ASICs. Weak acid (pH 5) stimulated the release of ATP from primary human esophageal epithelial cells (HEECs). This effect was significantly reduced after pretreatment with 5-iodoresiniferatoxin (IRTX), a TRPV1-specific antagonist, or with amiloride, a nonselective ASIC blocker. TRPV1 and ASIC3 small interfering RNA (siRNA) transfection also decreased weak acid-induced ATP release. Pretreatment of HEECs with trypsin, tryptase, or a PAR-2 agonist enhanced weak acid-induced ATP release. Trypsin treatment led to the phosphorylation of TRPV1. Acid-induced ATP release enhancement by trypsin was partially blocked by IRTX, amiloride, or a PAR-2 antagonist. Conversely, acid-induced ATP release was augmented by PAR-2 activation through TRPV1 and ASICs. These findings suggested that the pathophysiology of heartburn sensation or esophageal hypersensitivity may be associated with the activation of PAR-2, TRPV1, and ASICs. Copyright © 2015 the American Physiological Society.

40 CFR 270.140 - What else must the Director prepare in addition to the draft RAP or notice of intent to deny?

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 26 2010-07-01 2010-07-01 false What else must the Director prepare in... the Director prepare in addition to the draft RAP or notice of intent to deny? Once the Director has... Regional office or published material that is generally available need not be physically included with the...

Structural basis for type VI secreted peptidoglycan dl-endopeptidase function, specificity and neutralization in Serratia marcescens

Energy Technology Data Exchange (ETDEWEB)

Srikannathasan, Velupillai; English, Grant [University of Dundee, Dundee DD1 5EH, Scotland (United Kingdom); Bui, Nhat Khai [Newcastle University, Newcastle upon Tyne NE2 4HH (United Kingdom); Trunk, Katharina; O’Rourke, Patrick E. F.; Rao, Vincenzo A. [University of Dundee, Dundee DD1 5EH, Scotland (United Kingdom); Vollmer, Waldemar [Newcastle University, Newcastle upon Tyne NE2 4HH (United Kingdom); Coulthurst, Sarah J., E-mail: s.j.coulthurst@dundee.ac.uk; Hunter, William N., E-mail: s.j.coulthurst@dundee.ac.uk [University of Dundee, Dundee DD1 5EH, Scotland (United Kingdom)

2013-12-01

Crystal structures of type VI secretion system-associated immunity proteins, a peptidoglycan endopeptidase and a complex of the endopeptidase and its cognate immunity protein are reported together with assays of endopeptidase activity and functional assessment. Some Gram-negative bacteria target their competitors by exploiting the type VI secretion system to extrude toxic effector proteins. To prevent self-harm, these bacteria also produce highly specific immunity proteins that neutralize these antagonistic effectors. Here, the peptidoglycan endopeptidase specificity of two type VI secretion-system-associated effectors from Serratia marcescens is characterized. These small secreted proteins, Ssp1 and Ssp2, cleave between γ-d-glutamic acid and l-meso-diaminopimelic acid with different specificities. Ssp2 degrades the acceptor part of cross-linked tetratetrapeptides. Ssp1 displays greater promiscuity and cleaves monomeric tripeptides, tetrapeptides and pentapeptides and dimeric tetratetra and tetrapenta muropeptides on both the acceptor and donor strands. Functional assays confirm the identity of a catalytic cysteine in these endopeptidases and crystal structures provide information on the structure–activity relationships of Ssp1 and, by comparison, of related effectors. Functional assays also reveal that neutralization of these effectors by their cognate immunity proteins, which are called resistance-associated proteins (Raps), contributes an essential role to cell fitness. The structures of two immunity proteins, Rap1a and Rap2a, responsible for the neutralization of Ssp1 and Ssp2-like endopeptidases, respectively, revealed two distinct folds, with that of Rap1a not having previously been observed. The structure of the Ssp1–Rap1a complex revealed a tightly bound heteromeric assembly with two effector molecules flanking a Rap1a dimer. A highly effective steric block of the Ssp1 active site forms the basis of effector neutralization. Comparisons with Ssp2–Rap2

Structural basis for type VI secreted peptidoglycan dl-endopeptidase function, specificity and neutralization in Serratia marcescens

International Nuclear Information System (INIS)

Srikannathasan, Velupillai; English, Grant; Bui, Nhat Khai; Trunk, Katharina; O’Rourke, Patrick E. F.; Rao, Vincenzo A.; Vollmer, Waldemar; Coulthurst, Sarah J.; Hunter, William N.

2013-01-01

Crystal structures of type VI secretion system-associated immunity proteins, a peptidoglycan endopeptidase and a complex of the endopeptidase and its cognate immunity protein are reported together with assays of endopeptidase activity and functional assessment. Some Gram-negative bacteria target their competitors by exploiting the type VI secretion system to extrude toxic effector proteins. To prevent self-harm, these bacteria also produce highly specific immunity proteins that neutralize these antagonistic effectors. Here, the peptidoglycan endopeptidase specificity of two type VI secretion-system-associated effectors from Serratia marcescens is characterized. These small secreted proteins, Ssp1 and Ssp2, cleave between γ-d-glutamic acid and l-meso-diaminopimelic acid with different specificities. Ssp2 degrades the acceptor part of cross-linked tetratetrapeptides. Ssp1 displays greater promiscuity and cleaves monomeric tripeptides, tetrapeptides and pentapeptides and dimeric tetratetra and tetrapenta muropeptides on both the acceptor and donor strands. Functional assays confirm the identity of a catalytic cysteine in these endopeptidases and crystal structures provide information on the structure–activity relationships of Ssp1 and, by comparison, of related effectors. Functional assays also reveal that neutralization of these effectors by their cognate immunity proteins, which are called resistance-associated proteins (Raps), contributes an essential role to cell fitness. The structures of two immunity proteins, Rap1a and Rap2a, responsible for the neutralization of Ssp1 and Ssp2-like endopeptidases, respectively, revealed two distinct folds, with that of Rap1a not having previously been observed. The structure of the Ssp1–Rap1a complex revealed a tightly bound heteromeric assembly with two effector molecules flanking a Rap1a dimer. A highly effective steric block of the Ssp1 active site forms the basis of effector neutralization. Comparisons with Ssp2–Rap2

Influence of WFIKKN1 on BMP1-mediated activation of latent myostatin.

Science.gov (United States)

Szláma, György; Vásárhelyi, Viktor; Trexler, Mária; Patthy, László

2016-12-01

The NTR domain of WFIKKN1 protein has been shown to have significant affinity for the prodomain regions of promyostatin and latent myostatin but the biological significance of these interactions remained unclear. In view of its role as a myostatin antagonist, we tested the assumption that WFIKKN1 inhibits the release of myostatin from promyostatin and/or latent myostatin. WFIKKN1 was found to have no effect on processing of promyostatin by furin, the rate of cleavage of latent myostatin by BMP1, however, was significantly enhanced in the presence of WFIKKN1 and this enhancer activity was superstimulated by heparin. Unexpectedly, WFIKKN1 was also cleaved by BMP1 and our studies have shown that the KKN1 fragment generated by BMP1-cleavage of WFIKKN1 contributes most significantly to the observed enhancer activity. Analysis of a pro-TGF-β -based homology model of homodimeric latent myostatin revealed that the BMP1-cleavage sites are buried and not readily accessible to BMP1. In view of this observation, the most plausible explanation for the BMP1-enhancer activity of the KKN1 fragment is that it shifts a conformational equilibrium of latent myostatin from the closed circular structure of the homodimer to a more open form, making the cleavage sites more accessible to BMP1. On the other hand, the observation that the enhancer activity of KKN1 is superstimulated in the presence of heparin is explained by the fact KKN1, latent myostatin, and BMP1 have affinity for heparin and these interactions with heparin increase the local concentrations of the reactants thereby facilitating the action of BMP1. Furin: EC 3.4.21.75; BMP1, bone morphogentic protein 1 or procollagen C-endopeptidase: EC 3.4.24.19. © 2016 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Method for enhancing amidohydrolase activity of fatty acid amide hydrolase

Science.gov (United States)

John, George; Nagarajan, Subbiah; Chapman, Kent; Faure, Lionel; Koulen, Peter

2016-10-25

A method for enhancing amidohydrolase activity of Fatty Acid Amide Hydrolase (FAAH) is disclosed. The method comprising administering a phenoxyacylethanolamide that causes the enhanced activity. The enhanced activity can have numerous effects on biological organisms including, for example, enhancing the growth of certain seedlings. The subject matter disclosed herein relates to enhancers of amidohydrolase activity.

RAP-3A Computer code for thermal and hydraulic calculations in steady state conditions for fuel element clusters

International Nuclear Information System (INIS)

Popescu, C.; Biro, L.; Iftode, I.; Turcu, I.

1975-10-01

The RAP-3A computer code is designed for calculating the main steady state thermo-hydraulic parameters of multirod fuel clusters with liquid metal cooling. The programme provides a double accuracy computation of temperatures and axial enthalpy distributions of pressure losses and axial heat flux distributions in fuel clusters before boiling conditions occur. Physical and mathematical models as well as a sample problem are presented. The code is written in FORTRAN-4 language and is running on a IBM-370/135 computer

Intragenic HIV-1 env sequences that enhance gag expression

International Nuclear Information System (INIS)

Suptawiwat, Ornpreya; Sutthent, Ruengpung; Lee, T.-H.; Auewarakul, Prasert

2003-01-01

Expression of HIV-1 genes is regulated at multiple levels including the complex RNA splicing and transport mechanisms. Multiple cis-acting elements involved in these regulations have been previously identified in various regions of HIV-1 genome. Here we show that another cis-acting element was present in HIV-1 env region. This element enhanced the expression of Gag when inserted together with Rev response element (RRE) into a truncated HIV-1 genome in the presence of Rev. The enhancing activity was mapped to a 263-bp fragment in the gp41 region downstream to RRE. RNA analysis showed that it might function by promoting RNA stability and Rev-dependent RNA export. The enhancement was specific to Rev-dependent expression, since it did not enhance Gag expression driven by Sam68, a cellular protein that has been shown to be able to substitute for Rev in RNA export function

The Nucleosome Assembly Activity of NAP1 Is Enhanced by Alien▿

OpenAIRE

Eckey, Maren; Hong, Wei; Papaioannou, Maria; Baniahmad, Aria

2007-01-01

The assembly of nucleosomes into chromatin is essential for the compaction of DNA and inactivation of the DNA template to modulate and repress gene expression. The nucleosome assembly protein 1, NAP1, assembles nucleosomes independent of DNA synthesis and was shown to enhance coactivator-mediated gene expression, suggesting a role for NAP1 in transcriptional regulation. Here, we show that Alien, known to harbor characteristics of a corepressor of nuclear hormone receptors such as of the vitam...

Chronic alcohol consumption enhances iNKT cell maturation and activation

Energy Technology Data Exchange (ETDEWEB)

Zhang, Hui, E-mail: hzhang@wsu.edu; Zhang, Faya; Zhu, Zhaohui; Luong, Dung; Meadows, Gary G.

2015-01-15

Alcohol consumption exhibits diverse effects on different types of immune cells. NKT cells are a unique T cell population and play important immunoregulatory roles in different types of immune responses. The effects of chronic alcohol consumption on NKT cells remain to be elucidated. Using a mouse model of chronic alcohol consumption, we found that alcohol increases the percentage of NKT cells, especially iNKT cells in the thymus and liver, but not in the spleen or blood. Alcohol consumption decreases the percentage of NK1.1{sup −} iNKT cells in the total iNKT cell population in all of the tissues and organs examined. In the thymus, alcohol consumption increases the number of NK1.1{sup +}CD44{sup hi} mature iNKT cells but does not alter the number of NK1.1{sup −} immature iNKT cells. A BrdU incorporation assay shows that alcohol consumption increases the proliferation of thymic NK1.1{sup −} iNKT cells, especially the NK1.1{sup −}CD44{sup lo} Stage I iNKT cells. The percentage of NKG2A{sup +} iNKT cells increases in all of the tissues and organs examined; whereas CXCR3{sup +} iNKT cells only increases in the thymus of alcohol-consuming mice. Chronic alcohol consumption increases the percentage of IFN-γ-producing iNKT cells and increases the blood concentration of IFN-γ and IL-12 after in vivo α-galactosylceramide (αGalCer) stimulation. Consistent with the increased cytokine production, the in vivo activation of iNKT cells also enhances the activation of dendritic cells (DC) and NK, B, and T cells in the alcohol-consuming mice. Taken together the data indicate that chronic alcohol consumption enhances iNKT cell maturation and activation, which favors the Th1 immune response. - Highlights: • Chronic alcohol consumption increases iNKT cells in the thymus and liver • Chronic alcohol consumption enhances thymic Stage I iNKT cell proliferation • Chronic alcohol consumption enhances iNKT cell maturation in thymus and periphery • Chronic alcohol

Chronic alcohol consumption enhances iNKT cell maturation and activation

International Nuclear Information System (INIS)

Zhang, Hui; Zhang, Faya; Zhu, Zhaohui; Luong, Dung; Meadows, Gary G.

2015-01-01

Alcohol consumption exhibits diverse effects on different types of immune cells. NKT cells are a unique T cell population and play important immunoregulatory roles in different types of immune responses. The effects of chronic alcohol consumption on NKT cells remain to be elucidated. Using a mouse model of chronic alcohol consumption, we found that alcohol increases the percentage of NKT cells, especially iNKT cells in the thymus and liver, but not in the spleen or blood. Alcohol consumption decreases the percentage of NK1.1 − iNKT cells in the total iNKT cell population in all of the tissues and organs examined. In the thymus, alcohol consumption increases the number of NK1.1 + CD44 hi mature iNKT cells but does not alter the number of NK1.1 − immature iNKT cells. A BrdU incorporation assay shows that alcohol consumption increases the proliferation of thymic NK1.1 − iNKT cells, especially the NK1.1 − CD44 lo Stage I iNKT cells. The percentage of NKG2A + iNKT cells increases in all of the tissues and organs examined; whereas CXCR3 + iNKT cells only increases in the thymus of alcohol-consuming mice. Chronic alcohol consumption increases the percentage of IFN-γ-producing iNKT cells and increases the blood concentration of IFN-γ and IL-12 after in vivo α-galactosylceramide (αGalCer) stimulation. Consistent with the increased cytokine production, the in vivo activation of iNKT cells also enhances the activation of dendritic cells (DC) and NK, B, and T cells in the alcohol-consuming mice. Taken together the data indicate that chronic alcohol consumption enhances iNKT cell maturation and activation, which favors the Th1 immune response. - Highlights: • Chronic alcohol consumption increases iNKT cells in the thymus and liver • Chronic alcohol consumption enhances thymic Stage I iNKT cell proliferation • Chronic alcohol consumption enhances iNKT cell maturation in thymus and periphery • Chronic alcohol consumption induces Th1 immune response upon i

Loss of p53 enhances the function of the endoplasmic reticulum through activation of the IRE1α/XBP1 pathway

Science.gov (United States)

Kodama, Rika; Byun, Sanguine; Yoon, Kyoung Wan; Hiraki, Masatsugu; Mandinova, Anna; Lee, Sam W.

2015-01-01

Altered regulation of ER stress response has been implicated in a variety of human diseases, such as cancer and metabolic diseases. Excessive ER function contributes to malignant phenotypes, such as chemoresistance and metastasis. Here we report that the tumor suppressor p53 regulates ER function in response to stress. We found that loss of p53 function activates the IRE1α/XBP1 pathway to enhance protein folding and secretion through upregulation of IRE1α and subsequent activation of its target XBP1. We also show that wild-type p53 interacts with synoviolin (SYVN1)/HRD1/DER3, a transmembrane E3 ubiquitin ligase localized to ER during ER stress and removes unfolded proteins by reversing transport to the cytosol from the ER, and its interaction stimulates IRE1α degradation. Moreover, IRE1α inhibitor suppressed protein secretion, induced cell death in p53-deficient cells, and strongly suppressed the formation of tumors by p53-deficient human tumor cells in vivo compared with those that expressed wild-type p53. Therefore, our data imply that the IRE1α/XBP1 pathway serves as a target for therapy of chemoresistant tumors that express mutant p53. PMID:26254280

Estrogen increases smooth muscle expression of alpha2C-adrenoceptors and cold-induced constriction of cutaneous arteries.

Science.gov (United States)

Eid, A H; Maiti, K; Mitra, S; Chotani, M A; Flavahan, S; Bailey, S R; Thompson-Torgerson, C S; Flavahan, N A

2007-09-01

Raynaud's phenomenon, which is characterized by intense cold-induced constriction of cutaneous arteries, is more common in women compared with men. Cold-induced constriction is mediated in part by enhanced activity of alpha(2C)-adrenoceptors (alpha(2C)-ARs) located on vascular smooth muscle cells (VSMs). Experiments were therefore performed to determine whether 17beta-estradiol regulates alpha(2C)-AR expression and function in cutaneous VSMs. 17beta-Estradiol (0.01-10 nmol/l) increased expression of the alpha(2C)-AR protein and the activity of the alpha(2C)-AR gene promoter in human cultured dermal VSMs, which was assessed following transient transfection of the cells with a promoter-reporter construct. The effect of 17beta-estradiol was associated with increased accumulation of cAMP and activation of the cAMP-responsive Rap2 GTP-binding protein. Transient transfection of VSMs with a dominant-negative mutant of Rap2 inhibited the 17beta-estradiol-induced activation of the alpha(2C)-AR gene promoter, whereas a constitutively active mutant of Rap2 increased alpha(2C)-AR promoter activity. The effects of 17beta-estradiol were inhibited by the estrogen receptor (ER) antagonist, ICI-182780 (1 micromol/l), and were mimicked by a cell-impermeable form of the hormone (estrogen:BSA) or by the selective ER-alpha receptor agonist 4,4',4'''-(4-propyl-[(1)H]-pyrazole-1,3,5-triyl)tris-phenol (PPT; 10 nmol/l) or the selective ER-beta receptor agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN; 10 nmol/l). Therefore, 17beta-estradiol increased expression of alpha(2C)-ARs by interacting with cell surface receptors to cause a cAMP/Rap2-dependent increase in alpha(2C)-AR transcription. In mouse tail arteries, 17beta-estradiol (10 nmol/l) increased alpha(2C)-AR expression and selectively increased the cold-induced amplification of alpha(2)-AR constriction, which is mediated by alpha(2C)-ARs. An estrogen-dependent increase in expression of cold-sensitive alpha(2C)-ARs may contribute

PKA and Epac cooperate to augment bradykinin-induced interleukin-8 release from human airway smooth muscle cells

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Halayko Andrew J

2009-09-01

Full Text Available Abstract Background Airway smooth muscle contributes to the pathogenesis of pulmonary diseases by secreting inflammatory mediators such as interleukin-8 (IL-8. IL-8 production is in part regulated via activation of Gq-and Gs-coupled receptors. Here we study the role of the cyclic AMP (cAMP effectors protein kinase A (PKA and exchange proteins directly activated by cAMP (Epac1 and Epac2 in the bradykinin-induced IL-8 release from a human airway smooth muscle cell line and the underlying molecular mechanisms of this response. Methods IL-8 release was assessed via ELISA under basal condition and after stimulation with bradykinin alone or in combination with fenoterol, the Epac activators 8-pCPT-2'-O-Me-cAMP and Sp-8-pCPT-2'-O-Me-cAMPS, the PKA activator 6-Bnz-cAMP and the cGMP analog 8-pCPT-2'-O-Me-cGMP. Where indicated, cells were pre-incubated with the pharmacological inhibitors Clostridium difficile toxin B-1470 (GTPases, U0126 (extracellular signal-regulated kinases ERK1/2 and Rp-8-CPT-cAMPS (PKA. The specificity of the cyclic nucleotide analogs was confirmed by measuring phosphorylation of the PKA substrate vasodilator-stimulated phosphoprotein. GTP-loading of Rap1 and Rap2 was evaluated via pull-down technique. Expression of Rap1, Rap2, Epac1 and Epac2 was assessed via western blot. Downregulation of Epac protein expression was achieved by siRNA. Unpaired or paired two-tailed Student's t test was used. Results The β2-agonist fenoterol augmented release of IL-8 by bradykinin. The PKA activator 6-Bnz-cAMP and the Epac activator 8-pCPT-2'-O-Me-cAMP significantly increased bradykinin-induced IL-8 release. The hydrolysis-resistant Epac activator Sp-8-pCPT-2'-O-Me-cAMPS mimicked the effects of 8-pCPT-2'-O-Me-cAMP, whereas the negative control 8-pCPT-2'-O-Me-cGMP did not. Fenoterol, forskolin and 6-Bnz-cAMP induced VASP phosphorylation, which was diminished by the PKA inhibitor Rp-8-CPT-cAMPS. 6-Bnz-cAMP and 8-pCPT-2'-O-Me-cAMP induced GTP

Phagocytosis of haemozoin (malarial pigment enhances metalloproteinase-9 activity in human adherent monocytes: Role of IL-1beta and 15-HETE

Directory of Open Access Journals (Sweden)

Giribaldi Giuliana

2008-08-01

Full Text Available Abstract Background It has been shown previously that human monocytes fed with haemozoin (HZ or trophozoite-parasitized RBCs displayed increased matrix metalloproteinase-9 (MMP-9 enzyme activity and protein/mRNA expression and increased TNF production, and showed higher matrix invasion ability. The present study utilized the same experimental model to analyse the effect of phagocytosis of: HZ, delipidized HZ, beta-haematin (lipid-free synthetic HZ and trophozoites on production of IL-1beta and MMP-9 activity and expression. The second aim was to find out which component of HZ was responsible for the effects. Methods Native HZ freshly isolated from Plasmodium falciparum (Palo Alto strain, Mycoplasma-free, delipidized HZ, beta-haematin (lipid-free synthetic HZ, trophozoites and control meals such as opsonized non-parasitized RBCs and inert latex particles, were fed to human monocytes. The production of IL-1beta by differently fed monocytes, in presence or absence of specific MMP-9 inhibitor or anti-hIL-1beta antibodies, was quantified in supernatants by ELISA. Expression of IL-1beta was analysed by quantitative real-time RT-PCR. MMP-9 activity and protein expression were quantified by gelatin zymography and Western blotting. Results Monocytes fed with HZ or trophozoite-parasitized RBCs generated increased amounts of IL-1beta and enhanced enzyme activity (in cell supernatants and protein/mRNA expression (in cell lysates of monocyte MMP-9. The latter appears to be causally related to enhanced IL-1beta production, as enhancement of both expression and enzyme activity were abrogated by anti-hIL-1beta Abs. Upregulation of IL-1beta and MMP-9 were absent in monocytes fed with beta-haematin or delipidized HZ, indicating a role for HZ-attached or HZ-generated lipid components. 15-HETE (15(S,R-hydroxy-6,8,11,13-eicosatetraenoic acid a potent lipoperoxidation derivative generated by HZ from arachidonic acid via haem-catalysis was identified as one mediator

Rivaroxaban in antiphospholipid syndrome (RAPS) protocol: a prospective, randomized controlled phase II/III clinical trial of rivaroxaban versus warfarin in patients with thrombotic antiphospholipid syndrome, with or without SLE.

Science.gov (United States)

Cohen, H; Doré, C J; Clawson, S; Hunt, B J; Isenberg, D; Khamashta, M; Muirhead, N

2015-09-01

The current mainstay of the treatment of thrombotic antiphospholipid syndrome (APS) is long-term anticoagulation with vitamin K antagonists (VKAs) such as warfarin. Non-VKA oral anticoagulants (NOACs), which include rivaroxaban, have been shown to be effective and safe compared with warfarin for the treatment of venous thromboembolism (VTE) in major phase III prospective, randomized controlled trials (RCTs), but the results may not be directly generalizable to patients with APS. The primary aim is to demonstrate, in patients with APS and previous VTE, with or without systemic lupus erythematosus (SLE), that the intensity of anticoagulation achieved with rivaroxaban is not inferior to that of warfarin. Secondary aims are to compare rates of recurrent thrombosis, bleeding and the quality of life in patients on rivaroxaban with those on warfarin. Rivaroxaban in antiphospholipid syndrome (RAPS) is a phase II/III prospective non-inferiority RCT in which eligible patients with APS, with or without SLE, who are on warfarin, target international normalized ratio (INR) 2.5 for previous VTE, will be randomized either to continue warfarin (standard of care) or to switch to rivaroxaban. Intensity of anticoagulation will be assessed using thrombin generation (TG) testing, with the primary outcome the percentage change in endogenous thrombin potential (ETP) from randomization to day 42. Other TG parameters, markers of in vivo coagulation activation, prothrombin fragment 1.2, thrombin antithrombin complex and D-dimer, will also be assessed. If RAPS demonstrates i) that the anticoagulant effect of rivaroxaban is not inferior to that of warfarin and ii) the absence of any adverse effects that cause concern with regard to the use of rivaroxaban, this would provide sufficient supporting evidence to make rivaroxaban a standard of care for the treatment of APS patients with previous VTE, requiring a target INR of 2.5. © The Author(s) 2015.

Enhanced Effector Function of CD8+ T Cells From Healthy Controls and HIV-Infected Patients Occurs Through Thrombin Activation of Protease-Activated Receptor 1

Science.gov (United States)

Hurley, Amanda; Smith, Mindy; Karpova, Tatiana; Hasley, Rebecca B.; Belkina, Natalya; Shaw, Stephen; Balenga, Nariman; Druey, Kirk M.; Nickel, Erin; Packard, Beverly; Imamichi, Hiromi; Hu, Zonghui; Follmann, Dean; McNally, James; Higgins, Jeanette; Sneller, Michael; Lane, H. Clifford; Catalfamo, Marta

2013-01-01

Disruption of vascular integrity by trauma and other tissue insults leads to inflammation and activation of the coagulation cascade. The serine protease thrombin links these 2 processes. The proinflammatory function of thrombin is mediated by activation of protease-activated receptor 1 (PAR-1). We found that peripheral blood effector memory CD4+ and CD8+ T lymphocytes expressed PAR-1 and that expression was increased in CD8+ T cells from human immunodeficiency virus (HIV)–infected patients. Thrombin enhanced cytokine secretion in CD8+ T cells from healthy controls and HIV-infected patients. In addition, thrombin induced chemokinesis, but not chemotaxis, of CD8+ T cells, which led to structural changes, including cell polarization and formation of a structure rich in F-actin and phosphorylated ezrin-radexin-moesin proteins. These findings suggest that thrombin mediates cross-talk between the coagulation system and the adaptive immune system at sites of vascular injury through increased T-cell motility and production of proinflammatory cytokines. PMID:23204166

Enhanced effector function of CD8(+) T cells from healthy controls and HIV-infected patients occurs through thrombin activation of protease-activated receptor 1.

Science.gov (United States)

Hurley, Amanda; Smith, Mindy; Karpova, Tatiana; Hasley, Rebecca B; Belkina, Natalya; Shaw, Stephen; Balenga, Nariman; Druey, Kirk M; Nickel, Erin; Packard, Beverly; Imamichi, Hiromi; Hu, Zonghui; Follmann, Dean; McNally, James; Higgins, Jeanette; Sneller, Michael; Lane, H Clifford; Catalfamo, Marta

2013-02-15

Disruption of vascular integrity by trauma and other tissue insults leads to inflammation and activation of the coagulation cascade. The serine protease thrombin links these 2 processes. The proinflammatory function of thrombin is mediated by activation of protease-activated receptor 1 (PAR-1). We found that peripheral blood effector memory CD4(+) and CD8(+) T lymphocytes expressed PAR-1 and that expression was increased in CD8(+) T cells from human immunodeficiency virus (HIV)-infected patients. Thrombin enhanced cytokine secretion in CD8(+) T cells from healthy controls and HIV-infected patients. In addition, thrombin induced chemokinesis, but not chemotaxis, of CD8(+) T cells, which led to structural changes, including cell polarization and formation of a structure rich in F-actin and phosphorylated ezrin-radexin-moesin proteins. These findings suggest that thrombin mediates cross-talk between the coagulation system and the adaptive immune system at sites of vascular injury through increased T-cell motility and production of proinflammatory cytokines.

Cyclophilin B enhances HIV-1 infection

Energy Technology Data Exchange (ETDEWEB)

DeBoer, Jason; Madson, Christian J. [Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE (United States); Belshan, Michael, E-mail: michaelbelshan@creighton.edu [Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE (United States); The Nebraska Center for Virology, University of Nebraska, Lincoln, NE (United States)

2016-02-15

Cyclophilin B (CypB) is a member of the immunophilin family and intracellular chaperone. It predominantly localizes to the ER, but also contains a nuclear localization signal and is secreted from cells. CypB has been shown to interact with the Gag protein of human immunodeficiency type 1 (HIV-1). Several proteomic and genetic studies identified it as a potential factor involved in HIV replication. Herein, we show that over-expression of CypB enhances HIV infection by increasing nuclear import of viral DNA. This enhancement was unaffected by cyclosporine treatment and requires the N-terminus of the protein. The N-terminus contains an ER leader sequence, putative nuclear localization signal, and is required for secretion. Deletion of the N-terminus resulted in mislocalization from the ER and suppression of HIV infection. Passive transfer experiments showed that secreted CypB did not impact HIV infection. Combined, these experiments show that intracellular CypB modulates a pathway of HIV nuclear import. - Highlights: • CypB has been identified in several proteomic studies of HIV-1 infection. • CypB expression is upregulated in activated and infected T-cells. • Over-expression of CypB enhances HIV nuclear import and infection. • The N-terminus of CypB is necessary for these effects.

Cyclophilin B enhances HIV-1 infection

International Nuclear Information System (INIS)

DeBoer, Jason; Madson, Christian J.; Belshan, Michael

2016-01-01

Cyclophilin B (CypB) is a member of the immunophilin family and intracellular chaperone. It predominantly localizes to the ER, but also contains a nuclear localization signal and is secreted from cells. CypB has been shown to interact with the Gag protein of human immunodeficiency type 1 (HIV-1). Several proteomic and genetic studies identified it as a potential factor involved in HIV replication. Herein, we show that over-expression of CypB enhances HIV infection by increasing nuclear import of viral DNA. This enhancement was unaffected by cyclosporine treatment and requires the N-terminus of the protein. The N-terminus contains an ER leader sequence, putative nuclear localization signal, and is required for secretion. Deletion of the N-terminus resulted in mislocalization from the ER and suppression of HIV infection. Passive transfer experiments showed that secreted CypB did not impact HIV infection. Combined, these experiments show that intracellular CypB modulates a pathway of HIV nuclear import. - Highlights: • CypB has been identified in several proteomic studies of HIV-1 infection. • CypB expression is upregulated in activated and infected T-cells. • Over-expression of CypB enhances HIV nuclear import and infection. • The N-terminus of CypB is necessary for these effects.

Differentiation and fiber type-specific activity of a muscle creatine kinase intronic enhancer

Directory of Open Access Journals (Sweden)

Tai Phillip WL

2011-07-01

Full Text Available Abstract Background Hundreds of genes, including muscle creatine kinase (MCK, are differentially expressed in fast- and slow-twitch muscle fibers, but the fiber type-specific regulatory mechanisms are not well understood. Results Modulatory region 1 (MR1 is a 1-kb regulatory region within MCK intron 1 that is highly active in terminally differentiating skeletal myocytes in vitro. A MCK small intronic enhancer (MCK-SIE containing a paired E-box/myocyte enhancer factor 2 (MEF2 regulatory motif resides within MR1. The SIE's transcriptional activity equals that of the extensively characterized 206-bp MCK 5'-enhancer, but the MCK-SIE is flanked by regions that can repress its activity via the individual and combined effects of about 15 different but highly conserved 9- to 24-bp sequences. ChIP and ChIP-Seq analyses indicate that the SIE and the MCK 5'-enhancer are occupied by MyoD, myogenin and MEF2. Many other E-boxes located within or immediately adjacent to intron 1 are not occupied by MyoD or myogenin. Transgenic analysis of a 6.5-kb MCK genomic fragment containing the 5'-enhancer and proximal promoter plus the 3.2-kb intron 1, with and without MR1, indicates that MR1 is critical for MCK expression in slow- and intermediate-twitch muscle fibers (types I and IIa, respectively, but is not required for expression in fast-twitch muscle fibers (types IIb and IId. Conclusions In this study, we discovered that MR1 is critical for MCK expression in slow- and intermediate-twitch muscle fibers and that MR1's positive transcriptional activity depends on a paired E-box MEF2 site motif within a SIE. This is the first study to delineate the DNA controls for MCK expression in different skeletal muscle fiber types.

Alterations in HIV-1 LTR promoter activity during AIDS progression

International Nuclear Information System (INIS)

Hiebenthal-Millow, Kirsten; Greenough, Thomas C.; Bretttler, Doreen B.; Schindler, Michael; Wildum, Steffen; Sullivan, John L.; Kirchhoff, Frank

2003-01-01

HIV-1 variants evolving in AIDS patients frequently show increased replicative capacity compared to those present during early asymptomatic infection. It is known that late stage HIV-1 variants often show an expanded coreceptor tropism and altered Nef function. In the present study we investigated whether enhanced HIV-1 LTR promoter activity might also evolve during disease progression. Our results demonstrate increased LTR promoter activity after AIDS progression in 3 of 12 HIV-1-infected individuals studied. Further analysis revealed that multiple alterations in the U3 core-enhancer and in the transactivation-response (TAR) region seem to be responsible for the enhanced functional activity. Our findings show that in a subset of HIV-1-infected individuals enhanced LTR transcription contributes to the increased replicative potential of late stage virus isolates and might accelerate disease progression

Method for enhancing amidohydrolase activity of fatty acid amide hydrolase

Science.gov (United States)

John, George; Nagarajan, Subbiah; Chapman, Kent; Faure, Lionel; Koulen, Peter

2017-12-26

A method for enhancing amidohydrolase activity of Fatty Acid Amide Hydrolase (FAAH) is disclosed. The method comprising administering a phenoxyacyl-ethanolamide that causes the enhanced activity. The enhanced activity can have numerous effects on biological organisms including, for example, enhancing the growth of certain seedlings.

Differential roles of the infralimbic and prelimbic areas of the prefrontal cortex in reconsolidation of a traumatic memory.

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Levin, Natali; Kritman, Milly; Maroun, Mouna; Akirav, Irit

2017-09-01

Studies about reconsolidation of conditioned fear memories have shown that pharmacological manipulation at memory reactivation can attenuate or enhance the subsequent expression of the conditioned fear response. Here we examined the effects of a single injection of the mTOR inhibitor rapamycin (Rap) into the infralimbic (IL) and prelimbic (PL) areas [which compose the ventromedial prefrontal cortex (PFC)] on reconsolidation and extinction of a traumatic fear memory. We found opposite effects of Rap infused into the PL and IL on reconsolidation and extinction: intra-PL Rap and systemic Rap impaired reconsolidation and facilitated extinction whereas intra-IL Rap enhanced reconsolidation and impaired extinction. These effects persisted at least 10 days after reactivation. Shock exposure induced anxiety-like behavior and impaired working memory and intra-IL and -PL Rap normalized these effects. Finally, when measured after fear retrieval, shocked rats exhibited reduced and increased phosphorylated p70s6K levels in the IL and basolateral amygdala, respectively. No effect on phosphorylated p70s6K levels was observed in the PL. The study points to the differential roles of the IL and PL in memory reconsolidation and extinction. Moreover, inhibiting mTOR via rapamycin following reactivation of a fear memory may be a novel approach in attenuating enhanced fear memories. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

Activation of the complement cascade enhances motility of leukemic cells by downregulating expression of HO-1.

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Abdelbaset-Ismail, A; Borkowska-Rzeszotek, S; Kubis, E; Bujko, K; Brzeźniakiewicz-Janus, K; Bolkun, L; Kloczko, J; Moniuszko, M; Basak, G W; Wiktor-Jedrzejczak, W; Ratajczak, M Z

2017-02-01

As a crucial arm of innate immunity, the complement cascade (ComC) is involved both in mobilization of normal hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM) into peripheral blood and in their homing to BM. Despite the fact that ComC cleavage fragments alone do not chemoattract normal HSPCs, we found that leukemia cell lines as well as clonogenic blasts from chronic myeloid leukemia and acute myeloid leukemia patients respond robustly to C3 and C5 cleavage fragments by chemotaxis and increased adhesion. This finding was supported by the detection of C3a and C5a receptors in cells from human malignant hematopoietic cell lines and patient blasts at the mRNA (reverse transcriptase-polymerase chain reaction) and protein level (fluorescence-activated cell sorting), and by the demonstration that these receptors respond to stimulation by C3a and C5a by phosphorylation of p42/44 and p38 mitogen-activated protein kinases (MAPK), and protein kinase B (PKB/AKT). We also found that inducible heme oxygenase 1 (HO-1) is a negative regulator of ComC-mediated trafficking of leukemic cells, and that stimulation of leukemic cells by C3 or C5 cleavage fragments activates p38 MAPK, which downregulates HO-1 expression, rendering cells more mobile. We conclude that activation of the ComC in leukemia/lymphoma patients (for example, as a result of accompanying infections) enhances the motility of malignant cells and contributes to their spread in a p38 MAPK-HO-1-dependent manner. Therefore, inhibition of p38 MAPK or upregulation of HO-1 by small-molecule modulators would have a beneficial effect on ameliorating cell migration-mediated expansion of leukemia/lymphoma cells when the ComC becomes activated.

Activation of the complement cascade enhances motility of leukemic cells by downregulating expression of HO-1

Science.gov (United States)

Abdelbaset-Ismail, A; Borkowska-Rzeszotek, S; Kubis, E; Bujko, K; Brzeźniakiewicz-Janus, K; Bolkun, L; Kloczko, J; Moniuszko, M; Basak, G W; Wiktor-Jedrzejczak, W; Ratajczak, M Z

2017-01-01

As a crucial arm of innate immunity, the complement cascade (ComC) is involved both in mobilization of normal hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM) into peripheral blood and in their homing to BM. Despite the fact that ComC cleavage fragments alone do not chemoattract normal HSPCs, we found that leukemia cell lines as well as clonogenic blasts from chronic myeloid leukemia and acute myeloid leukemia patients respond robustly to C3 and C5 cleavage fragments by chemotaxis and increased adhesion. This finding was supported by the detection of C3a and C5a receptors in cells from human malignant hematopoietic cell lines and patient blasts at the mRNA (reverse transcriptase-polymerase chain reaction) and protein level (fluorescence-activated cell sorting), and by the demonstration that these receptors respond to stimulation by C3a and C5a by phosphorylation of p42/44 and p38 mitogen-activated protein kinases (MAPK), and protein kinase B (PKB/AKT). We also found that inducible heme oxygenase 1 (HO-1) is a negative regulator of ComC-mediated trafficking of leukemic cells, and that stimulation of leukemic cells by C3 or C5 cleavage fragments activates p38 MAPK, which downregulates HO-1 expression, rendering cells more mobile. We conclude that activation of the ComC in leukemia/lymphoma patients (for example, as a result of accompanying infections) enhances the motility of malignant cells and contributes to their spread in a p38 MAPK–HO-1-dependent manner. Therefore, inhibition of p38 MAPK or upregulation of HO-1 by small-molecule modulators would have a beneficial effect on ameliorating cell migration-mediated expansion of leukemia/lymphoma cells when the ComC becomes activated. PMID:27451975

Mechanisms of morphine enhancement of spontaneous seizure activity.

Science.gov (United States)

Saboory, Ehsan; Derchansky, Miron; Ismaili, Mohammed; Jahromi, Shokrollah S; Brull, Richard; Carlen, Peter L; El Beheiry, Hossam

2007-12-01

High-dose opioid therapy can precipitate seizures; however, the mechanism of such a dangerous adverse effect remains poorly understood. The aim of our study was to determine whether the neuroexcitatory activity of high-dose morphine is mediated by selective stimulation of opioid receptors. Mice hippocampi were resected intact and bathed in low magnesium artificial cerebrospinal fluid to induce spontaneous seizure-like events recorded from CA1 neurons. Application of morphine had a biphasic effect on the recorded spontaneous seizure-like events. In a low concentration (10 microM), morphine depressed electrographic seizure activity. Higher morphine concentrations (30 and 100 microM) enhanced seizure activity in an apparent dose-dependent manner. Naloxone, a nonselective opiate antagonist blocked the proconvulsant action of morphine. Selective mu and kappa opiate receptor agonists and antagonists enhanced and suppressed the spontaneous seizure activity, respectively. On the contrary, delta opioid receptor ligands did not have an effect. The proseizure effect of morphine is mediated through selective stimulation of mu and kappa opiate receptors but not the activation of the delta receptor system. The observed dose-dependent mechanism of morphine neuroexcitation underscores careful adjustment and individualized opioid dosing in the clinical setting.

Responsiveness of the rehabilitation activities profile and the Barthel index

NARCIS (Netherlands)

van Bennekom, C. A.; Jelles, F.; Lankhorst, G. J.; Bouter, L. M.

1996-01-01

The goal of this study was to compare the responsiveness for clinically meaningful change over time of a newly designed functional status scale, the Rehabilitation Activities Profile (RAP), with more frequently used Barthel Index (BI). Four techniques for the quantification of responsiveness were

Enhanced Proton Translocating Pyrophosphatase Activity Improves Nitrogen Use Efficiency in Romaine Lettuce1[C][W][OA

Science.gov (United States)

Paez-Valencia, Julio; Sanchez-Lares, Jonathan; Marsh, Ellen; Dorneles, Liane T.; Santos, Mirella P.; Sanchez, Diego; Winter, Alexander; Murphy, Sean; Cox, Jennifer; Trzaska, Marcin; Metler, Jason; Kozic, Alex; Facanha, Arnoldo R.; Schachtman, Daniel; Sanchez, Charles A.; Gaxiola, Roberto A.

2013-01-01

Plant nitrate (NO3−) acquisition depends on the combined activities of root high- and low-affinity NO3− transporters and the proton gradient generated by the plasma membrane H+-ATPase. These processes are coordinated with photosynthesis and the carbon status of the plant. Here, we present the characterization of romaine lettuce (Lactuca sativa ‘Conquistador’) plants engineered to overexpress an intragenic gain-of-function allele of the type I proton translocating pyrophosphatase (H+-PPase) of Arabidopsis (Arabidopsis thaliana). The proton-pumping and inorganic pyrophosphate hydrolytic activities of these plants are augmented compared with control plants. Immunohistochemical data show a conspicuous increase in H+-PPase protein abundance at the vasculature of the transgenic plants. Transgenic plants displayed an enhanced rhizosphere acidification capacity consistent with the augmented plasma membrane H+-ATPase proton transport values, and ATP hydrolytic capacities evaluated in vitro. These transgenic lines outperform control plants when challenged with NO3− limitations in laboratory, greenhouse, and field scenarios. Furthermore, we report the characterization of a lettuce LsNRT2.1 gene that is constitutive up-regulated in the transgenic plants. Of note, the expression of the LsNRT2.1 gene in control plants is regulated by NO3− and sugars. Enhanced accumulation of 15N-labeled fertilizer by transgenic lettuce compared with control plants was observed in greenhouse experiments. A negative correlation between the level of root soluble sugars and biomass is consistent with the strong root growth that characterizes these transgenic plants. PMID:23307651

Analysis of personnel monitoring results of external radiation doses received by occupationally exposed workers obtained using CaSO4: Dy TLD personnel monitoring badges at RAPS (2000-2004)

International Nuclear Information System (INIS)

Chourasiya, G.; Kher, R.K.; Rao, B.S.; Pradhan, S.M.

2006-01-01

Personnel monitoring is a key step in radiation protection programme. It helps in keeping a check on radiation hazards and safety aspects of the operating unit. Moreover, analysis of the temporal trends in exposure histories of the individuals/groups play an important role in assessing the need of improved standards of protection and the impact of implementation of such measures. The paper presents the analysis of annual effective dose and collective dose to the radiation workers, which are indicators of individual risk and the impact of the practice. The present study also gives the analysis of the effective dose, cumulative dose and various dose distribution ratios (SR E and NR E ) for the block of 5 years (2000-2004) of RAPS 1 and 2 the oldest PHWR in the country and RAPS 3 and 4 the latest in the series incorporating many improvements in design and operation. It is seen that occupational exposures at NPPs have been showing a steadily decreasing trend, which is a result of a number of design improvements, operation and protection measures. However, to achieve world standards, we have to go a long way by further carrying out identification of areas of improvement, good operating practices along with the desired modifications in design. (author)

Modeling cancer registration processes with an enhanced activity diagram.

Science.gov (United States)

Lyalin, D; Williams, W

2005-01-01

Adequate instruments are needed to reflect the complexity of routine cancer registry operations properly in a business model. The activity diagram is a key instrument of the Unified Modeling Language (UML) for the modeling of business processes. The authors aim to improve descriptions of processes in cancer registration, as well as in other public health domains, through the enhancements of an activity diagram notation within the standard semantics of UML. The authors introduced the practical approach to enhance a conventional UML activity diagram, complementing it with the following business process concepts: timeline, duration for individual activities, responsibilities for individual activities within swimlanes, and descriptive text. The authors used an enhanced activity diagram for modeling surveillance processes in the cancer registration domain. Specific example illustrates the use of an enhanced activity diagram to visualize a process of linking cancer registry records with external mortality files. Enhanced activity diagram allows for the addition of more business concepts to a single diagram and can improve descriptions of processes in cancer registration, as well as in other domains. Additional features of an enhanced activity diagram allow to advance the visualization of cancer registration processes. That, in turn, promotes the clarification of issues related to the process timeline, responsibilities for particular operations, and collaborations among process participants. Our first experiences in a cancer registry best practices development workshop setting support the usefulness of such an approach.

The Rehabilitation Activities Profile: a validation study of its use as a disability index with stroke patients

NARCIS (Netherlands)

van Bennekom, C. A.; Jelles, F.; Lankhorst, G. J.; Bouter, L. M.

1995-01-01

This study evaluates the criterion, content, and construct validity of the Rehabilitation Activities Profile (RAP) in patients with stroke. This instrument is constructed for screening, monitoring, and prognosis purposes to assist clinical rehabilitation. It consists of 21 activities, covering the

Frequency of Natural Resistance within NS5a Replication Complex Domain in Hepatitis C Genotypes 1a, 1b: Possible Implication of Subtype-Specific Resistance Selection in Multiple Direct Acting Antivirals Drugs Combination Treatment

Directory of Open Access Journals (Sweden)

Sabrina Bagaglio

2016-03-01

Full Text Available Different HCV subtypes may naturally harbor different resistance selection to anti-NS5a inhibitors. 2761 sequences retrieved from the Los Alamos HCV database were analyzed in the NS5a domain 1, the target of NS5a inhibitors. The NS5a resistance-associated polymorphisms (RAPs were more frequently detected in HCV G1b compared to G1a. The prevalence of polymorphisms associated with cross-resistance to compounds in clinical use (daclatasvir, DCV, ledipasvir, LDV, ombitasvir, and OMV or scheduled to come into clinical use in the near future (IDX719, elbasvir, and ELV was higher in G1b compared to G1a (37/1552 (2.4% in 1b sequences and 15/1209 (1.2% in 1a isolates, p = 0.040. Interestingly, on the basis of the genotype-specific resistance pattern, 95 (6.1% G1b sequences had L31M RAP to DCV/IDX719, while 6 sequences of G1a (0.5% harbored L31M RAP, conferring resistance to DCV/LDV/IDX719/ELV (p < 0.0001. Finally, 28 (2.3% G1a and none of G1b isolates harbored M28V RAP to OMV (p < 0.0001. In conclusion, the pattern of subtype-specific resistance selection in the naturally occurring strains may guide the treatment option in association with direct acting antivirals (DAAs targeting different regions, particularly in patients that are difficult to cure, such as those with advanced liver disease or individuals who have failed previous DAAs.

A calpain-2 selective inhibitor enhances learning & memory by prolonging ERK activation.

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Liu, Yan; Wang, Yubin; Zhu, Guoqi; Sun, Jiandong; Bi, Xiaoning; Baudry, Michel

2016-06-01

While calpain-1 activation is required for LTP induction by theta burst stimulation (TBS), calpain-2 activation limits its magnitude during the consolidation period. A selective calpain-2 inhibitor applied either before or shortly after TBS enhanced the degree of potentiation. In the present study, we tested whether the selective calpain-2 inhibitor, Z-Leu-Abu-CONH-CH2-C6H3 (3, 5-(OMe)2 (C2I), could enhance learning and memory in wild-type (WT) and calpain-1 knock-out (C1KO) mice. We first showed that C2I could reestablish TBS-LTP in hippocampal slices from C1KO mice, and this effect was blocked by PD98059, an inhibitor of ERK. TBS resulted in PTEN degradation in hippocampal slices from both WT and C1KO mice, and C2I treatment blocked this effect in both mouse genotypes. Systemic injection of C2I 30 min before training in the fear-conditioning paradigm resulted in a biphasic dose-response curve, with low doses enhancing and high doses inhibiting freezing behavior. The difference between the doses needed to enhance and inhibit learning matches the difference in concentrations producing inhibition of calpain-2 and calpain-1. A low dose of C2I also restored normal learning in a novel object recognition task in C1KO mice. Levels of SCOP, a ERK phosphatase known to be cleaved by calpain-1, were decreased in dorsal hippocampus early but not late following training in WT mice; C2I treatment did not affect the early decrease in SCOP levels but prevented its recovery at the later time-point and prolonged ERK activation. The results indicate that calpain-2 activation limits the extent of learning, an effect possibly due to temporal limitation of ERK activation, as a result of SCOP synthesis induced by calpain-2-mediated PTEN degradation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enhanced venous thrombus resolution in plasminogen activator inhibitor type-2 deficient mice.

Science.gov (United States)

Siefert, S A; Chabasse, C; Mukhopadhyay, S; Hoofnagle, M H; Strickland, D K; Sarkar, R; Antalis, T M

2014-10-01

The resolution of deep vein thrombosis requires an inflammatory response and mobilization of proteases, such as urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs), to degrade the thrombus and remodel the injured vein wall. Plasminogen activator inhibitor type 2 (PAI-2) is a serine protease inhibitor (serpin) with unique immunosuppressive and cell survival properties that was originally identified as an inhibitor of uPA. To investigate the role of PAI-2 in venous thrombus formation and resolution. Venous thrombus resolution was compared in wild-type C57BL/6, PAI-2(-/-) , and PAI-1(-/-) mice using the stasis model of deep vein thrombosis. Formed thrombi were harvested, thrombus weights were recorded, and tissue was analyzed for uPA and MMP activities, PAI-1 expression, and the nature of inflammatory cell infiltration. We found that the absence of PAI-2 enhanced venous thrombus resolution, while thrombus formation was unaffected. Enhanced venous thrombus resolution in PAI-2(-/-) mice was associated with increased uPA activity and reduced levels of PAI-1, with no significant effect on MMP-2 and -9 activities. PAI-1 deficiency resulted in an increase in thrombus resolution similar to PAI-2 deficiency, but additionally reduced venous thrombus formation and altered MMP activity. PAI-2-deficient thrombi had increased levels of the neutrophil chemoattractant CXCL2, which was associated with early enhanced neutrophil recruitment. These data identify PAI-2 as a novel regulator of venous thrombus resolution, which modulates several pathways involving both inflammatory and uPA activity mechanisms, distinct from PAI-1. Further examination of these pathways may lead to potential therapeutic prospects in accelerating thrombus resolution. © 2014 International Society on Thrombosis and Haemostasis.

Developing design-based STEM education learning activities to enhance students' creative thinking

Science.gov (United States)

Pinasa, Siwa; Siripun, Kulpatsorn; Yuenyong, Chokchai

2018-01-01

Creative thinking on applying science and mathematics knowledge is required by the future STEM career. The STEM education should be provided for the required skills of future STEM career. This paper aimed to clarify the developing STEM education learning activities to enhance students' creative thinking. The learning activities were developed for Grade 10 students who will study in the subject of independent study (IS) of Khon Kaen Wittayayon School, Khon Kaen, Thailand. The developing STEM education learning activities for enhancing students' creative thinking was developed regarding on 6 steps including (1) providing of understanding of fundamental STEM education concept, (2) generating creative thinking from prototype, (4) revised ideas, (5) engineering ability, and (6) presentation and discussion. The paper will clarify the 18 weeks activities that will be provided based these 6 steps of developing learning activities. Then, these STEM learning activities will be discussed to provide the chance of enhancing students' creative thinking. The paper may have implication for STEM education in school setting.

Severity of murine collagen-induced arthritis correlates with increased CYP7B activity: enhancement of dehydroepiandrosterone metabolism by interleukin-1beta.

Science.gov (United States)

Dulos, John; Verbraak, Evert; Bagchus, Wilma M; Boots, Annemieke M H; Kaptein, Allard

2004-10-01

The endogenous steroid dehydroepiandrosterone (DHEA) has been reported to play a role in rheumatoid arthritis (RA). DHEA is metabolized by the P450 enzyme CYP7B into 7alpha-OH-DHEA, which has immunostimulating properties. This study was undertaken to investigate the putative role of CYP7B in arthritis using murine collagen-induced arthritis (CIA), an interleukin-1beta (IL-1beta)-dependent model. DBA/1J mice were immunized and administered a booster with type II collagen. The presence of 7alpha-OH-DHEA was determined in both arthritic and nonarthritic joints and the serum of CIA mice by radioimmunoassay. CYP7B messenger RNA (mRNA) expression was analyzed in synovial biopsy samples, and in fibroblast-like synoviocytes (FLS) isolated from these synovial biopsy samples, by reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, the regulatory role of IL-1beta on CYP7B activity in FLS was determined using RT-PCR, Western blotting, and high-performance liquid chromatography. In knee joint synovial biopsy samples from arthritic mice, 7alpha-OH-DHEA levels were 5-fold higher than in nonarthritic mice. Elevated levels of 7alpha-OH-DHEA were accompanied by an increase in CYP7B mRNA expression and were positively correlated with disease severity. In serum, no differences in 7alpha-OH-DHEA levels were observed between arthritic and nonarthritic mice. Incubation of FLS with IL-1beta resulted in a dose-dependent increase in 7alpha-OH-DHEA formation. In addition, IL-1beta enhanced CYP7B mRNA and CYP7B protein levels in FLS. Disease progression in CIA is correlated with enhanced CYP7B activity, which leads to locally enhanced 7alpha-OH-DHEA levels. Elevated IL-1beta levels within the arthritic joint may regulate this increase in CYP7B activity. Copyright 2004 American College of Rheumatology

Stronger activation of SREBP-1a by nucleus-localized HBx

International Nuclear Information System (INIS)

Wu, Qi; Qiao, Ling; Yang, Jian; Zhou, Yan; Liu, Qiang

2015-01-01

We previously showed that hepatitis B virus (HBV) X protein activates the sterol regulatory element-binding protein-1a (SREBP-1a). Here we examined the role of nuclear localization of HBx in this process. In comparison to the wild-type and cytoplasmic HBx, nuclear HBx had stronger effects on SREBP-1a and fatty acid synthase transcription activation, intracellular lipid accumulation and cell proliferation. Furthermore, nuclear HBx could activate HBV enhancer I/X promoter and was more effective on up-regulating HBV mRNA level in the context of HBV replication than the wild-type HBx, while the cytoplasmic HBx had no effect. Our results demonstrate the functional significance of the nucleus-localized HBx in regulating host lipogenic pathway and HBV replication. - Highlights: • Nuclear HBx is more effective on activating SREBP-1a and FASN transcription. • Nuclear HBx is more effective on enhancing intracellular lipid accumulation. • Nuclear HBx is more effective on enhancing cell proliferation. • Nuclear HBx up-regulates HBV enhancer I/X promoter activity. • Nuclear HBx increases HBV mRNA level in the context of HBV replication

Stronger activation of SREBP-1a by nucleus-localized HBx

Energy Technology Data Exchange (ETDEWEB)

Wu, Qi [VIDO-InterVac, Veterinary Microbiology, University of Saskatchewan, Saskatoon (Canada); Qiao, Ling [VIDO-InterVac, University of Saskatchewan, Saskatoon, Saskatchewan (Canada); Yang, Jian [Drug Discovery Group, University of Saskatchewan, Saskatoon, Saskatchewan (Canada); Zhou, Yan [VIDO-InterVac, Veterinary Microbiology, Vaccinology and Immunotherapeutics, University of Saskatchewan, Saskatoon, Saskatchewan (Canada); Liu, Qiang, E-mail: qiang.liu@usask.ca [VIDO-InterVac, Veterinary Microbiology, Vaccinology and Immunotherapeutics, University of Saskatchewan, Saskatoon, Saskatchewan (Canada)

2015-05-08

We previously showed that hepatitis B virus (HBV) X protein activates the sterol regulatory element-binding protein-1a (SREBP-1a). Here we examined the role of nuclear localization of HBx in this process. In comparison to the wild-type and cytoplasmic HBx, nuclear HBx had stronger effects on SREBP-1a and fatty acid synthase transcription activation, intracellular lipid accumulation and cell proliferation. Furthermore, nuclear HBx could activate HBV enhancer I/X promoter and was more effective on up-regulating HBV mRNA level in the context of HBV replication than the wild-type HBx, while the cytoplasmic HBx had no effect. Our results demonstrate the functional significance of the nucleus-localized HBx in regulating host lipogenic pathway and HBV replication. - Highlights: • Nuclear HBx is more effective on activating SREBP-1a and FASN transcription. • Nuclear HBx is more effective on enhancing intracellular lipid accumulation. • Nuclear HBx is more effective on enhancing cell proliferation. • Nuclear HBx up-regulates HBV enhancer I/X promoter activity. • Nuclear HBx increases HBV mRNA level in the context of HBV replication.

Discovery of stimulation-responsive immune enhancers with CRISPR activation

Science.gov (United States)

Simeonov, Dimitre R.; Gowen, Benjamin G.; Boontanrart, Mandy; Roth, Theodore L.; Gagnon, John D.; Mumbach, Maxwell R.; Satpathy, Ansuman T.; Lee, Youjin; Bray, Nicolas L.; Chan, Alice Y.; Lituiev, Dmytro S.; Nguyen, Michelle L.; Gate, Rachel E.; Subramaniam, Meena; Li, Zhongmei; Woo, Jonathan M.; Mitros, Therese; Ray, Graham J.; Curie, Gemma L.; Naddaf, Nicki; Chu, Julia S.; Ma, Hong; Boyer, Eric; van Gool, Frederic; Huang, Hailiang; Liu, Ruize; Tobin, Victoria R.; Schumann, Kathrin; Daly, Mark J.; Farh, Kyle K.; Ansel, K. Mark; Ye, Chun J.; Greenleaf, William J.; Anderson, Mark S.; Bluestone, Jeffrey A.; Chang, Howard Y.; Corn, Jacob E.; Marson, Alexander

2017-09-01

The majority of genetic variants associated with common human diseases map to enhancers, non-coding elements that shape cell-type-specific transcriptional programs and responses to extracellular cues. Systematic mapping of functional enhancers and their biological contexts is required to understand the mechanisms by which variation in non-coding genetic sequences contributes to disease. Functional enhancers can be mapped by genomic sequence disruption, but this approach is limited to the subset of enhancers that are necessary in the particular cellular context being studied. We hypothesized that recruitment of a strong transcriptional activator to an enhancer would be sufficient to drive target gene expression, even if that enhancer was not currently active in the assayed cells. Here we describe a discovery platform that can identify stimulus-responsive enhancers for a target gene independent of stimulus exposure. We used tiled CRISPR activation (CRISPRa) to synthetically recruit a transcriptional activator to sites across large genomic regions (more than 100 kilobases) surrounding two key autoimmunity risk loci, CD69 and IL2RA. We identified several CRISPRa-responsive elements with chromatin features of stimulus-responsive enhancers, including an IL2RA enhancer that harbours an autoimmunity risk variant. Using engineered mouse models, we found that sequence perturbation of the disease-associated Il2ra enhancer did not entirely block Il2ra expression, but rather delayed the timing of gene activation in response to specific extracellular signals. Enhancer deletion skewed polarization of naive T cells towards a pro-inflammatory T helper (TH17) cell state and away from a regulatory T cell state. This integrated approach identifies functional enhancers and reveals how non-coding variation associated with human immune dysfunction alters context-specific gene programs.

Adolescência e Tendência Antissocial: o Rap como Expressão de uma Privação Emocional

Directory of Open Access Journals (Sweden)

Cláudia Yaísa Gonçalves da Silva

Full Text Available O presente estudo objetiva refletir sobre a tendência antissocial no adolescente/jovem, por meio da análise do conteúdo descrito nas letras de músicas de rap brasileiro, as quais em geral surgem carregadas de revolta, inconformismo, denúncias sociais e esperança. A pesquisa se caracteriza como exploratória, documental e qualitativa. Para tanto, foi realizada análise de conteúdo das letras, e posterior discussão embasada na teoria de Donald Woods Winnicott, buscando nos trechos das músicas indícios referentes a privações ambientais e o sentido que as letras carregam no contexto do comportamento antissocial. Na análise de conteúdo encontraram-se três categorias: a falha ambiental como princípio para a tendência antissocial, a tendência antissocial enquanto esperança de reparação, e o rappara além da música. Nos excertos das letras de rapselecionadas, os comportamentos antissociais mostraram-se enquanto saída emocional encontrada pelos adolescentes/jovens com histórico de privação, fazendo-os adotarem uma conduta desafiadora socialmente como forma de buscar uma contenção externa para reparar a falha vivenciada antes por alguma figura referencial. Conclui-se que o rap se instaurou como solução positiva para a expressão dos sentimentos e a conquista de uma identidade e reconhecimento social frente aos pares.

Enhanced supercapacitance of activated vertical graphene nanosheets in hybrid electrolyte

Science.gov (United States)

Ghosh, Subrata; Sahoo, Gopinath; Polaki, S. R.; Krishna, Nanda Gopala; Kamruddin, M.; Mathews, Tom

2017-12-01

Supercapacitors are becoming the workhorse for emerging energy storage applications due to their higher power density and superior cycle life compared to conventional batteries. The performance of supercapacitors depends on the electrode material, type of electrolyte, and interaction between them. Owing to the beneficial interconnected porous structure with multiple conducting channels, vertical graphene nanosheets (VGN) have proved to be leading supercapacitor electrode materials. Herein, we demonstrate a novel approach based on the combination of surface activation and a new organo-aqueous hybrid electrolyte, tetraethylammonium tetrafluoroborate in H2SO4, to achieve significant enhancement in supercapacitor performance of VGN. As-synthesized VGN exhibits an excellent supercapacitance of 0.64 mF/cm2 in H2SO4. However, identification of a novel electrolyte for performance enhancement is the subject of current research. The present manuscript demonstrates the potential of the hybrid electrolyte in enhancing the areal capacitance (1.99 mF/cm2) with excellent retention (only 5.4% loss after 5000 cycles) and Coulombic efficiency (93.1%). In addition, a five-fold enhancement in the capacitance of VGNs (0.64 to 3.31 mF/cm2) with a reduced internal resistance is achieved by the combination of KOH activation and the hybrid electrolyte.

NOD1 cooperates with TLR2 to enhance T cell receptor-mediated activation in CD8 T cells.

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Blandine C Mercier

Full Text Available Pattern recognition receptors (PRR, like Toll-like receptors (TLR and NOD-like receptors (NLR, are involved in the detection of microbial infections and tissue damage by cells of the innate immune system. Recently, we and others have demonstrated that TLR2 can additionally function as a costimulatory receptor on CD8 T cells. Here, we establish that the intracytosolic receptor NOD1 is expressed and functional in CD8 T cells. We show that C12-iEDAP, a synthetic ligand for NOD1, has a direct impact on both murine and human CD8 T cells, increasing proliferation and effector functions of cells activated via their T cell receptor (TCR. This effect is dependent on the adaptor molecule RIP2 and is associated with an increased activation of the NF-κB, JNK and p38 signaling pathways. Furthermore, we demonstrate that NOD1 stimulation can cooperate with TLR2 engagement on CD8 T cells to enhance TCR-mediated activation. Altogether our results indicate that NOD1 might function as an alternative costimulatory receptor in CD8 T cells. Our study provides new insights into the function of NLR in T cells and extends to NOD1 the recent concept that PRR stimulation can directly control T cell functions.

Platelets are required for enhanced activation of the endothelium and fibrinogen in a mouse thrombosis model of APS.

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Proulle, Valerie; Furie, Richard A; Merrill-Skoloff, Glenn; Furie, Barbara C; Furie, Bruce

2014-07-24

Antiphospholipid syndrome (APS) is defined by thrombosis, fetal loss, and the presence of antiphospholipid antibodies, including anti-β2-glycoprotein-1 autoantibodies (anti-β2GP1) that have a direct role in the pathogenesis of thrombosis in vivo. The cellular targets of the anti-β2GP1 autoantibody/β2GP1 complex in vivo were studied using a laser-induced thrombosis model of APS in a live mouse and human anti-β2GP1 autoantibodies affinity-purified from APS patients. Cell binding of fluorescently labeled β2GP1 and anti-β2GP1 autoantibodies revealed their colocalization on the platelet thrombus but not the endothelium. Anti-β2GP1 autoantibodies enhanced platelet activation, monitored by calcium mobilization, and endothelial activation, monitored by intercellular adhesion molecule-1 expression. When eptifibatide was infused to block platelet thrombus formation, enhanced fibrin generation and endothelial cell activation were eliminated. Thus, the anti-β2GP1 autoantibody/β2GP1 complex binds to the thrombus, enhancing platelet activation, and platelet secretion leads to enhanced endothelium activation and fibrin generation. These results lead to a paradigm shift away from the concept that binding of the anti-β2GP1 autoantibody/β2GP1 complex activates both endothelial cells and platelets toward one in which activation of platelets in response to anti-β2GP1 autoantibody/β2GP1 complex binding leads to subsequent enhanced endothelium activation and fibrin generation. © 2014 by The American Society of Hematology.

Resonance Raman Optical Activity and Surface Enhanced Resonance Raman Optical Activity analysis of Cytochrome C

DEFF Research Database (Denmark)

Johannessen, Christian; Abdali, Salim; White, Peter C.

2007-01-01

High quality Resonance Raman (RR) and resonance Raman Optical Activity (ROA) spectra of cytochrome c were obtained in order to perform full assignment of spectral features of the resonance ROA spectrum. The resonance ROA spectrum of cytochrome c revealed a distinct spectral signature pattern due...... to resonance enhanced skeletal porphyrin vibrations, more pronounced than any contribution from the protein back-bone. Combining the intrinsic resonance enhancement of cytochrome c with surface plasmon enhancement by colloidal silver particles, the Surface Enhanced Resonance Raman Scattering (SERRS) and Chiral...... Enhanced Raman Spectroscopy (ChERS) spectra of the protein were successfully obtained at very low concentration (as low as 1 µM). The assignment of spectral features was based on the information obtained from the RR and resonance ROA spectra. Excellent agreement between RR and SERRS spectra is reported...

HTLV-1 Tax protein recruitment into IKKε and TBK1 kinase complexes enhances IFN-I expression.

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Diani, Erica; Avesani, Francesca; Bergamo, Elisa; Cremonese, Giorgia; Bertazzoni, Umberto; Romanelli, Maria Grazia

2015-02-01

The Tax protein expressed by human T-cell leukemia virus type 1 (HTLV-1) plays a pivotal role in the deregulation of cellular pathways involved in the immune response, inflammation, cell survival, and cancer. Many of these effects derive from Tax multiple interactions with host factors, including the subunits of the IKK-complex that are required for NF-κB activation. IKKɛ and TBK1 are two IKK-related kinases that allow the phosphorylation of interferon regulatory factors that trigger IFN type I gene expression. We observed that IKKɛ and TBK1 recruit Tax into cellular immunocomplexes. We also found that TRAF3, which regulates cell receptor signaling effectors, forms complexes with Tax. Transactivation analyses revealed that expression of Tax, in presence of IKKɛ and TBK1, enhances IFN-β promoter activity, whereas the activation of NF-κB promoter is not modified. We propose that Tax may be recruited into the TBK1/IKKɛ complexes as a scaffolding-adaptor protein that enhances IFN-I gene expression. Copyright © 2014 Elsevier Inc. All rights reserved.

Daily physical activity enhances resilient resources for symptom management in middle-aged women.

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Kishida, Moé; Elavsky, Steriani

2015-07-01

The aim of the present study was to evaluate the direct and indirect associations between physical activity and menopausal symptoms. Community-dwelling middle-aged women (N = 103; age range 40-60 years) completed daily Internet surveys at the end of the day and wore an accelerometer for the objective assessment of physical activity for 21-days. 1-1-1 multilevel mediation models were estimated to test whether resilient resources (i.e., positive affect and coping efficacy) mediated the association between physical activity and symptom burden at the between- and within-person level. Analyses demonstrated physical activity had an indirect effect (-0.16) on symptom burden through the enhancement of positive affect at the within-person level (p physical activity on symptom burden at the within-person level was -0.08 (p physical activity may help a woman to cope with her symptoms is through the enhancement of positive affect and coping efficacy on a day-to-day basis. (c) 2015 APA, all rights reserved.

Ultrasound enhanced activation of peroxydisulfate by activated carbon fiber for decolorization of azo dye.

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Huang, Tianyin; Zhang, Ke; Qian, Yajie; Fang, Cong; Chen, Jiabin

2018-02-20

Activated carbon fiber (ACF) has become an emerging activator for peroxydisulfate (PDS) to generate sulfate radical (SO 4 •- ). However, the relative low activation efficiency and poor contaminant mineralization limited its widespread application. Herein, ultrasound (US) was introduced to the ACF activated PDS system, and the synergistic effect of US and ACF in PDS activation and the enhancement of contaminant mineralization were investigated. The synergistic effect of US and ACF was observed in the PDS activation to decolorize orange G (OG). The decolorization efficiency increased with increasing ACF loading and US power, and PDS/OG ratio from 1 to 40. The activation energy was determined to be 24.065 kJ/mol. The radical-induced decolorization of OG took place on the surface of ACF, and both SO 4 •- and hydroxyl radical ( • OH) contributed to OG decolorization. The azo bond and naphthalene ring on OG were destructed to other aromatic intermediates and finally mineralized to CO 2 and H 2 O. The introduction of US in the ACF/PDS system significantly enhanced the mineralization of OG. The combination of US and PDS was highly efficient to activate PDS to decolorize azo dyes. Moreover, the introduction of US remarkably improved the contaminant mineralization.

Coactivator-associated arginine methyltransferase 1 enhances transcriptional activity of the human T-cell lymphotropic virus type 1 long terminal repeat through direct interaction with Tax.

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Jeong, Soo-Jin; Lu, Hanxin; Cho, Won-Kyung; Park, Hyeon Ung; Pise-Masison, Cynthia; Brady, John N

2006-10-01

In this study, we demonstrate that the coactivator-associated arginine methyltransferase 1 (CARM1), which methylates histone H3 and other proteins such as p300/CBP, is positively involved in the regulation of Tax transactivation. First, transfection studies demonstrated that overexpression of CARM1 wild-type protein resulted in increased Tax transactivation of the human T-cell lymphotropic virus type 1 (HTLV-1) long terminal repeat (LTR). In contrast, transfection of a catalytically inactive CARM1 methyltransferase mutant did not enhance Tax transactivation. CARM1 facilitated Tax transactivation of the CREB-dependent cellular GEM promoter. A direct physical interaction between HTLV-1 Tax and CARM1 was demonstrated using in vitro glutathione S-transferase-Tax binding assays, in vivo coimmunoprecipitation, and confocal microscopy experiments. Finally, chromatin immunoprecipitation analysis of the activated HTLV-1 LTR promoter showed the association of CARM1 and methylated histone H3 with the template DNA. In vitro, Tax facilitates the binding of CARM1 to the transcription complex. Together, our data provide evidence that CARM1 enhances Tax transactivation of the HTLV-1 LTR through a direct interaction between CARM1 and Tax and this binding promotes methylation of histone H3 (R2, R17, and R26).

Inecalcitol, an analog of 1,25D₃, displays enhanced antitumor activity through the induction of apoptosis in a squamous cell carcinoma model system

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Ma, Yingyu; Yu, Wei-Dong; Hidalgo, Alejandro A.; Luo, Wei; Delansorne, Remi; Johnson, Candace S.; Trump, Donald L.

2013-01-01

Epidemiological data suggest an important role of vitamin D signaling in cancer development and progression, and experimental studies demonstrate that the active vitamin D metabolite 1α, 25-dihydroxyvitamin D₃ (1,25D₃) has broad spectrum antitumor activity. Hypercalcemia has often been suggested to limit the clinical application of these data. The 14-epi-analog of 1,25D₃, inecalcitol [19-nor-14-epi-23-yne-1,25-(OH)₂D₃; TX522], was developed to have superagonistic antitumor activities but low hypercalcemia potential. We examined the antitumor activity of inecalcitol and the underlying mechanisms in a murine squamous cell carcinoma (SCC) model system. In vitro, compared with 1,25D₃, inecalcitol showed enhanced vitamin D receptor (VDR)-mediated transcriptional activity. Inecalcitol suppressed SCC cell proliferation in a dose-dependent manner with an IC₅₀ value 30 times lower than that of 1,25D₃. Both inecalcitol and 1,25D₃ induced a comparable level of G₀/G₁ cell cycle arrest in SCC cells. The level of apoptosis induced by inecalcitol was markedly higher than that of 1,25D₃. Apoptosis was mediated through the activation of the caspase 8/10- caspase 3 pathway. Further, inecalcitol markedly inhibited the mRNA and protein expression of c-IAP1 and XIAP compared with 1,25D₃. In vivo, inecalcitol inhibits SCC tumor growth in a dose-dependent fashion. Notably, inecalcitol induced a significantly higher level of apoptosis in the SCC xenograft model. While in vitro inecalcitol demonstrates apparent enhanced VDR binding and antiproliferative effects compared to 1,25D₃, in vivo these advantages disappear; at doses of inecalcitol that have equivalent antitumor effects, similar hypercalcemia is seen. This may be explained by the pharmacokinetics of 1,25D₃ vs. inecalcitol and attributed to the much shorter serum half-life of inecalcitol.We show that inecalcitol has potent antitumor activity in the SCC model system, and this is associated with a

Memory-enhancing activity of Anacyclus pyrethrum in albino Wistar rats

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K Sujith

2012-08-01

Full Text Available Objective: To explore the potential effect of ethanolic extract of Anacyclus pyrethrum (A. pyrethrum in memory dysfunction. Methods: Memory impairment was produced by administration of scopolamine (1mg/kg i. p in rats. Passive avoidance paradigms, elevated plus maze and social learning task was used to assess learning and memory. Results: A. pyrethrum extract treated group decreased transfer latency in elevated plus maze model paradigm which is an indicative of cognition improvement. In case of passive avoidance paradigm extract treated group exhibited prounced effect in reversal of scopolamine induced amnesia which was revealed by increase in step down latency. Social learning task also revealed the memory enhancing activity of A. pyrethrum extract. Conclusions: Ethanolic extract of A. pyrethrum has been demonstrated to improve cognitive processes by enhancing memory in different experimental paradigms such as passive avoidance paradigms, elevated plus maze and social learning task when administered orallyBrain cholinesterase level was measured to assess central cholinergic activity. The treatment with drugs, which increase cholinergic neurotransmission, causes an improvement in cognitive deficits. The present study suggest that ethanolic extract of A. pyrethrum increased brain cholinesterase level and hence it possess memory enhancing activity in scopolamine induced amnesia model by enhancing central cholinergic neurotransmission.

Procarcinogenic effects of cyclosporine A are mediated through the activation of TAK1/TAB1 signaling pathway

International Nuclear Information System (INIS)

Xu, Jianmin; Walsh, Stephanie B.; Verney, Zoe M.; Kopelovich, Levy; Elmets, Craig A.; Athar, Mohammad

2011-01-01

Research highlights: → Organ transplant recipients are highly susceptible to early skin cancer development. → CsA-mediated TGFB1-dependent TAK1/TAB1 signaling augments invasive tumor growth. → CsA enhances accumulation of upstream kinases, ZMP, AMPK and IRAK to activate TAK1. → TAK1 mediates enhanced proliferation and reduced apoptosis via CsA-dependent NFκB. -- Abstract: Cyclosporine A (CsA) is an immunosuppressive drug commonly used for maintaining chronic immune suppression in organ transplant recipients. It is known that patients receiving CsA manifest increased growth of aggressive non-melanoma skin cancers. However, the underlying mechanism by which CsA augments tumor growth is not fully understood. Here, we show that CsA augments the growth of A431 epidermoid carcinoma xenograft tumors by activating tumor growth factor β-activated kinase1 (TAK1). The activation of TAK1 by CsA occurs at multiple levels by kinases ZMP, AMPK and IRAK. TAK1 forms heterodimeric complexes with TAK binding protein 1 and 2 (TAB1/TAB2) which in term activate nuclear factor κB (NFκB) and p38 MAP kinase. Transcriptional activation of NFκB is evidenced by IKKβ-mediated phosphorylation-dependent degradation of IκB and consequent nuclear translocation of p65. This also leads to enhancement in the expression of its transcriptional target genes cyclin D1, Bcl2 and COX-2. Similarly, activation of p38 leads to enhanced inflammation-related signaling shown by increased phosphorylation of MAPKAPK2 and which in turn phosphorylates its substrate HSP27. Activation of both NFκB and p38 MAP kinase provide mitogenic stimuli to augment the growth of SCCs.